Metaherpetic corneal disease in a dog associated with partial limbal stem cell deficiency and neurotrophic keratitis.

Science.gov (United States)

Ledbetter, Eric C; Marfurt, Carl F; Dubielzig, Richard R

2013-07-01

To describe clinical, in vivo confocal microscopic, histopathologic, and immunohistochemical features of a dog with metaherpetic corneal disease that developed subsequent to a protracted episode of canine herpesvirus-1 (CHV-1) dendritic ulcerative keratitis. A 7-year-old, spayed-female, Miniature Schnauzer was treated for bilateral CHV-1 dendritic ulcerative keratitis. Following resolution of ulcerative keratitis, sectoral peripheral superficial corneal gray opacification, vascularization, and pigmentation slowly migrated centripetally to the axial cornea of both eyes. Corneal sensitivity measured with a Cochet-Bonnet esthesiometer was dramatically and persistently reduced. In vivo corneal confocal microscopic examination revealed regions of epithelium with a conjunctival phenotype. In these areas, the surface epithelium was thin, disorganized, and composed of hyper-reflective epithelial cells. Goblet cells and Langerhans cells were frequent, and the subbasal nerve plexus was completely absent or markedly diminished. Histopathologic abnormalities in the globes were restricted to the superficial cornea and included sectoral corneal conjunctivalization, increased anterior stromal spindle cells, and vascularization. Immunohistochemical evaluation of the corneas with anti-neurotublin antibody demonstrated attenuation of the epithelial and subbasal nerve plexuses with marked stromal hyperinnervation and increased numbers of morphologically abnormal neurites. Similar to herpes simplex virus keratitis in humans, CHV-1 ulcerative keratitis may be associated with the development of chronic degenerative corneal disease in dogs. In the described dog, this chronic corneal disease included progressive corneal opacification because of partial limbal stem cell deficiency and neurotrophic keratitis. Long-term monitoring of dogs following resolution of active CHV-1 keratitis may be indicated, particularly when ulcerations persist for an extended period. © 2012 American College of

Femtosecond laser cutting of multiple thin corneal stromal lamellae for endothelial bioengineering.

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Bernard, Aurélien; He, Zhiguo; Forest, Fabien; Gauthier, Anne-Sophie; Peocʼh, Michel; Dumollard, Jean-Marc; Acquart, Sophie; Montard, Romain; Delbosc, Bernard; Gain, Philippe; Thuret, Gilles

2015-02-01

To assess the feasibility of cutting multiple thin stromal lamellae in human donor corneas using a commercial femtosecond laser (FSL) to provide cell carriers for future endothelial graft bioengineering. Eight edematous organ-cultured corneas not suitable for grafting for endothelial reasons were mounted on a Ziemer anterior chamber and cut with a Z6 FSL with 6 successive parallel cuts, from depth to surface. Target thickness of each lamella ranged from 100 to 150 μm depending on initial corneal thickness. Thickness was measured using anterior segment optical coherence tomography before and after cutting on mounted corneas, and on each stromal lamella after detachment. Scanning electron microscopy observation was performed on 4 lamellae and histological cross sections on 1 cornea before detachment. A median of 5 (minimum 3, maximum 7) lamellae was obtained per cornea. All lamellae still attached were the most posterior ones, suggesting that FSL was less efficient because of light scattering by edematous stroma. Cut precision and postdetachment swelling were correlated with anterior-posterior position within the cornea. Median lamella thickness was 127 μm (56-222 μm) before detachment and 196 μm (80-304 μm) after detachment. Surface state was consistent with previously reported FSL lamellar cuts during Descemet stripping automated endothelial keratoplasty. Up to 7 thin lamellae can be cut in stored corneas with an FSL. This method, once optimized primarily by using deswelled, more transparent corneas, could prove effective for recycling unsuitable donor corneas in corneal bioengineering processes.

Role of Decorin Core Protein in Collagen Organisation in Congenital Stromal Corneal Dystrophy (CSCD.

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Christina S Kamma-Lorger

Full Text Available The role of Decorin in organising the extracellular matrix was examined in normal human corneas and in corneas from patients with Congenital Stromal Corneal Dystrophy (CSCD. In CSCD, corneal clouding occurs due to a truncating mutation (c.967delT in the decorin (DCN gene. Normal human Decorin protein and the truncated one were reconstructed in silico using homology modelling techniques to explore structural changes in the diseased protein. Corneal CSCD specimens were also examined using 3-D electron tomography and Small Angle X-ray diffraction (SAXS, to image the collagen-proteoglycan arrangement and to quantify fibrillar diameters, respectively. Homology modelling showed that truncated Decorin had a different spatial geometry to the normal one, with the truncation removing a major part of the site that interacts with collagen, compromising its ability to bind effectively. Electron tomography showed regions of abnormal stroma, where collagen fibrils came together to form thicker fibrillar structures, showing that Decorin plays a key role in the maintenance of the order in the normal corneal extracellular matrix. Average diameter of individual fibrils throughout the thickness of the cornea however remained normal.

Role of Bone Morphogenetic Protein 7 (BMP7 in the Modulation of Corneal Stromal and Epithelial Cell Functions

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Bhavani S. Kowtharapu

2018-05-01

Full Text Available In the cornea, healing of the wounded avascular surface is an intricate process comprising the involvement of epithelial, stromal and neuronal cell interactions. These interactions result to the release of various growth factors that play prominent roles during corneal wound healing response. Bone morphogenetic proteins (BMPs are unique multi-functional potent growth factors of the transforming growth factor-beta (TGF-β superfamily. Treatment of corneal epithelial cells with substance P and nerve growth factor resulted to an increase in the expression of BMP7 mRNA. Since BMP7 is known to modulate the process of corneal wound healing, in this present study, we investigated the influence of exogenous rhBMP7 on human corneal epithelial cell and stromal cell (SFs function. To obtain a high-fidelity expression profiling of activated biomarkers and pathways, transcriptome-wide gene-level expression profiling of epithelial cells in the presence of BMP7 was performed. Gene ontology analysis shows BMP7 stimulation activated TGF-β signaling and cell cycle pathways, whereas biological processes related to cell cycle, microtubule and intermediate filament cytoskeleton organization were significantly impacted in corneal epithelial cells. Scratch wound healing assay showed increased motility and migration of BMP7 treated epithelial cells. BMP7 stimulation studies show activation of MAPK cascade proteins in epithelial cells and SFs. Similarly, a difference in the expression of claudin, Zink finger E-box-binding homeobox 1 was observed along with phosphorylation levels of cofilin in epithelial cells. Stimulation of SFs with BMP7 activated them with increased expression of α-smooth muscle actin. In addition, an elevated phosphorylation of epidermal growth factor receptor following BMP7 stimulation was also observed both in corneal epithelial cells and SFs. Based on our transcriptome analysis data on epithelial cells and the results obtained in SFs, we

Evaluation of Topical Cyclosporine in Preventing the Development of Corneal Haze after Photorefractive Keratectomy

Science.gov (United States)

2014-05-13

NAME OF RESPONSIBLE PERSON: a. REPORT UNCLASSIFIED b. ABSTRACT UNCLASSIFIED c. THIS PAGE UNCLASSIFIED 19b. TELEPHONE NUMBER...fibroblast proliferation and concomitant fibrotic scar deposition at the corneal wound site. Unfortunately, mitomycin C also inhibits epithelial...stromal, and endothelial replication and can lead to vascular endothelial injury and secondary tissue necrosis. 3 Due to these side effects, steroids are

Terrien's marginal degeneration accompanied by latticed stromal opacities.

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Zhang, Yibing; Jia, Hui

2014-05-01

We report a case of Terrien's marginal degeneration (TMD) with a unilaterally typical narrow band of peripheral corneal stroma thinning, accompanied by the presence of an unusual network of opacities diffusing throughout the anterior stroma layers. A 43-year-old woman presented with superior nasal peripheral corneal thinning and an unusual network of polygonal stromal opacities in the anterior corneal stroma of the right eye. Latticed corneal changes were unusually extensive and distributed diffusely in the stroma. No abnormalities were found in the corneal epithelium and in the basal epithelial cells. No noticeable changes were found in the left eye. Because of a progressively worse ocular irritation of the right eye, a diagnosis of TMD was made for this patient. This case of TMD accompanied by keratopathy was unusual. The branching stromal lattice pattern of the corneal opacities was difficult to distinguish from lattice corneal dystrophy. In this case, the polygonal stromal opacities were located in the anterior corneal stroma and therefore were distinguished from a similar manifestation in posterior crocodile shagreen.

Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy

OpenAIRE

Costa, M.; Cerqueira, Mariana Teixeira; Santos, T. C.; Marques, Belém Sampaio; Ludovico, Paula; Marques, A. P.; Pirraco, Rogério P.; Reis, R. L.

2017-01-01

Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditi...

Progress in corneal wound healing

Science.gov (United States)

Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh

2015-01-01

Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and

Terrien’s Marginal Degeneration Accompanied by Latticed Stromal Opacities

Science.gov (United States)

Zhang, Yibing; Jia, Hui

2014-01-01

ABSTRACT Purpose We report a case of Terrien’s marginal degeneration (TMD) with a unilaterally typical narrow band of peripheral corneal stroma thinning, accompanied by the presence of an unusual network of opacities diffusing throughout the anterior stroma layers. Case Report A 43-year-old woman presented with superior nasal peripheral corneal thinning and an unusual network of polygonal stromal opacities in the anterior corneal stroma of the right eye. Latticed corneal changes were unusually extensive and distributed diffusely in the stroma. No abnormalities were found in the corneal epithelium and in the basal epithelial cells. No noticeable changes were found in the left eye. Because of a progressively worse ocular irritation of the right eye, a diagnosis of TMD was made for this patient. Conclusions This case of TMD accompanied by keratopathy was unusual. The branching stromal lattice pattern of the corneal opacities was difficult to distinguish from lattice corneal dystrophy. In this case, the polygonal stromal opacities were located in the anterior corneal stroma and therefore were distinguished from a similar manifestation in posterior crocodile shagreen. PMID:24681833

Isolated corneal papilloma-like lesion associated with human papilloma virus type 6.

Science.gov (United States)

Park, Choul Yong; Kim, Eo-Jin; Choi, Jong Sun; Chuck, Roy S

2011-05-01

To report a case of a corneal papilloma-like lesion associated with human papilloma virus type 6. A 48-year-old woman presented with a 2-year history of ocular discomfort and gradual visual deterioration in her right eye. Ophthalmic examination revealed an elevated, semitranslucent, well-defined vascularized mass approximately 4 × 2.5 mm in size localized to the right cornea. The surface of the mass appeared smooth and many small, shallow, and irregular elevations were noted. An excisional biopsy was performed. The underlying cornea was markedly thinned, and fine ramifying vasculature was also noted on the exposed corneal stroma. Typical koilocytic change was observed on the histopathologic examination. Polymerase chain reaction revealed the existence of human papilloma virus type 6 DNA. Here we describe a case of an isolated corneal papilloma-like lesion. Although the corneal extension of the limbal or the conjunctival papillomas has been commonly observed, an isolated corneal papilloma-like lesion with underlying stromal destruction has only rarely been reported.

Migraine and tension-type headache treated with stromal vascular fraction: a case series.

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Bright, Ralph; Bright, Matthew; Bright, Pelin; Hayne, Shannon; Thomas, Wayne D

2014-06-30

Chronic migraines and tension-type headaches are debilitating diseases affecting 1.4 to 2.2% of the population with both quality of life and economic implications. To date, the pain associated with migraine and tension-type headaches has been controlled with a range of medications, with varying levels of success. In addition, the side-effect profile of these medications, as well as their potential for addiction, has been a cause for concern for both patients and physicians. Four women with long histories of migraine or frequent tension-type headache that meet the International Classification of Headache Disorders criteria for Chronic Migraine or Tension-type Headaches were given a systemic treatment(s) of autologous stromal vascular fraction or autologous 'StroMed' isolated from lipoaspirate. StroMed is stromal vascular fraction cells prepared by ultrasonic cavitation. Two of the four patients, both of whom are Arab women aged 40 and 36 years, ceased having migraines after 1 month, for a period of 12 to 18 months. The third patient, a Slavic woman aged 43 years, had a significant decrease in the frequency and severity of migraines with only seven migraines over 18 months. The fourth patient, an Asian woman aged 44 years, obtained a temporary decrease for a period of a month and was retreated 18 months later and has been free of migraines to date for 1 month. Pain medication was typically reduced from prescribed opioid analgesia to non-steroidal anti-inflammatory drugs and paracetamol. This case series is the first to provide evidence of the efficacy of autologous StroMed and stromal vascular fraction in the treatment of migraine and tension-type headache. The treatment of this disease by stromal vascular fraction adds a new dimension to its clinical applicability and suggests a relatively simple treatment that may help address the symptoms of the disease. Given what is known about the components of the stromal vascular fraction and how they act, the information

Regulation of corneal stroma extracellular matrix assembly.

Science.gov (United States)

Chen, Shoujun; Mienaltowski, Michael J; Birk, David E

2015-04-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Altered corneal stromal matrix organization is associated with mucopolysaccharidosis I, III and VI.

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Alroy, J; Haskins, M; Birk, D E

1999-05-01

The presence of cloudy corneas is a prominent feature of mucopolysaccharidosis (MPS) types I and VI, but not MPS IIIA or IIIB. The cause of corneal cloudiness in MPS I and VI is speculative. Transparency of the cornea is dependent on the uniform diameter and the regular spacing and arrangement of the collagen fibrils within the stroma. Alterations in the spacing of collagen fibrils in a variety of conditions including corneal edema, scars, and macular corneal dystrophy is clinically manifested as corneal opacity. The purpose of this study was to compare the structural organization of the stromal extracellular matrix of normal corneas with that of MPS corneas. The size and arrangement of collagen fibrils in cloudy corneas from patients with MPS I were examined. The alterations observed were an increased mean fibril diameter with a broader distribution in the MPS corneas. The MPS I corneas also had altered fibril spacing and more irregular packing compared with normal control corneas. The clear corneas of patients with MPS IIIA and IIIB also showed increases in mean fibril diameter and fibril spacing. However, there was less variation indicating more regularity than seen in MPS I. In addition, corneas from cat models of certain MPS were compared to the human corneas. Cats with MPS I and VI, as well as normal control cats, were examined. Structural alterations comparable to those seen in human MPS corneas were seen in MPS I and VI cats relative to normal clear corneas. The findings suggest that cloudy corneas in MPS I and VI are in part a consequence of structural alterations in the corneal stroma, including abnormal spacing, size, and arrangement of collagen fibrils. Copyright 1999 Academic Press.

Isolation and differentiation of stromal vascular cells to beige/brite cells

DEFF Research Database (Denmark)

Aune, Ulrike Liisberg; Ruiz, Lauren; Kajimura, Shingo

2013-01-01

cold exposure or by PPARγ agonists, therefore, this cell type has potential as a therapeutic target for obesity treatment. Although most immortalized adipocyte lines cannot recapitulate the process of "browning" of white fat in culture, primary adipocytes isolated from stromal vascular fraction...

Collagen based film with well epithelial and stromal regeneration as corneal repair materials: Improving mechanical property by crosslinking with citric acid

International Nuclear Information System (INIS)

Zhao, Xuan; Liu, Yang; Li, Weichang; Long, Kai; Wang, Lin; Liu, Sa; Wang, Yingjun; Ren, Li

2015-01-01

Corneal disease can lead to vision loss. It has become the second greatest cause of blindness in the world, and keratoplasty is considered as an effective treatment method. This paper presents the crosslinked collagen (Col)–citric acid (CA) films developed by making use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The results showed that the Col–CA films had necessary optical performance, water content. The collagenase resistance of CA crosslinked films was superior to that of EDC crosslinked films. And CA5 film (Col:CA:EDC:NHS = 60:3:10:10) had the best mechanical properties. Cell experiments showed that CA5 film was non-cytotoxic and human corneal epithelial cells could proliferate well on the films. Lamellar keratoplasty showed that the CA5 film could be sutured in the rabbit eyes and was epithelialized completely in about 10 days, and the transparency was restored quickly in 30 ± 5 days. No inflammation and corneal neovascularization were observed at 6 months. Corneal stroma had been repaired; stromal cells and neo-stroma could be seen in the area of operation from the hematoxylin–eosin stained histologic sections and anterior segment optical coherence tomography images. These results indicated that Col–CA films were highly promising biomaterials that could be used in corneal tissue engineering and a variety of other tissue engineering applications. - Highlights: • Adding different amounts of citric acid could change the properties of films. • The crosslinked films had better mechanical property than non-modified films. • Crosslinked collagen–citric acid films could tolerate suture during operation. • The films showed good ability of epithelial and stromal repair

Collagen based film with well epithelial and stromal regeneration as corneal repair materials: Improving mechanical property by crosslinking with citric acid

Energy Technology Data Exchange (ETDEWEB)

Zhao, Xuan; Liu, Yang; Li, Weichang; Long, Kai; Wang, Lin; Liu, Sa; Wang, Yingjun [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China); Ren, Li, E-mail: psliren@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China)

2015-10-01

Corneal disease can lead to vision loss. It has become the second greatest cause of blindness in the world, and keratoplasty is considered as an effective treatment method. This paper presents the crosslinked collagen (Col)–citric acid (CA) films developed by making use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The results showed that the Col–CA films had necessary optical performance, water content. The collagenase resistance of CA crosslinked films was superior to that of EDC crosslinked films. And CA5 film (Col:CA:EDC:NHS = 60:3:10:10) had the best mechanical properties. Cell experiments showed that CA5 film was non-cytotoxic and human corneal epithelial cells could proliferate well on the films. Lamellar keratoplasty showed that the CA5 film could be sutured in the rabbit eyes and was epithelialized completely in about 10 days, and the transparency was restored quickly in 30 ± 5 days. No inflammation and corneal neovascularization were observed at 6 months. Corneal stroma had been repaired; stromal cells and neo-stroma could be seen in the area of operation from the hematoxylin–eosin stained histologic sections and anterior segment optical coherence tomography images. These results indicated that Col–CA films were highly promising biomaterials that could be used in corneal tissue engineering and a variety of other tissue engineering applications. - Highlights: • Adding different amounts of citric acid could change the properties of films. • The crosslinked films had better mechanical property than non-modified films. • Crosslinked collagen–citric acid films could tolerate suture during operation. • The films showed good ability of epithelial and stromal repair.

Corneal hydrops induced by Bell’s paralysis in a case of corneal ectasia

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Lokman Aslan

2017-09-01

Full Text Available An 18-year-old male patient presented with suddenly decreased vision, itching, corneal edema and an inability to close the left eye. They had left Bell’s paralysis for two weeks and had used high diopter glasses for five years. The best corrected visual acuity was 0.4 in their right eye and counting fingers in the left eye. Biomicroscopic examination revealed thinning and steepening of the cornea in the right eye and anterior protrusion of the cornea, stromal edema and punctate disruption of the epithelium in the left eye. Topographic image of the right eye was consistent with keratoconus. Six months later, stromal edema gradually regressed and a corneal scar ensued. This case presentation emphasizes that Bell’s palsy may induce disease progression in a patient with preexisting corneal ectasia and results in corneal hydrops. [Arch Clin Exp Surg 2017; 6(3.000: 165-167

Role of corneal collagen fibrils in corneal disorders and related pathological conditions

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Hong-Yan Zhou

2017-05-01

Full Text Available The cornea is a soft tissue located at the front of the eye with the principal function of transmitting and refracting light rays to precisely sense visual information. Corneal shape, refraction, and stromal stiffness are to a large part determined by corneal fibrils, the arrangements of which define the corneal cells and their functional behaviour. However, the modality and alignment of native corneal collagen lamellae are altered in various corneal pathological states such as infection, injury, keratoconus, corneal scar formation, and keratoprosthesis. Furthermore, corneal recuperation after corneal pathological change is dependent on the balance of corneal collagen degradation and contraction. A thorough understanding of the characteristics of corneal collagen is thus necessary to develop viable therapies using the outcome of strategies using engineered corneas. In this review, we discuss the composition and distribution of corneal collagens as well as their degradation and contraction, and address the current status of corneal tissue engineering and the progress of corneal cross-linking.

Corneal Toxicity Following Exposure to Asclepias Tuberosa

OpenAIRE

Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; G?l, Cigdem Altuntas; Heegaard, Steffen

2017-01-01

PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa.METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine.RESULTS: The corneal ...

Analysis for apoptosis and necrosis on adipocytes, stromal vascular fraction, and adipose-derived stem cells in human lipoaspirates after liposuction.

Science.gov (United States)

Wang, Wei Z; Fang, Xin-Hua; Williams, Shelley J; Stephenson, Linda L; Baynosa, Richard C; Wong, Nancy; Khiabani, Kayvan T; Zamboni, William A

2013-01-01

Adipose-derived stem cells have become the most studied adult stem cells. The authors examined the apoptosis and necrosis rates for adipocyte, stromal vascular fraction, and adipose-derived stem cells in fresh human lipoaspirates. Human lipoaspirate (n = 8) was harvested using a standard liposuction technique. Stromal vascular fraction cells were separated from adipocytes and cultured to obtain purified adipose-derived stem cells. A panel of stem cell markers was used to identify the surface phenotypes of cultured adipose-derived stem cells. Three distinct stem cell subpopulations (CD90/CD45, CD105/CD45, and CD34/CD31) were selected from the stromal vascular fraction. Apoptosis and necrosis were determined by annexin V/propidium iodide assay and analyzed by flow cytometry. The cultured adipose-derived stem cells demonstrated long-term proliferation and differentiation evidenced by cell doubling time and positive staining with oil red O and alkaline phosphatase. Isolated from lipoaspirates, adipocytes exhibited 19.7 ± 3.7 percent apoptosis and 1.1 ± 0.3 percent necrosis; stromal vascular fraction cells revealed 22.0 ± 6.3 percent of apoptosis and 11.2 ± 1.9 percent of necrosis; stromal vascular fraction cells had a higher rate of necrosis than adipocytes (p vascular fraction cells, 51.1 ± 3.7 percent expressed CD90/CD45, 7.5 ± 1.0 percent expressed CD105/CD45, and 26.4 ± 3.8 percent expressed CD34/CD31. CD34/CD31 adipose-derived stem cells had lower rates of apoptosis and necrosis compared with CD105/CD45 adipose-derived stem cells (p necrosis than adipocytes. However, the extent of apoptosis and necrosis was significantly different among adipose-derived stem cell subpopulations.

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model.

Science.gov (United States)

Gore, Daniel M; O'Brart, David; French, Paul; Dunsby, Chris; Allan, Bruce D

2015-07-01

To measure depth-specific riboflavin concentrations in corneal stroma using two-photon fluorescence microscopy and compare commercially available transepithelial corneal collagen cross-linking (CXL) protocols. Transepithelial CXL riboflavin preparations--MedioCross TE, Ribocross TE, Paracel plus VibeX Xtra, and iontophoresis with Ricrolin+--were applied to the corneal surface of fresh postmortem rabbit eyes in accordance with manufacturers' recommendations for clinical use. Riboflavin 0.1% (VibeX Rapid) was applied after corneal epithelial debridement as a positive control. After riboflavin application, eyes were snap frozen in liquid nitrogen. Corneal cross sections 35-μm thick were cut on a cryostat, mounted on a slide, and imaged by two-photon fluorescence microscopy. Mean (SD) concentrations were calculated from five globes tested for each protocol. Peak riboflavin concentration of 0.09% (± 0.01) was observed within the most superficial stroma (stromal depth 0-10 μm) in positive controls (epithelium-off). At the same depth, peak stromal riboflavin concentrations for MedioCross TE, Ricrolin+, Paracel/Xtra, and Ribocross TE were 0.054% (± 0.01), 0.031% (0.003), 0.021% (± 0.001), and 0.015% (± 0.004), respectively. At a depth of 300 μm (within the demarcation zone commonly seen after corneal cross-linking), the stromal concentration in epithelium-off positive controls was 0.075% (± 0.006), while at the same depth MedioCross TE and Ricrolin+ achieved 0.018% (± 0.006) and 0.016% (0.002), respectively. None of the remaining transepithelial protocols achieved concentrations above 0.005% at this same 300-μm depth. Overall, MedioCross TE was the best-performing transepithelial formulation. Corneal epithelium is a significant barrier to riboflavin absorption into the stroma. Existing commercial transepithelial CXL protocols achieve relatively low riboflavin concentrations in the anterior corneal stroma when compared to gold standard epithelium-off absorption

Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy.

Science.gov (United States)

Costa, Marina; Cerqueira, Mariana T; Santos, Tírcia C; Sampaio-Marques, Belém; Ludovico, Paula; Marques, Alexandra P; Pirraco, Rogério P; Reis, Rui L

2017-06-01

Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditions for up to 8days in the absence of extrinsic growth factors. Immunocytochemistry against CD31 and CD146 revealed spontaneous organization in capillary-like structures, more complex after hypoxic conditioning. Inhibition of HIF-1α pathway hindered capillary-like structure formation in SVF cells cultured in hypoxia, suggesting a role of HIF-1α. Moreover, hypoxic SVF cells showed a trend for increased secretion of angiogenic factors, which was reflected in increased network formation by endothelial cells cultured on matrigel using that conditioned medium. In vivo implantation of SVF CS in a mouse hind limb ischemia model revealed that hypoxia-conditioned CS led to improved restoration of blood flow. Both in vitro and in vivo data suggest that SVF CS can be used as simple and cost-efficient tools to promote functional vascularization of TE constructs. Neovascularization after implantation is a major obstacle for producing clinically viable cell sheet-based tissue engineered constructs. Strategies using endothelial cells and extrinsic angiogenic growth factors are expensive and time consuming and may raise concerns of tumorigenicity. In this manuscript, we describe a simplified approach using angiogenic cell sheets fabricated from the stromal vascular fraction of adipose tissue. The strong angiogenic behavior of these cell sheets, achieved without the use of external growth factors, was further stimulated by low oxygen culture. When implanted in an in vivo model of hind limb

Adipose derived stromal vascular fraction improves early tendon healing: an experimental study in rabbits

Directory of Open Access Journals (Sweden)

Mehdi Behfar

2011-11-01

Full Text Available Tendon never restores the complete biological and mechanical properties after healing. Bone marrow and recently adipose tissue have been used as the sources of mesenchymal stem cells, which have been proven to enhance tendon healing. Stromal vascular fraction (SVF, derived from adipose tissue by an enzymatic digestion, represents an alternative source of multipotent cells, which undergo differentiation into multiple lineages to be used in regenerative medicine. In the present study, we investigated potentials of this source on tendon healing. Twenty rabbits were divided into control and treatment groups. Five rabbits were used as donors of adipose tissue. The injury model was unilateral complete transection through the middle one third of deep digital flexor tendon. Immediately after suture repair, either fresh stromal vascular fraction from enzymatic digestion of adipose tissue or placebo was intratendinously injected into the suture site in treatments and controls, respectively. Cast immobilization was continued for two weeks after surgery. Animals were sacrificed at the third week and tendons underwent histological, immunohistochemical, and mechanical evaluations. By histology, improved fibrillar organization and remodeling of neotendon were observed in treatment group. Immunohistochemistry revealed an insignificant increase in collagen type III and I expression in treatments over controls. Mechanical testing showed significant increase in maximum load and energy absorption in SVF treated tendons. The present study showed that intratendinous injection of uncultured adipose derived stromal vascular fraction improved structural and mechanical properties of repaired tendon and it could be an effective modality for treating tendon laceration.

A Comparison of Different Corneal Iontophoresis Protocols for Promoting Transepithelial Riboflavin Penetration.

Science.gov (United States)

Gore, Daniel M; O'Brart, David P; French, Paul; Dunsby, Chris; Allan, Bruce D

2015-12-01

To measure corneal riboflavin penetration using different transepithelial iontophoresis protocols. Freshly enucleated rabbit eyes were divided into nine treatment groups of 4 eyes. One group, in which 0.1% wt/vol riboflavin was applied for 30 minutes without iontophoresis after corneal epithelial debridement, acted as a control. The remaining groups were treated with an intact epithelium using different riboflavin formulations and varying iontophoresis current, soak, and rinse times. After riboflavin application, eyes were snap frozen in liquid nitrogen. Corneal cross sections 35 μm thick were then imaged immediately by two-photon fluorescence microscopy, using image processing software to quantify stromal riboflavin concentration at different corneal depths. In the epithelium-on iontophoresis treatment groups, greater stromal riboflavin penetration was achieved with higher-concentration riboflavin solutions, greater iontophoresis dosage, and longer solution contact times. A protocol utilizing 0.25% wt/vol riboflavin with benzalkonium chloride (BAC) 0.01% and two cycles of applied current and subsequent soaking (1 mA 5 minutes, soak 5 minutes; 0.5 mA 5 minutes, soak 5 minutes) achieved similar stromal riboflavin penetration to epithelium-off controls. The best-performing non-BAC-containing protocol produced stromal riboflavin penetration approximately 60% that of epithelium-off controls. Riboflavin solutions containing saline resulted in minimal stromal penetration. Riboflavin loading within the epithelium was equivalent to or higher than that in the subjacent stroma, despite rinsing the ocular surface with balanced salt solution. Modified iontophoresis protocols can significantly improve transepithelial riboflavin penetration in experimental corneal collagen cross-linking.

Safety and Efficacy of Epithelium-On Corneal Collagen Cross-Linking Using a Multifactorial Approach to Achieve Proper Stromal Riboflavin Saturation

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Aleksandar Stojanovic

2012-01-01

Full Text Available Purpose. To evaluate the efficacy and safety of epithelium-on corneal collagen cross-linking (CXL using a multifactorial approach to achieve proper stromal riboflavin saturation. Methods. This non-randomized retrospective study comprised 61 eyes with progressive keratoconus treated with epithelium-on CXL. Chemical epithelial penetration enhancement (benzalkonium chloride-containing local medication and hypotonic riboflavin solution, mechanical disruption of the superficial epithelium, and prolongation of the riboflavin-induction time until verification of stromal saturation were used before the UVA irradiation. Uncorrected and corrected distance visual acuity (UDVA, CDVA, refraction, corneal topography, and aberrometry were evaluated at baseline and at 1, 3, 6, and 12 months postoperative. Results. At 12-month, UDVA and CDVA improved significantly. None of the eyes lost lines of CDVA, while 27.4% of the eyes gained 2 or more lines. Mean spherical equivalent decreased by 0.74 D, and mean cylindrical reduction was 1.15 D. Irregularity index and asymmetry from Scheimpflug-based topography and Max-K at the location of cone from Placido-based topography showed a significant decrease. Higher-order-aberration data demonstrated a slight reduction in odd-order aberrations S 3, 5,7 (=0.04. Postoperative pain without other complications was recorded. Conclusion. Epithelium-on CXL with our novel protocol appeared to be safe and effective in the treatment of progressive keratoconus.

Extrusão do anel intra-estromal corneano e vascularização do túnel Extrusion and vascularization of the intrastromal corneal ring tunnel

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Larissa Casteluber

2007-12-01

Full Text Available O objetivo deste trabalho é relatar e discutir os aspectos de um caso clínico em que foi observada a formação de neovascularização no túnel do anel intra-estromal corneano. Trata-se de paciente com ectasia corneana 4 anos após LASIK, comprovada pela paquimetria e topografia, e submetido ao implante de anel intra-estromal corneano. No terceiro ano de acompanhamento após implante do anel intraestromal, com o paciente em uso de lente de contato gelatinosa, verificou-se extrusão de um segmento e neovascularização no túnel. Removeu-se o segmento afetado, realizou-se fotocoagulação vascular, observando-se regressão completa do quadro neovascular.The purpose of this paper is to describe the clinical aspects of one case with deep corneal vascularization after corneal ring implantation to treat corneal ectasia due to LASIK 4 years before. The corneal ectasia diagnostic was performed by corneal pachimetry and topography. Intrastromal corneal ring segment was implanted. On the third year of follow-up, extrusion of one segment was noted and deep corneal neovascularization was found. The segment was removed, laser photocoagulation was applied and complete vascular regression was observed.

Tissue and cellular biomechanics during corneal wound injury and repair.

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Raghunathan, Vijay Krishna; Thomasy, Sara M; Strøm, Peter; Yañez-Soto, Bernardo; Garland, Shaun P; Sermeno, Jasmyne; Reilly, Christopher M; Murphy, Christopher J

2017-08-01

Corneal wound healing is an enormously complex process that requires the simultaneous cellular integration of multiple soluble biochemical cues, as well as cellular responses to the intrinsic chemistry and biophysical attributes associated with the matrix of the wound space. Here, we document how the biomechanics of the corneal stroma are altered through the course of wound repair following keratoablative procedures in rabbits. Further we documented the influence that substrate stiffness has on stromal cell mechanics. Following corneal epithelial debridement, New Zealand white rabbits underwent phototherapeutic keratectomy (PTK) on the right eye (OD). Wound healing was monitored using advanced imaging modalities. Rabbits were euthanized and corneas were harvested at various time points following PTK. Tissues were characterized for biomechanics with atomic force microscopy and with histology to assess inflammation and fibrosis. Factor analysis was performed to determine any discernable patterns in wound healing parameters. The matrix associated with the wound space was stiffest at 7days post PTK. The greatest number of inflammatory cells were observed 3days after wounding. The highest number of myofibroblasts and the greatest degree of fibrosis occurred 21days after wounding. While all clinical parameters returned to normal values 400days after wounding, the elastic modulus remained greater than pre-surgical values. Factor analysis demonstrated dynamic remodeling of stroma occurs between days 10 and 42 during corneal stromal wound repair. Elastic modulus of the anterior corneal stroma is dramatically altered following PTK and its changes coincide initially with the development of edema and inflammation, and later with formation of stromal haze and population of the wound space with myofibroblasts. Factor analysis demonstrates strongest correlation between elastic modulus, myofibroblasts, fibrosis and stromal haze thickness, and between edema and central corneal

Corneal Toxicity Following Exposure to Asclepias Tuberosa

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Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas

2017-01-01

PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small...... epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. RESULTS: The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa, whose latex contains cardenolides...... that inhibit the Na+/ K+-ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. CONCLUSION: Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity...

Corneal Regeneration After Photorefractive Keratectomy: A Review

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Javier Tomás-Juan

2015-07-01

Full Text Available Photorefractive keratectomy (PRK remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain.

Corneal Toxicity Following Exposure to Asclepias Tuberosa.

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Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas; Heegaard, Steffen

2017-01-01

To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa . Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa , whose latex contains cardenolides that inhibit the Na + / K + -ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity caused by exposure to latex from Asclepias tuberosa . Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity.

A case of corneal cystinosis in a patient with rickets and chronic renal failure

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Jae Yon Won

2015-01-01

Full Text Available A 22-year-old man diagnosed with nephropathic cystinosis at the age of 4 years was found to have progressive bilateral corneal crystal deposition. He presented with severe photophobia and decreased visual acuity. Ocular cystinosis was diagnosed on observing the typical crystals. Optical coherence tomography showed multiple areas of stromal hyperreflectivity due to crystal deposits within the corneal stroma. Ex vivo transmission electron microscopy of the cornea showed pathognomonic crystal deposits in corneal stromal keratocytes. Using polymerase chain reaction sequencing of the entire coding region, we identified five gene mutations, including two unreported mutations.

Corneal regeneration by induced human buccal mucosa cultivated on an amniotic membrane following alkaline injury.

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Man, Rohaina Che; Yong, Then Kong; Hwei, Ng Min; Halim, Wan Haslina Wan Abdul; Zahidin, Aida Zairani Mohd; Ramli, Roszalina; Saim, Aminuddin Bin; Idrus, Ruszymah Binti Hj

2017-01-01

Various clinical disorders and injuries, such as chemical, thermal, or mechanical injuries, may lead to corneal loss that results in blindness. PURPOSE : The aims of this study were to differentiate human buccal mucosa (BMuc) into corneal epithelial-like cells, to fabricate engineered corneal tissue using buccal mucosal epithelial cells, and to reconstruct a damaged corneal epithelium in a nude rat model. BMuc were subjected to 10 d of induction factors to investigate the potential of cells to differentiate into corneal lineages. Corneal stem cell markers β1-integrin, C/EBPδ, ABCG2, p63, and CK3 were upregulated in the gene expression analysis in induced BMuc, whereas CK3 and p63 showed significant protein expression in induced BMuc compared to the uninduced cells. BMuc were then left to reach 80% confluency after differential trypsinization. The cells were harvested and cultivated on a commercially available untreated air-dried amniotic membrane (AM) in a Transwell system in induction medium. The corneal constructs were fabricated and then implanted into damaged rat corneas for up to 8 weeks. A significant improvement was detected in the treatment group at 8 weeks post-implantation, as revealed by slit lamp biomicroscopy analysis. The structure and thickness of the corneal layer were also analyzed using histological staining and time-domain optical coherence tomography scans and were found to resemble a native corneal layer. The protein expression for CK3 and p63 were continuously detected throughout the corneal epithelial layer in the corneal construct. In conclusion, human BMuc can be induced to express a corneal epithelial-like phenotype. The addition of BMuc improves corneal clarity, prevents vascularization, increases corneal thickness and stromal alignment, and appears to have no adverse effect on the host after implantation.

Corneal Regeneration After Photorefractive Keratectomy: A Review.

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Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger

2015-01-01

Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Reconstruction of limbal stem cell deficient corneal surface with induced human bone marrow mesenchymal stem cells on amniotic membrane.

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Rohaina, Che Man; Then, Kong Yong; Ng, Angela Min Hwei; Wan Abdul Halim, Wan Haslina; Zahidin, Aida Zairani Mohd; Saim, Aminuddin; Idrus, Ruszymah B H

2014-03-01

The cornea can be damaged by a variety of clinical disorders or chemical, mechanical, and thermal injuries. The objectives of this study were to induce bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface defects in a limbal stem cell deficiency model. BMSCs were induced to corneal lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation of corneal stem cell markers; β1-integrin, C/EBPδ, ABCG2, and p63, increased protein expression of CK3 and p63 significantly compared with the uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on amniotic membrane in a transwell co-culture system and were grown in limbal medium. Limbal stem cell deficiency models were induced by alkaline injury, and the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed remarkable improvement in corneal regeneration in terms of corneal clarity and reduced vascularization. Histologic and optical coherence tomography analyses demonstrated comparable corneal thickness and achieved stratified epithelium with a compact stromal layer resembling that of normal cornea. CK3 and p63 were expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced into corneal epithelial lineage, and these cells are viable for the formation of TEC, to be used for the reconstruction of the corneal surface in the limbal stem cell deficient model. Copyright © 2014 Mosby, Inc. All rights reserved.

Clinical correlates of common corneal neovascular diseases:a literature review

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Nizar Saleh Abdelfattah

2015-02-01

Full Text Available A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization, leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far.

A case report of central toxic keratopathy in a patient post TransPRK (followed by corneal collagen cross-linking).

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Davey, Nicholas; Aslanides, Ioannis M; Selimis, Vasilis

2017-01-01

The purpose of this article is to report a case of central toxic keratopathy in a patient post transepithelial photorefractive keratectomy (TransPRK), followed immediately by corneal collagen cross-linking. This article describes the case of a 26-year-old male after bilateral aberration-free, TransPRK laser (Schwind Amaris 750S). The procedure was performed for compound myopic astigmatism in November 2015, followed immediately by accelerated corneal collagen cross-linking for early keratoconus. From day 3 post-op, tear film debris underneath both contact lenses with corneal haze and early, progressive central anterior stromal opacity formation only in the left eye were noted. At 2 weeks post-op, the left eye was noted to have a significant hyperopic shift with central corneal thinning in the anterior stroma. A central anterior stromal dense opacity had formed in the left eye with the surrounding superficial stromal haze. As of month 2, the opacity gradually started to improve in size and density. The hyperopic shift peaked at 2 months and continued to improve, largely due to epithelial compensation with a gradual recovery of stromal thickness. The question remains as to what provokes the typical central corneal necrosis/thinning in central toxic keratopathy. We hypothesize that the space between the contact lens and the corneal surface post TransPRK is prone to a "pseudo-interface pathology" that could mimic diffuse lamellar keratitis-like pathology. Suboptimal lid hygiene, resulting in tear film combinations of bacteria, inflammatory cells, matrix metalloproteinases and other proteolytic enzymes, contributes to the degradation of vulnerable, exposed collagen stromal tissue post TransPRK or any surface corneal ablation. Refractive surgeons should maintain a healthy lid margin and tear film, especially in contact lens wearers, to prevent potential complications in refractive surgery procedures.

Changes in adipose tissue stromal-vascular cells in primary culture due to porcine sera

International Nuclear Information System (INIS)

Jewell, D.E.; Hausman, G.J.

1986-01-01

This study was conducted to determine the response of rat stromal-vascular cells to pig sea. Sera were collected from unselected contemporary (lean) and high backfat thickness selected (obese) pigs. Sera from obese pigs were collected either by exsanguination or cannulation. sera from lean pigs during the growing phase (45 kg) and the fattening phase (100-110 kg) were collected. Stromal-vascular cells derived rom rat inguinal tissue were cultured on either 25 cm 2 flasks, collagen-coated coverslips or petri dishes. Cell proliferation was measured by [ 3 H]-thymidine incorporation during the fourth day of culture. Coverslip cultures were used for histochemical analysis. Petri dish cultures were used for analysis of Sn-glycerol-3-phosphate dehydrogenase (GPDH) activity. All cells were plated for 24 hours in media containing 10 fetal bovine sera. Test media contained 2.5, 5.0, 10.0% sera. Sera from obese pigs increased GPDH activity and fat cell production when compared to the lean controls. The increased concentration of sera increased esterase activity and lipid as measured with oil red O. The sera from obese pigs collected at slaughter stimulated more fat cell production than obese sera collected by cannulation. These studies show there are adipogenic factors in obese pigs sera which promote fat cell development in primary cell culture

Riboflavin for corneal cross-linking.

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O'Brart, D P S

2016-06-01

Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A (UVA) radiation is the first therapeutic modality that appears to arrest the progression of keratoconus and other corneal ectasias. Riboflavin is central to the process, acting as a photosensitizer for the production of oxygen singlets and riboflavin triplets. These free radicals drive the CXL process within the proteins of the corneal stroma, altering its biomechanical properties. Riboflavin also absorbs the majority of the UVA radiation, which is potentially cytotoxic and mutagenic, within the anterior stroma, preventing damage to internal ocular structures, such as the corneal endothelium, lens and retina. Clinical studies report cessation of ectatic progression in over 90% of cases and the majority document significant improvements in visual, keratometric and topographic parameters. Clinical follow-up is limited to 5-10 years, but suggests sustained stability and enhancement in corneal shape. Sight-threatening complications are rare. The optimal stromal riboflavin dosage for CXL is as yet undetermined. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

Resolvin E1 analog RX-10045 0.1% reduces corneal stromal haze in rabbits when applied topically after PRK.

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Torricelli, Andre A M; Santhanam, Abirami; Agrawal, Vandana; Wilson, Steven E

2014-01-01

To perform a masked study to determine whether resolvin E1 (RvE1), a lipid-derived immunomodulator, could regulate the development of corneal haze and opacity-related myofibroblasts after opacity-generating high correction photorefractive keratectomy (PRK) in rabbits. Three groups of eight rabbits each were included in the study. Nine diopter (D) PRK for myopia was performed in each test cornea, and the eyes were treated with 30 µl of topical solution every 4 h (six times a day) for 5 days starting immediately after PRK. Group 1 was treated with 0.1% RX-10045, a prodrug of an RvE1 analog; group 2 was treated with 0.01% RX-10045; and group 3 was treated with vehicle control solution. At 1 month after PRK, haze was graded at the slit-lamp by a masked observer. Immunohistochemistry for α-smooth muscle actin (SMA) was performed on the central cornea of each test eye to determine the anterior stromal myofibroblast density. Corneal opacity was significantly lower in the 0.1% RX-10045 group, but not the 0.01% RX-10045 group, compared to the vehicle control group (p=0.029), at 1 month after -9.0D PRK. At 1 month after -9.0D PRK, SMA+ myofibroblast densities in the anterior stroma were not statistically significantly different among the three groups, although a trend toward lower myofibroblast generation was noted in the 0.1% RX-10045 group. Topical 0.1% RX-10045, a prodrug of an RvE1 analog, reduces corneal opacity after haze-generating PRK in rabbits. Further studies are needed to determine the precise points at which RvE1 decreases corneal opacity after injury.

A Case of Retained Graphite Anterior Chamber Foreign Body Masquerading as Stromal Keratitis

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Han, Eun Ryung; Wee, Won Ryang; Lee, Jin Hak

2011-01-01

We report a case of a retained graphite anterior chamber foreign body that was masquerading as stromal keratitis. A 28-year-old male visited with complaints of visual disturbance and hyperemia in his right eye for four weeks. On initial examination, he presented with a stromal edema involving the inferior half of the cornea, epithelial microcysts, and moderate chamber inflammation. Suspecting herpetic stromal keratitis, he was treated with anti-viral and anti-inflammatory agents. One month after the initial visit, anterior chamber inflammation was improved and his visual acuity recovered to 20/20, but subtle corneal edema still remained. On tapering the medication, after three months, a foreign body was incidentally identified in the inferior chamber angle and was surgically removed resulting in complete resolution of corneal edema. The removed foreign body was a fragment of graphite and he subsequently disclosed a trauma with mechanical pencil 12 years earlier. This case showed that the presence of an anterior chamber foreign body should always be considered in the differential diagnosis of idiopathic localized corneal edema. PMID:21461226

Corneal structure and transparency

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Meek, Keith M.; Knupp, Carlo

2015-01-01

The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID:26145225

The Influence of Lamellar Orientation on Corneal Material Behavior: Biomechanical and Structural Changes in an Avian Corneal Disorder

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Elsheikh, Ahmed; Kassem, Wael; Kamma-Lorger, Christina S.; Hocking, Paul M.; White, Nick; Inglehearn, Chris F.; Ali, Manir; Meek, Keith M.

2011-01-01

Purpose. Retinopathy, globe enlarged (RGE) is an inherited genetic disease of chickens with a corneal phenotype characterized by loss of tissue curvature and changes in peripheral collagen fibril alignment. This study aimed to characterize the material behavior of normal and RGE chicken corneas under inflation and compare this with new spatial- and depth-resolved microstructural information to investigate how stromal fibril architecture determines corneal behavior under intraocular pressure (IOP). Methods. Six RGE chicken corneas and six age-matched normal controls were tested using trephinate inflation and their stress-strain behavior determined as a function of posterior pressure. Second harmonic generation mulitphoton microscopy was used to compare the in-plane appearance and degree of through-plane interlacing of collagen lamellae between normal and mutant corneas. Results. RGE corneas displayed a 30–130% increase in material stiffness [Etangent(RGE) = 0.94 ± 0.18 MPa to 3.09 ± 0.66 MPa; Etangent(normals) = 0.72 ± 0.13 MPa to 1.34 ± 0.35 MPa] (P ≤ 0.05). The normal in-plane disposition of anterior collagen in the peripheral cornea was altered in RGE but through-plane lamellar interlacing was unaffected. Conclusions. This article demonstrates changes in corneal material behavior in RGE that are qualitatively consistent with microstructural collagen alterations identified both herein and previously. This study indicates that, in general, changes in stromal fibril orientation may significantly affect corneal material behavior and thereby its response to IOP. PMID:21051696

A case report of central toxic keratopathy in a patient post TransPRK (followed by corneal collagen cross-linking

Directory of Open Access Journals (Sweden)

Davey N

2017-04-01

Full Text Available Nicholas Davey, Ioannis M Aslanides, Vasilis Selimis Emmetropia Mediterranean Eye Institute, Heraklion, Crete, Greece Purpose: The purpose of this article is to report a case of central toxic keratopathy in a patient post transepithelial photorefractive keratectomy (TransPRK, followed immediately by corneal collagen cross-linking.Methods: This article describes the case of a 26-year-old male after bilateral aberration-free, TransPRK laser (Schwind Amaris 750S. The procedure was performed for compound myopic astigmatism in November 2015, followed immediately by accelerated corneal collagen cross-linking for early keratoconus.Results: From day 3 post-op, tear film debris underneath both contact lenses with corneal haze and early, progressive central anterior stromal opacity formation only in the left eye were noted. At 2 weeks post-op, the left eye was noted to have a significant hyperopic shift with central corneal thinning in the anterior stroma. A central anterior stromal dense opacity had formed in the left eye with the surrounding superficial stromal haze. As of month 2, the opacity gradually started to improve in size and density. The hyperopic shift peaked at 2 months and continued to improve, largely due to epithelial compensation with a gradual recovery of stromal thickness.Conclusion: The question remains as to what provokes the typical central corneal necrosis/thinning in central toxic keratopathy. We hypothesize that the space between the contact lens and the corneal surface post TransPRK is prone to a “pseudo-interface pathology” that could mimic diffuse lamellar keratitis-like pathology. Suboptimal lid hygiene, resulting in tear film combinations of bacteria, inflammatory cells, matrix metalloproteinases and other proteolytic enzymes, contributes to the degradation of vulnerable, exposed collagen stromal tissue post TransPRK or any surface corneal ablation. Refractive surgeons should maintain a healthy lid margin and tear

Automated Detection and Classification of Corneal Haze Using Optical Coherence Tomography in Patients With Keratoconus After Cross-Linking.

Science.gov (United States)

Dhaini, Ahmad R; Abdul Fattah, Maamoun; El-Oud, Sara Maria; Awwad, Shady T

2018-03-13

To evaluate a proposed technology for offering objective grading and mapping of corneal haze as detected by corneal spectral domain optical coherence tomography after corneal cross-linking. This was a retrospective study to evaluate corneal optical coherence tomography images performed on 44 eyes of 44 patients who underwent corneal cross-linking between January 2014 and May 2015, at the American University of Beirut Medical Center. Overall average brightness of the cornea was markedly increased from 43.4% (±6.0) at baseline to 50.2% (±4.4) at 1 month, 47.9% (±4.4) at 3 months, and 46.4% (±5.7) at 6 months with P <0.001, <0.001, and 0.005, respectively. In the anterior stroma, the average brightness significantly increased at 1, 3, and 6 months with values of 54.8% (±3.9), 52.5% (±5.2), and 49.7% (±6.9) with P <0.001, <0.001, and 0.003, respectively. In the mid stroma, the change was clinically significant at 1 and 3 months, whereas in the posterior stroma, it was only significant at 1 month compared with baseline (P = 0.003). Overall, haze was mostly present at 1 month after surgery in all regions, especially in the anterior (32.1%; ±19.2) and mid stromal regions (9.1%; ±18.8), P <0.001 and 0.001, respectively. In contrast, haze in the posterior stromal region peaks at 3 and 6 months after surgery. Anterior stromal haze was the greatest in intensity and area and it was present for a longer time span than mid and posterior stromal haze. At 12 months, the anterior stroma had still more haze intensity than preoperatively. This image-based software can provide objective and valuable quantitative measurements of corneal haze, which may impact clinical decision-making after different corneal surgeries.

Control of Scar Tissue Formation in the Cornea: Strategies in Clinical and Corneal Tissue Engineering

Directory of Open Access Journals (Sweden)

Samantha L. Wilson

2012-09-01

Full Text Available Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation.

Penetrating keratoplasty for treatment of corneal abscesses in horses – case report

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Zita Makra

2013-01-01

Full Text Available This case report describes the surgical technique and outcome of allograft transplantation to treat full thickness corneal abscesses in three horses. In all three cases penetrating keratoplasty was performed. Each affected eye had an abscess within the corneal stroma. An initial full thickness circular corneal incision was made around the lesion. After excision of the stromal abscess the created defect was replaced with a larger diameter full thickness donor graft and the initial corneal incision was repaired. All of the horses that underwent penetrating keratoplasty procedure healed with a scar at the graft site and remained visual. Penetrating keratoplasty is an effective technique for surgical removal of medically nonresponsive full thickness stromal abscess in horses and results in a visual and cosmetically acceptable globe. The advantages of this technique compared to medical therapy are that there is less scarring, shorter healing times and less damage of the globe because of the concurrent uveitis. To the authors’ knowledge, clinical experience with penetrating keratoplasty in horses has not been reported in Europe so far.

The relationship between corneal biomechanical properties and confocal microscopy findings in normal and keratoconic eyes.

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Hurmeric, Volkan; Sahin, Afsun; Ozge, Gokhan; Bayer, Atilla

2010-06-01

To investigate the relationship between corneal biomechanical properties and confocal microscopy (CM) findings in normal and keratoconic eyes. The study consisted of 28 eyes of 28 healthy volunteers and 23 eyes of 15 patients with keratoconus. The diagnosis of keratoconus was made with corneal topography and clinical findings. The corneal hysteresis (CH) and corneal resistance factor (CRF) were measured by the ocular response analyzer. In vivo CM was performed with NIDEK Confoscan 3. CH and CRF were compared with corneal morphological findings (detailed cell counts of endothelial, stromal, and epithelial cells) in vivo. CH was 10.1 +/- 1.3 mm Hg in normal eyes and 7.4 +/- 1.5 mm Hg in keratoconic eyes (P < 0.0001). CRF was 10.1 +/- 1.8 mm Hg in normal eyes and 6.2 +/- 1.4 mm Hg in keratoconic eyes (P < 0.0001). CH and CRF were negatively correlated with full-thickness stromal keratocyte density (P < 0.01; r = -0.52 and P < 0.001; r = -0.67, respectively) in healthy eyes. Keratocyte density of the posterior half of the stroma was found to be significantly related with CRF in healthy eyes (beta = -0.404; P = 0.01). There was no significant relationship among CH, CRF, and CM findings in eyes with keratoconus. There is a significant relationship between CRF and keratocyte density of the posterior half of the stroma in healthy eyes. Our results suggest that corneal elasticity is related to not only stromal matrix but also cellular structure of the cornea.

High Aldehyde Dehydrogenase Activity Identifies a Subset of Human Mesenchymal Stromal Cells with Vascular Regenerative Potential.

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Sherman, Stephen E; Kuljanin, Miljan; Cooper, Tyler T; Putman, David M; Lajoie, Gilles A; Hess, David A

2017-06-01

During culture expansion, multipotent mesenchymal stromal cells (MSCs) differentially express aldehyde dehydrogenase (ALDH), an intracellular detoxification enzyme that protects long-lived cells against oxidative stress. Thus, MSC selection based on ALDH-activity may be used to reduce heterogeneity and distinguish MSC subsets with improved regenerative potency. After expansion of human bone marrow-derived MSCs, cell progeny was purified based on low versus high ALDH-activity (ALDH hi ) by fluorescence-activated cell sorting, and each subset was compared for multipotent stromal and provascular regenerative functions. Both ALDH l ° and ALDH hi MSC subsets demonstrated similar expression of stromal cell (>95% CD73 + , CD90 + , CD105 + ) and pericyte (>95% CD146 + ) surface markers and showed multipotent differentiation into bone, cartilage, and adipose cells in vitro. Conditioned media (CDM) generated by ALDH hi MSCs demonstrated a potent proliferative and prosurvival effect on human microvascular endothelial cells (HMVECs) under serum-free conditions and augmented HMVEC tube-forming capacity in growth factor-reduced matrices. After subcutaneous transplantation within directed in vivo angiogenesis assay implants into immunodeficient mice, ALDH hi MSC or CDM produced by ALDH hi MSC significantly augmented murine vascular cell recruitment and perfused vessel infiltration compared with ALDH l ° MSC. Although both subsets demonstrated strikingly similar mRNA expression patterns, quantitative proteomic analyses performed on subset-specific CDM revealed the ALDH hi MSC subset uniquely secreted multiple proangiogenic cytokines (vascular endothelial growth factor beta, platelet derived growth factor alpha, and angiogenin) and actively produced multiple factors with chemoattractant (transforming growth factor-β, C-X-C motif chemokine ligand 1, 2, and 3 (GRO), C-C motif chemokine ligand 5 (RANTES), monocyte chemotactic protein 1 (MCP-1), interleukin [IL]-6, IL-8) and matrix

Acute corneal hydrops in keratoconus

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Prafulla K Maharana

2013-01-01

Full Text Available Acute corneal hydrops is a condition characterized by stromal edema due to leakage of aqueous through a tear in descemet membrane. The patient presents with sudden onset decrease in vision, photophobia, and pain. Corneal thinning and ectasias combined with trivial trauma to the eye mostly by eye rubbing is considered as the underlying cause. With conservative approach self-resolution takes around 2 to 3 months. Surgical intervention is required in cases of non-resolution of corneal edema to avoid complications and for early visual rehabilitation. Intracameral injection of air or gas such as perflouropropane is the most common surgical procedure done. Recent investigative modality such as anterior segment optical coherence tomography is an extremely useful tool for diagnosis, surgical planning, and postoperative follow up. Resolution of hydrops may improve the contact lens tolerance and visual acuity but most cases require keratoplasty for visual rehabilitation.

Culture of equine bone marrow mononuclear fraction and adipose tissue-derived stromal vascular fraction cells in different media

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Gesiane Ribeiro

2013-12-01

Full Text Available The objective of this study was to evaluate the culture of equine bone marrow mononuclear fraction and adipose tissue - derived stromal vascular fraction cells in two different cell culture media. Five adult horses were submitted to bone marrow aspiration from the sternum, and then from the adipose tissue of the gluteal region near the base of the tail. Mononuclear fraction and stromal vascular fraction were isolated from the samples and cultivated in DMEM medium supplemented with 10% fetal bovine serum or in AIM-V medium. The cultures were observed once a week with an inverted microscope, to perform a qualitative analysis of the morphology of the cells as well as the general appearance of the cell culture. Colony-forming units (CFU were counted on days 5, 15 and 25 of cell culture. During the first week of culture, differences were observed between the samples from the same source maintained in different culture media. The number of colonies was significantly higher in samples of bone marrow in relation to samples of adipose tissue.

The effect of vitamin C deficiency and chronic ultraviolet-B exposure on corneal ultrastructure: a preliminary investigation

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Hayes, Sally; Cafaro, Thamara A.; Boguslawska, Patrycja J.; Kamma-Lorger, Christina S.; Boote, Craig; Harris, Jonathan; Young, Robert; Hiller, Jennifer; Terrill, Nicholas; Meek, Keith M.

2011-01-01

Purpose In the visually debilitating condition of climatic droplet keratopathy, corneal transparency is progressively lost. Although the precise cause of the disease and the mechanism by which it progresses are not known, a lifetime exposure to high solar radiation and a vitamin C–deficient diet may be involved in its development. This study examines the effect of dietary ascorbate levels and ultraviolet (UV)-B exposure on corneal stromal structure. Methods Eight guinea pigs were divided into four treatment groups (A, B, C, and D). For 15 weeks, Groups A and C were fed an ascorbate-rich diet (2 mg/100 g bodyweight/day), while Groups B and D received an ascorbate-deficient diet (0.07 mg/100 g bodyweight/day). For the last 12 weeks of the study, Groups C and D also experienced chronic UVB exposure (0.12 J/cm2 for 40 min/day). Following euthanasia, the corneas were enucleated and their stromal ultrastructure examined using X-ray scattering and electron microscopy. Results UVB exposure resulted in an increased corneal thickness (p<0.001), but this was not accompanied by a widespread expansion of the collagen fibrillar array, and in the case of ascorbate-deficient animals, stromal thickening was associated with the compaction of collagen fibrils (p<0.01). Neither UVB exposure nor ascorbic acid deficiency caused any change in the average diameter or D-periodicity of the stromal collagen fibrils. Conclusions UVB-induced changes in the corneal ultrastructure were most pronounced in animals fed an ascorbic acid–deficient diet. This suggests that ascorbic acid may play a vital role in protecting the corneal stroma from the harmful effects of UVB. PMID:22171156

Removal of the basement membrane enhances corneal wound healing.

