Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases

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Li, W; Chen, Y-T; Hayashida, Y; Blanco, G; Kheirkah, A; He, H; Chen, S-Y; Liu, C-Y; Tseng, SCG

2010-01-01

Pax6 is the universal master control gene for eye morphogenesis. Other than retina and lens, Pax6 also expressed in the ocular surface epithelium from early gestation until the postnatal stage, in which little is known about the function of Pax6. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens–Johnson syndrome (SJS), chemical burn, aniridia and recurrent pterygium were investigated. Our results showed that normal ocular surface epithelial cells expressed Pax6. However, corneal pannus epithelial cells from the above patients showed a decline or absence of Pax6 expression, accompanied by a decline or absence of K12 keratin but an increase of K10 keratin and filaggrin expression. Pannus basal epithelial cells maintained nuclear p63 expression and showed activated proliferation, evidenced by positive Ki67 and K16 keratin staining. On 3T3 fibroblast feeder layers, Pax6 immunostaining was negative in clones generated from epithelial cells harvested from corneal pannus from SJS or aniridia, but positive in those from the normal limbal epithelium; whereas western blots showed that some epithelial clones expanded from pannus retained Pax6 expression. Transient transfection of an adenoviral vector carrying EGFP–Pax6 transgenes into these Pax6− clones increased both Pax6 and K12 keratin expression. These results indicate that Pax6 helps to maintain the normal corneal epithelial phenotype postnatally, and that down-regulation of Pax6 is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the Pax6 gene might be useful in treating squamous metaplasia of the ocular surface epithelium. PMID:18027901

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

OpenAIRE

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-MSC...

Expression of S100B during the innate immune of corneal epithelium against fungi invasion

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Jie Zhang

2016-02-01

Full Text Available AIM: To explore the expression of S100B in corneal epithelial cells under Aspergillus stimulation both in vivo and in vitro. METHODS: Immortalized human corneal epithelial cells (HCECs were exposed to inactive Aspergillus fumigatus (A. fumigatus conidia at 0, 4, 8, 12, 16, and 24h respectively. The corneas of Wistar rats were exposed to active A. fumigatus at 0, 12, 24, 48h and the normal rat corneas were used for normal control. The mRNA level of S100B was evaluated by real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR. S100B protein expression in cornea epithelium was detected by immunohistochemical/immunocytochemical staining (IHC/ICC. RESULTS: Histopathology revealed a significant inflammatory cell infiltration in fungal keratitis human and rat cornea. Corneal epithelial cells didn’t express or rarely express S100B at baseline. A. fumigatus significantly induced S100B mRNA expression in cultured corneal epithelial cells in a time depended manner in vitro, the mRNA began to rise significantly at 8h in vitro (P<0.05 and continue to rise as time prolonged (P<0.01. In vivo, S100B mRNA level was low in the normal corneas. However, it was increased in keratitis corneas from 12h after infection (P<0.05 and reached to a peak at 24h (P<0.001. Immunochemistry revealed an obvious staining in fungal keratitis corneas as well as immortalized HCECs compared to the normal ones respectively, indicating an increased expression of S100B protein. CONCLUSION: S100B exists in corneal epithelial cells and is over-expressed under A. fumigatus stimulation. S100B may play an important role in the innate immune response of the corneal epithelium during A. fumigatus infection.

Expression of S100B during the innate immune of corneal epithelium against fungi invasion

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Zhang, Jie; Zhao, Gui-Qiu; Qu, Jing; Che, Cheng-Ye; Lin, Jing; Jiang, Nan; Zhao, Han; Wang, Xue-Jun

2016-01-01

AIM To explore the expression of S100B in corneal epithelial cells under Aspergillus stimulation both in vivo and in vitro. METHODS Immortalized human corneal epithelial cells (HCECs) were exposed to inactive Aspergillus fumigatus (A. fumigatus) conidia at 0, 4, 8, 12, 16, and 24h respectively. The corneas of Wistar rats were exposed to active A. fumigatus at 0, 12, 24, 48h and the normal rat corneas were used for normal control. The mRNA level of S100B was evaluated by real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). S100B protein expression in cornea epithelium was detected by immunohistochemical/immunocytochemical staining (IHC/ICC). RESULTS Histopathology revealed a significant inflammatory cell infiltration in fungal keratitis human and rat cornea. Corneal epithelial cells didn't express or rarely express S100B at baseline. A. fumigatus significantly induced S100B mRNA expression in cultured corneal epithelial cells in a time depended manner in vitro, the mRNA began to rise significantly at 8h in vitro (P<0.05) and continue to rise as time prolonged (P<0.01). In vivo, S100B mRNA level was low in the normal corneas. However, it was increased in keratitis corneas from 12h after infection (P<0.05) and reached to a peak at 24h (P<0.001). Immunochemistry revealed an obvious staining in fungal keratitis corneas as well as immortalized HCECs compared to the normal ones respectively, indicating an increased expression of S100B protein. CONCLUSION S100B exists in corneal epithelial cells and is over-expressed under A. fumigatus stimulation. S100B may play an important role in the innate immune response of the corneal epithelium during A. fumigatus infection. PMID:26949634

Corneal epithelium expresses a variant of P2X(7 receptor in health and disease.

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Courtney Mankus

Full Text Available Improper wound repair of the corneal epithelium can alter refraction of light resulting in impaired vision. We have shown that ATP is released after injury, activates purinergic receptor signaling pathways and plays a major role in wound closure. In many cells or tissues, ATP activates P2X(7 receptors leading to cation fluxes and cytotoxicity. The corneal epithelium is an excellent model to study the expression of both the full-length P2X(7 form (defined as the canonical receptor and its truncated forms. When Ca(2+ mobilization is induced by BzATP, a P2X(7 agonist, it is attenuated in the presence of extracellular Mg(2+ or Zn(2+, negligible in the absence of extracellular Ca(2+, and inhibited by the competitive P2X7 receptor inhibitor, A438079. BzATP enhanced phosphorylation of ERK. Together these responses indicate the presence of a canonical or full-length P2X(7 receptor. In addition BzATP enhanced epithelial cell migration, and transfection with siRNA to the P2X(7 receptor reduced cell migration. Furthermore, sustained activation did not induce dye uptake indicating the presence of truncated or variant forms that lack the ability to form large pores. Reverse transcription-polymerase chain reaction and Northern blot analysis revealed a P2X(7 splice variant. Western blots identified a full-length and truncated form, and the expression pattern changed as cultures progressed from monolayer to stratified. Cross-linking gels demonstrated the presence of homo- and heterotrimers. We examined epithelium from age matched diabetic and non-diabetic corneas patients and detected a 4-fold increase in P2X(7 mRNA from diabetic corneal epithelium compared to non-diabetic controls and an increased trend in expression of P2X(7variant mRNA. Taken together, these data indicate that corneal epithelial cells express full-length and truncated forms of P2X(7, which ultimately allows P2X(7 to function as a multifaceted receptor that can mediate cell proliferation and

Immunohistochemical expression of matrix metalloproteinases in the rabbit corneal epithelium upon UVA and UVB irradiation

Czech Academy of Sciences Publication Activity Database

Ardan, Taras; Čejková, Jitka

2012-01-01

Roč. 114, č. 6 (2012), s. 540-546 ISSN 0065-1281 R&D Projects: GA ČR GPP302/10/P155 Institutional research plan: CEZ:AV0Z50390512 Keywords : cornea * corneal epithelium * eye Subject RIV: FF - HEENT, Dentistry Impact factor: 1.608, year: 2012

Delayed healing of corneal epithelium after phototherapeutic keratectomy for lattice dystrophy.

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Das, Sujata; Langenbucher, Achim; Seitz, Berthold

2005-04-01

To evaluate the time period necessary for complete epithelial healing after phototherapeutic keratectomy (o-PTK) carried out for various superficial corneal opacities. A total of 197 eyes were divided into 9 groups: group 1, Cogan dystrophy including recurrences (n = 15); group 2, Reis Bucklers dystrophy including recurrences (n = 12); group 3, granular dystrophy including recurrences (n = 63); group 4, lattice dystrophy including recurrences (n = 19); group 5, macular dystrophy including recurrences (n = 10); group 6, herpetic scars (n = 5); group 7, corneal scars of nonherpetic origin (including scrofulous, traumatic, central keratoconus, post-pterygium surgery) (n = 31); group 8, Salzmann nodular degeneration (n = 22); and group 9, miscellaneous (such as bullous keratopathy, acute chemical burn, corneal degeneration) (n = 20). After o-PTK, patients were examined daily at the slit lamp using fluorescein and blue light. The time period necessary for complete healing of the epithelial defect was compared among these groups. Delayed healing was considered where the epithelium was not closed after 7 days. One hundred sixty-one eyes (95%) healed within 7 days. Overall, 63%, 80%, and 85% of epithelial defects were closed within 3, 4, and 5 days, respectively. Out of 9 eyes that had delayed healing, 6 eyes (67%) belonged to lattice dystrophy category. Mean time taken for healing in group 4 (8.6 +/- 8.4 days) was significantly longer than those in group 1 (3.0 +/- 1.5 days, P = 0.009), group 2 (3.7 +/- 3.1 days, P = 0.03), group 3 (3.1 +/- 1.5 days, P = 0.001), group 5 (2.7 +/- 0.8 days, P = 0.01), group 7 (3.6 +/- 2.4 days, P = 0.007), group 8 (3.3 +/- 1.3 days, P = 0.009), and group 9 (3.0 +/- 1.9 days, P = 0.011). Eyes with lattice corneal dystrophy suffered from delayed epithelial healing after o-PTK. In addition to adequate counseling, these patients should be followed up closely until complete closure of the epithelium to avoid ulceration, scarring, or even

Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway.

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Pelegrino, F S A; Pflugfelder, S C; De Paiva, C S

2012-01-01

Patients with tear dysfunction often experience increased irritation symptoms when subjected to drafty and/or low humidity environmental conditions. The purpose of this study was to investigate the effects of low humidity stress (LHS) on corneal barrier function and expression of cornified envelope (CE) precursor proteins in the epithelium of C57BL/6 and c-jun N-terminal kinase 2 (JNK2) knockout (KO) mice. LHS was induced in both strains by exposure to an air draft for 15 (LHS15D) or 30 days (LHS30D) at a relative humidity LHS15D showed corneal barrier dysfunction, decreased apical corneal epithelial cell area, higher MMP-9 expression and gelatinase activity and increased involucrin and SPRR-2 immunoreactivity in the corneal epithelium compared to NS mice. JNK2KO mice were resistant to LHS-induced corneal barrier disruption. MMP-3,-9,-13, IL-1α, IL-1β, involucrin and SPRR-2a RNA transcripts were significantly increased in C57BL/6 mice at LHS15D, while no change was noted in JNK2KO mice. LHS is capable of altering corneal barrier function, promoting pathologic alteration of the TJ complex and stimulating production of CE proteins by the corneal epithelium. Activation of the JNK2 signaling pathway contributes to corneal epithelial barrier disruption in LHS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence

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Natalie J. Dorà

2015-11-01

Full Text Available The limbal epithelial stem cell (LESC hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6 weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14 weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks.

Caveolin-1 as a novel indicator of wound-healing capacity in aged human corneal epithelium.

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Rhim, Ji Heon; Kim, Jae Hoon; Yeo, Eui-Ju; Kim, Jae Chan; Park, Sang Chul

2010-01-01

Excess caveolin-1 has been reported to play a role in age-dependent hyporesponsiveness to growth factors in vitro. Therefore, we hypothesized that caveolin-1-dependent hyporesponsiveness to growth factors in aged corneal epithelial cells might be responsible for delayed wound healing in vivo. To test this hypothesis, we evaluated corneal wound-healing time by vital staining using fluorescein after laser epithelial keratomileusis (LASEK). We compared wound-healing times in young, middle-aged and elderly patients. We also examined caveolin-1 levels and other aging markers, such as p53 and p21, in the corneal epithelium. Elderly patients generally had higher caveolin-1 levels in the corneal epithelia than young patients. There were, however, variations among individuals with increased caveolin-1 in some young patients and decreased levels in some elderly patients. Wound-healing time after LASEK correlated well with the corneal caveolin-1 status. Therefore, we suggest that caveolin-1 status might be responsible for delayed wound healing in elderly patients after LASEK. Caveolin-1 status might be a regulator for wound-healing capacity and a novel target for in vivo adjustment.

Assessment of corneal epithelial thickness in dry eye patients.

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Cui, Xinhan; Hong, Jiaxu; Wang, Fei; Deng, Sophie X; Yang, Yujing; Zhu, Xiaoyu; Wu, Dan; Zhao, Yujin; Xu, Jianjiang

2014-12-01

To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients. In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum - maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated. The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) μm, 52.00 (±3.39) μm, and 53.03 (±3.67) μm in normal eyes and 52.71 (±2.83) μm, 50.58 (±3.44) μm, and 52.53 (±3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p = 0.037), whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.

Development of a human corneal epithelium model utilizing a collagen vitrigel membrane and the changes of its barrier function induced by exposing eye irritant chemicals.

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Takezawa, Toshiaki; Nishikawa, Kazunori; Wang, Pi-Chao

2011-09-01

The brief TEER (trans-epithelial electrical resistance) assay after exposing chemicals to corneal epithelium in vivo is known as a suitable method for evaluating corneal irritancy and permeability quantitatively and continuously. A collagen vitrigel membrane we previously developed is a thin (about 20 μm thick) and transparent membrane composed of high density collagen fibrils equivalent to connective tissues in vivo, e.g. corneal Bowman's membrane. To develop such a TEER assay system in vitro utilizing a human corneal epithelial model, HCE-T cells (a human corneal epithelial cell line) were cultured on the collagen vitrigel membrane substratum prepared in a Millicell chamber suitable for TEER measurement. Human corneal epithelium model possessing 5-6 cell layers sufficient for TEER assay was successfully reconstructed on the substratum in the Millicell chamber by culturing the cells in monolayer for 2 days and subsequently in air-liquid interface for 7 days. The exposure of chemicals to the model induced the time-dependent relative changes of TEER in response to the characteristic of each chemical within a few minutes. These results suggest that the TEER assay using the human corneal epithelial model is very useful for an ocular irritancy evaluation as an alternative to the Draize eye irritation test. Copyright © 2011 Elsevier Ltd. All rights reserved.

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...

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

Science.gov (United States)

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

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.

Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in [3H]-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone

International Nuclear Information System (INIS)

Scheving, L.E.; Tsai, T.H.; Powell, E.W.; Pasley, J.N.; Halberg, F.; Dunn, J.

1983-01-01

Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of [ 3 H]-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a ''phase-resetter'' and as a modulator of rhythm amplitude

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.

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

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

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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.

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.

Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye.

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Lin, Hui; Li, Wei; Dong, Nuo; Chen, Wensheng; Liu, Jing; Chen, Lelei; Yuan, Hongxia; Geng, Zhixin; Liu, Zuguo

2010-01-01

To investigate the morphology, distribution, and density of inflammatory cells in the corneal epithelium of aqueous tear-deficient dry eye. Thirty-two patients with non-Sjögren's syndrome (NSS) dry eye, 14 patients with Sjögren's syndrome (SS) dry eye, and 33 healthy volunteers were studied. In vivo laser scanning confocal microscopy was used to investigate both Langerhans cell (LCs) and leukocyte distribution and density in the peripheral and central corneal epithelium. LC morphology was also evaluated. Multifactor regression analysis assessed whether there is a correlation between clinical manifestations and inflammatory cell densities. LCs were present in both central (34.9 +/- 5.7 cells/mm(2)) and peripheral (90.7 +/- 8.2 cells/mm(2)) parts of the normal corneal epithelium. Moreover, LC density increased dramatically in the central corneal epithelium in patients with NSS (89.8 +/- 10.8 cells/mm(2)) and SS (127.9 +/- 23.7 cells/mm(2)). The ratio of LCs with obvious processes was much higher in patients with dry eye than in healthy volunteers. LC density also increased in peripheral corneal epithelium in patients with SS, but not in those with NSS. Leukocyte density in normal corneal epithelium was very low, whereas it increased in the central corneal epithelium (4.6 +/- 1.0 cells/mm(2)) in NSS and in both central (49.0 +/- 12.9 cells/mm(2)) and peripheral (84.2 +/- 36.8 cells/mm(2)) corneal epithelium in SS. Densities of LCs and leukocytes showed significant correlation with the severity found in clinical evaluation. The LC and leukocyte changes in the corneal epithelium suggest their involvement in aqueous tear-deficient dry eye pathophysiology. In vivo dynamic assessment of central corneal inflammatory cell density may serve as an indicator of dry eye severity and provide new insight for dry eye treatment.

Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals.

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Higuchi, Akihiro; Inoue, Hiroyoshi; Kaneko, Yoshio; Oonishi, Erina; Tsubota, Kazuo

2016-11-11

The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism.

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.

Can Riboflavin Penetrate Stroma Without Disrupting Integrity of Corneal Epithelium in Rabbits? Iontophoresis and Ultraperformance Liquid Chromatography With Electrospray Ionization Tandem Mass Spectrometry.

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Novruzlu, Şahin; Türkcü, Ümmühani Özel; Kvrak, İbrahim; Kvrak, Şeyda; Yüksel, Erdem; Deniz, Nuriye Gökçen; Bilgihan, Ayşe; Bilgihan, Kamil

2015-08-01

To examine riboflavin concentrations in corneas and aqueous humor from rabbits with standard and transepithelial methods and iontophoresis without disrupting the integrity of the corneal epithelium before corneal collagen cross-linking. Twenty-four eyes of 12 adult New Zealand rabbits were used. They were assigned to 4 groups, each including 6 eyes. Group 1 was exposed to the standard method and given riboflavin 0.1% after epithelial debridement. Group 2 was exposed to the transepithelial method and given benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA), trometamol (TRIS), hydroxypropylmethylcellulose (HPMC), and riboflavin 0.2% 3 times at 1.5-minute intervals followed by riboflavin 0.2%. Group 3 was given riboflavin 0.1% by using 1-mA electric current for 10 minutes with the help of iontophoresis without using substances disrupting the integrity of the corneal epithelium. Group 4 received the same treatment as did group 3, except that it was given riboflavin 0.2%. Following these treatments, riboflavin concentrations in aqueous humor and corneas were measured with ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). Riboflavin concentrations in the cornea and aqueous humor were higher in group 1 (42.4 ± 5.4 μg/g) than in the other groups. They were significantly higher in group 4 (34.2 ± 6.6 μg/g) than in group 2 (24.4 ± 1.2 μg/g) (P = 0.009) and group 3 (23.6 ± 6.1 μg/g) (P = 0.026). There was not a significant difference in corneal riboflavin concentrations between group 2 and group 3 (P = 0.937). Intrastromal and aqueous riboflavin concentrations after administration of riboflavin 0.2% through iontophoresis without disrupting the integrity of the corneal epithelium were lower than those after the standard method, but higher than those after the transepithelial method. In this study, in which riboflavin concentrations were measured with a very sensitive method

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.

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.

Clinical effects of conjunctival sac flushing using different concentration of povidoneiodine on corneal epithelium before cataract surgeries

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Xue-Lian Gu

2015-10-01

Full Text Available AIM:To determine the most optimal concentration of the safe usage of povidone-iodine(PVP-Iin the flushing to disinfect the conjunctive sac before cataract surgeries, in order to provide a scientific basis for clinical eye surgery work.METHODS:Sixty-two patients with phacoemulsification and intraocular lens implantation in our hospital from October 2012 to October 2014 were randomly divided into 0.25g/L PVP-I group(Ⅰand 5g/L PVP-I group(Ⅱ. Sterilizing effect and the complications postoperative were analyzed.RESULTS:The sterilizing effects of the two groups after flushing conjunctiva sac using different concentrations of PVP-I were both remarkable, but the difference between the two groups was not statistically significant(P>0.05. No endophthalmitis occurred in the two groups. Observing the corneal condition after rinsing, no severe conjunctival hyperemia, corneal edema and other serious complications occurred. There was slightly punctate corneal epithelial shedding in groupⅡ, and the difference was statistically significant(PPCONCLUSION:Using 0.25g/L PVP-I in the conjunctiva sac rinsing before surgeries can inhibit the growth of bacteria in the conjunctival sac, reduce the impact on the corneal epithelium thereby reducing the incidence of postoperative complications and the positive rate of bacterial culture, increasing the comfort degree of patients, bringing a better area for the surgeries.

Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model.

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Khoh-Reiter, Su; Jessen, Bart A

2009-07-28

Benzalkonium chloride (BAC) is a common preservative used in ophthalmic solutions. The aim of this study was to compare the cytotoxic effects of BAC-containing ophthalmic solutions with a BAC-free ophthalmic solution using an organotypic 3-dimensional (3-D) corneal epithelial model and to determine the effects of latanoprost ophthalmic solution and its BAC-containing vehicle on corneal thickness in a monkey model. The cytotoxicity of commercially available BAC-containing ophthalmic formulations of latanoprost (0.02% BAC) and olopatadine (0.01% BAC) was compared to that of BAC-free travoprost and saline in a corneal organotypic 3-D model using incubation times of 10 and 25 minutes. To compare the extent of differentiation of 3-D corneal cultures to monolayer transformed human corneal epithelial (HCE-T) cell cultures, expression levels (mRNA and protein) of the corneal markers epidermal growth factor receptor, transglutaminase 1 and involucrin were quantified. Finally, latanoprost ophthalmic solution or its vehicle was administered at suprapharmacologic doses (two 30 microL drops twice daily in 1 eye for 1 year) in monkey eyes, and corneal pachymetry was performed at baseline and at weeks 4, 13, 26 and 52. In the 3-D corneal epithelial culture assays, there were no significant differences in cytotoxicity between the BAC-containing latanoprost and olopatadine ophthalmic solutions and BAC-free travoprost ophthalmic solution at either the 10- or 25-minute time points. The 3-D cultures expressed higher levels of corneal epithelial markers than the HCE-T monolayers, indicating a greater degree of differentiation. There were no significant differences between the corneal thickness of monkey eyes treated with latanoprost ophthalmic solution or its vehicle (both containing 0.02% BAC) and untreated eyes. The lack of cytotoxicity demonstrated in 3-D corneal cultures and in monkey studies suggests that the levels of BAC contained in ophthalmic solutions are not likely to cause

Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model

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Jessen Bart A

2009-07-01

Full Text Available Abstract Background Benzalkonium chloride (BAC is a common preservative used in ophthalmic solutions. The aim of this study was to compare the cytotoxic effects of BAC-containing ophthalmic solutions with a BAC-free ophthalmic solution using an organotypic 3-dimensional (3-D corneal epithelial model and to determine the effects of latanoprost ophthalmic solution and its BAC-containing vehicle on corneal thickness in a monkey model. Methods The cytotoxicity of commercially available BAC-containing ophthalmic formulations of latanoprost (0.02% BAC and olopatadine (0.01% BAC was compared to that of BAC-free travoprost and saline in a corneal organotypic 3-D model using incubation times of 10 and 25 minutes. To compare the extent of differentiation of 3-D corneal cultures to monolayer transformed human corneal epithelial (HCE-T cell cultures, expression levels (mRNA and protein of the corneal markers epidermal growth factor receptor, transglutaminase 1 and involucrin were quantified. Finally, latanoprost ophthalmic solution or its vehicle was administered at suprapharmacologic doses (two 30 μL drops twice daily in 1 eye for 1 year in monkey eyes, and corneal pachymetry was performed at baseline and at weeks 4, 13, 26 and 52. Results In the 3-D corneal epithelial culture assays, there were no significant differences in cytotoxicity between the BAC-containing latanoprost and olopatadine ophthalmic solutions and BAC-free travoprost ophthalmic solution at either the 10- or 25-minute time points. The 3-D cultures expressed higher levels of corneal epithelial markers than the HCE-T monolayers, indicating a greater degree of differentiation. There were no significant differences between the corneal thickness of monkey eyes treated with latanoprost ophthalmic solution or its vehicle (both containing 0.02% BAC and untreated eyes. Conclusion The lack of cytotoxicity demonstrated in 3-D corneal cultures and in monkey studies suggests that the levels of BAC

Pax6 downregulation mediates abnormal lineage commitment of the ocular surface epithelium in aqueous-deficient dry eye disease.

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Ying Ting Chen

Full Text Available Keratinizing squamous metaplasia (SQM of the ocular surface is a blinding consequence of systemic autoimmune disease and there is no cure. Ocular SQM is traditionally viewed as an adaptive tissue response during chronic keratoconjunctivitis sicca (KCS that provokes pathological keratinization of the corneal epithelium and fibrosis of the corneal stroma. Recently, we established the autoimmune regulator-knockout (Aire KO mouse as a model of autoimmune KCS and identified an essential role for autoreactive CD4+ T cells in SQM pathogenesis. In subsequent studies, we noted the down-regulation of paired box gene 6 (Pax6 in both human patients with chronic KCS associated with Sjögren's syndrome and Aire KO mice. Pax6 encodes a pleiotropic transcription factor guiding eye morphogenesis during development. While the postnatal function of Pax6 is largely unknown, we hypothesized that its role in maintaining ocular surface homeostasis was disrupted in the inflamed eye and that loss of Pax6 played a functional role in the initiation and progression of SQM. Adoptive transfer of autoreactive T cells from Aire KO mice to immunodeficient recipients confirmed CD4+ T cells as the principal downstream effectors promoting Pax6 downregulation in Aire KO mice. CD4+ T cells required local signaling via Interleukin-1 receptor (IL-1R1 to provoke Pax6 loss, which prompted a switch from corneal-specific cytokeratin, CK12, to epidermal-specific CK10. The functional role of Pax6 loss in SQM pathogenesis was indicated by the reversal of SQM and restoration of ocular surface homeostasis following forced expression of Pax6 in corneal epithelial cells using adenovirus. Thus, tissue-restricted restoration of Pax6 prevented aberrant epidermal-lineage commitment suggesting adjuvant Pax6 gene therapy may represent a novel therapeutic approach to prevent SQM in patients with chronic inflammatory diseases of the ocular surface.

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

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

2013-01-01

This study investigated ocular surface components that contribute to matrix-metalloproteinase (MMP)-2 and MMP-9 found in tears following corneal epithelial wounding. Laboratory short-haired cats underwent corneal epithelial debridement in one randomly chosen eye (n = 18). Eye-flush tears were collected at baseline and during various healing stages. Procedural control eyes (identical experimental protocol as wounded eyes except for wounding, n = 5) served as controls for tear analysis. MMP activity was analyzed in tears using gelatin zymography. MMP staining patterns were evaluated in ocular tissues using immunohistochemistry and used to determine MMP expression sites responsible for tear-derived MMPs. The proMMP-2 and proMMP-9 activity in tears was highest in wounded and procedural control eyes during epithelial migration (8 to 36 hours post-wounding). Wounded eyes showed significantly higher proMMP-9 in tears only during and after epithelial restratification (day 3 to 4 and day 7 to 28 post-wounding, respectively) as compared to procedural controls (pTears from wounded and procedural control eyes showed no statistical differences for pro-MMP-2 and MMP-9 (p>0.05). Immunohistochemistry showed increased MMP-2 and MMP-9 expression in the cornea during epithelial migration and wound closure. The conjunctival epithelium exhibited highest levels of both MMPs during wound closure, while MMP-9 expression was reduced in conjunctival goblet cells during corneal epithelial migration followed by complete absence of the cells during wound closure. The immunostaining for both MMPs was elevated in the lacrimal gland during corneal healing, with little/no change in the meibomian glands. Conjunctival-associated lymphoid tissue (CALT) showed weak MMP-2 and intense MMP-9 staining. Following wounding, migrating corneal epithelium contributed little to the observed MMP levels in tears. The major sources assessed in the present study for tear-derived MMP-2 and MMP-9 following

An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva

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Tiago Ramos

2015-01-01

Full Text Available The human ocular surface (front surface of the eye is formed by two different types of epithelia: the corneal epithelium centrally and the conjunctival epithelium that surrounds this. These two epithelia are maintained by different stem cell populations (limbal stem cells for the corneal epithelium and the conjunctival epithelial stem cells. In this review, we provide an update on our understanding of these epithelia and their stem cells systems, including embryology, new markers, and controversy around the location of these stem cells. We also provide an update on the translation of this understanding into clinical applications for the treatment of debilitating ocular surface diseases.

Dynamic Corneal Surface Mapping with Electronic Speckle Pattern Interferometry

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Iqbal, S.; Gualini, M. M. S.

2013-06-01

In view of the fast advancement in ophthalmic technology and corneal surgery, there is a strong need for the comprehensive mapping and characterization techniques for corneal surface. Optical methods with precision non-contact approaches have been found to be very useful for such bio measurements. Along with the normal mapping approaches, elasticity of corneal surface has an important role in its characterization and needs to be appropriately measured or estimated for broader diagnostics and better prospective surgical results, as it has important role in the post-op corneal surface reconstruction process. Use of normal corneal topographic devices is insufficient for any intricate analysis since these devices operate at relatively moderate resolution. In the given experiment, Pulsed Electronic Speckle Pattern Interferometry has been utilized along with an excitation mechanism to measure the dynamic response of the sample cornea. A Pulsed ESPI device has been chosen for the study because of its micron-level resolution and other advantages in real-time deformation analysis. A bovine cornea has been used as a sample in the subject experiment. The dynamic response has been taken on a chart recorder and it is observed that it does show a marked deformation at a specific excitation frequency, which may be taken as a characteristic elasticity parameter for the surface of that corneal sample. It was seen that outside resonance conditions the bovine cornea was not that much deformed. Through this study, the resonance frequency and the corresponding corneal deformations are mapped and plotted in real time. In these experiments, data was acquired and processed by FRAMES plus computer analysis system. With some analysis of the results, this technique can help us to refine a more detailed corneal surface mathematical model and some preliminary work was done on this. Such modelling enhancements may be useful for finer ablative surgery planning. After further experimentation

A minimal model of epithelial tissue dynamics and its application to the corneal epithelium

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Henkes, Silke; Matoz-Fernandez, Daniel; Kostanjevec, Kaja; Coburn, Luke; Sknepnek, Rastko; Collinson, J. Martin; Martens, Kirsten

Epithelial cell sheets are characterized by a complex interplay of active drivers, including cell motility, cell division and extrusion. Here we construct a particle-based minimal model tissue with only division/death dynamics and show that it always corresponds to a liquid state with a single dynamic time scale set by the division rate, and that no glassy phase is possible. Building on this, we construct an in-silico model of the mammalian corneal epithelium as such a tissue confined to a hemisphere bordered by the limbal stem cell zone. With added cell motility dynamics we are able to explain the steady-state spiral migration on the cornea, including the central vortex defect, and quantitatively compare it to eyes obtained from mice that are X-inactivation mosaic for LacZ.

Comparison of parametric methods for modeling corneal surfaces

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Bouazizi, Hala; Brunette, Isabelle; Meunier, Jean

2017-02-01

Corneal topography is a medical imaging technique to get the 3D shape of the cornea as a set of 3D points of its anterior and posterior surfaces. From these data, topographic maps can be derived to assist the ophthalmologist in the diagnosis of disorders. In this paper, we compare three different mathematical parametric representations of the corneal surfaces leastsquares fitted to the data provided by corneal topography. The parameters obtained from these models reduce the dimensionality of the data from several thousand 3D points to only a few parameters and could eventually be useful for diagnosis, biometry, implant design etc. The first representation is based on Zernike polynomials that are commonly used in optics. A variant of these polynomials, named Bhatia-Wolf will also be investigated. These two sets of polynomials are defined over a circular domain which is convenient to model the elevation (height) of the corneal surface. The third representation uses Spherical Harmonics that are particularly well suited for nearly-spherical object modeling, which is the case for cornea. We compared the three methods using the following three criteria: the root-mean-square error (RMSE), the number of parameters and the visual accuracy of the reconstructed topographic maps. A large dataset of more than 2000 corneal topographies was used. Our results showed that Spherical Harmonics were superior with a RMSE mean lower than 2.5 microns with 36 coefficients (order 5) for normal corneas and lower than 5 microns for two diseases affecting the corneal shapes: keratoconus and Fuchs' dystrophy.

System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency

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Boadi, J.; Sangwal, V.; MacNeil, S.; Matcher, S. J.

2015-03-01

The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells is continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. Limbal Stem Cell Deficiency (LSCD), in which the stem cell population is depleted, can lead to blindness. LSCD can be caused by chemical and thermal burns to the eye. A popular treatment, especially in emerging economies such as India, is the transplantation of limbal stem cells onto damaged limbus with hope of repopulating the region. Hence regenerating the corneal epithelium. In order to gain insights into the success rates of this treatment, new imaging technologies are needed in order to track the transplanted cells. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images of the retina. A custom OCT system has been built to image the corneal surface, to investigate the fate of transplanted limbal stem cells. We evaluate two methods to label and track transplanted cells: melanin labelling and magneto-labelling. To evaluate melanin labelling, stem cells are loaded with melanin and then transplanted onto a rabbit cornea denuded of its epithelium. The melanin displays strongly enhanced backscatter relative to normal cells. To evaluate magneto-labelling the stem cells are loaded with magnetic nanoparticles (20-30nm in size) and then imaged with a custom-built, magneto-motive OCT system.

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.

Increase of corneal epithelium cell radioresistance during regeneration

International Nuclear Information System (INIS)

Popova, M.F.; Bulyakova, N.V.; Azarova, V.S.

1985-01-01

A comparative study of the radiosensitivity of the normal and regenerating cornea epithelium of C 57 Bl mice was performed on the cellular level, the duration of the cell cycle being taken into account. Criteria of radiation injuries were the number of chromosome aberrations, mitotic index and duration of mitotic block. The anterior part of the head was irradiated singly with 1.75, 3.5 or 7.0 Gy and also repeatedly 3.5 + 3.5 at a 24-hours interval. The corneas were fixed 2, 4, 6, 12, 24, 48, 72 and 96 hours after irradiation. In all cases of irradiated mice the regenerating epithelium showed a shorter mitotic block and significantly lower cytogenetic injury as compared with the controls. Effects of fractionated irradiation were only shown in the regenerating epithelium. The results obtained indicate that regenerating epithelium cells of the cornea are significantly more radioresistant than normal epithelium due to activation of post-radiation recovery, and also, possibly, due to an increase in the content of endogenous radioprotectors. (author)

Edge detection and mathematic fitting for corneal surface with Matlab software.

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Di, Yue; Li, Mei-Yan; Qiao, Tong; Lu, Na

2017-01-01

To select the optimal edge detection methods to identify the corneal surface, and compare three fitting curve equations with Matlab software. Fifteen subjects were recruited. The corneal images from optical coherence tomography (OCT) were imported into Matlab software. Five edge detection methods (Canny, Log, Prewitt, Roberts, Sobel) were used to identify the corneal surface. Then two manual identifying methods (ginput and getpts) were applied to identify the edge coordinates respectively. The differences among these methods were compared. Binomial curve (y=Ax 2 +Bx+C), Polynomial curve [p(x)=p1x n +p2x n-1 +....+pnx+pn+1] and Conic section (Ax 2 +Bxy+Cy 2 +Dx+Ey+F=0) were used for curve fitting the corneal surface respectively. The relative merits among three fitting curves were analyzed. Finally, the eccentricity (e) obtained by corneal topography and conic section were compared with paired t -test. Five edge detection algorithms all had continuous coordinates which indicated the edge of the corneal surface. The ordinates of manual identifying were close to the inside of the actual edges. Binomial curve was greatly affected by tilt angle. Polynomial curve was lack of geometrical properties and unstable. Conic section could calculate the tilted symmetry axis, eccentricity, circle center, etc . There were no significant differences between 'e' values by corneal topography and conic section ( t =0.9143, P =0.3760 >0.05). It is feasible to simulate the corneal surface with mathematical curve with Matlab software. Edge detection has better repeatability and higher efficiency. The manual identifying approach is an indispensable complement for detection. Polynomial and conic section are both the alternative methods for corneal curve fitting. Conic curve was the optimal choice based on the specific geometrical properties.

Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

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Zhao-Qin Hao

2016-11-01

Full Text Available AIM: To observe the therapeutic effect of corneal collagen cross-linking (CXL in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS: New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each. The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM at 4wk. RESULTS: A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (P<0.05. The corneal epithelium defect areas of the combined group was smaller than that of the CXL group (P<0.05 on 7 and 14d, but there were no statistical differences on 3, 21 and 28d. The corneal epithelium defects of the two treatment groups have been healed by day 21. The corneal epithelium defects of the control group were healed on 28d. The diameters of the corneal collagen fiber bundles (42.960±7.383 nm in the CXL group and 37.040±4.160 nm in the combined group were thicker than that of the control group (24.900±1.868 nm, but there was no difference between the two treatment groups. Some corneal collagen fiber bundles were distorted and with irregular arrangement, a large number of fibroblasts could be seen among them but no inflammatory cells in both treatment groups. CONCLUSION: CXL combined with liposomal amphotericin B have beneficial effects on fungal corneal ulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease.

Subepithelial corneal fibrosis partially due to epithelial-mesenchymal transition of ocular surface epithelium

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Kawashima, Motoko; Higa, Kazunari; Satake, Yoshiyuki; Omoto, Masahiro; Tsubota, Kazuo; Shimmura, Shigeto; Shimazaki, Jun

2010-01-01

Purpose To determine whether epithelial-mesenchymal transition is involved in the development of corneal subepithelial fibrosis (pannus). Methods Frozen samples of pannus tissue removed from human corneas with a diagnosis of total limbal stem cell deficiency were characterized by immunostaining for both epithelial and mesenchymal markers. We selected transformation-related protein 63 (p63) and pancytokeratin as epithelial markers and vimentin and α-smooth muscle actin (α-SMA) as mesenchymal markers. Immunostaining for β-catenin and E-cadherin was performed to determine wingless-Int (Wnt)-pathway activation. RT–PCR analysis was also performed on epithelial tissue obtained from pannus samples after dispase digestion. Results Immunohistochemistry revealed strong nuclear expression of p63 and weak intercellular expression of E-cadherin in epithelial basal cells of pannus tissue. Furthermore, translocation of β-catenin from intercellular junctions to the nucleus and cytoplasm was also observed. Double-positive cells for both p63 and α-SMA were observed in the subepithelial stroma of pannus tissue, which was supported by RT–PCR and cytospin analysis. Conclusions Epithelial-mesenchymal transition may be partially involved in the development of subepithelial corneal fibrosis due to total limbal stem cell deficiency. PMID:21179238

Activation of cell division and nucleic acid synthesis in the corneal epithelium of albino rats by repeated stress

International Nuclear Information System (INIS)

Berezhnova, N.I.; Timoshin, S.S.

1985-01-01

Adaption to unfavorable factors is accompanied by activation of nucleic acid and protein synthesis in systems responsible for adaption. The authors investigate the possibility of similar changes taking place in structures not actively participating in adaptation. The corneas of the dead male albin rats were preincubated with tritium-uridine for 1.5 hours. The mitotic index, the index of tritium-thymidine-labeled nuclei and the intensity of thymidine labeling were determined. The results indicate that after a single exposure to hypoxia, hyperthermia, and immobilization, mitotic index in the corneal epithelium decreased and DNA synthesis under these circumstances remained stable

Resolvin D1 promotes corneal epithelial wound healing and restoration of mechanical sensation in diabetic mice.

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Zhang, Zhenzhen; Hu, Xiaoli; Qi, Xia; Di, Guohu; Zhang, Yangyang; Wang, Qian; Zhou, Qingjun

2018-01-01

To investigate the effect and mechanism of proresolving lipid mediator resolvin D1 (RvD1) on the corneal epithelium and the restoration of mechanical sensation in diabetic mice. Type 1 diabetes was induced in mice with intraperitoneal streptozocin injections. The healthy and diabetic mice underwent removal of the central corneal epithelium, and then 100 ng/ml RvD1 or its formyl peptide receptor 2 (FPR2) antagonist WRW4 was used to treat the diabetic mice. Regeneration of the corneal epithelium and nerves was observed with sodium fluorescein staining and whole-mount anti-β3-tubulin fluorescence staining. The inflammatory response level was measured with hematoxylin and eosin staining (inflammatory cell infiltration), enzyme-linked immunosorbent assay (tumor necrosis factor alpha and interleukin-1 beta content), myeloperoxidase activity, and fluorescence staining (macrophage content). The reactive oxygen species (ROS) and glutathione (GSH) levels were examined with incubation with fluorescent probes, and oxidative stress-related protein expression levels were evaluated with fluorescence staining and western blotting. Topical application of RvD1 promoted regeneration of the corneal epithelium in diabetic mice, accompanied by the reactivation of signaling and inflammation resolution related to regeneration of the epithelium. Furthermore, RvD1 directly attenuated the accumulation of ROS and nicotinamide adenine dinucleotide phosphate oxidase 2/4 expression, while RvD1 enhanced GSH synthesis and reactivated the Nrf2-ARE signaling pathway that was impaired in the corneal epithelium in the diabetic mice. More interestingly, topical application of RvD1 promoted regeneration of corneal nerves and completely restored impaired mechanical sensitivity of the cornea in diabetic mice. In addition, the promotion of corneal epithelial wound healing by RvD1 in diabetic mice was abolished by its FPR2 antagonist WRW4. Topical application of RvD1 promotes corneal epithelial wound

Experiment of amnion epithelial cell suspension liquid used for acute rabbit corneal alkali burn

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Yan-Yan Zhang

2017-10-01

Full Text Available AIM: To investigate the effects of amnion epithelial cell(AECsuspension liquid on the biological behavior of the rabbit's corneal epithelium, combined with the in vitro and in vivo experiments. METHODS: The rabbit's corneal epithelium were cultured in the lower chamber of transwell, and AEC suspension liquid was dropwised in the upper chamber. There was only culture medium in the upper chamber of the control group. The proliferation of rabbit's corneal epithelium was observed with CCK-8 automated colorimetry and the expression of PCNA was detected by immunocytochemistry. We used the scratch wound assay to detect the migration of corneal epithelial cell(CEC. The in vivo models were established by placing a 10mm diameter corneal trephine in the center of the cornea, within 1mol/L NaOH for 1min. We divided those into three groups: treatment group of AEC suspension liquid eye drop, AEC suspension liquid subconjunctival injection and the control group without any treatment. Using the slit-lamp biomicroscope and fluorescence staining to observe the cornea per week. After 28d we took the eyeballs with the HE staining. The expression of VEGF was detected by immunohistochemistry. RESULTS: The activity of CEC with AEC treatment was much higher than the control group(PPIn vivo, the inflammation of the corneal and the CNV of the AEC group were all significantly reduced compared with the control group(PPCONCLUSION: AEC suspension liquid can promote the proliferation and migration of the rabbit's corneal epithelium. The potential of AEC suspension liquid as a therapy for acute corneal alkali burn.

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.

[Alterations in the metabolism of cornmeal epithelium during medium-term storage (author's transl)].

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Schmidt-Martens, F W; Hennighausen, U; Wirz, K; Teping, C

1977-08-08

Freshly prepared bovine corneas were stored in medium TC 199 with penicillin and fetal calf serum at +4 degrees C over a storage period of 168h. Every 24h, the levels of glucose, lactate, and pyruvate in the corneal epithelium were estimated. Also the glucose levels in the corneal epithelium and stroma were compared at the same time intervals. Furthermore, alterations in the enzyme pattern of the epithelial cells during storage were observed.

Preserved and unpreserved 12 anti-allergic ophthalmic solutions and ocular surface toxicity: in vitro assessment in four cultured corneal and conjunctival epithelial cell lines.

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Ayaki, Masahiko; Iwasawa, Atsuo; Yaguchi, Shigeo; Koide, Ryohei

2010-12-01

In the present study, we evaluated the cytotoxicity of anti-allergic ophthalmic solutions in cultured corneal and conjunctival cells, namely SIRC (rabbit corneal epithelium), BCE C/D-1b (bovine corneal epithelial cells), RC-1 (rabbit corneal epithelium), and Chang (human conjunctival cells). The viability of cell cultures was determined following the exposure of cells to 12 commercially available anti-allergic ophthalmic solutions for varying exposure times and at various dilutions using the MTT and neutral red assays. The cell viability score (CVS) was used to compare the toxicity of different drugs. Based on CVS data, the order of cell viability after exposure to the drugs was Zepelin ≥ Tramelas PF ≥ Cumorol PF ≥ Ketotifen PF ≥ Eyevinal = Fumarton ≥ Cumorol > Intal ≥ Rizaben ≥ Tramelas ≥ Patanol Livostin. In conclusion, cell viability was mostly affected by the concentration of benzalkonium chloride rather than the active component and/or the anti-allergic action of the drug. The CVS was useful in comparing the toxicity of different drugs.

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.

Parametric fitting of corneal height data to a biconic surface.

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Janunts, Edgar; Kannengießer, Marc; Langenbucher, Achim

2015-03-01

As the average corneal shape can effectively be approximated by a conic section, a determination of the corneal shape by biconic parameters is desired. The purpose of the paper is to introduce a straightforward mathematical approach for extracting clinically relevant parameters of corneal surface, such as radii of curvature and conic constants for principle meridians and astigmatism. A general description for modeling the ocular surfaces in a biconic form is given, based on which an implicit parametric surface fitting algorithm is introduced. The solution of the biconic fitting is obtained by a two sequential least squares optimization approach with constrains. The data input can be raw information from any corneal topographer with not necessarily a uniform data distribution. Various simulated and clinical data are studied including surfaces with rotationally symmetric and non-symmetric geometries. The clinical data was obtained from the Pentacam (Oculus) for the patient having undergone a refractive surgery. A sub-micrometer fitting accuracy was obtained for all simulated surfaces: 0,08 μm RMS fitting error at max for rotationally symmetric and 0,125 μm for non-symmetric surfaces. The astigmatism was recovered in a sub-minutes resolution. The equality in rotational symmetric and the superiority in non-symmetric surfaces of the presented model over the widely used quadric fitting model is shown. The introduced biconic surface fitting algorithm is able to recover the apical radii of curvature and conic constants in principle meridians. This methodology could be a platform for advanced IOL calculations and enhanced contact lens fitting. Copyright © 2014. Published by Elsevier GmbH.

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

Improvement of chronic corneal opacity in ocular surface disease with prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

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Cressey, Anna; Jacobs, Deborah S; Remington, Crystal; Carrasquillo, Karen G

2018-06-01

To demonstrate clearing of chronic corneal opacities and improvement of visual acuity with the use of BostonSight prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in ocular surface disease. We undertook retrospective analysis of the medical records of a series of patients who underwent PROSE treatment from August 2006 to December 2014. Patients were referred for ocular surface disease of various etiologies. Primary inclusion criterion was corneal opacity that improved with PROSE treatment. Patients were excluded if topical steroids or adjuvant therapy used once PROSE treatment was initiated. Underlying disease, prior treatment, clinical presentation, and clinical course were extracted from the medical record. Four patients are included in this series. There were three females and one male; median age at time of treatment initiation was 30 years (range = 0.5-58 years). Median duration of PROSE treatment at time of retrospective analysis was 3.5 years (range = 1-8 years). Two cases had corneal opacification in the context of neurotrophic keratopathy: a unilateral case due to presumed herpes simplex keratitis and a bilateral case due to congenital corneal anesthesia associated with familial dysautonomia. One case had corneal opacity from exposure related to seventh nerve palsy, and one had corneal opacification associated with recurrent surface breakdown, neurotrophic keratopathy, and limbal stem deficiency of uncertain etiology. After consistent wear of prosthetic devices used in PROSE treatment for support of the ocular surface, visual acuity improved and clearing of the opacities was observed, without use of topical steroids or adjuvant therapy. These cases demonstrate clearing of chronic corneal opacity with PROSE treatment for ocular surface disease. This clearing can occur with no adjuvant therapy, suggesting that restoration of ocular surface function and integrity allows for corneal remodeling.

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

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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

Protective effects of trehalose on the corneal epithelial cells.

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Aragona, Pasquale; Colosi, Pietro; Rania, Laura; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

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

Inhibition of Corneal Neovascularization with the Combination of Bevacizumab and Plasmid Pigment Epithelium-Derived Factor-Synthetic Amphiphile INTeraction-18 (p-PEDF-SAINT-18 Vector in a Rat Corneal Experimental Angiogenesis Model

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Ching-Hsein Chen

2013-04-01

Full Text Available Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups (Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μg of p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV. The bFGF and PEDF genes were successfully expressed as shown by western blot analysis, and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival.Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonalantibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeabilityproperties. In this study, we demonstrated that the combination of bevacizumaband plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and

Healing of corneal epithelial wounds in marine and freshwater fish.

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Ubels, J L; Edelhauser, H F

The corneal epithelium of a fish is in direct contact with the aquatic environment and is a barrier to movement of ions and water into and through the cornea. This tissue layer is thus important in maintenance of corneal transparency. When the epithelium is wounded, its protective function is lost and corneal transparency remains compromised until the epithelial barrier is re-established. This study was undertaken to investigate the healing response of the fish cornea to epithelial abrasion. Wounds were stained with fluorescein and photographed during healing. Wound areas were measured by planimetry. The cornea of the sculpin, a marine teleost, becomes edematous after wounding and heals at 2.54 to 3.42 mm2/hr. Nonswelling corneas of the elasmobranchs--dogfish shark and skate--heal at 1.29 mm2/hr, respectively. The wounded eye of the rainbow trout, a freshwater teleost, is stressed by the low osmolality of the environment. Severe corneal edema and cataracts develop following epithelial wounding, and the cornea heals at 0.64 mm2/hr. Although the healing rates in teleosts differ from those in mammals, histology shows that the corneal healing mechanism is essentially the same in fish and mammals.

Effects of Pentacam on the posterior corneal surface height changes after LASEK and LASIK operation

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Qing-Song Zhang

2014-05-01

Full Text Available AIM: To explore the application of Pentacam excimer laser epithelial keratomileusis(LASEKand excimer laser in situ keratomileusis(LASIKafter the changes of posterior corneal surface height.METHODS: Retrospective analysis of clinical data of 100 patients with myopia by using LASEK and LASIK for the treatment of the 50 patients(100 eyesin our hospital from January 2013 to June 2013, surface height changes after preoperative and postoperative 3 months were compared by measuring Pentacam corneal analysis system.RESULTS: Three months after operation, the LASEK posterior corneal surface height was 7.4±5.0mm, significantly higher than 5.6±3.4mm before operation, LASIK posterior corneal surface height was 7.5±5.1mm, significantly higher than 5.5±3.5mm before operation, the differences were statistically significant(PP>0.05.CONCLUSION: LASEK and LASIK on corneal posterior surface forward, LASIK is slightly obvious in early period.

Resolution of persistent corneal erosion after administration of topical rebamipide

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Kashima T

2012-08-01

Full Text Available Tomoyuki Kashima,1,2 Hideo Akiyama,1 Fumihide Miura,2 Shoji Kishi11Department of Ophthalmology, Gunma University School of Medicine, Maebashi, Japan; 2Department of Ophthalmology, Saku Central Hospital, Saku, JapanAbstract: Rebamipide is an antiulcer agent used to treat gastric ulcer and gastritis. Biological effects of rebamipide include cytoprotection, wound healing, and anti-inflammatory properties that are known to be universal for a variety of tissues in addition to gastrointestinal mucosa. The therapeutic effects of rebamipide eye drops are due to its ability to increase corneal and conjunctival mucin-like substances and improve corneal and conjunctival injury in vivo. In this paper, we report a case of Sjögren's syndrome with complete disappearance of corneal erosion after administration of rebamipide eye drops. This was observed even though corneal erosion had not improved for 6 months after punctal occlusion surgery. The patient was a 33-year-old female, diagnosed with Sjögren's syndrome by a salivary gland biopsy. The corneal and conjunctival surfaces were filled with dense erosions, which did not improve with topical drugs. Punctal plugs were applied several times; however, the plugs were repeatedly shed. All four puncta of both eyelids were surgically occluded, and both corneal and conjunctival erosion was clearly improved. However, the erosion in the inferior cornea of both eyes had not improved for 6 months after surgery. We used the newly approved topical rebamipide for treatment of this patient. The corneal erosion gradually improved and completely disappeared 4 weeks after administration of the drug. Dry eye sensation disappeared at the same time. Both membrane-associated mucin and secreted mucin in the ocular surface are thought to be essential for maintenance of the tear film. Induction of mucin from ocular surface epithelium could be an effective treatment in cases of dry eye caused by mucin deficiency. Through its various

Laser-induced corneal cross-linking upon photorefractive ablation with riboflavin

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Kornilovskiy IM

2016-04-01

Full Text Available Igor M Kornilovskiy,1 Elmar M Kasimov,2 Ayten I Sultanova,2 Alexander A Burtsev1 1Department of Eye Diseases, Federal State Budgetary Institution “National Pirogov Medical Surgical Centre”, Ministry of Health, Moscow, Russia; 2Department of Eye Diseases, Zarifa Aliyeva National Ophthalmology Center, Ministry of Health, Baku, Azerbaijan Aim: To estimate the biomechanical effect of the laser-induced cross-linking resulting from photorefractive ablation of the cornea with riboflavin.Methods: Excimer laser ablation studies were performed ex vivo (32 eyes of 16 rabbits by phototherapeutic keratectomy (PTK and in vivo (24 eyes of 12 rabbits by transepithelial photorefractive keratectomy (TransPRK, with and without riboflavin saturation of the stroma. Then, we performed corneal optical coherence tomography on 36 eyes of 18 patients with varying degrees of myopia at different times after the TransPRK was performed with riboflavin saturation of the stroma.Results: Biomechanical testing of corneal samples saturated with riboflavin revealed cross-linking effect accompanied by the increase in tensile strength and maximum strength. PTK showed increase in tensile strength from 5.1±1.4 to 7.2±1.6 MPa (P=0.001, while TransPRK showed increase in tensile strength from 8.8±0.9 to 12.8±1.3 MPa (P=0.0004. Maximum strength increased from 8.7±2.5 to 12.0±2.8 N (P=0.005 in PTK and from 12.8±1.6 to 18.3±1.2 N (P=0.0004 in TransPRK. Clinical optical coherence tomography studies of the biomicroscopic transparent cornea at different times after TransPRK showed increased density in the surface layers of the stroma and membrane-like structure beneath the epithelium.Conclusion: Photorefractive ablation of the preliminary corneal stroma saturation with riboflavin causes the effect of laser-induced cross-linking, which is attended with an increase in corneal tensile strength, maximum strength, increased density in the surface layers of the stroma, and formation of

Treatment with solubilized Silk-Derived Protein (SDP enhances rabbit corneal epithelial wound healing.

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Waleed Abdel-Naby

Full Text Available There is a significant clinical need to improve current therapeutic approaches to treat ocular surface injuries and disease, which affect hundreds of millions of people annually worldwide. The work presented here demonstrates that the presence of Silk-Derived Protein (SDP on the healing rabbit corneal surface, administered in an eye drop formulation, corresponds with an enhanced epithelial wound healing profile. Rabbit corneas were denuded of their epithelial surface, and then treated for 72-hours with either PBS or PBS containing 5 or 20 mg/mL SDP in solution four times per day. Post-injury treatment with SDP formulations was found to accelerate the acute healing phase of the injured rabbit corneal epithelium. In addition, the use of SDP corresponded with an enhanced tissue healing profile through the formation of a multi-layered epithelial surface with increased tight junction formation. Additional biological effects were also revealed that included increased epithelial proliferation, and increased focal adhesion formation with a corresponding reduction in the presence of MMP-9 enzyme. These in vivo findings demonstrate for the first time that the presence of SDP on the injured ocular surface may aid to improve various steps of rabbit corneal wound healing, and provides evidence that SDP may have applicability as an ingredient in therapeutic ophthalmic formulations.

Protective Effects of Trehalose on the Corneal Epithelial Cells

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Pasquale Aragona

2014-01-01

Full Text Available Purpose. Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Methods. Twelve patients undergoing laser subepithelial keratomileusis (LASEK were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. Results. In both trehalose-untreated eyes (TUE and trehalose-treated eyes (TTE, the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Conclusions. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing

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After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6 (+) IL-17(+) gamma delta T cells migrate into the epithelium. Gamma delta T-cell-deficient (TCRd(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mR...

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

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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.

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

14-3-3{sigma} controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway

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Xin, Ying [Stem Cell Institute, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Lu, Qingxian [Tumor Immunobiology Group, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Li, Qiutang, E-mail: q.li@louisville.edu [Stem Cell Institute, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States)

2010-02-19

14-3-3{sigma} (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3{sigma} mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3{sigma} activity in corneal epithelial cells by overexpressing dominative negative 14-3-3{sigma} led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3{sigma} mutant-expressing corneal epithelial cells. We conclude that 14-3-3{sigma} is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity.

14-3-3σ controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway

International Nuclear Information System (INIS)

Xin, Ying; Lu, Qingxian; Li, Qiutang

2010-01-01

14-3-3σ (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3σ mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3σ activity in corneal epithelial cells by overexpressing dominative negative 14-3-3σ led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3σ mutant-expressing corneal epithelial cells. We conclude that 14-3-3σ is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity.

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

Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis.

Science.gov (United States)

Chen, Wei; Zhang, Xiaobo; Liu, Mimi; Zhang, Jingna; Ye, Ya; Lin, Ying; Luyckx, Jacques; Qu, Jia

2009-09-01

The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01 M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 microl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum

Corneal photoablation in vivo with the erbium:YAG laser: first report

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Jean, Benedikt J.; Bende, Thomas; Matallana, Michael; Kriegerowski, Martin

1995-05-01

As an alternative to far-UV lasers for corneal refractive surgery, the Erbium:YAG laser may be used in TEM00 mode. The resulting gaussian beam profile leads to a certain amount of myopic correction per laser pulse. Although animal data suggest that the clinical outcome should be comparable to the UV-lasers, no human data were available until now. We performed Erbium:YAG laser areal ablation in 5 blind human eyes. In TEM00 mode, the laser parameters were: effective diameter of laser spot equals 3.4 mm, fluence equals 380 mJ/cm2, pulse duration equals 250 microsecond(s) , Repetition rate equals 4 Hz, Number of applied laser pulses equals 15. Four patients with no light perception, one with intact light projection on one eye (some of them scheduled for enucleation) were treated under topical anaesthesia. Patient selection and informed consent were agreed to by the University's independent Ethics Committee. Prior to laser irradiation, corneal epithelium was removed. A postoperative silicone cast of the cornea was analyzed with a confocal laser micro-topometer for the ablation profile. The eyes were treated with antibiotic ointment until the epithelium was closed. Clinical appearance and, where possible, profilometry of the ablated area was observed. The ablation profile in cornea was gaussian shaped with a maximal depth of 30 micrometers . During laser treatment, the corneal surface becomes opaque, clearing in a matter of seconds. Epithelial healing and clinical appearance was similar to excimer laser treatment. However, during the first week, the irradiated area shows subepithelial irregularities, resembling small bubbles, disappearing thereafter.

Choline transport in the isolated rabbit corneal epithelium

International Nuclear Information System (INIS)

Faust, R.L.

1988-01-01

In the present study, isolated epithelial sheets were obtained by performing two sequential anterior keratectomies, three weeks apart, on rabbit corneas. Light microscopy of the isolated sheets revealed a multilayered epithelium with an intact basal cell layer without contamination from other cell types. The accumulation of [ 3 H]choline into the epithelial sheets was studied at substrate concentrations varying from 1 to 100 μMoles with and without the addition of specific metabolic and stereochemical inhibitors. Accumulation of [ 3 H]choline into these sheets was saturable. Kinetic analysis, performed by estimation from double-reciprocal plots, revealed a single component system with a K m of 24.9 μM. The metabolic inhibitors potassium cyanide and ouabain showed no effect on the uptake of [ 3 H]choline; however, the stereochemical inhibitor hemicholinium-3 significantly reduced the accumulation of radiolabel at both high and low substrate concentrations. The results suggest a non-energy dependent yet a highly specific transport system for the accumulation of choline into the rabbit epithelium

Corneal cell adhesion to contact lens hydrogel materials enhanced via tear film protein deposition.

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Claire M Elkins

Full Text Available Tear film protein deposition on contact lens hydrogels has been well characterized from the perspective of bacterial adhesion and viability. However, the effect of protein deposition on lens interactions with the corneal epithelium remains largely unexplored. The current study employs a live cell rheometer to quantify human corneal epithelial cell adhesion to soft contact lenses fouled with the tear film protein lysozyme. PureVision balafilcon A and AirOptix lotrafilcon B lenses were soaked for five days in either phosphate buffered saline (PBS, borate buffered saline (BBS, or Sensitive Eyes Plus Saline Solution (Sensitive Eyes, either pure or in the presence of lysozyme. Treated contact lenses were then contacted to a live monolayer of corneal epithelial cells for two hours, after which the contact lens was sheared laterally. The apparent cell monolayer relaxation modulus was then used to quantify the extent of cell adhesion to the contact lens surface. For both lens types, lysozyme increased corneal cell adhesion to the contact lens, with the apparent cell monolayer relaxation modulus increasing up to an order of magnitude in the presence of protein. The magnitude of this increase depended on the identity of the soaking solution: lenses soaked in borate-buffered solutions (BBS, Sensitive Eyes exhibited a much greater increase in cell attachment upon protein addition than those soaked in PBS. Significantly, all measurements were conducted while subjecting the cells to moderate surface pressures and shear rates, similar to those experienced by corneal cells in vivo.

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

Science.gov (United States)

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.

The application of excimer lasers for corneal sculpturing

International Nuclear Information System (INIS)

King, M.C.

1990-01-01

Of the broad selection of lasers available for surgery, the argon fluoride excimer laser offers a set of attributes that make it uniquely suited for the removal of corneal tissue. With ultraviolet radiation at 193mm, the energy of an individual photon (6.3 electron volts) is sufficient to break bonds in protein molecules without generating molecular vibration (heat). A single laser pulse is capable of removing 0.25 microns of corneal tissue over a well defined area 80 mm 2 in extent. This excision with a lateral precision to a fraction of a micron causes no discernible damage to neighboring cells. The smooth surface left after the tissue is removed promotes a quick and predictable regrowth of the epithelium. The penetration of radiation into the underlying tissue is the order of a micron so there is no potential harm to the lens or retinal tissue. Insignificant mutagenesis or unscheduled DNA synthesis has been detected as a result of tissue irradiation at this wavelength. In the past few years major progress has been made towards developing ophthalmic procedures which utilize the unique properties of this laser. To date there are FDA IDE's (Investigational Device Exemptions) for the following procedures: Photorefractive Keratectomy (PRK) or corneal reshaping for correcting near-sightedness, far-sightedness and astigmatism without the need for eye glasses, contact lenses or conventional refractive surgery (Radial Keratotomy); Partial Excimer Trabeculectomy for relieving the pressure build-up caused by glaucoma; T-Excisons for reducing astigmatism; Myopic Keratomileusis (MKM) for the refractive correction of severe myopia; superficial Keratectomy (corneal smoothing) for treating various corneal scars, dystrophies, recurrent corneal erosion etc. In this paper the fundamentals of beam tissue interaction at 193nm will be discussed

Toxicological effects and recovery of the corneal epithelium in Cyprinus carpio communis Linn. exposed to monocrotophos: an scanning electron microscope study.

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Uppal, Ravneet Kaur; Johal, Mohinder Singh; Sharma, Madan Lal

2015-05-01

This study was conducted based on the evidence of fish habitats in North India being affected by organophosphate pesticides draining from agricultural fields into bodies of water, especially during the rainy season. Various tissues of fish such as scales, gills ovaries, kidney, and liver have been studied from the toxicological point of view, but the toxicological effects of aquatic pollutants on fish cornea have not been investigated to date. We conducted comparative toxicological studies on the cornea of Cyprinus carpio communis using two sublethal (0.038 and 0.126 ppm) concentrations of monocrotophos pesticide for 30 days. Corneas from all the groups were evaluated by a scanning electron microscope. The fish exposed to the monocrotophos pesticide developed corneal necrosis due to the formation of crystalloid-like structures, thinning and shrinkage of microridges on the corneal epithelium. After 30 days, fish from the monocrotophos-treated tank were transferred to normal environmental conditions. After 60 days under natural condition, epithelial cells did not fully recover. In conclusion, exposure to monocrotophos induces irreversible changes in the cornea of C. carpio communis. As fish and mammalian visual systems share many similarities, the reported finding may offer useful insights for further toxicological and ophthalmological studies in humans. © 2013 American College of Veterinary Ophthalmologists.

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.

Regional variations of cell surface carbohydrates in human oral stratified epithelium

DEFF Research Database (Denmark)

Vedtofte, P; Dabelsteen, Erik; Hakomori, S

1984-01-01

The distribution of blood group carbohydrate chains with antigen A, B, H type 2 chain (A and B precursor), and N-acetyllactosamine (H type 2 precursor) specificity was studied in human oral epithelium from different anatomical regions. These represented various epithelial differentiation patterns...... epithelium from nine blood group A, two blood group B, and nine blood group O individuals. The blood group carbohydrate chains were examined in tissue sections by immunofluorescence microscopy. The A and B blood group antigens were detected by human blood group sera, and antigen H type 2 chains and N...... antigen H type 2 chains in metaplastically keratinized buccal epithelium was found to differ significantly from that seen in normal non-keratinized buccal epithelium. The regional variations demonstrated in cell surface carbohydrates are suggested to reflect differences in tissue differentiation....