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Pal-Ghosh, Sonali; Pajoohesh-Ganji, Ahdeah; Tadvalkar, Gauri; Stepp, Mary Ann

2011-12-01

Recurrent corneal erosions are painful and put patients' vision at risk. Treatment typically begins with debridement of the area around the erosion site followed by more aggressive treatments. An in vivo mouse model has been developed that reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously within two weeks after a single 1.5 mm corneal debridement wound created using a dulled-blade. This study was conducted to determine whether 1) inhibiting MMP9 function during healing after dulled-blade wounding impacts erosion development and 2) wounds made with a rotating-burr heal without erosions. Oral or topical inhibition of MMPs after dulled-blade wounding does not improve healing. Wounds made by rotating-burr heal with significantly fewer erosions than dulled-blade wounds. The localization of MMP9, β4 integrin and basement membrane proteins (LN332 and type VII collagen), immune cell influx, and reinnervation of the corneal nerves were compared after both wound types. Rotating-burr wounds remove the anterior basement membrane centrally but not at the periphery near the wound margin, induce more apoptosis of corneal stromal cells, and damage more stromal nerve fibers. Despite the fact that rotating-burr wounds do more damage to the cornea, fewer immune cells are recruited and significantly more wounds resolve completely. Copyright © 2011 Elsevier Ltd. All rights reserved.

Response of human corneal fibroblasts on silk film surface patterns.

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Gil, Eun Seok; Park, Sang-Hyug; Marchant, Jeff; Omenetto, Fiorenzo; Kaplan, David L

2010-06-11

Transparent, biodegradable, mechanically robust, and surface-patterned silk films were evaluated for the effect of surface morphology on human corneal fibroblast (hCF) cell proliferation, orientation, and ECM deposition and alignment. A series of dimensionally different surface groove patterns were prepared from optically graded glass substrates followed by casting poly(dimethylsiloxane) (PDMS) replica molds. The features on the patterned silk films showed an array of asymmetric triangles and displayed 37-342 nm depths and 445-3 582 nm widths. hCF DNA content on all patterned films were not significantly different from that on flat silk films after 4 d in culture. However, the depth and width of the grooves influenced cell alignment, while the depth differences affected cell orientation; overall, deeper and narrower grooves induced more hCF orientation. Over 14 d in culture, cell layers and actin filament organization demonstrated that confluent hCFs and their cytoskeletal filaments were oriented along the direction of the silk film patterned groove axis. Collagen type V and proteoglycans (decorin and biglycan), important markers of corneal stromal tissue, were highly expressed with alignment. Understanding corneal stromal fibroblast responses to surface features on a protein-based biomaterial applicable in vivo for corneal repair potential suggests options to improve corneal tissue mimics. Further, the approaches provide fundamental biomaterial designs useful for bioengineering oriented tissue layers, an endemic feature in most biological tissue structures that lead to critical tissue functions.

Therapeutic Effects of Topical Netrin-4 Inhibits Corneal Neovascularization in Alkali-Burn Rats

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Han, Yun; Shao, Yi; Liu, Tingting; Qu, Yang-Luowa; Li, Wei; Liu, Zuguo

2015-01-01

Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues. PMID:25853509

Area and depth of surfactant-induced corneal injury predicts extent of subsequent ocular responses.

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Jester, J V; Petroll, W M; Bean, J; Parker, R D; Carr, G J; Cavanagh, H D; Maurer, J K

1998-12-01

To correlate area and depth of initial corneal injury induced by surfactants of differing type and irritant properties with corneal responses and outcome in the same animals over time by using in vivo confocal microscopy (CM). Six groups of six adult rabbits were treated with anionic, cationic, and nonionic surfactants that caused different levels of ocular irritation. Test materials included slight irritants: 5% sodium lauryl sulfate (SLS), polyoxyethylene glycol monoalkyl ether (POE), and 5% 3-isotridecyloxypropyl-bis(polyoxyethylene) ammonium chloride (ITDOP); mild irritants: 5% 3-decyloxypropyl-bis(polyoxyethylene) amine (DOP) and sodium linear alkylbenzene sulfonate (LAS); and a moderate irritant: a proprietary detergent (DTRGT). Ten microliters surfactant were directly applied to the cornea of one eye of each rabbit. Ten untreated rabbits served as control subjects. Area and depth of initial injury was determined by using in vivo CM to measure epithelial thickness, epithelial cell size, corneal thickness, and depth of stromal injury in four corneal regions at 3 hours and at day 1. Area and depth of corneal responses to injury were evaluated at various times from days 3 through 35 by macroscopic grading and quantitative confocal microscopy through-focusing (CMTF). In vivo CM revealed corneal injury with slight irritants to be restricted to the epithelium, whereas the mild and moderate irritants caused complete epithelial cell loss with increasing anterior stromal damage: DOP < LAS < DTRGT. With the slight ocular irritants there was little or no change in corneal thickness or the CMTF intensity profiles. Three hours after treatment, mild and moderate ocular irritants caused a significant increase in corneal thickness, which peaked at day 1 with DOP (483.3+/-80.1 microm) and LAS (572.3+/-60.0 microm) and day 3 with DTRGT (601.4+/-68.7 microm); returning to normal (similar to control values) by day 7 with DOP and day 35 with LAS and DTRGT. The CMTF intensity

A Rare Form of Corneal Opacity Associated with Spondyloepiphyseal Dysplasia Congenita

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Yuichiro Ishida

2018-02-01

Full Text Available A 13-year-old Japanese female diagnosed with spondyloepiphyseal dysplasia congenita (SEDC was referred for ophthalmologic evaluation. Examination with slit-lamp and optical coherence tomography revealed bilateral thin cornea with diffuse corneal opacity which was localised at the posterior stromal depth in the central cornea. Unlike the two previously reported cases of diffuse and nodular patterns of corneal opacity in SEDC, the current case exhibited a rare form of corneal opacity. SEDC is one of the type II collagenopathies, characterised by dwarfism because the mutations in COL2A1 prevent bone growth. Although the existence of type II collagen has not been reported in the human corneal stroma, the aetiology of the opacity in the corneal stroma in SEDC type II collagenopathy is of interest.

Corneal Stromal Cell Growth on Gelatin/Chondroitin Sulfate Scaffolds Modified at Different NHS/EDC Molar Ratios

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Jui-Yang Lai

2013-01-01

Full Text Available A nanoscale modification strategy that can incorporate chondroitin sulfate (CS into the cross-linked porous gelatin materials has previously been proposed to give superior performance for designed corneal keratocyte scaffolds. The purpose of this work was to further investigate the influence of carbodiimide chemistry on the characteristics and biofunctionalities of gelatin/CS scaffolds treated with varying N-hydroxysuccinimide (NHS/1-ethyl-3-(3-dimethyl aminopropyl carbodiimide hydrochloride (EDC molar ratios (0-1 at a constant EDC concentration of 10 mM. Results of Fourier transform infrared spectroscopy and dimethylmethylene blue assays consistently indicated that when the NHS to EDC molar ratio exceeds a critical level (i.e., 0.5, the efficiency of carbodiimide-mediated biomaterial modification is significantly reduced. With the optimum NHS/EDC molar ratio of 0.5, chemical treatment could achieve relatively high CS content in the gelatin scaffolds, thereby enhancing the water content, glucose permeation, and fibronectin adsorption. Live/Dead assays and interleukin-6 mRNA expression analyses demonstrated that all the test samples have good cytocompatibility without causing toxicity and inflammation. In the molar ratio range of NHS to EDC from 0 to 0.5, the cell adhesion ratio and proliferation activity on the chemically modified samples significantly increased, which is attributed to the increasing CS content. Additionally, the materials with highest CS content (0.143 ± 0.007 nmol/10 mg scaffold showed the greatest stimulatory effect on the biosynthetic activity of cultivated keratocytes. These findings suggest that a positive correlation is noticed between the NHS to EDC molar ratio and the CS content in the biopolymer matrices, thereby greatly affecting the corneal stromal cell growth.

Latrunculin B and substratum stiffness regulate corneal fibroblast to myofibroblast transformation.

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Thomasy, Sara M; Raghunathan, Vijay Krishna; Miyagi, Hidetaka; Evashenk, Alexander T; Sermeno, Jasmyne C; Tripp, Geneva K; Morgan, Joshua T; Murphy, Christopher J

2018-05-01

The transformation of keratocytes and fibroblasts to myofibroblasts is important to corneal wound healing as well as formation of stromal haze. The purpose of this study was to determine the effect of latrunculin B, an actin cytoskeleton disruptor in conjunction with a fundamental biophysical cue, substrate stiffness, on myofibroblast transformation in vitro and in vivo. Rabbit corneal fibroblasts were cultured on substrates of differing compliance (1.5, 22, and 71 kPa) and tissue culture plastic (TCP; > 1 GPa) in media containing 0 or 10 ng/ml TGFβ1 for 72 h. Cells were treated with 0.4 μM Lat-B or DMSO for 30 min every 24 h for 72 h. RNA was collected from cells and expression of alpha-smooth muscle actin (α-SMA), keratocan, and ALDH1A1 determined using qPCR; immunocytochemistry was used to assess α-SMA protein expression. A rabbit phototherapeutic keratectomy (PTK) model was used to assess the impact of 0.1% Lat-B (n = 3) or 25% DMSO (vehicle control, n = 3) on corneal wound healing by assessment of epithelial wound size with fluorescein stain and semi-quantitative stromal haze scoring by an observer masked to treatment group as well as Fourier-domain optical coherence tomography (FD-OCT) at set time points. Statistical analysis was completed using one-way or two-way analysis of variance. Treatment with Lat-B versus DMSO resulted in significantly less αSMA mRNA (P ≤ 0.007) for RCF cells grown on 22 and 71 kPa substrates as well as TCP without or with TGFβ1, and significantly decreased α-SMA protein expression in RCFs cultured on the intermediate (22 kPa) stiffness in the absence (P = 0.028) or presence (P = 0.018) of TGFβ1. Treatment with Lat-B versus DMSO but did not significantly alter expression of keratocan or ALDH1A1 mRNA in RCFs (P > 0.05) in the absence or presence of TGFβ1, but RCFs grown on stiff hydrogels (71 kPa) had significantly more keratocan mRNA expression versus the 22 kPa hydrogel or

Corneal ring infiltration in contact lens wearers

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Seyed Ali Tabatabaei

2017-01-01

Full Text Available To report a case of atypical sterile ring infiltrates during wearing soft silicone hydrogel contact lens due to poor lens care. A 29-year-old woman presented with complaints of pain, redness, and morning discharge. She was wearing soft silicone hydrogel contact lens previously; her current symptoms began 1 week before presentation. On examination, best-corrected visual acuity was 20/40 in that eye. Slit-lamp examination revealed dense, ring-shaped infiltrate involving both the superficial and deep stromal layers with lucid interval to the limbus, edema of the epithelium, epithelial defect, and vascularization of the superior limbus. Cornea-specific in vivo laser confocal microscopy (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM, Heidelberg Engineering GmbH, Dossenheim, Germany revealed Langerhans cells and no sign of Acanthamoeba or fungal features, using lid scraping and anti-inflammatory drops; her vision completely recovered. We reported an atypical case of a sterile corneal ring infiltrate associated with soft contact lens wearing; smear, culture, and confocal microscopy confirmed a sterile inflammatory reaction.

Corneal Biomechanics in Ectatic Diseases: Refractive Surgery Implications

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Ambrósio, Jr, Renato; Correia, Fernando Faria; Lopes, Bernardo; Salomão, Marcella Q.; Luz, Allan; Dawson, Daniel G.; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Roberts, Cynthia J.

2017-01-01

Background: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. Method: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. Conclusions: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy. PMID:28932334

Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

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Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

2011-01-01

Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

Generation of Femtosecond Laser-Cut Decellularized Corneal Lenticule Using Hypotonic Trypsin-EDTA Solution for Corneal Tissue Engineering

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Man-Il Huh

2018-01-01

Full Text Available Purpose. To establish an optimized and standardized protocol for the development of optimal scaffold for bioengineering corneal substitutes, we used femtosecond laser to process human corneal tissue into stromal lenticules and studied to find the most efficient decellularization method among various reagents with different tonicities. Methods. The decellularization efficacy of several agents (0.1%, 0.25%, and 0.5% of Triton X-100, SDS, and trypsin-EDTA (TE, resp. with different tonicities was evaluated. Of all protocols, the decellularization methods, which efficiently removed nuclear materials examined as detected by immunofluorescent staining, were quantitatively tested for sample DNA and glycosaminoglycan (GAG contents, recellularization efficacy, and biocompatibilities. Results. 0.5% SDS in hypertonic and isotonic buffer, 0.25% TE in hypotonic buffer, and 0.5% TE in all tonicities completely decellularized the corneal lenticules. Of the protocols, decellularization with hypotonic 0.25 and 0.5% TE showed the lowest DNA contents, while the GAG content was the highest. Furthermore, the recellularization efficacy of the hypotonic TE method was better than that of the SDS-based method. Hypotonic TE-treated decellularized corneal lenticules (DCLs were sufficiently transparent and biocompatible. Conclusion. We generated an ideal protocol for DCLs using a novel method. Furthermore, it is possible to create a scaffold using a bioengineered corneal substitute.

Hair follicle growth by stromal vascular fraction-enhanced adipose transplantation in baldness

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Perez-Meza D

2017-07-01

Full Text Available David Perez-Meza,1 Craig Ziering,2 Marcos Sforza,3 Ganesh Krishnan,4 Edward Ball,5 Eric Daniels6 1Ziering Medical, Marbella, Spain; 2Ziering Medical, Los Angeles, CA, USA; 3The Hospital Group, Bromsgrove, Worcestershire, 4Ziering Medical, Birmingham, 5Ziering Medical, London, UK; 6Kerastem Technologies, San Diego, CA, USA Abstract: Great interest remains in finding new and emerging therapies for the treatment of male and female pattern hair loss. The autologous fat grafting technique is >100 years old, with a recent and dramatic increase in clinical experience over the past 10–15 years. Recently, in 2001, Zuk et al published the presence of adipose-derived stem cells, and abundant research has shown that adipose is a complex, biological active, and important tissue. Festa et al, in 2011, reported that adipocyte lineage cells support the stem cell niche and help drive the complex hair growth cycle. Adipose-derived regenerative cells (also known as stromal vascular fraction [SVF] is a heterogeneous group of noncultured cells that can be reliably extracted from adipose by using automated systems, and these cells work largely by paracrine mechanisms to support adipocyte viability. While, today, autologous fat is transplanted primarily for esthetic and reconstructive volume, surgeons have previously reported positive skin and hair changes posttransplantation. This follicular regenerative approach is intriguing and raises the possibility that one can drive or restore the hair cycle in male and female pattern baldness by stimulating the niche with autologous fat enriched with SVF. In this first of a kind patient series, the authors report on the safety, tolerability, and quantitative, as well as photographic changes, in a group of patients with early genetic alopecia treated with subcutaneous scalp injection of enriched adipose tissue. The findings suggest that scalp stem cell-enriched fat grafting may represent a promising alternative approach to

Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration.

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Lin, Ko-Jo; Loi, Mei-Xue; Lien, Gi-Shih; Cheng, Chieh-Feng; Pao, Hsiang-Yin; Chang, Yun-Chuang; Ji, Andrea Tung-Qian; Ho, Jennifer Hui-Chun

2013-06-14

Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound. Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 10(5)) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control. Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The therapeutic effect of the

Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration

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2013-01-01

Introduction Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound. Methods Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 105) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control. Results Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The

Detecting thermal phase transitions in corneal stroma by fluorescence micro-imaging analysis

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Matteini, P.; Rossi, F.; Ratto, F.; Bruno, I.; Nesi, P.; Pini, R.

2008-02-01

Thermal modifications induced in corneal stroma were investigated by the use of fluorescence microscopy. Freshly extracted porcine corneas were immersed for 5 minutes in a water bath at temperatures in the 35-90°C range and stored in formalin. The samples were then sliced in 200-μm-thick transversal sections and analyzed under a stereomicroscope to assess corneal shrinkage. Fluorescence images of the thermally treated corneal samples were acquired using a slow-scan cooled CCD camera, after staining the slices with Indocyanine Green (ICG) fluorescent dye which allowed to detect fluorescence signal from the whole tissue. All measurements were performed using an inverted epifluorescence microscope equipped with a mercury lamp. The thermally-induced modifications to the corneal specimens were evaluated by studying the grey level distribution in the fluorescence images. For each acquired image, Discrete Fourier Transform (DFT) and entropy analyses were performed. The spatial distribution of DFT absolute value indicated the spatial orientation of the lamellar planes, while entropy was used to study the image texture, correlated to the stromal structural transitions. As a result, it was possible to indicate a temperature threshold value (62°C) for high thermal damage, resulting in a disorganization of the lamellar planes and in full agreement with the measured temperature for corneal shrinkage onset. Analysis of the image entropy evidenced five strong modifications in stromal architecture at temperatures of ~45°C, 53°C, 57°C, 66°C, 75°C. The proposed procedure proved to be an effective micro-imaging method capable of detecting subtle changes in corneal tissue subjected to thermal treatment.

All-Optical Method to Assess Stromal Concentration of Riboflavin in Conventional and Accelerated UV-A Irradiation of the Human Cornea.

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Lombardo, Giuseppe; Micali, Norberto Liborio; Villari, Valentina; Serrao, Sebastiano; Lombardo, Marco

2016-02-01

We investigated the concentration of riboflavin in human donor corneas during corneal cross-linking using two-photon optical microscopy and spectrophotometry. Eight corneal tissues were de-epithelialized and soaked with 20% dextran-enriched 0.1% riboflavin solution for 30 minutes. After stromal soaking, three tissues were irradiated using a 3 mW/cm2 UV-A device for 30 minutes and three tissues irradiated using a 10 mW/cm2 device for 9 minutes. Two additional tissues were used as positive controls. A Ti:sapphire laser at 810 nm was used to perform two-photon emission fluorescence (TPEF) and second harmonic generation axial scanning measurements in all specimens before and after stromal soaking and after UV-A irradiation. In addition, spectrophotometry was used to collect the absorbance spectra of each tissue at the same time intervals. Analysis of the absorbance spectra and TPEF signals provided measures of the concentration depth profile of riboflavin in corneal stroma. After stromal soaking, the average peak concentration of riboflavin (0.020% ± 0.001%) was found between a stromal depth of 100 and 250 μm; the concentration of riboflavin was almost constant up to 320 ± 53 μm depth, then decreased toward the endothelium, though riboflavin was still enriched in the posterior stroma (0.016%% ± 0.001%). After conventional and accelerated UV-A irradiation, the concentration of riboflavin decreased uniformly 87% ± 2% and 67% ± 3% (P riboflavin in corneal stroma. The method can assist with the assessment of novel riboflavin formulations and different UV-A irradiation protocols.

Construction of Anterior Hemi-Corneal Equivalents Using Nontransfected Human Corneal Cells and Transplantation in Dog Models.

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Xu, Bin; Song, Zhan; Fan, Tingjun

2017-11-01

Tissue-engineered human anterior hemi-cornea (TE-aHC) is a promising equivalent for treating anterior lamellar keratopathy to surmount the severe shortage of donated corneas. This study was intended to construct a functional TE-aHC with nontransfected human corneal stromal (ntHCS) and epithelial (ntHCEP) cells using acellular porcine corneal stromata (aPCS) as a carrier scaffold, and evaluate its biological functions in a dog model. To construct a TE-aHC, ntHCS cells were injected into an aPCS scaffold and cultured for 3 days; then, ntHCEP cells were inoculated onto the Bowman's membrane of the scaffold and cultured for 5 days under air-liquid interface condition. After its morphology and histological structure were characterized, the constructed TE-aHC was transplanted into dog eyes via lamellar keratoplasty. The corneal transparency, thickness, intraocular pressure, epithelial integrity, and corneal regeneration were monitored in vivo, and the histological structure and histochemical property were examined ex vivo 360 days after surgery, respectively. The results showed that the constructed TE-aHC was highly transparent and composed of a corneal epithelium of 7-8 layer ntHCEP cells and a corneal stroma of regularly aligned collagen fibers and well-preserved glycosaminoglycans with sparsely distributed ntHCS cells, mimicking a normal anterior hemi-cornea (aHC). Moreover, both ntHCEP and ntHCS cells maintained positive expression of their marker and functional proteins. After transplantation into dog eyes, the constructed TE-aHC acted naturally in terms of morphology, structure and inherent property, and functioned well in maintaining corneal clarity, thickness, normal histological structure, and composition in dog models by reconstructing a normal aHC, which could be used as a promising aHC equivalent in corneal regenerative medicine and aHC disorder therapy. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

International Nuclear Information System (INIS)

Arias-Pulido, Hugo; Chaher, Nabila; Gong, Yun; Qualls, Clifford; Vargas, Jake; Royce, Melanie

2012-01-01

Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to

Suture associated corneal abscess three years after cataract surgery ...

African Journals Online (AJOL)

The abscess was carefully removed on slit lamp using blunt tipped forceps without breaking the thin membrane covering it. There was a deep corneal depression at the bottom of which was found a loose 10/0 nylon corneoscleral suture. Another loose suture was present at the 12 o'clock position surrounded by stromal ...

Generation of corneal epithelial cells from induced pluripotent stem cells derived from human dermal fibroblast and corneal limbal epithelium.

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Ryuhei Hayashi

Full Text Available Induced pluripotent stem (iPS cells can be established from somatic cells. However, there is currently no established strategy to generate corneal epithelial cells from iPS cells. In this study, we investigated whether corneal epithelial cells could be differentiated from iPS cells. We tested 2 distinct sources: human adult dermal fibroblast (HDF-derived iPS cells (253G1 and human adult corneal limbal epithelial cells (HLEC-derived iPS cells (L1B41. We first established iPS cells from HLEC by introducing the Yamanaka 4 factors. Corneal epithelial cells were successfully induced from the iPS cells by the stromal cell-derived inducing activity (SDIA differentiation method, as Pax6(+/K12(+ corneal epithelial colonies were observed after prolonged differentiation culture (12 weeks or later in both the L1B41 and 253G1 iPS cells following retinal pigment epithelial and lens cell induction. Interestingly, the corneal epithelial differentiation efficiency was higher in L1B41 than in 253G1. DNA methylation analysis revealed that a small proportion of differentially methylated regions still existed between L1B41 and 253G1 iPS cells even though no significant difference in methylation status was detected in the specific corneal epithelium-related genes such as K12, K3, and Pax6. The present study is the first to demonstrate a strategy for corneal epithelial cell differentiation from human iPS cells, and further suggests that the epigenomic status is associated with the propensity of iPS cells to differentiate into corneal epithelial cells.

A Prospective Study

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Nandeesh BN

2014-08-01

Lattice and Avellino's dystrophies among dystrophies and Salzmann's nodular degeneration showed specific stromal deposits making them easily diagnosable at histopathology, whereas the rest showed non-specific stromal changes mandating correlation with clinical findings. Seven regraft corneas showed stromal fibrosis making identification of primary dystrophy impossible. However, transmural vascularization and lymphocytic stromal infiltrate were prominently noted in failed grafts though their numbers were few. Conclusion: This histopathologic study characterizes classic features of macular, Avellino's, lattice corneal dystrophies and Salzmann's degeneration for their microscopic diagnosis, while the rest showed non-specific changes. Stromal edema was prominently noted in degenerations than in dystrophies. Degree of stromal vascularization and type of cellular infiltrate need attention in regrafts. [J Interdiscipl Histopathol 2014; 2(4.000: 197-204

Late onset corneal ectasia after LASIK surgery.

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Said, Ashraf; Hamade, Issam H; Tabbara, Khalid F

2011-07-01

To report late onset corneal ectasia following myopic LASIK. A retrospective cohort case series. Nineteen patients with late onset corneal ectasia following LASIK procedure were examined at The Eye Center, Riyadh, Saudi Arabia. Patients underwent LASIK for myopia with spherical equivalent ranging from -1.4 to -13.75 diopters. Age and gender, history of systemic or local diseases, and time of onset of corneal ectasia were recorded. Eye examination and corneal topographical analyses were done before and after LASIK surgery. Nineteen patients (29 eyes) with late onset corneal ectasia were identified from 1998 to 2008 in 13 male and six female patients. The mean follow-up period was 108 ± 23 months (range 72-144 months). No patient had pre-operative identifiable risk factors for corneal ectasia and the mean time of onset was 57 ± 24 months (range 24-120 months after LASIK). The pre-operative values included mean central pachymetry 553 ± 25 μm, mean keratometry reading of 42.9 ± 1.5 diopters, average oblique cylinder of 1.4 ± 1.2 diopters, posterior surface elevation of 26 ± 2.1 diopters, corneal flap thickness of 160 μm, mean spherical equivalent of -5.6 ± 3.6 diopters, and calculated residual corneal stromal bed thickness was 288 ± 35 μm. Three (5 eyes) patients developed ectasia after pregnancy. Three (4 eyes) patients developed corneal ectasia following severe adenoviral keratoconjunctivitis and had positive PCR for adenovirus type 8. Corneal ectasia may develop many years after LASIK surgery and symptoms could go undetected for some time. Pregnancy and adenoviral keratoconjunctivitis occurred post-operatively in six patients.

RECURRENT CORNEAL EROSION SYNDROME (a review

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S. V. Trufanov

2015-01-01

Full Text Available Recurrent corneal erosion (RCE syndrome is characterized by episodes of recurrent spontaneous epithelial defects. Main clinical symptoms (pain, redness, photophobia, lacrimation occurred at night. Corneal lesions revealed by slit lamp exam vary depending on the presence of corneal epithelium raise, epithelial microcysts or epithelial erosions, stromal infiltrates and opacities. Microtraumas, anterior corneal dystrophies, and herpesvirus give rise to RCE. Other causes or factors which increase the risk of RCE syndrome include meibomian gland dysfunction, keratoconjunctivitis sicca, diabetes, and post-LASIK conditions. Basal membrane abnormalities and instability of epithelial adhesion to stroma play a key role in RCE pathogenesis. Ultrastructural changes in RCE include abnormalities of basal epithelial cells and epithelial basal membrane, absence or deficiency of semi-desmosomes, loss of anchor fibrils. Increase in matrix metalloproteinases and collagenases which contribute to basal membrane destruction results in recurrent erosions and further development of abnormal basal membrane. The goals of RCE therapy are to reduce pain (in acute stage, to stimulate re-epithelization, and to restore «adhesion complex» of basal membrane. In most cases, RCE responds to simple conservative treatment that includes lubricants, healing agents, and eye patches. RCEs that are resistant to simple treatment, require complex approach. Non-invasive methods include long-term contact lens use, instillations of autologous serum (eye drops, injections of botulinum toxin (induces ptosis, antiviral agent use or oral intake of metalloproteinase inhibitors. Cell membrane stabilizers, i.e., antioxidants, should be included into treatment approaches as well. Antioxidant effect of Emoxipine promotes tissue reparation due to the prevention of cell membrane lipid peroxidation as well as due to its anti-hypoxic, angioprotective, and antiplatelet effects. If conservative therapy

Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks.

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Sorkio, Anni; Koch, Lothar; Koivusalo, Laura; Deiwick, Andrea; Miettinen, Susanna; Chichkov, Boris; Skottman, Heli

2018-07-01

There is a high demand for developing methods to produce more native-like 3D corneal structures. In the present study, we produced 3D cornea-mimicking tissues using human stem cells and laser-assisted bioprinting (LaBP). Human embryonic stem cell derived limbal epithelial stem cells (hESC-LESC) were used as a cell source for printing epithelium-mimicking structures, whereas human adipose tissue derived stem cells (hASCs) were used for constructing layered stroma-mimicking structures. The development and optimization of functional bioinks was a crucial step towards successful bioprinting of 3D corneal structures. Recombinant human laminin and human sourced collagen I served as the bases for the functional bioinks. We used two previously established LaBP setups based on laser induced forward transfer, with different laser wavelengths and appropriate absorption layers. We bioprinted three types of corneal structures: stratified corneal epithelium using hESC-LESCs, lamellar corneal stroma using alternating acellular layers of bioink and layers with hASCs, and finally structures with both a stromal and epithelial part. The printed constructs were evaluated for their microstructure, cell viability and proliferation, and key protein expression (Ki67, p63α, p40, CK3, CK15, collagen type I, VWF). The 3D printed stromal constructs were also implanted into porcine corneal organ cultures. Both cell types maintained good viability after printing. Laser-printed hESC-LESCs showed epithelial cell morphology, expression of Ki67 proliferation marker and co-expression of corneal progenitor markers p63α and p40. Importantly, the printed hESC-LESCs formed a stratified epithelium with apical expression of CK3 and basal expression of the progenitor markers. The structure of the 3D bioprinted stroma demonstrated that the hASCs had organized horizontally as in the native corneal stroma and showed positive labeling for collagen I. After 7 days in porcine organ cultures, the 3D bioprinted

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

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Chang, Che-Yi; Wang, Ming-Chen; Miyagawa, Takuya; Chen, Zhi-Yu; Lin, Feng-Huei; Chen, Ko-Hua; Liu, Guei-Sheung; Tseng, Ching-Li

2017-01-01

Neovascularization (NV) of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG), presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine–glycine–aspartic acid (RGD) peptide–hyaluronic acid (HA)-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs) was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs) in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV), with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a spherical shape and shell structure of about 200 nm. A slow-release pattern was observed in the nanoformulation at about 30% after 30 hours. Surface plasmon resonance confirmed that GEH-RGD NPs specifically bound to the integrin αvβ3. In vitro cell-viability assay showed that GEH-RGD efficiently inhibited HUVEC proliferation at low EGCG concentrations (20 μg/mL) when compared with EGCG or non-RGD-modified NPs. Furthermore, GEH-RGD NPs significantly inhibited HUVEC migration down to 58%, lasting for 24 hours. In the corneal NV mouse model, fewer and thinner vessels were observed in the alkali-burned cornea after treatment with GEH-RGD NP eyedrops. Overall, this study indicates that GEH-RGD NPs were successfully developed and synthesized as an inhibitor of vascular endothelial cells with specific targeting capacity. Moreover, they can be used in eyedrops to inhibit angiogenesis in corneal NV

Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell-derived factor 1 in human endometrial stromal cells.

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Okada, Hidetaka; Okamoto, Rika; Tsuzuki, Tomoko; Tsuji, Shoko; Yasuda, Katsuhiko; Kanzaki, Hideharu

2011-09-01

To investigate whether 17β-estradiol (E(2)) and progestins exert direct effects on vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1/CXCL12) in human endometrial stromal cells (ESCs) and thereby to clarify the regulatory function of these local angiogenic factors in the endometrium. In vitro experiment. Research laboratory at Kansai Medical University. Fourteen patients undergoing hysterectomy for benign reasons. ESCs were cultured with E(2) and/or various clinically relevant progestins (medroxyprogesterone acetate [MPA], norethisterone [NET], levonorgestrel [LNG], dienogest [DNG], and progesterone [P]). The mRNA levels and production of VEGF and SDF-1 were assessed by real-time reverse-transcription polymerase chain reaction and ELISA, respectively. E(2) significantly induced the mRNA levels and protein production of VEGF and SDF-1 in ESCs. MPA could antagonize the E(2)-stimulated effects in a time- and dose-dependent manner, and this effect could be reversed by RU-486 (P receptor antagonist). All of the progestins (MPA, NET, LNG, and DNG; 10(-9) to 10(-7) mol/L) attenuated E(2)-induced VEGF and SDF-1 production, whereas P showed these inhibitory effects only when present in a high concentration (10(-7) mol/L). Progestins have inhibitory effects on E(2)-induced VEGF and SDF-1 in ESCs. These results may indicate a potential mechanism for action of the female sex steroids in the human endometrium that can be helpful for various clinical applications. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fluorouracil as a treatment for corneal papilloma in a Malayan tapir.

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Karpinski, Lorraine G; Miller, Christine L

2002-09-01

A 26-year-old, wild caught, male Malayan tapir at the Miami Metrozoo with bilateral corneal papillomas was serially immobilized and given subconjunctival injections of fluorouracil. Over the course of 17 weeks five bilateral injections of 25 mg fluorouracil were given. This treatment caused regression of the corneal lesions as evidenced by decreased lesion diameter, decreased corneal vascularity, increased corneal clarity, and improved visual function. No adverse drug effects were observed.

Effect of chemical composition on corneal cellular response to photopolymerized materials comprising 2-hydroxyethyl methacrylate and acrylic acid

International Nuclear Information System (INIS)

Lai, Jui-Yang

2013-01-01

Characterization of corneal cellular response to hydrogel materials is an important issue in ophthalmic applications. In this study, we aimed to investigate the relationship between the feed composition of 2-hydroxyethyl methacrylate (HEMA)/acrylic acid (AAc) and material compatibility towards corneal stromal and endothelial cells. The monomer solutions of HEMA and AAc were mixed at varying volume ratios of 92:0, 87:5, 82:10, 77:15, and 72:20, and were subjected to UV irradiation. Results of electrokinetic measurements showed that an increase in absolute zeta potential of photopolymerized membranes is observed with increasing the volume ratios of AAc/HEMA. Following 4 days of incubation with various hydrogels, the primary rabbit corneal stromal and endothelial cell cultures were examined for viability, proliferation, and pro-inflammatory gene expression. The samples prepared from the solution mixture containing 0–10 vol.% AAc displayed good cytocompatibility. However, with increasing volume ratio of AAc and HEMA from 15:77 to 20:72, the decreased viability, inhibited proliferation, and stimulated inflammation were noted in both cell types, probably due to the stronger charge–charge interactions. On the other hand, the ionic pump function of corneal endothelial cells exposed to photopolymerized membranes was examined by analyzing the Na + ,K + -ATPase alpha 1 subunit (ATP1A1) expression level. The presence of material samples having higher anionic charge density (i.e., zeta potential of − 38 to − 56 mV) may lead to abnormal transmembrane transport. It is concluded that the chemical composition of HEMA/AAc has an important influence on the corneal stromal and endothelial cell responses to polymeric biomaterials. - Highlights: • We examine the corneal cellular responses to photopolymerized biomaterials. • Charge density of membranes was increased with increasing volume ratio of AAc/HEMA. • 15–20 vol.% AAc decreased viability and proliferation of all

Effect of chemical composition on corneal cellular response to photopolymerized materials comprising 2-hydroxyethyl methacrylate and acrylic acid

Energy Technology Data Exchange (ETDEWEB)

Lai, Jui-Yang, E-mail: jylai@mail.cgu.edu.tw

2013-10-15

Characterization of corneal cellular response to hydrogel materials is an important issue in ophthalmic applications. In this study, we aimed to investigate the relationship between the feed composition of 2-hydroxyethyl methacrylate (HEMA)/acrylic acid (AAc) and material compatibility towards corneal stromal and endothelial cells. The monomer solutions of HEMA and AAc were mixed at varying volume ratios of 92:0, 87:5, 82:10, 77:15, and 72:20, and were subjected to UV irradiation. Results of electrokinetic measurements showed that an increase in absolute zeta potential of photopolymerized membranes is observed with increasing the volume ratios of AAc/HEMA. Following 4 days of incubation with various hydrogels, the primary rabbit corneal stromal and endothelial cell cultures were examined for viability, proliferation, and pro-inflammatory gene expression. The samples prepared from the solution mixture containing 0–10 vol.% AAc displayed good cytocompatibility. However, with increasing volume ratio of AAc and HEMA from 15:77 to 20:72, the decreased viability, inhibited proliferation, and stimulated inflammation were noted in both cell types, probably due to the stronger charge–charge interactions. On the other hand, the ionic pump function of corneal endothelial cells exposed to photopolymerized membranes was examined by analyzing the Na{sup +},K{sup +}-ATPase alpha 1 subunit (ATP1A1) expression level. The presence of material samples having higher anionic charge density (i.e., zeta potential of − 38 to − 56 mV) may lead to abnormal transmembrane transport. It is concluded that the chemical composition of HEMA/AAc has an important influence on the corneal stromal and endothelial cell responses to polymeric biomaterials. - Highlights: • We examine the corneal cellular responses to photopolymerized biomaterials. • Charge density of membranes was increased with increasing volume ratio of AAc/HEMA. • 15–20 vol.% AAc decreased viability and proliferation

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

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Chang CY

2016-12-01

Full Text Available Che-Yi Chang,1,2,* Ming-Chen Wang,2,* Takuya Miyagawa,1 Zhi-Yu Chen,1 Feng-Huei Lin,3,4 Ko-Hua Chen,5,6 Guei-Sheung Liu,7 Ching-Li Tseng1 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 2Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, 4Institute of Biomedical Engineering, National Taiwan University, 5Department of Ophthalmology, Taipei Veterans General Hospital, 6Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia *These authors contributed equally to this work Abstract: Neovascularization (NV of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG, presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine–glycine–aspartic acid (RGD peptide–hyaluronic acid (HA-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV, with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a

Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

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Dietmar Abraham

2013-09-01

Full Text Available The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF. PlGF is a member of the vascular endothelial growth factor (VEGF family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.

Pathophysiology of Corneal Scarring in Persistent Epithelial Defects After PRK and Other Corneal Injuries.

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Wilson, Steven E; Medeiros, Carla S; Santhiago, Marcony R

2018-01-01

To analyze corneal persistent epithelial defects that occurred at 3 to 4 weeks after -4.50 diopter (D) photorefractive keratectomy (PRK) in rabbits and apply this pathophysiology to the treatment of persistent epithelial defects that occur after any corneal manipulations or diseases. Two of 168 corneas that had -4.50 D PRK to study epithelial basement membrane regeneration developed spontaneous persistent epithelial defects that did not heal at 3 weeks after PRK. These were studied with slit-lamp photographs, immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin (α-SMA), and transmission electron microscopy. Myofibroblasts developed at the stromal surface within the persistent epithelial defect and for a short distance peripheral to the leading edge of the epithelium. No normal epithelial basement membrane was detectable within the persistent epithelial defect or for up to 0.3 mm behind the leading edge of the epithelium, although epithelial basement membrane had normally regenerated in other areas of the zone ablated by an excimer laser where the epithelium healed promptly. A persistent epithelial defect in the cornea results in the development of myofibroblasts and disordered extracellular matrix produced by these cells that together cause opacity within, and a short distance beyond, the persistent epithelial defect. Clinicians should treat persistent epithelial defects within 10 days of non-closure of the epithelium to facilitate epithelial healing to prevent long-term stromal scarring (fibrosis). [J Refract Surg. 2018;34(1):59-64.]. Copyright 2018, SLACK Incorporated.

Changing indications and techniques for corneal transplantations at a tertiary referral center in Turkey, from 1995 to 2014

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Altay Y

2016-06-01

Full Text Available Yesim Altay, Ayse Burcu, Gozde Aksoy, Evin Singar Ozdemir, Firdevs Ornek Department of Ophthalmology, Ankara Training and Research Hospital, Ankara, Turkey Background: Indications for corneal transplantation in developed and developing nations differ according to the different spectrum of corneal disease in each country. Objective: The purpose of this study is to analyze the changing indications and surgical techniques for corneal transplantation over the past 20 years at a tertiary referral center in Turkey. Methods: We retrospectively reviewed the records of patients who underwent keratoplasty from January 1995 to December 2014 (between 1995 and 2004, period 1, and between 2005 and 2014, period 2. Patients’ demographic data, indications for corneal transplantation, and the type of surgery were recorded. Results: The number of keratoplasties performed ranged from 548 in period 1 to 782 in period 2. Between 1995 and 2004, the leading indications were keratoconus (34.1%, bullous keratopathy (17%, and non-herpetic corneal scar (13.3%, and between 2005 and 2014, they were keratoconus (33.8%, corneal stromal dystrophy (14.2%, and bullous keratopathy (12.7%. All the keratoplasties performed in the 1995–2004 period were penetrating keratoplasty (PKP. During the period 2005–2014, PKP accounted for 93%, automated lamellar keratoplasty 5.8%, and deep anterior lamellar keratoplasty 1.2% of all corneal transplantations. Conclusion: Keratoconus was the leading indication for keratoplasty in both periods. In the 2005–2014 period, corneal stromal dystrophy increased significantly. All the keratoplasties performed in period 1 and 93% of all keratoplasties performed in period 2 were PKP. Keywords: corneal transplantation, indication, keratoconus, keratoplasty technique, pene­trating keratoplasty

Controlling human corneal stromal stem cell contraction to mediate rapid cell and matrix organization of real architecture for 3-dimensional tissue equivalents.

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Mukhey, Dev; Phillips, James B; Daniels, Julie T; Kureshi, Alvena K

2018-02-01

The architecture of the human corneal stroma consists of a highly organized extracellular matrix (ECM) interspersed with keratocytes. Their progenitor cells; corneal stromal stem cells (CSSC) are located at the periphery, in the limbal stroma. A highly organized corneal ECM is critical for effective transmission of light but this structure may be compromised during injury or disease, resulting in loss of vision. Re-creating normal organization in engineered tissue equivalents for transplantation often involves lengthy culture times that are inappropriate for clinical use or utilisation of synthetic substrates that bring complications such as corneal melting. CSSC have great therapeutic potential owing to their ability to reorganize a disorganized matrix, restoring transparency in scarred corneas. We examined CSSC contractile behavior to assess whether this property could be exploited to rapidly generate cell and ECM organization in Real Architecture For 3D Tissues (RAFT) tissue equivalents (TE) for transplantation. Free-floating collagen gels were characterized to assess contractile behavior of CSSC and establish optimum cell density and culture times. To mediate cell and collagen organization, tethered collagen gels seeded with CSSC were cultured and subsequently stabilized with the RAFT process. We demonstrated rapid creation of biomimetic RAFT TE with tunable structural properties. These displayed three distinct regions of varying degrees of cellular and collagen organization. Interestingly, increased organization coincided with a dramatic loss of PAX6 expression in CSSC, indicating rapid differentiation into keratocytes. The organized RAFT TE system could be a useful bioengineering tool to rapidly create an organized ECM while simultaneously controlling cell phenotype. For the first time, we have demonstrated that human CSSC exhibit the phenomenon of cellular self-alignment in tethered collagen gels. We found this mediated rapid co-alignment of collagen fibrils

Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

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Greene, Carol Ann, E-mail: carol.greene@auckland.ac.nz; Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

2014-03-10

Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

International Nuclear Information System (INIS)

Greene, Carol Ann; Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

2014-01-01

Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors

Corneal ablation depth readout of the MEL 80 excimer laser compared to Artemis three-dimensional very high-frequency digital ultrasound stromal measurements.

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Reinstein, Dan Z; Archer, Timothy J; Gobbe, Marine

2010-12-01

To evaluate the accuracy of the ablation depth readout for the MEL 80 excimer laser (Carl Zeiss Meditec). Artemis 1 very high-frequency digital ultrasound measurements were obtained before and at least 3 months after LASIK in 121 eyes (65 patients). The Artemis-measured ablation depth was calculated as the maximum difference in stromal thickness before and after treatment. Laser in situ keratomileusis was performed using the MEL 80 excimer laser and the Hansatome microkeratome (Bausch & Lomb). The Aberration Smart Ablation profile was used in 56 eyes and the Tissue Saving Ablation profile was used in 65 eyes. All ablations were centered on the corneal vertex. Comparative statistics and linear regression analysis were performed between the laser readout ablation depth and Artemis-measured ablation depth. The mean maximum myopic meridian was -6.66±2.40 diopters (D) (range: -1.50 to -10.00 D) for Aberration Smart Ablation-treated eyes and -6.50±2.56 D (range: -1.34 to -11.50 D) for Tissue Saving Ablation-treated eyes. The MEL 80 readout was found to overestimate the Artemis-measured ablation depth by 20±12 μm for Aberration Smart Ablation and by 21±12 μm for Tissue Saving Ablation profiles. The accuracy of ablation depth measurement was improved by using the Artemis stromal thickness profile measurements before and after surgery to exclude epithelial changes. The MEL 80 readout was found to overestimate the achieved ablation depth. The linear regression equations could be used by MEL 80 users to adjust the ablation depth for predicted residual stromal thickness calculations without increasing the risk of ectasia due to excessive keratectomy depth as long as a suitable flap thickness bias is included. Copyright 2010, SLACK Incorporated.

Low temperature corneal laser welding investigated by atomic force microscopy

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Matteini, Paolo; Sbrana, Francesca; Tiribilli, Bruno; Pini, Roberto

2009-02-01

The structural modifications in the stromal matrix induced by low-temperature corneal laser welding were investigated by atomic force microscopy (AFM). This procedure consists of staining the wound with Indocyanine Green (ICG), followed by irradiation with a near-infrared laser operated at low-power densities. This induces a local heating in the 55-65 °C range. In welded tissue, extracellular components undergo heat-induced structural modifications, resulting in a joining effect between the cut edges. However, the exact mechanism generating the welding, to date, is not completely understood. Full-thickness cuts, 3.5 mm in length, were made in fresh porcine cornea samples, and these were then subjected to laser welding operated at 16.7 W/cm2 power density. AFM imaging was performed on resin-embedded semi-thin slices once they had been cleared by chemical etching, in order to expose the stromal bulk of the tissue within the section. We then carried out a morphological analysis of characteristic fibrillar features in the laser-treated and control samples. AFM images of control stromal regions highlighted well-organized collagen fibrils (36.2 +/- 8.7 nm in size) running parallel to each other as in a typical lamellar domain. The fibrils exhibited a beaded pattern with a 22-39 nm axial periodicity. Laser-treated corneal regions were characterized by a significant disorganization of the intralamellar architecture. At the weld site, groups of interwoven fibrils joined the cut edges, showing structural properties that were fully comparable with those of control regions. This suggested that fibrillar collagen is not denatured by low-temperature laser welding, confirming previous transmission electron microscopy (TEM) observations, and thus it is probably not involved in the closure mechanism of corneal cuts. The loss of fibrillar organization may be related to some structural modifications in some interfibrillar substance as proteoglycans or collagen VI. Furthermore, AFM

Anterior stromal puncture with staining: A modified technique for preoperative reference corneal marking for toric lenses and its retrospective analyses

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Sahil Bhandari

2016-01-01

Full Text Available Introduction: Toric intraocular lenses (IOLs are an effective way of compensating preexisting corneal astigmatism during cataract surgery. To achieve success, it is imperative to align the toric IOLs in desired position and preoperative reference marking is one among the three important steps for accurate alignment. To make the marking procedure simpler and effective, we have modified the conventional three-step slit lamp-based technique. Materials and Methods: Patient is seated in front of the slit lamp and asked to keep the chin over chin rest. A 26-gauge bent needle with tip stained by sterile blue ink marker is used to make anterior stromal puncture (ASP at the edges of horizontal 180° axis near the limbus. Results: A total of 58 eyes were retrospectively evaluated. Mean (+/-SD IOL deviation on day 1 and day 30 was 5.7 ± 6.5° and 4.7 ± 5.6°, respectively. Median IOL misalignment on day 1 and day 30 was 3°. Redialing of IOL was required in 2 (3.4% eyes only, all of which were performed within 1 week of surgery. In total, 2 (3.7% eyes had a residual astigmatism of − 0.5 Dcyl and − 1.0 Dcyl, respectively. Conclusion: ASP is an effective technique for reference marking, technically simpler and can be practiced by most of the surgeons. It avoids the necessity of high-end sophisticated machinery and gives a better platform for the reference corneal marking along with the benefit of reproducibility and simplicity.

In vivo architectural analysis of clear corneal incisions using anterior segment optical coherence tomography.

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Dupont-Monod, Sylvère; Labbé, Antoine; Fayol, Nicolas; Chassignol, Alexis; Bourges, Jean-Louis; Baudouin, Christophe

2009-03-01

To use anterior segment optical coherence tomography (AS-OCT) to analyze the in vivo architecture of clear corneal incisions after phacoemulsification using different techniques. Department of Ophthalmology, Quinze-Vingts National Ophthalmology Hospital, Paris, France. This prospective observational study analyzed clear corneal incisions used in phacoemulsification. All wounds were evaluated 1 day and 8 days postoperatively by AS-OCT (Visante). Incision architecture and pachymetry at the wound level were analyzed. Thirty-five clear corneal incisions were analyzed. Six eyes had 2.75 mm coaxial phacoemulsification, 19 had 2.20 mm microincision coaxial phacoemulsification, and 10 had 1.30 mm bimanual microincision phacoemulsification. The 1.30 mm incision had a straight-line configuration. The 2.20 mm and 2.75 mm incisions had an arcuate configuration. The angles of incidence of 1.30 mm incisions were greater than those of 2.20 mm incisions (P<.001). All incisions had slight corneal edema limited to the incision area. The edema was slightly greater around 1.30 mm incisions (mean pachymetry 1143 microm +/- 140 [SD]) than around 2.20 mm incisions (mean 1012 +/- 101 microm) (P = .001). Bimanual procedures had satisfactory endothelial apposition in the enlarged areas, where stromal edema was less than that surrounding the unenlarged 1.30 mm incisions. The 3 phacoemulsification techniques induced gaping of the endothelial edge, minor inadequate endothelial apposition, and mild stromal edema in the area of the clear corneal incisions. Bimanual microincision sleeveless phacoemulsification may alter the wound slightly more than coaxial 2.75 mm and microcoaxial 2.20 mm sleeved-tip phacoemulsification.

Microkeratome-assisted lamellar keratoplasty for keratoconus: stromal sandwich.

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Bilgihan, Kamil; Ozdek, Sengül C; Sari, Ayça; Hasanreisoglu, Berati

2003-07-01

To evaluate microkeratome-assisted lamellar keratoplasty for the treatment of keratoconus when it is not possible to correct the astigmatic ametropia with contact lenses. Ophthalmology Department, School of Medicine, Gazi University, Ankara, Turkey. This prospective study comprised 9 eyes of 7 keratoconus patients with contact lens intolerance. The donor cornea was prepared with a microkeratome and punched with a 7.25 mm or 7.50 mm trephine. Following the creation of a standard 9.0 mm corneal flap in the host cornea, the donor stromal button was implanted under this corneal flap like a sandwich. Transepithelial photorefractive keratectomy or laser in situ keratomileusis was performed when the corneal topography and refraction stabilized by the end of the sixth postoperative month. Follow-up ranged from 7 to 22 months. All patients gained 5 or more lines (mean 7.2 lines +/- 1.6 [SD]), and no patient lost a line of vision. The mean corneal thickness was 432.7 +/- 36.1 micrometers preoperatively and 578.1 +/- 45.1 micrometers after refractive surgery. The early visual results of this surgical technique are promising and seem to be comparable to those with penetrating keratoplasty.

Clinical observation of cutting fluctuations on central corneal thickness after laser subepithelial keratomileusis

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Wei Cheng

2017-09-01

Full Text Available AIM:To evaluate the percentage of cutting fluctuations of central corneal thickness(CCTintraoperative used low concentration(0.02%mitomycin C(MMCafter laser-assisted subepithelial keratomileusis(LASEK. METHODS: In this prospective study, low and medium myopia group(spherical equivalent≤6.0DShas 138 patients(276 eyes. Low concentration MMC used topically in 69 patients(138 eyesrandomized after excimer laser ablation; the another traditional LASEK as control. High myopia group(6.0DSt test and their repeatability was assessed using the coefficient of variation(CV.RESULTS: At 3mo after operation, the difference of central corneal thickness and cutting value between different treatment groups was statistically significant(PPPPCONCLUSION: The study on percentage of cutting fluctuations of central corneal thickness, further confirmed low concentrations MMC in reducing postoperative corneal stromal proliferation reaction, inhibition of haze production.

Nodular Epithelial Hyperplasia after Photorefractive Keratectomy Followed by Corneal Collagen Cross-Linking

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Bogoni, Ayla; Salerno, Liberdade Cezaro; Ghanem, Vinícius Coral; Ghanem, Ramon Coral

2013-01-01

This study describes a case of nodular epithelial hyperplasia and stromal alterations in a patient with keratoconus who was submitted to topography-guided photorefractive keratectomy (PRK) followed by corneal collagen cross-linking. Debridement of the epithelial nodule was performed. After a 2-year followup, a new topography-guided PRK was indicated.

Thick keratoconic cornea associated with posterior polymorphous corneal dystrophy.

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Zaarour, K; Slim, E; Antoun, J; Waked, N

2017-03-01

We herein report a case of bilateral unusually thick non-edematous keratoconic corneas with associated endothelial features of posterior polymorphous corneal dystrophy (PPCD). We report the case of a 27-year-old myopic woman who presented for refractive surgery. Slit lamp exam showed bilateral corneal protrusion with diffuse deep stromal and endothelial vesicular opacities and small paracentral bands. Topography showed generalized advanced corneal steepening in both eyes with increased anterior and posterior central corneal elevations in comparison to the best fit sphere. Ultrasound pachymetry showed central corneal thickness of 605μm (RE) and 612μm (LE). On specular biomicroscopy, cell density of 2503 cells/mm 2 RE and 1526 cells/mm 2 LE with significant cellular pleomorphism and polymegathism were noted. Clinical and paraclinical findings together suggest the presence of simultaneous keratoconus and PPCD. The literature has suggested an association between PPCD and steep cornea. Moreover, many reports have also described cases of associated PPCD and keratoconus with characteristic thinning and ectasia, in comparison to the unusual thick corneas noted in our patient, despite the absence of edema. Identification of genetics factors is further needed to clarify this association. This case describes a patient whose corneas present features of both keratoconus and PPCD and is unique due to the presence of increased corneal thickness despite the absence of edema. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells

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Tratwal, Josefine; Mathiasen, Anders Bruun; Juhl, Morten

2015-01-01

INTRODUCTION: Stimulation of mesenchymal stromal cells and adipose tissue-derived stromal cells (ASCs) with vascular endothelial growth factor (VEGF) has been used in multiple animal studies and clinical trials for regenerative purposes. VEGF stimulation is believed to promote angiogenesis and VEGF...... stimulation is usually performed under serum deprivation. Potential regenerative molecular mechanisms are numerous and the role of contributing factors is uncertain. The aim of the current study was to investigate the effect of in vitro serum deprivation and VEGF stimulation on gene expression patterns...... of ASCs. METHODS: Gene expressions of ASCs cultured in complete medium, ASCs cultured in serum-deprived medium and ASCs stimulated with VEGF in serum-deprived medium were compared. ASC characteristics according to criteria set by the International Society of Cellular Therapy were confirmed by flow...

Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye.

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Hirata, Harumitsu; Mizerska, Kamila; Dallacasagrande, Valentina; Guaiquil, Victor H; Rosenblatt, Mark I

2017-05-01

It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease. NEW & NOTEWORTHY In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may also be capable of transducing

Indications for Corneal Transplantation at a Tertiary Referral Center in Tehran

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Mohammad Zare

2010-01-01

Full Text Available Purpose: To report the indications and techniques of corneal transplantation at a tertiary referral center in Tehran over a 3-year period. Methods: Records of patients who had undergone any kind of corneal transplantation at Labbafinejad Medical Center, Tehran, Iran from March 2004 to March 2007 were reviewed to determine the indications and types of corneal transplantation. Results: During this period, 776 eyes of 756 patients (including 504 male subjects with mean age of 41.3±21.3 years underwent corneal transplantation. The most common indication was keratoconus (n=317, 40.8% followed by bullous keratopathy (n=90, 11.6%, non-herpetic corneal scars (n=62, 8.0%, infectious corneal ulcers (n=61, 7.9%, previously failed grafts (n=61, 7.9%, endothelial and stromal corneal dystrophies (n=28, 3.6%, and trachoma keratopathy (n=26, 3.3%. Other indications including Terrien′s marginal degeneration, post-LASIK keratectasia, trauma, chemical burns, and peripheral ulcerative keratitis constituted the rest of cases. Techniques of corneal transplantation included penetrating keratoplasty (n=607, 78.2%, deep anterior lamellar keratoplasty (n=108, 13.9%, conventional lamellar keratoplasty (n=44, 5.7%, automated lamellar therapeutic keratoplasty (n=8, 1.0%, and Descemet stripping endothelial keratoplasty (n=6, 0.8% in descending order. The remaining cases were endothelial keratoplasty and sclerokeratoplasty. Conclusion: In this study, keratoconus was the most common indication for penetrating keratoplasty which was the most prevalent technique of corneal transplantation. However, deep anterior lamellar keratoplasty is emerging as a growing alternative for corneal pathologies not involving the endothelium.

The treatment of acute corneal hydrops by subtotal penetrating keratoplasty. Clinical case

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I. A. Loskutov

2014-07-01

Full Text Available Clinical case of acute hydrops treatment using subtotal penetrating keratoplasty (PK is presented. The diagnosis of acute hydrops was based on clinical and functional evaluations including optical coherent tomography (OCT. A part of diseased cornea was removed and examined under a light microscope. These studies revealed morphological changes in almost all corneal layers. OCT and histology demonstrated that PK was indicated to this patient. Recent literature data on the epidemiology and pathogenesis of acute hydrops are presented. This rare disease results from tears in the Descemet’s membrane that allow aqueous humor to enter the stroma. Current treatment is aimed to suppress corneal inflammation, restore endothelium and Descemet’s membrane integrity and drain stromal cysts to optimize cornea healing. In this case, subtotal PK was performed due to the significant corneal thinning and a high risk of its melting. «Material for corneal graft» (iLab, Moscow, Russia was used as a donor material.

Management of corneal bee sting

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Razmjoo H

2011-12-01

Full Text Available Hassan Razmjoo1,2, Mohammad-Ali Abtahi1,2,4, Peyman Roomizadeh1,3, Zahra Mohammadi1,2, Seyed-Hossein Abtahi1,3,41Medical School, Isfahan University of Medical Sciences (IUMS; 2Ophthalmology Ward, Feiz Hospital, IUMS; 3Isfahan Medical Students Research Center (IMSRC, IUMS; 4Isfahan Ophthalmology Research Center (IORC, Feiz Hospital, IUMS, Isfahan, IranAbstract: Corneal bee sting is an uncommon environmental eye injury that can result in various ocular complications with an etiology of penetrating, immunologic, and toxic effects of the stinger and its injected venom. In this study we present our experience in the management of a middle-aged male with a right-sided deep corneal bee sting. On arrival, the patient was complaining of severe pain, blurry vision with acuity of 160/200, and tearing, which he had experienced soon after the injury. Firstly, we administered conventional drugs for eye injuries, including topical antibiotic, corticosteroid, and cycloplegic agents. After 2 days, corneal stromal infiltration and edema developed around the site of the sting, and visual acuity decreased to 100/200. These conditions led us to remove the stinger surgically. Within 25 days of follow-up, the corneal infiltration decreased gradually, and visual acuity improved to 180/200. We suggest a two-stage management approach for cases of corneal sting. For the first stage, if the stinger is readily accessible or primary dramatic reactions, including infiltration, especially on the visual axis, exist, manual or surgical removal would be indicated. Otherwise, we recommend conventional treatments for eye injuries. Given this situation, patients should be closely monitored for detection of any worsening. If the condition does not resolve or even deteriorates, for the second stage, surgical removal of the stinger under local or generalized anesthesia is indicated.Keywords: bee sting, stinger, cornea, removal, management, surgery

Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT).