Comparison of transepithelial corneal crosslinking with epithelium-off crosslinking (epithelium-off CXL in adult Pakistani population with progressive keratoconus

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Bushra Akbar

2017-01-01

CONCLUSION: Transepithelial CXL is not recommended to be replaced completely by standard epithelium-off CXL due to continued ectatic progression in 25% of cases. However, thin corneas, unfit for standard epithelium-off CXL, can benefit from transepithelial CXL.

An examination of surface epithelium structures of the embryo across the genus Poeciliopsis (Poeciliidae).

Science.gov (United States)

Panhuis, Tami M; Fris, Megan; Tuhela, Laura; Kwan, Lucia

2017-12-01

In viviparous, teleost fish, with postfertilization maternal nutrient provisioning, embryonic structures that facilitate maternal-fetal nutrient transfer are predicted to be present. For the family Poeciliidae, only a handful of morphological studies have explored these embryonic specializations. Here, we present a comparative morphological study in the viviparous poeciliid genus, Poeciliopsis. Using microscopy techniques, we examine the embryonic surface epidermis of Poeciliopsis species that vary in their level of postfertilization maternal nutrient provisioning and placentation across two phylogenetic clades and three independent evolutionary origins of placentation. We focus on surface features of the embryo that may facilitate maternal-fetal nutrient transfer. Specifically, we studied cell apical-surface morphology associated with the superficial epithelium that covers the body and sac (yolk and pericardial) of embryos at different developmental stages. Scanning electron microscopy revealed common surface epithelial cells across species, including pavement cells with apical-surface microridges or microvilli and presumed ionocytes and/or mucus-secreting cells. For three species, in the mid-stage embryos, the surface of the body and sac were covered in microvillus epithelium. The remaining species did not display microvillus epithelium at any of the stages examined. Instead, their epithelium of the body and sac were composed of cells with apical-surface microridges. For all species, in the late stage embryos, the surface of the body proper was composed of apical-surface microridges in a "fingerprint-like arrangement." Despite the differences in the surface epithelium of embryos across Poeciliopsis species and embryonic developmental stages, this variation was not associated with the level of postfertilization maternal nutrient provisioning. We discuss these results in light of previous morphological studies of matrotrophic, teleost fish, phylogenetic

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

Science.gov (United States)

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.

Effect of topical vitamin E on ethanol-induced corneal epithelial apoptosis.

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Bilgihan, Kamil; Konuk, Onur; Hondur, Ahmet; Akyürek, Nalan; Ozogul, Candan; Hasanreisoglu, Berati

2005-01-01

Ethanol is used to loosen the corneal epithelium before photoablation in laser subepithelial keratomileusis (LASEK). In this study, the apoptotic index of corneal epithelium after ethanol exposure and the effects of topical vitamin E were evaluated. The study was performed on 28 rabbit eyes in four groups. Group 1 comprised the controls. In group 2, 20% ethanol was applied topically for 20 seconds. In group 3, topical vitamin E was applied following 20% ethanol application. In group 4, only topical vitamin E was applied. Apoptosis was evaluated with TUNEL assay and transmission electron microscopy. Epithelial apoptosis was detected in all specimens in group 2. No apoptosis was detected in other groups except for one eye in group 1. The apoptotic index in group 2 was statistically higher than other groups (P < .001).

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.

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.

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

Science.gov (United States)

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.

Plasma polymer-coated contact lenses for the culture and transfer of corneal epithelial cells in the treatment of limbal stem cell deficiency.

Science.gov (United States)

Brown, Karl David; Low, Suet; Mariappan, Indumathi; Abberton, Keren Maree; Short, Robert; Zhang, Hong; Maddileti, Savitri; Sangwan, Virender; Steele, David; Daniell, Mark

2014-02-01

Extensive damage to the limbal region of the cornea leads to a severe form of corneal blindness termed as limbal stem cell deficiency (LSCD). Whereas most cases of corneal opacity can be treated with full thickness corneal transplants, LSCD requires stem cell transplantation for successful ocular surface reconstruction. Current treatments for LSCD using limbal stem cell transplantation involve the use of murine NIH 3T3 cells and human amniotic membranes as culture substrates, which pose the threat of transmission of animal-derived pathogens and donor tissue-derived cryptic infections. In this study, we aimed to produce surface modified therapeutic contact lenses for the culture and delivery of corneal epithelial cells for the treatment of LSCD. This approach avoids the possibility of suture-related complications and is completely synthetic. We used plasma polymerization to deposit acid functional groups onto the lenses at various concentrations. Each surface was tested for its suitability to promote corneal epithelial cell adhesion, proliferation, retention of stem cells, and differentiation and found that acid-based chemistries promoted better cell adhesion and proliferation. We also found that the lenses coated with a higher percentage of acid functional groups resulted in a higher number of cells transferred onto the corneal wound bed in rabbit models of LSCD. Immunohistochemistry of the recipient cornea confirmed the presence of autologous, transplanted 5-bromo-2'-deoxyuridine (BrdU)-labeled cells. Hematoxylin staining has also revealed the presence of a stratified epithelium at 26 days post-transplantation. This study provides the first evidence for in vivo transfer and survival of cells transplanted from a contact lens to the wounded corneal surface. It also proposes the possibility of using plasma polymer-coated contact lenses with high acid functional groups as substrates for the culture and transfer of limbal cells in the treatment of LSCD.

Conditional inactivation of p53 in mouse ovarian surface epithelium does not alter MIS driven Smad2-dominant negative epithelium-lined inclusion cysts or teratomas.

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Suzanne M Quartuccio

Full Text Available Epithelial ovarian cancer is the most lethal gynecological malignancy among US women. The etiology of this disease, although poorly understood, may involve the ovarian surface epithelium or the epithelium of the fallopian tube fimbriae as the progenitor cell. Disruptions in the transforming growth factor beta (TGFβ pathway and p53 are frequently found in chemotherapy-resistant serous ovarian tumors. Transgenic mice expressing a dominant negative form of Smad2 (Smad2DN, a downstream transcription factor of the TGFβ signaling pathway, targeted to tissues of the reproductive tract were created on a FVB background. These mice developed epithelium-lined inclusion cysts, a potential precursor lesion to ovarian cancer, which morphologically resembled oviductal epithelium but exhibited protein expression more closely resembling the ovarian surface epithelium. An additional genetic "hit" of p53 deletion was predicted to result in ovarian tumors. Tissue specific deletion of p53 in the ovaries and oviducts alone was attempted through intrabursal or intraoviductal injection of Cre-recombinase expressing adenovirus (AdCreGFP into p53 (flox/flox mice. Ovarian bursal cysts were detected in some mice 6 months after intrabursal injection. No pathological abnormalities were detected in mice with intraoviductal injections, which may be related to decreased infectivity of the oviductal epithelium with adenovirus as compared to the ovarian surface epithelium. Bitransgenic mice, expressing both the Smad2DN transgene and p53 (flox/flox, were then exposed to AdCreGFP in the bursa and oviductal lumen. These mice did not develop any additional phenotypes. Exposure to AdCreGFP is not an effective methodology for conditional deletion of floxed genes in oviductal epithelium and tissue specific promoters should be employed in future mouse models of the disease. In addition, a novel phenotype was observed in mice with high expression of the Smad2DN transgene as validated

Effect of Schizandra chinensis lignans on cell division in the corneal epithelium and tongue of albino rats exposed to chronic cold stress

International Nuclear Information System (INIS)

Mel'nik, E.I.; Lupandin, A.V.; Timoshin, S.S.

1985-01-01

The authors study the possibility of correcting cellular manifestations of disadaptation following chronic exposure to cold stress by means of preparations of Sch. chinensis. The model of chronic stress was cooling male albino rats daily for 1.5 h to a temperature of 28-30 C for 28 days. Since differences between levels of proliferation in intact animals and in the rats receiving 1.9% ethanol solution were absent, values obtained in the group of intact animals are presented in a table as the control. The animals underwent euthanasia 48 hours after the final exposure to the cold. The rats received an injection of tritium-thymidine one hour before sacrifice. It is shown that the results confirm those in previous studies of stimulation of DNA synthesis and mitotic activity in the corneal and lingual epithelium of albino rats during chronic exposure to stress

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

Science.gov (United States)

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

A novel collagen film with micro-rough surface structure for corneal epithelial repair fabricated by freeze drying technique

International Nuclear Information System (INIS)

Liu, Yang; Ren, Li; Wang, Yingjun

2014-01-01

Highlights: • Collagen film with micro-rough surface is fabricated by freeze drying technique. • The film has suitable water uptake capability and toughness performance. • The film has good optical performance. • Human corneal epithelial cells studies confirmed the biocompatibility of the film. - Abstract: Corneal epithelial defect is a common disease and keratoplasty is a common treatment method. A collagen film with micro-rough surface was fabricated through a simple freeze drying technique in this study. Compared with the air-dried collagen film (AD-Col), this freeze-dried collagen film (FD-Col) has a more suitable water uptake capability (about 85.5%) and toughness performance. Both of the two films have good optical properties and the luminousness of them is higher than 80%. Besides, the adhesion and proliferation rate of human corneal epithelial cells on the micro-rough surface of FD-Col film is higher than that on the smooth surface of AD-Col film. The results indicate that this FD-Col film may have potential applications for corneal epithelial repair

A novel collagen film with micro-rough surface structure for corneal epithelial repair fabricated by freeze drying technique

Energy Technology Data Exchange (ETDEWEB)

Liu, Yang [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China); Ren, Li, E-mail: psliren@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China); Wang, Yingjun, E-mail: imwangyj@163.com [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China)

2014-05-01

Highlights: • Collagen film with micro-rough surface is fabricated by freeze drying technique. • The film has suitable water uptake capability and toughness performance. • The film has good optical performance. • Human corneal epithelial cells studies confirmed the biocompatibility of the film. - Abstract: Corneal epithelial defect is a common disease and keratoplasty is a common treatment method. A collagen film with micro-rough surface was fabricated through a simple freeze drying technique in this study. Compared with the air-dried collagen film (AD-Col), this freeze-dried collagen film (FD-Col) has a more suitable water uptake capability (about 85.5%) and toughness performance. Both of the two films have good optical properties and the luminousness of them is higher than 80%. Besides, the adhesion and proliferation rate of human corneal epithelial cells on the micro-rough surface of FD-Col film is higher than that on the smooth surface of AD-Col film. The results indicate that this FD-Col film may have potential applications for corneal epithelial repair.

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.

Corneal modeling for analysis of photorefractive keratectomy

Science.gov (United States)

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

Anterior corneal profile with variable asphericity.

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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.

Mutations in LOXHD1, a Recessive-Deafness Locus, Cause Dominant Late-Onset Fuchs Corneal Dystrophy

Science.gov (United States)

Riazuddin, S. Amer; Parker, David S.; McGlumphy, Elyse J.; Oh, Edwin C.; Iliff, Benjamin W.; Schmedt, Thore; Jurkunas, Ula; Schleif, Robert; Katsanis, Nicholas; Gottsch, John D.

2012-01-01

Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHD1 mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes. PMID:22341973

Estimation of the in vitro eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust by using reconstituted human corneal epithelium tissue cultures

DEFF Research Database (Denmark)

Cao, Yi; Arenholt-Bindslev, Dorthe; Kjærgaard, Søren K

2015-01-01

CONTEXT: Eye irritation is a common complaint in indoor environment, but the causes have still not been identified among the multiple exposures in house environments. To identify the potential environmental factors responsible for eye irritation and study the possible mechanisms, an in vitro model...... AND CONCLUSION: LPS and dust showed in vitro eye irritating and inflammatory potential, and cytokines/chemokines like IL-1β and IL-8 may be involved in the mechanisms of eye irritation. The HCE tissue culture may be used as an in vitro model to study environmental exposure induced eye irritation and inflammation....... for eye irritation is suggested. MATERIALS AND METHODS: In this study, reconstituted human corneal epithelium (HCE) tissue cultures were used to study the eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust. HCE tissue cultures were exposed to a range of concentrations of LPS...

Corneal wound healing is compromised by immunoproteasome deficiency.

Directory of Open Access Journals (Sweden)

Deborah A Ferrington

Full Text Available Recent studies have revealed roles for immunoproteasome in regulating cell processes essential for maintaining homeostasis and in responding to stress and injury. The current study investigates how the absence of immunoproteasome affects the corneal epithelium under normal and stressed conditions by comparing corneas from wildtype (WT mice and those deficient in two immunoproteasome catalytic subunits (lmp7(-/-/mecl-1(-/-, L7M1. Immunoproteasome expression was confirmed in WT epithelial cells and in cells of the immune system that were present in the cornea. More apoptotic cells were found in both corneal explant cultures and uninjured corneas of L7M1 compared to WT mice. Following mechanical debridement, L7M1 corneas displayed delayed wound healing, including delayed re-epithelialization and re-establishment of the epithelial barrier, as well as altered inflammatory cytokine production compared to WT mice. These results suggest that immunoproteasome plays an important role in corneal homeostasis and wound healing.

Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

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Jastrzebski, Andre; Brownstein, Seymour; Ziai, Setareh; Saleh, Solin; Lam, Kay; Jackson, W Bruce

2017-06-01

We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). Retrospective case report. A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

Surface to nuclear distances in human bronchial epithelium: Relationships to penetration by Rn daughters

International Nuclear Information System (INIS)

Baldwin, F.; Hovey, A.; McEwen, T.; O'Connor, R.; Unruh, H.; Bowden, D.H.

1991-01-01

Lung cancer in U miners is thought to be related to the inhalation of particulate Rn daughters. Since the depth of penetration by alpha particles is short, the thickness of the epithelium lining the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the study were to measure the thickness of the epithelium at all levels of the human bronchial tree, to determine the distances of epithelial nuclei from the mucociliary surface, and to compare these parameters in smokers and nonsmokers. Twenty-nine surgically removed specimens were examined; 26 were from smokers. No significant differences were found between smokers and nonsmokers, allowing us to treat the 29 cases as a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness, and distances of nuclei from the surface are also less in the peripheral bronchi. Allowing for artefacts of tissue preparation, the mean distance from the mucociliary surface to the underlying nuclei varies between 17 and 38 microns

Dry eye evaluation and correlation analysis between tear film stability and corneal surface regularity after small incision lenticule extraction.

Science.gov (United States)

Zhang, Hui; Wang, Yan

2017-09-22

To investigate the dry eye after small incision lenticule extraction (SMILE) and explore the correlations between changes in the tear film stability, the tear secretion and the corneal surface regularity. Sixty-two eyes of 22 men and 13 women who underwent SMILE were included in this study. Corneal topography was measured to assess the index of surface variance (ISV) and the index of vertical asymmetry (IVA). Dry eye tests including subjective symptom questionnaire, tear breakup time (TBUT), corneal fluorescein staining and Schirmer's test (ST) were evaluated before and at 1 and 6 months postoperatively. TBUT was found to be significantly decreased from 9.8 ± 3.4 s preoperatively to 7.4 ± 3.8 s at 1 month and 6.5 ± 3.6 s at 6 months (both P short-TBUT type of dry eye. Corneal surface regularity indices might be helpful in the assessment of tear film stability following SMILE procedure.

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

Posterior corneal surface differences between non-laser in situ keratomileusis (LASIK) and 10-year post-LASIK myopic eyes.

Science.gov (United States)

Dai, Ma-Li; Wang, Qin-Mei; Lin, Zu-Shun; Yu, Ye; Huang, Jin-Hai; Savini, Giacomo; Zhang, Jia; Wang, Ling; Xu, Chen-Chen

2018-03-01

To evaluate the posterior corneal surface differences between non-laser in situ keratomileusis (LASIK) and 10-year post-LASIK myopic eyes. The study included 130 eyes from 65 patients, who were treated with myopic LASIK 10 years ago. In addition, 130 eyes from 65 unoperated myopic patients of matching present age and preoperative refraction were divided into control group. Data on the posterior corneal surface and anterior chamber were obtained from Pentacam software and compared between the groups. Postoperative visual acuity (VA) and refractive error were also analysed. The mean preoperative spherical equivalent (SE) was -6.99 ± 1.78 dioptre (D) in the LASIK group. Ten years after surgery, the mean SE was -0.45 ± 1.22 D, the efficacy index was 0.98, and the safety index was 1.01. The posterior corneal elevations of the LASIK group at 2 mm corneal diameter were significantly lower than those of the control group. However, posterior corneal elevations at 6 mm corneal diameter were higher in the LASIK group than the controls (p LASIK group than in controls. Meanwhile, the anterior chamber volumes (ACV) were smaller in the LASIK group than in the control group. Our results demonstrated that the posterior corneal surface tends to show signs of central flattening and peripheral steepening 10 years after myopic LASIK surgery compared to that of non-operated myopic eyes. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The effect of Gonioscopy on keratometry and corneal surface topography.

Science.gov (United States)

George, Mathew K; Kuriakose, Thomas; DeBroff, Brian M; Emerson, John W

2006-06-17

Biometric procedures such as keratometry performed shortly after contact procedures like gonioscopy and applanation tonometry could affect the validity of the measurement. This study was conducted to understand the short-term effect of gonioscopy on corneal curvature measurements and surface topography based Simulated Keratometry and whether this would alter the power of an intraocular lens implant calculated using post-gonioscopy measurements. We further compared the effect of the 2-mirror (Goldmann) and the 4-mirror (Sussman) Gonioscopes. A prospective clinic-based self-controlled comparative study. 198 eyes of 99 patients, above 50 years of age, were studied. Exclusion criteria included documented dry eye, history of ocular surgery or trauma, diabetes mellitus and connective tissue disorders. Auto-Keratometry and corneal topography measurements were obtained at baseline and at three follow-up times - within the first 5 minutes, between the 10th-15th minute and between the 20th-25th minute after intervention. One eye was randomized for intervention with the 2-mirror gonioscope and the other underwent the 4-mirror after baseline measurements. t-tests were used to examine differences between interventions and between the measurement methods. The sample size was calculated using an estimate of clinically significant lens implant power changes based on the SRK-II formula. Clinically and statistically significant steepening was observed in the first 5 minutes and in the 10-15 minute interval using topography-based Sim K. These changes were not present with the Auto-Keratometer measurements. Although changes from baseline were noted between 20 and 25 minutes topographically, these were not clinically or statistically significant. There was no significant difference between the two types of gonioscopes. There was greater variability in the changes from baseline using the topography-based Sim K readings. Reversible steepening of the central corneal surface is produced by

Caveolin-1 as a Novel Indicator of Wound-Healing Capacity in Aged Human Corneal Epithelium

OpenAIRE

Rhim, Ji Heon; Kim, Jae Hoon; Yeo, Eui-Ju; Kim, Jae Chan; Park, Sang Chul

2010-01-01

Excess caveolin-1 has been reported to play a role in age-dependent hyporesponsiveness to growth factors in vitro. Therefore, we hypothesized that caveolin-1–dependent hyporesponsiveness to growth factors in aged corneal epithelial cells might be responsible for delayed wound healing in vivo. To test this hypothesis, we evaluated corneal wound-healing time by vital staining using fluorescein after laser epithelial keratomileusis (LASEK). We compared wound-healing times in young, middle-aged a...

Effect of the Regenerative Agent Poly(Carboxymethylglucose Sulfate) on Corneal Wound Healing After Corneal Cross-Linking for Keratoconus.

Science.gov (United States)

Kymionis, George D; Liakopoulos, Dimitrios A; Grentzelos, Michael A; Tsoulnaras, Konstantinos I; Detorakis, Efstathios T; Cochener, Béatrice; Tsilimbaris, Miltiadis K

2015-08-01

To evaluate the effect of a regenerative agent (RGTA) [Cacicol20-poly(carboxymethyl glucose sulfate); OTR3, Paris, France] on corneal reepithelialization and pain after corneal cross-linking (CXL) for keratoconus. In this prospective comparative (contralateral) clinical study, patients with bilateral progressive keratoconus underwent CXL treatment. The corneal epithelium during CXL was removed using transepithelial phototherapeutic keratectomy (Cretan protocol). One eye of each patient was randomly instilled with an RGTA (Cacicol20) once a day (study group), whereas the fellow eye was instilled with artificial tears (control group). Patients were examined daily until complete reepithelialization. Postoperative examinations included slit-lamp biomicroscopy to assess the epithelial defect size and subjective evaluation of pain. The study enrolled 18 patients (36 eyes). The mean epithelial defect size for study and control groups was 19.6 ± 4.2 mm versus 21.5 ± 2.8 mm, respectively, at day 1 (P = 0.019) and 6.4 ± 3.4 mm versus 7.9 ± 4.3 mm, respectively, at day 2 (P = 0.014). At day 3 postoperatively, 61.1% of study eyes were fully reepithelialized, compared with 11.1% of control eyes (P = 0.002). RGTA (Cacicol20) instillation seems to result in faster corneal reepithelialization after CXL in this study. However, there was no significant effect in subjective pain/discomfort.

The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

Science.gov (United States)

Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

2014-05-02

The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

Higher order optical aberrations and visual acuity in a randomized controlled trial comparing transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus

Directory of Open Access Journals (Sweden)

Godefrooij DA

2017-10-01

Full Text Available Daniel A Godefrooij, Mustapha El Kandoussi, Nienke Soeters, Robert PL Wisse Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands Purpose: The purpose of this study was to compare the effects of transepithelial crosslinking (trans-CXL versus epithelium-off crosslinking (epi-off CXL for progressive keratoconus with respect to the development of higher order aberrations (HOAs and their effects on visual acuity.Materials and methods: A total of 61 patients were randomized and examined preoperatively and 1, 3, 6, and 12 months postoperatively in an academic referral center. Total corneal HOAs were compared between the two treatment groups using mixed linear modeling. Types of HOAs (coma, trefoil, and spherical aberration that differed between groups were entered in a multivariable analysis to test their effect on uncorrected distance visual acuity (UDVA and corrected distance visual acuity (CDVA.Results: The epi-off CXL group had more flattening in maximal keratometry compared to the trans-CXL group (P=0.02. UDVA did not differ significantly between the groups (P=0.59; however, CDVA was significantly more improved in the trans-CXL group (P=0.02. Horizontal trefoil improved more in the epi-off group compared to the trans-CXL group (P=0.04, whereas the other HOAs were virtually unchanged in both groups. Differences in changes in HOAs between the two groups had no effect on either UCVA (P=0.76 or CDVA (P=0.96.Conclusion: Although HOAs are clinically relevant determinants of vision quality in keratoconus patients, the change in total HOAs post treatment did not differ between the trans-CXL and epi-off CXL groups. Only horizontal trefoil differed significantly post treatment between the trans-CXL and epi-off CXL groups. However, this difference did not independently affect either UDVA or CDVA. Trans-CXL provides no benefit over epi-off CXL regarding visual relevant HOAs. Keywords

Ocular surface alterations and in vivo confocal microscopic characteristics of corneas in patients with myasthenia gravis.

Science.gov (United States)

Erkan Turan, Kadriye; Kocabeyoglu, Sibel; Bekircan-Kurt, Can Ebru; Bezci, Figen; Erdem-Ozdamar, Sevim; Irkec, Murat

2018-03-01

To evaluate ocular surface alterations and characteristics of corneal basal epithelium and subbasal nerves in patients with myasthenia gravis. Myasthenia gravis patients (n = 21) and healthy controls (n = 20) were enrolled. All participants underwent ocular surface testing in the following order: tear break-up time, lissamine green staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index questionnaire. The Cochet-Bonnet esthesiometer was used to measure corneal sensitivity. Basal epithelial cells and subbasal nerves were evaluated using in vivo confocal microscopy. Myasthenia gravis patients had higher Ocular Surface Disease Index score (13.9 ± 15.0 vs 1.4 ± 2.2, p myasthenia gravis had lower basal epithelial cell density (3775.7 ± 938.1 vs 4983.1 ± 608.5, p myasthenia gravis and the number of corneal nerves (rho = -0.497, p = 0.022). Significant alterations of basal epithelial cells and subbasal nerves were demonstrated in myasthenia gravis patients although there was no difference of corneal sensitivity between myasthenia gravis patients and healthy controls. Thus, it should be borne in mind that myasthenia gravis patients deserve further evaluation with regard to ocular surface disease.

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.

Elevated IGFBP3 levels in diabetic tears: a negative regulator of IGF-1 signaling in the corneal epithelium.

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Wu, Yu-Chieh; Buckner, Benjamin R; Zhu, Meifang; Cavanagh, H Dwight; Robertson, Danielle M

2012-04-01

To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. Tear samples were collected noninvasively from diabetic subjects and non-diabetic controls; corneal sensitivity was assessed using a Cochet-Bonnet Aesthesiometer. Conditioned media were collected following culture of hTCEpi cells in normal (5 mM) and elevated (25 mM) glucose conditions; mannitol was used as an osmotic control. IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). Total and phosphorylated IGF-1R expression in whole cell lysates was assessed by western blot. There was a 2.8-fold increase in IGFBP3 in diabetic tears compared to non-diabetic controls (P=0.006); IGF-1 levels were not significantly altered. No difference in corneal sensitivity was detected between groups. The concentration of IGFBP3 in tears was independent of IGF-1. Consistent with human tear measurements in vivo, IGFBP3 secretion was increased 2.2 fold (Ptears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (Ptears may attenuate IGF-1R signaling in the diabetic cornea. A long-term increase in IGFBP3 may contribute to epithelial compromise and the pathogenesis of ocular surface complications reported in diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

Microspectroscopy of spectral biomarkers associated with human corneal stem cells

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Nakamura, Takahiro; Kelly, Jemma G.; Trevisan, J?lio; Cooper, Leanne J.; Bentley, Adam J.; Carmichael, Paul L.; Scott, Andrew D.; Cotte, Marine; Susini, Jean; Martin-Hirsch, Pierre L.; Kinoshita, Shigeru; Fullwood, Nigel J.; Martin, Francis L.

2010-01-01

Purpose Synchrotron-based radiation (SRS) Fourier-transform infrared (FTIR) microspectroscopy potentially provides novel biomarkers of the cell differentiation process. Because such imaging gives a ?biochemical-cell fingerprint? through a cell-sized aperture, we set out to determine whether distinguishing chemical entities associated with putative stem cells (SCs), transit-amplifying (TA) cells, or terminally-differentiated (TD) cells could be identified in human corneal epithelium. Methods D...

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

Primary Outcomes of Accelerated Epithelium-Off Corneal Cross-Linking in Progressive Keratoconus in Children: A 1-Year Prospective Study

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Sherif A. Eissa

2017-01-01

Full Text Available Purpose. To evaluate corneal transparency following accelerated collagen cross-linking (ACXL in pediatric keratoconus. Design. A prospective interventional case series. Methods. This study included 47 eyes (25 patients, aged 9–14 years, with documented progressive keratoconus. After applying 0.1% riboflavin drops, ACXL was performed. Assessment included corrected distance visual acuity (CDVA, uncorrected visual acuity (UCVA, corneal haze, and corneal densitometry in grayscale units (GSU. Result. The mean baseline and corneal densitometry peaked at 3 months post-ACXL while central and posterior densitometry showed a statistically significant increase (P<0.05 and peaked at 8 months postoperatively. By 12 months, densitometry in all corneal layers (P≥0.99 and concentric zones (P≥0.97 reached near baseline values. Slit-lamp graded haze peaked at 1 month to 1.82 ± 0.65 (P<0.05 and declined to near baseline at 12 months (0.39 ± 0.58. There was a statistically significant increase in the mean UCVA and CDVA at 12 months. Conclusion. Total and anterior corneal densitometry peaked after 3 months, while central and posterior densitometry peaked after 8 months. Maximum haze was at 1 month post-ACXL. All corneal layers, concentric zone densitometry and haze reached near baseline values after 1 year. Scheimpflug densitometry showed weak correlation with CDVA over the 12-month follow-up period (r=−0.193.

The effect of Gonioscopy on keratometry and corneal surface topography

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DeBroff Brian M

2006-06-01

Full Text Available Abstract Background Biometric procedures such as keratometry performed shortly after contact procedures like gonioscopy and applanation tonometry could affect the validity of the measurement. This study was conducted to understand the short-term effect of gonioscopy on corneal curvature measurements and surface topography based Simulated Keratometry and whether this would alter the power of an intraocular lens implant calculated using post-gonioscopy measurements. We further compared the effect of the 2-mirror (Goldmann and the 4-mirror (Sussman Gonioscopes. Methods A prospective clinic-based self-controlled comparative study. 198 eyes of 99 patients, above 50 years of age, were studied. Exclusion criteria included documented dry eye, history of ocular surgery or trauma, diabetes mellitus and connective tissue disorders. Auto-Keratometry and corneal topography measurements were obtained at baseline and at three follow-up times – within the first 5 minutes, between the 10th-15th minute and between the 20th-25th minute after intervention. One eye was randomized for intervention with the 2-mirror gonioscope and the other underwent the 4-mirror after baseline measurements. t-tests were used to examine differences between interventions and between the measurement methods. The sample size was calculated using an estimate of clinically significant lens implant power changes based on the SRK-II formula. Results Clinically and statistically significant steepening was observed in the first 5 minutes and in the 10–15 minute interval using topography-based Sim K. These changes were not present with the Auto-Keratometer measurements. Although changes from baseline were noted between 20 and 25 minutes topographically, these were not clinically or statistically significant. There was no significant difference between the two types of gonioscopes. There was greater variability in the changes from baseline using the topography-based Sim K readings

Reinstatement of "germinal epithelium" of the ovary

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Nishida Naoyo

2006-08-01

Full Text Available Abstract Background The existing dogma that the former term ovarian "germinal epithelium" resulted from a mistaken belief that it could give rise to new germ cells is now strongly challenged. Discussion Two years ago, a research group of the University of Tennessee led by Antonin Bukovsky successfully demonstrated the oogenic process from the human ovarian covering epithelium now commonly called the ovarian surface epithelium. They showed the new oocyte with zona pellucida and granulosa cells, both originated from the surface epithelium arising from mesenchymal cells in the tunica albuginea, and stressed that the human ovary could form primary follicles throughout the reproductive period. This gives a big impact not only to the field of reproductive medicine, but also to the oncologic area. The surface epithelium is regarded as the major source of ovarian cancers, and most of the neoplasms exhibit the histology resembling müllerian epithelia. Since the differentiating capability of the surface epithelium has now expanded, the histologic range of the neoplasms in this category may extend to include both germ cell tumors and sex cord-stromal cell tumors. Summary Since the oogenic capability of ovarian surface cells has been proven, it is now believed that the oocytes can originate from them. The term "germinal epithelium", hence, might reasonably be reinstated.

Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model.

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Zhang, Wei; Chen, Jialin; Backman, Ludvig J; Malm, Adam D; Danielson, Patrik

2017-03-01

The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm -1 optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% dome-shaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Corneal thickness changes during corneal collagen cross-linking with UV-A irradiation and hypo-osmolar riboflavin in thin corneas

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Belquiz Amaral Nassaralla

2013-06-01

Full Text Available PURPOSE: To evaluate the thinnest corneal thickness changes during and after corneal collagen cross-linking treatment with ultraviolet-A irradiation, using hypo-osmolar riboflavin solution in thin corneas. METHODS: Eighteen eyes of 18 patients were included in this study. After epithelium removal, iso-osmolar 0.1% riboflavin solution was instilled to the cornea every 3 minutes for 30 minutes. Hypo-osmolar 0.1% riboflavin solution was then applied every 20 seconds for 5 minutes or until the thinnest corneal thickness reached 400 µm. Ultraviolet-A irradiation was performed for 30 minutes. During irradiation, iso-osmolar 0.1% riboflavin drops were applied every 5 minutes. Ultrasound pachymetry was performed at approximately the thinnest point of the cornea preoperatively, after epithelial removal, after iso-osmolar riboflavin instillation, after hypo-osmolar riboflavin instillation, after ultraviolet-A irradiation, and at 1, 6 and 12 months after treatment. RESULTS: Mean preoperative thinnest corneal thickness was 380 ± 11 µm. After epithelial removal it decreased to 341 ± 11 µm, and after 30 minutes of iso-osmolar 0.1% riboflavin drops, to 330 ± 7.6 µm. After hypo-osmolar 0.1% riboflavin drops, mean thinnest corneal thickness increased to 418 ± 11 µm. After UVA irradiation, it was 384 ± 10 µm. At 1, 6 and 12 months after treatment, it was 372 ± 10 µm, 381 ± 12.7, and 379 ± 15 µm, respectively. No intraoperative, early postoperative, or late postoperative complications were noted. CONCLUSIONS: Hypo-osmolar 0.1% riboflavin solution seems to be effective for swelling thin corneas. The swelling effect is transient and short acting. Corneal thickness should be monitored throughout the procedure. Larger sample sizes and longer follow-up are required in order to make meaningful conclusions regarding safety.