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Bourin, Philippe; Bunnell, Bruce A; Casteilla, Louis; Dominici, Massimo; Katz, Adam J; March, Keith L; Redl, Heinz; Rubin, J Peter; Yoshimura, Kotaro; Gimble, Jeffrey M

2013-06-01

Adipose tissue is a rich and very convenient source of cells for regenerative medicine therapeutic approaches. However, a characterization of the population of adipose-derived stromal and stem cells (ASCs) with the greatest therapeutic potential remains unclear. Under the authority of International Federation of Adipose Therapeutics and International Society for Cellular Therapy, this paper sets out to establish minimal definitions of stromal cells both as uncultured stromal vascular fraction (SVF) and as an adherent stromal/stem cells population. Phenotypic and functional criteria for the identification of adipose-derived cells were drawn from the literature. In the SVF, cells are identified phenotypically by the following markers: CD45-CD235a-CD31-CD34+. Added value may be provided by both a viability marker and the following surface antigens: CD13, CD73, CD90 and CD105. The fibroblastoid colony-forming unit assay permits the evaluation of progenitor frequency in the SVF population. In culture, ASCs retain markers in common with other mesenchymal stromal/stem cells (MSCs), including CD90, CD73, CD105, and CD44 and remain negative for CD45 and CD31. They can be distinguished from bone-marrow-derived MSCs by their positivity for CD36 and negativity for CD106. The CFU-F assay is recommended to calculate population doublings capacity of ASCs. The adipocytic, chondroblastic and osteoblastic differentiation assays serve to complete the cell identification and potency assessment in conjunction with a quantitative evaluation of the differentiation either biochemically or by reverse transcription polymerase chain reaction. The goal of this paper is to provide initial guidance for the scientific community working with adipose-derived cells and to facilitate development of international standards based on reproducible parameters. Copyright © 2013 International Society for Cellular Therapy. All rights reserved.

Another Risk From Cigarette Smoking: Corneal Burn

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Volkan Hürmeriç

2012-12-01

Full Text Available A 21-year-old male presented with corneal injury in his left eye after one of his friends had moved his arm backwards and accidentally hit his eye with the lit end of a cigarette. Slit lamp examination revealed epithelial defect and significant stromal edema at the superior temporal quadrant of the cornea. Cigarette ashes were noted in his lashes and inferior conjunctival fornix at the initial examination in the emergency service. 6 weeks after the injury, slit lamp examination revealed stromal thinning and haze in the temporal part of the cornea. His best spectacle-corrected distance visual acuity was 20/25 with a refractive error of -6.75x135 diopters in the left eye. Our case demonstrates that ocular thermal injury due to cigarette smoking can cause serious damage to the ocular tissues. (Turk J Oph thal mol 2012; 42: 484-5

Use of Fourier-Domain Optical Coherence Tomography to Evaluate Anterior Stromal Opacities in Donor Corneas

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Matthew R. Bald

2013-01-01

Full Text Available Purpose. To evaluate Fourier-domain optical coherence tomography (FD-OCT as an adjunct to traditional slit lamp examination of donor corneas with suspected Anterior Stromal Opacities. Methods. Seven corneas suspected of having anterior stromal opacities by slit lamp examination were evaluated with FD-OCT. Each cornea was evaluated to confirm the presence of opacity and, if present, the depth of opacity was measured. Results. The opacity depth ranged from 82 μm to 624 μm. The initial slit lamp impressions of five of the seven corneas were confirmed by OCT. In two corneas, the OCT findings were different from the initial slit lamp impressions. Slit lamp examination of the first cornea gave the impression of anterior stromal scarring, but OCT showed that the opacity was limited to the epithelium. Slit lamp examination of the second cornea suggested opacity limited to the epithelium, but OCT identified significant sub-Bowman's scarring. In all cases, the Eye Bank Technicians reported that the location and depth of corneal opacity were more sharply defined by OCT than by slit lamp. Conclusion. The high resolution of OCT makes it easier to determine the location of corneal opacities compared to slit lamp examinations. This enhanced visualization can improve decisions regarding transplant suitability of donor corneas.

Accelerated Development of Supramolecular Corneal Stromal-Like Assemblies from Corneal Fibroblasts in the Presence of Macromolecular Crowders.

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Kumar, Pramod; Satyam, Abhigyan; Fan, Xingliang; Rochev, Yury; Rodriguez, Brian J; Gorelov, Alexander; Joshi, Lokesh; Raghunath, Michael; Pandit, Abhay; Zeugolis, Dimitrios I

2015-07-01

Tissue engineering by self-assembly uses the cells' secretome as a regeneration template and biological factory of trophic factors. Despite the several advantages that have been witnessed in preclinical and clinical settings, the major obstacle for wide acceptance of this technology remains the tardy extracellular matrix formation. In this study, we assessed the influence of macromolecular crowding (MMC)/excluding volume effect, a biophysical phenomenon that accelerates thermodynamic activities and biological processes by several orders of magnitude, in human corneal fibroblast (HCF) culture. Our data indicate that the addition of negatively charged galactose derivative (carrageenan) in HCF culture, even at 0.5% serum, increases by 12-fold tissue-specific matrix deposition, while maintaining physiological cell morphology and protein/gene expression. Gene analysis indicates that a glucose derivative (dextran sulfate) may drive corneal fibroblasts toward a myofibroblast lineage. Collectively, these results indicate that MMC may be suitable not only for clinical translation and commercialization of tissue engineering by self-assembly therapies, but also for the development of in vitro pathophysiology models.

Mice, double deficient in lysosomal serine carboxypeptidases Scpep1 and Cathepsin A develop the hyperproliferative vesicular corneal dystrophy and hypertrophic skin thickenings.

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Xuefang Pan

Full Text Available Vasoactive and mitogenic peptide, endothelin-1 (ET-1 plays an important role in physiology of the ocular tissues by regulating the growth of corneal epithelial cells and maintaining the hemodynamics of intraocular fluids. We have previously established that ET-1 can be degraded in vivo by two lysosomal/secreted serine carboxypeptidases, Cathepsin A (CathA and Serine Carboxypeptidase 1 (Scpep1 and that gene-targeted CathAS190A /Scpep1-/- mice, deficient in CathA and Scpep1 have a prolonged half-life of circulating ET-1 associated with systemic hypertension. In the current work we report that starting from 6 months of age, ~43% of CathAS190A /Scpep1-/- mice developed corneal clouding that eventually caused vision impairment. Histological evaluation of these mice demonstrated a selective fibrotic thickening and vacuolization of the corneas, resembling human hyperproliferative vesicular corneal stromal dystrophy and coexisting with a peculiar thickening of the skin epidermis. Moreover, we found that cultured corneal epithelial cells, skin fibroblasts and vascular smooth muscle cells derived from CathA/Scpep1-deficient mice, demonstrated a significantly higher proliferative response to treatment with exogenous ET-1, as compared with cells from wild type mice. We also detected increased activation level of ERK1/2 and AKT kinases involved in cell proliferation in the ET-1-treated cultured cells from CathA/Scpep1 deficient mice. Together, results from our experimental model suggest that; in normal tissues the tandem of serine carboxypeptidases, Scpep1 and CathA likely constitutes an important part of the physiological mechanism responsible for the balanced elimination of heightened levels of ET-1 that otherwise would accumulate in tissues and consequently contribute to development of the hyper-proliferative corneal dystrophy and abnormal skin thickening.

Outcome of corneal transplantation in a private institution in Saudi Arabia.

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Omar, Nazri; Bou Chacra, Charbel T; Tabbara, Khalid F

2013-01-01

The aim of this work was to describe the indications, complications, and outcomes of penetrating keratoplasty (PKP) in Saudi Arabia. In a retrospective, noncomparative interventional case series, the medical records of patients who underwent PKP from January 2000 to December 2008 and had a minimum follow-up of 6 months were reviewed. All corneas were obtained from eye banks in the US. Indications, complications, and outcomes of surgery were recorded. This study was approved by the institutional review board. Eighty-five consecutive eyes were included in this study. There were 52 (61.2%) males and 33 (38.8%) females. The median age was 35.0 years (range 3-85 years), and the median follow-up period was 24 months (range 6-108 months). The indications for PKP were keratoconus, bullous keratopathy, corneal scars, corneal dystrophy, and corneal regraft. The overall graft survival time was 88.9 months ± 4.9 months (mean ± standard error of mean, 95% confidence interval [CI] 79.4 months -98.4 months) while the 3-year and 5-year cumulative survival rates were 90.7% and 84.3%, respectively. Surgical indication (P = 0.038), immune rejection (P < 0.001), preoperative corneal vascularization (P = 0.022), and perioperative high intraocular pressure (P = 0.032) were associated significantly with corneal graft failure in univariate analysis. Multivariate analysis reduced these significant associations to rejection (P < 0.001) and vascularization (P = 0.009). Relative risk for failure in rejected cornea was 16.22 (95% CI 4.99-52.69) and in vascularized cornea was 3.89 (95% CI 1.36-11.09). At last visit following PKP, 34 (40%) eyes had best spectacle-corrected visual acuity of 20/40 or better, and 51 (60.0%) eyes had 20/80 or better. Best spectacle-corrected visual acuity was worse than 20/400 in 15 (17.6%) eyes. The overall corneal graft survival in a private setting in Saudi Arabia can be excellent. Thorough preoperative evaluation and comprehensive postoperative management are

Bone marrow stromal and vascular smooth muscle cells have chemosensory capacity via bitter taste receptor expression.

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Troy C Lund

Full Text Available The ability of cells to detect changes in the microenvironment is important in cell signaling and responsiveness to environmental fluctuations. Our interest is in understanding how human bone marrow stromal-derived cells (MSC and their relatives, vascular smooth muscle cells (VSMC, interact with their environment through novel receptors. We found, through a proteomics screen, that MSC express the bitter taste receptor, TAS2R46, a protein more typically localized to the taste bud. Expression was also confirmed in VSMCs. A prototypical bitter compound that binds to the bitter taste receptor class, denatonium, increased intracellular calcium release and decreased cAMP levels as well as increased the extracellular release of ATP in human MSC. Denatonium also bound and activated rodent VSMC with a change in morphology upon compound exposure. Finally, rodents given denatonium in vivo had a significant drop in blood pressure indicating a vasodilator response. This is the first description of chemosensory detection by MSC and VSMCs via a taste receptor. These data open a new avenue of research into discovering novel compounds that operate through taste receptors expressed by cells in the marrow and vascular microenvironments.

The effect of adipose derived stromal vascular fraction on stasis zone in an experimental burn model.

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Eyuboglu, Atilla Adnan; Uysal, Cagri A; Ozgun, Gonca; Coskun, Erhan; Markal Ertas, Nilgun; Haberal, Mehmet

2018-03-01

Stasis zone is the surrounding area of the coagulation zone which is an important part determining the extent of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). Thermal injury was applied on dorsum of Sprague-Dawley rats (n=20) by the "comb burn" model as described previously. When the burn injury was established on Sprague-Dawley rats (30min); rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of Sprague-Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density, gradient of fibrosis and epithelial thickness were determined via immunohistochemical assay. Macroscopic stasis zone tissue viability (32±3.28%, 57±4.28%) (p51, 1.50±0.43) (pzone on acute burn injuries. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Management of Corneal Bee Sting Injuries.

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Rai, Ruju R; Gonzalez-Gonzalez, Luis A; Papakostas, Thanos D; Siracuse-Lee, Donna; Dunphy, Robert; Fanciullo, Lisa; Cakiner-Egilmez, Tulay; Daly, Mary K

2017-01-01

To review the management of keratitis after corneal bee stings and to report a case of deep stromal corneal infiltrate secondary to a retained bee stinger managed conservatively in a patient who presented three days after unsanitary manipulation of the stinger apparatus. Case report and review of literature. A 57-year-old male beekeeper was evaluated for pain, blurry vision, and photosensitivity after a corneal bee sting. Of note, the venom sac had been removed with dirty tweezers three days prior to his visit. On exam, a focal infiltrate with diffuse edema was seen surrounding a retained bee stinger in the peripheral cornea. Trace cells in the anterior chamber were also noted. Based on a high suspicion for infectious keratitis, a conservative treatment strategy was elected. Administration of broad-spectrum topical antibiotics with concomitant abstention of corticosteroids led to rapid resolution of the symptoms. Over 16 months of follow-up, the stinger has remained in situ without migration and the patient has maintained 20/20 visual acuity without complications. There is debate on the preferred method for the management of corneal injury secondary to bee stings, especially when it is associated with a retained stinger. We herein present our findings in our appraisal of reported cases. In the aftermath of an ocular bee sting, close surveillance for inflammation and infection is essential. Individual manifestations of these injuries vary in timing, type, and severity; therefore, the accessibility of the stinger and the evolving clinical picture should guide therapeutic decisions.

Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization

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Halil Ibrahim Onder

2014-04-01

Full Text Available AIM:To evaluate the inhibitory effects of regorafenib (BAY 73-4506, a multikinase inhibitor, on corneal neovascularization (NV.METHODS:Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (n = 6 received 0.9% NaCl, Group 2 (n = 6 received dimethyl sulfoxide, Group 3 (n = 6 received regorafenib 1 mg/mL, Group 4 (n =6 received bevacizumab 5 mg/mL and Group 5 (n = 6 received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea’s total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.RESULTS:A statistically significant difference in the percent area of corneal NV was found among the groups (P <0.001. Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (P >0.005. There was a statistically significant difference among the groups in apoptotic cell density (P = 0.002. The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (P <0.05. The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2.CONCLUSION: Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats.

A role for topographic cues in the organization of collagenous matrix by corneal fibroblasts and stem cells.

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Dimitrios Karamichos

Full Text Available Human corneal fibroblasts (HCF and corneal stromal stem cells (CSSC each secrete and organize a thick stroma-like extracellular matrix in response to different substrata, but neither cell type organizes matrix on tissue-culture polystyrene. This study compared cell differentiation and extracellular matrix secreted by these two cell types when they were cultured on identical substrata, polycarbonate Transwell filters. After 4 weeks in culture, both cell types upregulated expression of genes marking differentiated keratocytes (KERA, CHST6, AQP1, B3GNT7. Absolute expression levels of these genes and secretion of keratan sulfate proteoglycans were significantly greater in CSSC than HCF. Both cultures produced extensive extracellular matrix of aligned collagen fibrils types I and V, exhibiting cornea-like lamellar structure. Unlike HCF, CSSC produced little matrix in the presence of serum. Construct thickness and collagen organization was enhanced by TGF-ß3. Scanning electron microscopic examination of the polycarbonate membrane revealed shallow parallel grooves with spacing of 200-300 nm, similar to the topography of aligned nanofiber substratum which we previously showed to induce matrix organization by CSSC. These results demonstrate that both corneal fibroblasts and stromal stem cells respond to a specific pattern of topographical cues by secreting highly organized extracellular matrix typical of corneal stroma. The data also suggest that the potential for matrix secretion and organization may not be directly related to the expression of molecular markers used to identify differentiated keratocytes.

Corneal neurotoxicity due to topical benzalkonium chloride.

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Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

2012-04-06

The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro. Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth. BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001). Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production.

Quantitative Assessment of Ultrastructure and Light Scatter in Mouse Corneal Debridement Wounds

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Boote, Craig; Du, Yiqin; Morgan, Sian; Harris, Jonathan; Kamma-Lorger, Christina S.; Hayes, Sally; Lathrop, Kira L.; Roh, Danny S.; Burrow, Michael K.; Hiller, Jennifer; Terrill, Nicholas J.; Funderburgh, James L.; Meek, Keith M.

2012-01-01

Purpose. The mouse has become an important wound healing model with which to study corneal fibrosis, a frequent complication of refractive surgery. The aim of the current study was to quantify changes in stromal ultrastructure and light scatter that characterize fibrosis in mouse corneal debridement wounds. Methods. Epithelial debridement wounds, with and without removal of basement membrane, were produced in C57BL/6 mice. Corneal opacity was measured using optical coherence tomography, and collagen diameter and matrix order were quantified by x-ray scattering. Electron microscopy was used to visualize proteoglycans. Quantitative PCR (Q-PCR) measured mRNA transcript levels for several quiescent and fibrotic markers. Results. Epithelial debridement without basement membrane disruption produced a significant increase in matrix disorder at 8 weeks, but minimal corneal opacity. In contrast, basement membrane penetration led to increases in light scatter, matrix disorder, and collagen diameter, accompanied by the appearance of abnormally large proteoglycans in the subepithelial stroma. This group also demonstrated upregulation of several quiescent and fibrotic markers 2 to 4 weeks after wounding. Conclusions. Fibrotic corneal wound healing in mice involves extensive changes to collagen and proteoglycan ultrastructure, consistent with deposition of opaque scar tissue. Epithelial basement membrane penetration is a deciding factor determining the degree of ultrastructural changes and resulting opacity. PMID:22467580

Experimental Models for Investigating Intra-Stromal Migration of Corneal Keratocytes, Fibroblasts and Myofibroblasts

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Lisha Ma

2012-03-01

Full Text Available Following laser vision correction, corneal keratocytes must repopulate areas of cell loss by migrating through the intact corneal stroma, and this can impact corneal shape and transparency. In this study, we evaluate 3D culture models for simulating this process in vitro. Buttons (8 mm diameter were first punched out of keratocyte populated compressed collagen matrices, exposed to a 3 mm diameter freeze injury, and cultured in serum-free media (basal media or media supplemented with 10% FBS, TGFb1 or PDGF BB. Following freeze injury, a region of cell death was observed in the center of the constructs. Although cells readily migrated on top of the matrices to cover the wound area, a limited amount of cell migration was observed within the constructs. We next developed a novel “sandwich” model, which better mimics the native lamellar architecture of the cornea. Using this model, significant migration was observed under all conditions studied. In both models, cells in TGFb and 10% FBS developed stress fibers; whereas cells in PDGF were more dendritic. PDGF stimulated the most inter-lamellar migration in the sandwich construct. Overall, these models provide insights into the complex interplay between growth factors, cell mechanical phenotypes and the structural properties of the ECM.

Outcome of corneal transplantation in a private institution in Saudi Arabia

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Omar N

2013-06-01

Full Text Available Nazri Omar,1,2 Charbel T Bou Chacra,1 Khalid F Tabbara1,3,4 1The Eye Center and The Eye Foundation for Research in Ophthalmology, Riyadh, Saudi Arabia; 2Department of Ophthalmology, Universiti Putra Malaysia, Serdang, Malaysia; 3Department of Ophthalmology, King Saud University, Riyadh, Saudi Arabia; 4The Wilmer Ophthalmological Institute of Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: The aim of this work was to describe the indications, complications, and outcomes of penetrating keratoplasty (PKP in Saudi Arabia. Methods: In a retrospective, noncomparative interventional case series, the medical records of patients who underwent PKP from January 2000 to December 2008 and had a minimum follow-up of 6 months were reviewed. All corneas were obtained from eye banks in the US. Indications, complications, and outcomes of surgery were recorded. This study was approved by the institutional review board. Results: Eighty-five consecutive eyes were included in this study. There were 52 (61.2% males and 33 (38.8% females. The median age was 35.0 years (range 3–85 years, and the median follow-up period was 24 months (range 6–108 months. The indications for PKP were keratoconus, bullous keratopathy, corneal scars, corneal dystrophy, and corneal regraft. The overall graft survival time was 88.9 months ± 4.9 months (mean ± standard error of mean, 95% confidence interval [CI] 79.4 months -98.4 months while the 3-year and 5-year cumulative survival rates were 90.7% and 84.3%, respectively. Surgical indication (P = 0.038, immune rejection (P < 0.001, preoperative corneal vascularization (P = 0.022, and perioperative high intraocular pressure (P = 0.032 were associated significantly with corneal graft failure in univariate analysis. Multivariate analysis reduced these significant associations to rejection (P < 0.001 and vascularization (P = 0.009. Relative risk for failure in rejected cornea was 16.22 (95% CI 4.99–52.69 and

Clinical evaluation and induced corneal vascularization study by native and anionic collagen membranes in rabbits corneas Avaliação clínica e estudo da vascularização corneal induzida pelas membranas de colágeno nativo e aniônico em córneas de coelhos

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Thaís Eliane Binotto

2009-12-01

Full Text Available PURPOSE: To evaluate the corneal vascularization (CV and the clinical aspects induced by interlamellar graft with native (NCM and anionic (ACM collagen membranes in rabbits corneas. METHODS: An interlamellar graft with a 0.25 x 0.25 cm NCM (group 1 or ACM (group 2 fragment was performed in the right eye (treated eye. In the left eye, an estromal tunnel was done (control eye. Sixteen rabbits were used, and they were subdivided into two experimental groups of eight animals each. The clinical evaluation was performed at the 1st, 3rd, 7th, 15th and 30th postoperative days. Corneal vascularization analysis was performed after 30 days by the Images Analizator System Leica Qwin-550®. RESULTS: After 7 days, corneal vascularization was observed at about 2.25 ± 0.71 mm (NCM and at about 1.0 ± 1.69 mm (ACM, respectively, from the limbus in direction to the central cornea. After 15 days, CV increased in both groups (5.25 ± 1.03 mm - NCM; 2.0 ± 2.39 mm - ACM and then progressively decreased until day 30 (2.25 ± 2.10 mm - NCM; 0.75 ± 2.12 mm - ACM. The statistical analysis indicated that the averages of the distances from the limb vessels to the grafts observed after 7 and 15 days had not differed statistically (p=0.17, and after 15 and 30 postoperative days had a tendency to differ statistically (p=0.09. The control eyes did not present any changes. CONCLUSION: The interlamellar graft with native and anionic collagen membranes induced corneal vascularization when applied to rabbit corneas, but anionic collagen membrane induced a smaller corneal vascularization when compared to native collagen membrane. Although further studies are required, the results found in this study demonstrated the usefulness of interlamellar graft with native and anionic collagen membranes in keratoplasties. These membranes consists in one more graft option for the surgical treatment of corneal repair in rabbits and others animals, when other forms of medical and surgical

Ocular surface changes in limbal stem cell deficiency caused by chemical injury: a histologic study of excised pannus from recipients of cultured corneal epithelium.

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Fatima, A; Iftekhar, G; Sangwan, V S; Vemuganti, G K

2008-09-01

To report histopathologic changes of the ocular surface pannus in patients with severe limbal stem cell deficiency (LSCD). Corneal and conjunctival pannus tissues from 29 patients undergoing ocular reconstruction with cultured limbal cell transplantation were included. The medical records of these patients were reviewed for demographics, aetiologic diagnosis, type of injury, interval between the initial insult and excision of pannus, and medical history involving human amniotic membrane (HAM) or limbal transplantation. The paraffin-embedded tissues were reviewed for epithelial changes, type-degree of fibrosis, degenerative changes, vascular changes, conjunctivalization of corneal surface, and evidence of residual HAM. We attempted a clinicopathologic correlation to understand the pathogenesis of pannus formation in LSCD. The 29 tissues were from 29 eyes of patients with primary aetiology of chemical burn in 89.6% (undetermined in 10.4%) of cases. The pannus showed epithelial hyperplasia in 62%, active fibrosis in 66%, severe inflammation in 21%, giant cell reaction in 28%, and stromal calcification in 14% cases. Goblet cells were seen over the cornea in 64% cases; their absence was associated with squamous metaplasia of the conjunctiva and with long duration of insult. Evidence of residual HAM was noted in 42% cases. The commonest cause of severe LSCD is alkali-induced injury. Goblet cells over the cornea were seen in 60% of cases. HAM used for ocular surface reconstruction could persist for long periods within the corneal pannus, thus raising the need for further studies with long-term follow-up.

Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1α and inhibits stromal cell-derived factor-1 in human endometrial stromal cells.

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Tsuzuki, Tomoko; Okada, Hidetaka; Cho, Hisayuu; Tsuji, Shoko; Nishigaki, Akemi; Yasuda, Katsuhiko; Kanzaki, Hideharu

2012-02-01

Hypoxia of the human endometrium is a physiologic event occurring during the perimenstrual period and the local stimulus for angiogenesis. The aim of this study was to investigate the effects of hypoxic stress on the regulation of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1/CXCL12), and the potential role of hypoxia-inducible factor-1α (HIF-1α) in the endometrium. Human endometrial stromal cells (ESCs, n= 22 samples) were studied in vitro. ESCs were cultured under hypoxic and normoxic conditions and treated with cobalt chloride (CoCl₂; a hypoxia-mimicking agent) and/or echinomycin, a small-molecule inhibitor of HIF-1α activity. The mRNA levels and production of VEGF and SDF-1 were assessed by real-time PCR and ELISA, respectively. The HIF-1α protein levels were measured using western blot analysis. Hypoxia simultaneously induced the expression of mRNA and production of VEGF and attenuated the expression and production of SDF-1 from ESCs in a time-dependent manner. Similar changes were observed in the ESCs after stimulation with CoCl₂ in a dose-dependent manner. CoCl₂ significantly induced the expression of HIF-1α protein, and its highest expression was observed at 6 h. Echinomycin inhibited hypoxia-induced VEGF production without affecting the HIF-1α protein level and cell toxicity and had no effect on SDF-1 secretion (P hypoxic conditions that could influence angiogenesis in the human endometrium.

Corneal conjunctivalization management with high Dk RGP contact lenses.

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Martin, Raul

2009-06-01

To describe the management of corneal conjunctivalization with a high Dk RGP contact lens (CL) fitting. A high Dk RGP CL (Menicon Z-alpha Dk=189, Japan) was fitted, after temporary suspension of CL wear (6 months and 3 weeks), in two patients (a 36-year-old female and a 38-year-old male) who had corneal conjunctivalization secondary to low Dk soft CL wear. Both patients had worn their soft CLs 12-14 h per day without symptoms for the previous 18-20 years. After 9-15 months of high Dk RGP wear, all signs of corneal conjunctivalization had disappeared (corneal vascularization, late fluorescein stain, etc.) and patients wore their RGP CL comfortably. Corneal conjunctivalization was resolved with non-invasive procedures (temporary discontinuation, preservative-free artificial tears and high Dk RGP CL fitting) and thus other treatments (topical or surgical treatments such as limbus transplantation, amniotic membrane transplant or others) were not necessary. Short temporary suspension of CL wear (3 weeks), preservative-free artificial tears and refitting with high oxygen permeability RGP CL may be an alternative for the management of corneal conjunctivalization secondary to CL wear.

Risk assessment for ectasia after corneal refractive surgery.

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Randleman, J Bradley; Woodward, Maria; Lynn, Michael J; Stulting, R Doyle

2008-01-01

To analyze the epidemiologic features of ectasia after excimer laser corneal refractive surgery, to identify risk factors for its development, and to devise a screening strategy to minimize its occurrence. Retrospective comparative and case-control study. All cases of ectasia after excimer laser corneal refractive surgery published in the English language with adequate information available through December 2005, unpublished cases seeking treatment at the authors' institution from 1998 through 2005, and a contemporaneous control group who underwent uneventful LASIK and experienced a normal postoperative course. Evaluation of preoperative characteristics, including patient age, gender, spherical equivalent refraction, pachymetry, and topographic patterns; perioperative characteristics, including type of surgery performed, flap thickness, ablation depth, and residual stromal bed (RSB) thickness; and postoperative characteristics including time to onset of ectasia. Development of postoperative corneal ectasia. There were 171 ectasia cases, including 158 published cases and 13 unpublished cases evaluated at the authors' institution. Ectasia occurred after LASIK in 164 cases (95.9%) and after photorefractive keratectomy (PRK) in 7 cases (4.1%). Compared with controls, more ectasia cases had abnormal preoperative topographies (35.7% vs. 0%; Pvs. 40.0 years; Pvs. -5.09 diopters; Pvs. 546.5 microm; Pvs. 317.3 microm; PLASIK that, if validated, represents a significant improvement over current screening strategies.

CD147 required for corneal endothelial lactate transport.

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Li, Shimin; Nguyen, Tracy T; Bonanno, Joseph A

2014-06-26

CD147/basigin is a chaperone for lactate:H(+) cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Corneal Graft Rejection: Incidence and Risk Factors

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Alireza Baradaran-Rafii

2008-12-01

Full Text Available

PURPOSE: To determine the incidence and risk factors of late corneal graft rejection after penetrating keratoplasty (PKP. METHODS: Records of all patients who had undergone PKP from 2002 to 2004 without immunosuppressive therapy other than systemic steroids and with at least one year of follow up were reviewed. The role of possible risk factors such as demographic factors, other host factors, donor factors, indications for PKP as well as type of rejection were evaluated. RESULTS: During the study period, 295 PKPs were performed on 286 patients (176 male, 110 female. Mean age at the time of keratoplasty was 38±20 (range, 40 days to 90 years and mean follow up period was 20±10 (range 12-43 months. Graft rejection occurred in 94 eyes (31.8% at an average of 7.3±6 months (range, 20 days to 39 months after PKP. The most common type of rejection was endothelial (20.7%. Corneal vascularization, regrafting, anterior synechiae, irritating sutures, active inflammation, additional anterior segment procedures, history of trauma, uncontrolled glaucoma, prior graft rejection, recurrence of herpetic infection and eccentric grafting increased the rate of rejection. Patient age, donor size and bilateral transplantation had no significant influence on graft rejection. CONCLUSION: Significant risk factors for corneal graft rejection include

Comparison of topical fixed-combination fortified vancomycin-amikacin (VA solution) to conventional separate therapy in the treatment of bacterial corneal ulcer.

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Chiang, C-C; Lin, J-M; Chen, W-L; Chiu, Y-T; Tsai, Y-Y

2009-02-01

In an in vitro study, fixed-combination fortified vancomycin and amikacin ophthalmic solutions (VA solution) had the same potency and stable physical properties as the separate components. In this retrospective clinical study, we evaluated the efficacy of the topical VA solution in the treatment of bacterial corneal ulcer and comparison with separate topical fortified vancomycin and amikacin. Separate topical fortified eye drops was used prior to January 2004 and switched to the VA solution afterwards in the treatment of bacterial corneal ulcer. The medical records of 223 patients diagnosed with bacterial corneal ulcers between January 2002 and December 2005 were reviewed retrospectively. There were 122 patients in the VA group and 101 in the separate group. Cure was defined as complete healing of the ulcer accompanied by a nonprogressive stromal infiltrate on two consecutive visits. No significant difference was found between the VA and separate therapy group. The mean treatment duration was 15.4 days in the VA group and 16.1 days in the separate therapy group. The average hospital stay was 5.4 days (VA) and 7.2 days (separate antibiotics). Stromal infiltration regressed significantly without further expansion in both groups. All corneal ulcers completely re-epithelialized without complications related to drugs. VA solution provided similar efficacy to the conventional separate therapy in the treatment of bacterial corneal ulcers; however, it is more convenient and tolerable, promotes patient's compliance, avoids the washout effect, and reduces nurse utilization. Hence, VA solution is a good alternative to separate therapy.

Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

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Hongshan Liu

Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

A new nanosecond UV laser at 355 nm: early results of corneal flap cutting in a rabbit model.

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Trost, Andrea; Schrödl, Falk; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Kaser-Eichberger, Alexandra; Krefft, Karolina; Vogel, Alfred; Linz, Norbert; Freidank, Sebastian; Hilpert, Andrea; Zimmermann, Inge; Grabner, Günther; Reitsamer, Herbert A

2013-12-03

A new 355 nm UV laser was used for corneal flap cutting in an animal model and tested for clinical and morphologic alterations. Corneal flaps were created (Chinchilla Bastards; n = 25) with an UV nanosecond laser at 355 nm (150 kHz, pulse duration 850 ps, spot-size 1 μm, spot spacing 6 × 6 μm, side cut Δz 1 μm; cutting depth 130 μm) and pulse energies of 2.2 or 2.5 μJ, respectively. Following slit-lamp examination, animals were killed at 6, 12, and 24 hours after treatment. Corneas were prepared for histology (hematoxylin and eosin [HE], TUNEL-assay) and evaluated statistically, followed by ultrastructural investigations. Laser treatment was tolerated well, flap lift was easier at 2.5 μJ compared with 2.2 μJ. Standard HE at 24 hours revealed intact epithelium in the horizontal cut, with similar increase in corneal thickness at both energies. Irrespective of energy levels, TUNEL assay revealed comparable numbers of apoptotic cells in the horizontal and vertical cut at 6, 12, and 24 hours, becoming detectable in the horizontal cut as an acellular stromal band at 24 hours. Ultrastructural analysis revealed regular morphology in the epi- and endothelium, while in the stroma, disorganized collagen lamellae were detectable representing the horizontal cut, again irrespective of energy levels applied. This new UV laser revealed no epi- nor endothelial damage at energies feasible for corneal flap cutting. Observed corneal swelling was lower compared with existing UV laser studies, albeit total energy applied here was much higher. Observed loss of stromal keratinocytes is comparable with available laser systems. Therefore, this new laser is suitable for refractive surgery, awaiting its test in a chronic environment.

Corneal Endothelial Safety of Intracameral Preservative-free 1% Xylocaine

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Shah Alpesh

2004-01-01

Full Text Available Purpose : To evaluate the effect of intracameral preservative-free 1% xylocaine on the corneal endothelium as an adjuvant to topical anaesthesia during phacoemulsification and Acrysof foldable IOL implantation. Material & Methods: This is a prospective, controlled, randomised, double-masked study. 106 patients with soft to moderately dense (Grade 1-3 senile cataract and corneal endothelial cell density of >1500/mm2 were randomised to the xylocaine group (n=53 and control group(n=53. Central endothelial specular microscopy and ultrasound corneal pachymetry were performed preoperatively. On the first postoperative day the eyes were evaluated for corneal oedema and Descemet′s folds. Ultrasound corneal pachymetry was performed at 1, 3 and 12 months. Specular microscopy was performed at 3 and 12 months. Cell loss was expressed as a percentage of preoperative cell density. Six patients could not complete one year follow-up. Chi-square and paired t test (2 tail statistical tests were applied for analysis. Results: Four (7.54% patients in the xylocaine group and 5 (9.43% in the control group had a few Descemet′s folds associated with mild central stromal oedema. Corneal thickness increased from 549.3µ ± 37.2µ to 555.5µ ± 36.5µ in the xylocaine group and from 553.1µ ± 36.2µ to 559.3µ ± 40.5µ in the control group at the one-month postoperative visit. Thickness returned to the preoperative level in xylocaine group 549.6µ ± 34.5µ and control group 554.7µ ± 41.1µ at three months. (P=0.484 The percentage of cell loss was 4.47 ± 2.53% in the xylocaine group and 4.49 ± 3.09 % in the control group at one year. (P=0.97 Conclusion: Intracameral preservative-free 1% xylocaine does not appear to affect corneal endothelium adversely during phacoemulsification.

Equine deep stromal abscesses (51 cases - 2004-2009) - Part 2

DEFF Research Database (Denmark)

Henriksen, Michala de Linde; Andersen, Pia Haubro; Mietelka, Kristy

2014-01-01

To investigate histopathologic and immunohistochemical aspects of equine deep stromal abscesses (DSA) with a focus on the histopathologic diagnosis, presumptive etiology, and the immunohistochemical expression of three angiogenesis-related factors: vascular endothelial growth factor-A (VEGF...

Thermal and infrared-diode laser effects on indocyanine-green-treated corneal collagen

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Timberlake, George T.; Patmore, Ann; Shallal, Assaad; McHugh, Dominic; Marshall, John

1993-07-01

It has been suggested that laser welds of collagenous tissues form by interdigitation and chemical bonding of thermally 'unraveled' collagen fibrils. We investigated this proposal by attempting to weld highly collagenous, avascular corneal tissue with an infrared (IR) diode laser as follows. First, the temperature at which corneal collagen shrinks and collagen fibrils 'split' into subfibrillary components was determined. Second, since use of a near-IR laser wavelength necessitated addition of an absorbing dye (indocyanine green (ICG) to the cornea, we measured absorption spectra of ICG-treated tissue to ensure that peak ICG absorbance did not change markedly when ICG was present in the cornea. Third, using gel electrophoresis of thermally altered corneal collagen, we searched for covalently crosslinked compounds predicted by the proposed welding mechanism. Finally, we attempted to weld partial thickness corneal incisions infused with ICG. Principal experimental findings were as follows: (1) Human corneal (type I) collagen splits into subfibrillary components at approximately 63 degree(s)C, the same temperature that produces collagen shrinkage. (2) Peak ICG absorption does not change significantly in corneal stroma or with laser heating. (3) No evidence was found for the formation of novel compounds or the loss of proteins as a result of tissue heating. All tissue treated with ICG, however, exhibited a novel 244 kD protein band indicating chemical activity between collagen and corneal stromal components. (4) Laser welding corneal incisions was unsuccessful possibly due to shrinkage of the sides of the incision, lack of incision compression during heating, or a less than optimal combination of ICG concentration and radiant exposure. In summary, these experiments demonstrate the biochemical and morphological complexity of ICG-enhanced IR laser-tissue welding and the need for further investigation of laser welding mechanisms.

Extensive bilateral corneal edema 6 weeks after cataract surgery: Keratopathy due to Asclepias physocarpa: a case report.

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Matsuura, Kazuki; Hatta, Shiro; Terasaka, Yuki; Inoue, Yoshitsugu

2017-01-18

Surgeons may be unaware of the ability of plant toxins to cause corneal damage. Therefore, corneal damage following intraocular surgery due to plant toxins may be misdiagnosed as postoperative infection. A 74-year-old man presented with hyperemia and reduced visual acuity in both eyes 6 weeks after uneventful cataract surgery. We observed extensive hyperemia and corneal stromal edema with Descemet's folds in both eyes. After obtaining a detailed patient history, we diagnosed plant toxin-induced corneal edema due to Asclepias physocarpa, which can induce corneal edema by inhibiting the Na + /K + ATPase activity of the corneal endothelium. Antimicrobial and steroid eye drops and an oral steroid were prescribed accordingly. Symptons began to improve on day 3 and had almost completely resolved by day 6. At 1 month, the patient had fully recovered without any sequelae. The correct diagnosis was possible in the present case as symptoms were bilateral and the patient was able to report his potential exposure to plant toxins. However, if the symptoms had been unilateral and the patient had been unaware of these toxins, he may have undergone unnecessary surgical interventions to treat non-existent postoperative endophthalmitis.

Effects of topical vitamin E on corneal superoxide dismutase, glutathione peroxidase activities and polymorphonuclear leucocyte infiltration after photorefractive keratectomy.

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Bilgihan, Ayse; Bilgihan, Kamil; Yis, Ozgür; Sezer, Cem; Akyol, Gülen; Hasanreisoglu, Berati

2003-04-01

Photorefractive keratectomy (PRK) induces free radical formation and polymorphonuclear (PMN) cell infiltration in the cornea. Vitamin E is a free radical scavenger and protects the cells from reactive oxygen species. We investigated the effects of topical vitamin E on corneal PMN cell infiltration and corneal antioxidant enzyme activities after PRK. We studied four groups, each consisting of seven eyes. Group 1 were control eyes. In group 2 the corneal epithelium was removed by a blunt spatula (epithelial scrape). In group 3, corneal photoablation (59 micro m, 5 dioptres) was performed after epithelial removal (traditional PRK). In group 4 we tested the effects of topical Vitamin E after traditional PRK. Corneal tissues were removed and studied with enzymatic analysis (measurement of corneal superoxide dismutase and glutathione peroxidase activities) and histologically. Stromal PMN leucocyte counts were significantly higher after mechanical epithelial removal and traditional PRK (p < 0.05). Corneal superoxide dismutase and glutathione peroxidase activities decreased significantly after mechanical epithelial removal and traditional PRK (p < 0.05). In group 4, treated with vitamin E, corneal superoxide dismutase activity did not differ significantly from that in the medically non-treated groups, nor did corneal PMN cell infiltration after traditional PRK. The reduction of corneal glutathione peroxidase activity after PRK was reduced significantly after topical vitamin E treatment. Topical vitamin E treatment may be useful for reducing the harmful effects of reactive oxygen radical after epithelial scraping and PRK in that it increases corneal glutathione peroxidase activity.

Human tears reveal insights into corneal neovascularization.

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Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

2012-01-01

Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

Lack of evidence for protein AA reactivity in amyloid deposits of lattice corneal dystrophy and amyloid corneal degeneration.

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Gorevic, P D; Rodrigues, M M; Krachmer, J H; Green, C; Fujihara, S; Glenner, G G

1984-08-15

Amyloid fibrils occurring in primary and myeloma-associated (AL), secondary (AA), and certain neuropathic hereditary forms of systemic amyloidosis can be distinguished biochemically or immunohistologically as being composed of immunoglobulin light chain, protein AA, or prealbumin respectively. All types of systemic and several localized forms of amyloidosis contain amyloid P component (protein AP). We studied formalin-fixed tissue from eight cases of lattice corneal dystrophy by the immunoperoxidase method using antisera to proteins AA and AP, to normal serum prealbumin and prealbumin isolated from a case of hereditary amyloidosis, and to light-chain determinants; additional cases were examined by indirect immunofluorescence of fresh-frozen material. We found weak (1:10 dilution) staining with anti-AP, but no reactivity with other antisera. Congo red staining was resistant to pretreatment of sections with potassium permanganate, a characteristic of non-AA amyloid. Two-dimensional gels of solubilized proteins from frozen tissue from two cases of lattice corneal dystrophy resembled those obtained from normal human cornea. Western blots of two cases of polymorphous amyloid degeneration and solubilized protein from normal cornea did not react with radioactive iodine-labeled anti-AA or anti-AP with purified protein AP and unfixed protein AA amyloid tissue as controls. We were unable to corroborate the presence of protein AA in the amyloid deposits of lattice corneal dystrophy. Although staining with antiserum to protein AP was demonstrable, the molecular configuration of this protein in stromal deposits remains to be defined.

Matrix metalloproteinases (MMP-2 and MMP-9) activity in corneal ulcer and ocular surface disorders determined by gelatin zymography.

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Singh, Arti; Maurya, O P S; Jagannadhan, M V; Patel, Ashok

2012-01-01

The purpose of this paper is to determine the active form of matrix metalloproteinases (MMP-2 and MMP-9) in corneal ulcer and ocular surface disorder patients. A total of 35 patients of corneal ulcer, 20 patients of ocular surface disorders and 10 control subjects were included in this study and estimation of active form of MMP-2 and MMP-9 was done by gelatin zymography. Tear samples were collected by capillary tube method. Both pro- and active forms of MMP-9 were detected in 24 out of 35 patients with corneal ulcer and 15 out of 20 patients with ocular surface disorders. None of the patients were showing MMP-2 activity. Neither MMP-2 nor MMP-9 was detected in the control group. Active forms of MMP-9 are present in tears of severe ulcerative and ocular surface disorder patients. Thus, proteinase inhibitors have been recommended for the treatment of corneal ulcer and ocular surface disorders to reduced the progression of stromal ulcer and to minimize corneal scarring.

Ultrastructural analysis of corneal exposure to UV radiation

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Pitts, D.G.; Bergmanson, J.P.G.; Chu, L.W.-F.

1987-01-01

The primate cornea was exposed to 300 nm UVR with five levels of radiant expsure from 0.08 to 0.6 Jcm/sup -2/. All cellular layers of the cornea were damaged at the 0.08 Jcm/sup -2/ exposure, and damage became more severe as the exposure level was increased. The corneal cells showed variable response in that essentially normal cells were found among damaged cells. Eight days post-exposure using the 0.6 Jcm/sup -2/ level, the epithelium had regained its normal thickness and was populated largely by normal appearing cells; however, the stroma showed damaged keratocytes and the loss of keratocytes. The corneal basement membranes (the epithelial basement membrane and the posterior limiting lamina) and the anterior limiting lamina were not damaged at any exposure level except for an isolated area along the epithelial basement membrane in one cornea. Therefore, one is lead to conclude that basement membranes are unaffected by UVR. The endothelium continued to demonstrate the loss of mitochondria, endoplasmic reticulum and some vacuoles at 8 days after exposure. However, the endothelium appeared to have resumed its physiological function as demonstrated by the reduced stromal oedema. This research gives the first complete description of UV-B induced corneal damage and repair of the full, in-depth cornea of the primate using the EM.

Ultrastructural analysis of corneal exposure to UV radiation

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Pitts, D.G.; Bergmanson, J.P.G.; Chu, L. W-F.

1987-01-01

The primate cornea was exposed to 300 nm UVR with five levels of radiant expsure from 0.08 to 0.6 Jcm -2 . All cellular layers of the cornea were damaged at the 0.08 Jcm -2 exposure, and damage became more severe as the exposure level was increased. The corneal cells showed variable response in that essentially normal cells were found among damaged cells. Eight days post-exposure using the 0.6 Jcm -2 level, the epithelium had regained its normal thickness and was populated largely by normal appearing cells; however, the stroma showed damaged keratocytes and the loss of keratocytes. The corneal basement membranes (the epithelial basement membrane and the posterior limiting lamina) and the anterior limiting lamina were not damaged at any exposure level except for an isolated area along the epithelial basement membrane in one cornea. Therefore, one is lead to conclude that basement membranes are unaffected by UVR. The endothelium continued to demonstrate the loss of mitochondria, endoplasmic reticulum and some vacuoles at 8 days after exposure. However, the endothelium appeared to have resumed its physiological function as demonstrated by the reduced stromal oedema. This research gives the first complete description of UV-B induced corneal damage and repair of the full, in-depth cornea of the primate using the EM. (author)

Wnt5a Regulates the Assembly of Human Adipose Derived Stromal Vascular Fraction-Derived Microvasculatures.

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Venkat M Ramakrishnan

Full Text Available Human adipose-derived stromal vascular fraction (hSVF cells are an easily accessible, heterogeneous cell system that can spontaneously self-assemble into functional microvasculatures in vivo. However, the mechanisms underlying vascular self-assembly and maturation are poorly understood, therefore we utilized an in vitro model to identify potential in vivo regulatory mechanisms. We utilized passage one (P1 hSVF because of the rapid UEA1+ endothelium (EC loss at even P2 culture. We exposed hSVF cells to a battery of angiogenesis inhibitors and found that the pan-Wnt inhibitor IWP2 produced the most significant hSVF-EC networking decrease (~25%. To determine which Wnt isoform(s and receptor(s may be involved, hSVF was screened by PCR for isoforms associated with angiogenesis, with only WNT5A and its receptor, FZD4, being expressed for all time points observed. Immunocytochemistry confirmed Wnt5a protein expression by hSVF. To see if Wnt5a alone could restore IWP2-induced EC network inhibition, recombinant human Wnt5a (0-150 ng/ml was added to IWP2-treated cultures. The addition of rhWnt5a significantly increased EC network area and significantly decreased the ratio of total EC network length to EC network area compared to untreated controls. To determine if Wnt5a mediates in vivo microvascular self-assembly, 3D hSVF constructs containing an IgG isotype control, anti-Wnt5a neutralizing antibody or rhWnt5a were implanted subcutaneously for 2w in immune compromised mice. Compared to IgG controls, anti-Wnt5a treatment significantly reduced vessel length density by ~41%, while rhWnt5a significantly increased vessel length density by ~62%. However, anti-Wnt5a or rhWnt5a did not significantly affect the density of segments and nodes, both of which measure vascular complexity. Taken together, this data demonstrates that endogenous Wnt5a produced by hSVF plays a regulatory role in microvascular self-assembly in vivo. These findings also suggest that

Hyperplastic corneal pannus: an immunohistochemical analysis and review.

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Jakobiec, Frederick A; Stacy, Rebecca C; Mendoza, Pia R; Chodosh, James

2014-01-01

An exuberant corneal pannus usually develops in adults with a history of surgery or trauma in the anterior central stroma and appears as a glistening, vascularized, moderately elevated, well circumscribed white nodule. We describe a 78-year-old woman with such a pannus, which in the past has typically been referred to as keloidal or hypertrophic. The involved eye had only light perception, and she underwent a penetrating keratoplasty that improved her vision to 20/100. Histopathologic and immunohistochemical evaluations of a the specimen disclosed a reactive spindle cell stromal proliferation of myofibroblasts that were smooth muscle actin positive with a low Ki67 proliferation index. Desmin, caldesmon, and calponin were negative, in keeping with the incomplete myofilamentary differentiation of a myofibroblast. There was a generous admixture of CD68/163-positive histiocytes and dispersed C3/5-positive T-lymphocytes. An absence of CD138- and IgG4-positive plasma cells ruled out an IgG4-related disease. For a lesion to be keloidal, the collagen must have a thick hyaline character, sharp edges, and a sparsity of intervening cells and vessels. A hypertrophic pannus would be composed of large swollen cells not necessarily increased in number. We therefore recommend adoption of the term hyperplastic for lesions like that described here because of the obvious increase in cellularity from proliferating myofibroblasts and the lack of true keloidal collagen. Copyright © 2014 Elsevier Inc. All rights reserved.

Surgical therapies for corneal perforations: 10 years of cases in a tertiary referral hospital

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Yokogawa H

2014-10-01

Full Text Available Hideaki Yokogawa, Akira Kobayashi, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: To report surgical therapies for corneal perforations in a tertiary referral hospital.Methods: Thirty-one eyes of 31 patients (aged 62.4±18.3 years with surgically treated corneal perforations from January 2002 to July 2013 were included in this study. Demographic data such as cause of corneal perforation, surgical procedures, and visual outcomes were retrospectively analyzed.Results: The causes of corneal perforation (n=31 were divided into infectious (n=8, 26% and noninfectious (n=23, 74% categories. Infectious causes included fungal ulcer, herpetic stromal necrotizing keratitis, and bacterial ulcer. The causes of noninfectious keratopathy included corneal melting after removal of a metal foreign body, severe dry eye, lagophthalmos, canaliculitis, the oral anticancer drug S-1, keratoconus, rheumatoid arthritis, neurotrophic ulcer, atopic keratoconjunctivitis, and unknown causes. Initial surgical procedures included central large corneal graft (n=17, small corneal graft (n=7, and amniotic membrane transplantation (n=7. In two cases the perforation could not be sealed during the first surgical treatment and required subsequent procedures. All infectious keratitis required central large penetrating keratoplasty to obtain anatomical cure. In contrast, several surgical options were used for the treatment of noninfectious keratitis. After surgical treatment, anatomical cure was obtained in all cases. Mean postoperative best corrected visual acuity was better at 6 months (logMAR 1.3 than preoperatively (logMAR 1.8.Conclusion: Surgical therapies for corneal perforations in our hospital included central large lamellar/penetrating keratoplasty, small peripheral patch graft, and amniotic membrane transplantation. All treatments were effective. Corneal

Efficacy of iontophoresis-assisted epithelium-on corneal cross-linking for keratoconus

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Hong-Zhen Jia

2018-04-01

Full Text Available Corneal cross-linking (CXL is a noninvasive therapeutic procedure for keratoconus that is aimed at improving corneal biomechanical properties by induction of covalent cross-links between stromal proteins. It is accomplished by ultraviolet A (UVA radiation of the cornea, which is first saturated with photosensitizing riboflavin. It has been shown that standard epithelium-off CXL (S-CXL is efficacious, and it has been recommended as the standard of care procedure for keratoconus. However, epithelial removal leads to pain, transient vision loss, and a higher risk of corneal infection. To avoid these disadvantages, transepithelial CXL was developed. Recently, iontophoresis has been adopted to increase riboflavin penetration through the epithelium. Several clinical observations have demonstrated the safety and efficacy of iontophoresis-assisted epithelium-on CXL (I-CXL for keratoconus. This review aimed to provide a comprehensive summary of the published studies regarding I-CXL and a comparison between I-CXL and S-CXL. All articles used in this review were mainly retrieved from the PubMed database. Original articles and reviews were selected if they were related to the I-CXL technique or related to the comparison between I-CXL and S-CXL.

Inhibition of Corneal Neovascularization by Topical and Subconjunctival Tigecycline

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Sertan Goktas

2014-01-01

Full Text Available Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization. Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1 or subconjunctival instillation of 1 mg/mL tigecycline (group 3 for 7 days. Control rats received topical (group 2 or subconjunctival (group 4 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically. Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI, 44.2–55.8% and 33.5% (95% CI, 26.6–39.2%, respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (P=0.03 and P<0.001, resp.. Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups. Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns

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Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

2016-01-01

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties. PMID:27057279

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

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Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

2016-01-01

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns

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Cestmir Cejka

2016-01-01

Full Text Available The aim of this study was to examine whether mesenchymal stem cells (MSCs and/or corneal limbal epithelial stem cells (LSCs influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs, with adipose tissue MSCs (Ad-MSCs, or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9, inducible nitric oxide synthase (iNOS, α-smooth muscle actin (α-SMA, transforming growth factor-β1 (TGF-β1, and vascular endothelial factor (VEGF were low. The central corneal thickness (taken as an index of corneal hydration increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy

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Yun Gu

2014-01-01

Full Text Available Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR δ had antifibrosis effects in a rat model of corneal damage. Adult Sprague-Dawley rats underwent bilateral phototherapeutic keratectomy (PTK. The eyes were randomized into four groups: PBS, GW501516 (a selective agonist of PPARδ, GSK3787 (a selective antagonist of PPARδ, or GW501516 combined with GSK3787. The agents were subconjunctivally administered twice a week until sacrifice. The cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and postmortem histology. A myofibroblast marker (α-smooth muscle actin and ECM production (fibronectin, collagen type III and collagen type I were examined by immunohistochemistry and RT-PCR. At the early stages of wound healing, GW501516 inhibited reepithelialization and promoted angiogenesis. During the remodeling phase of wound healing, GW501516 attenuated the activation and proliferation of keratocytes, which could be reversed by GSK3787. GW501516 decreased transdifferentiation from keratocytes into myofibroblasts, ECM synthesis, and corneal haze. These results demonstrate that GW501516 controls corneal fibrosis and suggest that PPARδ may potentially serve as a therapeutic target for treating corneal scars.

Corneal Absorption of a New Riboflavin-Nanostructured System for Transepithelial Collagen Cross-Linking

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Bottos, Katia M.; Oliveira, Anselmo G.; Bersanetti, Patrícia A.; Nogueira, Regina F.; Lima-Filho, Acácio A. S.; Cardillo, José A.; Schor, Paulo; Chamon, Wallace

2013-01-01

Corneal collagen cross-linking (CXL) has been described as a promising therapy for keratoconus. According to standard CXL protocol, epithelium should be debrided before treatment to allow penetration of riboflavin into the corneal stroma. However, removal of the epithelium can increase procedure risks. In this study we aim to evaluate stromal penetration of a biocompatible riboflavin-based nanoemulsion system (riboflavin-5-phosphate and riboflavin-base) in rabbit corneas with intact epithelium. Two riboflavin nanoemulsions were developed. Transmittance and absorption coefficient were measured on corneas with intact epithelia after 30, 60, 120, 180, and 240 minutes following exposure to either the nanoemulsions or standard 0.1% or 1% riboflavin-dextran solutions. For the nanoemulsions, the epithelium was removed after measurements to assure that the riboflavin had passed through the hydrophobic epithelium and retained within the stroma. Results were compared to de-epithelialized corneas exposed to 0.1% riboflavin solution and to the same riboflavin nanoemulsions for 30 minutes (standard protocol). Mean transmittance and absorption measured in epithelialized corneas receiving the standard 0.1% riboflavin solution did not reach the levels found on the debrided corneas using the standard technique. Neither increasing the time of exposure nor the concentration of the riboflavin solution from 0.1% to 1% improved riboflavin penetration through the epithelium. When using riboflavin-5-phosphate nanoemulsion for 240 minutes, we found no difference between the mean absorption coefficients to the standard cross-linking protocol (p = 0.54). Riboflavin nanoemulsion was able to penetrate the corneal epithelium, achieving, after 240 minutes, greater stromal concentration when compared to debrided corneas with the standard protocol (p = 0.002). The riboflavin-5-phosphate nanoemulsion diffused better into the stroma than the riboflavin-base nanoemulsion. PMID:23785497

Evaluation of Corneal Neovascularization Using Optical Coherence Tomography Angiography in Patients With Limbal Stem Cell Deficiency.

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Oie, Yoshinori; Nishida, Kohji

2017-11-01

Detection of the exact area of corneal neovascularization using slit-lamp photography is often difficult. Thus, we evaluated corneal neovascularization in patients with limbal stem cell deficiency using optical coherence tomography angiography (OCTA). Five patients with 5 eyes showing partial or total limbal stem cell deficiency were enrolled. Three eyes had severe corneal scarring. Five 6- × 6-mm images (frontal, upper, lower, nasal, and temporal) were obtained by OCTA. Slit-lamp photography was performed for all patients on the same day. OCTA has 2 advantages over slit-lamp photography for clear demonstration of corneal neovascularization. First, OCTA can show neovascularization in cases with severe corneal opacification. Second, OCTA can detect not only large vessels but also small vessels that cannot be seen by slit-lamp photography. OCTA is a powerful tool for objective evaluation of vascularization in the anterior and posterior segments of the eye. We have demonstrated that OCTA can visualize corneal neovascularization in patients with corneal diseases more clearly than slit-lamp photography.

Image-guided modified deep anterior lamellar keratoplasty (DALK) corneal transplant using intraoperative optical coherence tomography

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Tao, Yuankai K.; LaBarbera, Michael; Ehlers, Justis P.; Srivastava, Sunil K.; Dupps, William J.

2015-03-01

Deep anterior lamellar keratoplasty (DALK) is an alternative to full-thickness corneal transplant and has advantages including the absence of allograft rejection; shortened duration of topical corticosteroid treatment and reduced associated risk of glaucoma, cataract, or infection; and enables use of grafts with poor endothelial quality. DALK begins by performing a trephination of approximately 80% stromal thickness, as measured by pachymetry. After removal of the anterior stoma, a needle is inserted into the residual stroma to inject air or viscoelastic to dissect Descemet's membrane. These procedures are inherently difficult and intraoperative rates of Descemet's membrane perforation between 4-39% have been reported. Optical coherence tomography (OCT) provides high-resolution images of tissue microstructures in the cornea, including Descemet's membrane, and allows quantitation of corneal layer thicknesses. Here, we use crosssectional intraoperative OCT (iOCT) measurements of corneal thickness during surgery and a novel micrometeradjustable biopsy punch to precision-cut the stroma down to Descemet's membrane. Our prototype cutting tool allows us to establish a dissection plane at the corneal endothelium interface, mitigates variability in cut-depths as a result of tremor, reduces procedure complexity, and reduces complication rates. iOCT-guided modified DALK procedures were performed on 47 cadaveric porcine eyes by non-experts and achieved a perforation rate of ~5% with a mean corneal dissection time care.

Comparative Confocal and Histopathological Study of Corneal Changes in Multiple Myeloma.

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Micali, Antonio; Roszkowska, Anna M; Postorino, Elisa I; Rania, Laura; Aragona, Emanuela; Wylegala, Edward; Nowinska, Anna; Ieni, Antonio; Calimeri, Sebastiano; Pisani, Antonina; Aragona, Pasquale; Puzzolo, Domenico

2017-01-01

Corneal opacities rarely occur in multiple myeloma (MM). Our study correlates the findings of in vivo confocal microscopy (IVCM), a useful diagnostic tool, with histopathological features of corneal opacities appearing in a patient with MM. Case report. A 53-year-old man developed corneal opacities in both eyes, more pronounced in the left eye. After IVCM examination, he underwent penetrating keratoplasty in the left eye, and the button was processed for light and electron microscopy and immunohistochemistry. The diagnosis of MM was made, as confirmed by the elevation of IgGk light chains. IVCM demonstrated hyperreflective areas at the epithelial level, hyperreflective keratocytes of dendritic and lamellar morphology in whole stroma, and hyperreflective endothelial cells. Histopathological examination disclosed many vacuoles in the epithelial cell cytoplasm and a homogenous granular material in the Bowman layer. In stroma, keratocytes of different shape and size, with vesicles laden with an abnormal material, were evident. In Descemet membrane, the posterior nonbanded zone had a honeycomb appearance because of the presence of many roundish spaces among wide-spaced collagen fibers. Endothelial cells demonstrated vesicles filled with a material of uneven electron density. Immunohistochemical analysis showed strong positivity for IgGk light chains in keratocytes and among stromal lamellae. This is the first study describing a correspondence between IVCM features and histopathological alterations observed in corneal opacities in MM. The results of this study improve the current understanding of the pictures obtained by IVCM studies.

Topical versus subconjunctival anti-vascular endothelial growth factor therapy (Bevacizumab, Ranibizumab and Aflibercept for treatment of corneal neovascularization

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Tariq Al-Debasi

2017-04-01

Anti-VEGF agents (Bevacizumab, Ranibizumab and Aflibercept seem to have a higher efficiency and efficacy for corneal NV treatment. Both subconjunctival therapy and topical therapy of bevacizumab prohibit corneal NV, while early treatment with subconjunctival administration of ranibizumab may successfully reduce corneal NV. Therefore, establishment of safe doses is highly important before these drugs can be involved in the clinical setting. Further investigations and studies are highly warranted to adjust the dose and route of administration for the antibodies directed against VEGF to be the key therapeutic agents in the corneal NV treatment.

Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft

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Qiu, Ying; Yun, Mark M; Han, Xia; Zhao, Ruidong; Zhou, Erxia; Yun, Sheng

2014-01-01

Background: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. Methods: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. Results: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. Conclusions: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID:25126177

[Morphological features of stromal-vascular component of the thymus of stillborn children and children under one year of life from mothers that do not follow a healthy lifestyle

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Gorianikova I.N.

2015-01-01

Background. Morphofunctional state of the thymus of child in most cases is directly dependent on the mother health and her lifestyle. Objective. The purpose of the research was to reveal the morphological features of stromal-vascular component of the thymus of stillborn children and children under one year of life born from women who conducted a sedentary lifestyle, smoked, drank alcohol and ate the foods containing tartrazine. Methods. The material of the study was 67 thymuses of stillborn c...

Queratectomía fototerapéutica en distrofia reticular corneal Phototherapeutical keratetocomy in corneal lattice dystrophy

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Miguel O Mokey Castellanos

2007-06-01

Full Text Available Se realizó un estudio retrospectivo en pacientes con distrofia corneal reticular en los que la recurrencia de la afección ocurrió después de diez años o más de realizada la queratoplastia perforante y en pacientes que presentaban la afección sin tratamiento quirúrgico previo, a los cuales se les realizó queratectomía fototerapéutica con excímer láser. Esta alternativa terapéutica se aplica en afecciones del estroma anterior de la córnea en la que se producen irregularidades en la superficie de esta y disminución de la visión. Fueron tratados 5 ojos correspondientes a 4 pacientes, 3 de ellos pertenecían a una misma familia. Los resultados terapéuticos y visuales mejoraron la calidad de vida de los pacientes, y se postergó la necesidad de retrasplante o trasplante. No tuvimos complicaciones. El excímer láser se convirtió en una alternativa, segura y eficaz en el tratamiento de estas afeccionesA retrospective study was performed on patients with lattice corneal dystrophy, who suffered recurrence ten or more years after penetrating keratoplasty and on patients suffering the same problem but without any previous surgical treatment, who had undergone phototherapeutical keratectomy with Excimer laser. This therapeutic alternative is useful for anterior stromal keratopathy in where corneal irregularities decrease the vision. Five eyes have been treated from 4 patients, 3 of them were relatives. The visual and therapeutical results improved the quality of life of patients, thus postponing the need for transplant or retransplant. No complications were encountered. Laser Excímer became an effective and safe alternative in the treatment of such diseases

Corneal Laceration

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Full Text Available ... Eye Health A-Z Symptoms Glasses & Contacts Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye ... Causes Corneal Laceration? Corneal Laceration Diagnosis Corneal Laceration Treatment What Is Corneal Laceration? Leer en Español: ¿Qué ...

Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formation.

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Franz, Marcus; Wolheim, Anke; Richter, Petra; Umbreit, Claudia; Dahse, Regine; Driemel, Oliver; Hyckel, Peter; Virtanen, Ismo; Kosmehl, Hartwig; Berndt, Alexander

2010-04-01

The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains alpha2, alpha3, alpha4, alpha5 and gamma2 in the stromal compartment/vascular structures in OSCC was analysed. Frozen tissue of OSCC (9x G1, 24x G2, 8x G3) and normal (2x)/hyperplastic (11x) oral mucosa was subjected to laminin chain and alpha-smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31. Stromal laminin alpha2 chain significantly decreases and alpha3, alpha4, alpha5 and gamma2 chains and also ASMA significantly increase with rising grade. The amount of stromal alpha3, alpha4 and gamma2 chains significantly increased with rising ASMA positivity. There is a significant decrease in alpha3 chain positive vessels with neoplastic transformation. Mediated by myofibroblasts, OSCC development is associated with a stromal up-regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning alpha3 and gamma2 chain laminins during tumour angioneogenesis is suggested.

3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

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Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

2017-07-17

Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

Spontaneous Corneal Hydrops in a Patient with a Corneal Ulcer

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Hatim Batawi

2016-01-01

Full Text Available Purpose: We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. Method: This is an observational case report study. Results: A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. Conclusion: Corneal hydrops can occur in the setting of corneal infections.

Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

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Mirco Galiè

2007-11-01

Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

Corneal biomechanical properties from air-puff corneal deformation imaging

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Marcos, Susana; Kling, Sabine; Bekesi, Nandor; Dorronsoro, Carlos

2014-02-01

The combination of air-puff systems with real-time corneal imaging (i.e. Optical Coherence Tomography (OCT), or Scheimpflug) is a promising approach to assess the dynamic biomechanical properties of the corneal tissue in vivo. In this study we present an experimental system which, together with finite element modeling, allows measurements of corneal biomechanical properties from corneal deformation imaging, both ex vivo and in vivo. A spectral OCT instrument combined with an air puff from a non-contact tonometer in a non-collinear configuration was used to image the corneal deformation over full corneal cross-sections, as well as to obtain high speed measurements of the temporal deformation of the corneal apex. Quantitative analysis allows direct extraction of several deformation parameters, such as apex indentation across time, maximal indentation depth, temporal symmetry and peak distance at maximal deformation. The potential of the technique is demonstrated and compared to air-puff imaging with Scheimpflug. Measurements ex vivo were performed on 14 freshly enucleated porcine eyes and five human donor eyes. Measurements in vivo were performed on nine human eyes. Corneal deformation was studied as a function of Intraocular Pressure (IOP, 15-45 mmHg), dehydration, changes in corneal rigidity (produced by UV corneal cross-linking, CXL), and different boundary conditions (sclera, ocular muscles). Geometrical deformation parameters were used as input for inverse finite element simulation to retrieve the corneal dynamic elastic and viscoelastic parameters. Temporal and spatial deformation profiles were very sensitive to the IOP. CXL produced a significant reduction of the cornea indentation (1.41x), and a change in the temporal symmetry of the corneal deformation profile (1.65x), indicating a change in the viscoelastic properties with treatment. Combining air-puff with dynamic imaging and finite element modeling allows characterizing the corneal biomechanics in-vivo.

Corneal Laceration

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Full Text Available ... Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive ... Corneal Laceration Sections What Is Corneal Laceration? Corneal Laceration Symptoms What Causes ...

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

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AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

2016-01-01

Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients

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Khaled AbouSeif

2016-01-01

Full Text Available Disorders associated with the hepatitis C virus (HCV have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC and corneal and conjunctival calcification (CCC in maintenance hemodialysis (MHD patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51 and seronegative patients (n = 49 regarding grading of AAC and CCC (P <0.001. Significant positive correlation was found between grading of CCC, AAC, age (P <0.001, duration on HD (P <0.001, HCV-antibody positivity (P <0.001, serum calcium level (P <0.001, serum phosphorus level (P <0.001, calcium × phosphorus product (P <0.001, and i-parathormone level (P < 0.001. In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear.

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Gumucio, Jonathan P; Flood, Michael D; Roche, Stuart M; Sugg, Kristoffer B; Momoh, Adeyiza O; Kosnik, Paul E; Bedi, Asheesh; Mendias, Christopher L

2016-04-01

Rotator cuff injuries are associated with atrophy and fat infiltration into the muscle, commonly referred to as "fatty degeneration." As the poor function of chronically torn muscles may limit recovery after surgical repair, there is considerable interest in finding therapies to enhance muscle regeneration. Stromal vascular fraction stem cells (SVFCs) can improve muscle regeneration in other chronic injury states, and our objective was to evaluate the ability of SVFCs to reduce fibrosis and fat accumulation, and enhance muscle fibre specific force production after chronic rotator cuff tear. Chronic supraspinatus tears were induced in adult immunodeficient rats, and repaired one month following tear. Rats received vehicle control, or injections of 3 × 10(5) or 3 × 10(6) human SVFCs into supraspinatus muscles. Two weeks following repair, we detected donor human DNA and protein in SVFC treated muscles. There was a 40 % reduction in fibrosis in the treated groups compared to controls (p = 0.03 for 3 × 10(5), p = 0.04 for 3 × 10(6)), and no differences between groups for lipid content or force production were observed. As there has been much interest in the use of stem cell-based therapies in musculoskeletal regenerative medicine, the reduction in fibrosis and trend towards an improvement in single fiber contractility suggest that SVFCs may be beneficial to enhance the treatment and recovery of patients with chronic rotator cuff tears.

Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

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Mingliang Sun

2017-01-01

Full Text Available Mesenchymal stem cells are an attractive cell type for cytotherapy in wound healing. The authors recently developed a novel, adipose-tissue-derived, injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel for stem cell therapy. This study was designed to assess the therapeutic effects of ECM/SVF-gel on wound healing and potential mechanisms. ECM/SVF-gel was prepared for use in nude mouse excisional wound healing model. An SVF cell suspension and phosphate-buffered saline injection served as the control. The expression levels of vascular endothelial growth factor (VEGF, basic fibroblast growth factor (bFGF, and monocyte chemotactic protein-1 (MCP-1 in ECM/SVF-gel were analyzed at different time points. Angiogenesis (tube formation assays of ECM/SVF-gel extracts were evaluated, and vessels density in skin was determined. The ECM/SVF-gel extract promoted tube formation in vitro and increased the expression of the angiogenic factors VEGF and bFGF compared with those in the control. The expression of the inflammatory chemoattractant MCP-1 was high in ECM/SVF-gel at the early stage and decreased sharply during the late stage of wound healing. The potent angiogenic effects exerted by ECM/SVF-gel may contribute to the improvement of wound healing, and these effects could be related to the enhanced inflammatory response in ECM/SVF-gel during the early stage of wound healing.

Effects of three blood derived products on equine corneal cells, an in vitro study.

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Rushton, J O; Kammergruber, E; Tichy, A; Egerbacher, M; Nell, B; Gabner, S

2018-05-01

Despite advances in therapy of corneal ulcerative diseases in horses, a vast number of cases require surgical intervention, due to poor response to treatment. Topical application of serum has been used for many years, based on its anticollagenolytic properties and the presence of growth factors promoting corneal wound healing. However, although other blood derived products i.e. platelet rich plasma (PRP), plasma rich in growth factors (PRGF) have been widely used in equine orthopaedics and in human ophthalmology, no reports of the effects of these blood derived products exist in equine ophthalmology. To determine in vitro effects of PRGF and PRP on equine corneal cells compared with serum. Prospective controlled cohort study. Blood from 35 healthy horses was used to produce serum, PRGF (Endoret ® ), and PRP (E-PET™). Limbal- and stromal cells were isolated from healthy corneas of six horses and treated with 20% serum, 20% PRGF or 20% PRP. Proliferation rates and migration capacity were analysed in single cell cultures as well as co-culture systems. Cell proliferation increased with PRP treatment, remained constant in PRGF treated cells, and declined upon serum treatment over a period of 48 h. Migration capacity was significantly enhanced with PRP treatment, compared with PRGF treatment. Intact leucocytes, mainly eosinophils, were only detected in PRP. Due to the study design use of autologous blood products on corneal cells was not possible. The results demonstrate beneficial effects of PRP on proliferation as well as migration capacity of equine corneal cells in vitro. In vivo studies are warranted to determine further beneficial effects of PRP in horses with corneal ulcers. © 2017 EVJ Ltd.

First-in-man intravenous implantation of stromal vascular fraction in psoriasis: a case study.

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Comella, Kristin; Parlo, Michelle; Daly, Rosemary; Dominessy, Kellie

2018-01-01

Stromal vascular fraction (SVF) is a mixture of adipose-derived stem cells/mesenchymal stem cells, endothelial/progenitors, pericytes, fibroblasts, and other cells obtained from fat tissue. A small sample of fat or adipose tissue can be obtained under local anesthesia using a cannula. After an enzymatic digestion and centrifugation, the adipocytes (fat cells) are removed to obtain an SVF. Here, we describe the rationale and, to our knowledge, the first clinical implementation of SVF intravenously in a patient with severe psoriasis. Adipose tissue (60 mL) was collected under local anesthesia via a mini-lipoaspirate procedure. The SVF was separated from the adipocytes via centrifugation after an enzymatic digestion. The cells were resuspended in normal saline and injected via bolus push intravenous. The subject was monitored over a period of 12 months for safety (adverse events), medication changes, and quality of life parameters. The patient did not report any safety concerns and did not experience any severe adverse events. The patient demonstrated a significant decrease in symptoms with a noticeable difference in skin quality appearance. Psoriasis area and severity index score went from 50.4 at baseline to 0.3 at 1 month follow-up. Overall, the patient reported improved quality of life and willingness to continue treatments. This successful initial case study demonstrates that this may be a feasible treatment plan for patients suffering from psoriasis.

Cerebellar hemangioblastomas: A study of the immunoprofile of neoplastic stromal component

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Tasić Desanka

2004-01-01

Full Text Available Background. Central nervous system hemangioblastomas (HBs are uncommon highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. Methods. A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg, CD34, vimentin, factor XIIIa (FXIIIa, S-100 protein, glial fibrillary acidic protein (GFAP, neuron-specific enolase (NSE neurofilaments (NF, synaptophysin, chromogranin, and somatostatin. Results. Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34 GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". Conclusion. The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme in the HBs stromal cells might be related to the loss of the VHL protein function.

Stromal haze, myofibroblasts, and surface irregularity after PRK.

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Netto, Marcelo V; Mohan, Rajiv R; Sinha, Sunilima; Sharma, Ajay; Dupps, William; Wilson, Steven E

2006-05-01

The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze. Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups: [see table in text]. Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr or 4 weeks after surgery and histochemical analysis was performed on corneas for apoptosis (TUNEL assay), myofibroblast marker alpha-smooth muscle actin (SMA), and integrin alpha4 to delineate the epithelial basement membrane. Slit-lamp grading revealed severe haze formation in corneas in groups IV and VI, with significantly less haze in groups II, III, and VII and insignificant haze compared with the unwounded control in groups I and V. Analysis of SMA staining at 4 weeks after surgery, the approximate peak of haze formation in rabbits, revealed low myofibroblast formation in group I (1.2+/-0.2 cells/400x field) and group V (1.8+/-0.4), with significantly more in groups II (3.5+/-1.8), III (6.8+/-1.6), VII (7.9+/-3.8), IV (12.4+/-4.2) and VI (14.6+/-5.1). The screened groups were significantly different from each other (p PRK groups. The -9.0 diopter PRK group VI had significantly more myofibroblast generation than the -9.0 diopter PRK with PTK-smoothing group VII (p PRK and the level of stromal surface irregularity. PTK-smoothing with methylcellulose was an effective method to reduce stromal surface irregularity and decreased both haze and associated myofibroblast density. We hypothesize that stromal surface irregularity after PRK for high myopia results in defective basement membrane

The tissue-engineered human cornea as a model to study expression of matrix metalloproteinases during corneal wound healing.

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Couture, Camille; Zaniolo, Karine; Carrier, Patrick; Lake, Jennifer; Patenaude, Julien; Germain, Lucie; Guérin, Sylvain L

2016-02-01

Corneal injuries remain a major cause of consultation in the ophthalmology clinics worldwide. Repair of corneal wounds is a complex mechanism that involves cell death, migration, proliferation, differentiation, and extracellular matrix (ECM) remodeling. In the present study, we used a tissue-engineered, two-layers (epithelium and stroma) human cornea as a biomaterial to study both the cellular and molecular mechanisms of wound healing. Gene profiling on microarrays revealed important alterations in the pattern of genes expressed by tissue-engineered corneas in response to wound healing. Expression of many MMPs-encoding genes was shown by microarray and qPCR analyses to increase in the migrating epithelium of wounded corneas. Many of these enzymes were converted into their enzymatically active form as wound closure proceeded. In addition, expression of MMPs by human corneal epithelial cells (HCECs) was affected both by the stromal fibroblasts and the collagen-enriched ECM they produce. Most of all, results from mass spectrometry analyses provided evidence that a fully stratified epithelium is required for proper synthesis and organization of the ECM on which the epithelial cells adhere. In conclusion, and because of the many characteristics it shares with the native cornea, this human two layers corneal substitute may prove particularly useful to decipher the mechanistic details of corneal wound healing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Corneal ectasia after myopic laser in situ keratomileusis: a long-term study

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Spadea L

2012-11-01

Full Text Available Leopoldo Spadea,1 Emilia Cantera,2 Magdalena Cortes,2 Nicole Evangelista Conocchia,1 Charles WM Stewart11University of L’Aquila, Department of Biotechnological and Applied Clinical Sciences, Eye Clinic, L’Aquila, 2Villa Stuart Clinic, Department of Ophthalmic Sciences, Rome, ItalyBackground: The purpose of this study was to evaluate the long-term postoperative incidence of and key factors in the genesis of corneal ectasia after myopic laser-assisted in situ keratomileusis (LASIK in a large number of cases.Methods: A retrospective review of one surgeon's myopic LASIK database was performed. Patients were stratified into two groups based on date of surgery, ie, group 1 (1313 eyes from 1999 to 2001 and group 2 (2714 eyes from 2001 to 2003. Visual acuity, refraction, pachymetry, and corneal topography data were available for each patient from examinations performed both before and after the refractive procedures.Results: Of the 4027 surgically treated eyes, 23 (0.57% developed keratectasia during the follow-up period, which was a minimum seven years; nine eyes (0.69% were from group 1 and 14 eyes (0.51% were from group 2. The onset of corneal ectasia was at 2.57 ± 1.04 (range 1–4 years and 2.64 ± 1.29 (range 0.5–5 years, respectively, for groups 1 and 2. The most important preoperative risk factors using the Randleman Ectasia Risk Score System were manifest refractive spherical error in group 1 and a thin residual stromal bed in group 2. Each of the cases that developed corneal ectasia had risk factors that were identified.Conclusion: Ectasia was an uncommon outcome after an otherwise uncomplicated laser in situ keratomileusis procedure. The variables present in eyes developing postoperative LASIK ectasia can be better understood using the Randleman Ectasia Risk Score System.Keywords: corneal topography, Ectasia Risk Score System, keratectasia, myopia, LASIK

Comparison of Corneal Riboflavin Gradients Using Dextran and HPMC Solutions.

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Ehmke, Tobias; Seiler, Theo G; Fischinger, Isaak; Ripken, Tammo; Heisterkamp, Alexander; Frueh, Beatrice E

2016-12-01

To determine the riboflavin concentration gradient in the anterior corneal stroma when using hydroxypropyl methylcellulose (HPMC) or dextran as the carrier agent. Four different groups of porcine corneas (5 each) were compared regarding the riboflavin concentration in the anterior stroma. Prior to all experiments, stable hydration conditions were established for the corresponding solution. The dextran groups were treated with 0.1% riboflavin in 20% dextran for 10 and 30 minutes and the HPMC groups with 0.1% riboflavin in 1.1% HPMC for 10 and 30 minutes. After imbibition, nonlinear microscopy and consecutive image analysis were used to determine two-photon fluorescence intensities. To determine the riboflavin concentration, corneas were saturated and measured a second time by two-photon microscopy. With this measurement, a proper correction for absorption and scattering could be performed. Ultraviolet-A (UVA) transmission was measured after the application time for each group. Riboflavin concentration decreased with increasing depth and increased with longer application times in all groups. Comparing the dextran for 30 minutes and HPMC for 10 minutes groups, a significantly higher stromal riboflavin concentration was found within the most anterior 70 µm in the dextran group for 30 minutes, whereas deeper than 260 µm HPMC-assisted imbibition for 10 minutes yielded higher concentrations. In dextran-treated corneas, values obtained from pachymetry were substantially reduced, whereas HPMC-assisted imbibition led to a decent swelling. UVA transmission values were higher in dextran-assisted imbibition than in HPMC-assisted imbibition. Stromal riboflavin gradients are similar when applied in dextran for 30 minutes and HPMC for 10 minutes. When using HPMC solutions, a shallower cross-linked volume is expected due to a higher corneal hydration. [J Refract Surg. 2016;32(12):798-802.]. Copyright 2016, SLACK Incorporated.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

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Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

2015-07-17

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

International Nuclear Information System (INIS)

Yang, Bin; Li, Wei; Zheng, Qichang; Qin, Tao; Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen; Liu, Sanguang; Song, Zifang

2015-01-01

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation

Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

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Park, Susanna S

2016-04-01

Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

The effect of two novel amino acid-coated magnetic nanoparticles on survival in vascular endothelial cells, bone marrow stromal cells, and macrophages

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Wu, Qinghua; Meng, Ning; Zhang, Yanru; Han, Lei; Su, Le; Zhao, Jing; Zhang, Shangli; Zhang, Yun; Zhao, Baoxiang; Miao, Junying

2014-09-01

Magnetic nanoparticles (MNPs) have been popularly used in many fields. Recently, many kinds of MNPs are modified as new absorbents, which have attracted considerable attention and are promising to be applied in waste water. In our previous study, we synthesized two novel MNPs surface-coated with glycine or lysine, which could efficiently remove many anionic and cationic dyes under severe conditions. It should be considered that MNP residues in water may exert some side effects on human health. In the present study, we evaluated the potential nanotoxicity of MNPs in human endothelial cells, macrophages, and rat bone marrow stromal cells. The results showed that the two kinds of nanoparticles were consistently absorbed into the cell cytoplasm. The concentration of MNPs@Gly that could distinctly decrease survival was 15 μg/ml in human umbilical vascular endothelial cells (HUVECs) or bone marrow stromal cells (BMSCs) and 10 μg/ml in macrophages. While the concentration of MNPs@Lys that obviously reduced viability was 15 μg/ml in HUVECs or macrophages and 50 μg/ml in BMSCs. Furthermore, cell nucleus staining and cell integrity assay indicated that the nanoparticles induced cell apoptosis, but not necrosis even at a high concentration. Altogether, these data suggest that the amino acid-coated magnetic nanoparticles exert relatively high cytotoxicity. By contrast, lysine-coated magnetic nanoparticles are more secure than glycine-coated magnetic nanoparticles.

Corneal densitometry and its correlation with age, pachymetry, corneal curvature, and refraction.

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Garzón, Nuria; Poyales, Francisco; Illarramendi, Igor; Mendicute, Javier; Jáñez, Óscar; Caro, Pedro; López, Alfredo; Argüeso, Francisco

2017-12-01

To determine normative corneal densitometry values in relation to age, sex, refractive error, corneal thickness, and keratometry, measured using the Oculus Pentacam system. Three hundred and thirty-eight healthy subjects (185 men; 153 women) with no corneal disease underwent an exhaustive ocular examination. Corneal densitometry was expressed in standardized grayscale units (GSU). The mean corneal densitometry over the total area was 16.46 ± 1.85 GSU. The Pearson correlation coefficient for total densitometry was r = 0.542 (p  0.05). This is the first report of normative corneal densitometry values in relation to keratometry, corneal thickness, and spherical equivalent measured with the latest Oculus Pentacam software. Corneal densitometry increases with age, but corneal keratometry and refractive parameters do not affect light scattering in the human cornea.

Therapeutic effects of zerumbone in an alkali-burned corneal wound healing model.

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Kim, Jong Won; Jeong, Hyuneui; Yang, Myeon-Sik; Lim, Chae Woong; Kim, Bumseok

2017-07-01

Cornea is an avascular transparent tissue. Ocular trauma caused by a corneal alkali burn induces corneal neovascularization (CNV), inflammation, and fibrosis, leading to vision loss. The purpose of this study was to examine the effects of Zerumbone (ZER) on corneal wound healing caused by alkali burns in mice. CNV was induced by alkali-burn injury in BALB/C female mice. Topical ZER (three times per day, 3μl each time, at concentrations of 5, 15, and 30μM) was applied to treat alkali-burned mouse corneas for 14 consecutive days. Histopathologically, ZER treatment suppressed alkali burn-induced CNV and decreased corneal epithelial defects induced by alkali burns. Corneal tissue treated with ZER showed reduced mRNA levels of pro-angiogenic genes, including vascular endothelial growth factor, matrix metalloproteinase-2 and 9, and pro-fibrotic factors such as alpha smooth muscle actin and transforming growth factor-1 and 2. Immunohistochemical analysis demonstrated that the infiltration of F4/80 and/or CCR2 positive cells was significantly decreased in ZER-treated corneas. ZER markedly inhibited the mRNA and protein levels of monocyte chemoattractant protein-1 (MCP-1) in human corneal fibroblasts and murine peritoneal macrophages. Immunoblot analysis revealed that ZER decreased the activation of signal transducer and activator of transcription 3 (STAT3), with consequent reduction of MCP-1 production by these cells. In conclusion, topical administration of ZER accelerated corneal wound healing by inhibition of STAT3 and MCP-1 production. Copyright © 2017. Published by Elsevier B.V.

Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin.

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Höllhumer, Roland; Watson, Stephanie; Beckingsale, Peter

2017-03-01

Collagen cross-linking (CXL) is a commonly performed procedure to prevent the progression of keratoconus. Riboflavin is an essential part of the procedure, which facilitates both the cross-linking process and protection of intraocular structures. Dextran can be added to riboflavin to create an isotonic solution. This case report highlights the importance of compounding riboflavin with the correct dextran solution. A retrospective case series. Six eyes of 4 male patients with keratoconus aged from 20 to 38 years underwent CXL with substitution of 20% dextran (T-500) with 20% dextran sulfate in a compounded riboflavin 0.1% solution. Postoperatively, persistent corneal epithelial defects, stromal haze, and then scarring occurred. Corneal transplantation was performed for visual rehabilitation but was complicated by graft rejection followed by failure (n = 1 eye), dehiscence (n = 4), cataract (n = 2), post-laser ablation haze (n = 1), and steroid-induced glaucoma (n = 2). The visual outcome was dextran (T-500) with dextran sulfate in riboflavin solutions during CXL results in loss of vision from permanent corneal opacity. Residual host changes may compromise the results of corneal transplantation.

Small incision lenticule extraction (SMILE) and femtosecond laser LASIK: comparison of corneal wound healing and inflammation

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Dong, Zixian; Zhou, Xingtao; Wu, Jihong; Zhang, Zhehuan; Li, Tao; Zhou, Zimei; Zhang, Shenghai; Li, Gang

2014-01-01

Aim To evaluate and compare early corneal wound healing and inflammatory responses after small incision lenticule extraction (SMILE) versus femtosecond laser laser in situ keratomileusis (LASIK). Methods Thirty-six eyes of 36 rabbits underwent SMILE, while another 36 eyes of 36 rabbits were treated with femtosecond laser LASIK. All the eyes were subjected to the same refractive correction of −6.00 DS/−1.00 DC. Twelve eyes that had no surgery were included for control. After euthanisation, corneal tissue sections were evaluated with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay to detect apoptosis at postoperative 4 and 24 h, immunocytochemistry for Ki67 to detect keratocyte proliferation at postoperative day 3, week 1 and month 1, and immunocytochemistry for CD11b to detect inflammation at postoperative day 1, day 3 and week 1, respectively. Results No adverse effects were noted after SMILE or LASIK. Corneal healing postoperatively was uneventful in all cases. There were significantly fewer TUNEL-positive corneal stromal cells after the SMILE procedure at 4 and 24 h postoperatively (pLASIK procedure. In addition, immunocytochemistry showed significantly fewer Ki67-positive cells in the SMILE group than those in the femtosecond laser LASIK group at day 3 and week 1 postoperatively (pLASIK. PMID:24227802

Lipoinjerto laminar: un tratamiento prometedor con factores vasculares estromales para las vulvo-vaginitis crónicas Lipoenxertia laminar: um tratamento promissor com factores vasculares estromais para as vulvo-vaginetes crônicas Lamellar fatgrafting: a promissing treatment with stromal vascular fraction in recurrent vulvo-vaginitis

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Ithamar N. Stocchero

2009-09-01

Full Text Available Una de las situaciones más problemáticas para la vida íntima de una mujer, sobre todo si es joven, son las vulvo-vaginitis de repetición. Junto al herpes genital recidivante, suele ser causa de disarmonía en la relación de pareja por la situación en sí y por la frecuente presencia de dolor. Presentamos un caso exitoso en el que se aplicó un nuevo tratamiento consistente en la utilización de liponinjerto laminar submucoso, con preservación de la fracción vascular estromal (FVE, rica en células tronco derivadas de ese tejido (ADSCs, capaces de inducir neoangiogénesis que promoverá la defensa inmunológica normal de la mucosa de la vagina. De esta forma evitamos el uso de antibióticos y de otras terapias más costosas y, sobre todo, favoreciendo una vida sexual normal. Describimos en el presente artículo la técnica empleada.Uma das situações mais inconvenientes para a vida íntima de uma mulher, mormente jovem, é a vulvo-vaginite de repetição. Se acompanhada de herpes genital recidivante, não raro estabelece a desarmonia entre o casal dada à inconveniência da situação, além da dor, freqüentemente presente. Buscar o tratamento adequado, não prescrevendo apenas a antibióticoterapia, mas visando aumentar a resistência imunológica local da paciente, tem sido o objetivo de pesquisas nos últimos anos. Com o conhecimento da ação inflamatória induzida pelo tecido adiposo, associada à transferência de fatores vasculares estromais (FVE, grande fonte de células-tronco derivadas daquele tecido (ADSCs - Adipose- Derived Stromal/Stem Cells,bem como de indutores da angiogênese, facilitadora do acesso de células de defesa, foi idealizada uma nova e promissora linha de tratamento para estas pacientes: a lipoenxertia laminar. Relata-se a técnica bem sucedida, utilizada neste caso.One of the most inconvenient situations for a woman, mostly if young, is the recurrent vulvo-vaginitis. With the presence of a returning genital

Progress of research on corneal collagen cross-linking for corneal melting

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Ke-Ren Xiao

2016-06-01

Full Text Available Corneal collagen cross-linking(CXLcould increase the mechanical strength, biological stability and halt ectasia progression due to covalent bond formed by photochemical reaction between ultraviolet-A and emulsion of riboflavin between collagen fibers in corneal stroma. Corneal melting is an autoimmune related noninfectious corneal ulcer. The mechanism of corneal melting, major treatment, the basic fundamental of ultraviolet-A riboflavin induced CXL and the clinical researches status and experiment in CXL were summarized in the study.

Stromal vascular fraction isolated from lipo-aspirates using an automated processing system: bench and bed analysis.

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Doi, Kentaro; Tanaka, Shinsuke; Iida, Hideo; Eto, Hitomi; Kato, Harunosuke; Aoi, Noriyuki; Kuno, Shinichiro; Hirohi, Toshitsugu; Yoshimura, Kotaro

2013-11-01

The heterogeneous stromal vascular fraction (SVF), containing adipose-derived stem/progenitor cells (ASCs), can be easily isolated through enzymatic digestion of aspirated adipose tissue. In clinical settings, however, strict control of technical procedures according to standard operating procedures and validation of cell-processing conditions are required. Therefore, we evaluated the efficiency and reliability of an automated system for SVF isolation from adipose tissue. SVF cells, freshly isolated using the automated procedure, showed comparable number and viability to those from manual isolation. Flow cytometric analysis confirmed an SVF cell composition profile similar to that after manual isolation. In addition, the ASC yield after 1 week in culture was also not significantly different between the two groups. Our clinical study, in which SVF cells isolated with the automated system were transplanted with aspirated fat tissue for soft tissue augmentation/reconstruction in 42 patients, showed satisfactory outcomes with no serious side-effects. Taken together, our results suggested that the automated isolation system is as reliable a method as manual isolation and may also be useful in clinical settings. Automated isolation is expected to enable cell-based clinical trials in small facilities with an aseptic room, without the necessity of a good manufacturing practice-level cell processing area. Copyright © 2012 John Wiley & Sons, Ltd.

Expanded Stem Cells, Stromal-Vascular Fraction, and Platelet-Rich Plasma Enriched Fat: Comparing Results of Different Facial Rejuvenation Approaches in a Clinical Trial.

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Rigotti, Gino; Charles-de-Sá, Luiz; Gontijo-de-Amorim, Natale Ferreira; Takiya, Christina Maeda; Amable, Paola Romina; Borojevic, Radovan; Benati, Donatella; Bernardi, Paolo; Sbarbati, Andrea

2016-03-01

In a previous study, the authors demonstrated that treatment with expanded adipose-derived stem cells or stromal vascular fraction (SVF)-enriched fat modify the pattern of the dermis in human beings, representing a skin rejuvenation effect. Considering that expanded stem cells require a cell factor, the authors wanted to assess similar results by replacing them with platelet-rich plasma (PRP), which is easier to obtain and for which an empirical regenerative effect has been already described. To determine if PRP injection could replace the cutaneous regenerative effect of adipose-derived stem cells. This study was performed in 13 patients who were candidates for facelift. The patients underwent sampling of fat by liposuction from the abdomen and submitted to one of three protocols: injection of SVF-enriched fat or expanded adipose-derived stem cells or fat plus PRP in the preauricular areas. Fragments of skin were removed before and 3 months after treatment and analyzed by optical and electron microscopy. The use of fat plus PRP led to the presence of more pronounced inflammatory infiltrates and a greater vascular reactivity, increasing in vascular permeability and a certain reactivity of the nervous component. The addition of PRP did not improve the regenerative effect. The use of PRP did not have significant advantages in skin rejuvenation over the use of expanded adipose-derived stem cells or SVF-enriched fat. The effect of increased vascular reactivity may be useful in pathological situations in which an intense angiogenesis is desirable, such as tissular ischemia. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Penetrating and Intrastromal Corneal Arcuate Incisions in Rabbit and Human Cadaver Eyes: Manual Diamond Blade and Femtosecond Laser-Created Incisions.

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Gray, Brad; Binder, Perry S; Huang, Ling C; Hill, Jim; Salvador-Silva, Mercedes; Gwon, Arlene

2016-07-01

To compare morphologic differences between freehand diamond or femtosecond laser-assisted penetrating and intrastromal arcuate incisions. Freehand diamond blade, corneal arcuate incisions (180° apart, 60° arc lengths) and 150 kHz femtosecond laser (80% scheimpflug pachymetry depth corneal thickness) arcuate incisions were performed in rabbits. Intrastromal arcuate incisions (100 μm above Descemet's membrane, 100 μm below epithelium) were performed in rabbit corneas (energy 1.2 μJ, spot line separation 3 × 3 μm, 90° side cut angle). Eyes were examined by slit lamp and light microscopy up to 47 days post-procedure. Freehand diamond blade penetrating incisions, and femtosecond laser penetrating and intrastromal arcuate incisions (energy 1.8 μJ, spot line separation 2 × 2 μm) were performed in cadaver eyes. Optical coherence tomography was performed immediately after surgery and the corneas were fixed for light scanning and transmission electron microscopy. The rabbit model showed anterior stromal inflammation with epithelial hyperplasia in penetrating blade and laser penetrating wounds. The laser intrastromal and penetrating incisions showed localized constriction of the stromal layers of the cornea near the wound. In cadaver eyes, penetrating wound morphology was similar between blade and laser whereas intrastromal wounds did not affect the cornea above or below incisions. Penetrating femtosecond laser arcuate incisions have more predictable and controlled outcomes shown by less post-operative scarring than incisions performed with a diamond blade. Intrastromal incisions do not affect uncut corneal layers as demonstrated by histopathology. The femtosecond laser has significant advantages in its ability to make intrastromal incisions which are not achievable by traditional freehand or mechanical diamond blades.

Regeneration of defective epithelial basement membrane and restoration of corneal transparency

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Marino, Gustavo K.; Santhiago, Marcony R.; Santhanam, Abirami; Torricelli, Andre A. M.; Wilson, Steven E.

2018-01-01

PURPOSE To study regeneration of the normal ultrastructure of the epithelial basement membrane (EBM) in rabbit corneas that had -9D photorefractive keratectomy (PRK) and developed late haze (fibrosis) with restoration of transparency over one to four months after surgery and in corneas that had incisional wounds. METHODS Twenty-four rabbits had one of their eyes included into one of the two procedure groups (-9D PRK or nearly full-thickness incisional wounds), while the opposite eye serving as unwounded controls. All corneas were evaluated with slit lamp photos, transmission electron microscopy and immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin and collagen type III. RESULTS In the ‘-9D PRK group’, corneas at one month after surgery had dense corneal haze and no evidence of regenerated EBM ultrastructure. By two months after surgery, however, small areas of stromal clearing began to appear within the confluent opacity (lacunae), and these corresponded to small islands of normally-regenerated EBM detected within larger area of the excimer laser-ablated zone with no evidence of normal EBM. By four months after surgery, the EBM was fully-regenerated and the corneal transparency was completely restored to the ablated zone. In the ‘Incisional wound group’, the two dense, linear corneal opacities were observed at one month after surgery and progressively faded by two and three months after surgery. The EBM ultrastructure was fully regenerated at the site of the incisions, including around epithelial plugs that extended into the stroma, by one month after surgery in all eyes. CONCLUSIONS In the rabbit model, spontaneous resolution of corneal fibrosis (haze) after high correction PRK is triggered by regeneration of EBM with normal ultrastructure in the excimer laser- ablated zone. Conversely, incisional wounds heal in rabbit corneas without the development of myofibroblasts because the EBM regenerates normally by one month after surgery

The Role of Titanium Surface Microtopography on Adhesion, Proliferation, Transformation, and Matrix Deposition of Corneal Cells.

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Zhou, Chengxin; Lei, Fengyang; Chodosh, James; Paschalis, Eleftherios I

2016-04-01

Titanium (Ti) is an excellent implantable biomaterial that can be further enhanced by surface topography optimization. Despite numerous data from orthopedics and dentistry, the effect of Ti surface topography on ocular cells is still poorly understood. In light of the recent adaptation of Ti in the Boston Keratoprosthesis artificial cornea, we attempted to perform an extended evaluation of the effect of Ti surface topography on corneal cell adhesion, proliferation, cytotoxicity, transformation, and matrix deposition. Different surface topographies were generated on medical grade Ti-6Al-4V-ELI (extra-low interstitial), with linearly increased roughness (polished to grit blasted). Biological response was evaluated in vitro using human corneal limbal epithelial (HCLE) cells, stromal fibroblasts (HCF), and endothelial cells (HCEnC). None of the Ti surface topographies caused cytotoxicity to any of the three corneal cell types. However, rough Ti surface inhibited HCLE and HCF cell adhesion and proliferation, while HCEnC proliferation was unaffected. Long-term experiments with HCF revealed that rough Ti surface with R(a) (the arithmetic average of the profile height from the mean line) ≥ 1.15 μm suppressed HCF focal adhesion kinase phosphorylation, changed fibroblast morphology, and caused less aligned and reduced deposition of collagen matrix as compared to smooth Ti (R(a) ≤ 0.08 μm). In the presence of transforming growth factor β1 (TGFβ1) stimulation, rough Ti inhibited alpha-smooth muscle actin (α-SMA) expression and collagen deposition, leading to decreased myofibroblast transformation and disorganization of the collagen fibrils as compared to smooth Ti. This study suggests that Ti surface topography regulates corneal cell behavior in a tissue-dependent manner that varies across the corneal strata. Contrary to the accepted paradigm, smooth surface topography can enhance cell adhesion and proliferation and increase matrix deposition by corneal cells.

Intraocular pressure, corneal thickness, and corneal hysteresis in Steinert's myotonic dystrophy

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Carlos Alexandre de A. Garcia Filho

2011-06-01

Full Text Available PURPOSE: Low intraocular pressure (IOP measured by Goldmann applanation tonometry (GAT is one of the ocular manifestations of Steinert's myotonic dystrophy. The goal of this study was to evaluate the corneal-compensated IOP as well as corneal properties (central corneal thickness and corneal hysteresis in patients with myotonic dystrophy. METHODS: A total of 12 eyes of 6 patients with Steinert's myotonic dystrophy (dystrophy group and 12 eyes of 6 age-, race-, and gender-matched healthy volunteers (control group were included in the study. GAT, Dynamic Contour Tonometry (DCT-Pascal and Ocular Response Analyzer (ORA were used to assess the IOP. Central corneal thickness was obtained by ultrasound pachymetry, and corneal hysteresis was analyzed using the ORA device. In light of the multiplicity of tests performed, the significance level was set at 0.01 rather than 0.05. RESULTS: The mean (standard deviation [SD] GAT, DCT, and corneal-compensated ORA IOP in the dystrophy group were 5.4 (1.4 mmHg, 9.7 (1.5 mmHg, and 10.1 (2.6 mmHg, respectively. The mean (SD GAT, DCT, and corneal-compensated ORA IOP in the control group was 12.6 (2.9 mmHg, 15.5 (2.7 mmHg, and 15.8 (3.4 mmHg, respectively. There were significant differences in IOP values between dystrophy and control groups obtained by GAT (mean, -7.2 mmHg; 99% confidence interval [CI], -10.5 to -3.9 mmHg; P<0.001, DCT (mean, -5.9 mmHg; 99% CI, -8.9 to -2.8 mmHg; P<0.001, and corneal-compensated ORA measurements (mean, -5.7 mmHg; 99% CI, -10.4 to -1.0 mmHg; P=0.003. The mean (SD central corneal thickness was similar in the dystrophy (542 [31] µm and control (537 [11] µm groups (P=0.65. The mean (SD corneal hysteresis in the dystrophy and control groups were 11.2 (1.5 mmHg and 9.7 (1.2 mmHg, respectively (P=0.04. CONCLUSIONS: Patients with Steinert's myotonic dystrophy showed lower Goldmann and corneal-compensated IOP in comparison with healthy individuals. Since central corneal thickness and

Riboflavin/UVA Collagen Cross-Linking-Induced Changes in Normal and Keratoconus Corneal Stroma

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Hayes, Sally; Boote, Craig; Kamma-Lorger, Christina S.; Rajan, Madhavan S.; Harris, Jonathan; Dooley, Erin; Hawksworth, Nicholas; Hiller, Jennifer; Terill, Nick J.; Hafezi, Farhad; Brahma, Arun K.; Quantock, Andrew J.; Meek, Keith M.

2011-01-01

Purpose To determine the effect of Ultraviolet-A collagen cross-linking with hypo-osmolar and iso-osmolar riboflavin solutions on stromal collagen ultrastructure in normal and keratoconus ex vivo human corneas. Methods Using small-angle X-ray scattering, measurements of collagen D-periodicity, fibril diameter and interfibrillar spacing were made at 1 mm intervals across six normal post-mortem corneas (two above physiological hydration (swollen) and four below (unswollen)) and two post-transplant keratoconus corneal buttons (one swollen; one unswollen), before and after hypo-osmolar cross-linking. The same parameters were measured in three other unswollen normal corneas before and after iso-osmolar cross-linking and in three pairs of swollen normal corneas, in which only the left was cross-linked (with iso-osmolar riboflavin). Results Hypo-osmolar cross-linking resulted in an increase in corneal hydration in all corneas. In the keratoconus corneas and unswollen normal corneas, this was accompanied by an increase in collagen interfibrillar spacing (priboflavin solutions are more likely a consequence of treatment-induced changes in tissue hydration rather than cross-linking. PMID:21850225

Corneal power, thickness, and stiffness: results of a prospective randomized controlled trial of PRK and LASIK for myopia.

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Hjortdal, Jesper Ø; Møller-Pedersen, Torben; Ivarsen, Anders; Ehlers, Niels

2005-01-01

significantly in both groups. The apparent IOP increased significantly more in PRK eyes. Differences between LASIK and PRK related to time-dependent events affecting corneal shape and structural integrity were present. Peripheral changes in flap hydration in LASIK eyes and epithelial and/or stromal thickening in PRK eyes appeared to be the most important factors in optical power changes in the first year after treatment. The changes in apparent IOP suggest that some interlamellar healing occurred during the first year after LASIK. After LASIK and PRK, corneal bending stiffness seemed permanently decreased, although some restiffening may occur in PRK eyes in the long term.

Intrastromal corneal ring implants for corneal thinning disorders: an evidence-based analysis.

Science.gov (United States)

2009-01-01

The purpose of this project was to determine the role of corneal implants in the management of corneal thinning disease conditions. An evidence-based review was conducted to determine the safety, effectiveness and durability of corneal implants for the management of corneal thinning disorders. The evolving directions of research in this area were also reviewed. SUBJECT OF THE EVIDENCE-BASED ANALYSIS: The primary treatment objectives for corneal implants are to normalize corneal surface topography, improve contact lens tolerability, and restore visual acuity in order to delay or defer the need for corneal transplant. Implant placement is a minimally invasive procedure that is purported to be safe and effective. The procedure is also claimed to be adjustable, reversible, and both eyes can be treated at the same time. Further, implants do not limit the performance of subsequent surgical approaches or interfere with corneal transplant. The evidence for these claims is the focus of this review. The specific research questions for the evidence review were as follows: SafetyCorneal Surface Topographic Effects:Effects on corneal surface remodellingImpact of these changes on subsequent interventions, particularly corneal transplantation (penetrating keratoplasty [PKP])Visual AcuityRefractive OutcomesVISUAL QUALITY (SYMPTOMS): such as contrast vision or decreased visual symptoms (halos, fluctuating vision)Contact lens toleranceFunctional visual rehabilitation and quality of lifePatient satisfaction:Disease Process:Impact on corneal thinning processEffect on delaying or deferring the need for corneal transplantation TARGET POPULATION AND CONDITION Corneal ectasia (thinning) comprises a range of disorders involving either primary disease conditions such as keratoconus and pellucid marginal corneal degeneration or secondary iatrogenic conditions such as corneal thinning occurring after LASIK refractive surgery. The condition occurs when the normally round dome-shaped cornea

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia.

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Cınar, Yasin; Cingü, Abdullah Kürşat; Sahin, Alparslan; Türkcü, Fatih Mehmet; Yüksel, Harun; Caca, Ihsan

2014-03-01

Abstract Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases. The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30 min, and after 10 min of ultraviolet A irradiation. Eleven eyes of eleven patients with progressive keratoconus (n = 10) and iatrogenic corneal ectasia (n = 1) were included in this study. The mean thinnest pachymetric measurements were 391.82 ± 30.34 µm (320-434 µm) after de-epithelialization of the cornea, 435 ± 21.17 µm (402-472 µm) following 30 min instillation of isotonic riboflavin solution without dextran and 431.73 ± 20.64 µm (387-461 µm) following 10 min of ultraviolet A irradiation to the cornea. Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.

The survival condition and immunoregulatory function of adipose stromal vascular fraction (SVF in the early stage of nonvascularized adipose transplantation.

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Ziqing Dong

Full Text Available INTRODUCTION: Adipose tissue transplantation is one of the standard procedures for soft-tissue augmentation, reconstruction, and rejuvenation. However, it is unknown as to how the graft survives after transplantation. We thus seek out to investigate the roles of different cellular components in the survival of graft. MATERIALS & METHODS: The ratios of stromal vascular fraction (SVF cellular components from human adipose tissue were evaluated using flow cytometry. Human liposuction aspirates that were either mixed with marked SVF cells or PBS were transplanted into nude mice. The graft was harvested and stained on days 1,4,7 and 14. The inflammation level of both SVF group and Fat-only group were also evaluated. RESULTS: Flow cytometric analysis showed SVF cells mainly contained blood-derived cells, adipose-derived stromal cells (ASCs, and endothelial cells. Our study revealed that most cells are susceptible to death after transplantation, although CD34+ ASCs can remain viable for 14 days. Notably, we found that ASCs migrated to the peripheral edge of the graft. Moreover, the RT-PCR and the immuno-fluorescence examination revealed that although the SVF did not reduce the number of infiltrating immune cells (macrophages in the transplant, it does have an immunoregulatory function of up-regulating the expression of CD163 and CD206 and down-regulating that of IL-1β, IL-6. CONCLUSIONS: Our study suggests that the survival of adipose tissue after nonvascularized adipose transplantation may be due to the ASCs in SVF cells. Additionally, the immunoregulatory function of SVF cells may be indirectly contributing to the remolding of adipose transplant, which may lead to SVF-enriched adipose transplantation.

Viabilidade celular da fração mononuclear da medula óssea e fração vascular estromal do tecido adiposo de equinos após o processo de congelamento e descongelamento Viability of equine bone marrow mononuclear fraction and adipose tissue-derived stromal vascular fraction after freezing and thawing process

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Gesiane Ribeiro

2012-12-01

Full Text Available Cinco cavalos adultos foram submetidos à coleta de medula óssea do esterno e de tecido adiposo da região glútea. As amostras foram processadas para obtenção da fração mononuclear da medula óssea e fração vascular estromal do tecido adiposo, o número de células obtidas e a viabilidade celular foram determinados. Em seguida, realizou-se o congelamento das amostras em solução contendo 20% de soro fetal bovino e 10% de dimetilsulfóxido. Depois de um mês, realizou-se o descongelamento das amostras e a viabilidade celular foi novamente mensurada. Os resultados revelaram que as técnicas utilizadas tanto para coleta de medula óssea quanto de tecido adiposo em equinos são simples, rápidas e seguras. As metodologias adotadas para o processamento das amostras foram eficientes, obtendo-se aproximadamente 95% de viabilidade celular. Após o descongelamento, a viabilidade média das amostras de células mononucleares da medula óssea foi de 86% e da fração vascular estromal do tecido adiposo de 64%. Frente à importância da terapia celular na clínica médica de equinos, concluiu-se que é necessária a realização de mais estudos, visando padronizar uma técnica de criopreservação que mantenha a integridade das células da fração mononuclear da medula óssea e da fração vascular estromal do tecido adiposo de equinos.In five adult horses, bone marrow was aspirated from the sternum and adipose tissue extracted from the gluteal region. The samples were processed to obtain the mononuclear fraction of bone marrow and stromal vascular fraction of adipose tissue, and the number of cells obtained and cell viability were determined. Next, the cell samples were frozen in medium containing 20% fetal bovine serum and 10% dimethylsulfoxide. After one month, the cells were thawed and cell viability was again determined. The results revealed that the techniques for collecting both bone marrow and adipose tissue in horses are simple, rapid and

Corneal injection track:an unusual complication of intraocular lens implantation and review

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Julie Y.C. Lok

2015-06-01

Full Text Available Phacoemulsification is the main gold standard for cataract operation in the developed world together with foldable intraocular lens (IOL implantation by injection, allowing for stable wound construction and less postoperative astigmatism. It is a safe procedure with high success rate with the advancement in machines, improvement of IOL injection systems and further maturation of surgeons’ techniques. Despite the large number of operations performed every day, foldable IOL injection leading to an intra-stromal corneal track is a very rare complication. We report a case of this unusual finding in a 70-year-old gentleman who has undergone cataract operation in November 2011 in our hospital and will review on the complications related to foldable IOL injection.

Minocycline inhibits alkali burn-induced corneal neovascularization in mice.

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Ou Xiao

Full Text Available The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV. A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS or minocycline twice a day (60 mg/kg or 30 mg/kg for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs. The mRNA expression levels of vascular endothelial growth factor (VEGF and its receptors (VEGFRs, basic fibroblast growth factor (bFGF, matrix metalloproteinases (MMPs, interleukin-1α, 1β, 6 (IL-1α, IL-1β, IL-6 were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1β and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1β, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1β, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d. can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs.

Unilateral congenital corneal keloid with anterior segment mesenchymal dysgenesis and subluxated lens: case report and review of literature.

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Vanathi, M; Sen, Seema; Panda, Anita; Dada, Tanuj; Behera, Geeta; Khokhar, Sudharshan

2007-01-01

To report the unusual association of unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens. A 20-year old man presented with a mass lesion involving the left cornea. The corneal lesion had been present since birth. On biomicroscopic examination, a well-defined vascularized, grayish-white mass occupying the whole of the left cornea was seen. The right eye showed multiple peripheral corneal opacities with iridocorneal adhesions, a poorly defined supranasal limbus, and a subluxated lens. Excision biopsy of the mass was done for histopathologic examination. Histopathologic examination of the excised corneal mass showed features consistent with that of a corneal keloid: thickened keratinized epithelium, absent Bowman membrane layer, and fibrovascular hyperplasia composed of hyalinized collagen fibers with irregular orientation of the collagen lamellae. During penetrating keratoplasty of the left eye, an anomalous iris pattern with poorly defined angle and a supranasal subluxated lens was also observed. Extraction of the subluxated lens was also done. The graft failed subsequent to a nonhealing persistent epithelial defect. Our case report highlights the rare association of a unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens.

Topical flurbiprofen or prednisolone. Effect on corneal wound healing in rabbits.

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Miller, D; Gruenberg, P; Miller, R; Bergamini, M V

1981-04-01

Flurbiprofen is a nonsteroidal anti-inflammatory (NSAI) agent currently undergoing clinical investigation. Anti-inflammatory steroids have long been known to delay the healing of corneal stromal wounds. This was designed to compare the effects of equipotent anti-inflammatory doses of flurbiprofen and of prednisolone acetate on the inflammation and the healing (as measured by the wound bursting pressure) or 4-mm through-and-through incisions treated four times a day for ten postoperative days. The results suggest that flurbiprofen and prednisolone are not different in their effect on both postoperative inflammation and postoperative wound healing. Since NSAI agents and steroids inhibit prostaglandin formation at different enzymatic steps, it is possible that prostaglandins not only are responsible for postoperative inflammation but also are required for postoperative wound healing.

Inhibition of corneal neovascularization by recombinant adenovirus-mediated sFlk-1 expression

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Yu Hui; Wu Jihong; Li Huiming; Wang Zhanli; Chen Xiafang; Tian Yuhua; Yi Miaoying; Ji Xunda; Ma Jialie; Huang Qian

2007-01-01

The interaction of vascular endothelial growth factor (VEGF) and its receptors (Flt-1, Flk-1/KDR) is correlated with neovascularization in the eyes. Therefore, blocking the binding of VEGF and the corresponding receptor has become critical for inhibiting corneal neovascularization. In this study, we have expressed the cDNA for sFlk-1 under the control of cytomegalovirus immediate-early promoter (CMV) from an E1/partial E3 deleted replication defective recombinant adenovirus, and Ad.sflk-1 expression was determined by Western blotting. We have shown that conditioned media from Ad.sflk-1-infected ARPE-19 cells significantly reduced VEGF-induced human umbilical vein endothelial cells (HUVEC) and murine endothelial cells (SVEC) proliferation in vitro compared with the control vector. In vivo, adenoviral vectors expressing green fluorescent protein alone (Ad.GFP) were utilized to monitor gene transfer to the cornea. Moreover, in the models of corneal neovascularization, the injection of Ad.sflk-1 (10 8 PFU) into the anterior chamber could significantly inhibit angiogenic changes compared with Ad.null-injected and vehicle-injected models. Immunohistochemical analysis showed that corneal endothelial cells and corneal stroma of cauterized rat eyes were efficiently transduced and expressed sFlk-1. These results not only support that adenoviral vectors are capable of high-level transgene expression but also demonstrate that Ad.sflk-1 gene therapy might be a feasible approach for inhibiting the development of corneal neovascularization

Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

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Hertsenberg, Andrew J; Funderburgh, James L

2016-01-01

Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

Anti-inflammatory effect of topical administration of tofacitinib on corneal inflammation.

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Sakimoto, Tohru; Ishimori, Akiko

2016-04-01

We evaluated an anti-inflammatory effect of topical administration of tofacitinib, janus kinase (JAK) blocker, on corneal inflammation. Topical instillation of either tofacitinib or PBS was applied after wounding BALB/c mice corneas with alkali burn. Topical instillation was performed until day 14 after injury and injured eye was analyzed. The vascularized area in the alkali burned cornea was significantly reduced in the tofacitinib group compared with that in the PBS group. The immunoreactivity of Gr-1, F4/80, IFN-γ, and phosphorylated STAT(signal transducer and activator of transcription)1 in corneal stroma was diminished significantly in the tofacitinib group. Using laser capture microdissection system and quantitative PCR array analysis, the expression levels of CXCL9, CXCL5, CCL7, CCL2, MMP(matrix metalloproteinase)-9, and STAT1 in corneal stroma were down-regulated in the tofacitinib group. In in vitro study, human fibroblast pretreated by IFN-γ showed phosphorylation of STAT1, and this phosphorylation was down-regulated by adding tofacitinib to the culture medium. These results indicate the topical application of JAK inhibitor causes down-regulation of JAK- or IFN-γ-related molecules. Therefore, we deduce that application of JAK inhibitor for topical instillation may contribute to the treatment of corneal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantification of stromal vascular cell mechanics with a linear cell monolayer rheometer

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Elkins, Claire M., E-mail: cma9@stanford.edu; Fuller, Gerald G. [Department of Chemical Engineering, Stanford University, Stanford, California 94305 (United States); Shen, Wen-Jun; Khor, Victor K.; Kraemer, Fredric B. [Division of Endocrinology, Gerontology and Metabolism, Stanford University, Stanford, California 94305 and Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304 (United States)

2015-01-15

Over the past few decades researchers have developed a variety of methods for measuring the mechanical properties of whole cells, including traction force microscopy, atomic force microscopy (AFM), and single-cell tensile testing. Though each of these techniques provides insight into cell mechanics, most also involve some nonideal conditions for acquiring live cell data, such as probing only one portion of a cell at a time, or placing the cell in a nonrepresentative geometry during testing. In the present work, we describe the development of a linear cell monolayer rheometer (LCMR) and its application to measure the mechanics of a live, confluent monolayer of stromal vascular cells. In the LCMR, a monolayer of cells is contacted on both top and bottom by two collagen-coated plates and allowed to adhere. The top plate then shears the monolayer by stepping forward to induce a predetermined step strain, while a force transducer attached to the top plate collects stress information. The stress and strain data are then used to determine the maximum relaxation modulus recorded after step-strain, G{sub r}{sup 0}, referred to as the zero-time relaxation modulus of the cell monolayer. The present study validates the ability of the LCMR to quantify cell mechanics by measuring the change in G{sub r}{sup 0} of a confluent cell monolayer upon the selective inhibition of three major cytoskeletal components (actin microfilaments, vimentin intermediate filaments, and microtubules). The LCMR results indicate that both actin- and vimentin-deficient cells had ∼50% lower G{sub r}{sup 0} values than wild-type, whereas tubulin deficiency resulted in ∼100% higher G{sub r}{sup 0} values. These findings constitute the first use of a cell monolayer rheometer to quantitatively distinguish the roles of different cytoskeletal elements in maintaining cell stiffness and structure. Significantly, they are consistent with results obtained using single-cell mechanical testing methods

Late Stage of Corneal Decompensation Caused by Progressive Keratoconus: Can We Treat It and Save the Cornea?