Enhanced detection method for corneal protein identification using shotgun proteomics

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Schlager John J

2009-06-01

Full Text Available Abstract Background The cornea is a specialized transparent connective tissue responsible for the majority of light refraction and image focus for the retina. There are three main layers of the cornea: the epithelium that is exposed and acts as a protective barrier for the eye, the center stroma consisting of parallel collagen fibrils that refract light, and the endothelium that is responsible for hydration of the cornea from the aqueous humor. Normal cornea is an immunologically privileged tissue devoid of blood vessels, but injury can produce a loss of these conditions causing invasion of other processes that degrade the homeostatic properties resulting in a decrease in the amount of light refracted onto the retina. Determining a measure and drift of phenotypic cornea state from normal to an injured or diseased state requires knowledge of the existing protein signature within the tissue. In the study of corneal proteins, proteomics procedures have typically involved the pulverization of the entire cornea prior to analysis. Separation of the epithelium and endothelium from the core stroma and performing separate shotgun proteomics using liquid chromatography/mass spectrometry results in identification of many more proteins than previously employed methods using complete pulverized cornea. Results Rabbit corneas were purchased, the epithelium and endothelium regions were removed, proteins processed and separately analyzed using liquid chromatography/mass spectrometry. Proteins identified from separate layers were compared against results from complete corneal samples. Protein digests were separated using a six hour liquid chromatographic gradient and ion-trap mass spectrometry used for detection of eluted peptide fractions. The SEQUEST database search results were filtered to allow only proteins with match probabilities of equal or better than 10-3 and peptides with a probability of 10-2 or less with at least two unique peptides isolated within

Conjunctival-limbal autograft in total unilateral limbal stem cell deficiency

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Petra Schollmayer

2017-09-01

Full Text Available Background: Corneal epithelium is renewed by stem cells (SC that reside at the corneal limbus. Reduced number of SC or their abnormal function lead to the ocular surface disease called limbal stem cell deficiency (LSCD, characterized by corneal conjunctivalization, vascularization, persistent epithelial defects, chronic inflammation, and loss of vision. In a case of total unilateral LSCD, autologous transplantation of limbal epithelial stem cells (LESC from the healthy eye is needed. We describe the surgical technique of choice for autologous limbal transplantation, called conjunctival limbal autograft (CLAU that we combined with amniotic membrane (AM use. We present the results of CLAU in three patients with total unilateral LSCD due to chemical injury.Methods: Autologous limbal transplantation CLAU begins with the removal of fibrovascular pannus from the diseased corneal surface and the harvesting of two conjunctival-limbal grafts from the healthy eye. The grafts are then transplanted on to the limbal area of the recipient eye. AM is used as a patch to cover the denuded cornea and limbal grafts, as well as a barrier preventing the conjunctival epithelium from encroaching on to the temporal and nasal side of the corneal surface. In the donor eye, AM is used to cover the donor sites. CLAU with the use of AM was performed in 3 patients with unilateral LSCD due to chemical eye injury. In one patient limbal transplantation was combined with symblepharon lysis for entropium repair. In all cases AM was removed 3–6 days postoperatively to assess the growth of new epithelium from the limbal grafts. In all patients the ocular surface was covered with another AM until the cornea was completely epithelized and the new epithelium stable. In one patient the corneal regrafting and cataract removal was performed subsequently.Results: CLAU was successful in 2 patients and partially successful in 1 patient during the follow up. In all cases the growth of new

4A syndrome: ocular surface investigation in an Italian young patient.

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Aragona, Pasquale; Rania, Laura; Roszkowska, Anna Maria; Puzzolo, Domenico; Micali, Antonio; Pisani, Antonina; Salzano, Giuseppina; Messina, Maria Francesca

2014-12-08

Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

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Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

2013-08-01

To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

Epidermal Growth Factor Receptor Transactivation by the Cannabinoid Receptor (CB1) and Transient Receptor Potential Vanilloid 1 (TRPV1) Induces Differential Responses in Corneal Epithelial Cells

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2010-01-01

inflammatory cytokine release in corneal epithelium through MAPK signaling. J. Cell Physiol. 213, 730e739. Zhang, J., Li , H., Wang, J., Dong, Z., Mian ...Kang, S.S., Li , T., Xu, D., Reinach, P.S., Lu, L., 2000. Inhibitory effect of PGE2 on EGF- induced MAP kinase activity and rabbit corneal epithelial

Different Use of Cell Surface Glycosaminoglycans As Adherence Receptors to Corneal Cells by Gram Positive and Gram Negative Pathogens

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García, Beatriz; Merayo-Lloves, Jesús; Rodríguez, David; Alcalde, Ignacio; García-Suárez, Olivia; Alfonso, José F.; Baamonde, Begoña; Fernández-Vega, Andrés; Vazquez, Fernando; Quirós, Luis M.

2016-01-01

The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive, and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies. PMID:27965938

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

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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

Serous papillary adenocarcinoma possibly related to the presence of primitive oocyte-like cells in the adult ovarian surface epithelium: a case report

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Virant-Klun Irma

2011-08-01

Full Text Available Abstract Introduction The presence of oocytes in the ovarian surface epithelium has already been confirmed in the fetal ovaries. We report the presence of SSEA-4, SOX-2, VASA and ZP2-positive primitive oocyte-like cells in the adult ovarian surface epithelium of a patient with serous papillary adenocarcinoma. Case presentation Ovarian tissue was surgically retrieved from a 67-year old patient. Histological analysis revealed serous papillary adenocarcinoma. A proportion of ovarian cortex sections was deparaffinized and immunohistochemically stained for the expression of markers of pluripotency SSEA-4 and SOX-2 and oocyte-specific markers VASA and ZP2. The analysis confirmed the presence of round, SSEA-4, SOX-2, VASA and ZP2-positive primitive oocyte-like cells in the ovarian surface epithelium. These cells were possibly related to the necrotic malignant tissue. Conclusion Primitive oocyte-like cells present in the adult ovarian surface epithelium persisting probably from the fetal period of life or developed from putative stem cells are a pathological condition which is not observed in healthy adult ovaries, and might be related to serous papillary adenocarcinoma manifestation in the adult ovarian surface epithelium. This observation needs attention to be further investigated.

Diclofenac protects cultured human corneal epithelial cells against hyperosmolarity and ameliorates corneal surface damage in a rat model of dry eye.

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Sawazaki, Ryoichi; Ishihara, Tomoaki; Usui, Shinya; Hayashi, Erika; Tahara, Kayoko; Hoshino, Tatsuya; Higuchi, Akihiro; Nakamura, Shigeru; Tsubota, Kazuo; Mizushima, Tohru

2014-04-21

Dry eye syndrome (DES) is characterized by an increase in tear osmolarity and induction of the expression and nuclear localization of an osmoprotective transcription factor (nuclear factor of activated T-cells 5 [NFAT5]) that plays an important role in providing protection against hyperosmotic tears. In this study, we screened medicines already in clinical use with a view of finding compounds that protect cultured human corneal epithelial cells against hyperosmolarity-induced cell damage. Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and cellular NFAT5 level was measured by immunoblotting. The rat model for DES was developed by removal of the lacrimal glands, with an assessment of corneal surface damage based on levels of fluorescein staining and epithelial apoptosis. Some nonsteroidal anti-inflammatory drugs (NSAIDs), including diclofenac sodium (diclofenac), were identified during the screening procedure. These NSAIDs were able to suppress hyperosmolarity-induced apoptosis and cell growth arrest. In contrast, other NSAIDs, including bromfenac sodium (bromfenac), did not exert such a protective action. Treatment of cells with diclofenac, but not bromfenac, stimulated both the nuclear localization and expression of NFAT5 under hyperosmotic conditions. In the rat model for DES, topical administration of diclofenac (but not bromfenac) to eyes reduced corneal surface damage without affecting the volume of tear fluid. Diclofenac appears to protect cells against hyperosmolarity-induced cell damage and NFAT5 would play an important role in this protective action. The findings reported here may also indicate that the topical administration of diclofenac to eyes may be therapeutically beneficial for DES patients.

Corneal Collagen Cross-Linking with Hypoosmolar Riboflavin Solution in Keratoconic Corneas

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Shaofeng Gu

2014-01-01

Full Text Available Purpose. To report the 12-month outcomes of corneal collagen cross-linking (CXL with a hypoosmolar riboflavin and ultraviolet-A (UVA irradiation in thin corneas. Methods. Eight eyes underwent CXL using a hypoosmolar riboflavin solution after epithelial removal. The corrected distance visual acuity (CDVA, manifest refraction, the mean thinnest corneal thickness (MTCT, and the endothelial cell density (ECD were evaluated before and 6 and 12 months after CXL. Results. The MTCT was 413.9 ± 12.4 μm before treatment and reduced to 381.1 ± 7.3 μm after the removal of the epithelium. After CXL, the thickness decreased to 410.3 ± 14.5 μm at the last follow-up. Before treatment, the mean K-value of the apex of the keratoconus corneas was 58.7 ± 3.5 diopters and slightly decreased (57.7 ± 4.9 diopters at 12 months. The mean CDVA was 0.54 ± 0.23 logarithm of the minimal angle of resolution before treatment and increased to 0.51 ± 0.21 logarithm at the last follow-up. The ECD was 2731.4 ± 191.8 cells/mm2 before treatment and was 2733.4 ± 222.6 cells/mm2 at 12 months after treatment. Conclusions. CXL with a hypoosmolar riboflavin in thin corneas seems to be a promising method for keratoconic eyes with the mean thinnest corneal thickness less than 400 μm without epithelium.

Hyperopic correction: clinical validation with epithelium-on and epithelium-off protocols, using variable fluence and topographically customized collagen corneal crosslinking

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Kanellopoulos AJ

2014-12-01

Full Text Available Anastasios John Kanellopoulos,1,2 George Asimellis1 1LaserViison.gr Clinical and Research Eye Institute, Athens, Greece; 2Department of Ophthalmology, New York University Medical School, New York, NY, USAPurpose: To report novel application of topographically-customized collagen crosslinking aiming to achieve hyperopic refractive changes. Two approaches were evaluated, one based on epithelium-off and one based on epithelium-on (transepithelial. Methods: A peripheral annular-shaped topographically customizable design was employed for high-fluence ultraviolet (UV-A irradiation aiming to achieve hyperopic refractive changes. A total of ten eyes were involved in this study. In group-A (five eyes, a customizable ring pattern was employed to debride the epithelium by excimer laser ablation, while in group-B (also five eyes, the epithelium remained intact. In both groups, specially formulated riboflavin solutions were applied. Visual acuity, cornea clarity, keratometry, topography, and pachymetry with a multitude of modalities, as well as endothelial cell counts were evaluated. Results: One year postoperatively, the following changes have been noted: in group-A, average uncorrected distance visual acuity changed from 20/63 to 20/40. A mean hyperopic refractive increase of +0.75 D was achieved. There was some mild reduction in the epithelial thickness. In group-B, average uncorrected distance visual acuity changed from 20/70 to 20/50. A mean hyperopic refractive increase of +0.85 D was achieved. Epithelial thickness returned to slightly reduced levels (compared to baseline in group-A, whereas to slightly increased levels in group-B. Conclusion: We introduce herein the novel application of a topographically-customizable collagen crosslinking to achieve a hyperopic refractive effect. This novel technique may be applied either with epithelial removal, offering a more stable result or with a non-ablative and non-incisional approach, offering a minimally

Assessment of the effect of cyclosporine-A 0.05% emulsion on the ocular surface and corneal sensation following cataract surgery.

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Hamada, Samer; Moore, Tara C B; Moore, Jonathan E; Al-Dreihi, Madonna G; Anbari, Anas; Shah, Sunil

2016-02-01

To assess the effect of cyclosporine-A (CsA) 0.05% ophthalmic emulsion on corneal sensation and ocular surface problems following cataract surgery. Prospective, randomized, double masked clinical trial. Consecutive case series of patients attending for bilateral cataract surgery. Subject's eyes were randomized to receive either topical CsA or carboxymethylcellulose 0.5% (CMC) eye drops twice daily for one month following routine cataract surgery. Subjective and objective assessments were performed pre-operatively, one week, and one month after surgery. Primary safety parameters included best spectacle-corrected visual acuity and incidence of adverse events. Objective assessments included tests of tear film (osmolarity, tear break-up time, and Schirmer's type-I test), ocular surface staining, corneal sensitivity and a subjective assessment: ocular surface disease index (OSDI) questionnaire. 30 subjects (60 eyes) were recruited. At one month following cataract surgery, osmolarity, ocular surface staining, TBUT, Schirmer's results showed a greater improvement after CsA drops compared to CMC and this was statistically significant for all measures (psensation measurements were reduced after one week and one month. Eyes receiving CsA had higher recovery of corneal sensation at both time points post operatively and this was statistically significant at one month. OSDI questionnaire results did not show a statistically significant difference between the two eyes. CsA is effective and safe in the management of ocular surface problems after cataract surgery and allows faster recovery of corneal sensation. This recovery of sensation may be relevant to the improvement in ocular surface problems in all patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea.

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Chaiyasan, Wanachat; Praputbut, Sakonwun; Kompella, Uday B; Srinivas, Sangly P; Tiyaboonchai, Waree

2017-01-01

Topical application of drugs to the eyes suffers from poor bioavailability at the ocular surface and in the anterior chamber. This is due to rapid clearance of the drug because of tear secretion and outflow. This study has investigated mucoadhesive and penetration characteristics of chitosan-dextran sulfate nanoparticles (CDNs), prepared by polyelectrolyte complexation technique, following topical administration to the ocular surface. Topical FITC-labeled CDNs (FCDNs; mean size of 400nm and a surface charge of +48mV) were retained on the porcine ocular surface for more than 4h. Topical FCDNs were partially endocytosed into porcine corneal epithelial cells via a clathrin-dependent pathway. After 6h of topical FCDNs, particles accumulated in the corneal epithelium but not found in the corneal stroma. When epithelium was removed, FCDNs penetrated the stroma. Thus, CDNs are potentially useful for drug/gene delivery to the ocular surface and to stroma when epithelium is damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

Bilateral congenital corneal keloids and anterior segment mesenchymal dysgenesis in a case of Rubinstein-Taybi syndrome.

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Rao, Srinivas K; Fan, Dorothy S P; Pang, C P; Li, Winnie W Y; Ng, Joan S K; Good, William V; Lam, Dennis S C

2002-01-01

To report the unusual association of bilateral corneal keloids and anterior segment mesenchymal dysgenesis in a child with Rubinstein-Taybi syndrome. Case report of a 2-year-old boy. Excision of the epicorneal mass in the right eye was followed by recurrence of the lesion. Multiple penetrating keratoplasties were unsuccessful in reconstructing the anterior segment because of recurrent corneal epithelial breakdown, suggesting limbal stem cell insufficiency. Histopathology and electron microscopy of the excised mass lesion showed features typical of a corneal keloid: thickened keratinized epithelium, absent Bowman's layer, and fibrovascular hyperplasia, with haphazard orientation of the collagen lamellae. Ultrasound biomicroscopy and intraoperative findings suggested a diagnosis of Peter anomaly, but genetic analysis did not show a PAX6 mutation. The findings in our patient add to the spectrum of ocular changes described in Rubinstein-Taybi syndrome and confirm earlier reports of poor ocular prognosis in corneal keloids and Rubinstein-Taybi syndrome.

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

Science.gov (United States)

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.

Evaluation of corneal changes after myopic LASIK using the Pentacam®

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Khairat YM

2013-09-01

Full Text Available Yehia M Khairat, Yasser H Mohamed, Ismail ANO Moftah, Narden N Fouad Department of Ophthalmology, Faculty of Medicine, El-Minya University, Egypt Background: In this study, we used a Pentacam® device to evaluate the corneal changes that occur after laser-assisted in situ keratomileusis (LASIK. Methods: Our study included 60 eyes of 32 patients. All patients were treated for myopia and myopic astigmatism using LASIK. The eyes were examined preoperatively and 3 months postoperatively using a Pentacam to assess corneal changes with regard to curvature, elevation, and asphericity of the cornea. Results: A statistically significant decrease in mean keratometric power of the anterior corneal surface (P = 0.001 compared with its pre-LASIK value was detected after 3 months, but there was no significant change in keratometric power of the posterior surface (P = 0.836. Asphericity (Q-value of the anterior and posterior surfaces increased significantly after LASIK (P = 0.001. A significant forward bulge of the anterior corneal surface 4 mm and 7 mm from the central zone was detected 3 months post-LASIK (P = 0.001 for both, but there was no significant increase in posterior elevation at 4 mm and 7 mm from the center (P = 0.637 and P = 0.26, respectively. No cases of post-LASIK ectasia were detected. Correlation between different parameters of the corneal surface revealed an indirect relation between changes in pachymetry and anterior corneal elevation at 4 mm and 7 mm from the central zone (r = −0.27, P = 0.13, and r = −0.37, P = 0.04, respectively, and a direct proportion between changes in pachymetry and mean keratometric power of the anterior and posterior corneal surfaces (r = 0.7, P = 0.001 and r = 0.4, P = 0.028, respectively. Conclusion: LASIK causes significant changes at the anterior corneal surface but the effect is subtle and insignificant at the posterior surface. Keywords: LASIK, laser-assisted in situ keratomileusis, Pentacam®, corneal

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.

Comparative analysis of human conjunctival and corneal epithelial gene expression with oligonucleotide microarrays.

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Turner, Helen C; Budak, Murat T; Akinci, M A Murat; Wolosin, J Mario

2007-05-01

To determine global mRNA expression levels in corneal and conjunctival epithelia and identify transcripts that exhibit preferential tissue expression. cDNA samples derived from human conjunctival and corneal epithelia were hybridized in three independent experiments to a commercial oligonucleotide array representing more than 22,000 transcripts. The resultant signal intensities and microarray software transcript present/absent calls were used in conjunction with the local pooled error (LPE) statistical method to identify transcripts that are preferentially or exclusively expressed in one of the two tissues at significant levels (expression >1% of the beta-actin level). EASE (Expression Analysis Systematic Explorer software) was used to identify biological systems comparatively overrepresented in either epithelium. Immuno-, and cytohistochemistry was performed to validate or expand on selected results of interest. The analysis identified 332 preferential and 93 exclusive significant corneal epithelial transcripts. The corresponding numbers of conjunctival epithelium transcripts were 592 and 211, respectively. The overrepresented biological processes in the cornea were related to cell adhesion and oxiredox equilibria and cytoprotection activities. In the conjunctiva, the biological processes that were most prominent were related to innate immunity and melanogenesis. Immunohistochemistry for antigen-presenting cells and melanocytes was consistent with these gene signatures. The transcript comparison identified a substantial number of genes that have either not been identified previously or are not known to be highly expressed in these two epithelia, including testican-1, ECM1, formin, CRTAC1, and NQO1 in the cornea and, in the conjunctiva, sPLA(2)-IIA, lipocalin 2, IGFBP3, multiple MCH class II proteins, and the Na-Pi cotransporter type IIb. Comparative gene expression profiling leads to the identification of many biological processes and previously unknown genes that

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 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�

Comparative Ultrastructural Studies on the Impact of Moderate and Hyperthermic Environment on the Corneal Structure of two Species of Wild Rodents

International Nuclear Information System (INIS)

Naguib, N.I.; El-Dawi, E.F.

2011-01-01

This study was carried out to investigate the impact of environmental climate (temperature) on the corneal structure of two wild rodents; the nocturnal Norway rats (Rattus norvegicus) and the diurnal golden spiny mouse (Acomys russatus). Both rodents were collected from two extreme climatic environment and their dissected corneas were prepared for light, scanning and transmission electron microscopy. The corneas of both rodents are composed of three main layers; an outer epithelium, stroma, Descemet's membrane, and an inner endothelium. The mean thickness of the epithelium, stroma, Descemet's membrane and inner endothelium of both rodents were measured. The scanning electron microscopy revealed that in R. norvegicus and A. russatus; the outermost cells of the corneal epithelium, are mostly polygonal in shape with nearly regular borders and show dense pattern of microplicae with different scatter electron that exhibits three polymorphic appearances (A, B, C) and two (A, B), respectively. Numerous A-light cells with dense microplicae, many B-dark cells with a moderate density of microplicae and few C-dark cells with a less density of microplicae were observed. Using transmission electron microscope, the epithelial cells of both species possess glycocalyx and the cytokeratin filaments are more extensive in the apical epithelial cells in A. russatus. The stroma in R. norvegicus is formed of outer and inner lamellar zones with spaces in between its wavy bundles. In A. russatus, the stroma is formed of one lamellar zone of flattened bundles of highly wavy and branched collagen fibrils. On the other hand, the surface of the endothelial cells in R. norvegicus is slightly bulging with many blebs whereas it showed flattened and nearly smooth surface in A. russatus. In conclusion, the differences in the number of the superficial epithelial cells and the thickness of the stroma and structure of the endothelium of R. norvegicus (nocturnal) and A. russatus (diurnal) are most

Ovarian Surface Epithelium in Patients with Severe Ovarian Infertility: A Potential Source of Cells Expressing Markers of Pluripotent/Multipotent Stem Cells

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Irma Virant-Klun

2011-01-01

Full Text Available The aim of this study was to confirm the presence of stem cells in the ovarian surface epithelium of patients with premature ovarian failure and no mature follicles and oocytes. In these patients, small round cells of unknown origin expressing SOX-2 marker of pluripotency were observed among the epithelial cells just after the ovarian surface epithelium scraping. These cells were an integral part of the ovarian surface epithelium. When the scraped cells were cultured in a medium with added follicular fluid to provide some ovarian niche, primitive oocyte-like cells and typical round-shaped cell clusters positively stained on alkaline phosphatase, and markers of pluripotency, such as SOX-2 and SSEA-4, were developed. These markers were expressed early and also later in the culture. Single oocyte-like cells expressed genes OCT4A, SOX-2, NANOG, NANOS, STELLA, CD9, LIN28, KLF4, GDF3, and MYC, characteristic for pluripotent stem cells. The results of this study confirmed the presence of putative stem cells in the ovarian surface epithelium of these patients and provided some basis to create a stem cell line in the future.

Molecular mechanisms of water transport in the eye

DEFF Research Database (Denmark)

Hamann, Steffen

2002-01-01

The four major sites for ocular water transport, the corneal epithelium and endothelium, the ciliary epithelium, and the retinal pigment epithelium, are reviewed. The cornea has an inherent tendency to swell, which is counteracted by its two surface cell layers, the corneal epithelium...... and endothelium. The bilayered ciliary epithelium secretes the aqueous humor into the posterior chamber, and the retinal pigment epithelium transports water from the retinal to the choroidal site. For each epithelium, ion transport mechanisms are associated with fluid transport, but the exact molecular coupling...... sites between ion and water transport remain undefined. In the retinal pigment epithelium, a H+-lactate cotransporter transports water. This protein could be the site of coupling between salt and water in this epithelium. The distribution of aquaporins does not suggest a role for these proteins...

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.

Polysaccharide hydrogel combined with mesenchymal stem cells promotes the healing of corneal alkali burn in rats.

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Yifeng Ke

Full Text Available Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β, antiangiogenic cytokine (TSP-1 and decrease those promoting inflammation (TNF-α, chemotaxis (MIP-1α and MCP-1 and angiogenesis (VEGF and MMP-2. This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder.

Polysaccharide Hydrogel Combined with Mesenchymal Stem Cells Promotes the Healing of Corneal Alkali Burn in Rats

Science.gov (United States)

Liu, Xun; Yu, Min; Yang, Chunbo; Li, Xiaorong

2015-01-01

Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs) have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs) were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β), antiangiogenic cytokine (TSP-1) and decrease those promoting inflammation (TNF-α), chemotaxis (MIP-1α and MCP-1) and angiogenesis (VEGF and MMP-2). This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder. PMID:25789487

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.

Transplantation with cultured stem cells derived from the human amniotic membrane for corneal alkali burns: an experimental study.

Science.gov (United States)

Zeng, Wei; Li, Yanwei; Zeng, Guangwei; Yang, Bo; Zhu, Yu

2014-01-01

Amniotic membranes (AM) have been used in a wide range of clinical applications. We successfully extracted mesenchymal stem cells (MSCs) from human AM, but little is known about the use and efficacy of human amniotic membrane-derived mesenchymal stem cells (hAM-dMSCs) for the treatment of alkali burns. We utilized hAM-dMSCs transplantation, AM grafting, and their combined use in the treatment of alkali burns. An experimental model in rabbits was devised to analyze the use of these techniques with immunocytochemistry and ELISA. The survival and migration of hAM-dMSCs labeled by SPION in the host were assessed with Prussian blue staining. Compared with the control group, the treated groups demonstrated faster reconstruction of the corneal epithelium, and lower levels of corneal opacification and neovascularization within corneal alkali burns. Furthermore, dark blue-stained particles were detected in the limbus corneae at day 28. These results demonstrated the ability of hAM-dMSCs to enhance epithelial healing and reduce corneal opacification and neovascularization in corneal alkali wounds.

Amniotic membrane transplantation for reconstruction of corneal epithelial surface in cases of partial limbal stem cell deficiency.

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Sangwan Virender

2004-01-01

Full Text Available Purpose: To assess the efficacy of amniotic membrane for treatment of partial limbal stem cell deficiency (LSCD. Methods: Medical records of four patients with partial LSCD who underwent pannus resection and amniotic membrane transplantation (AMT were reviewed for ocular surface stability and improvement in visual acuity. Clinico-histopathological correlation was done with the resected pannus tissue. Results: All the eyes exhibited stable corneal epithelial surface by an average of 7 weeks postoperatively with improvement in subjective symptoms. Best corrected visual acuity improved from preoperative (range: 6/9p-6/120 to postoperative (range: 6/6p-6/15 by an average of 4.5 lines on Snellen visual acuity charts. Histopathological examination of excised tissue showed features of conjunctivalisation. Conclusion: Amniotic membrane transplantation appears to be an effective means of reconstructing the corneal epithelial surface and for visual rehabilitation of patients with partial limbal stem cell deficiency. It may be considered as an alternative primary procedure to limbal transplantation in these cases.

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.

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

Science.gov (United States)

Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

Selective corneal optical aberration (SCOA) for customized ablation

Science.gov (United States)

Jean, Benedikt J.; Bende, Thomas

2001-06-01

Wavefront analysis still have some technical problems which may be solved within the next years. There are some limitations to use wavefront as a diagnostic tool for customized ablation alone. An ideal combination would be wavefront and topography. Meanwhile Selective Corneal Aberration is a method to visualize the optical quality of a measured corneal surface. It is based on a true measured 3D elevation information of a video topometer. Thus values can be interpreted either using Zernike polynomials or visualized as a so called color coded surface quality map. This map gives a quality factor (corneal aberration) for each measured point of the cornea.

Successful transplantation of in vitro expanded human corneal endothelial precursors to corneal endothelial surface using a nanocomposite sheet

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Parikumar P

2011-01-01

Full Text Available Background: Though the transplantation of in vitro expanded human corneal endothelial precursors in animal models of endothelial damage by injecting into the anterior chamber has been reported, the practical difficulties of accomplishing such procedure in human patients have been a hurdle to clinical translation. Here we report the successful transplantation of in vitro expanded human corneal precursor cells to an animal eye using a transparent Nano-composite sheet and their engraftment.Materials and Methods: Human Corneal endothelial cells (HCEC were isolated from human cadaver eyes with informed consent and expanded in the lab using a sphere forming assay in a novel Thermoreversible Gelation Polymer (TGP for 26 days. HCEC obtained by sphere forming assay were seeded in a novel Nano-composite sheet, which was made of PNIPA-NC gels by in-situ, free-radical polymerization of NIPA monomer in the presence of exfoliated clay (synthetic hectorite “Laponite XLG” uniformly dispersed in aqueous media. After a further seven days in vitro culture of HCEC in the Nano-composite sheet, cells were harvested and transplanted on cadaver-bovine eyes (n=3. The cells were injected between the corneal endothelial layer and the Nano-composite sheet that had been placed prior to the injection in close proximity to the endothelial layer. After three hours, the transplanted Nano-composite sheets were removed from the bovine eyes and subjected to microscopic examination. The corneas were subjected to Histo-pathological studies along with controls. Results: HCEC formed sphere like colonies in TGP which expressed relevant markers as confirmed by RT-PCR. Microscopic studies of the Nanosheets and histopathological studies of the cornea of the Bull’s eye revealed that the HCEC got engrafted to the corneal endothelial layer of the bovine eyes with no remnant cells in the Nanosheet. Conclusion: Transplantation of in vitro expanded donor human corneal endothelial cells

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

International Nuclear Information System (INIS)

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)

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.

In vivo models of human airway epithelium repair and regeneration

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C. Coraux

2005-12-01

Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

Assessment of Corneal and Tear Film Parameters in Rheumatoid Arthritis Patients Using Anterior Segment Spectral Domain Optical Coherence Tomography.

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El-Fayoumi, Dina; Youssef, Maha Mohamed; Khafagy, Mohamed Mahmoud; Badr El Dine, Nashwa; Gaber, Wafaa

2018-01-01

To study the corneal changes in rheumatoid arthritis (RA) patients in vivo, using spectral domain anterior segment optical coherence tomography (AS-OCT). A case-control study was done on 43 RA patients and 40 controls. The disease activity score (DAS28-ESR) was calculated and all participants had lower tear meniscus, corneal thickness, and epithelial thickness evaluation using AS-OCT. The lower tear meniscus height (LTMH) and the lower tear meniscus area (LTMA) were significantly lower in the RA patients than in controls (p < 0.001). RA patients also had a significantly thinner central corneal thickness (p = 0.02) and their epithelium was found to be thinner in the superotemporal peripheral sector. The LTMH and LTMA are significantly reduced in RA patients, despite the absence of clinical diagnosis of dry eye. RA patients have thinner corneal thickness and epithelial thickness than controls, which did not correlate with either disease duration or activity.

Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo comparative study.

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

2014-06-01

The aim of this study was to compare the effect on corneal wound healing of 3 differently manufactured blood derivatives [autologous serum (AS), platelet-rich plasma, and serum derived from plasma rich in growth factors (s-PRGF)]. Scratch wound-healing assays were performed on rabbit primary corneal epithelial cultures and human corneal epithelial cells. Additionally, mechanical debridement of rabbit corneal epithelium was performed. Wound-healing progression was assessed by measuring the denuded areas remaining over time after treatment with each of the 3 blood derivatives or a control treatment. In vitro data show statistically significant differences in the healing process with all the derivatives compared with the control, but 2 of them (AS and s-PRGF) induced markedly faster wound healing. In contrast, although the mean time required to complete in vivo reepithelization was similar to that of AS and s-PRGF treatment, only wounds treated with s-PRGF were significantly smaller in size from 2.5 days onward with respect to the control treatment. All 3 blood derivatives studied are promoters of corneal reepithelization. However, the corneal wound-healing progresses differently with each derivative, being faster in vitro under AS and s-PRGF treatment and producing in vivo the greatest decrease in wound size under s-PRGF treatment. These findings highlight that the manufacturing process of the blood derivatives may modulate the efficacy of the final product.

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 ...

Aberration changes of the corneal anterior surface following discontinued use of rigid gas permeable contact lenses.

Science.gov (United States)

Yu, Qing; Wu, Jiang-Xiu; Zhang, He-Ning; Ye, Sheng; Dong, Shi-Qi; Zhang, Chen-Hao

2013-01-01

To record aberrations with a corneal topographic device on the anterior surface of the cornea at different time-points prior to wearing and following discontinued use of rigid gas permeable (RGP) contact lenses. The effect of wearing RGP on the anterior surface of the cornea was discussed to provide guidance for clinical refractive error correction. The study objects were 24 eyes from 24 patients. All patients underwent identical examination procedures prior to lens use, as well as afterwards, including slit-lamp examination, non-contact tonometer measurement, computer optometry and corneal curvature measurement, subjective refraction test, and corneal topography analysis. The patients wore contact lenses everyday for 1 month and then discontinued. Corneal topographies were recorded at certain time points of 30 minutes, 1 day, 3, 7 and 14 days following use. Total corneal aberration at each time point following discontinued use of RGP contact lenses was less than the time point prior to use. Detailed results were as follows: root mean square (RMS) (pre)=(1.438±0.328)µm, RMS (30 minutes)=(1.076±0.355)µm, RMS (1 day)=(1.362±0.402)µm, RMS (3 days)=(1.373±0.398)µm, RMS (7 days)=(1.387±0.415)µm, and RMS (14 days)=(1.430±0.423)µm. Results showed that at 30 minutes after discontinued use of RGP contact lenses, almost all 2(nd)- and 3(rd)-order aberrations change. Quadrafoil Z10 and spherical Z12 of the 4(th)-order were also changed. Alterations to Z5, Z6, and Z12 at 1 day after discontinued use were significant differences compared with the time period prior to RGP use: Z5 and Z6 decreased, and Z12 increased slightly. Z5 and Z6 remained decreased at 3 days after discontinued use, but Z9 and Z10 continued to increase and Z12 returned to levels prior to RGP use. At 14 days after discontinued use, all aberrations were not significantly different from the values prior to use. The use RGP contact lenses greatly reduced total aberration of the anterior surface of

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.