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Igor Knezović

2015-01-01

Full Text Available Aim. To report a case of 40-year-old male with progressive bilateral keratoconus who had undergone transepithelial phototherapeutic keratectomy (TE-PTK and corneal collagen cross-linking (CXL using hypoosmolar riboflavin solution in a same day procedure. Methods. Eye examination showed that UCDVA on both eyes was 0,01 according to Snellen charts, and slit lamp biomicroscopy showed paracentral diffuse intrastromal corneal haze. Anterior OCT marked stromal hyperreflective zones and localized paracentral thinning of the cornea. Scheimpflug tomography noted keratoconus stages III-IV on both eyes. After 40/35 microns TE-PTK, a CXL was performed for 30 minutes using hypoosmolar riboflavin solution. The left eye was treated first and the right eye 1 month after. Follow-up period was 10 months. Results. One month after the treatment both eyes showed improvement in corneal topography and the UCDVA was better. Eight months after the treatment BSCVA improved to 0,6 in both eyes using Rose K2 contact lenses and remained stable. Conclusion. TE-PTK and CXL using hypotonic riboflavin solution as a same day procedure have been shown to be a safe and promising method in this case of progressive keratoconus. It was necessary to consider certain parameters that could influence the safety and the final outcome of this combined protocol.

Dynamic corneal deformation response and integrated corneal tomography

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Marcella Q Salomão

2018-01-01

Full Text Available Measuring corneal biomechanical properties is still challenging. There are several clinical applications for biomechanical measurements, including the detection of mild or early forms of ectatic corneal diseases. This article reviews clinical applications for biomechanical measurements provided by the Corvis ST dynamic non contact tonometer

Iontophoresis Transcorneal Delivery Technique for Transepithelial Corneal Collagen Crosslinking With Riboflavin in a Rabbit Model.

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Cassagne, Myriam; Laurent, Camille; Rodrigues, Magda; Galinier, Anne; Spoerl, Eberhard; Galiacy, Stéphane D; Soler, Vincent; Fournié, Pierre; Malecaze, François

2016-02-01

We compared an iontophoresis riboflavin delivery technique for transepithelial corneal collagen crosslinking (I-CXL) with a conventional CXL (C-CXL). We designed three experimental sets using 152 New Zealand rabbits to study riboflavin application by iontophoresis using charged riboflavin solution (Ricrolin+) with a 1-mA current for 5 minutes. The first set was to compare riboflavin concentration measured by HPLC in corneas after iontophoresis or conventional riboflavin application. The second set was to analyze autofluorescence and stromal collagen modification immediately and 14 days after I-CXL or C-CXL, by using nonlinear two-photon microscopy (TP) and second harmonic generation (SHG). In the third set, physical modifications after I-CXL and C-CXL were evaluated by stress-strain measurements and by studying corneal resistance against collagenase digestion. Based on HPLC analysis, we found that iontophoresis allowed riboflavin diffusion with 2-fold less riboflavin concentration than conventional application (936.2 ± 312.5 and 1708 ± 908.3 ng/mL, respectively, P riboflavin delivery in crosslinking treatments, preserving the epithelium.

Ocular dimensions, corneal thickness, and corneal curvature in quarter horses with hereditary equine regional dermal asthenia.

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Badial, Peres R; Cisneros-Àlvarez, Luis Emiliano; Brandão, Cláudia Valéria S; Ranzani, José Joaquim T; Tomaz, Mayana A R V; Machado, Vania M; Borges, Alexandre S

2015-09-01

The aim of this study was to compare ocular dimensions, corneal curvature, and corneal thickness between horses affected with hereditary equine regional dermal asthenia (HERDA) and unaffected horses. Five HERDA-affected quarter horses and five healthy control quarter horses were used. Schirmer's tear test, tonometry, and corneal diameter measurements were performed in both eyes of all horses prior to ophthalmologic examinations. Ultrasonic pachymetry was performed to measure the central, temporal, nasal, dorsal, and ventral corneal thicknesses in all horses. B-mode ultrasound scanning was performed on both eyes of each horse to determine the dimensions of the ocular structures and to calculate the corneal curvature. Each corneal region examined in this study was thinner in the affected group compared with the healthy control group. However, significant differences in corneal thickness were only observed for the central and dorsal regions. HERDA-affected horses exhibited significant increases in corneal curvature and corneal diameter compared with unaffected animals. The ophthalmologic examinations revealed mild corneal opacity in one eye of one affected horse and in both eyes of three affected horses. No significant between-group differences were observed for Schirmer's tear test, intraocular pressure, or ocular dimensions. Hereditary equine regional dermal asthenia-affected horses exhibit decreased corneal thickness in several regions of the cornea, increased corneal curvature, increased corneal diameter, and mild corneal opacity. Additional research is required to determine whether the increased corneal curvature significantly impacts the visual accuracy of horses with HERDA. © 2014 American College of Veterinary Ophthalmologists.

[Experimental study on vascular bundle implantation combined with cellular transplantation in treating rabbit femoral head necrosis].

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Chen, Shuang-Tao; Zhang, Wei-Ping; Liu, Chang-An; Wang, Jun-Jiang; Song, Heng-Yi; Chai, Zhi-wen

2013-03-01

To discuss the feasibility of vascular bundle implantation combined with allogeneic bone marrow stromal cells (BMSCs) transplantation in treating rabbit femoral head osteonecrosis and bone defect, in order to explore a new method for the treatment of femoral head necrosis. Thirty-six New Zealand rabbits were randomly divided into three groups,with 12 rabbits in each group. Bilateral femoral heads of the rabbits were studied in the experiment. The models were made by liquid nitrogen frozen, and the femoral heads were drilled to cause bone defect. Group A was the control group,group B was stem cells transplantaion group of allograft marrow stromal,and group C was stem cells transplantation group of allograft marrow stromal combined with vascular bundle implantation. Three rabbits of each group were sacrificed respectively at 2, 4, 8, 12 weeks after operation. All specimens of the femoral heads were sliced for HE staining. Furthermore ,vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area were measured and analyzed statistically. In group C,new bone trabecula and original micrangium formed at the 2nd week after operation; new bone trabecula was lamellar and interlaced with abundant micrangium at the 8th week;at the 12th week,the broadened,coarsened bone trabecula lined up regularly,and the mature bone trabecula and new marrow were visible. At the 2nd week after operation,there was no statistical significance in the percentage of new bone trabecula of femoral head coronary section in defect area between group B and C. While at 4, 8, 12 week after operation, vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area of group C was higher than that of group B. Allogeneic bone marrow stromal cells cultured in vivo can form new bone trabecula, and can be applied to allotransplant. Vascular bundle implanted into the bone defect area of femoral head necrosis could improve blood

New Details of the Human Corneal Limbus Revealed With Second Harmonic Generation Imaging.

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Park, Choul Yong; Lee, Jimmy K; Zhang, Cheng; Chuck, Roy S

2015-09-01

To report novel findings of the human corneal limbus by using second harmonic generation (SHG) imaging. Corneal limbus was imaged by using an inverted two-photon excitation fluorescence microscope. Laser (Ti:Sapphire) was tuned at 850 nm for two-photon excitation. Backscatter signals of SHG and autofluorescence (AF) were collected through a 425/30-nm emission filter and a 525/45-emission filter, respectively. Multiple, consecutive, and overlapping image stacks (z-stack) were acquired for the corneal limbal area. Two novel collagen structures were revealed by SHG imaging at the limbus: an anterior limbal cribriform layer and presumed anchoring fibers. Anterior limbal cribriform layer is an intertwined reticular collagen architecture just beneath the limbal epithelial niche and is located between the peripheral cornea and Tenon's/scleral tissue. Autofluorescence imaging revealed high vascularity in this structure. Central to the anterior limbal cribriform layer, radial strands of collagen were found to connect the peripheral cornea to the limbus. These presumed anchoring fibers have both collagen and elastin and were found more extensively in the superficial layers than deep layer and were absent in very deep limbus near Schlemm's canal. By using SHG imaging, new details of the collagen architecture of human corneal limbal area were elucidated. High resolution images with volumetric analysis revealed two novel collagen structures.

Quantification of collagen ultrastructure after penetrating keratoplasty - implications for corneal biomechanics.

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Craig Boote

Full Text Available To quantify long-term changes in stromal collagen ultrastructure following penetrating keratoplasty (PK, and evaluate their possible implications for corneal biomechanics.A pair of 16 mm post-mortem corneo-scleral buttons was obtained from a patient receiving bilateral penetrating keratoplasty 12 (left/28 (right years previously. Small-angle x-ray scattering quantified collagen fibril spacing, diameter and spatial order at 0.5 mm or 0.25 mm intervals along linear scans across the graft margin. Corresponding control data was collected from two corneo-scleral buttons with no history of refractive surgery. Wide-angle x-ray scattering quantified collagen fibril orientation at 0.25 mm (horizontal×0.25 mm (vertical intervals across both PK specimens. Quantification of orientation changes in the graft margin were verified by equivalent analysis of data from a 13 year post-operative right PK specimen obtained from a second patient in a previous study, and comparison made with new and published data from normal corneas.Marked changes to normal fibril alignment, in favour of tangentially oriented collagen, were observed around the entire graft margin in all PK specimens. The total number of meridional fibrils in the wound margin was observed to decrease by up to 40%, with the number of tangentially oriented fibrils increasing by up to 46%. As a result, in some locations the number of fibrils aligned parallel to the wound outnumbered those spanning it by up to five times. Localised increases in fibril spacing and diameter, with an accompanying reduction in matrix order, were also evident.Abnormal collagen fibril size and spatial order within the PK graft margin are indicative of incomplete stromal wound remodelling and the long term persistence of fibrotic scar tissue. Lasting changes in collagen fibril orientation in and around PK wounds may alter corneal biomechanics and compromise the integrity of the graft-host interface in the long term.

Efficacy of Tectonic Corneal Patch Graft for Progressive Peripheral Corneal Thinning

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Cafer Tanrıverdio

2014-12-01

Full Text Available Objectives: To report the results of tectonic corneal patch graft (TCPG in patients with progressive peripheral corneal thinning (PCT. Materials and Methods: In this study, we included 8 patients who underwent TCPG for PCT or perforated corneal ulceration at Ankara Training and Research Hospital. Results: We performed TCPG in 7 patients for PCT and in 1 patient for perforated corneal ulceration. Mean age was 57.2±16.7 (38- 82 years. Postoperative follow-up time ranged from 6 to 24 months (mean 13.9±6.7. Possible etiologies leading to progressive PCT were trachoma, infectious corneal ulcer, and rheumatoid arthritis-severe dry eye in 2 patients each. Other 2 patients had a progressive PCT following ocular surgery. One of the patients with infectious corneal ulcer also had a trauma caused by a scissor. Amnion membrane transplantation was performed in 3 patients prior to TCPG. While the anatomic success was achieved in all 8 patients, best-corrected visual acuity (BCVA was 0.1 or better in 4 patients (50%. Postoperative BCVA was better than preoperative BCVA in 6 patients (75%. Local peripheral anterior synechiae developed in two eyes. Conclusion: TCPG is a useful therapeutic option in selected cases of corneal thinning and perforations because it effectively restores the integrity of the globe and allows acceptable visual results. (Turk J Ophthalmol 2014; 44: 440-4

A portable device for measuring donor corneal transparency in eye banks.

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Parekh, Mohit; Ferrari, Stefano; Ruzza, Alessandro; Pugliese, Mariarosaria; Ponzin, Diego; Salvalaio, Gianni

2014-03-01

To develop a portable device for measuring the donor corneal transparency and validate its efficacy for corneal evaluation in the eye-banks and for research. The transparency device (TD) has a light source, a detachable system for corneal insertion and a base for light transmission. The probe detects the transmitted light which is measured by a lux-meter. A contact lens was set as 'control' to reduce the light scattering concern, an empty petri-plate as 'blank' and the cornea as 'sample'. Two experts and non-experts (masked) observed the corneas for subjective analysis which was then compared using the TD. The parameters observed were scars, foreign-body, stromal-deformities, folds, thickness and opacity which were then converted to a relative overall percentage by the observer. Twenty corneas were evaluated for correlation, five tissues to obtain standard-deviation and twenty-four pairs for a comparative study. Experts mimicked the eye-banks with long-term experience while non-experts mimicked the emerging eye-banks. Subjective values by the experts closely resembled the measurements by TD. The average correlation between the experts and the non-experts to TD was 0.985 and 0.960 respectively. TD showed higher reproducibility than experts followed by the non-experts. The comparative study showed that increase in thickness reduces the transparency. TD is portable, easy, efficient, maintains sterility and less expensive hence the emerging eye-banks and researchers can use to raise their standards and evaluate the transparency for in vitro tests and comparative studies. The suitable transparency for the cornea deemed for clinical applications was found to be >75 %.

Corneal Laceration

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Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Corneal Laceration ... Laceration Treatment What Is Corneal Laceration? Leer en Español: ¿Qué es una laceración de la córnea? Written ...

Cefazolin-Gentamicin versus Vancomycin-Ceftazidime Eye Drops for Bacterial Corneal Ulcers; a Randomized Clinical Trial

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Ali-Reza Dehghani

2009-01-01

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PURPOSE: To compare the efficacy of topical cefazolin-gentamicin versus vancomycin-ceftazidime for treatment of bacterial corneal ulcers. METHODS: This randomized double-masked clinical trial was performed on consecutive patients with bacterial corneal ulcers referred to Feiz Hospital, Isfahan, Iran from 2004 to 2005. Patients were randomly assigned to cefazolin-gentamicin or vancomycin-ceftazidime eye drops in a masked fashion. Outcome measures included time for resolution of stromal infiltration, re-epithelization of the epithelial defect, and clearance of anterior chamber inflammation as well as culture results and complications. RESULTS: The study included 89 eyes of 89 patients with bacterial corneal ulcers consisting of 57 (64% male and 32 (36% female subjects. Specimens were culture-negative in 46% of cases. Forty-one eyes received cefazolin-gentamicin and 48 eyes were treated with vancomycin-ceftazidime. Time for resolution of stromal infiltration was 17.7±4.3 days versus 13.8±3.6 days (P=0.04, time to complete re-epithelization was 13.2±3.1 days versus 9.6±2.7 days (P=0.01 and time for clearing of the anterior chamber was 11.6±2.9 days versus 8.1±2.3 days (P

In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells

Directory of Open Access Journals (Sweden)

Vishnubalaji Radhakrishnan

2012-01-01

Full Text Available Abstract Background Multipotent stem cells have been successfully isolated from various tissues and are currently utilized for tissue-engineering and cell-based therapies. Among the many sources, skin has recently emerged as an attractive source for multipotent cells because of its abundance. Recent literature showed that skin stromal cells (SSCs possess mesoderm lineage differentiation potential; however, the endothelial differentiation and angiogenic potential of SSC remains elusive. In our study, SSCs were isolated from human neonatal foreskin (hNFSSCs and adult dermal skin (hADSSCs using explants cultures and were compared with bone marrow (hMSC-TERT and adipose tissue-derived mesenchymal stem cells (hADMSCs for their potential differentiation into osteoblasts, adipocytes, and endothelial cells. Results Concordant with previous studies, both MSCs and SSCs showed similar morphology, surface protein expression, and were able to differentiate into osteoblasts and adipocytes. Using an endothelial induction culture system combined with an in vitro matrigel angiogenesis assay, hNFSSCs and hADSSCs exhibited the highest tube-forming capability, which was similar to those formed by human umbilical vein endothelial cells (HUVEC, with hNFSSCs forming the most tightly packed, longest, and largest diameter tubules among the three cell types. CD146 was highly expressed on hNFSSCs and HUVEC followed by hADSSCs, and hMSC-TERT, while its expression was almost absent on hADMSCs. Similarly, higher vascular density (based on the expression of CD31, CD34, vWF, CD146 and SMA was observed in neonatal skin, followed by adult dermal skin and adipose tissue. Thus, our preliminary data indicated a plausible relationship between vascular densities, and the expression of CD146 on multipotent cells derived from those tissues. Conclusions Our data is the first to demonstrate that human dermal skin stromal cells can be differentiated into endothelial lineage. Hence, SSCs

Keratocyte apoptosis and corneal antioxidant enzyme activities after refractive corneal surgery.

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Bilgihan, K; Bilgihan, A; Adiguzel, U; Sezer, C; Yis, O; Akyol, G; Hasanreisoglu, B

2002-01-01

Refractive corneal surgery induces keratocyte apoptosis and generates reactive oxygen radicals (ROS) in the cornea. The purpose of the present study is to evaluate the correlation between keratocyte apoptosis and corneal antioxidant enzyme activities after different refractive surgical procedures in rabbits. Rabbits were divided into six groups. All groups were compared with the control group (Group 1), after epithelial scraping (Group 2), epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK: Group 3), transepithelial PRK (Group 4), creation of a corneal flap with microkeratome (Group 5) and laser-assisted in situ keratomileusis (LASIK, Group 6). Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy were used to detect apoptosis in rabbit eyes. Glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities of the corneal tissues were measured with spectrophotometric methods. Corneal Gpx and SOD activities decreased significantly in all groups when compared with the control group (P<0.05) and groups 2, 3 and 6 showed a significantly higher amount of keratocyte apoptosis (P<0.05). Not only a negative correlation was observed between corneal SOD activity and keratocyte apoptosis (cc: -0.3648) but Gpx activity also showed negative correlation with keratocyte apoptosis (cc: -0.3587). The present study illustrates the negative correlation between keratocyte apoptosis and corneal antioxidant enzyme activities. This finding suggests that ROS may be partly responsible for keratocyte apoptosis after refractive surgery.

Preparation of acellular scaffold for corneal tissue engineering by supercritical carbon dioxide extraction technology.

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Huang, Yi-Hsun; Tseng, Fan-Wei; Chang, Wen-Hsin; Peng, I-Chen; Hsieh, Dar-Jen; Wu, Shu-Wei; Yeh, Ming-Long

2017-08-01

In this study, we developed a novel method using supercritical carbon dioxide (SCCO 2 ) to prepare acellular porcine cornea (APC). Under gentle extraction conditions using SCCO 2 technology, hematoxylin and eosin staining showed that cells were completely lysed, and cell debris, including nuclei, was efficiently removed from the porcine cornea. The SCCO 2 -treated corneas exhibited intact stromal structures and appropriate mechanical properties. Moreover, no immunological reactions and neovascularization were observed after lamellar keratoplasty in rabbits. All transplanted grafts and animals survived without complications. The transplanted APCs were opaque after the operation but became transparent within 2weeks. Complete re-epithelialization of the transplanted APCs was observed within 4weeks. In conclusion, APCs produced by SCCO 2 extraction technology could be an ideal and useful scaffold for corneal tissue engineering. We decellularized the porcine cornea using SCCO 2 extraction technology and investigated the characteristics, mechanical properties, and biocompatibility of the decellularized porcine cornea by lamellar keratoplasty in rabbits. To the best of our knowledge, this is the first report describing the use of SCCO 2 extraction technology for preparation of acellular corneal scaffold. We proved that the cellular components of porcine corneas had been efficiently removed, and the biomechanical properties of the scaffold were well preserved by SCCO 2 extraction technology. SCCO 2 -treated corneas maintained optical transparency and exhibited appropriate strength to withstand surgical procedures. In vivo, the transplanted corneas showed no evidence of immunological reactions and exhibited good biocompatibility and long-term stability. Our results suggested that the APCs developed by SCCO 2 extraction technology could be an ideal and useful scaffold for corneal replacement and corneal tissue engineering. Copyright © 2017 Acta Materialia Inc. Published by

Quantification of Collagen Ultrastructure after Penetrating Keratoplasty – Implications for Corneal Biomechanics

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Gardner, Steven J.; Kamma-Lorger, Christina S.; Hayes, Sally; Nielsen, Kim; Hjortdal, Jesper; Sorensen, Thomas; Terrill, Nicholas J.; Meek, Keith M.

2013-01-01

Purpose To quantify long-term changes in stromal collagen ultrastructure following penetrating keratoplasty (PK), and evaluate their possible implications for corneal biomechanics. Methods A pair of 16 mm post-mortem corneo-scleral buttons was obtained from a patient receiving bilateral penetrating keratoplasty 12 (left)/28 (right) years previously. Small-angle x-ray scattering quantified collagen fibril spacing, diameter and spatial order at 0.5 mm or 0.25 mm intervals along linear scans across the graft margin. Corresponding control data was collected from two corneo-scleral buttons with no history of refractive surgery. Wide-angle x-ray scattering quantified collagen fibril orientation at 0.25 mm (horizontal)×0.25 mm (vertical) intervals across both PK specimens. Quantification of orientation changes in the graft margin were verified by equivalent analysis of data from a 13 year post-operative right PK specimen obtained from a second patient in a previous study, and comparison made with new and published data from normal corneas. Results Marked changes to normal fibril alignment, in favour of tangentially oriented collagen, were observed around the entire graft margin in all PK specimens. The total number of meridional fibrils in the wound margin was observed to decrease by up to 40%, with the number of tangentially oriented fibrils increasing by up to 46%. As a result, in some locations the number of fibrils aligned parallel to the wound outnumbered those spanning it by up to five times. Localised increases in fibril spacing and diameter, with an accompanying reduction in matrix order, were also evident. Conclusions Abnormal collagen fibril size and spatial order within the PK graft margin are indicative of incomplete stromal wound remodelling and the long term persistence of fibrotic scar tissue. Lasting changes in collagen fibril orientation in and around PK wounds may alter corneal biomechanics and compromise the integrity of the graft-host interface in the

The Effect of Riboflavin/UVA Collagen Cross-linking Therapy on the Structure and Hydrodynamic Behaviour of the Ungulate and Rabbit Corneal Stroma

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Hayes, Sally; Kamma-Lorger, Christina S.; Boote, Craig; Young, Robert D.; Quantock, Andrew J.; Rost, Anika; Khatib, Yasmeen; Harris, Jonathan; Yagi, Naoto; Terrill, Nicholas; Meek, Keith M.

2013-01-01

Purpose To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour. Methods One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep) and 3 pairs of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits) were untreated; Group 2 (24 pig) were exposed to UVA light (3.04 mW/cm2) for 30 minutes and Group 3 (29 pig) and Group 4 (31 pig, 3 sheep and 3 rabbits) had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm2). X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution) and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques. Results Corneal thickness decreased significantly following riboflavin application (priboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen. PMID:23349690

In Vivo-Like Culture Conditions in a Bioreactor Facilitate Improved Tissue Quality in Corneal Storage.

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Schmid, Richard; Tarau, Ioana-Sandra; Rossi, Angela; Leonhardt, Stefan; Schwarz, Thomas; Schuerlein, Sebastian; Lotz, Christian; Hansmann, Jan

2018-01-01

The cornea is the most-transplanted tissue worldwide. However, the availability and quality of grafts are limited due to the current methods of corneal storage. In this study, a dynamic bioreactor system is employed to enable the control of intraocular pressure and the culture at the air-liquid interface. Thereby, in vivo-like storage conditions are achieved. Different media combinations for endothelium and epithelium are tested in standard and dynamic conditions to enhance the viability of the tissue. In contrast to culture conditions used in eye banks, the combination of the bioreactor and biochrom medium 1 allows to preserve the corneal endothelium and the epithelium. Assessment of transparency, swelling, and the trans-epithelial-electrical-resistance (TEER) strengthens the impact of the in vivo-like tissue culture. For example, compared to corneas stored under static conditions, significantly lower optical densities and significantly higher TEER values were measured (p-value <0.05). Furthermore, healing of epithelial defects is enabled in the bioreactor, characterized by re-epithelialization and initiated stromal regeneration. Based on the obtained results, an easy-to-use 3D-printed bioreactor composed of only two parts was derived to translate the technology from the laboratory to the eye banks. This optimized bioreactor facilitates noninvasive microscopic monitoring. The improved storage conditions ameliorate the quality of corneal grafts and the storage time in the eye banks to increase availability and reduce re-grafting. © 2017 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

A study on the cellular stromal reaction and immunologic response of regional lymph nodes in gastric cancer

International Nuclear Information System (INIS)

Jyokoh, Hiroshi

1986-01-01

In an attempt to find a correlation between background factors and prognosis, cellular stromal reaction and PHA blastformation in the regional lymph nodes in gastric cancer were investigated in a total of 234 cases with advanced gastric cancer consisting of 104 patients who had undergone preoperative radiaiton therapy and 130 non-irradiated patients. The following results were obtained: 1) Interstitial matrix and fibrotic components around the gastric cancer cells proliferate. In addition, cellular components consisting mainly of lymphocytes appear in varied degrees. 2) In both non-irradiated and irradiated groups, there was no remarkable difference in the cellular stromal reaction among any major cancer sites. 3) In non-irradiated patients, no correlation existed between tumor diameters and cellular stromal reaction, while, in the irradiated cases, there were increases in the cellular stromal reaction where the tumor size is 5 cm or less. 4) In both non-irradiated and irradiated groups, cellular stromal reaction was more remarkable in highly differentiated carcinoma. 5) There were decreases in the cellular stromal reaction in ps(+) cases, of both non-irradiated and irradiated groups. 6) The cellular stromal reaction was remarkable in non-irradiated and irradiated patients who were found to be histologically negative in lymph node metastasis. 7) With the advance in staging, the cellular stromal reaction decreased in both irradiated and non-irradiated patients. 8) In both non-irradiated and irradiated groups, the cellular stromal reaction decreased in the patients who had shown vascular invasion. 9) PHA blastformation of the lymphocytes in lymph nodes of non-metastatic cases was more remarkable than that of metastatic cases, retaining high degrees of immunity. 10) In the non-metastatic patients in the lymph nodes outside the irradiated area, the lymphocytes in the lymph nodes demonstrated high degrees of PHA blastformation. (J.P.N.)

Limitations in imaging common conjunctival and corneal pathologies with fourier-domain optical coherence tomography.

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Demirci, Hakan; Steen, Daniel W

2014-01-01

To describe the limitations of Fourier-domain optical coherence tomography (OCT) in imaging common conjunctival and corneal pathology. Retrospective, single-center case series of 40 patients with conjunctival and cornea pathology. Fourier-domain OCT imaged laser in situ keratomileusis (LASIK) flaps in detail, including its relation to other corneal structures and abnormalities. Similarly, in infectious or degenerative corneal disorders, Fourier-domain OCT successfully showed the extent of infiltration or material deposition, which appeared as hyper-reflective areas. In cases with pterygium, the underlying cornea could not be imaged. All cases of common conjunctival pathologies, such as nevus or pinguecula, were successfully imaged in detail. Nevi, scleritis, pterygium, pinguecula, and subconjunctival hemorrhage were hyper-reflective lesions, while cysts and lymphangiectasia were hyporeflective. The details of the underlying sclera were not uniformly imaged in conjunctival pathologies. Fourier-domain OCT imaged the trabeculectomy bleb in detail, whereas the details of structures of the anterior chamber angle were not routinely visualized in all cases. Light scatter through vascularized, densely inflamed, or thick lesions limits the imaging capabilities of Fourier-domain anterior segment OCT.

Rate of riboflavin diffusion from intrastromal channels before corneal crosslinking.

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McQuaid, Rebecca; Mrochen, Michael; Vohnsen, Brian

2016-03-01

To determine the diffusion of riboflavin from intrastromal channels through the effective diffusion coefficients compared with traditional axial diffusion with epithelium on or off. Advanced Optical Imaging Laboratory, University College Dublin, and Wellington Eye Clinic, Sandyford, Dublin, Ireland. Experimental study. The rate of diffusion in whole-mounted porcine eyes was monitored for a 30 minutes using an optical setup with a charge-coupled device camera and a bandpass filter (central wavelength 550 nm and 40 nm bandpass) to image the fluorescence under ultraviolet illumination (365 nm wavelength). For comparison, an isotropic corneal stroma with an annular channel was modeled numerically for different diffusion constants and boundary conditions. Numerical and experimental results were compared, allowing determination of the effective diffusion coefficient for each case. Experimental results for 6 different riboflavin solutions were in all cases found to be higher than for the common crosslinking (CXL) riboflavin protocol, where the diffusion constant is D0 = 6.5 × 10(-5) mm(2)/sec. For the intrastromal channel, 2 isotonic solutions containing riboflavin 0.1% correlated with a diffusion constant of 5D0 = 32.5 × 10(-5) mm(2)/sec. Hypotonic solutions and transepithelium had a higher diffusion coefficient approaching 10D0 = 65.0 × 10(-5) mm(2)/sec, which is an order-of-magnitude increase compared with the typical diffusion coefficient found in standard CXL. In this study, riboflavin had a faster stromal diffusion when injected into a corneal channel than when applied as drops to the anterior corneal surface. Further numerical modeling might allow optimization of the channel structure for any specific choice of riboflavin. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Corneal tissue welding with infrared laser irradiation after clear corneal incision.

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Rasier, Rfat; Ozeren, Mediha; Artunay, Ozgür; Bahçecioğlu, Halil; Seçkin, Ismail; Kalaycoğlu, Hamit; Kurt, Adnan; Sennaroğlu, Alphan; Gülsoy, Murat

2010-09-01

The aim of this study was to investigate the potential of infrared lasers for corneal welding to seal corneal cuts done in an experimental animal model. Full-thickness corneal cuts on freshly enucleated bovine eyes were irradiated with infrared (809-nm diode, 980-nm diode, 1070-nm YLF, and 1980-nm Tm:YAP) lasers to get immediate laser welding. An 809-nm laser was used with the topical application of indocyanine green to enhance the photothermal interaction at the weld site. In total, 60 bovine eyes were used in this study; 40 eyes were used in the first part of the study for the determination of optimal welding parameters (15 eyes were excluded because of macroscopic carbonization, opacification, or corneal shrinkage; 2 eyes were used for control), and 20 eyes were used for further investigation of more promising lasers (YLF and Tm:YAP). Laser wavelength, irradiating power, exposure time, and spot size were the dose parameters, and optimal dose for immediate closure with minimal thermal damage was estimated through histological examination of welded samples. In the first part of the study, results showed that none of the applications was satisfactory. Full-thickness success rates were 28% (2 of 7) for 809-nm and for 980-nm diode lasers and 67% (2 of 3) for 1070-nm YLF and (4 of 6) for 1980-nm Tm:YAP lasers. In the second part of the study, YLF and Tm:YAP lasers were investigated with bigger sample size. Results were not conclusive but promising again. Five corneal incisions were full-thickness welded out of 10 corneas with 1070-nm laser, and 4 corneal incisions were partially welded out of 10 corneas with 1980-nm laser in the second part of the study. Results showed that noteworthy corneal welding could be obtained with 1070-nm YLF laser and 1980-nm Tm:YAP laser wavelengths. Furthermore, in vitro and in vivo studies will shed light on the potential usage of corneal laser welding technique.

Clinical applications of corneal confocal microscopy

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Mitra Tavakoli

2008-06-01

Full Text Available Mitra Tavakoli1, Parwez Hossain2, Rayaz A Malik11Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, UK; 2University of Southampton, Southampton Eye Unit, Southampton General Hospital, Southampton, UKAbstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cellular structure. It provides images which are comparable to in-vitro histochemical techniques delineating corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium. Because, corneal confocal microscopy is a non invasive technique for in vivo imaging of the living cornea it has huge clinical potential to investigate numerous corneal diseases. Thus far it has been used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post surgical evaluation (PRK, LASIK and LASEK, flap evaluations and Radial Keratotomy, and penetrating keratoplasty. Most recently it has been used as a surrogate for peripheral nerve damage in a variety of peripheral neuropathies and may have potential in acting as a surrogate marker for endothelial abnormalities.Keywords: corneal confocal microscopy, cornea, infective keratitis, corneal dystrophy, neuropathy

Neurotrophic corneal and conjunctival xerosis

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Svetlana Gennadyevna Zhurova

2014-03-01

Full Text Available Purpose: to develop a method of surgical treatment of patients with corneal ulcers of xerotic etiology and evaluate its efficacy in different time periods after operation. Materials and methods: 68 patients (86 eyes with severe dry eye syndrome complicated by xerotic corneal ulcers were examined. In all patients, the ulcer defect was covered with conjunctiva and amniotic membrane. The operation was combined with an outer tarsorrhaphy and temporary blepharorraphy. Results: All 86 eyes (100% achieved total closure of the ulcer defect, sealing of any perforation and maintaining of corneal transparency beyond the ulcer defect. Conclusion: Surgical closure of corneal ulcers with conjunctiva is an effective method of treatment of xerotic corneal ulcers. It could be recommended in patients with corneal perforation and tendency of descemetocele formation.

Uso de terapia antifactor de crecimiento vascular endotelial en patología corneal

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Tomás Rojas

2014-07-01

Conclusiones: Los resultados obtenidos en ensayos en animales y en humanos junto con la tolerancia de los pacientes ofrecen una perspectiva alentadora para el papel potencial de agentes anti-VEGF en el tratamiento de la neovascularización del segmento anterior. Es necesaria la realización de ensayos clínicos controlados aleatorizados para establecer a largo plazo la seguridad, la eficacia y las pautas de dosificación para el uso de anti-VEGF en la neovascularización corneal.

Myogel supports the ex-vivo amplification of corneal epithelial cells.

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Francis, D; Abberton, K; Thompson, E; Daniell, M

2009-03-01

Limbal stem cell deficiency leads to conjunctivalisation of the cornea and subsequent loss of vision. The recent development of transplantation of ex-vivo amplified corneal epithelium, derived from limbal stem cells, has shown promise in treating this challenging condition. The purpose of this research was to compare a variety of cell sheet carriers for their suitability in creating a confluent corneal epithelium from amplified limbal stem cells. Cadaveric donor limbal cells were cultured using an explant technique, free of 3T3 feeder cells, on a variety of cell sheet carriers, including denuded amniotic membrane, Matrigel, Myogel and stromal extract. Comparisons in rate of growth and degree of differentiation were made, using immunocytochemistry (CK3, CK19 and ABCG2). The most rapid growth was observed on Myogel and denuded amniotic membrane, these two cell carriers also provided the most reliable substrata for achieving confluence. The putative limbal stem cell marker, ABCG2, stained positively on cells grown over Myogel and Matrigel but not for those propagated on denuded amniotic membrane. In the clinical setting amniotic membrane has been demonstrated to provide a suitable carrier for limbal stem cells and the resultant epithelium has been shown to be successful in treating limbal stem cell deficiency. Myogel may provide an alternative cell carrier with a further reduction in risk as it is has the potential to be derived from an autologous muscle biopsy in the clinical setting.

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

Science.gov (United States)

2014-01-01

Introduction Regenerative medicine challenges researchers to find noncontroversial, safe and abundant stem cell sources. In this context, harvesting from asystolic donors could represent an innovative and unlimited reservoir of different stem cells. In this study, cadaveric vascular tissues were established as an alternative source of human cadaver mesenchymal stromal/stem cells (hC-MSCs). We reported the successful cell isolation from postmortem arterial segments stored in a tissue-banking facility for at least 5 years. Methods After thawing, hC-MSCs were isolated with a high efficiency (12 × 106) and characterized with flow cytometry, immunofluorescence, molecular and ultrastructural approaches. Results In early passages, hC-MSCs were clonogenic, highly proliferative and expressed mesenchymal (CD44, CD73, CD90, CD105, HLA-G), stemness (Stro-1, Oct-4, Notch-1), pericyte (CD146, PDGFR-β, NG2) and neuronal (Nestin) markers; hematopoietic and vascular markers were negative. These cells had colony and spheroid-forming abilities, multipotency for their potential to differentiate in multiple mesengenic lineages and immunosuppressive activity to counteract proliferation of phytohemagglutinin-stimulated blood mononuclear cells. Conclusions The efficient procurement of stem cells from cadaveric sources, as postmortem vascular tissues, demonstrates that such cells can survive to prolonged ischemic insult, anoxia, freezing and dehydration injuries, thus paving the way for a scientific revolution where cadaver stromal/stem cells could effectively treat patients demanding cell therapies. PMID:24429026

Corneal markers of diabetic neuropathy.

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Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2011-01-01

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Topical thrombin-related corneal calcification.

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Kiratli, Hayyam; Irkeç, Murat; Alaçal, Sibel; Söylemezoğlu, Figen

2006-09-01

To report a highly unusual case of corneal calcification after brief intraoperative use of topical thrombin. A 44-year-old man underwent sclerouvectomy for ciliochoroidal leiomyoma, during which 35 UNIH/mL lyophilized bovine thrombin mixed with 9 mL of diluent containing 1500 mmol/mL calcium chloride was used. From the first postoperative day, corneal and anterior lenticular capsule calcifications developed, and corneal involvement slightly enlarged thereafter. A year later, 2 corneal punch biopsies confirmed calcification mainly in the Bowman layer. Topical treatment with 1.5% ethylenediaminetetraacetic acid significantly restored corneal clarity. Six months later, a standard extracapsular cataract extraction with intraocular lens placement improved visual acuity to 20/60. This case suggests that topical thrombin drops with elevated calcium concentrations may cause acute corneal calcification in Bowman layer and on the anterior lens capsule.

Transcriptome profiling reveals novel expression markers that predispose patients to develop post- photorefractive keratectomy corneal haze

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Nimisha Nimisha

2017-10-01

Full Text Available Photorefractive keratectomy is an excimer laser [1] based ablation surgery of corneal surface used for correcting refractive errors. Corneal haze is the result of an aggressive wound healing response with an incidence rate [2] of 1.44% post PRK, making it an important health burden. Studies thus far have only focused on molecular alterations post haze development. Since the corneal epithelium is an important mediator of the stromal haze response, we studies its role in predisposing subjects to develop aberrant wound healing response. Corneal epithelium samples collected intra-operatively from clinically healthy patients during PRK. This epithelium from 6 eyes that developed haze postoperatively and 10 eyes of age matched controls without haze were compared. Gene expression microarrays were performed for the mRNA samples followed by ontological analysis of underlying molecular pathways. The identified targets were validated in an independent set of post haze epithelial samples from 3 subjects with PRK induced haze. In vitro studies were done on HCE cells for differential dose of TGFβ for inflammatory markers, corneal structure & fibrosis associated genes and regulators of signal transduction. In addition, loss and gain of function studies was performed using PREX1 as a novel, prototype target. Mean age of groups was 25-28 years. A total of 1100 up and 1700 down regulated genes were revealed by microarray. Alterations in Oxidative stress, ECM-Receptor interactions, Wnt signaling pathway and CXC motif containing chemokines contributes to cellular proliferation and wound healing, which is observed in in vitro model. In cornea novel target PREX1, an oxidative stress gene, when over expressed exhibits faster wound closure in HCE cells with and without TGFβ. Loss of function using PREX1 shRNA shows reduced wound closure. Our study shows that novel genes are involved in pathogenesis of post PRK haze. PREX1 over expression results in faster wound

Corneal Transplantation

DEFF Research Database (Denmark)

Hjortdal, Jesper Østergaard

with less risk of rejection episodes. Besides covering updated chapters on penetrating keratoplasty, and anterior and posterior lamellar procedures, this textbook also gives a thorough overview of the history of corneal transplantation and a detailed presentation of the microstructural components...... and to assist fellows and corneal surgeons in their advice and selection of patients for the best surgical procedure considering benefi ts and risks....

Applications of corneal topography and tomography: a review.

Science.gov (United States)

Fan, Rachel; Chan, Tommy Cy; Prakash, Gaurav; Jhanji, Vishal

2018-03-01

Corneal imaging is essential for diagnosing and management of a wide variety of ocular diseases. Corneal topography is used to characterize the shape of the cornea, specifically, the anterior surface of the cornea. Most corneal topographical systems are based on Placido disc that analyse rings that are reflected off the corneal surface. The posterior corneal surface cannot be characterized using Placido disc technology. Imaging of the posterior corneal surface is useful for diagnosis of corneal ectasia. Unlike corneal topographers, tomographers generate a three-dimensional recreation of the anterior segment and provide information about the corneal thickness. Scheimpflug imaging is one of the most commonly used techniques for corneal tomography. The cross-sectional images generated by a rotating Scheimpflug camera are used to locate the anterior and posterior corneal surfaces. The clinical uses of corneal topography include, diagnosis of corneal ectasia, assessment of corneal astigmatism, and refractive surgery planning. This review will discuss the applications of corneal topography and tomography in clinical practice. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Effects of artificial tear treatment on corneal epithelial thickness and corneal topography findings in dry eye patients.

Science.gov (United States)

Çakır, B; Doğan, E; Çelik, E; Babashli, T; Uçak, T; Alagöz, G

2018-05-01

To investigate the effects of artificial tear treatment on central corneal epithelial thickness, and central, mid-peripheral and peripheral corneal thicknesses in patients with dry eye disease (DED). Patients with DED underwent ocular examinations, including Schirmer-2 test, slit lamp examination for tear break-up time (BUT), corneal topography (CT) for measuring mean central, mid-peripheral and peripheral corneal thickness values and anterior segment optic coherence tomography (AS-OCT) for obtaining central corneal epithelial thickness. After artificial tear treatment (carboxymethylcellulose and sodium hyaluronate formulations) for one month, patients were examined again at a second visit and the results were compared. Sixty-one eyes of 33 female dry eye patients (mean age: 38.3±5.7 years) were enrolled. The mean follow-up time was 36.4±3.3 days. The mean tear BUT and Schirmer-1 tests revealed significant improvement after treatment (P=0.000, P=0.000, respectively). Central corneal epithelium and mean mid-peripheral corneal thicknesses measured significantly higher after treatment (P=0.001, P=0.02). Changes in central and peripheral corneal thicknesses were not statistically significant. Artificial tear treatment in dry eye patients seems to increase central corneal epithelial and mid-peripheral corneal thicknesses. Measurement of corneal epithelial thickness can be a useful tool for evaluation of treatment response in dry eye patients. Further long-term prospective studies are needed to investigate this item. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Topical Drug Formulations for Prolonged Corneal Anesthesia

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Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

2013-01-01

Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

Evaluation of intraocular pressure according to corneal thickness before and after excimer laser corneal ablation for myopia.

Science.gov (United States)

Hamed-Azzam, Shirin; Briscoe, Daniel; Tomkins, Oren; Shehedeh-Mashor, Raneen; Garzozi, Hanna

2013-08-01

Intraocular pressure is affected by corneal thickness and biomechanics. Following ablative corneal refractive surgery, corneal structural changes occur. The purpose of the study is to determine the relationship between the mean central corneal thickness (CCT) and the change in intraocular pressure measurements following various corneal ablation techniques, using different measurement methods. Two hundred myopic eyes undergoing laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) were enrolled into a prospective, non-randomized study. Corneal parameters examined included full ocular examination, measurement of CCT, corneal topography, corneal curvature and ocular refractivity. Intraocular pressure measurements were obtained using three different instruments-non-contact tonometer, Goldmann applanation tonometer and TonoPen XL (TonoPen-Central and TonoPen-Peripheral). All measurements were performed pre-operatively and 4 months post-operatively. Post-operative intraocular pressure was significantly lower than pre-operative values, with all instruments (p value tonometer and non-contact tonometer (p value < 0.001, ANOVA). Intraocular pressure readings are significantly reduced following corneal ablation surgery. We determined in our myopic patient cohort that the TonoPen XL intraocular pressure measurement method is the least affected following PRK and LASIK as compared to other techniques.

Trifluoperazine: corneal endothelial phototoxicity

International Nuclear Information System (INIS)

Hull, D.S.; Csukas, S.; Green, K.

1983-01-01

Trifluoperazine is used for the treatment of psychiatric disorders. Perfusion of corneal endothelial cells with trifluoperazine-HC1 concurrent with exposure to long wavelength ultraviolet light resulted in a corneal swelling rate greater than that found in perfused corneas not exposed to ultraviolet light. Exposure of endothelial cells to 25 W incandescent light during perfusion with trifluoperazine-HC1 did not result in a higher corneal swelling rate compared to those perfused in the dark. The increased corneal swelling rate could be produced by pre-exposure of the trifluoperazine-HC1 perfusing solution to ultraviolet light suggesting the production of toxic photoproducts during exposure of trifluoperazine-HC1 to ultraviolet light. Perfusion of corneal endothelial cells with non-ultraviolet illuminated trifluoperazine-HC1 had no effect on endothelial cell membranes or ultrastructure. This is in contrast to cells perfused with trifluoperazine-HC1 that had been exposed to ultraviolet light in which there was an alteration of mitochondria and a loss of cytoplasmic homogeneity. The data imply that the trifluoperazine-HC1 photoproduct had an adverse effect on cellular transport mechanisms. The study also further demonstrates the value of the corneal endothelial cell model for identifying the physiological and anatomical changes occuring in photo-induced toxic reactions. (author)

Herpetic keratouveitis mixed with bilateral Pseudomonas corneal ulcers in vitamin A deficiency

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Hung-Yuan Hsu

2015-02-01

Full Text Available A 56-year-old woman complained of blurred vision and pain in her right eye for several days. Slit lamp examination revealed a large epithelial defect and disciform stromal edema with ring infiltration in her right cornea. Unfortunately, hypopyon and purulent discharge subsequently developed in both eyes. Herpetic keratouveitis and a superimposed pseudomonas infection were diagnosed. A systemic review on the patient showed malnutrition due to her dietary preference and vegetarianism. After the infection was controlled, bilateral epithelial defects persisted for a long time. We performed amniotic membrane transplantation on both eyes and the clinical status improved with administration of vitamin and protein supplements. Although rare in Taiwan, vitamin A deficiency should be kept in mind when conjunctival and corneal xerosis occurred. Vitamin A supplements are suggested because of the increased susceptibility to infection in patients with this clinical status.

Corneal surface temperature change as the mode of stimulation of the non-contact corneal aesthesiometer.

Science.gov (United States)

Murphy, P J; Morgan, P B; Patel, S; Marshall, J

1999-05-01

The non-contact corneal aesthesiometer (NCCA) assesses corneal sensitivity by using a controlled pulse of air, directed at the corneal surface. The purpose of this paper was to investigate whether corneal surface temperature change was a component in the mode of stimulation. Thermocouple experiment: A simple model corneal surface was developed that was composed of a moistened circle of filter paper placed on a thermocouple and mounted on a glass slide. The temperature change produced by different stimulus pressures was measured for five different ambient temperatures. Thermal camera experiment: Using a thermal camera, the corneal surface temperature change was measured in nine young, healthy subjects after exposure to different stimulus air pulses. Pulse duration was set at 0.9 s but was varied in pressure from 0.5 to 3.5 millibars. Thermocouple experiment: An immediate drop in temperature was detected by the thermocouple as soon as the air flow was incident on the filter paper. A greater temperature change was produced by increasing the pressure of the incident air flow. A relationship was found and a calibration curve plotted. Thermal camera experiment: For each subject, a drop in surface temperature was detected at each stimulus pressure. Furthermore, as the stimulus pressure increased, the induced reduction in temperature also increased. A relationship was found and a calibration curve plotted. The NCCA air-pulse stimulus was capable of producing a localized temperature change on the corneal surface. The principal mode of corneal nerve stimulation, by the NCCA air pulse, was the rate of temperature change of the corneal surface.

CONTACT LENS RELATED CORNEAL ULCER

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AGARWAL P

2010-01-01

Full Text Available A corneal ulcer caused by infection is one of the major causes of blindness worldwide. One of the recent health concerns is the increasing incidence of corneal ulcers associated with contact lens user especially if the users fail to follow specific instruction in using their contact lenses. Risk factors associated with increased risk of contact lens related corneal ulcers are:overnight wear, long duration of continuous wear, lower socio-economic classes, smoking, dry eye and poor hygiene. The presenting symptoms of contact lens related corneal ulcers include eye discomfort, foreign body sensation and lacrimation. More serious symptoms are redness (especially circum-corneal injection, severe pain, photophobia, eye discharge and blurring of vision. The diagnosis is established by a thorough slit lamp microscopic examination with fluorescein staining and corneal scraping for Gram stain and culture of the infective organism. Delay in diagnosing and treatment can cause permanent blindness, therefore an early referral to ophthalmologist and commencing of antimicrobial therapy can prevent visual loss.

Nerve growth factor regulates neurolymphatic remodeling during corneal inflammation and resolution.

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Darci M Fink

Full Text Available The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that NGF-laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF-C. Adult human dermal lymphatic endothelial cells did not express canonical NGF receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors in the presence of NGF, although NGF treatment increased their migratory and tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a hierarchical relationship with NGF functioning upstream of the VEGF family members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together, these studies show that NGF stimulates lymphangiogenesis and that NGF may act as a pathogenic factor that negatively regulates the normal neural and lymphatic vascular remodeling events that accompany wound recovery.

Correlations between corneal and total wavefront aberrations

Science.gov (United States)

Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

2002-06-01

Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p the corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

Refractive Lenticule Implantation for Correction of Ametropia: Case Reports and Literature Review.

Science.gov (United States)

Lazaridis, A; Messerschmidt-Roth, A; Sekundo, W; Schulze, S

2017-01-01

The ReLEx® technique allows correction of refractive errors through the creation and extraction of refractive stromal lenticules. Contrary to excimer laser corneal refractive procedures, where the stromal tissue is photoablated, the extracted lenticules obtained with ReLEx® can be preserved. Recent studies and case reports have described autologous re-implantation and allogeneic implantation of refractive lenticules into femtosecond-laser created stromal pockets in order to reverse the refractive outcome of a myopic corneal refractive procedure, correct hyperopia, aphakia, presbyopia and treat keratoconus. The use of stromal lenticules has also been described for therapeutic purposes, with an allogenic lenticule being transplanted under a LASIK flap in order to restore corneal volume and reduce the refractive error in a case of excessive stromal tissue removal after LASIK. This review summarises the results of the latest case reports and studies that describe the implantation of cryopreserved or fresh refractive stromal lenticules and discusses the feasibility, safety and refractive outcomes of the procedure, on the basis of published literature as well as our own experience. Georg Thieme Verlag KG Stuttgart · New York.

Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase

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Silvia Baldari

2016-07-01

Full Text Available Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs, suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2. Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential.

Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2 and MMP-9 in feline tears following corneal epithelial wounding.

Science.gov (United States)

Petznick, Andrea; Madigan, Michele C; Garrett, Qian; Sweeney, Deborah F; Evans, Margaret D M

2013-01-01

corneal wounding are the lacrimal gland and CALT. Other sources included stromal keratocytes and conjunctiva with goblet cells.

PRELIMINARY CLINICAL RESULTS WITH LIPOASPIRATE STROMAL VASCULAR CELL FRACTION IN TREATMENT OF PATIENTS WITH KNEE OSTEOARTHRITIS

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E. Ya. Shevela

2017-01-01

Full Text Available The paper presents results of clinical application of autologous stromal-vascular fraction (SVF cells in patients with degenerative osteoarthritis (OA of the knee, grade II and III (Kellgren–Lawrence scale.We recruited six patients with knee OA (3 men and 3 women; median age 64 years with mean disease duration of 7 years. All the patients were administered a single intra-articular injection of autologous nucleated SVF cells at an average dose of 16.8±0.9 × 106 per joint (a total of 11 joints. The patients did not experience any serious side effects (allergic, toxic or inflammatory related to the knee injection. Patient surveys at 1 month after SVF administration revealed a decrease in the severity of pain, as measured by a visual analog scale (VAS and a specialized 100-point scale KOOS (subscale "pain" (p < 0.05 on both scales. Moreover, the patients reported improvement in the joint functions and quality of life related to affected joints on a KOOS scale (p < 0.05. These positive clinical changes persisted during 6 month follow up. Significant improvements were noted in ultrasound findings, with increased thickness of the cartilage layer at 3 months (in 73% of cases and at 6 months (in 82%. Our pilot study demonstrated the safety and tolerability of intra-articular injection of autologous SVF cells in patients with moderate to severe OA. The results obtained also indicate a significant antiinflammatory effect of autologous adipose tissue SVF cells, which is manifested at the early stages of cell therapy. Our further investigations will be focused on exploring the SVF stimulatory effects on regeneration of damaged joints.

Distrofia corneal de Schnyder

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Michel Guerra Almaguer

Full Text Available La principal entidad hereditaria con depósitos de lípidos en el estroma corneal es la distrofia cristalina central, conocida como distrofia de Schnyder, quien la describió en Suiza en 1927. Se caracteriza por depósitos blanco-amarillentos en el estroma corneal central y superficial. Se presenta un paciente de 28 años, del sexo masculino y piel negra, con antecedente de salud anterior. Acudió a consulta y refirió una disminución de la visión y cambio de coloración progresiva de ambos ojos, de años de evolución. En la exploración oftalmológica de ambos ojos se apreciaron lesiones blanquecinas anulares a nivel del estroma corneal, con ligera turbidez corneal central. Los estudios refractivos realizados constataron un astigmatismo hipermetrópico simple. El resto del examen oftalmológico fue negativo. Para el diagnóstico de certeza se empleó el microscopio confocal. Se concluye que el caso presenta una distrofia corneal estromal de tipo cristalina, de Schnyder.

Anterior corneal profile with variable asphericity.

Science.gov (United States)

Rosales, Marco A; Juárez-Aubry, Montserrat; López-Olazagasti, Estela; Ibarra, Jorge; Tepichín, Eduardo

2009-12-10

We present a corneal profile in which the eccentricity, e(Q=-e(2)), has a nonlinear continuous variation from the center outwards. This nonlinear variation is intended to fit and reproduce our current experimental data in which the anterior corneal surface of the human eye exhibits different values of e at different diameters. According to our clinical data, the variation is similar to an exponential decay. We propose a linear combination of two exponential functions to describe the variation of e. We then calculate the corneal sagittal height by substituting e in the first-order aspherical surface equation to obtain the corneal profile. This corneal profile will be used as a reference to analyze the resultant profiles of the customized corneal ablation in refractive surgery.

History of corneal transplantation in Australia.

Science.gov (United States)

Coster, Douglas J

2015-04-01

Corneal transplantation is a triumph of modern ophthalmology. The possibility of corneal transplantation was first raised in 1797 but a century passed before Zirm achieved the first successful penetrating graft in 1905. Gibson reported the first corneal graft in Australia from Brisbane in 1940 and English established the first eye bank there a few years later. Corneal transplantation evolved steadily over the twentieth century. In the second half of the century, developments in microsurgery, including surgical materials such as monofilament nylon and strong topical steroid drops, accounted for improvements in outcomes. In 2013, approximately 1500 corneal transplants were done in Australia. Eye banking has evolved to cope with the rising demands for donor corneas. Australian corneal surgeons collaborated to establish and support the Australian Corneal Graft Registry in 1985. It follows the outcomes of their surgery and has become an important international resource for surgeons seeking further improvement with the procedure. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Preoperative prediction of lymph node metastasis and deep stromal invasion in women with invasive cervical cancer: prospective multicenter study using 2D and 3D ultrasound.

Science.gov (United States)

Pálsdóttir, K; Fischerova, D; Franchi, D; Testa, A; Di Legge, A; Epstein, E

2015-04-01

To determine how various objective two-dimensional (2D) and three-dimensional (3D) ultrasound parameters allow prediction of deep stromal tumor invasion and lymph node involvement, in comparison to subjective ultrasound assessment, in women scheduled for surgery for cervical cancer. This was a prospective multicenter trial including 104 women with cervical cancer at FIGO Stages IA2-IIB, verified histologically. Patients scheduled for surgery underwent a preoperative ultrasound examination. The value of various 2D (size, color score) and 3D (volume, vascular indices) ultrasound parameters was compared to that of subjective assessment in the prediction of deep stromal tumor invasion and lymph node involvement. Histology obtained from radical hysterectomy or trachelectomy and pelvic lymphadenectomy was considered as the gold standard for assessment. All women underwent pelvic lymphadenectomy, with 99 (95%) undergoing subsequent radical surgery; five underwent only pelvic lymphadenectomy because of the presence of a positive sentinel lymph node. Women with deep stromal invasion or lymph node involvement had significantly larger tumors (diameter and volume) but there was no correlation with vascular indices measured on 3D ultrasound. Subjective evaluation was superior (AUC, 0.93; sensitivity, 90.5%; specificity, 97.2%) in the prediction of deep stromal invasion when compared to any objective measurement technique, with maximal tumor diameter at 20.5-mm cut-off (AUC, 0.83; sensitivity, 90.5%; specificity, 61.1%) and 3D tumor volume at 9.1-mm(3) cut-off (AUC, 0.85; sensitivity, 79.4%; specificity, 83.3%) providing the best performance among the objective parameters. Both subjective assessment and objective measurements were poorly predictive of lymph node involvement. In women with cervical cancer, subjective ultrasound evaluation allowed better prediction of deep stromal invasion than did objective measurements; however, neither subjective evaluation nor objective

Traumatic ulcerative granuloma with stromal eosinophilia of the palate showing an angiocentric/angiodestructive growth pattern

OpenAIRE

Brasileiro, Bernardo Ferreira; Alves, Daniel Berretta; Andrade, Bruno Augusto Benevenuto; Vargas, Pablo Agustin; León, Jorge Esquiche; Almeida, Oslei Paes De

2012-01-01

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a benign, self-limiting lesion of the oral mucosa with unknown pathogenesis. A 65-year-old male patient presented with an ulcerative palate lesion, which on microscopic examination exhibited an exuberant polymorphic lymphoid proliferation, numerous eosinophils, and extensive vascular destruction. The atypical lymphoid cells infiltrating the medium-sized vessels showed positivity for CD3, CD30, and granzyme B, implicating an a...

Glaucoma after corneal replacement.