Corneal biomechanical properties from air-puff corneal deformation imaging

Science.gov (United States)

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.

Recovery of Corneal Sensitivity and Increase in Nerve Density and Wound Healing in Diabetic Mice After PEDF Plus DHA Treatment.

Science.gov (United States)

He, Jiucheng; Pham, Thang Luong; Kakazu, Azucena; Bazan, Haydee E P

2017-09-01

Diabetic keratopathy decreases corneal sensation and tear secretion and delays wound healing after injury. In the current study, we tested the effect of treatment with pigment epithelium-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) on corneal nerve regeneration in a mouse model of diabetes with or without corneal injury. The study was performed in streptozotocin-induced diabetic mice (C57BL/6). Ten weeks after streptozotocin injection, diabetic mice showed significant decreases of corneal sensitivity, tear production, and epithelial subbasal nerve density when compared with age-matched normal mice. After diabetic mice were wounded in the right eye and treated in both eyes with PEDF+DHA for 2 weeks, there was a significant increase in corneal epithelial nerve regeneration and substance P-positive nerve density in both wounded and unwounded eyes compared with vehicle-treated corneas. There also was elevated corneal sensitivity and tear production in the treated corneas compared with vehicle. In addition, PEDF+DHA accelerated corneal wound healing, selectively recruited type 2 macrophages, and prevented neutrophil infiltration in diabetic wounded corneas. These results suggest that topical treatment with PEDF+DHA promotes corneal nerve regeneration and wound healing in diabetic mice and could potentially be exploited as a therapeutic option for the treatment of diabetic keratopathy. © 2017 by the American Diabetes Association.

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

Corneal Laceration

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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.

Efeito do colírio de 5-fluorouracil sobre o epitélio corneano íntegro de coelhos Effects of 5-fluorouracil eye drops on intact rabbit corneal epithelium

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Lucieni Cristina Barbarini Ferraz

2003-08-01

Full Text Available OBJETIVO: Observar os efeitos da aplicação tópica de 5-fluorouracil (5-FU sobre o epitélio corneano íntegro. MÉTODOS: Foram utilizados 10 coelhos albinos (14 olhos, divididos em: grupo controle (GC, 4 olhos nos quais não se administraram drogas, grupo 1 (G1, 5 olhos que receberam 5-fluorouracil na concentração 1,25% e grupo 2 (G2, 5 olhos que receberam 5-fluorouracil na concentração de 2,5%. A droga foi instilada 4 vezes por dia, durante 7 dias, quando os animais foram sacrificados, os olhos removidos, separando-se a córnea que foi preparada de modo convencional para estudo em microscópico eletrônico de varredura. RESULTADOS: GC: observaram-se células de formato hexagonal, claras, escuras e intermediárias, compondo o epitélio corneano de coelhos. Presença de numerosas microplicas, principalmente nas células claras. Cada célula possui cerca de 1 a 3 criptas. Nos animais do G1, observou-se maior número de células escuras, regiões com diminuição no número de criptas; alterações da superfície celular, protusão na região do núcleo e descamação de células epiteliais. Os do G2 tiveram aumento de microprojeções na superfície celular, modificações nas junções intercelulares até separação de células adjacentes; diminuição do número e variabilidade no tamanho das criptas. As alterações mais freqüentes ocorreram nas células da periferia da córnea. CONCLUSÃO: O 5-fluorouracil teve efeitos deletérios no epitélio íntegro corneano de coelhos. As alterações observadas foram mais importantes nos animais que receberam a droga mais concentrada (G2 e mais freqüentes na periferia da córnea.PURPOSE: To assess the influence of the antiproliferative agent (5-FU on the intact rabbit corneal epithelium. METHODS: 10 rabbits (14 eyes,were divided into: control group (CG, 4 eyes without drug administration; G1, 5 eyes underwent treatment with topical 12.5 mg/ml 5-fluorouracil and G2, 5 eyes received 5-fluorouracil

Extended latanoprost release from commercial contact lenses: in vitro studies using corneal models.

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Saman Mohammadi

Full Text Available In this study, we compared, for the first time, the release of a 432 kDa prostaglandin F2a analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution (131 μg = ml solution in phosphate buffered saline. The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC, and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment whereby, after 48 hours, between 4 to 6 μg of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 μg, was released, (p <0:001. The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

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.

Buccal Epithelium in treating Ocular Surface Disorders

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Srinivas KR

2008-11-01

Full Text Available Background - Ocular surface disorders due to limbal stem cell deficiency are an important cause of ocular morbidity and visual loss. Although autologous limbal stem cell transplants have helped in the management of unilateral disease, allografts in those with bilateral disease often fail due to immunological reasons. The use of autologous buccal epithelium cultivated on amniotic membrane has been described as a useful approach in the management of this condition. It is the purpose of this study to explore the feasibility of using a novel thermo-gelatin polymer (TGP as a substrate to culture these cells, and to characterize them using RNA extraction and RT-PCR. Methods - Oral cheek mucosal biopsies were obtained from 5 adult patients undergoing Modified Osteo-Odonto Keratoprosthesis surgery. The specimens were transported to the laboratory in transport medium. The cells were released using enzymatic digestion and seeded in both convention culture medium and TGP. The resulting cellular growth was characterized using RNA extraction and RT-PCR. Results - Cells could be cultured from 4 of the 5 specimens. In one specimen, contamination occurred and this was discarded. In the other specimens, the cheek epithelial cells could be cultured in both the conventional culture medium and TGP, with equal ease. RT-PCR revealed the presence of K3, a marker for epithelial cells, and GAPDH indicating the presence of some adipose tissue as well. Conclusions - It is possible to culture autologous cheek mucosal epithelial cells using TGP, a synthetic scaffold, without the need for other biological substrates. Since the specimens are obtained from the oral cavity, stringent asepsis is required. Further studies are required for histopathological characterization of the cultured cells and to create a model for delivery onto the ocular surface of eyes with bilateral surface disease due to limbal stem cell deficiency.

Surface characteristics of isopod digestive gland epithelium studied by SEM.

Science.gov (United States)

Millaku, Agron; Leser, Vladka; Drobne, Damjana; Godec, Matjaz; Torkar, Matjaz; Jenko, Monika; Milani, Marziale; Tatti, Francesco

2010-05-01

The structure of the digestive gland epithelium of a terrestrial isopod Porcellio scaber has been investigated by conventional scanning electron microscopy (SEM), focused ion beam-scanning electron microscopy (FIB/SEM), and light microscopy in order to provide evidence on morphology of the gland epithelial surface in animals from a stock culture. We investigated the shape of cells, extrusion of lipid droplets, shape and distribution of microvilli, and the presence of bacteria on the cell surface. A total of 22 animals were investigated and we found some variability in the appearance of the gland epithelial surface. Seventeen of the animals had dome-shaped digestive gland "normal" epithelial cells, which were densely and homogeneously covered by microvilli and varying proportions of which extruded lipid droplets. On the surface of microvilli we routinely observed sparsely distributed bacteria of different shapes. Five of the 22 animals had "abnormal" epithelial cells with a significantly altered shape. In three of these animals, the cells were much smaller, partly or completely flat or sometimes pyramid-like. A thick layer of bacteria was detected on the microvillous border, and in places, the shape and size of microvilli were altered. In two animals, hypertrophic cells containing large vacuoles were observed indicating a characteristic intracellular infection. The potential of SEM in morphological investigations of epithelial surfaces is discussed.

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

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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.

Femtosecond laser cutting of human corneas for the subbasal nerve plexus evaluation.

Science.gov (United States)

Kowtharapu, B S; Marfurt, C; Hovakimyan, M; Will, F; Richter, H; Wree, A; Stachs, O; Guthoff, R F

2017-01-01

Assessment of various morphological parameters of the corneal subbasal nerve plexus is a valuable method of documenting the structural and presumably functional integrity of the corneal innervation in health and disease. The aim of this work is to establish a rapid, reliable and reproducible method for visualization of the human corneal SBP using femtosecond laser cut corneal tissue sections. Trephined healthy corneal buttons were fixed and processed using TissueSurgeon-a femtosecond laser based microtome, to obtain thick tissue sections of the corneal epithelium and anterior stroma cut parallel to the ocular surface within approximately 15 min. A near infrared femtosecond laser was focused on to the cornea approximately 70-90 μm from the anterior surface to induce material separation using TissueSurgeon. The obtained corneal sections were stained following standard immunohistochemical procedures with anti-neuronal β-III tubulin antibody for visualization of the corneal nerves. Sections that contained the epithelium and approximately 20-30 μm of anterior stroma yielded excellent visualisation of the SBP with minimal optical interference from underlying stromal nerves. In conclusion, the results of this study have demonstrated that femtosecond laser cutting of the human cornea offers greater speed, ease and reliability than standard tissue preparation methods for obtaining high quality thick sections of the anterior cornea cut parallel to the ocular surface. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

Aberration changes of the corneal anterior surface following discontinued use of rigid gas permeable contact lenses

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Shi-Qi Dong

2013-04-01

Full Text Available AIM: To record aberrations with a corneal topographic device on the anterior surface of the cornea at different time-points prior to wearing and following discontinued use of rigid gas permeable (RGP contact lenses. The effect of wearing RGP on the anterior surface of the cornea was discussed to provide guidance for clinical refractive error correction. METHODS: The study objects were 24 eyes from 24 patients. All patients underwent identical examination procedures prior to lens use, as well as afterwards, including slit-lamp examination, non-contact tonometer measurement, computer optometry and corneal curvature measurement, subjective refraction test, and corneal topography analysis. The patients wore contact lenses everyday for 1 month and then discontinued. Corneal topographies were recorded at certain time points of 30 minutes, 1 day, 3, 7 and 14 days following use. RESULTS: Total corneal aberration at each time point following discontinued use of RGP contact lenses was less than the time point prior to use. Detailed results were as follows:root mean square (RMS (pre=(1.438±0.328μm, RMS (30 minutes=(1.076±0.355μm, RMS (1 day=(1.362±0.402μm, RMS (3 days=(1.373±0.398μm, RMS (7 days=(1.387±0.415μm, and RMS (14 days=(1.430±0.423μm. Results showed that at 30 minutes after discontinued use of RGP contact lenses, almost all 2nd- and 3rd-order aberrations change. Quadrafoil Z10 and spherical Z12 of the 4th-order were also changed. Alterations to Z5, Z6, and Z12 at 1 day after discontinued use were significant differences compared with the time period prior to RGP use:Z5 and Z6 decreased, and Z12 increased slightly. Z5 and Z6 remained decreased at 3 days after discontinued use, but Z9 and Z10 continued to increase and Z12 returned to levels prior to RGP use. At 14 days after discontinued use, all aberrations were not significantly different from the values prior to use. CONCLUSION: The use RGP contact lenses greatly reduced total

Late onset corneal ectasia after LASIK surgery.

Science.gov (United States)

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.

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.

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.

Ultrastructural Changes and Corneal Wound Healing After SMILE and PRK Procedures.

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Wei, Shengsheng; Wang, Yan; Wu, Di; Zu, PeiPei; Zhang, Hui; Su, Xiaolian

2016-10-01

To compare keratocyte activation, cellular morphologic changes and wound healing after SMILE and PRK procedures using transmission electron microscope (TEM). In this study, 22 New Zealand white rabbits (10- to 15-week old) were used. The right eyes of all animals underwent SMILE procedure and the left eyes underwent PRK procedure. Cornea samples taken 1 day and 1 week postoperatively were examined using TEM. Using TEM 1 day after SMILE procedure, the organization of collagen fibers seemed to have been preserved without thermal alterations. Keratocyte activation was observed in the anterior stroma. Disrupted collagen arrangement and debris of cells are visible in the area of damage, and some phagocytic cells and a large number of secondary lysosomes are visible in those cells. At the perimeter zone of the interface, many coenocytes and collagen fragments could be found within the phagocytic cell. One week after SMILE procedure, potential lacuna could be discerned. A large part of the interface of the lenticule extracted had an appearance of clearly being adhered to some mucus secretions. One day after PRK procedure, an irregular epithelial surface was visible using TEM. Keratocytes had been activated and the rough endoplasmic reticulum in those cells had expanded. One week after PRK procedure, the epithelial surface still was irregular and keratinization of the epithelium was still visible in some areas. Corneal endothelium cells were mildly damaged and some vacuoles within the cytoplasm could be discerned. In the anterior stroma, some unhealthy activated keratocytes could still be observed. New collagen fibrils were found present near the activated keratocytes. Using TEM, keratocyte activation could still be observed after SMILE compared to after PRK procedure. Fewer cellular ultrastructural changes were seen after SMILE procedure. Unlike in PRK procedure, no damaged epithelium and endothelium were found after SMILE.

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.

Discovery of molecular markers to discriminate corneal endothelial cells in the human body

NARCIS (Netherlands)

Yoshihara, Masahito; Ohmiya, Hiroko; Hara, Susumu; Kawasaki, Satoshi; Hayashizaki, Yoshihide; Itoh, Masayoshi; Kawaji, Hideya; Tsujikawa, Motokazu; Nishida, Kohji; Clevers, J.C.; van de Wetering, M.L.

2015-01-01

The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant

Discovery of Molecular Markers to Discriminate Corneal Endothelial Cells in the Human Body

NARCIS (Netherlands)

Yoshihara, Masahito; Ohmiya, Hiroko; Hara, Susumu; Kawasaki, Satoshi; Hayashizaki, Yoshihide; Itoh, Masayoshi; Kawaji, Hideya; Tsujikawa, Motokazu; Nishida, Kohji; Forrest, Alistair R. R.; Rehli, Michael; Baillie, J. Kenneth; de Hoon, Michiel J. L.; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Andersson, Robin; Mungall, Christopher J.; Meehan, Terrence F.; Schmeier, Sebastian; Bertin, Nicolas; Jørgensen, Mette; Dimont, Emmanuel; Arner, Erik; Schmidl, Christian; Schaefer, Ulf; Medvedeva, Yulia A.; Plessy, Charles; Vitezic, Morana; Severin, Jessica; Semple, Colin A.; Ishizu, Yuri; Francescatto, Margherita; Alam, Intikhab; Albanese, Davide; Altschuler, Gabriel M.; Archer, John A. C.; Arner, Peter; Babina, Magda; Baker, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Geijtenbeek, Teunis B.

2015-01-01

The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant

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

Clinical observation of corneal lamellar debridement combined with sutureless amniotic membrane transplantation for the treatment of superficial fungal keratitis

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Huang Zhang

2014-09-01

Full Text Available AIM:To evaluate the clinical efficacy of corneal lamellar debridement combined with sutureless amniotic membrane transplantation for the treatment of superficial fungal keratitis.METHODS:Totally 22 cases(22 eyeswith superficial fungal keratitis were referred to our hospital from April 2012 to October 2013. The patients with persistent cornea ulcer after treatment of local and systemic antifungal drugs underwent corneal lamellar debridement combined with sutureless amniotic membrane transplantation, and the recipient bed was covered with an amniotic membrane using fibrin sealant during the operation. All patients were still given topical antifungal therapy for 1-2mo after operation. The followed-up time was 3mo or above. We observed the corneal healing and amniotic membrane adhesion by split lamp microscope, and investigated the transformation of amniotic membrane and fungal infection recurrence with confocal microscope. RESULTS: Corneal edema and anterior chamber reaction of 21 patients disappeared gradually, and no amniotic membrane graft dissolved and shed off within 1-2wk postoperatively. Two weeks after operation, the graft integrated into the corneal and the corneal wounds' thickness increased gradually, the corneal epithelium reconstructed and corneas became clear. Four weeks after operation, the corneal scarring developed gradually and fluorescence staining was negative. Nineteen cases' amniotic membranes that adhered with the cornea dissolved 4wk after operation. There were different degrees of corneal nebula or macula remained 3mo postoperatively. All patients' vision improved in varying degrees, except in 1 case with fungal keratitis who had been cured by lamellar keratoplasty.CONCLUSION:Corneal lamellar debridement combined with sutureless amniotic membrane transplantation can effectively remove the foci of inflammation, improve the local efficacy, shorten the operation time, relieve the postoperative reaction, and promote cornea

Photographic-Based Optical Evaluation of Tissues and Biomaterials Used for Corneal Surface Repair: A New Easy-Applied Method.

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Miguel Gonzalez-Andrades

Full Text Available Tissues and biomaterials used for corneal surface repair require fulfilling specific optical standards prior to implantation in the patient. However, there is not a feasible evaluation method to be applied in clinical or Good Manufacturing Practice settings. In this study, we describe and assess an innovative easy-applied photographic-based method (PBM for measuring functional optical blurring and transparency in corneal surface grafts.Plastic compressed collagen scaffolds (PCCS and multilayered amniotic membranes (AM samples were optically and histologically evaluated. Transparency and image blurring measures were obtained by PBM, analyzing photographic images of a standardized band pattern taken through the samples. These measures were compared and correlated to those obtained applying the Inverse Adding-Doubling (IAD technique, which is the gold standard method.All the samples used for optical evaluation by PBM or IAD were histological suitable. PCCS samples presented transmittance values higher than 60%, values that increased with increasing wavelength as determined by IAD. The PBM indicated that PCCS had a transparency ratio (TR value of 80.3 ± 2.8%, with a blurring index (BI of 50.6 ± 4.2%. TR and BI obtained from the PBM showed a high correlation (ρ>|0.6| with the diffuse transmittance and the diffuse reflectance, both determined using the IAD (p<0.005. The AM optical properties showed that there was a largely linear relationship between the blurring and the number of amnion layers, with more layers producing greater blurring.This innovative proposed method represents an easy-applied technique for evaluating transparency and blurriness of tissues and biomaterials used for corneal surface repair.

Subthreshold UV radiation-induced peroxide formation in cultured corneal epithelial cells: the protective effects of lactoferrin

International Nuclear Information System (INIS)

Shimmura, Shigeto; Suematsu, Makoto; Shimoyama, Masaru; Oguchi, Yoshihisa; Ishimura, Yuzuru

1996-01-01

Acute exposure to suprathreshold ultraviolet B radiation (UV-B) is known to cause photokeratitis resulting from the necrosis and shedding of corneal epithelial cells. However, the corneal effects of low dose UV-B in the environmental range is less clear. In this study, subthreshold UV-B was demonstrated to cause non-necrotic peroxide formation in cultured corneal epithelial cells, which was attenuated by the major tear protein lactoferrin. Intracellular oxidative insults and cell viability of rabbit corneal epithelial cells (RCEC) were assessed by dual-color digital microfluorography using carboxydichlorofluorescin (CDCFH) diacetate bis (acetoxymethyl) ester, a hydroperoxide-sensitive fluoroprobe, and propidium iodode (PI) respectively. The magnitude of UV-induced oxidative insults was calibrated by concentrations of exogenously applied H 2 O 2 which evoke compatible levels of CDCFH oxidation. Exposure of RCEC to low-dose UV-B (2.0 mJ cm -2 at 313 nm, 10.0 mJ cm -2 total UV-B) caused intracellular oxidative changes which were equivalent to those elicited by 240 μM hydrogen peroxide under the conditions of the study. The changes were dose dependent, non-necrotic, and were partially inhibited by lactoferrin ( 1 mg ml -1 ) but not by iron-saturated lactoferrin. Pretreatment with deferoxamine (2 mΜ) or catalase (100 U ml -1 ) also attenuated the UV-induced oxidative stress. The results indicate that UV-B comparable to solar irradiation levels causes significant intracellular peroxide formation in corneal epithelial cells, and that lactoferrin in tears may have a physiological role in protecting the corneal epithelium from solar UV irradiation. (Author)

Molecular evidence and functional expression of multidrug resistance associated protein (MRP) in rabbit corneal epithelial cells.

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Karla, Pradeep K; Pal, Dananjay; Mitra, Ashim K

2007-01-01

Multidrug resistance associated protein (MRP) is a major family of efflux transporters involved in drug efflux leading to drug resistance. The objective of this study was to explore physical barriers for ocular drug absorption and to verify if the role of efflux transporters. MRP-2 is a major homologue of MRP family and found to express on the apical side of cell membrane. Cultured Rabbit Corneal Epithelial Cells (rCEC) were selected as an in vitro model for corneal epithelium. [14C]-erythromycin which is a proven substrate for MRP-2 was selected as a model drug for functional expression studies. MK-571, a known specific and potent inhibitor for MRP-2 was added to inhibit MRP mediated efflux. Membrane fraction of rCEC was used for western blot analysis. Polarized transport of [14C]-erythromycin was observed in rCEC and transport from B-->A was significantly high than from A-->B. Permeability's increased significantly from A-->B in the presence of MK-571 and ketoconozole. Uptake of [14C]-erythromycin in the presence of MK-571 was significantly higher than control in rCEC. RT-PCR analysis indicated a unique and distinct band at approximately 498 bp corresponding to MRP-2 in rCEC and MDCK11-MRP-2 cells. Immunoprecipitation followed by Western Blot analysis indicated a specific band at approximately 190 kDa in membrane fraction of rCEC and MDCK11-MRP-2 cells. For the first time we have demonstrated high expression of MRP-2 in rabbit corneal epithelium and its functional activity causing drug efflux. RT-PCR, immunoprecipitation followed by Western blot analysis further confirms the result.

Novel nuclear localization and potential function of insulin-like growth factor-1 receptor/insulin receptor hybrid in corneal epithelial cells.

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Yu-Chieh Wu

Full Text Available BACKGROUND: Type I insulin-like growth factor receptor (IGF-1R and insulin receptor (INSR are highly homologous molecules, which can heterodimerize to form an IGF-1R/INSR hybrid (Hybrid-R. The presence and biological significance of the Hybrid-R in human corneal epithelium has not yet been established. In addition, while nuclear localization of IGF-1R was recently reported in cancer cells and human corneal epithelial cells, the function and profile of nuclear IGF-1R is unknown. In this study, we characterized the nuclear localization and function of the Hybrid-R and the role of IGF-1/IGF-1R and Hybrid-R signaling in the human corneal epithelium. METHODOLOGY/PRINCIPLE FINDINGS: IGF-1-mediated signaling and cell growth were examined in a human telomerized corneal epithelial (hTCEpi cell line using co-immunoprecipitation, immunoblotting and cell proliferation assays. The presence of Hybrid-R in hTCEpi and primary cultured human corneal epithelial cells was confirmed by immunofluorescence and reciprocal immunoprecipitation of whole cell lysates. We found that IGF-1 stimulated Akt and promoted cell growth through IGF-1R activation, which was independent of the Hybrid-R. The presence of Hybrid-R, but not IGF-1R/IGF-1R, was detected in nuclear extracts. Knockdown of INSR by small interfering RNA resulted in depletion of the INSR/INSR and preferential formation of Hybrid-R. Chromatin-immunoprecipitation sequencing assay with anti-IGF-1R or anti-INSR was subsequently performed to identify potential genomic targets responsible for critical homeostatic regulatory pathways. CONCLUSION/SIGNIFICANCE: In contrast to previous reports on nuclear localized IGF-1R, this is the first report identifying the nuclear localization of Hybrid-R in an epithelial cell line. The identification of a nuclear Hybrid-R and novel genomic targets suggests that IGF-1R traffics to the nucleus as an IGF-1R/INSR heterotetrameric complex to regulate corneal epithelial homeostatic

Establishment of a new immortalized human corneal epithelial cell line (iHCE-NY1) for use in evaluating eye irritancy by in vitro test methods.

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Yamamoto, Naoki; Kato, Yoshinao; Sato, Atsushi; Hiramatsu, Noriko; Yamashita, Hiromi; Ohkuma, Mahito; Miyachi, Ei-Ichi; Horiguchi, Masayuki; Hirano, Koji; Kojima, Hajime

2016-08-01

In vitro test methods that use human corneal epithelial cells to evaluate the eye irritation potency of chemical substances do not use human corneal epithelium because it has been difficult to maintain more than four passages. In this study, we make a new cell line comprising immortalized human corneal epithelial cells (iHCE-NY1). The IC50 of iHCE-NY1 cells is slightly higher than that of Statens Seruminstitut Rabbit Cornea (SIRC) cells, which are currently used in some in vitro test methods. CDKN1A in iHCE-NY1 cells was used as a marker of gene expression to indicate cell cycle activity. This enabled us to evaluate cell recovery characteristics at concentrations lower than the IC50 of cytotoxic tests.

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.

Chronic pesticide exposure and consequential keratectasia & corneal neovascularisation.

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Sanyal, Shalini; Law, Atrayo; Law, Sujata

2017-11-01

Ocular toxicity as a consequence of chronic pesticide exposure is one of the health hazards caused due to extended exposure to pesticides. The cornea, due to its position as the outer ocular layer and its role in protecting the internal layers of the eye; is gravely affected by this xenobiotic insult to the eye, leading to ocular irritation and damage to normal vision. The deleterious effects of chronic pesticide exposure on the various corneal layers and the ocular risks involved therein, were explored by mimicking the on-field scenario. Cytological, histological and flowcytometric parameters were taken into consideration to determine the enhanced risk of corneal neovascularisation and keratectasia, specifically, keratoconus. Chronic exposure to pesticides leads to heightened ocular morbidity wherein there were visible pathophysiological changes to the ocular surface. The cornea was found to be adversely affected with visible protuberance in a cone-like shape, characteristic of keratoconus in a majority of the experimental animals. Further analyses revealed a detrimental impact on all the corneal layers and an amplified expression of inflammation markers such as TNF-α, VCAM-1 and ICAM-1. Additionally, it was found that post pesticide exposure, the corneal surface developed hypoxia, leading to a significant increase of angiogenesis promoting factors and consequential neovascularisation. Apart from ocular toxicity, chronic exposure to pesticides significantly increases the risks of keratectasia and corneal neovascularisation; disorders which lead to diminished vision and if untreated, blindness. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Communication between corneal epithelial cells and trigeminal neurons is facilitated by purinergic (P2) and glutamatergic receptors.

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Oswald, Duane J; Lee, Albert; Trinidad, Monique; Chi, Cheryl; Ren, Ruiyi; Rich, Celeste B; Trinkaus-Randall, Vickery

2012-01-01

Previously, we demonstrated that nucleotides released upon mechanical injury to corneal epithelium activate purinergic (P2) receptors resulting in mobilization of a Ca(2+) wave. However, the tissue is extensively innervated and communication between epithelium and neurons is critical and not well understood. Therefore, we developed a co-culture of primary trigeminal neurons and human corneal limbal epithelial cells. We demonstrated that trigeminal neurons expressed a repertoire of P2Yand P2X receptor transcripts and responded to P2 agonists in a concentration-dependent manner. Mechanical injuries to epithelia in the co-cultures elicited a Ca(2+) wave that mobilized to neurons and was attenuated by Apyrase, an ectonucleotidase. To elucidate the role of factors released from each cell type, epithelial and neuronal cells were cultured, injured, and the wound media from one cell type was collected and added to the other cell type. Epithelial wound media generated a rapid Ca(2+) mobilization in neuronal cells that was abrogated in the presence of Apyrase, while neuronal wound media elicited a complex response in epithelial cells. The rapid Ca(2+) mobilization was detected, which was abrogated with Apyrase, but it was followed by Ca(2+) waves that occurred in cell clusters. When neuronal wound media was preincubated with a cocktail of N-methyl-D-aspartate (NMDA) receptor inhibitors, the secondary response in epithelia was diminished. Glutamate was detected in the neuronal wound media and epithelial expression of NMDA receptor subunit transcripts was demonstrated. Our results indicate that corneal epithelia and neurons communicate via purinergic and NMDA receptors that mediate the wound response in a highly orchestrated manner.

Communication between corneal epithelial cells and trigeminal neurons is facilitated by purinergic (P2 and glutamatergic receptors.

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Duane J Oswald

Full Text Available Previously, we demonstrated that nucleotides released upon mechanical injury to corneal epithelium activate purinergic (P2 receptors resulting in mobilization of a Ca(2+ wave. However, the tissue is extensively innervated and communication between epithelium and neurons is critical and not well understood. Therefore, we developed a co-culture of primary trigeminal neurons and human corneal limbal epithelial cells. We demonstrated that trigeminal neurons expressed a repertoire of P2Yand P2X receptor transcripts and responded to P2 agonists in a concentration-dependent manner. Mechanical injuries to epithelia in the co-cultures elicited a Ca(2+ wave that mobilized to neurons and was attenuated by Apyrase, an ectonucleotidase. To elucidate the role of factors released from each cell type, epithelial and neuronal cells were cultured, injured, and the wound media from one cell type was collected and added to the other cell type. Epithelial wound media generated a rapid Ca(2+ mobilization in neuronal cells that was abrogated in the presence of Apyrase, while neuronal wound media elicited a complex response in epithelial cells. The rapid Ca(2+ mobilization was detected, which was abrogated with Apyrase, but it was followed by Ca(2+ waves that occurred in cell clusters. When neuronal wound media was preincubated with a cocktail of N-methyl-D-aspartate (NMDA receptor inhibitors, the secondary response in epithelia was diminished. Glutamate was detected in the neuronal wound media and epithelial expression of NMDA receptor subunit transcripts was demonstrated. Our results indicate that corneal epithelia and neurons communicate via purinergic and NMDA receptors that mediate the wound response in a highly orchestrated manner.

Irregularity of the posterior corneal surface during applanation using a curved femtosecond laser interface and microkeratome cutting head.

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Vetter, Jan M; Holtz, Carsten; Vossmerbaeumer, Urs; Pfeiffer, Norbert

2012-03-01

To evaluate the irregularity of the posterior corneal surface and intrastromal dissection during the preparation of donor tissue for Descemet stripping automated endothelial keratoplasty (DSAEK) using a curved interface femtosecond laser and microkeratome. Sixteen human donor corneas unsuitable for transplantation were divided into two groups: a femtosecond (FS) laser group (n=7) using the VisuMax femtosecond laser (Carl Zeiss Meditec) and a microkeratome group (n=9) using the Amadeus II microkeratome (Ziemer Ophthalmic Group). The corneas were fixed on artificial anterior chambers. Horizontal cross-sections were obtained using spectral-domain optical coherence tomography prior to applanation, during applanation, as well as during and after intrastromal dissection at 450-μm corneal depth. The posterior surface and the dissection line were evaluated for irregularity by fitting a second-order polynomial curve using regression analysis and obtaining the root-mean-square error (RMSE). Groups were compared using analysis of variance. The RMSE of the posterior surface prior to applanation was 9.7 ± 3.1 μm in the FS laser group and 10.2 ± 2.3 μm in the microkeratome group. The RMSE increased to 50.7 ± 9.4 μm and 20.9 ± 6.1 μm during applanation and decreased again to 10.6 ± 1.4 μm and 8.1 ± 1.8 μm after applanation in the FS laser and microkeratome groups, respectively. The RMSE of the intrastromal cut was 19.5 ± 5.7 μm in the FS laser group and 7.7 ± 3.0 μm in the microkeratome group (P<.001). Our results show significantly greater irregularity with the curved interface femtosecond laser-assisted cleavage compared to microkeratome-assisted corneal dissection, possibly due to applanation-derived deformation of the posterior cornea. Copyright 2012, SLACK Incorporated.

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 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.

Estimation of the in vitro eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust by using reconstituted human corneal epithelium tissue cultures.

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Cao, Yi; Bindslev, Dorthe A; Kjærgaard, Søren K

2015-01-01

Eye irritation is a common complaint in indoor environment, but the causes have still not been identified among the multiple exposures in house environments. To identify the potential environmental factors responsible for eye irritation and study the possible mechanisms, an in vitro model for eye irritation is suggested. In this study, reconstituted human corneal epithelium (HCE) tissue cultures were used to study the eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust. HCE tissue cultures were exposed to a range of concentrations of LPS for 6 h and dust for 24 h, respectively. After exposure, viability and secretion of interleukins (IL) IL-1β, IL-8, and tumor necrosis factor (TNFα) were examined. Histology was used to indicate the morphological changes after dust exposure. Both LPS and dust affected HCE viability. There was an increased level of IL-8 after LPS exposure, while the concentrations of IL-1β and TNFα remained unaffected. Dust exposure resulted in an elevation of both IL-1β and IL-8, but not TNFα. Histology study showed increased vacuolization and reduced thickness after 24 h exposure to 5 mg/mL dust. LPS and dust showed in vitro eye irritating and inflammatory potential, and cytokines/chemokines like IL-1β and IL-8 may be involved in the mechanisms of eye irritation. The HCE tissue culture may be used as an in vitro model to study environmental exposure induced eye irritation and inflammation.