Science.gov (United States)

Baltaziak, Monika; Chew, Hall F; Podbielski, Dominik W; Ahmed, Iqbal Ike K

Glaucoma is a well-known complication after corneal transplantation surgery. Traditional corneal transplantation surgery, specifically penetrating keratoplasty, has been slowly replaced by the advent of new corneal transplantation procedures: primarily lamellar keratoplasties. There has also been an emergence of keratoprosthesis implants for eyes that are high risk of failure with penetrating keratoplasty. Consequently, there are different rates of glaucoma, pathogenesis, and potential treatment in the form of medical, laser, or surgical therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Turning the tide of corneal blindness

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Matthew S Oliva

2012-01-01

Full Text Available Corneal diseases represent the second leading cause of blindness in most developing world countries. Worldwide, major investments in public health infrastructure and primary eye care services have built a strong foundation for preventing future corneal blindness. However, there are an estimated 4.9 million bilaterally corneal blind persons worldwide who could potentially have their sight restored through corneal transplantation. Traditionally, barriers to increased corneal transplantation have been daunting, with limited tissue availability and lack of trained corneal surgeons making widespread keratoplasty services cost prohibitive and logistically unfeasible. The ascendancy of cataract surgical rates and more robust eye care infrastructure of several Asian and African countries now provide a solid base from which to dramatically expand corneal transplantation rates. India emerges as a clear global priority as it has the world′s largest corneal blind population and strong infrastructural readiness to rapidly scale its keratoplasty numbers. Technological modernization of the eye bank infrastructure must follow suit. Two key factors are the development of professional eye bank managers and the establishment of Hospital Cornea Recovery Programs. Recent adaptation of these modern eye banking models in India have led to corresponding high growth rates in the procurement of transplantable tissues, improved utilization rates, operating efficiency realization, and increased financial sustainability. The widespread adaptation of lamellar keratoplasty techniques also holds promise to improve corneal transplant success rates. The global ophthalmic community is now poised to scale up widespread access to corneal transplantation to meet the needs of the millions who are currently blind.

Analysis of the horizontal corneal diameter, central corneal thickness, and axial length in premature infants

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Ozdemir Ozdemir

2014-08-01

Full Text Available Purpose: To determine the horizontal corneal diameter, central corneal thickness, and axial length in premature infants. Methods: Infants with a birth weight of less than 2,500 g or with a gestation period of less than 36 weeks were included in the study. Infants with retinopathy of prematurity (ROP were allocated to Group 1 (n=138, while those without ROP were allocated to Group 2 (n=236. All infants underwent a complete ophthalmologic examination, including corneal diameter measurements, pachymetry, biometry, and fundoscopy. Between-group comparisons of horizontal corneal diameter, central corneal thickness, and axial lengths were performed. Independent sample t-tests were used for statistical analysis. Results: Data was obtained from 374 eyes of 187 infants (102 female, 85 male. The mean gestational age at birth was 30.7 ± 2.7 weeks (range 25-36 weeks, the mean birth weight was 1,514 ± 533.3 g (range 750-1,970 g, and the mean postmenstrual age at examination was 40.0 ± 4.8 weeks. The mean gestational age and the mean birth weight of Group 1 were statistically lower than Group 2 (p0.05. Conclusions: The presence of ROP in premature infants does not alter the horizontal corneal diameter, central corneal thickness, or axial length.

Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

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Yibin Kang

2016-06-01

Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

Instillation of Sericin Enhances Corneal Wound Healing through the ERK Pathway in Rat Debrided Corneal Epithelium

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Noriaki Nagai

2018-04-01

Full Text Available Sericin is a major constituent of silk produced by silkworms. We previously found that the instillation of sericin enhanced the proliferation of corneal epithelial cells, and acted to promote corneal wound healing in both normal and diabetic model rats. However, the mechanisms by which sericin promotes the proliferation of corneal cells have not been established. In this study, we investigated the effects of sericin on Akt and ERK activation in a human corneal epithelial cell line (HCE-T cells and rat debrided corneal epithelium. Although Akt phosphorylation was not detected following the treatment of HCE-T cells with sericin, ERK1/2 phosphorylation was enhanced. The growth of HCE-T cells treated with sericin was significantly increased, with the cell growth of sericin-treated HCE-T cells being 1.7-fold higher in comparison with vehicle-treated HCE-T cells. On the other hand, both of an ERK inhibitor U0126 (non-specific specific inhibitor and SCH772984 (specific inhibitor attenuated the enhanced cell growth by sericin, and the growth level in the case of co-treatment with sericin and ERK1/2 inhibitor was similar to that of cells treated with ERK1/2 inhibitor alone. In an in vivo study using rat debrided corneal epithelium, the corneal wound healing rate was enhanced by the instillation of sericin, and this enhancement was also attenuated by the instillation of U0126. In addition, the corneal wound healing rate in rats co-instilled with sericin and U0126 was similar to that following the instillation of U0126 alone. In conclusion, we found that the instillation of sericin enhanced cell proliferation via the activation of the MAPK/ERK pathway, resulting in the promotion of corneal wound healing in rat eyes. These findings provide significant information for designing further studies to develop potent corneal wound-healing drugs.

Developing a Continuous Bioprocessing Approach to Stromal Cell Manufacture.

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Miotto, Martina; Gouveia, Ricardo; Abidin, Fadhilah Zainal; Figueiredo, Francisco; Connon, Che J

2017-11-29

To this day, the concept of continuous bioprocessing has been applied mostly to the manufacture of molecular biologics such as proteins, growth factors, and secondary metabolites with biopharmaceutical uses. The present work now sets to explore the potential application of continuous bioprocess methods to source large numbers of human adherent cells with potential therapeutic value. To this purpose, we developed a smart multifunctional surface coating capable of controlling the attachment, proliferation, and subsequent self-detachment of human corneal stromal cells. This system allowed the maintenance of cell cultures under steady-state growth conditions, where self-detaching cells were continuously replenished by the proliferation of those remaining attached. This facilitated a closed, continuous bioprocessing platform with recovery of approximately 1% of the total adherent cells per hour, a yield rate that was maintained for 1 month. Moreover, both attached and self-detached cells were shown to retain their original phenotype. Together, these results represent the proof-of-concept for a new high-throughput, high-standard, and low-cost biomanufacturing strategy with multiple potentials and important downstream applications.

Human corneal epithelial subpopulations

DEFF Research Database (Denmark)

Søndergaard, Chris Bath

2013-01-01

Corneal epithelium is being regenerated throughout life by limbal epithelial stem cells (LESCs) believed to be located in histologically defined stem cell niches in corneal limbus. Defective or dysfunctional LESCs result in limbal stem cell deficiency (LSCD) causing pain and decreased visual acuity...... subpopulations in human corneal epithelium using a combination of laser capture microdissection and RNA sequencing for global transcriptomic profiling. We compared dissociation cultures, using either expansion on γ-irradiated NIH/3T3 feeder cells in serum-rich medium or expansion directly on plastic in serum...

Corneal collagen crosslinking and pigment dispersion syndrome.

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LaHood, Benjamin R; Moore, Sacha

2017-03-01

We describe the case of a keratoconus patient with pigment dispersion syndrome (PDS) who was treated for progressive corneal ectasia with corneal collagen crosslinking (CXL). Pigment dispersion syndrome has been shown to have associated morphologic changes of the corneal endothelium. Corneal CXL has the potential to cause toxicity to the corneal endothelium, and adjacent pigment might increase the likelihood of damage. In this case, the presence of PDS had no detrimental effect on the outcome of treatment, and no complications were observed at 12 months follow-up, indicating that it may be safe to perform corneal CXL in the setting of PDS. This is an important observation as the number of indications for corneal CXL grows. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Corneal melanosis successfully treated using topical mitomycin-C and alcohol corneal epitheliectomy: a 3-year follow-up case report

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Mehmet Balcı

2015-08-01

Full Text Available ABSTRACTWe report a case of primary acquired corneal melanosis without atypia associated with corneal haze in a patient with a history of limbal malignant melanoma and the effect of mitomycin-C. A 75-year-old woman with a history of limbal malignant melanoma presented with loss of vision in right eye. Corneal examination showed a patchy melanotic pigmentation with a central haze. Topical mitomycin-C improved visual acuity and corneal haze. However, the pigmented lesions persisted, and they were removed with alcohol corneal epitheliectomy. Histopathological examination demonstrated primary acquired melanosis without atypia. The lesions were successfully removed, and there were no recurrences during the follow-up period of 36 months. The association of conjunctival and corneal melanosis without atypia is a rare condition. In addition, co-existence of central corneal haze and melanosis may decrease visual acuity. Topical mitomycin-C and alcohol corneal epitheliectomy can be useful treatments in this condition.

Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells

OpenAIRE

Chen, Weiwei; Tang, Tracy; Eastham-Anderson, Jeff; Dunlap, Debra; Alicke, Bruno; Nannini, Michelle; Gould, Stephen; Yauch, Robert; Modrusan, Zora; DuPree, Kelly J.; Darbonne, Walter C.; Plowman, Greg; de Sauvage, Frederic J.; Callahan, Christopher A.

2011-01-01

Hedgehog (Hh) signaling is critical to the patterning and development of a variety of organ systems, and both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligands, activation occurs within the stromal microenvironment. Testing whether ligand-driven Hh signaling promotes tumor angiogenesis, we found that Hh antagonism reduced the vascular density of Hh-producing LS180 and SW480 xenograf...

Healed corneal ulcer with keloid formation.

Science.gov (United States)

Alkatan, Hind M; Al-Arfaj, Khalid M; Hantera, Mohammed; Al-Kharashi, Soliman

2012-04-01

We are reporting a 34-year-old Arabic white female patient who presented with a white mass covering her left cornea following multiple ocular surgeries and healed corneal ulcer. The lesion obscured further view of the iris, pupil and lens. The patient underwent penetrating keratoplasty and the histopathologic study of the left corneal button showed epithelial hyperplasia, absent Bowman's layer and subepithelial fibrovascular proliferation. The histopathologic appearance was suggestive of a corneal keloid which was supported by further ultrastructural study. The corneal graft remained clear 6 months after surgery and the patient was satisfied with the visual outcome. Penetrating keratoplasty may be an effective surgical option for corneal keloids in young adult patients.

Current status of accelerated corneal cross-linking

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Michael Mrochen

2013-01-01

Full Text Available Corneal cross-linking with riboflavin is a technique to stabilize or reduce corneal ectasia, in diseases such as keratoconus and post-laser-assisted in situ keratomileusis (LASIK ectasia. There is an interest by patient as well as clinicians to reduce the overall treatment time. Especially, the introduction of corneal cross-linking in combination with corneal laser surgery demands a shorter treatment time to assure a sufficient patient flow. The principles and techniques of accelerated corneal cross-linking is discussed.

Evaluation of subbasal nerve morphology and corneal sensation after accelerated corneal collagen cross-linking treatment on keratoconus.

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Ozgurhan, Engin Bilge; Celik, Ugur; Bozkurt, Ercument; Demirok, Ahmet

2015-05-01

The aim of this study was to report on the evaluation of corneal nerve fiber density and corneal sensation after accelerated corneal collagen cross-linking on keratoconus patients. The study was performed on 30 keratoconus eyes (30 participants: 16 M, 14 F; 17-32 years old) treated with accelerated collagen cross-linking for disease stabilization. Mean outcome measures were corneal sensation evaluation by Cochet-Bonnet esthesiometry and subbasal nerve fiber density assessment by corneal in vivo confocal microscopy. All corneal measurements were performed using scanning slit confocal microscopy (ConfoScan 4, Nidek Technologies, Padova, Italy). The accelerated corneal collagen cross-linking procedure was performed on 30 eyes of 30 patients (19 right, 63.3%; 11 left, 27.7%). The mean age was 23.93 ± 4. The preoperative mean keratometry, apex keratometry and pachymetry values were 47.19 ± 2.82 D, 56.79 ± 5.39 and 426.1 ± 25.6 μm, respectively. Preoperative mean corneal sensation was 56.3 ± 5.4 mm (with a range from 40 to 60 mm), it was significantly decreased at 1st and 3rd month visit and increased to preoperative values after 6th month visit. Preoperative mean of subbasal nerve fiber density measurements was 22.8 ± 9.7 nerve fiber/mm(2) (with a range of 5-45 mm), it was not still at the preoperative values at 6th month (p = 0.0001), however reached to the preoperative values at 12th month (p = 0.914). Subbasal nerve fibers could reach the preoperative values at the 12th month after accelerated corneal collagen cross-linking treatment although the corneal sensation was improved at 6th month. These findings imply that the subjective healing process is faster than the objective evaluation of the keratoconus patients' cornea treated with accelerated corneal collagen cross-linking.

Pseudoangiomatous Stromal Hyperplasia in Core Needle Biopsies of Breast Specimens.

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Kelten Talu, Canan; Boyaci, Ceren; Leblebici, Cem; Hacihasanoglu, Ezgi; Bozkurt, Erol Rustu

2017-02-01

Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion of myofibroblasts that is composed of a network of slit-like channels that resemble vascular spaces. The aims of this study were to document the frequency of PASH in core needle biopsy specimens (CNBS) of the breast, to describe which histopathologic findings coexist with PASH and to examine any endothelial cell differentiation. We reevaluated hematoxylin and eosin-stained sections of all CNBS that were obtained during a 1-year period. First, we performed CD34 and CD31 immunostainings to highlight the areas of PASH, then performed D2-40/podoplanin (lymphatic endothelial marker) and Fli-1 (vascular endothelial cell marker) immunostains. The total number of CNBS was 412. Areas of PASH were noted in 37 of the 412 cases (9%), with a mean age of 38.5 years. The lesions that were described in association with PASH were "benign breast parenchyma with stromal fibrosis" (17/37; 46%), "fibroepithelial tumors" (17/37; 46%), "columnar cell changes (CCC)" (2/37; 5%), and "invasive carcinoma" (1/37; 3%). There were 2 cases of CCC within the foci of PASH (direct contact with PASH), and 8 additional cases of CCC that coexisted in the same specimen but were not in direct contact. There was no staining for D2-40 or Fli-1 within PASH foci. PASH lesions occurred with a frequency of 9% in CNBS and were mostly in association with benign breast lesions in premenopausal women. CCC was determined as an accompanying epithelial lesion within or near PASH areas. No obvious immunopositivity compatible with endothelial cell differentiation was revealed.

Corneal Reinnervation and Sensation Recovery in Patients With Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves.

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Cruzat, Andrea; Hamrah, Pedram; Cavalcanti, Bernardo M; Zheng, Lixin; Colby, Kathryn; Pavan-Langston, Deborah

2016-05-01

To study corneal reinnervation and sensation recovery in Herpes zoster ophthalmicus (HZO). Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis type 1 was implanted, and the explanted corneal tissues were examined by immunofluorescence histochemistry for βIII-tubulin to stain for corneal nerves. The initial central corneal IVCM performed in each patient showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later before undergoing surgery, case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, case 2 showed regeneration of the central subbasal nerves (4786 μm/mm) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in case 1 showed no corneal nerves, whereas case 2 showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the Boston keratoprosthesis in both patients to study innervation of the corneal transplant. Case 1 showed no nerves, whereas case 2 showed new nerves growing from the periphery into the corneal graft. We demonstrate that regaining corneal innervation and corneal function are possible in patients with HZO as shown by corneal sensation, IVCM, and ex vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time.

The inhibitory effect of different concentrations of KH902 eye drops on corneal neovascularization induced by alkali burn

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Yan Wu

2017-01-01

Full Text Available Purpose: The aim of this study was to evaluate the inhibitory effect of different concentrations of KH902 eye drops on rabbit corneal neovascularization (CNV induced by alkali burn. Methods: Forty-eight adult rabbits were randomized into four groups after alkali burning: Group A (2.5 mg/ml, Group B (5 mg/ml, and Group C (10 mg/ml by different concentrations of KH902 eye drops and Group D by saline solution as control with three times a day for 2 weeks. At days 7, 14, and 28, the anterior segment photographs, confocal microscopy, and histopathology were performed to evaluate corneal opacity, neovascularization, inflammatory cell density, vessel size, and edema. Immunohistochemistry was applied to analyze the vascular endothelial growth factor (VEGF level. Results: (1 The CNV in the medicine-treated groups showed a reduction without obvious corneal side effects histologically. (2 Compared to the control group, the three medicine-treated groups showed a reduction in the VEGF levels and CNV areas on days 7, 14, and 28 and in the inflammatory cell density on days 14 and 28 (P 0.05. Conclusion: KH902 eye drops in lower concentration showed an obvious reduction of the CNV growing for rabbit corneal alkali burn without side effects.

Evaluation of intracameral injection of ranibizumab and bevacizumab on the corneal endothelium by scanning electron microscopy.

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Ari, Seyhmus; Nergiz, Yusuf; Aksit, Ihsan; Sahin, Alparslan; Cingu, Kursat; Caca, Ihsan

2015-03-01

To evaluate the effects of intracameral injection of ranibizumab and bevacizumab on the corneal endothelium by scanning electron microscopy (SEM). Twenty-eight female rabbits were randomly divided into four equal groups. Rabbits in groups 1 and 2 underwent intracameral injection of 1 mg/0.1 mL and 0.5 mg/0.05 mL ranibizumab, respectively; group 3 was injected with 1.25 mg/0.05 mL bevacizumab. All three groups were injected with a balanced salt solution (BSS) into the anterior chamber of the left (fellow) eye. None of the rabbits in group 4 underwent an injection. Corneal thickness and intraocular pressure were measured before the injections, on the first day, and in the first month after injection. The rabbits were sacrificed and corneal tissues were excised in the first month after injection. Specular microscopy was used for the corneal endothelial cell count. Endothelial cell density was assessed and comparisons drawn between the groups and the control. Micrographs were recorded for SEM examination. The structure of the corneal endothelial cells, the junctional area of the cell membrane, the distribution of microvillus, and the cell morphology of the eyes that underwent intracameral injection of vascular endothelial growth factor (VEGF), BSS, and the control group were compared. Corneal thickness and intraocular pressure were not significantly different between the groups that underwent anti-VEGF or BSS injection and the control group on the first day and in the first month of injection. The corneal endothelial cell count was significantly diminished in all three groups; predominantly in group 1 and 2 (P<0.05). The SEM examination revealed normal corneal endothelial histology in group 3 and the control group. Eyes in group 1 exhibited indistinctness of corneal endothelial cell borders, microvillus loss in the luminal surface, excessive blebbing, and disintegration of intercellular junctions. In group 2, the cell structure of the corneal endothelium

Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature within the Process of Vascular Remodeling: Cellular Basis, Clinical Relevance, and Implications for Stem Cell Therapy.

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Klein, Diana

2016-01-01

Until some years ago, the bone marrow and the endothelial cell compartment lining the vessel lumen (subendothelial space) were thought to be the only sources providing vascular progenitor cells. Now, the vessel wall, in particular, the vascular adventitia, has been established as a niche for different types of stem and progenitor cells with the capacity to differentiate into both vascular and nonvascular cells. Herein, vascular wall-resident multipotent stem cells of mesenchymal nature (VW-MPSCs) have gained importance because of their large range of differentiation in combination with their distribution throughout the postnatal organism which is related to their existence in the adventitial niche, respectively. In general, mesenchymal stem cells, also designated as mesenchymal stromal cells (MSCs), contribute to the maintenance of organ integrity by their ability to replace defunct cells or secrete cytokines locally and thus support repair and healing processes of the affected tissues. This review will focus on the central role of VW-MPSCs within vascular reconstructing processes (vascular remodeling) which are absolute prerequisite to preserve the sensitive relationship between resilience and stability of the vessel wall. Further, a particular advantage for the therapeutic application of VW-MPSCs for improving vascular function or preventing vascular damage will be discussed.

Corneal laceration caused by river crab

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Vinuthinee N

2015-01-01

Full Text Available Naidu Vinuthinee,1,2 Anuar Azreen-Redzal,1 Jaafar Juanarita,1 Embong Zunaina2 1Department of Ophthalmology, Hospital Sultanah Bahiyah, Alor Setar, 2Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia Abstract: A 5-year-old boy presented with right eye pain associated with tearing and photophobia of 1-day duration. He gave a history of playing with a river crab when suddenly the crab clamped his fingers. He attempted to fling the crab off, but the crab flew and hit his right eye. Ocular examination revealed a right eye corneal ulcer with clumps of fibrin located beneath the corneal ulcer and 1.6 mm level of hypopyon. At presentation, the Seidel test was negative, with a deep anterior chamber. Culture from the corneal scrapping specimen grew Citrobacter diversus and Proteus vulgaris, and the boy was treated with topical gentamicin and ceftazidime eyedrops. Fibrin clumps beneath the corneal ulcer subsequently dislodged, and revealed a full-thickness corneal laceration wound with a positive Seidel test and shallow anterior chamber. The patient underwent emergency corneal toileting and suturing. Postoperatively, he was treated with oral ciprofloxacin 250 mg 12-hourly for 1 week, topical gentamicin, ceftazidime, and dexamethasone eyedrops for 4 weeks. Right eye vision improved to 6/9 and 6/6 with pinhole at the 2-week follow-up following corneal suture removal. Keywords: corneal ulcer, pediatric trauma, ocular injury

The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymphangiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure

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M. Notara

2018-01-01

Full Text Available The cornea is a clear structure, void of blood, and lymphatic vessels, functioning as our window to the world. Limbal epithelial stem cells, occupying the area between avascular cornea and vascularized conjunctiva, have been implicated in tissue border maintenance, preventing conjunctivalisation and propagation of blood and lymphatic vessels into the cornea. Defects in limbal epithelial stem cells are linked to corneal neovascularisation, including lymphangiogenesis, chronic inflammation, conjunctivalisation, epithelial abnormalities including the presence of goblet cells, breaks in Bowman’s membrane, persistent epithelial defects and ulceration, ocular surface squamous neoplasia, lipid keratopathy, pain, discomfort, and compromised vision. It has been postulated that pterygium is an example of focal limbal deficiency. Previous reports showing changes occurring in limbal epithelium during pterygium pathogenesis suggest that there is a link to stem cell damage. In this light, pterygium can serve as a model disease of UV-induced stem cell damage also characterised by corneal blood and lymphangiogenesis. This review focuses on the role of corneal and limbal epithelial cells and the stem cell niche in maintaining corneal avascularity and corneal immune privilege and how this may be deregulated following UV exposure. We present an overview of the PUBMED literature in the field as well as recent work from our laboratories.

Visual outcome after corneal transplantation for corneal perforation and iris prolapse in 37 horses

DEFF Research Database (Denmark)

Henriksen, Michala de Linde; Plummer, C. E.; Mangan, B.

2012-01-01

We wanted to investigate the visual outcome of horses presented with iris prolapse and treated with corneal transplantation.......We wanted to investigate the visual outcome of horses presented with iris prolapse and treated with corneal transplantation....

Corneal iron ring after conductive keratoplasty.

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Kymionis, George D; Naoumidi, Tatiana L; Aslanides, Ioannis M; Pallikaris, Ioannis G

2003-08-01

To report formation of corneal iron ring deposits after conductive keratoplasty. Observational case report. Case report. A 54-year-old woman underwent conductive keratoplasty for hyperopia. One year after conductive keratoplasty, iron ring pattern pigmentation was detected at the corneal epithelium of both eyes. This is the first report of the appearance of corneal iron ring deposits following conductive keratoplasty treatment in a patient. It is suggested that alterations in tear film stability, resulting from conductive keratoplasty-induced changes in corneal curvature, constitute the contributory factor for these deposits.

Explore the full thick layer of corneal transplantation in the treatment of pseudomonas aeruginosa corneal ulcer infection

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Xin Wang

2015-02-01

Full Text Available AIM: To explore the feasibility, safety and effect of the full-thickness lamellar keratoplasty for the treatment of pseudomonas aeruginosa corneal ulcer. METHODS: Based on a retrospective non-controlled study, 25 patients were given the full-thickness lamellar keratoplasty for clinical diagnosis of pseudomonas aeruginosa infection and corneal ulcer medication conventional anti-gram-negative bacteria. Routine follow-up were carried out at postoperative 1wk; 1, 3, 6, 12, 18mo to observe the situation of corneal epithelial healing, recurrent infection, immune rejection, graft transparency and best corrected visual acuity, etc. At the 6 and 12mo postoperative, corneal endothelial cell density was reexamined.RESULTS: No patients because of Descemet's membrane rupture underwent penetrating keratoplasty surgery: One only in cases of bacterial infection after 1mo, once again did not cultivate a culture of bacteria pseudomonas aeruginosa, and the remaining 24 cases average follow-up 14±6mo, corneal graft were transparent, the cure rate was 96%. At the sixth month after surgery, there were 16 cases of eye surgery best corrected visual acuity ≥4.5, of which 3 cases ≥4.8. At the sixth month after surgery, the average corneal endothelial cell density 2 425±278/mm2; At 12mo postoperatively, it was 2 257± 326/mm2.CONCLUSION: Full-thickness lamellar keratoplasty is an effective method of pseudomonas aeruginosa infection in the treatment of corneal ulcers, corneal drying material glycerol can be achieved by visual effects.

Contact Lens Related Corneal Ulcer

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Loh, KY; Agarwal, P

2010-01-01

A corneal ulcer caused by infection is one of the major causes of blindness worldwide. One of the recent health concerns is the increasing incidence of corneal ulcers associated with contact lens user especially if the users fail to follow specific instruction in using their contact lenses. Risk factors associated with increased risk of contact lens related corneal ulcers are: overnight wear, long duration of continuous wear, lower socio-economic classes, smoking, dry eye and poor hygiene. Th...

Chitosan and thiolated chitosan: Novel therapeutic approach for preventing corneal haze after chemical injuries.

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Zahir-Jouzdani, Forouhe; Mahbod, Mirgholamreza; Soleimani, Masoud; Vakhshiteh, Faezeh; Arefian, Ehsan; Shahosseini, Saeed; Dinarvand, Rasoul; Atyabi, Fatemeh

2018-01-01

Corneal haze, commonly caused by deep physical and chemical injuries, can greatly impair vision. Growth factors facilitate fibroblast proliferation and differentiation, which leads to haze intensity. In this study, the potential effect of chitosan (CS) and thiolated-chitosan (TCS) nanoparticles and solutions on inhibition of fibroblast proliferation, fibroblast to myofibroblast differentiation, neovascularization, extracellular matrix (ECM) deposition, and pro-fibrotic cytokine expression was examined. Transforming growth factor beta-1 (TGFβ 1 ) was induced by interleukin-6 (IL6) in human corneal fibroblasts and expression levels of TGFβ 1 , Platelet-derived growth factor (PDGF), α-smooth muscle actins (α-SMA), collagen type I (Col I), fibronectin (Fn) and vascular endothelial growth factor (VEGF) were quantified using qRT-PCR. To assess wound-healing capacity, TCS-treated mice were examined for α-SMA positive cells, collagen deposition, inflammatory cells and neovascularization through pathological immunohistochemistry. The results revealed that CS and TCS could down-regulate the expression levels of TGFβ 1 and PDGF comparable to that of TGFβ 1 knockdown experiment. However, down-regulation of TGFβ 1 was not regulated through miR29b induction. Neovascularization along with α-SMA and ECM deposition were significantly diminished. According to these findings, CS and TCS can be considered as potential anti-fibrotic and anti-angiogenic therapeutics. Furthermore, TCS, thiolated derivative of CS, will increase mucoadhesion of the polymer at the corneal surface which makes the polymer efficient and non-toxic therapeutic approach for corneal injuries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Correlation between the histological features of corneal surface pannus following ocular surface burns and the final outcome of cultivated limbal epithelial transplantation.

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Sati, Alok; Basu, Sayan; Sangwan, Virender S; Vemuganti, Geeta K

2015-04-01

To report the influence of histological features of corneal surface pannus following ocular surface burn on the outcome of cultivated limbal epithelial transplantation (CLET). On retrospectively reviewing the medical records of the patients who underwent autologous CLET from April 2002 to June 2012 at L V Prasad Eye Institute, Hyderabad, India, we could trace the histological reports in only 90 records. These 90 records, besides clinical parameters, were reviewed for the influence of various histological features on the final outcome of CLET. The histological features include epithelial hyperplasia (21.1%), surface ulceration (2.2%), goblet cells (62.2%), squamous metaplasia (11.1%), active fibrosis (31.1%), severe inflammation (8.9%), multinucleated giant cells (3.3%), stromal calcification (8.9%) and active proliferating vessels (5.6%). Among these histological features, patients with either hyperplasia or calcification in their excised corneal pannus show an unfavourable outcome compared with patients without hyperplasia (p=0.003) or calcification (p=0.018). A similar unfavourable outcome was not seen with other histological features and various clinical parameters. Presence of either calcific deposits or hyperplasia in the excised corneal pannus provides poor prognostication; hence, a proper counselling of such patients is mandatory along with a close follow-up. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chlorpromazine-induced corneal endothelial phototoxicity

International Nuclear Information System (INIS)

Hull, D.S.; Csukas, S.; Green, K.

1982-01-01

Chlorpromazine, which has been used extensively for the treatment of psychiatric disorders, is known to accumulate in the posterior corneal stroma, lens, and uveal tract. Because it is a phototoxic compound, the potential exists for it to cause cellular damage after light exposure. Specular microscopic perfusion of corneal endothelial cells in darkness with 0.5 mM chlorpromazine HCl resulted in a swelling rate of 18 +/- 2 micrometer/hr, whereas corneas exposed to long-wavelength ultraviolet light for 3 min in the presence of 0.5 mM chlorpromazine swelled at 37 +/- 9 micrometer/hr (p less than 0.01). Preirradiation of 0.5 mM chlorpromazine solution with ultraviolet light for 30 min and subsequent corneal perfusion with the solution resulted in a corneal swelling rate of 45 +/- 19 micrometer/hr. Cornea endothelial cells perfused with 0.5 mM chlorpromazine that was preirradiated with ultraviolet light showed marked swelling on scanning electron microscopic examination, whereas those perfused with nonirradiated chlorpromazine were flat and showed a normal mosaic pattern. Combining either 500 U/ml catalase or 290 U/ml superoxide dismutase with chlorpromazine did not alter photoinduction of corneal swelling. The data suggest that corneal endothelial chlorpromazine phototoxicity is secondary to cytotoxic products resulting from the photodynamically induced decomposition of chlorpromazine and is not caused by hydrogen peroxide or superoxide anion generated during the phototoxic reaction

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

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Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

2012-01-01

Topical application of benzalkonium chloride (BAK) to the eye causes dose-related corneal neurotoxicity. Corneal inflammation and reduction in aqueous tear production accompany neurotoxicity. Cessation of BAK treatment leads to recovery of corneal nerve density.

Long-term outcomes of wedge resection at the limbus for high irregular corneal astigmatism after repaired corneal laceration

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Jun Du

2016-06-01

Full Text Available AIM: To evaluate the clinical value of wedge resection at corneal limbus in patients with traumatic corneal scarring and high irregular astigmatism. METHODS: Patients with traumatic corneal astigmatism received wedge resection at least 6mo after suture removal from corneal wound. The uncorrected distance visual acuities (UCVA and best corrected distance visual acuities (BCVA, pre- and post-operation astigmatism, spherical equivalent (SE, safety and complications were evaluated. RESULTS: Ten eyes (10 patients were enrolled in this study. Mean follow-up time after wedge resection was 37.8±15.4mo (range, 20-61mo. The mean UCVA improved from +1.07±0.55 logMAR to +0.43±0.22 logMAR (P=0.000 and the mean BCVA from +0.50±0.30 logMAR to +0.15±0.17 logMAR (P=0.000. The mean astigmatism power measured by retinoscopy was -2.03±2.27 D postoperatively and -2.83±4.52 D preoperatively (P=0.310. The mean SE was -0.74±1.61 D postoperatively and -0.64±1.89 D preoperatively (P=0.601. Two cases developed mild pannus near the sutures. No corneal perforation, infectious keratitis or wound gape occurred. CONCLUSION: Corneal-scleral limbal wedge resection with compression suture is a safe, effective treatment for poor patients with high irregular corneal astigmatism after corneal-scleral penetrating injury. Retinoscopy can prove particularly useful for high irregular corneal astigmatism when other measurements are not amenable.

Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

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Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

2018-06-16

Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be

Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty.

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Holland, Edward J; Lane, Stephen S; Kim, Terry; Raizman, Michael; Dunn, Steven

2008-04-01

To compare the corneal and aqueous penetration and pharmacokinetics of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions and their effect on corneal reepithelialization after penetrating keratoplasty. In this randomized, open-label, parallel-controlled study, corneal and aqueous penetration and the pharmacokinetic parameters of topically applied gatifloxacin 0.3% and moxifloxacin 0.5% (2 preoperative doses of 1 drop given 5 minutes apart) were estimated by using a sparse sampling method. Corneal and aqueous samples were collected 0.25, 0.5, 1, or 2 hours after the final dose. The concentration was determined by a high-performance liquid chromatography method. Stromal Cmax:MBC50 (maximum drug concentration in serum to 50% minimum bactericidal concentration) ratios for selected ocular pathogens were also assessed. Postoperative corneal reepithelialization at days 1, 3, and 7 was evaluated and compared between groups. The calculated pharmacokinetic parameters were higher with moxifloxacin 0.5% than with gatifloxacin 0.3%. The stromal Cmax was 48.5 versus 15.7 microg/g (P = 0.04), and the stromal AUC0-2 (area under the concentration-time curve from 0 to 2 hours) was 30.9 versus 13.6 mug.h/g (P 0.05), and the endothelial AUC0-2 was 43.9 versus 9.8 microg.h/g (P 0.05), and the aqueous AUC0-2 was 1.2 versus 0.4 microg.h/mL (P < 0.05). Stromal Cmax:MBC50 ratios were higher in the moxifloxacin 0.5% group for each pathogen tested. The corneal reepithelialization rates were comparable between groups. Topical preoperative moxifloxacin 0.5% achieved greater corneal and aqueous penetration than did gatifloxacin 0.3%. The clinical significance of this difference is not known. Postoperative use of these agents had similar effects on corneal reepithelialization.

Induction of corneal collagen cross-linking in experimental corneal alkali burns in rabbits

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Marcello Colombo-Barboza

2014-10-01

Full Text Available Objective: To evaluate the effect of riboflavin-ultraviolet-A-induced cross-linking (CXL following corneal alkali burns in rabbits. Methods: The right corneas and limbi of ten rabbits were burned using a 1N solution of NaOH and the animals were then divided into two groups: a control group submitted to clinical treatment alone and an experimental group that was treated 1 h after injury with CXL, followed by the same clinical treatment as administered to the controls. Clinical parameters were evaluated post-injury at 1, 7, 15, and 30 days by two independent observers. Following this evaluation, the corneas were excised and examined histologically. Results: There were no statistically significant differences in clinical parameters, such as hyperemia, corneal edema, ciliary injection, limbal ischemia, secretion, corneal neovascularization, symblepharon, or blepharospasm, at any of the time-points evaluated. However, the size of the epithelial defect was significantly smaller in the CXL group (p<0.05 (day 15: p=0.008 and day 30: p=0.008 and the extent of the corneal injury (opacity lesion was also smaller (day 30: p=0.021. Histopathology showed the presence of collagen bridges linking the collagen fibers in only the CXL group. Conclusions: These results suggest that the use of CXL may improve the prognosis of acute corneal alkali burns.

Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells

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Chen, Weiwei; Tang, Tracy; Eastham-Anderson, Jeff; Dunlap, Debra; Alicke, Bruno; Nannini, Michelle; Gould, Stephen; Yauch, Robert; Modrusan, Zora; DuPree, Kelly J.; Darbonne, Walter C.; Plowman, Greg; de Sauvage, Frederic J.; Callahan, Christopher A.

2011-01-01

Hedgehog (Hh) signaling is critical to the patterning and development of a variety of organ systems, and both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligands, activation occurs within the stromal microenvironment. Testing whether ligand-driven Hh signaling promotes tumor angiogenesis, we found that Hh antagonism reduced the vascular density of Hh-producing LS180 and SW480 xenografts. In addition, ectopic expression of sonic hedgehog in low-Hh–expressing DLD-1 xenografts increased tumor vascular density, augmented angiogenesis, and was associated with canonical Hh signaling within perivascular tumor stromal cells. To better understand the molecular mechanisms underlying Hh-mediated tumor angiogenesis, we established an Hh-sensitive angiogenesis coculture assay and found that fibroblast cell lines derived from a variety of human tissues were Hh responsive and promoted angiogenesis in vitro through a secreted paracrine signal(s). Affymetrix array analyses of cultured fibroblasts identified VEGF-A, hepatocyte growth factor, and PDGF-C as candidate secreted proangiogenic factors induced by Hh stimulation. Expression studies of xenografts and angiogenesis assays using combinations of Hh and VEGF-A inhibitors showed that it is primarily Hh-induced VEGF-A that promotes angiogenesis in vitro and augments tumor-derived VEGF to promote angiogenesis in vivo. PMID:21597001

In vitro effects of three blood derivatives on human corneal epithelial cells.

Science.gov (United States)

Freire, Vanesa; Andollo, Noelia; Etxebarria, Jaime; Durán, Juan A; Morales, María-Celia

2012-08-15

We compared the effects of three blood derivatives, autologous serum (AS), platelet-rich plasma (PRP), and serum derived from plasma rich in growth factors (PRGF), on a human corneal epithelial (HCE) cell line to evaluate their potential as an effective treatment for corneal epithelial disorders. The concentrations of epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), and fibronectin were quantified by ELISA. The proliferation and viability of HCE cells were measured by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay. Cell morphology was assessed by phase-contrast microscopy. The patterns of expression of several connexin, involucrin, and integrin α6 genes were analyzed by real-time RT-PCR. We found significantly higher levels of EGF in PRGF compared to AS and PRP. However, AS and PRGF induced robust proliferation of HCE cells. In addition, PRGF cultured cells grew as heterogeneous colonies, exhibiting differentiated and non-differentiated cell phenotypes, whereas AS- and PRP-treated cultures exhibited quite homogeneous colonies. Finally, PRGF upregulated the expression of several genes associated with communication and cell differentiation, in comparison to AS or PRP. PRGF promotes biological processes required for corneal epithelialization, such as proliferation and differentiation. Since PRGF effects are similar to those associated with routinely used blood derivatives, the present findings warrant further research on PRGF as a novel alternative treatment for ocular surface diseases.

Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia.

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Barwinska, Daria; Traktuev, Dmitry O; Merfeld-Clauss, Stephanie; Cook, Todd G; Lu, Hongyan; Petrache, Irina; March, Keith L

2018-06-01

Cigarette smoking (CS) adversely affects the physiologic function of endothelial progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC from nonsmokers (nCS-ASC) and smokers (CS-ASC), and their activity to promote perfusion in hindlimb ischemia models, as well as endothelial cell (EC) survival and vascular morphogenesis in vitro were assessed. While nCS-ASC improved perfusion in ischemic limbs, CS-ASC completely lost this therapeutic effect. In vitro vasculogenesis assays revealed that human CS-ASC and ASC from CS-exposed mice showed compromised support of EC morphogenesis into vascular tubes, and the CS-ASC secretome was less potent in supporting EC survival/proliferation. Comparative secretome analysis revealed that CS-ASC produced lower amounts of hepatocyte growth factor (HGF) and stromal cell-derived growth factor 1 (SDF-1). Conversely, CS-ASC secreted the angiostatic/pro-inflammatory factor Activin A, which was not detected in nCS-ASC conditioned media (CM). Furthermore, higher Activin A levels were measured in EC/CS-ASC cocultures than in EC/nCS-ASC cocultures. CS-ASC also responded to inflammatory cytokines with 5.2-fold increase in Activin A secretion, whereas nCS-ASC showed minimal Activin A induction. Supplementation of EC/CS-ASC cocultures with nCS-ASC CM or with recombinant vascular endothelial growth factor, HGF, or SDF-1 did not rescue vasculogenesis, whereas inhibition of Activin A expression or activity improved network formation up to the level found in EC/nCS-ASC cocultures. In conclusion, ASC of CS individuals manifest compromised in vitro vasculogenic activity as well as in vivo therapeutic activity. Stem Cells 2018;36:856-867. © 2018 AlphaMed Press.

Corneal modeling for analysis of photorefractive keratectomy

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Della Vecchia, Michael A.; Lamkin-Kennard, Kathleen

1997-05-01

Procedurally, excimer photorefractive keratectomy is based on the refractive correction of composite spherical and cylindrical ophthalmic errors of the entire eye. These refractive errors are inputted for correction at the corneal plane and for the properly controlled duration and location of laser energy. Topography is usually taken to correspondingly monitor spherical and cylindrical corneorefractive errors. While a corneal topographer provides surface morphologic information, the keratorefractive photoablation is based on the patient's spherical and cylindrical spectacle correction. Topography is at present not directly part of the procedural deterministic parameters. Examination of how corneal curvature at each of the keratometric reference loci affect the shape of the resultant corneal photoablated surface may enhance the accuracy of the desired correction. The objective of this study was to develop a methodology to utilize corneal topography for construction of models depicting pre- and post-operative keratomorphology for analysis of photorefractive keratectomy. Multiple types of models were developed then recreated in optical design software for examination of focal lengths and other optical characteristics. The corneal models were developed using data extracted from the TMS I corneal modeling system (Computed Anatomy, New York, NY). The TMS I does not allow for manipulation of data or differentiation of pre- and post-operative surfaces within its platform, thus models needed to be created for analysis. The data were imported into Matlab where 3D models, surface meshes, and contour plots were created. The data used to generate the models were pre- and post-operative curvatures, heights from the corneal apes, and x-y positions at 6400 locations on the corneal surface. Outlying non-contributory points were eliminated through statistical operations. Pre- and post- operative models were analyzed to obtain the resultant changes in the corneal surfaces during PRK

Prevention of Herpes Simplex Virus Induced Stromal Keratitis by a Glycoprotein B-Specific Monoclonal Antibody

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Krawczyk, Adalbert; Dirks, Miriam; Kasper, Maren; Buch, Anna; Dittmer, Ulf; Giebel, Bernd; Wildschütz, Lena; Busch, Martin; Goergens, Andre; Schneweis, Karl E.; Eis-Hübinger, Anna M.; Sodeik, Beate; Heiligenhaus, Arnd; Roggendorf, Michael; Bauer, Dirk

2015-01-01

The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK) is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c) that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). Topical treatment was performed by periodical inoculations (5 times per day) of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c) was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans. PMID:25587898

Prevention of herpes simplex virus induced stromal keratitis by a glycoprotein B-specific monoclonal antibody.

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Adalbert Krawczyk

Full Text Available The increasing incidence of acyclovir (ACV and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis or 24, 40, and 56 hours after infection (post-exposure immunotherapy. Topical treatment was performed by periodical inoculations (5 times per day of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

Designing Hydrogel Adhesives for Corneal Wound Repair

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Grinstaff, Mark W.

2013-01-01

Today, corneal wounds are repaired using nylon sutures. Yet there are a number of complications associated with suturing the cornea, and thus there is interest in an adhesive to replace or supplement sutures in the repair of corneal wounds. We are designing and evaluating corneal adhesives prepared from dendrimers – single molecular weight, highly branched polymers. We have explored two strategies to form these ocular adhesives. The first involves a photocrosslinking reaction and the second uses a peptide ligation reactions to couple the individual dendrimers together to from the adhesive. These adhesives were successfully used to repair corneal perforations, close the flap produced in a LASIK procedure, and secure a corneal transplant. PMID:17889330

Granular corneal dystrophy Groenouw type I (GrI) and Reis-Bücklers' corneal dystrophy (R-B). One entity?

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Møller, H U

1989-12-01

This paper maintains that Reis-Bücklers' corneal dystrophy and granular corneal dystrophy Groenouw type I are one and the same disease. Included are some of the technically best photographs of Reis-Bücklers' dystrophy found in the literature, and these are compared with photographs from patients with granular corneal dystrophy examined by the author. It is argued that most of the histological and ultrastructural findings on Reis Bücklers' dystrophy described in the literature are either congruent with what is found in granular corneal dystrophy or unspecific.

Three-year changes in epithelial and stromal thickness after PRK or LASIK for high myopia.

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Ivarsen, Anders; Fledelius, Walther; Hjortdal, Jesper Ø

2009-05-01

To compare 3-year changes in corneal sublayer thickness after photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK). Forty-six patients with spheroequivalent refraction of -6.0 to -8.0 diopters (D) were randomly assigned to PRK or LASIK. One eye from each patient was included in the study. Examinations included manifest refraction and confocal microscopy through focusing (CMTF) and were performed preoperatively and postoperatively at 1 week and at 1, 3, 6, 12, and 36 months. From CMTF scans, the thicknesses of the central cornea (CT), epithelium (ET), stroma (ST), LASIK flap (FT), and residual stromal bed (BT) were calculated. After LASIK, spheroequivalent refraction averaged -0.76 D by 1 week and -1.19 D by 1 month, with no subsequent significant change. ET increased 9.0 +/- 7.0 microm within 1 week and remained constant thereafter. ST increased 12.9 +/- 9.4 microm within 1 year because of increased BT. One week after PRK, refraction averaged -0.23 D and stabilized at -1.42 D by 6 months. By 1 week, ET was reduced by 7.5 +/- 5.7 microm, reached preoperative thickness by 6 months, and increased further 7.3 +/- 6.0 microm by 3 years. ST increased 25.3 +/- 17.2 microm during 1 year, correlating with the postoperative refractive regression. After both procedures, changes in CT also correlated with refractive changes. No other correlations were identified. PRK and LASIK induce a persistent increase in ET that stabilizes 1 week after LASIK and 1 year after PRK. Stromal regrowth is most pronounced after PRK. After LASIK, regrowth is restricted to the residual stromal bed. Postoperative refractive changes correlate with changes in ST (PRK) and CT (PRK and LASIK) but not with changes in ET.

Easy xeno-free and feeder-free method for isolating and growing limbal stromal and epithelial stem cells of the human cornea.

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Djida Ghoubay-Benallaoua

Full Text Available Epithelial and stromal stem cells are required to maintain corneal transparency. The aim of the study was to develop a new method to isolate and grow both corneal stromal (SSC and epithelial limbal (LSC stem cells from small human limbal biopsies under culture conditions in accordance with safety requirements mandatory for clinical use in humans. Superficial limbal explants were retrieved from human donor corneo-scleral rims. Human limbal cells were dissociated by digestion with collagenase A, either after epithelial scraping or with no scraping. Isolated cells were cultured with Essential 8 medium (E8, E8 supplemented with EGF (E8+ or Green's medium with 3T3 feeder-layers. Cells were characterized by immunostaining, RT-qPCR, colony forming efficiency, sphere formation, population doubling, second harmonic generation microscopy and differentiation potentials. LSC were obtained from unscraped explants in E8, E8+ and Green's media and were characterized by colony formation and expression of PAX6, ΔNP63α, Bmi1, ABCG2, SOX9, CK14, CK15 and vimentin, with a few cells positive for CK3. LSC underwent 28 population doublings still forming colonies. SSC were obtained from both scraped and unscraped explants in E8 and E8+ media and were characterized by sphere formation, expression of PAX6, SOX2, BMI1, NESTIN, ABCG2, KERATOCAN, VIMENTIN, SOX9, SOX10 and HNK1, production of collagen fibrils and differentiation into keratocytes, fibroblasts, myofibroblasts, neurons, adipocytes, chondrocytes and osteocytes. SSC underwent 48 population doublings still forming spheres, Thus, this new method allows both SSC and LSC to be isolated from small superficial limbal biopsies and to be primary cultured in feeder-free and xeno-free conditions, which will be useful for clinical purposes.

Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment.

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Mahelkova, Gabriela; Jirsova, Katerina; Seidler Stangova, Petra; Palos, Michalis; Vesela, Viera; Fales, Ivan; Jiraskova, Nada; Dotrelova, Dagmar

2017-05-01

In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. © 2016 Optometry Australia.

EXPERIMENTAL REPAIR OF DEEP CORNEAL DEFECTS USING A BIO-CONSTRUCT COMPRISING A COLLAGEN TYPE I MATRIX LOADED WITH BUCCAL EPITHELIAL CELLS

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N. S. Egorova

2017-01-01

Full Text Available The  research  objective was  to study the  reparative effects of  the  collagen  type  I bio-construct loaded  with buccal epithelial cells, on the rabbit cornea after experimental keratectomy at various stages of treatment (on the 3rd, 7th, 14th, 3 0th days.Material  and methods.  The  experiments were  conducted on 20 rabbits  of  the  Chinchilla breed that  were  operated on cornea of both eyes aiming to inflict epithelial and stromal cornea defects. The collagen-based bio-construct bearing buccal epithelial cells was placed  over the cornea of the experimental eyes. The  cornea of the control  eyes was covered with smooth contact lens. After the surgery, a temporal blepharorrhaphy was performed and kept for 3 days. We studied macroand microscopic pattern of corneal regeneration at 3, 7, 14, and 30 days of experiment.Results. When  using the collaged-based bio-construct containing buccal epithelial cells, the complete epithelialization of the corneal defect occurred at mean 7 days earlier compared to that in the control eyes. Thus, the offered bio-construct stimulated the cell migration and proliferation at early stages of treatment (3–7 days reducing the inflammation activity.Conclusion. The bio-construct comprising a collagen type  I matrix loaded with buccal epithelial cells can provide an effective treatment option for corneal defects.

Ultraviolet A: Visible spectral absorbance of the human cornea after transepithelial soaking with dextran-enriched and dextran-free riboflavin 0.1% ophthalmic solutions.

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Lombardo, Marco; Micali, Norberto; Villari, Valentina; Serrao, Sebastiano; Pucci, Giuseppe; Barberi, Riccardo; Lombardo, Giuseppe

2015-10-01

To evaluate the stromal concentration of 2 commercially available transepithelial riboflavin 0.1% solutions in human donor corneas with the use of spectrophotometry. University of Calabria, Rende, Italy. Experimental study. The absorbance spectra of 12 corneal tissues were measured in the 330 to 700 nm wavelength range using a purpose-designed spectrophotometry setup before and after transepithelial corneal soaking with a 15% dextran-enriched riboflavin 0.1% solution (n = 6) or a hypotonic dextran-free riboflavin 0.1% solution (n = 6). Both ophthalmic solutions contained ethylenediaminetetraacetic acid and trometamol as enhancers. In addition, 4 deepithelialized corneal tissues underwent stromal soaking with a 20% dextran-enriched riboflavin 0.1% solution and were used as controls. All the riboflavin solutions were applied topically for 30 minutes. The stromal concentration of riboflavin was quantified by analysis of absorbance spectra of the cornea collected before and after application of each solution. The mean stromal riboflavin concentration was 0.012% ± 0.003% (SD), 0.0005% ± 0.0003% (P dextran-enriched, 15% dextran-enriched, and hypotonic dextran-free solutions, respectively. The difference of stromal riboflavin concentration between the 2 transepithelial solutions was statistically significant (P Dextran-enriched solutions required complete corneal deepithelialization to permit effective stromal soaking with riboflavin. Nevertheless, riboflavin in hypotonic dextran-free solution with enhancers permeates across stroma through an intact epithelium. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Anatomical characterization of central, apical and minimal corneal thickness

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Federico Saenz-Frances

2014-08-01

Full Text Available AIM: To anatomically locate the points of minimum corneal thickness and central corneal thickness (pupil center in relation to the corneal apex.METHODS: Observational, cross-sectional study, 299 healthy volunteers. Thickness at the corneal apex (AT, minimum corneal thickness (MT and corneal thickness at the pupil center (PT were determined using the pentacam. Distances from the corneal apex to MT (MD and PT (PD were calculated and their quadrant position (taking the corneal apex as the reference determined:point of minimum thickness (MC and point of central thickness (PC depending on the quadrant position. Two multivariate linear regression models were constructed to examine the influence of age, gender, power of the flattest and steepest corneal axes, position of the flattest axis, corneal volume (determined using the Pentacam and PT on MD and PD. The effects of these variables on MC and PC were also determined in two multinomial regression models.RESULTS: MT was located at a mean distance of 0.909 mm from the apex (79.4% in the inferior-temporal quadrant. PT was located at a mean distance of 0.156 mm from the apex. The linear regression model for MD indicated it was significantly influenced by corneal volume (B=-0.024; 95%CI:-0.043 to -0.004. No significant relations were identified in the linear regression model for PD or the multinomial logistic regressions for MC and PC.CONCLUSION: MT was typically located at the inferior-temporal quadrant of the cornea and its distance to the corneal apex tended to decrease with the increment of corneal volume.

Origin of hemopoietic stromal progenitor cells in chimeras

International Nuclear Information System (INIS)

Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

1985-01-01

Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

In vitro assessment of cytotoxicity and labeling efficiency of 99mTc-HMPAO with stromal vascular fraction of adipose tissue

International Nuclear Information System (INIS)

Verma, V.K.; Beevi, S.S.; Tabassum, A.; Kumaresan, K.; Kamaraju, R.S.; Arbab, A.S.; Chelluri, L.K.

2014-01-01

Introduction: Noninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime ( 99m Tc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of 99m Tc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy. Methods: Ten million cells of SVF were labeled with 99m Tc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of 99m Tc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H 2 DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1. Results: An encouraging labeling efficiency of 33% was observed with 99m Tc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays. Conclusion: 99m Tc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with 99m Tc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy

Preliminary study of the correlation between refractive error and corneal refractive power, corneal asphericity in myopic eye

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Qi-Chao Han

2014-05-01

Full Text Available AIM: To investigate the correlation between myopic refractive error and relative factors, including the corneal refractive power, posterior refractive power, axial length, corneal asphericity coefficient Q value, central cornea thickness(CCTand intraocular pressure(IOP. METHODS:According to the degree of myopia measured by subjective refraction, 138 myopia patients were divided into three subgroups: mild group(-1.00D--3.00D, moderate group(-3.25D--6.00D, high group(>6.00D. The Pentacam anterior segment tomographer(Germany, Oculus Companywas used to measure the corneal refractive power, posterior refractive power, and corneal asphericity in the right eye. IOP, CCT and axial length were measured by a non-contact tonometer and A-scan ultrasonic, respectively. The data was analyzed with a Pearson correlation analysis and one-way ANOVA. RESULTS: The myopic refractive error was negatively correlated with the axial length(r=-0.682, Pr=0.009, P=0.925. The axial length was negatively correlated with corneal refractive power(r=-0.554, Pr=0.674, Pr=-0.375, P=0.01. There was no significantly correlation between the myopic refractive error and CCT, IOP(r=-0.138, P=0.141; r=-0.121, P=0.157. CONCLUSION:The corneal refractive power plays the role of emmetropization during the development of myopia. There is clinic significance for the correlation between Q value and refractive error, IOP to guide the corneal refractive surgery.

Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology.

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Zhan, Han-Xiang; Zhou, Bin; Cheng, Yu-Gang; Xu, Jian-Wei; Wang, Lei; Zhang, Guang-Yong; Hu, San-Yuan

2017-04-28

Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a "passive bystander", stroma may play a role as a "partner in crime" in PC. However, the role of stromal components in PC is complex and requires further investigation. In this article, we review recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in PC. Crosstalk between stromal cells and cancer cells is thoroughly investigated. We also review the prognostic value and molecular therapeutic targets of stroma in PC. This review may help us further understand the molecular mechanisms of stromal biology and its role in PC development and therapeutic resistance. Moreover, targeting stroma components may provide new therapeutic strategies for this stubborn disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of Novel Drugs for Corneal Cell Regeneration

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Sang Beom Han

2018-01-01

Full Text Available Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.

STRUCTURAL BASIS OF THE VASCULAR HEMOSTATIC MECHANISM IN THE UTERINE CERVIX.

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Prokopchook-Lyckbäck, Alexander V

2015-01-01

The objective of the study was to investigate the angioarchitectonics and the functional morphology of the vessels of the cervix and to clarify the role of structural features of these vessels in preventing hemorrhaging in parturition during cervical dilatation. Cervixes uteri were obtained from corpses of 30 women of various ages and 5 ablated at labor. Series of histotopographical specimens of the cervixes were processed using histological and histochemical methods. Peculiar features of the angioarchitectonics, histotopography and structure of cervical vessels were encountered. Arteries penetrating the cervix are surrounded by tight muffs of anastomizing veins that are closely adjacent to the arteries. In other cases, the arteries are located within the lumen of veins--"vessels within vessels". Cervical arteries make up subendocervical convolutions. During pregnancy, smooth muscle "cushions" develop in the vessels. The cervix is pierced by a network of veins that divide the cervical tissue into separate stromal "lobules". This peculiar vascular architecture might be important structural basis of the vascular hemostatic mechanism in the neck of the uterus triggered by labor. It prevents vessel rupture, hemorrhaging and amniotic fluid and air embolism during cervical dilatation. The venous network that passes through the cervix makes it easy for the separate stromal "lobules" of the cervix to move relative to each other during cervical dilatation.

Short-term effects of extremely low-frequency pulsed electromagnetic field and pulsed low-level laser therapy on rabbit model of corneal alkali burn.

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Rezaei Kanavi, Mozhgan; Tabeie, Faraj; Sahebjam, Farzin; Poursani, Nima; Jahanbakhsh, Nazanin; Paymanpour, Pouya; AfsarAski, Sasha

2016-04-01

This study was conducted to investigate the effect of combining extremely low frequency-pulsed electromagnetic field (ELF-PEMF) and low-level laser therapy (LLLT) on alkali-burned rabbit corneas. Fifty alkali-burned corneas of 50 rabbits were categorized into five groups: ELF-PEMF therapy with 2 mT intensity (ELF 2) for 2 h daily; LLLT for 30 min twice daily; combined ELF-PEMF and LLLT (ELF + LLLT); medical therapy (MT); and control (i.e., no treatment). Clinical examination and digital photography of the corneas were performed on days 0, 2, 7, and 14. After euthanizing the rabbits, the affected eyes were evaluated by histopathology. The clinical and histopathologic results were compared between the groups. On days 7 and 14, no significant difference in the corneal defect area was evident between the ELF, LLLT, ELF + LLLT, and MT groups. Excluding the controls, none of the study groups demonstrated a significant corneal neovascularization in both routine histopathology and immunohistochemistry for CD31. Keratocyte loss was significantly higher in the MT group than in the ELF, LLLT, and ELF + LLLT groups. Moderate to severe stromal inflammation in the LLLT group was comparable with that in the MT group and was significantly lower than that in the other groups. In conclusion, combining LLLT and ELF was not superior to ELF alone or LLLT alone in healing corneal alkali burns. However, given the lower intensity of corneal inflammation and the lower rate of keratocytes loss with LLLT, this treatment may be superior to other proposed treatment modalities for healing alkali-burned corneas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Corneal topography with an aberrometry-topography system.