Enhancement and inhibition effects on the corneal permeability of timolol maleate: Polymers, cyclodextrins and chelating agents.

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Rodríguez, Isabel; Vázquez, José Antonio; Pastrana, Lorenzo; Khutoryanskiy, Vitaliy V

2017-08-30

This study investigates how both bioadhesive polymers (chitosan, hyaluronic acid and alginate) and permeability enhancers (ethylene glycol- bis(2-aminoethylether)- N, N, N', N'- tetraacetic acid (EGTA) and hydroxypropyl-ß-cyclodextrin) influence the permeability of the anti-glaucoma drug timolol maleate through ex vivo bovine corneas. Our results showed that only the permeability enhancers alone were able to increase drug permeability, whereas the polymers significantly reduced drug permeation, and however, they increased the pre-corneal residence of timolol. Ternary systems (polymer-enhancer-drug) showed a reduced drug permeability compared to the polymers alone. Fluorescence microscopy analysis of the epithelium surface confirmed there was no evidence of epithelial disruption caused by these formulations, suggesting that polymer-enhancer interactions reduce drug solubilization and counteract the disruptive effect of the permeability enhancers on the surface of the cornea. Further mucoadhesive tests, revealed a stable interaction of chitosan and hyaluronic acid with the epithelium, while alginate showed poor mucoadhesive properties. The differences in mucoadhesion correlated with the permeability of timolol maleate observed, i.e. formulations containing mucoadhesive polymers showed lower drug permeabilities. The results of the present study indicate polymers acting as an additional barrier towards drug permeability which is even more evident in the presence of permeability enhancers like EGTA and hydroxypropyl-ß-cyclodextrin. Then, this study highlights the need to adequately select additives intended for ocular applications since interactions between them can have opposite results to what expected in terms of drug permeability. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Excimer laser corneal surgery and free oxygen radicals.

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Bilgihan, K; Bilgihan, A; Akata, F; Hasanreisoğlu, B; Türközkan, N

1996-01-01

Corneal photoablation with 193 nm argon fluoride excimer laser is a new technique for the treatment of refractive errors and for removing corneal opacities and irregularities. Ultraviolet radiation and thermal injury induce free radical formation in the tissues. The aim of this study was to confirm the production of free radicals by excimer laser photoablation in rabbits. The thermal changes of the posterior corneal surface were recorded during excimer laser photoablation. The lipid peroxide (LPO) levels and superoxide dismutase (SOD) activities of aqueous humour were measured after excimer laser keratectomy. The aqueous LPO levels were not changed after excimer laser ablation, but both the thermal increase in the cornea during the photoablation and the decreased aqueous SOD activities suggest that free radicals are formed in the cornea during excimer laser keratectomy, and that they may be responsible for some of the complications of excimer laser corneal surgery.

Unilateral corneal leukoplakia without limbal involvement

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Hirano K

2015-05-01

Full Text Available Koji Hirano,1 Mihoko Koide,2 Yoshikazu Mizoguchi,3 Yasuhiro Osakabe,4 Kaoru-Araki Sasaki5 1Department of Ophthalmology, Ban Buntane Hotokukai Hospital, School of Medicine, Fujita Health University, Nagoya, Japan; 2Koide Internal Medicine and Eye Clinic, Nagoya, Japan; 3Department of Pathology, Ban Buntane Hotokukai Hospital, School of Medicine, Fujita Health University, Nagoya, Japan; 4Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan; 5Department of Ophthalmology, Japan Health Care Organization, Hoshigaoka Medical Center, Hirakata, Japan Purpose: Leukoplakia is the term given to a white patch or plaque that is found mainly on the oral mucus membrane. It can occasionally be seen on the corneal surface. We report our clinical and histopathological findings in a case of unilateral corneal leukoplakia. Methods: A 26-year-old woman was referred to our hospital because of a white patch on her right cornea that continued to expand. She first noticed the white patch when she was 20 years old, and the white patch had expanded to cover the pupillary area affecting her vision. After plastic surgery on both eyelids for bilateral entropion to alleviate the pain caused by the eyelashes rubbing the cornea, the white corneal patch decreased in size. Because of this reduction, we performed surgery to remove the patch with microforceps under topical anesthesia. The plaque was removed easily and completely, and submitted for histopathological examination. Results: Histopathological examination showed that the specimen had characteristics of epidermis with a basal cell layer, spinous cell layer, granular cell layer, and horny layer with hyperkeratosis. She was diagnosed with leukoplakia of the corneal surface. The basic structure of the squamous cell layer was preserved, and there were no signs of metaplasia. Six months after the removal of the leukoplakia, no recurrence was seen and her corrected decimal visual acuity recovered to 1

TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium.

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Martínez-Rendón, Jacqueline; Sánchez-Guzmán, Erika; Rueda, Angélica; González, James; Gulias-Cañizo, Rosario; Aquino-Jarquín, Guillermo; Castro-Muñozledo, Federico; García-Villegas, Refugio

2017-07-01

TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca 2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF-activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4-TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794-1807, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

[Analysis of aberration changes of the corneal anterior surface following discontinued use of rigid gas permeable contact lenses].

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Yu, Qing; Wu, Jiang-xiu; Zhang, He-ning; Ye, Sheng; Dong, Shi-qi; Zhang, Chen-hao

2011-04-01

The present study used a corneal topographic device to record aberrations on the anterior surface of the cornea at different time-points prior to wearing and following discontinued use of rigid gas permeable (RGP) contact lenses. The effect of wearing RGPCL on the anterior surface of the cornea was discussed to provide guidance for clinical refractive error correction. The study objects were 60 eyes from 30 patients. All patients underwent identical examination procedures prior to lens use, as well as afterwards, including slit-lamp examination, non-contact tonometer measurement, computer optometry & corneal curvature measurement, subjective refraction test, and corneal topography analysis. The patients wore contact lenses every day for 1 month and then discontinued. Corneal topographies were recorded at certain time points of 30 min, 1 day, 3 days, 1 week, and 2 weeks following use. Total corneal aberration at each time point following discontinued use of RGP contact lenses was less than the time point prior to use. Detailed results are as follows; root mean square (RMS) (pre) = (1.438 ± 0.328), RMS (30 min) = (1.076 ± 0.355), RMS (1 day) = (1.362 ± 0.402), RMS (3 day) = (1.373 ± 0.398), RMS (7 day) = (1.387 ± 0.415), and RMS (14 day) = (1.448 ± 0.423). Results showed that at 30 minutes after discontinued use of RGP contact lenses, almost all 2(nd)- and 3(rd)-order aberrations were altered. Quadrafoil Z10 and spherical Z12 of the 4(th)-order were also changed. Alterations to Z5, Z6, and Z12 at 1 day after discontinued use were significant compared with the time period prior to RGP use: Z5 and Z6 decreased, and Z12 increased slightly (F = 2.869 ∼ 5.549, P = 0.001 ∼ 0.042). Z5 and Z6 remained decreased at 3 days after discontinued use, but Z9 and Z10 continued to increase and Z12 returned to levels prior to RGP use (P > 0.05). At 2 weeks after discontinued use, all aberrations were not significantly different from the values prior to use (P > 0.05). The

Resveratrol enhances airway surface liquid depth in sinonasal epithelium by increasing cystic fibrosis transmembrane conductance regulator open probability.

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Shaoyan Zhang

Full Text Available Chronic rhinosinusitis engenders enormous morbidity in the general population, and is often refractory to medical intervention. Compounds that augment mucociliary clearance in airway epithelia represent a novel treatment strategy for diseases of mucus stasis. A dominant fluid and electrolyte secretory pathway in the nasal airways is governed by the cystic fibrosis transmembrane conductance regulator (CFTR. The objectives of the present study were to test resveratrol, a strong potentiator of CFTR channel open probability, in preparation for a clinical trial of mucociliary activators in human sinus disease.Primary sinonasal epithelial cells, immortalized bronchoepithelial cells (wild type and F508del CFTR, and HEK293 cells expressing exogenous human CFTR were investigated by Ussing chamber as well as patch clamp technique under non-phosphorylating conditions. Effects on airway surface liquid depth were measured using confocal laser scanning microscopy. Impact on CFTR gene expression was measured by quantitative reverse transcriptase polymerase chain reaction.Resveratrol is a robust CFTR channel potentiator in numerous mammalian species. The compound also activated temperature corrected F508del CFTR and enhanced CFTR-dependent chloride secretion in human sinus epithelium ex vivo to an extent comparable to the recently approved CFTR potentiator, ivacaftor. Using inside out patches from apical membranes of murine cells, resveratrol stimulated an ~8 picosiemens chloride channel consistent with CFTR. This observation was confirmed in HEK293 cells expressing exogenous CFTR. Treatment of sinonasal epithelium resulted in a significant increase in airway surface liquid depth (in µm: 8.08+/-1.68 vs. 6.11+/-0.47,control,p<0.05. There was no increase CFTR mRNA.Resveratrol is a potent chloride secretagogue from the mucosal surface of sinonasal epithelium, and hydrates airway surface liquid by increasing CFTR channel open probability. The foundation for a

The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair.

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Inna Maltseva

Full Text Available Corneal epithelial wound repair involves the migration of epithelial cells to cover the defect followed by the proliferation of the cells to restore thickness. Heparan sulfate proteoglycans (HSPGs are ubiquitous extracellular molecules that bind to a plethora of growth factors, cytokines, and morphogens and thereby regulate their signaling functions. Ligand binding by HS chains depends on the pattern of four sulfation modifications, one of which is 6-O-sulfation of glucosamine (6OS. SULF1 and SULF2 are highly homologous, extracellular endosulfatases, which post-synthetically edit the sulfation status of HS by removing 6OS from intact chains. The SULFs thereby modulate multiple signaling pathways including the augmentation of Wnt/ß-catenin signaling. We found that wounding of mouse corneal epithelium stimulated SULF1 expression in superficial epithelial cells proximal to the wound edge. Sulf1⁻/⁻, but not Sulf2⁻/⁻, mice, exhibited a marked delay in healing. Furthermore, corneal epithelial cells derived from Sulf1⁻/⁻ mice exhibited a reduced rate of migration in repair of a scratched monolayer compared to wild-type cells. In contrast, human primary corneal epithelial cells expressed SULF2, as did a human corneal epithelial cell line (THCE. Knockdown of SULF2 in THCE cells also slowed migration, which was restored by overexpression of either mouse SULF2 or human SULF1. The interchangeability of the two SULFs establishes their capacity for functional redundancy. Knockdown of SULF2 decreased Wnt/ß-catenin signaling in THCE cells. Extracellular antagonists of Wnt signaling reduced migration of THCE cells. However in SULF2- knockdown cells, these antagonists exerted no further effects on migration, consistent with the SULF functioning as an upstream regulator of Wnt signaling. Further understanding of the mechanistic action of the SULFs in promoting corneal repair may lead to new therapeutic approaches for the treatment of corneal injuries.

Evaluation of corneal symmetry after UV corneal crosslinking for keratoconus

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Mofty H

2017-11-01

influenced by temporal evolution of surface ablation and increased corneal haze. However, insignificant changes in symmetry attest the stabilization effect on cornea postoperatively as compared with controls. Keywords: keratoconus, crosslinking, topography, corneal haze, asphericity

Epithelium

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The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Kierszenbaum AL, Tres LL. Epithelium. In: Kierszenbaum AL, Tres LL, ... to Pathology . 4th ed. Philadelphia, PA: Elsevier Saunders; ...

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.

Confocal microscopy evaluation of stromal fluorescence intensity after standard and accelerated iontophoresis-assisted corneal cross-linking.

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Lanzini, Manuela; Curcio, Claudia; Spoerl, Eberhard; Calienno, Roberta; Mastropasqua, Alessandra; Colasante, Martina; Mastropasqua, Rodolfo; Nubile, Mario; Mastropasqua, Leonardo

2017-02-01

The aim of this study is to determine modifications in stromal fluorescence intensity after different corneal cross-linking (CXL) procedures and to correlate stromal fluorescence to corneal biomechanical resistance. For confocal microscopy study, 15 human cadaver corneas were examined. Three served as control (group 1), three were just soaked with iontophoresis procedure (group 2), three were treated with standard epi-off technique (group 3), and six underwent iontophoresis imbibition. Three of later six were irradiated for 30 min with 3 mW/cm 2 UVA (group 4) and three for 9 min at 10 mW/cm 2 UVA (group 5). Confocal microscopy was performed to quantify the fluorescence intensity in the cornea at different stromal depths. For biomechanical study, 30 human cadaver corneas were randomly divided into five groups and treated as previously described. Static stress-strain measurements of the corneas were performed. Iontophoresis imbibition followed by 10mW/cm 2 irradiation proved to increase stromal fluorescence into the corneal stroma and significant differences were revealed between group 3 and 5 both at 100 (p = 0.0171) and 250 µm (p = 0.0024), respectively. Biomechanical analysis showed an improvement of corneal resistance in group 5. Iontophoresis imbibition followed by accelerated irradiation increased the stromal fluorescence and is related to an improvement of biomechanical resistance. This approach may represent a new strategy to achieve greater concentrations of riboflavin without removing corneal epithelium and improve clinical results while reducing the side effects of CXL.

Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis.

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Karseladze, A I

2015-06-01

To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and fetuses were used. Traditional histological as well as immunohistochemical methods have been used. The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. Glandular epithelial coverings, as well as transitional epithelium, do not contain blood vessels. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus, the cells of squamous epithelium are more vulnerable to blood deficiency, since for instance in the pseudo-multilayered respiratory epithelium each cell is attached directly to the basal membrane and has more ample access to the blood supply. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels. The process of redistribution of vascular network occurring at the interface of epithelial-stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations.

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.

Polysaccharide coating of human corneal endothelium

DEFF Research Database (Denmark)

Schroder, H D; Sperling, S

1977-01-01

Electron microscopy revealed the presence of a 600-1500 A thick layer of polysaccharide on the surface of human corneal endothelial cells. The surface layer was visualized by combined fixation and staining in a mixture of ruthenium red and osmium tetroxide. The coating material was stable for at ...... for at least 39 h post mortem and was retained on disintegrating cells....

Equine corneal stromal abscesses

DEFF Research Database (Denmark)

Henriksen, M. D. L.; Andersen, P. H.; Plummer, C. E.

2013-01-01

The last 30 years have seen many changes in the understanding of the pathogenesis and treatment of equine corneal stromal abscesses (SAs). Stromal abscesses were previously considered an eye problem related to corneal bacterial infection, equine recurrent uveitis, corneal microtrauma and corneal....... Medical and surgical treatments are now directed towards elimination of fungal and bacterial infections, reduction and replacement of diseased corneal stroma, and suppression of iridocyclitis. If the abscess and anterior uveitis do not respond satisfactorily to medical therapy, full thickness or split...

Cytokeratin expression in mouse lacrimal gland germ epithelium.

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Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

2016-05-01

The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Tectonic DSAEK for the Management of Impending Corneal Perforation

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Enrique O. Graue-Hernandez

2012-01-01

Full Text Available Purpose. To report a case of severe corneal thinning secondary to dry eye treated with a tectonic Descemet stripping automated lamellar keratoplasty (DSAEK and amniotic membrane graft. Methods. A 72-year-old man with a history of long standing diabetes mellitus type 2 and dry eye presented with 80% corneal thinning and edema on the right eye and no signs of infectious disease, initially managed with topical unpreserved lubrication and 20% autologous serum drops. Eight weeks after, the defect advanced in size and depth until Descemetocele was formed. Thereafter, he underwent DSAEK for tectonic purposes. One month after the procedure, the posterior lamellar graft was well adhered but a 4 mm epithelial defect was still present. A multilayered amniotic membrane graft was then performed. Results. Ocular surface healed quickly and reepithelization occurred over a 2-week period. Eight months after, the ocular surface remained stable and structurally adequate. Conclusion. Tectonic DSAEK in conjunction with multilayered amniotic graft may not only provide structural support and avoid corneal perforation, but may also promote reepithelization and ocular surface healing and decrease concomitant inflammation.

Expression of hypoxia-inducible factor-1α and erythropoietin at corneal neovascularization in rats

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Ji-Min Wang

2014-12-01

Full Text Available AIM: To describe the expression of hypoxia-inducible factor-1α(HIF-1αand erythropoietin(EPOin rats' corneal and evaluate its potential effect on corneal neovascularization(CNVgrowth. METHODS: The young SD rats(3mowas chosen and randomly divided into 2 groups, which were experimental group and normal control group. CNV model was established by alkali burn, and the length and area of CNV was observed everyday after operation by slit lamp. After that, the expression of HIF-1α and EPO was measured by SABC and RT-PCR methods at 1, 3, 5, 7, and 14d after alkali burn. The data was analyzed by SPSS 20.0. RESULTS: The area of CNV was increasing at 1, 3, 5, 7, and 14d after alkali burn, and the peak point appear at 7d. The growth speed was decreased after 14d. SABC method told us that no HIF-1α and very tiny amount EPO was detected at normal rats' corneal. The expression of the two factors increased at 1d after alkali burn in corneal epithelium and endoderm. The results of RT-PCR showed that a few amounts of HIF-1α and EPO mRNA were detected at normal group. The expression of the two factors was increased at 3d after alkali burn, and the peak value was found at 7d, however, it was decreased at 14d. Statistical difference was found at different time(PCONCLUSION: HIF-1α and EPO is closely related to CNV.

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

Science.gov (United States)

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.

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

C-terminal cleavage of DeltaNp63alpha is associated with TSA-induced apoptosis in immortalized corneal epithelial cells.

Science.gov (United States)

Robertson, Danielle M; Ho, Su-Inn; Cavanagh, H Dwight

2010-08-01

In the central human corneal epithelium, loss of DeltaNp63 occurs in all surface epithelial cells preparing to undergo desquamation, suggesting a potential role for DeltaNp63 isoforms in mediating surface cell apoptotic shedding. In this study, the authors investigated a role for DeltaNp63 isoforms in caspase-mediated apoptosis in a telomerase-immortalized corneal epithelial cell line. For in vitro studies, hTCEpi cells were cultured in KGM-2 serum-free culture media containing 0.15 mM calcium. To assess dynamic protein interactions among individual DeltaNp63 isoforms, DeltaNp63-EGFP expression plasmids were transiently expressed in hTCEpi cells and evaluated by FRAP. Trichostatin-A (TSA; 3.31 muM) was used to induce cell death as measured by caspase activity. Cleavage and loss of endogenous DeltaNp63alpha, DeltaNp63-EGFP expression plasmids, and p53 were assessed after treatment with TSA and siRNA. Transient expression of DeltaNp63-EGFP alpha and beta isoforms resulted in the formation of a smaller isoform similar in size to DeltaNp63gamma-EGFP. FRAP demonstrated that DeltaNp63alpha-EGFP has greater immobile fraction than beta or gamma. TSA induced caspase-mediated apoptotic pathways; caspase induction was accompanied by a decrease in endogenous DeltaNp63alpha and p53. TSA upregulated DeltaNp63-EGFP plasmid expression; this was accompanied by a selective increase in cleavage of DeltaNp63alpha-EGFP. siRNA knockdown of DeltaNp63alpha correlated with a reduction in p53 independently of TSA. DeltaNp63alpha is the dominant active isoform in corneal epithelial cell nuclei. Loss of DeltaNp63alpha occurs during apoptotic signaling by cleavage at the C terminus. The corresponding loss of p53 suggests that a significant relationship appears to exist between these two regulatory proteins.

Corneal topographer based on the Hartmann test.

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Mejía, Yobani; Galeano, Janneth C

2009-04-01

The purpose of this article is to show the performance of a topographer based on the Hartmann test for convex surfaces of F/# approximately 1. This topographer, called "Hartmann Test topographer (HT topographer)," is a prototype developed in the Physics Department of the Universidad Nacional de Colombia. From the Hartmann pattern generated by the surface under test, and by the Fourier analysis and the optical aberration theory we obtain the sagitta (elevation map) of the surface. Then, taking the first and the second derivatives of the sagitta in the radial direction we obtain the meridional curvature map. The method is illustrated with an example. To check the performance of the HT topographer a toric surface, a revolution aspherical surface, and two human corneas were measured. Our results are compared with those obtained with a Placido ring topographer (Tomey TMS-4 videokeratoscope), and we show that our curvature maps are similar to those obtained with the Placido ring topographer. The HT topographer is able to reconstruct the corneal topography potentially eradicating the skew ray problem, therefore, corneal defects can be visualized more. The results are presented by elevation and meridional curvature maps.

Construction of a human corneal stromal equivalent with non-transfected human corneal stromal cells and acellular porcine corneal stromata.

Science.gov (United States)

Diao, Jin-Mei; Pang, Xin; Qiu, Yue; Miao, Ying; Yu, Miao-Miao; Fan, Ting-Jun

2015-03-01

A tissue-engineered human corneal stroma (TE-HCS) has been developed as a promising equivalent to the native corneal stroma for replacement therapy. However, there is still a crucial need to improve the current approaches to render the TE-HCS equivalent more favorable for clinical applications. At the present study, we constructed a TE-HCS by incubating non-transfected human corneal stromal (HCS) cells in an acellular porcine corneal stromata (aPCS) scaffold in 20% fetal bovine serum supplemented DMEM/F12 (1:1) medium at 37 °C with 5% CO2in vitro. After 3 days of incubation, the constructed TE-HCS had a suitable tensile strength for transplantation, and a transparency that is comparable to native cornea. The TE-HCS had a normal histological structure which contained regularly aligned collagen fibers and differentiated HCS cells with positive expression of marker and functional proteins, mimicking a native HCS. After transplantation into rabbit models, the TE-HCS reconstructed normal corneal stroma in vivo and function well in maintaining corneal clarity and thickness, indicating that the completely biological TE-HCS could be used as a HCS equivalent. The constructed TE-HCS has promising potentials in regenerative medicine and treatment of diseases caused by corneal stromal disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Slit-lamp photography and videography with high magnifications

Science.gov (United States)

Yuan, Jin; Jiang, Hong; Mao, Xinjie; Ke, Bilian; Yan, Wentao; Liu, Che; Cintrón-Colón, Hector R; Perez, Victor L; Wang, Jianhua

2015-01-01

Purpose To demonstrate the use of the slit-lamp photography and videography with extremely high magnifications for visualizing structures of the anterior segment of the eye. Methods A Canon 60D digital camera with Movie Crop Function was adapted into a Nikon FS-2 slit-lamp to capture still images and video clips of the structures of the anterior segment of the eye. Images obtained using the slit-lamp were tested for spatial resolution. The cornea of human eyes was imaged with the slit-lamp and the structures were compared with the pictures captured using the ultra-high resolution optical coherence tomography (UHR-OCT). The central thickness of the corneal epithelium and total cornea was obtained using the slit-lamp and the results were compared with the thickness obtained using UHR-OCT. Results High-quality ocular images and higher spatial resolutions were obtained by using the slit-lamp with extremely high magnifications and Movie Crop Function, rather than the traditional slit-lamp. The structures and characteristics of the cornea, such as the normal epithelium, abnormal epithelium of corneal intraepithelial neoplasia, LASIK interface, and contact lenses, were clearly visualized using this device. These features were confirmed by comparing the obtained images with those acquired using UHR-OCT. Moreover, the tear film debris on the ocular surface and the corneal nerve in the anterior corneal stroma were also visualized. The thicknesses of the corneal epithelium and total cornea were similar to that measured using UHR-OCT (P photography and videography with extremely high magnifications allows better visualization of the anterior segment structures of the eye, especially of the epithelium, when compared with the traditional slit-lamp. PMID:26020484

Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering.

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Jui-Yang Lai

Full Text Available Hyaluronic acid (HA is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function.

Keratoprostheses for corneal blindness: a review of contemporary devices

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Avadhanam, Venkata S; Smith, Helen E; Liu, Christopher

2015-01-01

According to the World Health Organization, globally 4.9 million are blind due to corneal pathology. Corneal transplantation is successful and curative of the blindness for a majority of these cases. However, it is less successful in a number of diseases that produce corneal neovascularization, dry ocular surface and recurrent inflammation, or infections. A keratoprosthesis or KPro is the only alternative to restore vision when corneal graft is a doomed failure. Although a number of KPros have been proposed, only two devices, Boston type-1 KPro and osteo-odonto-KPro, have came to the fore. The former is totally synthetic and the latter is semi-biological in constitution. These two KPros have different surgical techniques and indications. Keratoprosthetic surgery is complex and should only be undertaken in specialized centers, where expertise, multidisciplinary teams, and resources are available. In this article, we briefly discuss some of the prominent historical KPros and contemporary devices. PMID:25945031

The impact of lipid composition on the stability of the tear fluid lipid layer

DEFF Research Database (Denmark)

Kulovesi, P.; Telenius, J.; Koivuniemi, A.

2012-01-01

The tear fluid protects the corneal epithelium from drying and pathogens and it also provides nutrients to these cells. Tear fluid is composed of an aqueous layer as well as a lipid layer that resides at the air-tear interface. The function of the lipid layer is to lower the surface tension of th......-neutral lipid ratio. The results provide a plausible rationale for the development of dry eye syndrome in blepharitis patients.......The tear fluid protects the corneal epithelium from drying and pathogens and it also provides nutrients to these cells. Tear fluid is composed of an aqueous layer as well as a lipid layer that resides at the air-tear interface. The function of the lipid layer is to lower the surface tension...

Corneal Crosslinking With Rose Bengal and Green Light: Efficacy and Safety Evaluation.

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Zhu, Hong; Alt, Clemens; Webb, Robert H; Melki, Samir; Kochevar, Irene E

2016-09-01

To evaluate crosslinking of cornea in vivo using green light activation of Rose Bengal (RGX) and assess potential damaging effects of the green light on retina and iris. Corneas of Dutch belted rabbits were de-epithelialized, then stained with Rose Bengal and exposed to green light, or not further treated. Corneal stiffness was measured by uniaxial tensiometry. Re-epithelialization was assessed by fluorescein fluorescence. Keratocytes were counted on hematoxylin and eosin (H&E)-stained sections, and iris cell damage was assessed by lactate dehydrogenase staining. Thermal effects on the blood-retinal barrier (BRB) were assessed by fluorescein angiography and those on photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris by light microscopy and transmission electron microscopy. RGX (10-min irradiation; 150 J/cm) increased corneal stiffness 1.9-fold on day 1 (1.25 ± 0.21 vs. 2.38 ± 0.59 N/mm; P = 0.036) and 2.8-fold compared with controls on day 28 (1.70 ± 0.74 vs. 4.95 ± 1.86 N/mm; P = 0.003). Keratocytes decreased only in the anterior stroma on day 1 (24.0 ± 3.0 vs. 3.67 ± 4.73, P = 0.003) and recovered by day 28 (37.7 ± 8.9 vs. 34.5 ± 2.4, P = 0.51). Iris cells were not thermally damaged. No evidence of BRB breakdown was detected on days 1 or 28. Retina from RGX-treated eyes seemed normal with RPE cells showing intact nuclei shielded apically by melanosomes, morphologically intact photoreceptor outer segments, normal outer nuclear layer thickness, and choriocapillaris containing intact erythrocytes. The substantial corneal stiffening produced by RGX together with the lack of significant effects on keratocytes and no evidence for retina or iris damage suggest that RGX-initiated corneal crosslinking may be a safe, rapid, and effective treatment.

Corneal Laceration

Medline Plus

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 ...

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

Science.gov (United States)

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.

Modalities of Tonometry and their Accuracy with Respect to Corneal Thickness and Irregularities

OpenAIRE

Carlos Gustavo V. De Moraes; Tiago S. Prata; Jeffrey Liebmann; Robert Ritch

2008-01-01

Recent advances in tonometry have led to the development of a number of devices with differing clinical applications. Their role in cases of abnormal corneal thickness and surface irregularities is particularly important, as inaccurate estimation of the true intraocular pressure (IOP) in such cases may lead to suboptimal evaluation. The purpose of the present review was to evaluate the accuracy of the most widely used devices in cases of corneal thickness and surface irregularities, based ...

Medicina regenerativa y superficie ocular Regenerative medicine and ocular surface

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Taimi Cárdenas Díaz

2012-06-01

Full Text Available En los últimos años se ha producido un extraordinario avance en los conocimientos relacionados con diferentes ramas biomédicas, entre ellas, la biología celular. Esto ha dado un notable impulso a una nueva rama de la medicina denominada medicina regenerativa. Esta nueva disciplina médica se basa fundamentalmente en los nuevos conocimientos sobre las células madre y en su capacidad de convertirse en células de diferentes tejidos. Una de las estructuras que tiene más interés, desde el punto de vista de la medicina regenerativa, es la superficie ocular. Por esto, se ha logrado notables progresos en la reconstrucción de la superficie ocular mediante la aplicación de procederes regenerativos. Los cultivos de células del epitelio corneal humano están siendo utilizados en el tratamiento de la insuficiencia limbar. Esto permite disminuir la incidencia de opacidades tipo Haze tras queratectomía fotorrefractiva, acelerar la curación y evitar la aparición de leucomas en pacientes con defectos epiteliares persistentes e intentar disminuir la incidencia de opacidades corneales en pacientes sometidos a queratectomía fototerapéutica por diferentes distrofias corneales.In the last few years, an extraordinary advance has taken place in the knowledge about several biomedical branches as is the case of cellular biology, which has remarkably encouraged the development of a new medical branch called regenerative medicine. This medical discipline is fundamentally based on the new knowledge on the stem cells and their capacity to become cells for different tissues. One of the most interesting structures for the regenerative medicine is the ocular surface. In the last few years, significant advances have been achieved in the field of the ocular surface reconstruction with regenerative procedures. Some cell cultures of the human corneal epithelium are being used to treat limber insufficiency, to reduce the incidence of haze-type opacities after

Precision of anterior and posterior corneal curvature measurements taken with the Oculus Pentacam

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Elizabeth Chetty

2016-06-01

Full Text Available In the era of rapid advances in technology, new ophthalmic instruments are constantly influencing health sciences and necessitating investigations of the accuracy and precision of the new technology. The Oculus Pentacam (70700 has been available for some time now and numerous studies have investigated the precision of some of the parameters that the Pentacam is capable of measuring. Unfortunately some of these studies fall short in confusing the meaning of accuracy and precision and in not being able to analyse the data correctly or completely. The aim of this study was to investigate the precision of the anterior and posterior corneal curvature measurements taken with the Oculus Pentacam (70700 holistically with sound multivariate statistical methods. Twenty successive Pentacam measurements were taken over three different measuring sessions on one subject. Keratometric data for both the anterior and posterior corneal surfaces were analysed using multivariate statistics to determine the precision of the Oculus Pentacam. This instrument was found to have good precision both clinically and statistically for anterior corneal measurements but only good clinical precision for the posterior corneal surface. Key words: Oculus Pentacam; keratometric variation; corneal curvature; multivariate statistics

Alternatives to eye bank native tissue for corneal stromal replacement.

Science.gov (United States)

Brunette, Isabelle; Roberts, Cynthia J; Vidal, François; Harissi-Dagher, Mona; Lachaine, Jean; Sheardown, Heather; Durr, Georges M; Proulx, Stéphanie; Griffith, May

2017-07-01

Corneal blindness is a major cause of blindness in the world and corneal transplantation is the only widely accepted treatment to restore sight in these eyes. However, it is becoming increasingly difficult for eye banks to meet the increasing demand for transplantable tissue, which is in part due to population aging. Donor tissue shortage is therefore a growing concern globally and there is a need for alternatives to human donor corneas. Biosynthetic corneal substitutes offer several significant advantages over native corneas: Large-scale production offers a powerful potential solution to the severe shortage of human donor corneas worldwide; Good manufacturing practices ensure sterility and quality control; Acellular corneal substitutes circumvent immune rejection induced by allogeneic cells; Optical and biomechanical properties of the implants can be adapted to the clinical need; and finally these corneal substitutes could benefit from new advances in biomaterials science, such as surface coating, functionalization and nanoparticles. This review highlights critical contributions from laboratories working on corneal stromal substitutes. It focuses on synthetic inert prostheses (keratoprostheses), acellular scaffolds with and without enhancement of endogenous regeneration, and cell-based replacements. Accent is put on the physical properties and biocompatibility of these biomaterials, on the functional and clinical outcome once transplanted in vivo in animal or human eyes, as well as on the main challenges of corneal stromal replacement. Regulatory and economic aspects are also discussed. All of these perspectives combined highlight the founding principles of the clinical application of corneal stromal replacement, a concept that has now become reality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.