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Mülhaupt, Michael; Dietzko, Sven; Wolffsohn, James; Bandlitz, Stefan

2018-05-07

To investigate the agreement between the central corneal radii and corneal eccentricity measurements generated by the new Wave Analyzer 700 Medica (WAV) compared to the Keratograph 4 (KER) and to test the repeatability of the instruments. 20 subjects (10 male, mean age 29.1 years, range 21-50 years) were recruited from the students and staff of the Cologne School of Optometry. Central corneal radii for the flat (r c/fl ) and steep (r c/st ) meridian as well as corneal eccentricity for the nasal (e nas ), temporal (e temp ), inferior (e inf ) and superior (e sup ) directions were measured using WAV and KER by one examiner in a randomized order. Central radii of the flat (r c/fl ) and steep (r c/st ) meridian measured with both instruments were statically significantly correlated (r = 0.945 and r = 0.951; p  0.05). Limits of agreement (LoA) indicate a better repeatability for the KER compared to WAV. Corneal topography measurements captured with the WAV were strongly correlated with the KER. However, due to the differences in measured corneal radii and eccentricities, the devices cannot be used interchangeably. For corneal topography the KER demonstrated better repeatability. Copyright © 2018 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Rechazo y retrasplante corneal Corneal rejection and re-transplantation

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Miguel O Mokey Castellanos

2007-06-01

Full Text Available Se efectuó una investigación observacional análítica retrospectiva, sobre los transplantes corneales efectuados en el Servicio de Oftalmología del Hospital "Hermanos Ameijeiras. Rechazaron 76 pacientes, que se compararon con un control de 89 pacientes, que en un período similar no tuvieron rechazo. El queratocono fue la afección corneal que predominó. El primer lugar en los rechazos correspondió a queratoherpes (43,5 %. El menor índice de rechazo fue para el queratocono (8,8 %. Se analizó la multiplicidad de rechazos; y fue frecuente que se presentara un solo rechazo, aunque sí hubo congruencia entre el número de rechazos y la necesidad de retrasplantes. Se encontró que los resultados de la conducta médica o quirúrgica se relacionaban con la causa. Se calcula un índice de supervivencia (Kaplan-Meier, que concluye que en los primeros dos años existe menos posibilidad de aparición de rechazoAn retrospective observational analytical research was conducted on corneal transplants performed at Ophthalmological Service in “Hermanos Ameijeiras” hospital . Seventy six patients had graft rejection and were compared to a control group of 89 patients that did not present rejection in the same period of time. Keratoconus was the prevailing corneal problem. The highest rejection rate corresponded to keratoherpes (43,5% whereas the lowest rate was for keratoconus (8,8%. Multiplicity of rejections was analyzed and it was found that mostly one graft rejection occured, but number of rejections was associated with the need of re-transplantation. It was found that the results of medical or surgical performance were related to the cause of graft rejection. A survival index (Kaplan-Meier was estimated, which showed that occurence of graf rejection is less probable in the first two years

Granular corneal dystrophy

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Castillo Pérez, Alexeide de la C; Vilches Lescaille, Daysi; Noriega, Justo Luis; Martínez Balido, Daneel; León Balbón, Bárbaro Ramón; León Bernal, Danysleidi

2015-01-01

Las distrofias corneales constituyen un conjunto de enfermedades que presentan, en su mayoría, una baja incidencia y se caracterizan por acúmulo de material hialino o amiloide que disminuyen la transparencia corneal. La distrofia granular es una enfermedad autosómica dominante que presenta opacidades grises en el estroma superficial central de la córnea y se hacen visibles en la primera y segunda décadas de la vida, lo que provoca disminución de la visión más significativa cerca de los 40 año...

Biocompatibility of a fish scale-derived artificial cornea: Cytotoxicity, cellular adhesion and phenotype, and in vivo immunogenicity.

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van Essen, T H; van Zijl, L; Possemiers, T; Mulder, A A; Zwart, S J; Chou, C-H; Lin, C C; Lai, H J; Luyten, G P M; Tassignon, M J; Zakaria, N; El Ghalbzouri, A; Jager, M J

2016-03-01

To determine whether a fish scale-derived collagen matrix (FSCM) meets the basic criteria to serve as an artificial cornea, as determined with in vitro and in vivo tests. Primary corneal epithelial and stromal cells were obtained from human donor corneas and used to examine the (in)direct cytotoxicity effects of the scaffold. Cytotoxicity was assessed by an MTT assay, while cellular proliferation, corneal cell phenotype and adhesion markers were assessed using an EdU-assay and immunofluorescence. For in vivo-testing, FSCMs were implanted subcutaneously in rats. Ologen(®) Collagen Matrices were used as controls. A second implant was implanted as an immunological challenge. The FSCM was implanted in a corneal pocket of seven New Zealand White rabbits, and compared to sham surgery. The FSCM was used as a scaffold to grow corneal epithelial and stromal cells, and displayed no cytotoxicity to these cells. Corneal epithelial cells displayed their normal phenotypical markers (CK3/12 and E-cadherin), as well as cell-matrix adhesion molecules: integrin-α6 and β4, laminin 332, and hemi-desmosomes. Corneal stromal cells similarly expressed adhesion molecules (integrin-α6 and β1). A subcutaneous implant of the FSCM in rats did not induce inflammation or sensitization; the response was comparable to the response against the Ologen(®) Collagen Matrix. Implantation of the FSCM in a corneal stromal pocket in rabbits led to a transparent cornea, healthy epithelium, and, on histology, hardly any infiltrating immune cells. The FSCM allows excellent cell growth, is not immunogenic and is well-tolerated in the cornea, and thus meets the basic criteria to serve as a scaffold to reconstitute the cornea. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence and causes of corneal blindness.

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Wang, Haijing; Zhang, Yaoguang; Li, Zhijian; Wang, Tiebin; Liu, Ping

2014-04-01

The study aimed to assess the prevalence and causes of corneal blindness in a rural northern Chinese population. Cross-sectional study. The cluster random sampling method was used to select the sample. This population-based study included 11 787 participants of all ages in rural Heilongjiang Province, China. These participants underwent a detailed interview and eye examination that included the measurement of visual acuity, slit-lamp biomicroscopy and direct ophthalmoscopy. An eye was considered to have corneal blindness if the visual acuity was blindness and low vision. Among the 10 384 people enrolled in the study, the prevalence of corneal blindness is 0.3% (95% confidence interval 0.2-0.4%). The leading cause was keratitis in childhood (40.0%), followed by ocular trauma (33.3%) and keratitis in adulthood (20.0%). Age and illiteracy were found to be associated with an increased prevalence of corneal blindness. Blindness because of corneal diseases in rural areas of Northern China is a significant public health problem that needs to be given more attention. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

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Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

2010-01-01

To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

Applanation optical coherence elastography: noncontact measurement of intraocular pressure, corneal biomechanical properties, and corneal geometry with a single instrument

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Singh, Manmohan; Han, Zhaolong; Nair, Achuth; Schill, Alexander; Twa, Michael D.; Larin, Kirill V.

2017-02-01

Current clinical tools provide critical information about ocular health such as intraocular pressure (IOP). However, they lack the ability to quantify tissue material properties, which are potent markers for ocular tissue health and integrity. We describe a single instrument to measure the eye-globe IOP, quantify corneal biomechanical properties, and measure corneal geometry with a technique termed applanation optical coherence elastography (Appl-OCE). An ultrafast OCT system enabled visualization of corneal dynamics during noncontact applanation tonometry and direct measurement of micro air-pulse induced elastic wave propagation. Our preliminary results show that the proposed Appl-OCE system can be used to quantify IOP, corneal biomechanical properties, and corneal geometry, which builds a solid foundation for a unique device that can provide a more complete picture of ocular health.

Risk factors for corneal ectasia after LASIK.

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Tabbara, Khalid F; Kotb, Amgad A

2006-09-01

To establish a grading system that helps identify high-risk individuals who may experience corneal ectasia after LASIK. Retrospective, comparative, interventional case series. One hundred forty-eight consecutive patients (148 eyes) were included in this study. Thirty-seven patients who underwent LASIK at other refractive centers experienced corneal ectasia in 1 eye after LASIK. One hundred eleven eyes of 111 patients who underwent successful LASIK during the same period were age and gender matched and served as controls. All patients underwent preoperative and postoperative topographic analysis of the cornea. The follow-up period in both groups of patients ranged from 2 to 5 years, with a mean follow-up of 3.6 years. All patients underwent LASIK for myopia (spherical equivalent, -4.00 to -8.00 diopters). Corneal keratometry, oblique cylinder, pachymetry, posterior surface elevation, difference between the inferior and superior corneal diopteric power, and posterior best sphere fit (BSF) over anterior BSF were given a grade of 1 to 3 each. An ectasia grading system was established, and the cumulative risk score was assessed. Patients who had a grade of 7 or less showed no evidence of corneal ectasia, whereas 16 (59%) of 27 patients who had a grade of 8 to 12 had corneal ectasia. Twenty-one (100%) of 21 patients with a grade of more than 12 had corneal ectasia after LASIK (P<0.0001). A risk score may help in the prediction of patients who are at risk of experiencing corneal ectasia after LASIK. A prospective clinical study is needed to assess the validity of these risk factors.

Customized toric intraocular lens implantation for correction of extreme corneal astigmatism due to corneal scarring

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R Bassily

2010-03-01

Full Text Available R Bassily, J LuckOphthalmology Department, Royal United Hospital, Combe Park, Bath, UKAbstract: A 76-year-old woman presented with decreased visual function due to cataract formation. Twenty-five years prior she developed right sided corneal ulceration that left her with 10.8 diopters (D of irregular astigmatism at 71.8° (steep axis. Her uncorrected visual acuity was 6/24 and could only ever wear a balanced lens due to the high cylindrical error. Cataract surgery was planned with a custom designed toric intraocular lens (IOL with +16.0 D sphere inserted via a wound at the steep axis of corneal astigmatism. Postoperative refraction was -0.75/+1.50 × 177° with a visual acuity of 6/9 that has remained unchanged at six-week follow-up with no IOL rotation. This case demonstrates the value of high power toric IOLs for the correction of pathological corneal astigmatism.Keywords: intraocular lens, corneal ulceration, visual acuity, scarring

The molecular mechanisms of action of PPAR-γ agonists in the treatment of corneal alkali burns (Review)

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Zhou, Hongyan; Zhang, Wensong; Bi, Miaomiao; Wu, Jie

2016-01-01

Corneal alkali burns (CAB) are characterized by injury-induced inflammation, fibrosis and neovascularization (NV), and may lead to blindness. This review evaluates the current knowledge of the molecular mechanisms responsible for CAB. The processes of cytokine production, chemotaxis, inflammatory responses, immune response, cell signal transduction, matrix metalloproteinase production and vascular factors in CAB are discussed. Previous evidence indicates that peroxisome proliferator-activated receptor γ (PPAR-γ) agonists suppress immune responses, inflammation, corneal fibrosis and NV. This review also discusses the role of PPAR-γ as an anti-inflammatory, anti-fibrotic and anti-angiogenic agent in the treatment of CAB, as well as the potential role of PPAR-γ in the pathological process of CAB. There have been numerous studies evaluating the clinical profiles of CAB, and the aim of this systematic review was to summarize the evidence regarding the treatment of CAB with PPAR-γ agonists. PMID:27499172

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection.

Science.gov (United States)

Tabbara, Khalid F

2008-06-01

Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

Study on the establishment of corneal alkali chemical injury on rats

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Nan Hu

2013-06-01

Full Text Available AIM:To investigate the appropriate methods to establish corneal alkali chemical injury on rats. METHODS:The rats(n=87were randomly divided into three groups. Corneal alkali injury was induced by placing 1mol/L NaOH soaked filter paper on the limbus of right cornea for 20 seconds(group A, n=34or 40 seconds(group B, n=23, and on the central axis of the right cornea for 40 seconds(group C, n=30respectively. Corneal transparency, corneal ulceration, and corneal neovascularization were observed and recorded under slit- lamp biomicroscope on day 7 post-operation. RESULTS: Incidence of corneal ulceration, corneal perforation and positive rate of corneal fluorescein staining in limbal corneal injury groups(group A and Bwere significantly higher than that of central corneal injury group(group C(P<0.05. Incidence of corneal ulceration and corneal perforation in group B was significantly higher than group A(P<0.05. Corneal neovascularization was observed in all three groups. CONCLUSION: Corneal alkali burns induced by 3mm diameter central cornea injury are fit for the study of corneal neovascularization, while those induced by limbus injury for 20 seconds are fit for the study on limbal stem cells deficiency.

Punctiform and Polychromatophilic Dominant Pre-Descemet Corneal Dystrophy.

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Lagrou, Lisa; Midgley, Julian; Romanchuk, Kenneth Gerald

2016-04-01

To describe the slit-lamp appearance and corneal confocal microscopy of autosomal dominant punctiform and polychromatophilic pre-Descemet corneal dystrophy in 3 members of the same family. Slit-lamp examination of a 9-year-old boy showed bilateral polychromatophilic corneal opacities in a pre-Descemet membrane location evenly deposited limbus to limbus, both horizontally and vertically, with an intervening clear cornea. The corneal endothelium was normal on corneal confocal microscopy, with hyperreflective opacities of various sizes located pre-Descemet membrane. Slit-lamp examination of the patient's father and brother revealed identical crystalline deposition in the pre-Descemet corneal stroma. The remainders of the eye examinations were otherwise normal in all 3 individuals, and all were asymptomatic. The general physical examination and laboratory investigations of the patient were all normal, as were the laboratory investigations of the other 2 family members. There was no progression in the corneal findings over 6 months of follow-up. These patients likely illustrate a rare autosomal dominant pre-Descemet crystalline keratopathy that has been reported only once previously.

Recovery of Corneal Endothelial Cells from Periphery after Injury.

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Sang Ouk Choi

Full Text Available Wound healing of the endothelium occurs through cell enlargement and migration. However, the peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium in endothelial injury.To investigate the recovery process of corneal endothelial cells (CECs from corneal endothelial injury.Three patients with unilateral chemical eye injuries, and 15 rabbit eyes with corneal endothelial chemical injuries were studied. Slit lamp examination, specular microscopy, and ultrasound pachymetry were performed immediately after chemical injury and 1, 3, 6, and 9 months later. The anterior chambers of eyes from New Zealand white rabbits were injected with 0.1 mL of 0.05 N NaOH for 10 min (NaOH group. Corneal edema was evaluated at day 1, 7, and 14. Vital staining was performed using alizarin red and trypan blue.Specular microscopy did not reveal any corneal endothelial cells immediately after injury. Corneal edema subsided from the periphery to the center, CEC density increased, and central corneal thickness decreased over time. In the animal study, corneal edema was greater in the NaOH group compared to the control at both day 1 and day 7. At day 1, no CECs were detected at the center and periphery of the corneas in the NaOH group. Two weeks after injury, small, hexagonal CECs were detected in peripheral cornea, while CECs in mid-periphery were large and non-hexagonal.CECs migrated from the periphery to the center of the cornea after endothelial injury. The peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium.

Evaluation of corneal symmetry after UV corneal crosslinking for keratoconus

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Mofty H

2017-11-01

Full Text Available Hanan Mofty,1,2 Khaled Alzahrani,2 Fiona Carley,3 Sophie Harper,3 Arun Brahma,3 Leon Au,3 Debbie Morley,3 M Chantal Hillarby2 1Optometry Department, College of Applied Medical Science, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, 3Manchester Royal Eye Hospital, Manchester, UK Purpose: The purpose of this study was to assess UV corneal crosslinking (CXL treatment outcomes for keratoconus by evaluating the corneal regularity in patients through follow-up using the Oculus Pentacam.Patients and methods: A total of 18 eyes from CXL patients with keratoconus were studied before and after CXL treatment, and six eyes from six patients who were not treated with CXL served as controls. Treated patients had Pentacam images taken before CXL treatment and regularly 3 months post treatment up to the 12th month. Controls were imaged during their first appointment and after 12 months. Symmetry and asphericity were evaluated and correlated with both best-corrected visual acuity (BCVA and maximum K-readings.Results: In the CXL-treated group, there was a significant improvement in the index of symmetrical variation (ISV and keratoconus index (KI at 3 months and in the index of height asymmetry (IHA and minimum radius of curvature (Rmin at 9 months post treatment. On the contrary, the untreated group’s indices showed some significant worsening in ISV, KI, central keratoconus index (CKI, and Rmin. A novel finding in our study was a slight positive shift of anterior asphericity in the 6 mm, 7 mm, and 8 mm 3 months after treatment, which had a correlation with BCVA (R2=0.390, p=0.053 and a strong correlation with maximum K-reading (R2=0.690, p=0.005. However, the untreated group had no significant changes after 1 year.Conclusion: The corneal asymmetrical shape is associated with the spherical aberration alteration

The Effect of Pseudoexfoliation and Pseudoexfoliation Induced Dry Eye on Central Corneal Thickness.

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Akdemir, M Orcun; Kirgiz, Ahmet; Ayar, Orhan; Kaldirim, Havva; Mert, Metin; Cabuk, Kubra Serefoglu; Taskapili, Muhittin

2016-01-01

The aim of this study is to investigate the effect of pseudoexfoliation (PEX) and PEX-induced dry eye on central corneal thickness (CCT). This cross-sectional study consists of total 270 eyes of 135 patients (67 females, 68 males) in total. After excluding the PEX (-) 32 eyes with PEX in the other eye, totally 130 eyes in PEX (-) group and 108 eyes in the PEX (+) group were included in the study. The PEX (+) group was regrouped as PEX syndrome (80 eyes of 50 patients) and PEX glaucoma (28 eyes of 20 patients). In the PEX (-) group, the mean Schirmer test result was 12 ± 4 mm (4-25 mm), in the PEX syndrome group 10 ± 4 mm (4-22 mm), in the PEX glaucoma group 9 ± 3 mm (4-15 mm). The difference among the PEX (-) group, the PEX syndrome and the PEX glaucoma groups was statistically significant (p eyes with PEX (r = 0.307, p = 0.001). However, there was no statistically significant correlation between CCT, Schirmer and tear break up time tests in the eyes with PEX. PEX material can cause decrease in tear film secretion and disturb tear film stability. There is no effect of PEX-induced dry eye on CCT. Lower CCT values in the eyes with PEX material may be a result of decrease in corneal stromal cell density. Moreover, higher CCT values may be because of decreased endothelial cells in PEX glaucoma patients.

Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and Photorefractive Keratectomy for Corneal Ectasia after Laser in situ Keratomileusis.

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Zhu, Wei; Han, Yunfei; Cui, Changxia; Xu, Wenwen; Wang, Xuan; Dou, Xiaoxiao; Xu, Linlin; Xu, Yanyun; Mu, Guoying

2018-01-01

The aim of this study was to analyze the effects of corneal crosslinking (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) in halting the progression and improving the visual function of corneal ectasia after laser in situ keratomileusis (LASIK). PTK-PRK-CXL was performed on 14 eyes of 14 patients who developed corneal ectasia after LASIK. The visual acuity, spherical refraction and cylinder, corneal topography indices, thinnest corneal thickness (TCT), and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. The mean uncorrected visual acuity improved significantly from 0.64 ± 0.36 logMAR preoperatively to 0.19 ± 0.12 logMAR at 12 months of follow-up (p 0.05) beyond 6 months after treatment. PTK-PRK-CXL is a promising procedure to halt the progression of post-LASIK keratectasia with significant visual quality improvement. © 2018 S. Karger AG, Basel.

Research on mouse model of grade II corneal alkali burn

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Jun-Qiang Bai

2016-04-01

Full Text Available AIM: To choose appropriate concentration of sodium hydroxide (NaOH solution to establish a stable and consistent corneal alkali burn mouse model in grade II. METHODS: The mice (n=60 were randomly divided into four groups and 15 mice each group. Corneal alkali burns were induced by placing circle filter paper soaked with NaOH solutions on the right central cornea for 30s. The concentrations of NaOH solutions of groups A, B, C, and D were 0.1 mol/L, 0.15 mol/L , 0.2 mol/L, and 1.0 mol/L respectively. Then these corneas were irrigated with 20 mL physiological saline (0.9% NaCl. On day 7 postburn, slit lamp microscope was used to observe corneal opacity, corneal epithelial sodium fluorescein staining positive rate, incidence of corneal ulcer and corneal neovascularization, meanwhile pictures of the anterior eyes were taken. Cirrus spectral domain optical coherence tomography was used to scan cornea to observe corneal epithelial defect and corneal ulcer. RESULTS: Corneal opacity scores ( were not significantly different between the group A and group B (P=0.097. Incidence of corneal ulcer in group B was significantly higher than that in group A (P=0.035. Incidence of corneal ulcer and perforation rate in group B was lower than that in group C. Group C and D had corneal neovascularization, and incidence of corneal neovascularization in group D was significantly higher than that in group C (P=0.000. CONCLUSION: Using 0.15 mol/L NaOH can establish grade II mouse model of corneal alkali burns.

Primary observation on adherent function of bone marrow stromal cells in mice post combined radiation-burn injury

International Nuclear Information System (INIS)

Chen Xinghua; Luo Chengji; Guo Chaohua; Wang Ping; Deng Xuecai

1999-01-01

Objective: To investigate the adherent function of bone marrow stromal cells in hematopoietic inductive microenvironment post combined radiation-burn injury. Methods: The expression of cell adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1), fibro-connection (Fn), laminin (Ln) and collagen type IV (Col IV) on bone marrow stromal cells cultured in vitro was detected by flow cytometry and the binding capacity of bone marrow mononuclear cells to stromal cell adherence layer was tested by cell binding assay and cell binding blocking assay respectively from mice treated with 5.0 Gy γ-ray 15% of total body surface area (TBSA), third-degree burn injury and combined irradiation-burn injury, respectively. Results: 1. The expression levels of molecules mentioned above in burn-injured mice were the highest. The molecules levels in control mice were greater than those in radiation-injured mice, which were lower than those in mice with combined radiation-burn injury. 2. The binding capacity of stromal cell adherence layer in burn-injured mice was greater than that in control mice, and significantly increased from 3 to 7 days post injury as compared with that in controls, radiation-injured mice and combined radiation-burn-injured mice, respectively (P < 0.05-0.01). Contrarily, the capacity of binding in the radiation-injured and combined radiation-burn-injured mice was the lowest from 3 to 7 days post injury. 3. The binding rate of bone marrow mononuclear cells to stromal cell adherence layer descended in different degrees after pre-treatment with monoclonal antibodies directed to VCAM-1, Fn, Ln, or Col IV respectively or VCAM-1 combined with anti-Fn, anti-Ln or anti-Col IV, respectively, in stromal cell adherence layer. Conclusion: The damage of cell adherent function for bone marrow hematopoietic inductive microenvironment post combined radiation-burn injury might be one of the important factors in hematopoietic disorder in combined radiation-burn injury

Corneal Laceration

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Full Text Available ... to Full Corneal Transplantation Nov 29, 2016 Follow The Academy Professionals: Education Guidelines News Multimedia Public & Patients: Contact Us About the Academy Jobs at the Academy Financial Relationships with Industry ...

Using corneal topography design personalized cataract surgery programs

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Jin-Ou Huang

2014-08-01

Full Text Available AIM:To investigate how to design personalized cataract surgery programs to achieve surgical correction of preoperative corneal astigmatism with surgical astigmatism under the guidance of corneal topography, improve postoperative visual quality and reduce the cost of treatment. METHODS: Totally 202 cases(226 eyescataract patients were divided into randomized treatment group and individualized treatment group. According to the method and location of the incision, randomized treatment group were divided into 8 groups. Surgical astigmatism after different incision were calculated with the use of preoperative and postoperative corneal astigmatism through vector analysis method. Individualized treatment groups were designed personably for surgical method with reference of every surgically induced astigmatism, the surgical method chooses the type of surgical incision based on close link between preoperative corneal astigmatism and surgically induced astigmatism, and the incision was located in the steep meridian. The postoperative corneal astigmatism of individualized treatment group was observed. RESULTS: Postoperative corneal astigmatism of individualized treatment group were lower than that of 3.0mm clear corneal tunnel incision in the randomized treatment group, there were statistically significance difference, while with 3.0mm sclera tunnel incision group there were no statistically significance difference. After 55.8% of patients with the use of individualized surgical plan could undergo the operation of extracapsular cataract extraction with relatively low cost and rigid intraocular lens implantation, the per capita cost of treatment could be reduced. CONCLUSION: Personalized cataract surgery programs are designed to achieve surgical correction of preoperative corneal astigmatism under the use of corneal topography, improve postoperative visual quality and reduce the cost of treatment.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

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Rosa Dolz-Marco

2014-01-01

Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

Science.gov (United States)

Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

2014-01-01

Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

The influence of perivascular adipose tissue on vascular homeostasis.

Science.gov (United States)

Szasz, Theodora; Bomfim, Gisele Facholi; Webb, R Clinton

2013-01-01

The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT.

Adipose Derived Stromal Cell (ADSC) Injections for Pain Management of Osteoarthritis in the Human Knee Joint.

Science.gov (United States)

Fodor, Peter B; Paulseth, Stephen G

2016-02-01

This safety and feasibility study used autologous adipose-derived stromal vascular cells (the stromal vascular fraction [SVF] of adipose tissue), to treat 8 osteoarthritic knees in 6 patients of grade I to III (K-L scale) with initial pain of 4 or greater on a 10-point Visual Analog Scale (VAS). The primary objective of the study was evaluation of the safety of intra-articular injection of SVF. The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees. Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate, resuspension in 3 mL of Lactated Ringer's Solution, and injection directly into the intra-articular space of the knee, with a mean of 14.1 million viable, nucleated SVF cells per knee. Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the VAS pain scale, range of motion (ROM), timed up-and-go (TUG), and MRI. No infections, acute pain flares, or other adverse events were reported. At 3-months postoperative, there was a statistically significant improvement in WOMAC and VAS scores (P knee pain. Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee. LEVEL OF EVIDENCE 4: Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Topical Ranibizumab as a Treatment of Corneal Neovascularization

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Ferrari, Giulio; Dastjerdi, Mohammad H.; Okanobo, Andre; Cheng, Sheng-Fu; Amparo, Francisco; Nallasamy, Nambi; Dana, Reza

2014-01-01

Purpose To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). Methods This was a prospective, open-label, monocentric, uncontrolled, non-comparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up of 16 weeks. The main corneal neovascularization outcome measures were: neovascular area (NA), the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA, USA. Results Statistically significant decreases in NA (55.3%, P<0.001), which lasted through 16 weeks, and VC (59%, P<0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P=0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. Conclusions Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA. PMID:23407316

Corneal changes with accommodation using dual Scheimpflug photography.

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Sisó-Fuertes, Irene; Domínguez-Vicent, Alberto; del Águila-Carrasco, Antonio; Ferrer-Blasco, Teresa; Montés-Micó, Robert

2015-05-01

To assess whether corneal parameters and aberrations are affected by accommodation. Optics Department, University of Valencia, Valencia, Spain. Prospective cross-sectional study. The Galilei G4 dual Scheimpflug device was used to obtain data on the anterior and posterior axial curvatures, total corneal power (TCP), and corneal pachymetry from 3 corneal zones (central: 0.0 up to 4.0 mm; paracentral or mid: 4.0 up to 7.0 mm; peripheral: 7.0 up to 10.0 mm) in young emmetropic eyes in the unaccommodated and 4 accommodated states (from -1.0 to -4.0 diopters [D] in 1.0 D steps). The 2nd-, 3rd-, and 4th-order aberrations as well as the root mean square (RMS) were also determined for the entire cornea at the same accommodative demands. The study evaluated 7 subjects (12 eyes). No significant changes in any measured parameter were found during accommodation for any corneal zone (P > .05). Statistically significant differences were found in the various corneal zones when it was assumed they were constant with accommodation (P the high standard deviation values. Different parameters in various zones of the cornea as well as corneal aberrations were stable during accommodation. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Corneal biomechanical properties in healthy children measured by corneal visualization scheimpflug technology.

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He, Miao; Ding, Hui; He, Hong; Zhang, Chi; Liu, Liangping; Zhong, Xingwu

2017-05-17

The aim of this study was to evaluate corneal biomechanical properties in a population of healthy children in China using corneal visualization Scheimpflug technology (CST). All children underwent complete bi-ocular examinations. CST provided intraocular pressure (IOP) and corneal biomechanical parameters, including time, velocity, length and deformation amplitude at first applanation (A1T, A1V, A1L, A1DA), at second applanation (A2T, A2V, A2L, A2DA), highest concavity time (HCT), maximum deformation amplitude (MDA), peak distance (PD), and radius of curvature (RoC). Pearson correlation analysis was used to assess the impacts of demographic factors, central corneal thickness (CCT), spherical equivalent (SE), and IOP on corneal biomechanics. One hundred eight subjects (32 girls and 76 boys) with the mean age of 10.80 ± 4.13 years (range 4 to18 years) were included in the final analyses. The right and left eyes were highly symmetrical in SE (p = 0.082), IOP (p = 0.235), or CCT (p = 0.210). Mean A1T of the right eyes was 7.424 ± 0.340 ms; the left eyes 7.451 ± 0.365 ms. MDA was 0.993 ± 0.102 mm in the right eyes and 0.982 ± 0.100 mm in the left eyes. Mean HCT of the right eyes was 16.675 ± 0.502 ms; the left eyes 16.735 ± 0.555 ms. All CST parameters of both eye were remarkably symmetrical with the exception of A2L (p = 0.006), A1DA (p = 0.025). The majority of CST parameters of both eyes were significantly correlated with CCT and IOP (p children eyes. Several CST biomechanical parameters in children are modified by CCT and IOP.

Therapy of canine corneal pannus with strontium-90

International Nuclear Information System (INIS)

Hoecht, S.; Nausner, M.; Hinkelbein, W.; Gruening, G.; Allgoewer, I.; Brunnberg, L.

2002-01-01

Background: Corneal pannus is a disease which, if untreated, nearly always is progressive and may lead to blindness of the affected dog. A therapeutic standard is yet to be defined. Beta-ray irradiation with Sr-90 is often recommended on a casuistic basis, but systematic studies are sparse. The aim of the present study was to evaluate efficacy and to document side effects of radiotherapy with Sr-90. Material and Methods: 17 animals were treated. 13 of them received treatment of 15 Gy surface dose twice within 2 days with additional medical therapy with ciclosporin and prednisolon. Only the more affected eye was treated with radiation which was applied with an eye-applicator, the other eye served as control. Four animals with already advanced impairment of vision received keratectomy, afterwards radiation was applied on both sides. Results: Medical treatment alone led to deterioration in vascularization and spread of pigmentation in eleven of 13 (85%) of the control-eyes, density of pigmentation increased in eight of 13 (62%). After radiation therapy, almost all animals showed a marked initial improvement. Even if progressive disease occurred later on, further worsening as it happened in the control-eyes could be stopped in nine resp. ten of 13 eyes (69% and 77%). All animals with keratectomy and radiotherapy regained and preserved adequate vision. Besides short-term blepharospasm, no side effects were recorded. Conclusion: Corneal pannus is responsive to radiation therapy with Sr-90 and long-term benefit can be achieved. Side effects are minimal. Optimal sequencing of therapy and dosage still have to be examined. (orig.) [de

Corneal Laceration

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Full Text Available ... by something sharp flying into the eye. It can also be caused by something striking the eye ... If the corneal laceration is deep enough it can cause a full thickness laceration. This is when ...

In Vivo Corneal Biomechanical Properties with Corneal Visualization Scheimpflug Technology in Chinese Population

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Ying Wu

2016-01-01

Full Text Available Purpose. To determine the repeatability of recalculated corneal visualization Scheimpflug technology (CorVis ST parameters and to study the variation of biomechanical properties and their association with demographic and ocular characteristics. Methods. A total of 783 healthy subjects were included in this study. Comprehensive ophthalmological examinations were conducted. The repeatability of the recalculated biomechanical parameters with 90 subjects was assessed by the coefficient of variation (CV and intraclass correlation coefficient (ICC. Univariate and multivariate linear regression models were used to identify demographic and ocular factors. Results. The repeatability of the central corneal thickness (CCT, deformation amplitude (DA, and first/second applanation time (A1/A2-time exhibited excellent repeatability (CV% ≤ 3.312% and ICC ≥ 0.929 for all measurements. The velocity in/out (Vin/out, highest concavity- (HC- radius, peak distance (PD, and DA showed a normal distribution. Univariate linear regression showed a statistically significant correlation between Vin, Vout, DA, PD, and HC-radius and IOP, CCT, and corneal volume, respectively. Multivariate analysis showed that IOP and CCT were negatively correlated with Vin, DA, and PD, while there was a positive correlation between Vout and HC-radius. Conclusion. The ICCs of the recalculated parameters, CCT, DA, A1-time, and A2-time, exhibited excellent repeatability. IOP, CCT, and corneal volume significantly influenced the biomechanical properties of the eye.

Triptolide Suppresses Alkali Burn-Induced Corneal Angiogenesis Along with a Downregulation of VEGFA and VEGFC Expression.

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Wang, Geng; Li, Na; Lv, Xiaohong; Ahmed, Naila; Li, Xinlei; Liu, Huidong; Ma, Jing; Zhang, Yafang

2017-07-01

Triptolide (TPL) is an active compound extracted from a Chinese herbal medicine tripterygium wilfordii Hook. f. (Celastraceae), which has been used as an anti-inflammatory drug for years. It also inhibits the growth and proliferation of different types of cancer cells. The inhibitory effect of TPL on angiogenesis after chemical-induced corneal inflammation was studied in vivo. The effects of TPL on the proliferation, apoptosis, migration, and tube formation of rat aortic endothelial cells (RAECs) were studied in vitro. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. Migration was analyzed using the scratch wound healing assay and transwell assay. Tube formation assay was used to examine angiogenesis. Real-time PCR and Western blot were used to determine the expression of vascular endothelial growth factor A (VEGFA) and VEGFC. To study the in vivo effects of TPL, the mouse model of alkali burn-induced corneal angiogenesis was used. The angiogenesis was analyzed by determining the density of the newly generated blood vessels in corneas. We found that TPL induced apoptosis and inhibited the proliferation of RAECs in a dose-dependent manner. TPL inhibited migration and tube formation of RAECs and decreased the expression of VEGFA and VEGFC in vitro. Furthermore, TPL suppressed alkali burn-induced corneal angiogenesis and inhibited the expression of VEGFA and VEGFC in corneas in vivo. In conclusion, topical TPL as a pharmacological agent has the ability to reduce angiogenesis in cornea and may have clinical indications for the treatment of corneal angiogenesis diseases which have to be further explored. Anat Rec, 300:1348-1355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Alloimmunity and Tolerance in Corneal Transplantation.

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Amouzegar, Afsaneh; Chauhan, Sunil K; Dana, Reza

2016-05-15

Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction. Copyright © 2016 by The American Association of Immunologists, Inc.

Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization.

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Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo; Jung, Sang Hoon

2016-01-01

The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats.

Ocular fibropapillomas of green turtles (Chelonia mydas).

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Brooks, D E; Ginn, P E; Miller, T R; Bramson, L; Jacobson, E R

1994-05-01

Histologic evaluation of four eyes from three stranded juvenile green turtles (Chelonia mydas) from Florida, USA revealed ocular fibropapillomas composed of an overlying hyperplastic epithelium, various amounts of a thickened, well vascularized, collagenous stroma, and a moderate-to-dense population of reactive fibroblasts. The histologic morphology of the ocular fibropapillomas varied depending on whether the eyelid, conjunctiva, limbus, or cornea was the primary site of tumor origin. Fibropapillomas arising from the limbus, conjunctiva, or eyelid tended to be polyploid or pedunculated with a high degree of arborization. They often filled the conjunctival fornices and extended externally to be ulcerated on the distal aspects. Corneal fibropapillomas were more sessile and multinodular with less arborization. Some corneal tumors consisted primarily of a broad fibrovascular stroma and mild epithelial hyperplasia, whereas others had a markedly hyperplastic epithelium supported by stalks of fibrovascular stromal tissue. In green turtles ocular fibropapillomas may be locally invasive and associated with severe blindness and systemic debilitation.

Corneal thickness: measurement and implications.

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Ehlers, Niels; Hjortdal, Jesper

2004-03-01

The thickness of the cornea was reported in more than 100-year-old textbooks on physiological optics (Helmholtz, Gullstrand). Physiological interest was revived in the 1950s by David Maurice, and over the next 50 years, this 'simple' biological parameter has been studied extensively. Several techniques for its measurement have been described and physiological and clinical significance have been studied. In this review, the different methods and techniques of measurement are briefly presented (optical, ultrasound). While the corneal thickness of many animals are the same over a considerable part of the surface, in the human cornea anterior and posterior curvature are not concentric giving rise to a problem of definition. Based on this the precision and accuracy of determining the central corneal thickness are discussed. Changes in corneal thickness reflects changes in function of the boundary layers, in particular the endothelial barrier. The absolute value of thickness is of importance for the estimation of IOP but also in diagnosis of corneal and systemic disorders. Finally it is discussed to what extent the thickness is a biometric parameter of significance, e.g. in the progression of myopia or in the development of retinal detachment.

An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model.

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Uchiyama, Masaaki; Shimizu, Akira; Masuda, Yukinari; Nagasaka, Shinya; Fukuda, Yuh; Takahashi, Hiroshi

2013-01-01

We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing.

First-in-man intraglandular implantation of stromal vascular fraction and adipose-derived stem cells plus platelet-rich plasma in irradiation-induced gland damage: a case study

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Comella K

2017-08-01

Full Text Available Kristin Comella,1 Walter Bell2 1US Stem Cell, Inc, Sunrise, FL, USA; 2South African Stem Cell Institute, Parys, South Africa Background: Stromal vascular fraction (SVF is a mixture of cells which can be isolated from a mini-lipoaspirate of fat tissue. Platelet-rich plasma (PRP is a mixture of growth factors and other nutrients which can be obtained from peripheral blood. Adipose-derived stem/stromal cells (ADSCs can be isolated from fat tissue and expanded in culture. The SVF includes a variety of different cells such as ADSCs, pericytes, endothelial/progenitor cells, and a mix of different growth factors. The adipocytes (fat cells can be removed via centrifugation. Here, we describe the rationale and, to our knowledge, the first clinical implementation of SVF and PRP followed by repeat dosing of culture-expanded ADSCs into a patient with severe xerostomia postirradiation. Methods: Approximately 120 mLs of adipose tissue was removed via mini-lipoaspirate procedure under local anesthetic. The SVF was prepared from half of the fat and resuspended in PRP. The mixture was delivered via ultrasound directly into the submandibular and parotid glands on both the right and left sides. The remaining 60 mLs of fat was processed to culture-expand ADSCs. The patient received seven follow-up injections of the ADSCs plus PRP at 5, 8, 16, 18, 23, 28, and 31 months postliposuction. The subject was monitored over a period of 31 months for safety (adverse events, glandular size via ultrasound and saliva production. Results: Throughout the 31-month monitoring period, no safety events such as infection or severe adverse events were reported. The patient demonstrated an increase in gland size as measured by ultrasound which corresponded to increased saliva production. Conclusion: Overall, the patient reported improved quality of life and willingness to continue treatments. The strong safety profile and preliminary efficacy results warrant larger studies to determine

Treatment Results of Corneal Collagen Cross-Linking Combined with Riboflavin and 440 Nm Blue Light for Bacterial Corneal Ulcer in Rabbits.

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Wei, Shufang; Zhang, Cuiying; Zhang, Shaoru; Xu, Yanyun; Mu, Guoying

2017-10-01

To study the treatment effect of corneal collagen cross-linking (CXL) combined with 440 nm blue light and riboflavin on bacterial corneal ulcer using animal experiments. A total of 21 New Zealand white rabbits that developed Staphylococcus aureus corneal ulcer were randomly divided into three groups. Seven rabbits were used as blank control groups; seven rabbits were treated with CXL combined with riboflavin and 440 nm blue light; and seven rabbits were treated with CXL combined with riboflavin and 370 nm ultraviolet A light. Necrotic tissues or secretions from the ulcer surface, eye secretions, conjunctival hyperemia, hypopyon, corneal infiltration, and pathological changes of the cornea were all observed. The 1st, 3th, and 7th day after CXL treatment, a statistically significant difference was found among the inflammation scores of the three groups. The scores of 440 and 370 groups decreased gradually, significantly lower than that of the control group. Bacterial cultures of 440 and 370 groups turned to be negative while that of the control group remained positive. After 1 day of CXL treatment, pathology pictures of the three groups all showed loss of corneal epithelia with many inflammatory cells in deep stroma. After 7 days of CXL treatment, abscess formed in almost all corneal area in the control group, while in 440 and 370 groups, multilayer healing of corneal epithelia, neovascularization, and many inflammatory cells within ulcers and proliferation of a small amount of fibroblast were seen. CXL combined with riboflavin and 440 nm blue light is effective in treating S. aureus corneal ulcer.

Extrauterine Low-Grade Endometrial Stromal Sarcoma

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Yu-Ju Chen

2005-12-01

Conclusions: Low-grade endometrial stromal sarcoma typically has an indolent clinical course and favorable prognosis. Surgical resection is the primary therapeutic approach, and adjuvant therapy with radiotherapy, chemotherapy, or progesterone therapy should be considered for the management of residual or recurrent low-grade endometrial stromal sarcomas.

Clinical Validation of Point-Source Corneal Topography in Keratoplasty

NARCIS (Netherlands)

Vrijling, A C L; Braaf, B.; Snellenburg, J.J.; de Lange, F.; Zaal, M.J.W.; van der Heijde, G.L.; Sicam, V.A.D.P.

2011-01-01

Purpose. To validate the clinical performance of point-source corneal topography (PCT) in postpenetrating keratoplasty (PKP) eyes and to compare it with conventional Placido-based topography. Methods. Corneal elevation maps of the anterior corneal surface were obtained from 20 post-PKP corneas using

Corneal donations in South Africa: A 15-year review.

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York, Nicholas J; Tinley, Christopher

2017-07-28

Corneal pathology is one of the leading causes of preventable blindness in South Africa (SA). A corneal transplant can restore or significantly improve vision in most cases. However, in SA there is a gross shortage of corneal tissue available to ophthalmologists. Little has been published describing the magnitude of the problem. To describe trends in the number of corneal donors per year in SA, the number of corneal transplants performed each year, the origin of donors, the allocation of corneas to the public or private sector, and the demographics of donors. This was a retrospective review of all corneal donations to SA eye banks over the 15-year period 1 January 2002 - 31 December 2016. There was a progressive year-on-year decline in corneal donors over the study period, from 565 per year in 2002 to 89 in 2016. As a direct result, there has been an 85.5% decrease in the number of corneal transplants performed per year using locally donated corneas, from 1 049 in 2002 to 152 in 2016. Of the donors, 48.8% originated from mortuaries, 39.0% from private hospitals and 12.2% from government hospitals; donors from mortuaries showed the most significant decline over the 15-year period, decreasing by 94.8%. Of donated corneas, 79.3% were allocated to the private sector and 21.7% to the public sector. Males comprised 69.1% of donors, while 77.2% were white, 14.0% coloured, 6.3% black and 2.5% Indian/Asian. Donor age demonstrated a bimodal peak at 25 and 55 years. The number of corneal donations in SA has declined markedly, causing the burden of corneal disease requiring transplantation to rise steadily. Population groups with a low donor rate may have cultural and other objections to corneal donation, which should be a major focus of future research and initiatives aimed at reversing the current trends.

Effect of Cycloplegia on Corneal Biometrics and Refractive State.

Science.gov (United States)

Bagheri, Abbas; Feizi, Mohadeseh; Shafii, Aliakbar; Faramarzi, Amir; Tavakoli, Mehdi; Yazdani, Shahin

2018-01-01

To determine changes in refractive state and corneal parameters after cycloplegia with cyclopentolate hydrochloride 1% using a dual Scheimpflug imaging system. In this prospective cross-sectional study patients aged 10 to 40 years who were referred for optometric evaluation enrolled and underwent autorefraction and corneal imaging with the Galilei dual Scheimpflug system before and 30 minutes after twice instillation of medication. Changes in refraction and astigmatism were investigated. Corneal biometrics including anterior and posterior corneal curvatures, total corneal power and corneal pachymetry were compared before and after cycloplegia. Two hundred and twelve eyes of 106 subjects with mean age of 28 ± 5 years including 201 myopic and 11 hyperopic eyes were evaluated. Mean spherical equivalent refractive error before cycloplegia was -3.4 ± 2.6 D. A mean hyperopic shift of 0.4 ± 0.5 D occurred after cycloplegia ( P biometrics should be considered before cataract and refractive surgeries.

Surgically induced astigmatism after phacoemulsification by temporal clear corneal and superior clear corneal approach: a comparison

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Nikose AS

2018-01-01

Full Text Available Archana Sunil Nikose, Dhrubojyoti Saha, Pradnya Mukesh Laddha, Mayuri Patil Department of Ophthalmology, N.K.P. Salve Institute and LMH, Nagpur, Maharashtra, India Introduction: Cataract surgery has undergone various advances since it was evolved from ancient couching to the modern phacoemulsification cataract surgery. Surgically induced astigmatism (SIA remains one of the most common complications. The introduction of sutureless clear corneal incision has gained increasing popularity worldwide because it offers several advantages over the traditional sutured limbal incision and scleral tunnel. A clear corneal incision has the benefit of being bloodless and having an easy approach, but SIA is still a concern.Purpose: In this study, we evaluated the SIA in clear corneal incisions with temporal approach and superior approach phacoemulsification. Comparisons between the two incisions were done using keratometric readings of preoperative and postoperative refractive status.Methodology: It was a hospital-based prospective interventional comparative randomized control trial of 261 patients conducted in a rural-based tertiary care center from September 2012 to August 2014. The visual acuity and detailed anterior segment and posterior segment examinations were done and the cataract was graded according to Lens Opacification Classification System II. Patients were divided for phacoemulsification into two groups, group A and group B, who underwent temporal and superior clear corneal approach, respectively. The patients were followed up on day 1, 7, 30, and 90 postoperatively. The parameters recorded were uncorrected visual acuity, best-corrected visual acuity, slit lamp examination, and keratometry. The mean difference of SIA between 30th and 90th day was statistically evaluated using paired t-test, and all the analyses were performed using SPSS 18.0 (SPSS Inc. software.Results: The mean postoperative SIA in group A was 0.998 D on the 30th day, which

Sclerosing Stromal Tumor of Ovary: A Case Report

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Menka Khanna

2012-01-01

Full Text Available Sclerosing stromal tumor (SST is an extremely rare and distinctive sex cord stromal tumor which occurs predominantly in the second and third decades of life. We report a case of a 32-year-old woman who developed a sclerosing stromal tumor of ovary and presented with irregular menstruation and pelvic pain. Her hormonal status was normal but CA-125 was raised. She was suspected to have a malignant tumor on computed tomography and underwent bilateral salpingo-oopherectomy. It is therefore necessary to keep in mind the possibility of sclerosing stromal tumor in a young woman.

Depósitos corneales de ciprofloxacino Corneal deposits of ciprofloxacin

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Taimi Cárdenas Díaz

2010-01-01

Full Text Available Las fluoroquinolonas son ampliamente utilizadas para el tratamiento de infecciones oculares bacterianas, ya que tienen actividad tanto para grampositivos, como para gramnegativos. Son fármacos seguros, pero se han descrito depósitos blancos cristalinianos en pacientes con administración frecuente y prolongada;en la mayoría de los casos, ellos resuelven de forma lenta al interrumpir el tratamiento. Si esto no ocurre, los depósitos se deben desbridar. Se ilustran 3 casos operados de catarata que llevaron tratamiento con ciprofloxacino en el posoperatorio, en los cuales se presentaron depósitos corneales y aunque disminuyó la agudeza visual, esta se recuperó después de la queratectomía.Fluoroquinolones are broadly used for the treatment of bacterial ocular infections, since they can act upon both grampositive and gramnegative bacteria. They are safe drugs, but white corneal deposits have been described in patients who frequently take this drug for a long period of time. In most of the cases, the deposits disappear slowly after the treatment is interrupted. If this does not happen, the deposits should be eliminated. Three cases operated on from cataract were presented, who had been taken ciprofloxacin in the postoperative stage and had corneal deposits. Although their visual acuity decreased, it recovered after keratectomy.

Effects of administration of adipose-derived stromal vascular fraction and platelet-rich plasma to dogs with osteoarthritis of the hip joints.

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Upchurch, David A; Renberg, Walter C; Roush, James K; Milliken, George A; Weiss, Mark L

2016-09-01

OBJECTIVE To evaluate effects of simultaneous intra-articular and IV injection of autologous adipose-derived stromal vascular fraction (SVF) and platelet-rich plasma (PRP) to dogs with osteoarthritis of the hip joints. ANIMALS 22 client-owned dogs (12 placebo-treated [control] dogs and 10 treated dogs). PROCEDURES Dogs with osteoarthritis of the hip joints that caused signs of lameness or discomfort were characterized on the basis of results of orthopedic examination, goniometry, lameness score, the Canine Brief Pain Inventory (CBPI), a visual analogue scale, and results obtained by use of a pressure-sensing walkway at week 0 (baseline). Dogs received a simultaneous intraarticular and IV injection of SVF and PRP or a placebo. Dogs were examined again 4, 8, 12, and 24 weeks after injection. RESULTS CBPI scores were significantly lower for the treatment group at week 24, compared with scores for the control group. Mean visual analogue scale score for the treatment group was significantly higher at week 0 than at weeks 4, 8, or 24. Dogs with baseline peak vertical force (PVF) in the lowest 25th percentile were compared, and the treatment group had a significantly higher PVF than did the control group. After the SVF-PRP injection, fewer dogs in the treated group than in the control group had lameness confirmed during examination. CONCLUSIONS AND CLINICAL RELEVANCE For dogs with osteoarthritis of the hip joints treated with SVF and PRP, improvements in CBPI and PVF were evident at some time points, compared with results for the control group.

In vitro assessment of cytotoxicity and labeling efficiency of {sup 99m}Tc-HMPAO with stromal vascular fraction of adipose tissue

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Verma, V. K.; Beevi, S. S. [Department of Transplant Biology, Immunology and Stem Cell Lab, Global Hospitals, Hyderabad (India); Tabassum, A.; Kumaresan, K. [KK Nuclear Scans, Raj Bhavan Road, Somajiguda, Hyderabad (India); Kamaraju, R. S. [Department of Transplant Biology, Immunology and Stem Cell Lab, Global Hospitals, Hyderabad (India); Arbab, A. S. [Cancer Centre, GA Regents University, Augusta, GA (United States); Chelluri, L.K., E-mail: lkiran@globalhospitalsindia.com [Department of Transplant Biology, Immunology and Stem Cell Lab, Global Hospitals, Hyderabad (India)

2014-10-15

Introduction: Noninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime ({sup 99m}Tc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of {sup 99m}Tc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy. Methods: Ten million cells of SVF were labeled with {sup 99m}Tc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of {sup 99m}Tc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H{sub 2}DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1. Results: An encouraging labeling efficiency of 33% was observed with {sup 99m}Tc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays. Conclusion: {sup 99m}Tc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with {sup 99m}Tc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy.

Combined therapy for critical limb ischemia: biomimetic PLGA microcarriers potentiates the pro-angiogenic effect of adipose tissue stromal vascular fraction cells.

Science.gov (United States)

Hoareau, Laurence; Fouchet, Florian; Planesse, Cynthia; Mirbeau, Sophie; Sindji, Laurence; Delay, Emmanuel; Roche, Régis; Montero-Menei, Claudia N; Festy, Franck

2018-04-14

We propose a regenerative solution in the treatment of critical limb ischemia. Poly-lactic/glycolic acid (PLGA) microcarriers were prepared and coated with laminin to be sterilized through γ-irradiation of 25 kGy at low temperature. Stromal vascular fraction (SVF) cells were extracted through enzymatic digestion of adipose tissue. Streptozotocin-induced diabetic mice underwent arteriotomy and received an administration of SVF cells combined or not with biomimetic microcarriers. Functional evaluation of the ischemic limb was then reported and tissue reperfusion was evaluated through fluorescence molecular tomography (FMT). Microcarriers were stable and functional after γ-irradiation until at least 12 months storage. Mice which received an injection of SVF cells in the ischemic limb have 22 % of supplementary blood supply within this limb 7 days after surgery compared to vehicle, whereas no difference was observed at day 14. With the combined therapy, the improvement of blood flow is significantly higher compared to vehicle, of about 31 % at day 7 and of about 11 % at day 14. Injection of SVF cells induces a significant 27 % decrease of necrosis compared to vehicle. This effect is more important when SVF cells were mixed with biomimetic microcarriers: - 37% compared to control. Although SVF cells injection leads to a non-significant 22 % proprioception recovery, the combined therapy induces a significant recovery of about 27 % compared to vehicle. We show that the combination of SVF cells from adipose tissue with laminin-coated PLGA microcarriers is efficient for CLI therapy in a diabetic mouse model. This article is protected by copyright. All rights reserved.

Gastrointestinal Stromal Tumors: A Case Report

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Palankezhe Sashidharan

2014-03-01

Full Text Available Advances in the identification of gastrointestinal stromal tumors, its molecular and immunohiostochemical basis, and its management have been a watershed in the treatment of gastrointestinal tumors. This paradigm shift occurred over the last two decades and gastrointestinal stromal tumors have now come to be understood as rare gastrointestinal tract tumors with predictable behavior and outcome, replacing the older terminologies like leiomyoma, schwannoma or leiomyosarcoma. This report presents a case of gastric gastrointestinal stromal tumor operated recently in a 47-year-old female patient and the outcome, as well as literature review of the pathological identification, sites of origin, and factors predicting its behavior, prognosis and treatment.

Effects of two different incision phacoemulsification on corneal astigmatism

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Lu Huo

2014-12-01

Full Text Available AIM:To compare the effect of different incision in corneal astigmatism after phacoemulsification. METHODS: Totally 88 cases(122 eyeswith pure cataract were randomly divided into two groups. Forty cases(60 eyeswere clarity corneal incision in group A, and 48 cases(62 eyeswere sclera tunnel incision in group B. Mean corneal astigmatism, surgically induced astigmatism(SIA, uncorrected visual acuity(UCVAand best correct vision acuity(BCVAwere observed in pre- and post-operation at 1d; 1wk; 1mo.RESULTS: The mean astigmatism had statistically significant difference between two groups at 1d; 1wk; 1mo after operation(PPP>0.05. UCVA≥0.5 and BCVA≥0.8 had statistically significant difference at 1d; 1wk(PP>0.05.CONCLUSION: Phacoemulsification with scleral tunnel incision remove combined intraocular lens(IOLimplantation has small changes to corneal astigmatism. By selecting personalized corneal incision according to the corneal topography might be more beneficial.

Do Unilateral Herpetic Stromal Keratitis and Neurotrophic Ulcers Cause Bilateral Dry Eye?

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Jabbarvand, Mahmoud; Hashemian, Hesam; Khodaparast, Mehdi; Rafatnejad, Amin; Beheshtnejad, Amirhooshang; Salami, Amir

2015-07-01

To evaluate and compare the ocular surface condition in herpetic interstitial stromal keratitis and neurotrophic ulcer groups and their normal fellow eyes. In this observational, cross-sectional case-control study, 85 consecutive patients were included, including 56 cases of treated herpetic interstitial keratitis and 29 patients with neurotrophic ulcers. Fifty-six age- and sex-matched participants were also recruited from a normal population as the control group. We evaluated and scored the subjective and objective measures of dry eye for both eyes of all patients. Then, we compared the score of the groups with one another and also with the control group. The main outcome measures were the discomfort level, visual symptoms of dry eye, conjunctival injection, conjunctival staining, corneal staining, corneal tear signs of dry eye, meibomian gland dysfunction, tear break-up time, Schirmer test score with anesthesia, and tear osmolarity. The normal fellow eye of the herpetic keratitis group had significantly higher discomfort levels (1.4 ± 0.9 vs. 1.3 ± 0.5, P = 0.003), visual symptoms (1.7 ± 0.8 vs. 1.3 ± 0.7, P = 0.002), tear break-up time (8.3 ± 3.2 vs. 12.1 ± 3.3 seconds, P = 0.003), Schirmer test scores (9.2 ± 3.9 vs. 12.9 ± 3 mm, P = 0.04), and tear osmolarity (9.2 ± 3.9 vs. 12.9 ± 3 mm, P = 0.003) in comparison with normal controls. The normal fellow eyes of the neurotrophic ulcer group had significantly worse values for discomfort level (1.9 ± 0.9 vs. 1.3 ± 0.5, P eyes of patients with neurotrophic ulcer and interstitial herpetic keratitis have a significantly poorer ocular surface condition compared with that of normal controls.

Modulation of hemopoiesis by novel stromal cell factors

International Nuclear Information System (INIS)

Zipori, D.

1988-01-01

The microenvironment of the bone marrow in mammals is a crucial site for the maintenance of a pluripotent hemopoietic stem cell pool. Our previous studies and present findings support the notion that both this function and the fine architecture of hemopoietic organs, i.e., the spatial arrangement of blood cells within the tissue, may be directed by stromal cells. Despite the ability of cloned stromal cells to support prolonged hempoiesis and maintenance in vitro of stem cells with high radioprotective ability, they are a poor source of colony stimulating factor-1 (CSF-1) and do not secrete the other species of CSF. Furthermore, cultured stromal cells antagonize the activity of CSF. It is proposed that stromal cell factors distinct from known CSFs, regulate stem cell renewal. An additional phenomenon that is mediated by stromal cells and can not be attributed to CSF, is their ability to specifically inhibit the accumulation of cells of particular lineage and stage of differentiation. A glycoprotein that inhibits the growth of plasmacytomas but not a variety of other cell types was isolated from one type of cloned stromal cells. Such specific inhibitors may account for the control of cell localization in the hemopoietic system

Metanephric stromal tumor: A novel pediatric renal neoplasm

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Rajalakshmi V

2009-07-01

Full Text Available Metanephric stromal tumor of kidney is a novel pediatric benign stromal specific renal neoplasm. A few cases have been reported in adults also. This tumor is usually centered in the renal medulla with a characteristic microscopic appearance which differentiates this lesion from congenital mesoblastic nephroma and clear cell sarcoma of the kidney. In most cases complete excision alone is curative. The differentiation of metanephric stromal tumor from clear cell sarcoma of the kidney will spare the child from the ill effects of adjuvant chemotherapy. In this communication we describe the gross and microscopic features of metanephric stromal tumor in a one-month-old child with good prognosis.

Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

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Recavarren, Rosemary A; Chivukula, Mamatha; Carter, Gloria; Dabbs, David J

2009-10-10

The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.

Effects of genipin corneal crosslinking in rabbit corneas.