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Kathryn L McCabe

Full Text Available To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs for transplantation in patients with corneal endothelial dystrophies.Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression.hESC-CECs were nearly identical morphologically to primary human corneal endothelial cells, expressed Zona Occludens 1 (ZO-1 and Na+/K+ATPaseα1 (ATPA1 on the apical surface in monolayer culture, and produced the key proteins of Descemet's membrane, Collagen VIIIα1 and VIIIα2 (COL8A1 and 8A2. Quantitative PCR analysis revealed expression of all corneal endothelial pump transcripts. hESC-CECs were 96% similar to primary human adult CECs by microarray analysis.hESC-CECs are morphologically similar, express corneal endothelial cell markers and express a nearly identical complement of genes compared to human adult corneal endothelial cells. hESC-CECs may be a suitable alternative to donor-derived corneal endothelium.

Corneal protection with high-molecular-weight hyaluronan against in vitro and in vivo sodium lauryl sulfate-induced toxic effects.

Science.gov (United States)

Pauloin, Thierry; Dutot, Mélody; Liang, Hong; Chavinier, Emilie; Warnet, Jean-Michel; Rat, Patrice

2009-10-01

The aim of this study was to investigate high-molecular-weight hyaluronan (HA-HMW) corneal protection against sodium lauryl sulfate (SLS)-induced toxic effects with in vitro and in vivo experimental approaches. In vitro experiments consisted of a human corneal epithelial cell line incubated with HA-HMW, rinsed, and incubated with SLS. Cell viability, oxidative stress, chromatin condensation, caspase-3, -8, -9, and P2X7 cell death receptor activation, interleukin-6, and interleukin-8 production were investigated. In vivo experiments consisted of 36 New Zealand white rabbits treated for 3 days, 3 times per day, with HA-HMW or phosphate-buffered salt solution. At day 4, eyes were treated with SLS. Clinical observation and in vivo confocal microscopy using the Rostock Cornea Module of the Heidelberg Retina Tomograph-II were performed to evaluate and to compare SLS-induced toxicity between eyes treated with HA-HMW and eyes treated with phosphate-buffered salt solution. In vitro data indicate that exposure of human corneal epithelial cells to HA-HMW significantly decreased SLS-induced oxidative stress, apoptosis, and inflammation cytokine production. In vivo data indicate that SLS cornea injuries, characterized by damaged corneal epithelium, damaged anterior stroma, and inflammatory infiltrations, were attenuated with HA-HMW treatment. A good correlation was seen between in vitro and in vivo findings showing that HA-HMW decreases SLS-induced toxic effects and protects cornea.

Iteratively re-weighted bi-cubic spline representation of corneal topography and its comparison to the standard methods.

Science.gov (United States)

Zhu, Zhongxia; Janunts, Edgar; Eppig, Timo; Sauer, Tomas; Langenbucher, Achim

2010-01-01

The aim of this study is to represent the corneal anterior surface by utilizing radius and height data extracted from a TMS-2N topographic system with three different mathematical approaches and to simulate the visual performance. An iteratively re-weighted bi-cubic spline method is introduced for the local representation of the corneal surface. For comparison, two standard mathematical global representation approaches are used: the general quadratic function and the higher order Taylor polynomial approach. First, these methods were applied in simulations using three corneal models. Then, two real eye examples were investigated: one eye with regular astigmatism, and one eye which had undergone refractive surgery. A ray-tracing program was developed to evaluate the imaging performance of these examples with each surface representation strategy at the best focus plane. A 6 mm pupil size was chosen for the simulation. The fitting error (deviation) of the presented methods was compared. It was found that the accuracy of the topography representation was worst using the quadratic function and best with bicubic spline. The quadratic function cannot precisely describe the irregular corneal shape. In order to achieve a sub-micron fitting precision, the Taylor polynomial's order selection behaves adaptive to the corneal shape. The bi-cubic spline shows more stable performance. Considering the visual performance, the more precise the cornea representation is, the worse the visual performance is. The re-weighted bi-cubic spline method is a reasonable and stable method for representing the anterior corneal surface in measurements using a Placido-ring-pattern-based corneal topographer. Copyright © 2010. Published by Elsevier GmbH.

Pseudomonas aeruginosa outer membrane vesicles triggered by human mucosal fluid and lysozyme can prime host tissue surfaces for bacterial adhesion

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Matteo Maria Emiliano Metruccio

2016-06-01

Full Text Available Pseudomonas aeruginosa is a leading cause of human morbidity and mortality that often targets epithelial surfaces. Host immunocompromise, or the presence of indwelling medical devices, including contact lenses, can predispose to infection. While medical devices are known to accumulate bacterial biofilms, it is not well understood why resistant epithelial surfaces become susceptible to P. aeruginosa. Many bacteria, including P. aeruginosa, release Outer Membrane Vesicles (OMVs in response to stress that can fuse with host cells to alter their function. Here, we tested the hypothesis that mucosal fluid can trigger OMV release to compromise an epithelial barrier. This was tested using tear fluid and corneal epithelial cells in vitro and in vivo. After 1 h both human tear fluid, and the tear component lysozyme, greatly enhanced OMV release from P. aeruginosa strain PAO1 compared to PBS controls (~100 fold. TEM and SDS-PAGE showed tear fluid and lysozyme-induced OMVs were similar in size and protein composition, but differed from biofilm-harvested OMVs, the latter smaller with fewer proteins. Lysozyme-induced OMVs were cytotoxic to human corneal epithelial cells in vitro and murine corneal epithelium in vivo. OMV exposure in vivo enhanced Ly6G/C expression at the corneal surface, suggesting myeloid cell recruitment, and primed the cornea for bacterial adhesion (~4-fold, P < 0.01. Sonication disrupted OMVs retained cytotoxic activity, but did not promote adhesion, suggesting the latter required OMV-mediated events beyond cell killing. These data suggest that mucosal fluid induced P. aeruginosa OMVs could contribute to loss of epithelial barrier function during medical device-related infections.

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

Science.gov (United States)

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.

Epithelium-on photorefractive intrastromal cross-linking (PiXL for reduction of low myopia

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Lim WK

2017-06-01

Full Text Available Wee Kiak Lim,1,2 Zhi Da Soh,1 Harold Kah Yen Choi,1 Julian Thiam Siew Theng1,3 1Eagle Eye Centre, Mount Alvernia Hospital, 2Department of Ophthalmology, Tan Tock Seng Hospital, 3Department of Ophthalmology, Khoo Teck Puat Hospital, Singapore Purpose: To report the 9–12-month outcomes of a novel procedure for reduction of low myopia through epithelium-on photorefractive intrastromal cross-linking (PiXL with customized control of topographic distribution of ultraviolet (UV-fluence. Method: Myopic patients with normal (non-ectatic corneas underwent the PiXL procedure for reduction of low myopia. PiXL treatments were delivered through selective application of UVA light based on the refractive error of each patient. Clinical evaluation included safety (corrected distance visual acuity, endothelial cell count, central corneal thickness, anterior ocular health and efficacy (uncorrected distance visual acuity, manifest refraction, K-mean examinations. In addition, a patient satisfaction survey was conducted at 9 months post-procedure to evaluate patients’ subjective experience with the procedure. Results: Fourteen myopic eyes (mean manifest refraction spherical equivalent –1.62±0.6D; range –0.75 to –2.65D of 8 subjects (mean age 30 years old; range 24–51 years old were enrolled in the study. At 12 months post-procedure, a mean manifest refraction spherical equivalent reduction of 0.72±0.43D (P<0.001 was observed, with a corresponding gain in uncorrected visual acuity of 0.25 logMAR and mean K-mean flattening of 0.47±0.46D. All patients achieved best corrected visual acuity of 20/20 or better from 1 month onward. There were no cases of ocular infection or secondary changes to the crystalline lens and retina due to UV exposure, while transient corneal haze subsided gradually. Conclusion: The epithelium-on PiXL procedure was safe and effective in reducing myopic refractive error in this study with up to 12 months follow-up. Early results of

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.

Neurotrophic corneal and conjunctival xerosis

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

Modalities of Tonometry and their Accuracy with Respect to Corneal Thickness and Irregularities

Science.gov (United States)

De Moraes, Carlos Gustavo V.; Prata, Tiago S.; Liebmann, Jeffrey; Ritch, Robert

2010-01-01

Recent advances in tonometry have led to the development of a number of devices with differing clinical applications. Their role in cases of abnormal corneal thickness and surface irregularities is particularly important, as inaccurate estimation of the true intraocular pressure (IOP) in such cases may lead to suboptimal evaluation. The purpose of the present review was to evaluate the accuracy of the most widely used devices in cases of corneal thickness and surface irregularities, based on a survey of the published literature. The analysis was based on a Medline search focusing mainly on papers that have evaluated the devices’ accuracy with respect to corneal thickness and irregularities. Nine device types (Goldmann tonometer, Tono-Pen, Perkins tonometer, Ocular Response Analyzer, non-contact tonometer, pneumatonometer, I-Care rebound tonometer, Pascal dynamic contour tonometer (DCT) and Phosphene tonometer) were described in detail. Moreover, the physical principles and major utility of each tonometer were compared. Each of the many different commercially available tonometers has specific advantages and disadvantages. New non-invasive technologies are getting closer to a precise estimation of the true IOP. However, among all tonometers, none is highly accurate when both corneal thickness and surface irregularities are present. Fifty years after its development, Goldmann tonometry remains the gold standard to which all other devices are compared.

A new 3D reconstituted human corneal epithelium model as an alternative method for the eye irritation test.

Science.gov (United States)

Jung, Kyoung-Mi; Lee, Su-Hyon; Ryu, Yang-Hwan; Jang, Won-Hee; Jung, Haeng-Sun; Han, Ju-Hee; Seok, Seung-Hyeok; Park, Jae-Hak; Son, Youngsook; Park, Young-Ho; Lim, Kyung-Min

2011-02-01

Many efforts are being made to develop new alternative in vitro test methods for the eye irritation test. Here we report a new reconstructed human corneal epithelial model (MCTT HCE model) prepared from primary-cultured human limbal epithelial cells as a new alternative in vitro eye irritation test method. In histological and immunohistochemical observation, MCTT HCE model displayed a morphology and biomarker expressions similar to intact human cornea. Moreover, the barrier function was well preserved as measured by high transepithelial electrical resistance, effective time-50 for Triton X-100, and corneal thickness. To employ the model as a new alternative method for eye irritation test, protocol refinement was performed and optimum assay condition was determined including treatment time, treatment volume, post-incubation time and rinsing method. Using the refined protocol, 25 reference chemicals with known eye irritation potentials were tested. With the viability cut-off value at 50%, chemicals were classified to irritant or non-irritant. When compared with GHS classification, the MCTT HCE model showed the accuracy of 88%, sensitivity of 100% and specificity of 77%. These results suggest that the MCTT HCE model might be useful as a new alternative eye irritation test method. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops.

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Koizumi, Noriko; Okumura, Naoki; Ueno, Morio; Kinoshita, Shigeru

2014-11-01

Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal endothelial transplantation. However, despite the value and potential of endothelial graft surgery, a strictly pharmacological approach for treating corneal endothelial dysfunction remains an attractive proposition. Previously, we reported that the selective Rho-associated kinase (ROCK) inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate corneal endothelial cells in culture. These findings have led us to develop a novel medical treatment for the early phase of corneal endothelial disease using ROCK inhibitor eye drops. In rabbit and monkey models of partial endothelial dysfunction, we showed that corneal endothelial wound healing was accelerated via the topical application of ROCK inhibitor to the ocular surface, resulting in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. Based on these animal studies, we are now attempting to advance the clinical application of ROCK inhibitor eye drops for patients with corneal endothelial dysfunction. A pilot clinical study was performed at the Kyoto Prefectural University of Medicine, and the effects of Y-27632 eye drops after transcorneal freezing were evaluated in 8 patients with corneal endothelial dysfunction. We observed a positive effect of ROCK inhibitor eye drops in treating patients with central edema caused by Fuchs corneal endothelial dystrophy. We believe that our new findings will contribute to the establishment of a new approach for the treatment of corneal endothelial dysfunction.

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....

Short-term corneal changes with gas-permeable contact lens wear in keratoconus subjects: a comparison of two fitting approaches.

Science.gov (United States)

Romero-Jiménez, Miguel; Santodomingo-Rubido, Jacinto; Flores-Rodríguez, Patricia; González-Méijome, Jose-Manuel

2015-01-01

To evaluate changes in anterior corneal topography and higher-order aberrations (HOA) after 14-days of rigid gas-permeable (RGP) contact lens (CL) wear in keratoconus subjects comparing two different fitting approaches. Thirty-one keratoconus subjects (50 eyes) without previous history of CL wear were recruited for the study. Subjects were randomly fitted to either an apical-touch or three-point-touch fitting approach. The lens' back optic zone radius (BOZR) was 0.4mm and 0.1mm flatter than the first definite apical clearance lens, respectively. Differences between the baseline and post-CL wear for steepest, flattest and average corneal power (ACP) readings, central corneal astigmatism (CCA), maximum tangential curvature (KTag), anterior corneal surface asphericity, anterior corneal surface HOA and thinnest corneal thickness measured with Pentacam were compared. A statistically significant flattening was found over time on the flattest and steepest simulated keratometry and ACP in apical-touch group (all p<0.01). A statistically significant reduction in KTag was found in both groups after contact lens wear (all p<0.05). Significant reduction was found over time in CCA (p=0.001) and anterior corneal asphericity in both groups (p<0.001). Thickness at the thinnest corneal point increased significantly after CL wear (p<0.0001). Coma-like and total HOA root mean square (RMS) error were significantly reduced following CL wearing in both fitting approaches (all p<0.05). Short-term rigid gas-permeable CL wear flattens the anterior cornea, increases the thinnest corneal thickness and reduces anterior surface HOA in keratoconus subjects. Apical-touch was associated with greater corneal flattening in comparison to three-point-touch lens wear. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Recovery of the sub-basal nerve plexus and superficial nerve terminals after corneal epithelial injury in mice.

Science.gov (United States)

Downie, Laura E; Naranjo Golborne, Cecilia; Chen, Merry; Ho, Ngoc; Hoac, Cam; Liyanapathirana, Dasun; Luo, Carol; Wu, Ruo Bing; Chinnery, Holly R

2018-06-01

Our aim was to compare regeneration of the sub-basal nerve plexus (SBNP) and superficial nerve terminals (SNT) following corneal epithelial injury. We also sought to compare agreement when quantifying nerve parameters using different image analysis techniques. Anesthetized, female C57BL/6 mice received central 1-mm corneal epithelial abrasions. Four-weeks post-injury, eyes were enucleated and processed for PGP9.5 to visualize the corneal nerves using wholemount immunofluorescence staining and confocal microscopy. The percentage area of the SBNP and SNT were quantified using: ImageJ automated thresholds, ImageJ manual thresholds and manual tracings in NeuronJ. Nerve sum length was quantified using NeuronJ and Imaris. Agreement between methods was considered with Bland-Altman analyses. Four-weeks post-injury, the sum length of nerve fibers in the SBNP, but not the SNT, was reduced compared with naïve eyes. In the periphery, but not central cornea, of both naïve and injured eyes, nerve fiber lengths in the SBNP and SNT were strongly correlated. For quantifying SBNP nerve axon area, all image analysis methods were highly correlated. In the SNT, there was poor correlation between manual methods and auto-thresholding, with a trend towards underestimating nerve fiber area using auto-thresholding when higher proportions of nerve fibers were present. In conclusion, four weeks after superficial corneal injury, there is differential recovery of epithelial nerve axons; SBNP sum length is reduced, however the sum length of SNTs is similar to naïve eyes. Care should be taken when selecting image analysis methods to compare nerve parameters in different depths of the corneal epithelium due to differences in background autofluorescence. Copyright © 2018 Elsevier Ltd. All rights reserved.

CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

Science.gov (United States)

Van Rompay, A R; Alépée, N; Nardelli, L; Hollanders, K; Leblanc, V; Drzewiecka, A; Gruszka, K; Guest, R; Kandarova, H; Willoughby, J A; Verstraelen, S; Adriaens, E

2018-06-01

Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies. Copyright © 2017. Published by Elsevier Ltd.

A histological study of rabbit corneas after transepithelial corneal crosslinking using partial epithelial photoablation or ethanol treatment.

Science.gov (United States)

Ozmen, Mehmet Cuneyt; Hondur, Ahmet; Yilmaz, Guldal; Bilgihan, Kamil; Hasanreisoglu, Berati

2014-01-01

To evaluate the histological changes after transepithelial corneal crosslinking (CXL) using partial thickness excimer laser ablation or epithelial ethanol application in an experimental rabbit study. Right eyes of twenty-four rabbits were studied. Four eyes received total epithelial debridement (group I). Four eyes received partial thickness epithelial ablation with excimer laser (group II). Twelve eyes were treated with different durations (30s and 60s) and concentrations (18% to 48%) of ethanol (group III). Riboflavin was applied for 30min intervals along with topical proparacaine drops with benzalkonium chloride, and 370 nm irradiation was performed for 30min, while riboflavin was instilled every 3min. Four eyes (group IV) received 48% ethanol for 30s without riboflavin and irradiation. Eyes were collected after 24h and examined histologically. All eyes in group I showed keratocyte loss in the superficial 300 µ of corneal storma. In group II, 1-4 layers of epithelium were preserved and no keratocyte loss occurred. In group III, CXL after treatment with ethanol up to 24% concentration and up to 60s revealed no keratocyte loss. CXL after treatment with 48% and higher ethanol concentrations yielded keratocyte loss in the superficial 200 µ to 300 µ of cornea. Incomplete excimer laser ablation of the epithelium or treatment with ethanol up to 24% concentration and up to 60s duration yielded no stromal keratocyte loss. To get the same histological appearance seen in epithelial debridement group, partial thickness excimer laser epithelial ablation or ethanol application is not adequate for transepithelial CXL.

A histological study of rabbit corneas after transepithelial corneal crosslinking using partial epithelial photoablation or ethanol treatment

Directory of Open Access Journals (Sweden)

Mehmet Cuneyt Ozmen

2014-12-01

Full Text Available AIM: To evaluate the histological changes after transepithelial corneal crosslinking (CXL using partial thickness excimer laser ablation or epithelial ethanol application in an experimental rabbit study.METHODS: Right eyes of twenty-four rabbits were studied. Four eyes received total epithelial debridement (group I. Four eyes received partial thickness epithelial ablation with excimer laser (group II. Twelve eyes were treated with different durations (30s and 60s and concentrations (18% to 48% of ethanol (group III. Riboflavin was applied for 30min intervals along with topical proparacaine drops with benzalkonium chloride, and 370 nm irradiation was performed for 30min, while riboflavin was instilled every 3min. Four eyes (group IV received 48% ethanol for 30s without riboflavin and irradiation. Eyes were collected after 24h and examined histologically.RESULTS: All eyes in group I showed keratocyte loss in the superficial 300 µ of corneal storma. In group II, 1-4 layers of epithelium were preserved and no keratocyte loss occurred. In group III, CXL after treatment with ethanol up to 24% concentration and up to 60s revealed no keratocyte loss. CXL after treatment with 48% and higher ethanol concentrations yielded keratocyte loss in the superficial 200 µ to 300 µ of cornea.CONCLUSION: Incomplete excimer laser ablation of the epithelium or treatment with ethanol up to 24% concentration and up to 60s duration yielded no stromal keratocyte loss. To get the same histological appearance seen in epithelial debridement group, partial thickness excimer laser epithelial ablation or ethanol application is not adequate for transepithelial CXL.

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)

The Comparison of Pain and Corneal Irritation by Different Methods of Surface Corneal Refractive Surgery%不同表层角膜屈光手术方式后疼痛及角膜刺激症状比较

Institute of Scientific and Technical Information of China (English)

聂新钢; 黄琰霞

2016-01-01

Objective To discuss the difference of pain and corneal irritation by different methods of surface corneal refrac-tive surgery. Methods Convenient selection to divided the 150 cases of patients from June 2014 ― December 2015 into the group A, B and C as the different methods of surgery that included the PRK (photorefractive keratectomy), LASEK (Laser Assisted Subepithelial Keratomileusis) and Epi-LASIK (Excimer laser epithelial keratomileusis), each 50 cases (100 eyes), to compared the difference of corneal irritation and aches-and-pains index of them. Results At the 1st day of surgery, A, B groups divided corneal irritation do not have 91, 86, pain index were 2.95,2.77, there was statistical significance (P0.05). Conclusion The has a certain difference of pain and corneal irritation by different methods of surface corneal refractive surgery, the postoperation pain is the main reason that caused the discomfort of patients.%目的：探究不同表层角膜屈光手术方式后疼痛及角膜刺激症状的差异。方法按术式不同将方便选取该院2014年6月―2015年12月期间行PRK(准分子激光屈光性角膜切削术﹚、LASEK(乙醇法准分子激光上皮瓣下角膜磨镶术﹚及Epi-LASIK(微型上皮刀法准分子激光上皮瓣下角膜磨镶术﹚的150例患者分别设为A、B、C3组,各50例(100眼﹚,对比三组角膜刺激症状及疼痛指数的差异。结果术后第1天,A、B两组出现角膜刺激症状分为别有91眼、86眼,疼痛指数分别为2.95、2.77,两组对比差异有统计学意义(P0.05﹚。结论不同表层角膜屈光手术术后疼痛及角膜刺激症状具有一定的差异,术后疼痛是引起患者不适的主要因素之一。

Computed estimation of visual acuity after laser refractive keratectomy

Science.gov (United States)

Rol, Pascal O.; Parel, Jean-Marie A.; Hanna, Khalil

1991-06-01

A number of surgical techniques has been developed to correct ametropia (refractive defaults) of the eye by changing the anterior corneal radius. Because the air-cornea interface makes up for about two-third of the refractive power of the eye, a refractive correction is obtained by a suitable photoablation of the cornea. For this purpose, e.g., an ArF excimer laser which emits a wavelength of 193 nm is being used. After a mechanical removal of the epithelium, the Bowman's layer and the corneal stroma are photoablated on typically 50% of the central surface of the cornea with various precomputed shapes. Methods using a variable diaphragm1 or a scanning slit2 are being utilized. After regrowth of the epithelium, a smooth interface with air develops itself, which can be attributed to a mechanical equilibration. Yet, SEM studies have shown that with such kind of treatments, irregularities can remain in the new stromal surface (Fig. 1). A possible explanation for this effect is associated with an inhomogeneous energy distribution of the laser beam profile3. To some extent, the stromal surface is equalized by the epithelial layer during healing& However, as the corneal epithelium and stroma have different refractive indices, a scatter of the incident light may result causing a haze in the cornea and a blur of the image at the retina. In such a case the resolution and the contrast performance of the eye which is expected from a successful operation, may be reduced. This study is an attempt to quantify the vision blur as a function of the deformation observed at the epithelium-stroma interface.

CONTACT LENS RELATED CORNEAL ULCER

Directory of Open Access Journals (Sweden)

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.

Reconstituted human corneal epithelium: a new alternative to the Draize eye test for the assessment of the eye irritation potential of chemicals and cosmetic products.

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Doucet, O; Lanvin, M; Thillou, C; Linossier, C; Pupat, C; Merlin, B; Zastrow, L

2006-06-01

The aim of this study was to evaluate the interest of a new three-dimensional epithelial model cultivated from human corneal cells to replace animal testing in the assessment of eye tolerance. To this end, 65 formulated cosmetic products and 36 chemicals were tested by means of this in vitro model using a simplified toxicokinetic approach. The chemicals were selected from the ECETOC data bank and the EC/HO International validation study list. Very satisfactory results were obtained in terms of concordance with the Draize test data for the formulated cosmetic products. Moreover, the response of the corneal model appeared predictive of human ocular response clinically observed by ophthalmologists. The in vitro scores for the chemicals tested strongly correlated with their respective scores in vivo. For all the compounds tested, the response of the corneal model to irritants was similar regardless of their chemical structure, suggesting a good robustness of the prediction model proposed. We concluded that this new three-dimensional epithelial model, developed from human corneal cells, could be promising for the prediction of eye irritation induced by chemicals and complex formulated products, and that these two types of materials should be tested using a similar protocol. A simple shortening of the exposure period was required for the chemicals assumed to be more aggressively irritant to the epithelial tissues than the cosmetic formulae.

Corneal Epithelial Remodeling and Its Effect on Corneal Asphericity after Transepithelial Photorefractive Keratectomy for Myopia

Directory of Open Access Journals (Sweden)

Jie Hou

2016-01-01

Full Text Available Purpose. To evaluate the changes in epithelial thickness profile following transepithelial photorefractive keratectomy (T-PRK for myopia and to investigate the effect of epithelial remodeling on corneal asphericity. Methods. Forty-four patients (44 right eyes who underwent T-PRK were retrospectively evaluated. Epithelial thickness was measured using spectral-domain optical coherence tomography at different corneal zones (central, 2 mm; paracentral, 2–5 mm; and mid-peripheral, 5-6 mm preoperatively and at 1 week and 1, 3, and 6 months postoperatively. The correlation between the changes in corneal epithelial thickness (ΔCET and postoperative Q-value changes (ΔQ was analyzed 6 months postoperatively. Results. Epithelial thickness at 6 months showed a negative meniscus-like lenticular pattern with less central thickening, which increased progressively toward the mid-periphery (3.69±4.2, 5.19±3.8, and 6.23±3.9 μm at the center, paracenter, and mid-periphery, resp., P<0.01. A significant positive relationship was observed between epithelial thickening and ΔQ 6 months postoperatively (r=0.438, 0.580, and 0.504, resp., P<0.01. Conclusions. Significant epithelial thickening was observed after T-PRK and showed a lenticular change with more thickening mid-peripherally, resulting in increased oblateness postoperatively. Epithelial remodeling may modify the epithelial thickness profile after surface ablation refractive surgery for myopia.

Evaluation of Corneal Topography and Biomechanical Parameters after Use of Systemic Isotretinoin in Acne Vulgaris

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Yusuf Yildirim

2014-01-01

Full Text Available Purpose. We report the effect of isotretinoin on corneal topography, corneal thickness, and biomechanical parameters in patients with acne vulgaris. Method. Fifty-four eyes of 54 patients who received oral isotretinoin for treatment of acne vulgaris were evaluated. All patients underwent a corneal topographical evaluation with a Scheimpflug camera combined with Placido-disk (Sirius, ultrasonic pachymetry measurements, and corneal biomechanical evaluation with an ocular response analyzer at baseline, in the 1st, 3rd, and 6th months of treatment, and 6 months after isotretinoin discontinuation. Results. The thinnest corneal thickness measured with Sirius differed significantly in the 1st, 3rd, and 6th months compared with the baseline measurement; there was no significant change in ultrasonic central corneal thickness measurements and biomechanical parameters (corneal hysteresis and corneal resistance factor throughout the study. Average simulated keratometry and surface asymmetry index increased significantly only in the first month of treatment according to the baseline. All changes disappeared 6 months after the end of treatment. Conclusion. Basal tear secretion and corneal morphologic properties were significantly influenced during the systemic isotretinoin treatment and the changes were reversible after discontinuation. No statistical important biomechanical differences were found to be induced by isotretinoin.

Correlations between corneal and total wavefront aberrations

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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.

Evaluation of central and peripheral corneal thicknesses in patients with rheumatoid arthritis

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Alime Gunes

2015-08-01

Full Text Available ABSTRACTPurpose:To evaluate central corneal thickness (CCT and peripheral corneal thickness (PCT in patients with rheumatoid arthritis (RA and to assess the relationships among the corneal parameters, dry eye disease, and clinical variables of RA.Methods:A total of 58 RA patients and 58 control subjects participated in this study. A detailed ophthalmological examination was performed on each subject. Dry eye evaluation was performed using Schirmer’s test, tear break-up time (TBUT, corneal fluorescein staining, and Ocular Surface Disease Index (OSDI. Corneal thickness at the apex point, the center of the pupil, the thinnest point, and PCT (3 mm from the apex to the superior, inferior, nasal, and temporal locations were evaluated using Scheimpflug imaging (Pentacam®. Additionally, the relative peripheral index (RPI was calculated by dividing the PCT by the CCT. The disease severity and quality of life were evaluated with DAS28 and HAQ, respectively. The laboratory evaluation comprised ESR and CRP.Results:The mean corneal thicknesses at the apex point, the center of the pupil, the thinnest point, and the superior, inferior, nasal, and temporal points were significantly thinner in RA patients than controls. Schirmer’s test scores and TBUT were significantly lower, and corneal staining and OSDI scores were significantly higher in RA patients. There were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests.Conclusion:The CCT and PCT were thinner in RA patients compared to those in control subjects. However, there were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests.

Alcohol-assisted versus Mechanical Epithelium Removal in Photorefractive Keratectomy

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Mohammad Ghoreishi,

2010-01-01

Full Text Available Purpose: To compare the outcomes and complications of alcohol-assisted versus mechanical corneal epithelial debridement for photorefractive keratectomy (PRK. Methods: This randomized controlled trial included 1,250 eyes of 625 patients undergoing PRK for correction of myopia and myopic astigmatism. Each patient was randomly assigned to alcohol-assisted or mechanical epithelial removal. Results: A total of 658 eyes underwent alcohol-assisted epithelial removal while the epithelium was removed mechanically in 592 eyes. Mean spherical equivalent was ‑4.37}2.3 D in the alcohol group and ‑3.8}1.3 D in the mechanical group (P = 0.78. There was no significant difference in postoperative pain between the study groups (P = 0.22. Uncorrected visual acuity ≥ 20/20 and ≥ 20/40 was achieved in 90.9% versus 93.4% (P = 0.08, and 98.9% versus 99.5% (P = 0.36 of eyes in the alcohol and mechanical groups, respectively. Final refractive error within 1D of emmetropia was achieved in 90% versus 92.2% of eyes in the alcohol and mechanical groups, respectively (P = 0.23. Alcohol-assisted debridement required less time than mechanical debridement (96±18 vs. 118±26 seconds, P=0.035. There was no significant difference between the two groups in terms of early and late postoperative complications. Conclusion: Alcohol-assisted and mechanical epithelium removal are comparable in terms of efficacy and side effects. The method of epithelial debridement in PRK may be left to the surgeon′s choice.

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.

Administration of Menadione, Vitamin K3, Ameliorates Off-Target Effects on Corneal Epithelial Wound Healing Due to Receptor Tyrosine Kinase Inhibition.

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Rush, Jamie S; Bingaman, David P; Chaney, Paul G; Wax, Martin B; Ceresa, Brian P

2016-11-01

The antiangiogenic receptor tyrosine kinase inhibitor (RTKi), 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-[[[[4-(1-pyrrolidinyl) butyl] amino] carbonyl]amino]-4-isothiazolecarboxamide hydrochloride, targets VEGFR2 (half maximal inhibitory concentration [IC50] = 11 nM); however, off-target inhibition of epidermal growth factor receptor (EGFR) occurs at higher concentrations. (IC50 = 5.8 μM). This study was designed to determine the effect of topical RTKi treatment on EGF-mediated corneal epithelial wound healing and to develop new strategies to minimize off-target EGFR inhibition. In vitro corneal epithelial wound healing was measured in response to EGF using a transformed human cell line (hTCEpi cells). In vivo corneal wound healing was assessed using a murine model. In these complementary assays, wound healing was measured in the presence of varying RTKi concentrations. Immunoblot analysis was used to examine EGFR and VEGFR2 phosphorylation and the kinetics of EGFR degradation. An Alamar Blue assay measured VEGFR2-mediated cell biology. Receptor tyrosine kinase inhibitor exposure caused dose-dependent inhibition of EGFR-mediated corneal epithelial wound healing in vitro and in vivo. Nanomolar concentrations of menadione, a vitamin K3 analog, when coadministered with the RTKi, slowed EGFR degradation and ameliorated the inhibitory effects on epithelial wound healing both in vitro and in vivo. Menadione did not alter the RTKi's IC50 against VEGFR2 phosphorylation or its inhibition of VEGF-induced retinal endothelial cell proliferation. An antiangiogenic RTKi exhibited off-target effects on the corneal epithelium that can be minimized by menadione without deleteriously affecting its on-target VEGFR2 blockade. These data indicate that menadione has potential as a topical supplement for individuals suffering from perturbations in corneal epithelial homeostasis, especially as an untoward side effect of kinase inhibitors.

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.