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Avila, Marcel Y; Narvaez, Mauricio; Castañeda, Juan P

2016-07-01

To evaluate the effect of genipin, a natural crosslinking agent, in rabbit eyes. Department of Ophthalmology, Universidad Nacional de Colombia Centro de Tecnologia Oftalmica, Bogotá, Colombia. Experimental study. Ex vivo rabbit eyes (16; 8 rabbits) were treated with genipin 1.00%, 0.50%, and 0.25% for 5 minutes with a vacuum device to increase corneal permeability. Penetration was evaluated using Scheimpflug pachymetry (Pentacam). In the in vivo model (20 rabbits; 1 eye treated, 1 eye with vehicle), corneas were crosslinked with genipin as described. Corneal curvature, corneal pachymetry, and intraocular pressure (IOP) assessments as well as slitlamp examinations were performed 0, 7, 30, and 60 days after treatment. In the ex vivo model, Scheimpflug pachymetry showed deep penetration in the rabbit corneas with an increase in corneal density and a dose-dependent relationship. Corneal flattening was observed in treated eyes (mean 4.4 diopters ± 0.5 [SD]) compared with the control eyes. Pachymetry and IOP were stable in all evaluations. No eye showed toxicity in the anterior chamber or in the lens. Corneal crosslinking induced by genipin produced significant flattening of the cornea with no toxicity in rabbit eyes. This crosslinking could be useful in the treatment of corneal ectasia and in the modification of corneal curvature. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Airbag induced corneal ectasia.

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Mearza, Ali A; Koufaki, Fedra N; Aslanides, Ioannis M

2008-02-01

To report a case of airbag induced corneal ectasia. Case report. A patient 3 years post-LASIK developed bilateral corneal ectasia worse in the right eye following airbag deployment in a road traffic accident. At last follow up, best corrected vision was 20/40 with -4.00/-4.00 x 25 in the right eye and 20/25 with -1.25/-0.50 x 135 in the left eye. This is a rare presentation of trauma induced ectasia in a patient post-LASIK. It is possible that reduction in biomechanical integrity of the cornea from prior refractive surgery contributed to this presentation.

Changes in corneal endothelial cell density and the cumulative risk of corneal decompensation after Ahmed glaucoma valve implantation.

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Kim, Kyoung Nam; Lee, Sung Bok; Lee, Yeon Hee; Lee, Jong Joo; Lim, Hyung Bin; Kim, Chang-Sik

2016-07-01

To evaluate changes in the corneal endothelial cell density (ECD) and corneal decompensation following Ahmed glaucoma valve (AGV) implantation. This study was retrospective and observational case series. Patients with refractory glaucoma who underwent AGV implantation and were followed >5 years were consecutively enrolled. We reviewed the medical records, including the results of central corneal specular microscopy. Of the 127 enrolled patients, the annual change in ECD (%) was determined using linear regression for 72 eyes evaluated at least four times using serial specular microscopic examination and compared with 31 control eyes (fellow glaucomatous eyes under medical treatment). The main outcome measures were cumulative risk of corneal decompensation and differences in the ECD loss rates between subjects and controls. The mean follow-up after AGV implantation was 43.1 months. There were no cases of postoperative tube-corneal touch. The cumulative risk of corneal decompensation was 3.3%, 5 years after AGV implantation. There was a more rapid loss of ECD in the 72 subject eyes compared with the 31 controls (-7.0% and -0.1%/year, respectively; p<0.001). However, the rate of loss decreased over time and statistical significance compared with control eyes disappeared after 2 years postoperatively: -10.7% from baseline to 1 year (p<0.01), -7.0% from 1 year to 2 years (p=0.037), -4.2% from 2 years to 3 years (p=0.230) and -2.7% from 3 years to the final follow-up (p=0.111). In case of uncomplicated AGV implantation, the cumulative risk of corneal decompensation was 3.3%, 5 years after the operation. The ECD loss was statistically greater in eyes with AGV than in control eyes without AGV, but the difference was significant only up to 2 years post surgery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

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Philipp Steven

Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

The application of PET-CT in gastrointestinal stromal tumor

International Nuclear Information System (INIS)

Xian Weijun; Feng Yanlin

2009-01-01

Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm of uncertain malignant potential that arises predominantly in the gastrointestinal tract. Due to lack of specific physical signs, imagin g-x examination is an important auxiliary means in diagnosing gastrointestinal stromal tumor. Compared to other conventional imaging examinations, PET-CT has demonstrated unique superiority in staging, response evaluation and follow-up of gastrointestinal stromal tumor. And now it presents an overview of the application valuation of PET-CT and related imaging technology in gastrointestinal stromal tumor as follow. (authors)

Corneal manifestations in systemic diseases

OpenAIRE

Zarranz-Ventura, J.; Nova, E. De; Moreno-Montañés, J.

2008-01-01

Un gran número de enfermedades sistémicas presentan manifestaciones corneales dentro de su espectro de enfermedad. El estudio detallado de todos los cuadros que asocian patología corneal resulta inabarcable, por ello se presentan las enfermedades más prevalentes o características. Este estudio contempla las enfermedades pulmonares y conectivopatías (colagenosis, enfermedades reumatológicas y enfermedades inflamatorias idiopáticas), las enfermedades dermatológicas, cardiovasculares, hematológi...

Assessment of ovarian stromal blood flow after metformin treatment in women with polycystic ovary syndrome.

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Makled, Ahmed K; El Sherbiny, Mohamed; Elkabarity, Rania

2014-04-01

To authenticate the effect of metformin treatment on ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS) using 3-dimensional (3D) power Doppler. The current case-control study was conducted at Ain Shams University Maternity Hospital. A total of 60 women diagnosed to have PCOS were included as group 1. Another 40 fertile women who were recruited from outpatient clinic for contraception without PCOS with regular menstrual cycles were included as control group (group 2). All women underwent 3D power Doppler evaluations of ovarian stroma. Anthropometric, hormonal and biochemical criteria were also measured. All women in group 1 received metformin hydrochloride 500 mg tablets, which were started in a step-up maneuver every 5 days, from one to three tablets per day. The same parameters were also measured after the 3 months duration of treatment. A total of 100 women were finally analyzed. At the start of the study, there were no statistically significant differences between group 1 and group 2 and regarding age and body mass index, but the waist/hip ratio and Ferriman-Gallwey scoring were statistically different between the 2 groups. The mean ovarian volume and stromal volume were significantly larger in group 1. 3D power Doppler indices [the vascularization index (VI), the flow index (FI) and the (VFI) vascularization-flow index] were much higher in group 1 than in group 2 (1.38 ± 0.76 vs. 4.69 ± 1.37, P treatment significantly reduce VI, FI and VFI (4.69 ± 1.37 vs. 2.95 ± 1.52, P < 0.05, 32.66 ± 4.37 vs. 29.48 ± 4.98, P < 0.05 and 1.54 ± 0.69 vs. 1.21 ± 0.7 P < 0.05, respectively). Using Receiver operator characteristic, there was no cut-off value of VI, FI or VFI to detect ovulation in women of PCOS. Metformin seems to have a beneficial effect in normal weight PCO women via correcting ovarian stromal blood flow and hormonal profiles.

Spontaneous Healing of Corneal Perforation after Temporary Discontinuation of Erlotinib Treatment

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Naoyuki Morishige

2014-01-01

Full Text Available Purpose: To report a case of corneal perforation associated with oral administration of erlotinib and its spontaneous healing after temporary discontinuation of drug treatment. Case Report: A 65-year-old man with metastatic lung cancer was treated with erlotinib (150 mg/day, a specific tyrosine kinase inhibitor of the epidermal growth factor receptor. He was referred to our corneal service for the treatment of bilateral corneal disorders, diagnosed with mild aqueous-deficient dry eye, and treated by insertion of punctal plugs. His corneal epithelial disorders initially improved, but subsequently worsened, as manifested by the development of bilateral corneal ulceration with corneal perforation in the right eye. The oral administration of erlotinib was interrupted in preparation for tectonic keratoplasty, but 2 days later the corneal perforation of the right eye and the bilateral epithelial defects had healed spontaneously. Treatment with erlotinib was resumed at half the initial dose, and the cornea of both eyes has remained apparently healthy. Discussion: Erlotinib may be secreted into tear fluid and thereby adversely affect the corneal epithelium. The development of corneal epithelial disorders in patients receiving this drug may be reversed by reducing its dose.

Mouse endometrial stromal cells produce basement-membrane components

DEFF Research Database (Denmark)

Wewer, U M; Damjanov, A; Weiss, J

1986-01-01

During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations. The dec......During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations....... Mouse decidual cells isolated from 6- to 7-day pregnant uteri explanted in vitro continue to synthesize basement-membrane-like extracellular matrix. Using immunohistochemistry and metabolic labeling followed by immunoprecipitation, SDS-PAGE, and fluorography, it was shown that the decidual cells...... to undergo pseudodecidualization. We thus showed that stromal cells from pregnant and nonpregnant mouse uteri synthesize significant amounts of basement-membrane components in vitro, and hence could serve as a good model for the study of normal basement-membrane components....

An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model

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Uchiyama, Masaaki; Masuda, Yukinari; Nagasaka, Shinya; Fukuda, Yuh; Takahashi, Hiroshi

2013-01-01

Purpose We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. Methods After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. Results After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. Conclusions The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing. PMID:24194635

Impact of Facial Conformation on Canine Health: Corneal Ulceration

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Packer, Rowena M. A.; Hendricks, Anke; Burn, Charlotte C.

2015-01-01

Concern has arisen in recent years that selection for extreme facial morphology in the domestic dog may be leading to an increased frequency of eye disorders. Corneal ulcers are a common and painful eye problem in domestic dogs that can lead to scarring and/or perforation of the cornea, potentially causing blindness. Exaggerated juvenile-like craniofacial conformations and wide eyes have been suspected as risk factors for corneal ulceration. This study aimed to quantify the relationship between corneal ulceration risk and conformational factors including relative eyelid aperture width, brachycephalic (short-muzzled) skull shape, the presence of a nasal fold (wrinkle), and exposed eye-white. A 14 month cross-sectional study of dogs entering a large UK based small animal referral hospital for both corneal ulcers and unrelated disorders was carried out. Dogs were classed as affected if they were diagnosed with a corneal ulcer using fluorescein dye while at the hospital (whether referred for this disorder or not), or if a previous diagnosis of corneal ulcer(s) was documented in the dogs’ histories. Of 700 dogs recruited, measured and clinically examined, 31 were affected by corneal ulcers. Most cases were male (71%), small breed dogs (mean± SE weight: 11.4±1.1 kg), with the most commonly diagnosed breed being the Pug. Dogs with nasal folds were nearly five times more likely to be affected by corneal ulcers than those without, and brachycephalic dogs (craniofacial ratio dogs. A 10% increase in relative eyelid aperture width more than tripled the ulcer risk. Exposed eye-white was associated with a nearly three times increased risk. The results demonstrate that artificially selecting for these facial characteristics greatly heightens the risk of corneal ulcers, and such selection should thus be discouraged to improve canine welfare. PMID:25969983

Study on phototherapeutic keratotomy for bacterial corneal lesions in rabbit

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Xin Zhou

2018-05-01

Full Text Available AIM: To study the effect of phototherapeutic keratectomy(PTKon rabbit bacterial corneal ulcer model and explore the clinical potential of this method. METHODS: Totally 48 eyes from all the 24 New Zealand rabbits were inoculated with Staphylococcus aureus and bacterial corneal ulcer model was established successfully. At 1d after inoculation, 48 eyes were given levofloxacin eye drops when corneal ulcer was confirmed. Then slit lamp inspection and optical coherence tomography(OCTwere performed to measure the central corneal ulcer depth. All the rabbits right eyes were treated with PTK, as an observation group, left eyes were not treated as a control group. The eye section were observed by slit lamp and central thickness of corneal ulcer was measured by OCT at 3 and 7d after this operation. Rabbits were sacrificed and the cornea was removed for pathological section 7d later. RESULTS: The corneal ulcers in both groups had a tendency to heal, showing a decrease in ulcer area and smoothness of the surface. There was no significant difference in the depth of corneal ulcer between the observation group and the control group before PTK(t=0.706, P=0.484. The difference between the two groups of eyes at 3 and 7d after PTK was obviously(PCONCLUSION: PTK can effectively cure rabbit Staphylococcus aureus corneal ulcer and promote ulcer wound healing, which may be used for clinical treatment of patients with bacterial corneal lesions.

Crosslinking and corneal cryotherapy in acanthamoeba keratitis -- a histological study.

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Hager, Tobias; Hasenfus, A; Stachon, T; Seitz, B; Szentmáry, N

2016-01-01

Acanthamoeba keratitis is rare, but difficult to treat. Penetrating keratoplasty is performed in therapy-resistant cases. Nevertheless, subsequent recurrences occur in 40 % of the cases. In addition to triple-topical therapy (polyhexamid, propamidinisoethionat, neomycin), treatment alternatives are corneal cryotherapy and/or crosslinking (CXL). The aim of our present histological study was to analyze the persistence of acanthamoebatrophozoites and cysts, the persistence of bacteria, and activation of keratocytes in corneas of acanthamoeba keratitis patients following corneal cryotherapy and/or CXL. We analyzed histologically corneal buttons (from penetrating keratoplasties) of nine patients with acanthamoeba keratitis, following corneal cryotherapy (two patients) or a combination of crosslinking and corneal cryotherapy (seven patients), using haematoxilin–eosin, periodic acid Schiff (PAS), Gram and alpha-smooth muscle actin (alpha-SMA) stainings. Acanthamoeba trophozoites persisted in three corneas after cryotherapy and CXL. Cysts persisted in one of two corneas following corneal cryotherapy and in six of seven corneas after a combination of CXL and cryotherapy. One cornea showed positive Gram staining, but there were no alpha-SMA positive keratocytes in any of the corneas. Crosslinking and corneal cryotherapy have only limited impact on killing of acanthamoeba trophozoites, cysts, or bacteria. Corneal cryotherapy and CXL did not stimulate myofibroblastic transformation of keratocytes.

Corneal topography

DEFF Research Database (Denmark)

Andersen, J.; Koch-Jensen, P.; Østerby, Ole

1993-01-01

The central corneal zone is depicted on keratoscope photographs using a small target aperture and a large object distance. Information on the peripheral area is included by employing a hemispherical target with a dense circular and radial pattern. On a 16 mm (R = 8 mm) reference steel sphere the ...

Prevalence and associated factors of corneal blindness in Ningxia in northwest China

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Xun-Lun Sheng

2014-06-01

Full Text Available AIM:To describe the prevalence and demographic characteristics of corneal blindness in an urban and rural region of Ningxia, located in the northwest part of China.METHODS:A stratified, randomized sampling procedure was employed in the study, including urban and rural area of all age group. Visual acuity, anterior segment and ocular fundus were checked. Related factor of corneal disease, including age, gender, education status, ethnic group, location and occupation, were identified according to uniform customized protocol. An eye was defined to be corneal blindness if the visual acuity was <20/400 due to a corneal disease.RESULTS:Three thousand individuals (1290 from urban area and 1710 from rural area participated in the investigation, with a response rate of 80.380%. The prevalence of corneal blindness was 0.023% in both eyes and 0.733% in at least one eye. The blindness in at least one eye with varied causes was present in 106 participants (3.533% and in bilateral eyes in 34 participants (1.133%. The corneal diseases accounted for 20.754% of blindness in at least one eye and 20.588% of bilateral blindness. The prevalence of corneal disease was higher in older and Han ethnic group, especially those who occupied in agriculture and outdoor work. People with corneal blindness were more likely to be older and lower education. Rural population were more likely to suffer from bilateral corneal blindness than the urban population in ≥59-year group (χ2=6.716, P=0.019. Infectious, trauma and immune corneal disease were the three leading causes of corneal disease. Trauma corneal disease was more likely leading to blindness in one eye. However, infectious and immune corneal diseases make more contribution to the bilateral corneal blindness.CONCLUSION: Corneal blindness is a significant burden of in Ningxia population, encompassing a variety of corneal infections and trauma; the majority of those were avoidable. Health promotion strategies and good

The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma.

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Sally Hayes

Full Text Available To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour.One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep and 3 pairs of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits were untreated; Group 2 (24 pig were exposed to UVA light (3.04 mW/cm(2 for 30 minutes and Group 3 (29 pig and Group 4 (31 pig, 3 sheep and 3 rabbits had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm(2. X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques.Corneal thickness decreased significantly following riboflavin application (p<0.01 and also to a lesser extent after UVA exposure (p<0.05. With the exception of the spatial order factor, which was higher in Group 4 than Group 1 (p<0.01, all other measured collagen parameters were unaltered by cross-linking, even within the most anterior 300 microns of the cornea. The cross-linking treatment had no effect on the hydrodynamic behaviour of the cornea but did cause a significant increase in its resistance to enzymatic digestion.It seems likely that cross-links formed during riboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen.

Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

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Li ZR

2012-03-01

Full Text Available Zhanrong Li1, Lin Yao1, Jingguo Li2, Wenxin Zhang1, Xianghua Wu1, Yi Liu1, Miaoli Lin1, Wenru Su1, Yongping Li1, Dan Liang11State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of ChinaPurpose: Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs on corneal neovascularization (CNV and determine the possible mechanism.Methods: To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol-block-poly(ε-caprolactone nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.Results: The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4 showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial

Extragastrointestinal Stromal Tumor during Pregnacy

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Ilay Gözükara

2012-01-01

Full Text Available Extragastrointestinal stromal tumors (EGISTs are mesenchymal neoplasms without connection to the gastrointestinal tract. Gastrointestinal stromal tumors (GISTs and EGIST are similar according to their clinicopathologic and histomorphologic features. Both of them most often express immunoreactivity for CD-117, a c-kit proto-oncogene protein. The coexistence of GIST and pregnancy is very rare, with only two cases reported in the literature. In this paper, we presented the first EGIST case during pregnancy in the literature.

Corneal Biomechanical Properties after FS-LASIK with Residual Bed Thickness Less Than 50% of the Original Corneal Thickness

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Haixia Zhang

2018-01-01

Full Text Available Background. The changes in corneal biomechanical properties after LASIK remain an unknown but important topic for surgical design and prognostic evaluation. This study aims to observe the postoperative corneal biomechanical properties one month after LASIK with amount of corneal cutting (ACC greater than 50% of the central corneal thickness (CCT. Methods. FS-LASIK was performed in 10 left rabbit eyes with ACC being 60% (L60 and 65% (L65 of the CCT, while the right eyes (R were the control. After 4 weeks, rabbits were executed and corneal strip samples were prepared for uniaxial tensile tests. Results. At the same strain, the stresses of L65 and L60 were larger than those of R. The elastic moduli of L60 and L65 were larger than those of R when the stress was 0.02 MPa, while they began to be less than those of R when stress exceeds the low-stress region. After 10 s relaxation, the stress of specimens L65, L60, and R increased in turn. Conclusion. The elastic moduli of the cornea after FS-LASIK with ACC greater than 50% of the CCT do not become less under normal rabbit IOP. The limit stress grows with the rise of ACC when relaxation becomes stable.

Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)

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Lai, Kuo-Pao; Huang, Chiung-Kuei; Fang, Lei-Ya; Izumi, Kouji; Lo, Chi-Wen; Wood, Ronald; Kindblom, Jon; Yeh, Shuyuan

2013-01-01

Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9®, led to the reduction of prostate size, which could be used in future therapy. PMID:23893956

Temporary corneal stem cell dysfunction after radiation therapy

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Hiroshi, Fujishima; Kazuo, Tsubota

1996-01-01

Radiation therapy can cause corneal and conjuctival abnormalities that sometimes require surgical treatment. Corneal stem cell dysfunction is described, which recovered after the cessation of radiation. Methods - A 44-year-old man developed a corneal epithelial abnormality associated with conjuctival and corneal inflammation following radiation therapy for maxillary cancer. Examination of brush cytology samples showed goblet cells in the upper and lower parts of the cornea, which showed increased fluorescein permeability, and intraepithelial lymphocytes. Impression cytology showed goblet cells in the same part of the cornea. Specular microscopy revealed spindle type epithelial cells. Patient follow up included artificial tears and an antibiotic ophthalmic ointment. The corneal abnormalities resolved after 4 months with improved visual acuity without any surgical intervention, but the disappearance of the palisades of Vogt did not recover at 1 year after radiation. Radiation therapy in this patient caused temporary stem cell dysfunction which resulted in conjunctivalisation in a part of the cornea. Although limbal stem cell function did not fully recover, this rare case suggested that medical options should be considered before surgery. (Author)

Effects of Silicone Hydrogel Contact Lens Application on Corneal High-order Aberration and Visual Guality in Patients with Corneal Opacities

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Sevda Aydın Kurna

2012-03-01

Full Text Available Pur po se: Evaluation of the corneal high-order aberrations and visual quality changes after application of silicone hydrogel contact lenses in patients with corneal opacities due to various etiologies. Ma te ri al and Met hod: Fifteen eyes of 13 patients with corneal opacities were included in the study. During the ophthalmologic examination before and after contact lens application, visual acuity was measured with Snellen acuity chart and contrast sensitivity - with Bailey-Lowie Charts in letters. Aberrations were measured with corneal aberrometer (NIDEK Magellan Mapper under a naturally dilated pupil. Spherical aberration, coma, trefoil, irregular astigmatism and total high-order root mean square (RMS values were recorded. Measurements were repeated with balafilcon A lenses (PureVision 2 HD, B&L on all patients. Re sults: Patient age varied between 23 and 50 years. Two eyes had subepithelial infiltrates due to adenoviral keratitis, 1 had nebulae due to previous infections or trauma, and 2 had Salzmann’s nodular degeneration. We observed a mean increase of 1 line in visual acuity and 5 letters in contrast sensitivity with contact lenses versus glasses in the patients. Mean RMS values of spherical aberration, irregular astigmatism and total high-order aberrations decreased significantly with contact lenses. Dis cus si on: Silicone hydrogel soft contact lenses may improve visual quality by decreasing the corneal aberrations in patients with corneal opacities. (Turk J Ophthalmol 2012; 42: 97-102

Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue

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Campioli, Enrico [Research Institute of the McGill University Health Centre (Canada); Department of Medicine, McGill University, Montréal, Québec (Canada); Duong, Tam B. [Research Institute of the McGill University Health Centre (Canada); Deschamps, François [Synthèse AptoChem Inc., Montréal, Québec (Canada); Papadopoulos, Vassilios, E-mail: vassilios.papadopoulos@mcgill.ca [Research Institute of the McGill University Health Centre (Canada); Department of Medicine, McGill University, Montréal, Québec (Canada); Department of Biochemistry, McGill University, Montréal, Québec (Canada); Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec (Canada)

2015-07-15

Plastics are generally mixed with additives like plasticizers to enhance their flexibility, pliability, and elasticity proprieties. Plasticizers are easily released into the environment and are absorbed mainly through ingestion, dermal contact, and inhalation. One of the main classes of plasticizers, phthalates, has been associated with endocrine and reproductive diseases. In 2002, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced in the market for use in plastic materials and articles intended to come into contact with food, and it received final approval from the European Food Safety Authority in 2006. At present, there is limited knowledge about the safety and potential metabolic and endocrine-disrupting properties of DINCH and its metabolites. The purpose of this study was to evaluate the biological effects of DINCH and its active metabolites, cyclohexane-1,2-dicarboxylic acid (CHDA) and cyclohexane-1,2-dicarboxylic acid mono isononyl ester (MINCH), on rat primary stromal vascular fraction (SVF) of adipose tissue. DINCH and its metabolite, CHDA, were not able to directly affect SVF differentiation. However, exposure of SVF to 50 μM and 100 μM concentrations of MINCH affected the expression of Cebpa and Fabp4, thus inducing SVF preadipocytes to accumulate lipids and fully differentiate into mature adipocytes. The effect of MINCH was blocked by the specific peroxisome proliferator-activated receptor (PPAR)-α antagonist, GW6471. Taken together, these results suggest that MINCH is a potent PPAR-α agonist and a metabolic disruptor, capable of inducing SVF preadipocyte differentiation, that may interfere with the endocrine system in mammals. - Highlights: • DINCH and CHDA did not affect the adipogenesis of the SVF. • MINCH affected the adipogenesis of the SVF. • MINCH effect was blocked by the specific PPAR-α antagonist GW6471. • MINCH exerted a similar effect as MEHP on SVF adipogenesis. • DINCH/MINCH are potential metabolic

Altered corneal biomechanical properties in children with osteogenesis imperfecta.

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Lagrou, Lisa M; Gilbert, Jesse; Hannibal, Mark; Caird, Michelle S; Thomas, Inas; Moroi, Sayoko E; Bohnsack, Brenda L

2018-04-07

To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI). A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test. A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P < 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P < 0.001]) and CCT (449.8 ± 30.8 μm vs 568 ± 47.6 μm [P < 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P < 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg). Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies. Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Dextran Preserves Native Corneal Structure During Decellularization.

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Lynch, Amy P; Wilson, Samantha L; Ahearne, Mark

2016-06-01

Corneal decellularization has become an increasingly popular technique for generating scaffolds for corneal regeneration. Most decellularization procedures result in tissue swelling, thus limiting their application. Here, the use of a polysaccharide, dextran, to reduce swelling and conserve the native corneal structure during decellularization was investigated. Corneas were treated with 1% Triton X-100, 0.5% sodium dodecyl sulfate, and nucleases under constant rotation followed by extensive washing. To reduce swelling, decellularization solutions were supplemented with 5% dextran either throughout the whole decellularization process or during the washing cycles only. Quantitative analysis of DNA content showed a 96% reduction after decellularization regardless of the addition of dextran. Dextran resulted in a significant reduction in swelling from 3.85 ± 0.43 nm without to 1.94 ± 0.29-2.01 ± 0.37 nm (p dextran must be present throughout the decellularization protocol to preserve the native corneal architecture, anisotropy analysis demonstrated comparable results (0.22 ± 0.03) to the native cornea (0.24 ± 0.02), p > 0.05. Dextran can counteract the detrimental effects of decellularizing agents on the biomechanical properties of the tissue resulting in similar compressive moduli (mean before decellularization: 5.40 ± 1.18 kPa; mean after decellularization with dextran: 5.64 ± 1.34 kPa, p > 0.05). Cells remained viable in the presence of decellularized scaffolds. The findings of this study indicate that dextran not only prevents significant corneal swelling during decellularization but also enhances the maintenance of the native corneal ultrastructure.

Comparison of the Keratometric Corneal Astigmatic Power after Phacoemulsification: Clear Temporal Corneal Incision versus Superior Scleral Tunnel Incision

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Yongqi He

2009-01-01

Full Text Available Objective. This is prospective randomized control trial to compare the mean keratometric corneal astigmatism diopter power (not surgical induced astigmatism among preop and one-month and three-month postop phacoemulcification of either a clear temporal corneal incision or a superior scleral tunnel Incision, using only keratometric astigmatic power reading to evaluate the difference between the two cataract surgery incisions. Methods. 120 patients (134 eyes underwent phacoemulcification were randomly assigned to two groups: Group A, the clear temporal corneal incision group, and Group B, the superior scleral tunnel incision group. SPSS11.5 Software was used for statistical analysis to compare the postsurgical changes of cornea astigmatism on keratometry. Results. The changes of corneal astigmatic diopter in Groups A and B after 3 month postop from keratometric reading were 1.04 + 0.76 and 0.94 + 0.27, respectively (=.84>.05, which showed no statistic significance difference. Conclusion. The incision through either temporal clear cornea or superior scleral tunnel in phacoemulcification shows no statistic difference in astigmatism change on keratometry 3-month postop.

The influence of perivascular adipose tissue on vascular homeostasis

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Szasz T

2013-03-01

Full Text Available Theodora Szasz,1 Gisele Facholi Bomfim,2 R Clinton Webb1 1Department of Physiology, Georgia Regents University, Augusta, USA; 2Department of Pharmacology, University of São Paulo, São Paulo, Brazil Abstract: The perivascular adipose tissue (PVAT is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT. Keywords: adipokines

Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth.

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Catherine To

Full Text Available Eph and ephrin proteins are essential cell guidance cues that orchestrate cell navigation and control cell-cell interactions during developmental tissue patterning, organogenesis and vasculogenesis. They have been extensively studied in animal models of embryogenesis and adult tissue regeneration, but less is known about their expression and function during human tissue and organ regeneration. We discovered the hypoxia inducible factor (HIF-1α-controlled expression of EphA3, an Eph family member with critical functions during human tumour progression, in the vascularised tissue of regenerating human endometrium and on isolated human endometrial multipotent mesenchymal stromal cells (eMSCs, but not in other highly vascularised human organs. EphA3 affinity-isolation from human biopsy tissue yielded multipotent CD29+/CD73+/CD90+/CD146+ eMSCs that can be clonally propagated and respond to EphA3 agonists with EphA3 phosphorylation, cell contraction, cell-cell segregation and directed cell migration. EphA3 silencing significantly inhibited the ability of transplanted eMSCs to support neovascularisation in immunocompromised mice. In accord with established roles of Eph receptors in mediating interactions between endothelial and perivascular stromal cells during mouse development, our findings suggest that HIF-1α-controlled expression of EphA3 on human MSCs functions during the hypoxia-initiated early stages of adult blood vessel formation.

Analysis of corneal topography in patients with pure microphthalmia in Eastern China.

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Hu, Pei-Hong; Gao, Gui-Ping; Yu, Yao; Pei, Chong-Gang; Zhou, Qiong; Huang, Xin; Zhang, Ying; Shao, Yi

2015-12-01

To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia. © The Author(s) 2015.

Hemangioblastomas: histogenesis of the stromal cell studied by immunocytochemistry.

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Jurco, S; Nadji, M; Harvey, D G; Parker, J C; Font, R L; Morales, A R

1982-01-01

Twenty-one cases of hemangioblastoma from the cerebellum, spinal cord and retina were studied using the unlabeled antibody peroxidase-antiperoxidase technique with antibodies directed against glial fibrillary acidic protein (GFAP) and factor VIII related antigen (VIIIR:Ag). In 19 of 21 cases studied with anti-GFAP, astrocytes were identified peripherally, and in 13 cases they were found centrally within the tumor. In no instance did stromal cells react positively for GFAP. Sixteen cases with anti-VIIIR:Ag antibody were examined, and in all cases many stromal cells showed positive staining. It is concluded that the stromal cells were of endothelial origin. The occasional stromal cells that other investigators have identified as reacting positively for GFAP may represent stromal cells capable of ingesting extracellular GFAP derived from reactive astrocytes within the tumor, or they may be lipidized astrocytes.

Congenital Corneal Anesthesia and Neurotrophic Keratitis: Diagnosis and Management

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Flavio Mantelli

2015-01-01

Full Text Available Neurotrophic keratitis (NK is a rare degenerative disease of the cornea caused by an impairment of corneal sensory innervation, characterized by decreased or absent corneal sensitivity resulting in epithelial keratopathy, ulceration, and perforation. The aetiopathogenesis of corneal sensory innervation impairment in children recognizes the same range of causes as adults, although they are much less frequent in the pediatric population. Some extremely rare congenital diseases could be considered in the aetiopathogenesis of NK in children. Congenital corneal anesthesia is an extremely rare condition that carries considerable diagnostic and therapeutic problems. Typically the onset is up to 3 years of age and the cornea may be affected in isolation or the sensory deficit may exist as a component of a congenital syndrome, or it may be associated with systemic somatic anomalies. Accurate diagnosis and recognition of risk factors is important for lessening long-term sequelae of this condition. Treatment should include frequent topical lubrication and bandage corneal or scleral contact lenses. Surgery may be needed in refractory cases. The purpose of this review is to summarize and update data available on congenital causes and treatment of corneal hypo/anesthesia and, in turn, on congenital NK.

Analysis of corneal esthesia in patients undergoing photorefractive keratectomy

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Elmar Torres Neto

2015-12-01

Full Text Available ABSTRACT Purpose: To quantitatively analyze corneal esthesia in patients undergoing photorefractive keratectomy (PRK surgery. Methods: Forty-five patients selected for PRK in one eye underwent corneal esthesia using a Cochet-Bonnet esthesiometer preoperatively and 30 and 90 days postoperatively. Patients with a refractive diopter error of 4 or greater received intraoperative 0.02% mitomycin C for 20 s. Results: Twenty-four (53.3% of the 45 eyes received intraoperative 0.02% mitomycin. Decreased sensitivity was observed on postoperative day 30. By postoperative day 90, corneal esthesia had normalized but remained 14.9% lower than preoperative levels. In the mitomycin group, no recovery of corneal esthesia to normal sensitivity levels was observed. The mean esthesiometer level was 39.2 mm on postoperative day 90 (P<0.001. Conclusions: The results of the present study demonstrate recovery of corneal esthesia to normal levels at 90 days postoperatively in patients who did not receive mitomycin C. In patients administered mitomycin C, a 23.59% reduction in the corneal touch threshold was observed compared with preoperative levels indicating a failure of recovery to normal levels.

Bioactive self-assembled peptide nanofibers for corneal stroma regeneration.

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Uzunalli, G; Soran, Z; Erkal, T S; Dagdas, Y S; Dinc, E; Hondur, A M; Bilgihan, K; Aydin, B; Guler, M O; Tekinay, A B

2014-03-01

Defects in the corneal stroma caused by trauma or diseases such as macular corneal dystrophy and keratoconus can be detrimental for vision. Development of therapeutic methods to enhance corneal regeneration is essential for treatment of these defects. This paper describes a bioactive peptide nanofiber scaffold system for corneal tissue regeneration. These nanofibers are formed by self-assembling peptide amphiphile molecules containing laminin and fibronectin inspired sequences. Human corneal keratocyte cells cultured on laminin-mimetic peptide nanofibers retained their characteristic morphology, and their proliferation was enhanced compared with cells cultured on fibronectin-mimetic nanofibers. When these nanofibers were used for damaged rabbit corneas, laminin-mimetic peptide nanofibers increased keratocyte migration and supported stroma regeneration. These results suggest that laminin-mimetic peptide nanofibers provide a promising injectable, synthetic scaffold system for cornea stroma regeneration. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Pirfenidone nanoparticles improve corneal wound healing and prevent scarring following alkali burn.

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Sushovan Chowdhury

Full Text Available To evaluate the effects of pirfenidone nanoparticles on corneal re-epithelialization and scarring, major clinical challenges after alkali burn.Effect of pirfenidone on collagen I and α-smooth muscle actin (α-SMA synthesis by TGFβ induced primary corneal fibroblast cells was evaluated by immunoblotting and immunocytochemistry. Pirfenidone loaded poly (lactide-co-glycolide (PLGA nanoparticles were prepared, characterized and their cellular entry was examined in primary corneal fibroblast cells by fluorescence microscopy. Alkali burn was induced in one eye of Sprague Dawley rats followed by daily topical treatment with free pirfenidone, pirfenidone nanoparticles or vehicle. Corneal re-epithelialization was assessed daily by flourescein dye test; absence of stained area indicated complete re-epithelialization and the time for complete re-epithelialization was determined. Corneal haze was assessed daily for 7 days under slit lamp microscope and graded using a standard method. After 7 days, collagen I deposition in the superficial layer of cornea was examined by immunohistochemistry.Pirfenidone prevented (P<0.05 increase in TGF β induced collagen I and α-SMA synthesis by corneal fibroblasts in a dose dependent manner. Pirfenidone could be loaded successfully within PLGA nanoparticles, which entered the corneal fibroblasts within 5 minutes. Pirfenidone nanoparticles but not free pirfenidone significantly (P<0.05 reduced collagen I level, corneal haze and the time for corneal re-epithelialization following alkali burn.Pirfenidone decreases collagen synthesis and prevents myofibroblast formation. Pirfenidone nanoparticles improve corneal wound healing and prevent fibrosis. Pirfenidone nanoparticles are of potential value in treating corneal chemical burns and other corneal fibrotic diseases.

Corneal iron ring after hyperopic photorefractive keratectomy.

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Bilgihan, K; Akata, F; Gürelik, G; Adigüzel, U; Akpinar, M; Hasanreisoğlu, B

1999-05-01

To report the incidence and course of corneal iron deposition after hyperopic photorefractive keratectomy (PRK). Gazi University, Medical School, Department of Ophthalmology, Ankara, Turkey. Between January 1995 and December 1997, 62 eyes had PRK to correct hyperopia. Nine eyes developed corneal iron ring 5 to 8 months (mean 6.25 months +/- 1.3 [SD]) after PRK for hyperopia. The rings persisted during the mean follow-up of 19 +/- 11.09 months. The ring-shaped iron deposition after PRK for hyperopia must be differentiated from the Fleischer ring. Our results suggest that the slitlamp findings of peripheral corneal iron deposition in hyperopic PRK patients correlate with achieved correction.

Corneal collagen crosslinking for keratoconus. A review

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M. M. Bikbov

2014-10-01

Full Text Available Photochemical crosslinking is widely applied in ophthalmology. Its biochemical effect is due to the release of singlet oxygen that promotes anaerobic photochemical reaction. Keratoconus is one of the most common corneal ectasia affecting 1 in 250 to 250 000 persons. Currently, the rate of iatrogenic ectasia following eximer laser refractive surgery increases due to biomechanical weakening of the cornea. Morphologically and biochemically, ectasia is characterized by corneal layers thinning, contact between the stroma and epithelium resulting from Bowman’s membrane rupture, chromatin fragmentation in keratocyte nuclei, phagocytosis, abnormal staining and arrangement of collagen fibers, enzyme system disorders, and keratocyte apoptosis. In corneal ectasia, altered enzymatic processes result in the synthesis of abnormal collagen. Collagen packing is determined by the activity of various extracellular matrix enzymes which bind amines and aldehydes of collagen fiber amino acids. In the late stage, morphological changes of Descemet’s membrane (i.e., rupture and detachment develop. Abnormal hexagonal-shaped keratocytes and their apoptosis are the signs of endothelial dystrophy. The lack of analogs in domestic ophthalmology encouraged the scientists of Ufa Eye Research Institute to develop a device for corneal collagen crosslinking. The parameters of ultraviolet (i.e., wavelength, exposure time, power to achieve the desired effect were identified. The specifics of some photosensitizers in the course of the procedure were studied. UFalink, a device for UV irradiation of cornea, and photosensitizer Dextralink were developed and adopted. Due to the high risk of endothelial damage, this treatment is contraindicated in severe keratoconus (CCT less than 400 microns. Major effects of corneal collagen crosslinking are the following: Young’s modulus (modulus of elasticity increase by 328.9 % (on average, temperature tolerance increase by 5�

[The status quo and expectation of corneal research in China].

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Shi, Weiyun; Xie, Lixin

2014-09-01

In China, corneal disease is currently the second leading cause of blindness. Severe donor shortage, insufficient technique supports and promotion, and the lack of corneal disease specialists due to poor systematic training are all urgent problems to be resolved. The last 5 years have witnessed a considerable progress in basic and clinical researches of corneal disease. Investigations on the pathogenesis and treatment of fungal keratitis have won an international reputation. Results from the study of corneal reconstruction with tissue-engineered and acellular matrix corneas have been tested in clinical trials with good preliminary performance. Moreover, the clinical researches of corneal refractive surgery have kept pace with the latest international progresses. However, Descemet's membrane endothelial keratoplasty needs further promotion, and the development and application of keratoprosthesis remains a blank. Although keratoprosthesis and corneal collagen cross-linking have been widely applied in Europe with satisfactory clinical efficacy, they are still under assessment by China Food and Drug Administration for approval of use.

Semi-automated extraction and characterization of Stromal Vascular Fraction using a new medical device.

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Hanke, Alexander; Prantl, Lukas; Wenzel, Carina; Nerlich, Michael; Brockhoff, Gero; Loibl, Markus; Gehmert, Sebastian

2016-01-01

The stem cell rich Stromal Vascular Fraction (SVF) can be harvested by processing lipo-aspirate or fat tissue with an enzymatic digestion followed by centrifugation. To date neither a standardised extraction method for SVF nor a generally admitted protocol for cell application in patients exists. A novel commercially available semi-automated device for the extraction of SVF promises sterility, consistent results and usability in the clinical routine. The aim of this work was to compare the quantity and quality of the SVF between the new system and an established manual laboratory method. SVF was extracted from lipo-aspirate both by a prototype of the semi-automated UNiStation™ (NeoGenesis, Seoul, Korea) and by hand preparation with common laboratory equipment. Cell composition of the SVF was characterized by multi-parametric flow-cytometry (FACSCanto-II, BD Biosciences). The total cell number (quantity) of the SVF was determined as well the percentage of cells expressing the stem cell marker CD34, the leucocyte marker CD45 and the marker CD271 for highly proliferative stem cells (quality). Lipo-aspirate obtained from six patients was processed with both the novel device (d) and the hand preparation (h) which always resulted in a macroscopically visible SVF. However, there was a tendency of a fewer cell yield per gram of used lipo-aspirate with the device (d: 1.1×105±1.1×105 vs. h: 2.0×105±1.7×105; p = 0.06). Noteworthy, the percentage of CD34+ cells was significantly lower when using the device (d: 57.3% ±23.8% vs. h: 74.1% ±13.4%; p = 0.02) and CD45+ leukocyte counts tend to be higher when compared to the hand preparation (d: 20.7% ±15.8% vs. h: 9.8% ±7.1%; p = 0.07). The percentage of highly proliferative CD271+ cells was similar for both methods (d:12.9% ±9.6% vs. h: 13.4% ±11.6%; p = 0.74) and no differences were found for double positive cells of CD34+/CD45+ (d: 5.9% ±1.7% vs. h: 1.7% ±1.1%; p = 0.13), CD34+/CD271+ (d: 24

Corynebacterium macginleyi isolated from a corneal ulcer

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Kathryn Ruoff

2010-02-01

Full Text Available We report the isolation of Corynebacterium macginleyi from the corneal ulcer culture of a patient, later enrolled in the Steroids for Corneal Ulcer Trial (SCUT. To our knowledge this is the first published report from North America of the recovery of C. macginleyi from a serious ocular infection.

21 CFR 886.4070 - Powered corneal burr.

Science.gov (United States)

2010-04-01

...) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4070 Powered corneal burr. (a) Identification. A powered corneal burr is an AC-powered or battery-powered device that is a motor and drilling tool intended to remove rust rings from the cornea of the eye. (b) Classification. Class I (general controls). When...

Comparative analysis of corneal morphological changes after transversal and torsional phacoemulsification through 2.2 mm corneal incision.

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Assaf, Ahmed; Roshdy, Maged Maher

2013-01-01

This paper compares and evaluates the corneal morphological changes occurring after cataract surgery through a 2.2 mm corneal incision. We use two platforms for comparison and evaluation, transversal and torsional phacoemulsification. This study includes 139 consecutive cataractous eyes (nuclear color 2-4, according to the Lens Opacities Classification System III [LOCSIII]) of 82 patients undergoing cataract surgery through a 2.2 mm corneal incision. Two different phacoemulsification platforms were used and assigned randomly: we used the WhiteStar Signature(®) system with the Ellips™ FX transversal continuous ultrasound (US) mode for group I (mean age: 65.33 ± 6.97 years), and we used the Infiniti(®) system with the OZil(®) Intelligent Phaco (IP) torsional US mode for group II (mean age: 64.02 ± 7.55 years). The corneal endothelium and pachymetry were evaluated preoperatively and at 1 month postoperatively. Incision size changes were also evaluated. All surgeries were uneventful. Before intraocular lens implantation, the mean incision size was 2.24 ± 0.06 mm in both groups (P = 0.75). In terms of corneal endothelial cell density, neither preoperative (I vs II: 2304.1 ± 122.5 cell/mm(2) vs 2315.6 ± 83.1 cell/mm(2), P = 0.80) nor postoperative (I vs II: 2264.1 ± 124.3 cell/mm(2) vs 2270.3 ± 89.9 cell/mm(2), P = 0.98) differences between the groups were statistically significant. The mean endothelial cell density loss was 1.7% ± 1.6% and 2.0% ± 1.4% in groups I and II, respectively. Furthermore, no significant differences between groups I and II were found preoperatively (P = 0.40) and postoperatively (P = 0.68) in central pachymetry. With surgery, the mean increase in central pachymetry was 28.1 ± 23.6 μm and 24.0 ± 24.0 μm in groups I and II, respectively (P = 0.1). Ellips™ FX transversal and OZil(®) IP torsional phacoemulsification modes are safe for performing cataract surgery, inducing minimal corneal thickness and endothelial changes.

PHD-2 Suppression in Mesenchymal Stromal Cells Enhances Wound Healing.

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Ko, Sae Hee; Nauta, Allison C; Morrison, Shane D; Hu, Michael S; Zimmermann, Andrew S; Chung, Michael T; Glotzbach, Jason P; Wong, Victor W; Walmsley, Graham G; Peter Lorenz, H; Chan, Denise A; Gurtner, Geoffrey C; Giaccia, Amato J; Longaker, Michael T

2018-01-01

Cell therapy with mesenchymal stromal cells is a promising strategy for tissue repair. Restoration of blood flow to ischemic tissues is a key step in wound repair, and mesenchymal stromal cells have been shown to be proangiogenic. Angiogenesis is critically regulated by the hypoxia-inducible factor (HIF) superfamily, consisting of transcription factors targeted for degradation by prolyl hydroxylase domain (PHD)-2. The aim of this study was to enhance the proangiogenic capability of mesenchymal stromal cells and to use these modified cells to promote wound healing. Mesenchymal stromal cells harvested from mouse bone marrow were transduced with short hairpin RNA (shRNA) against PHD-2; control cells were transduced with scrambled shRNA (shScramble) construct. Gene expression quantification, human umbilical vein endothelial cell tube formation assays, and wound healing assays were used to assess the effect of PHD knockdown mesenchymal stromal cells on wound healing dynamics. PHD-2 knockdown mesenchymal stromal cells overexpressed HIF-1α and multiple angiogenic factors compared to control (p cells treated with conditioned medium from PHD-2 knockdown mesenchymal stromal cells exhibited increased formation of capillary-like structures and enhanced migration compared with human umbilical vein endothelial cells treated with conditioned medium from shScramble-transduced mesenchymal stromal cells (p cells healed at a significantly accelerated rate compared with wounds treated with shScramble mesenchymal stromal cells (p cells (p cells augments their proangiogenic potential in wound healing therapy. This effect appears to be mediated by overexpression of HIF family transcription factors and up-regulation of multiple downstream angiogenic factors.

Gastrointestinal Stromal Tumors: A Case Report

OpenAIRE

Sashidharan, Palankezhe; Matele, Apoorva; Matele, Usha; Al Felahi, Nowfel; Kassem, Khalid F.

2014-01-01

Advances in the identification of gastrointestinal stromal tumors, its molecular and immunohiostochemical basis, and its management have been a watershed in the treatment of gastrointestinal tumors. This paradigm shift occurred over the last two decades and gastrointestinal stromal tumors have now come to be understood as rare gastrointestinal tract tumors with predictable behavior and outcome, replacing the older terminologies like leiomyoma, schwannoma or leiomyosarcoma. This report present...

The Correlation Analysis between Corneal Biomechanical Properties and the Surgically Induced Corneal High-Order Aberrations after Small Incision Lenticule Extraction and Femtosecond Laser In Situ Keratomileusis

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Wenjing Wu

2015-01-01

Full Text Available Background. To investigate the correlation between corneal biomechanics and the surgically induced corneal high-order aberrations (HOAs after small incision lenticule extraction (SMILE and femtosecond laser in situ keratomileusis (FS-LASIK. Methods. A total of 150 right myopic eyes that underwent SMILE or FS-LASIK surgery were included in this retrospective study, 75 eyes in each group. The corneal hysteresis (CH and the corneal resistance factor (CRF with the corneal HOAs of the anterior, posterior, and total cornea were assessed preoperatively and three months postoperatively. Multivariate linear regression was applied to determine the correlations. Results. The preoperative CRF was significantly correlated with the induced 3rd–6th-order HOAs and spherical aberration of the anterior surface and the total cornea after SMILE and FS-LASIK surgeries (P<0.05, postoperatively. The CRF was significantly correlated with the induced vertical coma of the anterior and posterior surfaces and the total cornea after SMILE surgery (P<0.05. There was a significant correlation between the CRF and the induced posterior corneal horizontal coma after FS-LASIK surgery (P=0.013. Conclusions. The corneal biomechanics affect the surgically induced corneal HOAs after SMILE and FS-LASIK surgery, which may be meaningful for screening the patients preoperatively and optimizing the visual qualities postoperatively.

Corneal graft reversal: Histopathologic report of two cases

OpenAIRE

Qahtani, Abdullah A.; Alkatan, Hind M.

2014-01-01

Graft reversal is a rare cause for failed PKP. In this case report we are presenting 2 graft failure cases in which the corneal grafts were reversed unintentionally. The onset of signs of graft failure, however was variable. We have included their clinical course and the histopathologic findings of the removed corneal grafts. A total of 6 cases including ours have been reported so far. The aim of this report is to attract the attention of corneal surgeons to an additional rare cause for faile...

Contact lens rehabilitation following repaired corneal perforations

Science.gov (United States)

Titiyal, Jeewan S; Sinha, Rajesh; Sharma, Namrata; Sreenivas, V; Vajpayee, Rasik B

2006-01-01

Background Visual outcome following repair of post-traumatic corneal perforation may not be optimal due to presence of irregular keratometric astigmatism. We performed a study to evaluate and compare rigid gas permeable contact lens and spectacles in visual rehabilitation following perforating corneal injuries. Method Eyes that had undergone repair for corneal perforating injuries with or without lens aspiration were fitted rigid gas permeable contact lenses. The fitting pattern and the improvement in visual acuity by contact lens over spectacle correction were noted. Results Forty eyes of 40 patients that had undergone surgical repair of posttraumatic corneal perforations were fitted rigid gas permeable contact lenses for visual rehabilitation. Twenty-four eyes (60%) required aphakic contact lenses. The best corrected visual acuity (BCVA) of ≥ 6/18 in the snellen's acuity chart was seen in 10 (25%) eyes with spectacle correction and 37 (92.5%) eyes with the use of contact lens (p < 0.001). The best-corrected visual acuity with spectacles was 0.20 ± 0.13 while the same with contact lens was 0.58 ± 0.26. All the patients showed an improvement of ≥ 2 lines over spectacles in the snellen's acuity chart with contact lens. Conclusion Rigid gas permeable contact lenses are better means of rehabilitation in eyes that have an irregular cornea due to scars caused by perforating corneal injuries. PMID:16536877

Intestinal stromal cells in mucosal immunity and homeostasis.

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Owens, B M J; Simmons, A

2013-03-01

A growing body of evidence suggests that non-hematopoietic stromal cells of the intestine have multiple roles in immune responses and inflammation at this mucosal site. Despite this, many still consider gut stromal cells as passive structural entities, with past research focused heavily on their roles in fibrosis, tumor progression, and wound healing, rather than their contributions to immune function. In this review, we discuss our current knowledge of stromal cells in intestinal immunity, highlighting the many immunological axes in which stromal cells have a functional role. We also consider emerging data that broaden the potential scope of their contribution to immunity in the gut and argue that these so-called "non-immune" cells are reclassified in light of their diverse contributions to intestinal innate immunity and the maintenance of mucosal homeostasis.

The pars intermedia: an anatomic basis for a coordinated vascular response to female genital arousal.

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Shih, Cheryl; Cold, Christopher J; Yang, Claire C

2013-06-01

The pars intermedia is an area of the vulva that has been inconsistently described in the literature. We conducted anatomic studies to better describe the tissues and vascular structures of the pars intermedia and proposed a functional rationale of the pars intermedia in the female sexual response. Nine cadaveric vulvectomy specimens were used. Each was serially sectioned and stained with hematoxylin and eosin and Masson's trichrome. Histologic ultrastructural description of the pars intermedia. The pars intermedia contains veins traveling longitudinally in the angle of the clitoris, supported by collagen-rich stromal tissues. These veins drain the different vascular compartments of the vulva, including the clitoris, the bulbs, and labia minora; also, the interconnecting veins link the different vascular compartments. The pars intermedia is not composed of erectile tissue, distinguishing it from the erectile tissues of the corpora cavernosa of the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs. The venous communications of the pars intermedia, linking the erectile tissues with the other vascular compartments of the vulva, appear to provide the anatomic basis for a coordinated vascular response during female sexual arousal. © 2012 International Society for Sexual Medicine.

Sclerosing stromal tumor of the ovary: A case report

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Navjot Kaur

2014-01-01

Full Text Available Sclerosing stromal tumors are benign ovarian neoplasms of the sex cord-stromal category, occurring predominantly in the second and third decades of life. Herein, we report a 23-year-old female who presented with pelvic pain, irregular menses but normal hormonal status and was diagnosed as having a right ovarian tumor. A right oophorectomy was performed, and microscopic examination revealed a sclerosing stromal tumor of the right ovary. We stress the importance of being familiar with sclerosing stromal tumors when evaluating ovarian neoplasms in young women, in order to contribute to the appropriate clinical management, preventing extensive and unnecessary surgery, and preserving fertility.

The Steroids for Corneal Ulcers Trial

Science.gov (United States)

Srinivasan, Muthiah; Mascarenhas, Jeena; Rajaraman, Revathi; Ravindran, Meenakshi; Lalitha, Prajna; Glidden, David V.; Ray, Kathryn J.; Hong, Kevin C.; Oldenburg, Catherine E.; Lee, Salena M.; Zegans, Michael E.; McLeod, Stephen D.; Lietman, Thomas M.; Acharya, Nisha R.

2013-01-01

Objectives To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. Methods Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbio-logical results, and patient demographics, for patients enrolled in the trial. Results Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P=.04) and deeper infiltrates (P=.04) and were more likely to be localized centrally (P=.002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n=366, 72%). Conclusions The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. PMID:21987581

Corneal graft reversal: Histopathologic report of two cases.

Science.gov (United States)

Qahtani, Abdullah A; Alkatan, Hind M

2014-10-01

Graft reversal is a rare cause for failed PKP. In this case report we are presenting 2 graft failure cases in which the corneal grafts were reversed unintentionally. The onset of signs of graft failure, however was variable. We have included their clinical course and the histopathologic findings of the removed corneal grafts. A total of 6 cases including ours have been reported so far. The aim of this report is to attract the attention of corneal surgeons to an additional rare cause for failed penetrating keratoplasty (PKP) which is donor graft reversal.

Evaluation of corneal higher order aberrations in normal topographic patterns

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Ali Mirzajani

2016-06-01

Conclusions: Based on results in this study, there were a good correlation between corneal topographic pattern and corneal HOAs in normal eyes. These results indicate that the corneal HOAs values are largely determined by the topographic patterns. A larger sample size would perhaps have been beneficial to yield in more accurate outcomes.

Algorithm for Correcting the Keratometric Error in the Estimation of the Corneal Power in Keratoconus Eyes after Accelerated Corneal Collagen Crosslinking

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David P. Piñero

2017-01-01

Full Text Available Purpose. To analyze the errors associated to corneal power calculation using the keratometric approach in keratoconus eyes after accelerated corneal collagen crosslinking (CXL surgery and to obtain a model for the estimation of an adjusted corneal refractive index nkadj minimizing such errors. Methods. Potential differences (ΔPc among keratometric (Pk and Gaussian corneal power (PcGauss were simulated. Three algorithms based on the use of nkadj for the estimation of an adjusted keratometric corneal power (Pkadj were developed. The agreement between Pk1.3375 (keratometric power using the keratometric index of 1.3375, PcGauss, and Pkadj was evaluated. The validity of the algorithm developed was investigated in 21 keratoconus eyes undergoing accelerated CXL. Results. Pk1.3375 overestimated corneal power between 0.3 and 3.2 D in theoretical simulations and between 0.8 and 2.9 D in the clinical study (ΔPc. Three linear equations were defined for nkadj to be used for different ranges of r1c. In the clinical study, differences between Pkadj and PcGauss did not exceed ±0.8 D nk=1.3375. No statistically significant differences were found between Pkadj and PcGauss (p>0.05 and Pk1.3375 and Pkadj (p<0.001. Conclusions. The use of the keratometric approach in keratoconus eyes after accelerated CXL can lead to significant clinical errors. These errors can be minimized with an adjusted keratometric approach.

Ultraviolet induced lysosome activity in corneal epithelium

International Nuclear Information System (INIS)

Cullen, A.P.

1980-01-01

A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm -2 to 10.000 Jm -2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm -2 and lens threshold (Hsub(L)) was 7.500 Jm -2 . The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. (orig.) [de

Alteraciones corneales en pacientes diabéticos

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Iraisi Hormigó Puertas

Full Text Available La diabetes mellitus, afección frecuente a nivel mundial, tiene gran impacto en la sociedad no solo por su alta prevalencia, sino por sus complicaciones crónicas y su alta mortalidad. Afecta a unos 180 millones de personas en el mundo. La prevalencia de la diabetes (tipos I y II se estima en el 13 % en pacientes mayores de 60 años. La estructura corneal sufre modificaciones en los pacientes diabéticos; la hiperglucemia afecta la hidratación de la córnea, y con esto varía el espesor corneal y aparecen cambios queratométricos visibles mediante topografía corneal. Las córneas de los pacientes con diabetes presentan alteraciones epiteliales, estromales y endoteliales. Además, existe una disminución de la permeabilidad endotelial durante la fase de hipoxia, que relacionan estos efectos de la diabetes en las células endoteliales. El objetivo de nuestro estudio es abordar las diferentes alteraciones corneales en los pacientes diabéticos.

Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

International Nuclear Information System (INIS)

Escobar, Guillermo A; Robinson, William A; Nydam, Trevor L; Heiple, Drew C; Weiss, Glen J; Buckley, Linda; Gonzalez, Rene; McCarter, Martin D

2007-01-01

Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, 'big' insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established

Effect of Viscous Agents on Corneal Density in Dry Eye Disease.

Science.gov (United States)

Wegener, Alfred R; Meyer, Linda M; Schönfeld, Carl-Ludwig

2015-10-01

To investigate the effect of the viscous agents, hydroxypropyl methylcellulose (HPMC), carbomer, povidone, and a combination of HPMC and povidone on corneal density in patients with dry eye disease. In total, 98 eyes of 49 patients suffering from dry eye and 65 eyes of 33 healthy age-matched individuals were included in this prospective, randomized study. Corneal morphology was documented with Scheimpflug photography and corneal density was analyzed in 5 anatomical layers (epithelium, bowman membrane, stroma, descemet's membrane, and endothelium). Corneal density was evaluated for the active ingredients HPMC, carbomer, povidone, and a combination of HPMC and povidone as the viscous agents contained in the artificial tear formulations used by the dry eye patients. Data were compared to the age-matched healthy control group without medication. Corneal density in dry eye patients was reduced in all 5 anatomical layers compared to controls. Corneal density was highest and very close to control in patients treated with HPMC containing ocular lubricants. Patients treated with lubricants, including carbomer as the viscous agent displayed a significant reduction of corneal density in layers 1 and 2 compared to control. HPMC containing ocular lubricants can help to maintain physiological corneal density and may be beneficial in the treatment of dry eye disease.

Healed corneal ulcer with keloid formation

OpenAIRE

Alkatan, Hind M.; Al-Arfaj, Khalid M.; Hantera, Mohammed; Al-Kharashi, Soliman

2012-01-01

We are reporting a 34-year-old Arabic white female patient who presented with a white mass covering her left cornea following multiple ocular surgeries and healed corneal ulcer. The lesion obscured further view of the iris, pupil and lens. The patient underwent penetrating keratoplasty and the histopathologic study of the left corneal button showed epithelial hyperplasia, absent Bowman’s layer and subepithelial fibrovascular proliferation. The histopathologic appearance was suggestive of a co...

A histological study of rabbit corneas after transepithelial corneal crosslinking using partial epithelial photoablation or ethanol treatment.