Bilateral corneal denting after surgery under general anesthesia: A case report

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Satsuki Obata

2018-06-01

Full Text Available Purpose: To report a case of temporary bilateral corneal denting in a patient who underwent cardiovascular surgery under general anesthesia. Observations: A 71-year-old male with no history of ophthalmological disease experienced bilateral corneal denting immediately after undergoing surgery for aneurysm of the thoracic aorta under general anesthesia. Anesthesia was induced with propofol and maintained with rocuronium bromide and remifentanil hydrochloride. The initial examination revealed significant denting on the surface of both the corneas and ocular hypotension. Visual evaluation could not be performed due to the patient's low level of consciousness resulting from delayed emergence from anesthesia. After applying tropicamide and phenylephrine ophthalmic solution for fundus examination, the ocular morphology improved. Ocular pressure was normal on the day after surgery, and creasing on the surface of the corneas had disappeared. Conclusions: and Importance: We experienced a patient with bilateral corneal denting following a cardiovascular surgery under general anesthesia. The dents could be attributed to augmentation of ocular hypotension using several types of anesthesia at relatively high doses. Keywords: General anesthesia, Cornea denting, Complication, Cardiovascular surgery

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.

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.

History of corneal transplantation in Australia.

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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.

Platelet lysate and chondroitin sulfate loaded contact lenses to heal corneal lesions.

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Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Delfino, Alessio; Riva, Federica; Icaro Cornaglia, Antonia; Marrubini, Giorgio; Musitelli, Giorgio; Del Fante, Claudia; Perotti, Cesare; Caramella, Carla; Ferrari, Franca

2016-07-25

Hemoderivative tear substitutes contain various ephiteliotrophic factors, such as growth factors (GF), involved in ocular surface homeostasis without immunogenic properties. The aim of the present work was the loading of platelet lysate into contact lenses to improve the precorneal permanence of platelet lysate growth factors on the ocular surface to enhance the treatment of corneal lesions. To this purpose, chondroitin sulfate, a sulfated glycosaminoglycan, which is normally present in the extracellular matrix, was associated with platelet lysate. In fact, chondroitin sulfate is capable of electrostatic interaction with positively charged growth factors, in particular, with bFGF, IGF, VEGF, PDGF and TGF-β, resulting in their stabilization and reduced degradation in solution. In the present work, various types of commercially available contact lenses have been loaded with chondroitin sulfate or chondroitin sulfate in association with platelet lysate to achieve a release of growth factors directly onto the corneal surface lesions. One type of contact lenses (PureVision(®)) showed in vitro good proliferation properties towards corneal cells and were able to enhance cut closure in cornea constructs. Copyright © 2016 Elsevier B.V. All rights reserved.

Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

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Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

2014-01-01

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

Glaucoma after corneal replacement.

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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.

Corneal Toxicity Following Exposure to Asclepias Tuberosa

DEFF Research Database (Denmark)

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...

Changes of Corneal Wavefront Aberrations in Dry Eye Patients after Treatment with Artificial Lubricant Drops

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Ning Lu

2016-01-01

Full Text Available Purpose. To evaluate the corneal aberration changes in dry eye patients after treatment with artificial eye drops. Methods. Thirty mild to moderate dry eye patients treated with artificial eye drops and twenty comparable dry eye patients were recruited as controls. Anterior corneal aberrations over 3 mm and 5 mm analytical zones including total, 3rd to 5th high order aberrations (HOAs, spherical aberration (SA, and vertical (V-coma and horizontal coma (H-coma obtained from corneal topography data at baseline and 2 weeks after treatment were evaluated. Results. For 3 mm zone, trefoils, V-coma, H-coma terms, and 3rd and 5th HOAs were significantly decreased (p0.05. Conclusions. Treatment with artificial eye drops can effectively improve the corneal optical quality of dry eye patients by ameliorating the HOAs of anterior corneal surface.

Biomechanical corneal changes induced by different flap thickness created by femtosecond laser

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Fabricio W. Medeiros

2011-01-01

Full Text Available OBJECTIVE: To evaluate the impact of the creation of corneal flaps at different thicknesses on the biomechanical properties of swine corneas. METHOD: Twelve swine eyes were obtained to form two groups: 100 μm flap thickness and 300 μm flap thickness. Each eye was submitted to the following examinations: raster topography to investigate corneal curvature alterations, ocular response analyzer to investigate corneal hysteresis change, optical coherence tomography to measure central corneal and flap thickness and sonic wave propagation velocity as a measure of stiffness, before and immediately after flap creation. After flap amputation, surface wave velocity measurements were repeated. RESULTS: Measured flap thicknesses were statistically different for thin and thick flap groups, with an average of 108.5 + 6.9 and 307.8 + 11.5 μm respectively. Hysteresis and corneal resistance factor did not change significantly after flap creation in the thin flap group. With thicker flaps, both parameters decreased significantly from 8.0 +1.0 to 5.1 +1.5 mmHg and from 8.2 + 1.6 to 4.1 +2.5 mmHg respectively. Simulated keratometry values increased in the thick flap group (from 39.5 + 1 D to 45.9+1.2 D after flap creation but not in the thin flap group (from 40.6 + 0.6 D to 41.4+ 1.0 D. Regarding surface wave velocity analysis, the surgical procedures induced statistically lower results in some positions. CONCLUSION: In the experimental conditions established by this model, thicker flaps presented a greater biomechanical impact on the cornea.

Corneal sensitivity, ocular surface health and tear film stability after punctal plug therapy of aqueous deficient dry eye

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Azza Mohamed Ahmed Said

2016-11-01

Full Text Available AIM: To evaluate the effect of punctal occlusion using thermosensitive (smart plug versus silicone plug for management of aqueous deficient dry eye on corneal sensitivity, ocular surface health and tear film stability. METHODS: A comparative prospective interventional case study included 45 patients with bilateral severe form of aqueous deficient dry eye. In each patient, the smart plug was inserted in the lower punctum of the right eye which was considered as study group 1 and silicone plug was inserted in the lower punctum of the left eye of the same patient which was considered as study group 2. All patients were subjected to careful history taking and questionnaire for subjective assessment of severity of symptoms. Corneal sensitivity, corneal fluorescein, rose bengal staining, Schirmer’s I test, tear film break up time and conjunctival impression cytology were performed pre and 1, 3 and 6mo post plug insertion. RESULTS: A statistically significant improvement in subjective and objective manifestations occurred following treatment with both types of plugs (P<0.01. The thermosensitive plug caused significant overall improvement, decrease in frequency of application of tear substitutes and improvement of conjunctival impression cytology parameters in the inserted side (P<0.01. Canaliculitis was reported in two eyes (4.4% following punctal occlusion using thermosensitive plug (study group 1. Spontaneous plug loss occurred in 21 eyes (46.6% in the silicone plug group (study group 2. CONCLUSION: Improvement of subjective and objective manifestations of aqueous deficient dry eye occurs following punctal plug occlusion. Thermosensitive plug has good patient's compliance with fewer complications and lower rates of loss compared to the silicone plug.

Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium Cultured In Vitro in the Presence of Follicular Fluid

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Irma Virant-Klun

2013-01-01

Full Text Available The aim of this study was to trigger the expression of genes related to oocytes in putative ovarian stem cells scraped from the ovarian surface epithelium of women with premature ovarian failure and cultured in vitro in the presence of follicular fluid, rich in substances for oocyte growth and maturation. Ovarian surface epithelium was scraped and cell cultures were set up by scrapings in five women with nonfunctional ovaries and with no naturally present mature follicles or oocytes. In the presence of donated follicular fluid putative stem cells grew and developed into primitive oocyte-like cells. A detailed single-cell gene expression profiling was performed to elucidate their genetic status in comparison to human embryonic stem cells, oocytes, and somatic fibroblasts. The ovarian cell cultures depleted/converted reproductive hormones from the culture medium. Estradiol alone or together with other substances may be involved in development of these primitive oocyte-like cells. The majority of primitive oocyte-like cells was mononuclear and expressed several genes related to pluripotency and oocytes, including genes related to meiosis, although they did not express some important oocyte-specific genes. Our work reveals the presence of putative stem cells in the ovarian surface epithelium of women with premature ovarian failure.

Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium

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Marthin, June Kehlet; Stevens, Elizabeth Munkebjerg; Larsen, Lars Allan

2017-01-01

BACKGROUND: Three-dimensional explant spheroid formation is an ex vivo technique previously used in studies of airway epithelial ion and water transport. Explanted cells and sheets of nasal epithelium form fully differentiated spheroids enclosing a partly fluid-filled lumen with the ciliated apical...... surface facing the outside and accessible for analysis of ciliary function. METHODS: We performed a two-group comparison study of ciliary beat pattern and ciliary beat frequency in spheroids derived from nasal airway epithelium in patients with primary ciliary dyskinesia (PCD) and in healthy controls...... in the investigation of pathophysiological aspects and drug effects in human nasal airway epithelium....

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 Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms.

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Spierer, Oriel; Felix, Elizabeth R; McClellan, Allison L; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J; Sarantopoulos, Constantine D; Levitt, Roy C; Ehrmann, Klaus; Galor, Anat

2016-02-01

To examine associations between corneal mechanical thresholds and metrics of dry eye. This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = -0.13 to -0.27, P eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints.

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms

Science.gov (United States)

Spierer, Oriel; Felix, Elizabeth R.; McClellan, Allison L.; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J.; Sarantopoulos, Constantine D.; Levitt, Roy C.; Ehrmann, Klaus; Galor, Anat

2016-01-01

Purpose To examine associations between corneal mechanical thresholds and metrics of dry eye. Methods This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. Results A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = −0.13 to −0.27, P eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Conclusions Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints. PMID:26886896

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

Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation.

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Shun Liang

Full Text Available The Phosphatidylinositol 3'-kinase is a key regulator in various cancer-associated signal transduction pathways. Genetic alterations of its catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in vivo data suggests that PIK3CA activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE is largely unclear.Using the Müllerian inhibiting substance type II receptor (MISIIR promoter, we generated transgenic mice that expressed activated PIK3CA in the Müllerian epithelium. Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able to malignantly transform OSE in vivo. The consistent result was also observed in primary cultured OSEs. Although enforced expression of PIK3CA could not induce OSE anchorage-independent growth, it significantly increased anchorage-independent growth of OSE transformed by mutant K-ras.While PIK3CA activation may not be able to initiate OSE transformation, we conclude that activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras.

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.

Noninvasive spectroscopic diagnosis of superficial ocular lesions and corneal infections

Energy Technology Data Exchange (ETDEWEB)

Mourant, J.R.; Bigio, I.J.; Johnson, T.; Shimada, T. [Los Alamos National Lab., NM (United States); Gritz, D.C.; Storey-Held, K. [Texas Univ. Health Science Center, San Antonio, TX (United States). Dept. of Ophthalmology

1994-02-01

The potential of a rapid noninvasive diagnostic system to detect tissue abnormalities on the surface of the eye has been investigated. The optical scatter signal from lesions and normal areas on the conjunctival sclera of the human eye were measured in vivo. It is possible to distinguish nonpigmented pingueculas from other lesions. The ability of the system to detect malignancies could not be tested because none of the measured and biopsied lesions were malignant. Optical scatter and fluorescence spectra of bacterial and fungal suspensions, and corneal irritations were also collected. Both scattering and fluorescence show potential for diagnosing corneal infections.

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.

Fibre optic spectrophotometry for the in vitro evaluation of ultraviolet radiation (UVR) spectral transmittance of rabbit corneas

International Nuclear Information System (INIS)

Walsh, J E; Fleming, D P; Bergmanson, J P G; Koehler, L V; Doughty, M J; Harmey, J H

2008-01-01

A fibre optic spectrophotometer front-end system for measuring corneas to overcome shortcomings associated with existing instruments was tested. The system allowed prompt measurement postmortem, minimizing beam pathlength to reduce the effects of scatter and unwanted refraction and eliminated optical interfaces and cuvette media. Rabbit corneas were excised immediately postmortem and placed on a detecting fibre optic coupled to an Ocean Optics spectrophotometer and illuminated by a deuterium–halogen source. The compact instrument with its small beam size allowed tissue profiling at test points across the corneal surface and efficient interchange for comparison of different tissues. This simplified system operation allowed rapid tissue altering to study induced changes on transmittance. The corneal transmittance data showed a consistent sharp cut-off at 320 nm in the ultraviolet radiation (UVR) spectrum, which decayed rapidly from postmortem swelling. Inter- and intra-corneal consistency was demonstrated by comparing data from different regions of the same cornea and those from opposite eyes. Changes to the spectra, particularly in the UVB below 300 nm, were evident when the corneal epithelium was removed, indicating that this layer is not the only corneal UVR filter. The new system reduced much of the variability associated with previous methods, as it rapidly measured corneal transmittance postmortem. Data are in broad agreement with published transmittance curves. The removal of the corneal epithelium revealed a substantial stromal contribution to the overall corneal UVR absorption, suggesting that corneas with pathologically or iatrogenically thinned stromas are less effective UVR blockers

The TMS-1 corneal topography measurement applied to calibrated ellipsoidal convex surfaces.

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Douthwaite, W A; Matilla, M T

1996-03-01

The purpose of this report is to assess the accuracy of the TMS-1 videokeratoscope (Computed Anatomy Inc.) by using convex ellipsoidal surfaces. The ellipsoids were calibrated using Form Talysurf analysis, which allowed for subsequent calculation of the vertex radius and p value. The videokeratoscope was used to examine the same ellipsoids. The data provided by the instrument software were used to plot a graph of r2 verses y2, where r is the measured radius at y, the distance from the corneal point being measured to the optical axis of the instrument. The intercept on the ordinate of this graph gives the vertex radius, and the slope give the p value. The results arising from the Talysurf and the TMS-1 techniques were compared. The TMS-1 videokeratoscope gave readings for the vertex radius that were generally higher than those of the Talysurf analysis. The vertex radius was up to 0.09 mm greater. The p value results were similar by the two methods for p values of approximately 0.8; however, the TMS-1 results were higher, and the discrepancy increased as the p value approached that of a paraboloid. Although the videokeratoscope may be useful in comparative studies of the cornea, there must be some doubt about the absolute values displayed as the surface becomes increasingly aspheric.

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.

Fabrication of silk fibroin film using centrifugal casting technique for corneal tissue engineering.

Science.gov (United States)

Lee, Min Chae; Kim, Dong-Kyu; Lee, Ok Joo; Kim, Jung-Ho; Ju, Hyung Woo; Lee, Jung Min; Moon, Bo Mi; Park, Hyun Jung; Kim, Dong Wook; Kim, Su Hyeon; Park, Chan Hum

2016-04-01

Films prepared from silk fibroin have shown potential as biomaterials in tissue engineering applications for the eye. Here, we present a novel process for fabrication of silk fibroin films for corneal application. In this work, fabrication of silk fibroin films was simply achieved by centrifugal force. In contrast to the conventional dry casting method, we carried out the new process in a centrifuge with a rotating speed of 4000 rpm, where centrifugal force was imposed on an aluminum tube containing silk fibroin solution. In the present study, we also compared the surface roughness, mechanical properties, transparency, and cell proliferation between centrifugal and dry casting method. In terms of surface morphology, films fabricated by the centrifugal casting have less surface roughness than those by the dry casting. For elasticity and transparency, silk fibroin films obtained from the centrifugal casting had favorable results compared with those prepared by dry casting. Furthermore, primary human corneal keratocytes grew better in films prepared by the centrifugal casting. Therefore, our results suggest that this new fabrication process for silk fibroin films offers important potential benefits for corneal tissue regeneration. © 2015 Wiley Periodicals, Inc.

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.

Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome.

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Tseng, Ching-Li; Chen, Zhi-Yu; Renn, Ting-Yi; Hsiao, Shun-Hung; Burnouf, Thierry

2016-01-01

Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer's test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S

Characterization of corneal pannus removed from patients with total limbal stem cell deficiency.

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Espana, Edgar M; Di Pascuale, Mario A; He, Hua; Kawakita, Tetsuya; Raju, Vadrevu K; Liu, Chia-Yang; Tseng, Scheffer C G

2004-09-01

To determine the epithelial lineage of origin in corneal pannus tissue surgically removed from patients with total limbal stem cell (SC) deficiency. The lineage of origin of the entire conjunctivalized pannus removed from eight corneas with a diagnosis of total limbal SC deficiency was characterized by anti-keratin (K)-3 and anti-K19 monoclonal antibodies. The protein and mRNA of epithelial outgrowth from segments of five such pannus specimens were analyzed by Western blot and reverse transcription-polymerase chain reaction, respectively. Cross sections of all eight specimens showed a stratified epithelium with goblet cells expressing mucin (MUC)-5AC, and a stroma showing blood vessels and inflammatory cell infiltrates. Immunostaining showed full-thickness expression of K19 in the entire pannus of all eight specimens. Expression of K3 was negative in seven patients, but was sporadically positive in a patient with Stevens-Johnson syndrome. In culture, all five pannus specimens generated a compact, small epithelial cell outgrowth, and except for one, reached confluence in 2 to 3 weeks. The K3/K12 pair was expressed by extracts of cell outgrowth from the control limbal epithelial explant, but not in all five pannus specimens. A 60-kDa band of DeltaNp63 was expressed in the control specimen and in all five pannus specimens. Cell outgrowth expressed K3 transcript in three, but none showed K12 transcript. The resultant epithelial phenotype of the pannus tissue was not corneal, as evidenced by the negative staining to cornea-specific K12 mRNA and protein, but was conjunctival, as evidenced by the presence of goblet cells, the weak expression of K3, and the strong expression of K19. The abundant expression of DeltaNp63 in such conjunctiva-derived epithelium in eyes with total limbal SC deficiency raises doubts as to its validity as a limbal SC marker. Copyright Association for Research in Vision and Ophthalmology

Inhibition of multiple pathogenic pathways by histone deacetylase inhibitor SAHA in a corneal alkali-burn injury model

Science.gov (United States)

Li, Xinyu; Zhou, Qinbo; Hanus, Jakub; Anderson, Chastain; Zhang, Hongmei; Dellinger, Michael; Brekken, Rolf; Wang, Shusheng

2013-01-01

Neovascularization (NV) in the cornea is a major cause of vision impairment and corneal blindness. Hemangiogenesis and lymphangiogenesis induced by inflammation underlie the pathogenesis of corneal NV. The current mainstay treatment, corticosteroid, treats the inflammation associated with corneal NV, but is not satisfactory due to such side effects as cataract and the increase in intraocular pressure. It is imperative to develop a novel therapy that specifically targets the hemangiogenesis, lymphangiogenesis and inflammation pathways underlying corneal NV. Histone deacetylase inhibitors (HDACi) have been in clinical trials for cancer and other diseases. In particular, HDACi suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The functional mechanism of SAHA in cancer and especially in corneal NV remains unclear. Here, we show that topical application of SAHA inhibits neovascularization in an alkali-burn corneal injury model. Mechanistically, SAHA inhibits corneal NV by repressing hemangiogenesis, inflammation pathways and previously overlooked lymphangiogenesis. Topical SAHA is well tolerated on the ocular surface. In addition, the potency of SAHA in corneal NV appears to be comparable to the current steroid therapy. SAHA may possess promising therapeutic potential in alkali-burn corneal injury and other inflammatory neovascularization disorders. PMID:23186311

Ocular Surface Reconstruction: Recent Innovations

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Madhavan HN

2009-01-01

Full Text Available The ocular surface is exceptionally rich in complexity and functionality. Severe ocular surface disorders/conditions, such as chemical or thermal injuries, Stevens-Johnson syndrome (SJS, ocular cicatricial pemphigoid, neurotrophic keratopathy, chronic limbitis, and severe microbial keratitis cause significant morbidities and even corneal blindness. Hypofunction may be caused by Aniridia, Neurotrophy, Endocrine, Pterygium and Chronic limbitis Approximately 6000 patients are seen in Ocular Surface Clinic every year; almost 80% have some form of dry eyes. About 125 new patients of Stevens Johnson Syndrome are seen in a year of which approximately 25% may benefit from Cultured Epithelial Transplant and 75 new patients of thermal/chemical injury in a year of which almost 80% will benefit from Stem Cell Transplantation. Of the 128 severe vernal keratoconjunctivitis which were seen in the ocular surface clinic, 10% require stem cell transplantation. Nearly 30 new cases of Ocular cicatrical pemphigoid every year are seen and they may need stem cell transplantation. In addition, several patients with persistent epithelial defects may benefit from limbal stem cell transplantation to alleviate, maintain conjunctivalization regression and corneal avascularity limbal deficiency, and restore vision. Even if granted that this statistics is for a single large ophthalmic hospital, for a large country as India with 1.1 billion populations, the number of patients requiring corneal stem cell transplantation is enormous. Stem cells in the palisades of Vogt participate in regeneration and preservation of corneal transparency and avascularity. The diminished regenerative capacity seen in LSCD is characterized by persistent epithelial defects, erosion and ulceration, conjunctivalization and neovascularization, and chronic inflammation. Standard corneal transplantation for restoration of corneal clarity and avascularity is a contraindication in the surgical management

Changes in corneal sensation, epithelial damage, and tear function after descemet stripping automated endothelial keratoplasty.

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Hirayama, Yumiko; Satake, Yoshiyuki; Hirayama, Masatoshi; Shimazaki-Den, Seika; Konomi, Kenji; Shimazaki, Jun

2013-09-01

To study the ocular surface changes in eyes after Descemet stripping automated endothelial keratoplasty (DSAEK) compared with those after penetrating keratoplasty (PKP). This prospective study compared the changes in 31 eyes of 28 patients who underwent DSAEK (DSAEK group) with those in 15 disease-matched eyes of 15 patients who underwent PKP (PKP group). Corneal epithelial integrity was evaluated using a fluorescein staining score. Corneal sensation was measured with a Cochet-Bonnet esthesiometer. Tear function was evaluated using the Schirmer test, tear clearance test, tear function index, and tear break-up time. The postoperative fluorescein staining score was significantly higher in the PKP group than in the DSAEK group (P = 0.02). Postoperative corneal sensation was significantly better in the DSAEK group than in the PKP group (P sensation after DSAEK was significantly better than the preoperative value (P = 0.02). There were no statistically significant changes in the Schirmer test, tear clearance test, tear function index, or break-up time before and after the surgery in both the DSAEK and PKP groups. No significant differences were observed between the DSAEK and PKP groups after the surgery. Corneal sensation was preserved, and epithelial damage was less severe after DSAEK compared with PKP. Preservation of corneal sensation may contribute to the early recovery of visual function and long-term maintenance of ocular surface health after DSAEK.

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

Why Does the Healthy Cornea Resist Pseudomonas aeruginosa Infection?

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Evans, David J.; Fleiszig, Suzanne M. J.

2013-01-01

Purpose To provide our perspective on why the cornea is resistant to infection based on our research results with Pseudomonas aeruginosa. Perspective We focus on our current understanding of the interplay between bacteria, tear fluid and the corneal epithelium that determine health as the usual outcome, and propose a theoretical model for how contact lens wear might change those interactions to enable susceptibility to P. aeruginosa infection. Methods Use of “null-infection” in vivo models, cultured human corneal epithelial cells, contact lens-wearing animal models, and bacterial genetics help to elucidate mechanisms by which P. aeruginosa survive at the ocular surface, adheres, and traverses multilayered corneal epithelia. These models also help elucidate the molecular mechanisms of corneal epithelial innate defense. Results and Discussion Tear fluid and the corneal epithelium combine to make a formidable defense against P. aeruginosa infection of the cornea. Part of that defense involves the expression of antimicrobials such as β-defensins, the cathelicidin LL-37, cytokeratin-derived antimicrobial peptides, and RNase7. Immunomodulators such as SP-D and ST2 also contribute. Innate defenses of the cornea depend in part on MyD88, a key adaptor protein of TLR and IL-1R signaling, but the basal lamina represents the final barrier to bacterial penetration. Overcoming these defenses involves P. aeruginosa adaptation, expression of the type three secretion system, proteases, and P. aeruginosa biofilm formation on contact lenses. Conclusion After more than two decades of research focused on understanding how contact lens wear predisposes to P. aeruginosa infection, our working hypothesis places blame for microbial keratitis on bacterial adaptation to ocular surface defenses, combined with changes to the biochemistry of the corneal surface caused by trapping bacteria and tear fluid against the cornea under the lens. PMID:23601656

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....

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

Directory of Open Access Journals (Sweden)

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

OpenAIRE

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...

Riboflavin for corneal cross-linking.

Science.gov (United States)

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.

准分子激光角膜表层切削术后的止痛措施%Pain control after excimer laser corneal surface ablation

Institute of Scientific and Technical Information of China (English)

曾原; 黄一飞; 高建华

2014-01-01

准分子激光角膜表层切削术因降低角膜膨隆的风险和避免准分子激光原位角膜磨镶术( LASIK)角膜瓣相关的并发症而受到青睐。但术后严重疼痛不适为表层切削的主要缺陷，因此表层切削术后疼痛不适的控制显得尤其重要。我们总结了表层切削术后疼痛的机制以及降低术后疼痛的措施的进展。%By reshaping the cornea without the creation of a stromal flap, excimer laser corneal surface ablation eliminates flap-related complications and avoids the risk of ectasia that may occur after laser assisted in situ keratomileusis ( LASIK ) . Post-operative pain is one of the most significant disadvantages of surface ablation and thus the management of pain and discomfort following surface ablation is of great importance. We summarize mechanism of corneal pain and current approaches to pain management after surface ablation.

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

The corneal epithelium: clinical relevance of cytokine-mediated responses to maintenance of corneal health O epitélio da córnea: relevância clínica das respostas mediadas por citocinas para manter a saúde da córnea

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PS Reinach

2008-12-01

Full Text Available We review the growth factor receptor-mediated cell signaling events that induce the responses required for the maintenance of corneal epithelial health. Our focus is to show how such responses contribute to sustaining corneal transparency and deturgescence, so basic to the pathogenesis of corneal diseases. Furthermore, we point out how alterations of receptor-mediated control of these responses account for losses in corneal transparency. In particular, the roles of growth factors in the mediation of normal corneal function, including epithelial cell proliferation, prevention of compromise of the barrier function of the cornea, and maintenance of normal renewal processes are discussed in relation to clinical entities involving the cornea.Revimos os eventos de sinalização celular mediados por receptores de fatores de crescimento, usados para manter a saúde do epitélio da córnea. O objetivo é mostrar como essas respostas contribuem para manter a transparência e a deturgescência da córnea, críticos na patogênese das doenças da córnea. Mais ainda, enfatizamos como alterações no controle mediado por receptor dessas respostas contribuem na transparência da córnea. Especificamente, o papel dos fatores de crescimento na mediação do controle funcional normal da córnea, incluindo proliferação epitelial, prevenção da quebra da função de barreira, manutenção do processo de renovação são discutidos em relação às entidades clínicas envolvidas na córnea.

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.

Assessment of refractive astigmatism and simulated therapeutic refractive surgery strategies in coma-like-aberrations-dominant corneal optics.

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Zhou, Wen; Stojanovic, Aleksandar; Utheim, Tor Paaske

2016-01-01

The aim of the study is to raise the awareness of the influence of coma-like higher-order aberrations (HOAs) on power and orientation of refractive astigmatism (RA) and to explore how to account for that influence in the planning of topography-guided refractive surgery in eyes with coma-like-aberrations-dominant corneal optics. Eleven eyes with coma-like-aberrations-dominant corneal optics and with low lenticular astigmatism (LA) were selected for astigmatism analysis and for treatment simulations with topography-guided custom ablation. Vector analysis was used to evaluate the contribution of coma-like corneal HOAs to RA. Two different strategies were used for simulated treatments aiming to regularize irregular corneal optics: With both strategies correction of anterior corneal surface irregularities (corneal HOAs) were intended. Correction of total corneal astigmatism (TCA) and RA was intended as well with strategies 1 and 2, respectively. Axis of discrepant astigmatism (RA minus TCA minus LA) correlated strongly with axis of coma. Vertical coma influenced RA by canceling the effect of the with-the-rule astigmatism and increasing the effect of the against-the-rule astigmatism. After simulated correction of anterior corneal HOAs along with TCA and RA (strategies 1 and 2), only a small amount of anterior corneal astigmatism (ACA) and no TCA remained after strategy 1, while considerable amount of ACA and TCA remained after strategy 2. Coma-like corneal aberrations seem to contribute a considerable astigmatic component to RA in eyes with coma-like-aberrations dominant corneal optics. If topography-guided ablation is programmed to correct the corneal HOAs and RA, the astigmatic component caused by the coma-like corneal HOAs will be treated twice and will result in induced astigmatism. Disregarding RA and treating TCA along with the corneal HOAs is recommended instead.

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.

Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy.

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Wei Liu

Full Text Available Vps35 (vacuolar protein sorting 35 is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD and Alzheimer's disease (AD. However, Vps35/retromer's function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea. Mouse cornea from Vps35 heterozygotes (Vps35+/- show features of dystrophy, such as loss of both endothelial and epithelial cell densities, disorganizations of endothelial, stroma, and epithelial cells, excrescences in the Descemet membrane, and corneal edema. Additionally, corneal epithelial cell proliferation was reduced in Vps35-deficient mice. Intriguingly, cell surface targeting of SLC4A11, a membrane transport protein (OH- /H+ /NH3 /H2O of corneal endothelium, whose mutations have been identified in patients with corneal dystrophy, was impaired in Vps35-deficient cells and cornea. Taken together, these results suggest that SLC4A11 appears to be a Vps35/retromer cargo, and Vps35-regulation of SLC4A11 trafficking may underlie Vps35/retromer regulation of corneal dystrophy.

Breakdown evaluation of corneal epithelial barrier caused by antiallergic eyedrops using an electrophysiologic method.

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Nakashima, Mikiro; Nakamura, Tadahiro; Teshima, Mugen; To, Hideto; Uematsu, Masafumi; Kitaoka, Takashi; Taniyama, Kotaro; Nishida, Koyo; Nakamura, Junzo; Sasaki, Hitoshi

2008-02-01

The aim of this study was to examine the usefulness of an electrophysiologic method for predicting corneal epithelial breakdown by antiallergic eyedrops and comparing the results with those in other appraisal methods. Six kinds of antiallergic eyedrops, including benzalkonium chloride (BK) as an ophthalmic preservative and two kinds of BK-free antiallergic eyedrops, were used in this study. Eyedrops were applied to excise rabbit corneas and monitoring was performed according to an electrophysiologic method, using a commercially available chamber system to mimic human tear turnover. Changes in transepithelial electrical resistance (TEER) in the corneal surface were recorded. The cytotoxicity of each kind of eyedrops in a normal rabbit corneal epithelial (NRCE) cell line and a human endothelial cell line EA.hy926 was also examined. The extent of decrease in the corneal TEER after applying antiallergic eyedrops was dependent on the concentration of the BK included as a preservative, but it was also affected by the different kinds of drugs when the BK concentration was low. Higher cytotoxicity of the eyedrops against the NRCE and EA.hy926 cell lines was observed with a reduction of TEER. Monitoring changes in the corneal TEER, according to the electrophysiologic method with the application of antiallergic eyedrops, is useful for predicting corneal epithelial breakdown caused by their instillation.

Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye.

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Ramsay, Eva; Del Amo, Eva M; Toropainen, Elisa; Tengvall-Unadike, Unni; Ranta, Veli-Pekka; Urtti, Arto; Ruponen, Marika

2018-07-01

On the surface of the eye, both the cornea and conjunctiva are restricting ocular absorption of topically applied drugs, but barrier contributions of these two membranes have not been systemically compared. Herein, we studied permeability of 32 small molecular drug compounds across an isolated porcine cornea and built a quantitative structure-property relationship (QSPR) model for the permeability. Corneal drug permeability (data obtained for 25 drug molecules) showed a 52-fold range in permeability (0.09-4.70 × 10 -6  cm/s) and the most important molecular descriptors in predicting the permeability were hydrogen bond donor, polar surface area and halogen ratio. Corneal permeability values were compared to their conjunctival drug permeability values. Ocular drug bioavailability and systemic absorption via conjunctiva were predicted for this drug set with pharmacokinetic calculations. Drug bioavailability in the aqueous humour was simulated to be drug across the conjunctiva to the blood circulation restricts significantly ocular drug bioavailability and, therefore, ocular absorption does not increase proportionally with the increasing corneal drug permeability. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Accelerated corneal collagen cross-linking in pediatric keratoconus: One year study

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Amani E. Badawi

2017-01-01

Conclusion: Accelerated CXL shows a stabilization and beneficial clinical outcomes in pediatric keratoconus. It seems an effective and safe procedure in this age group. Effects of accelerated CXL on the posterior corneal surface will need further evaluation.

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 ...

A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas

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Shao-Feng Gu

2015-02-01

Full Text Available AIM: To report the 3mo outcomes of collagen cross-linking (CXL with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 μm without epithelium. METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure. RESULTS: The mean thinnest thickness of the cornea was 408.5±29.0 μm before treatment and reduced to 369.8±24.8 μm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0±26.5 μm before CXL and recover to 412.5±22.7 μm at 3mo after treatment, P=0.659. Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6±4.0 diopters, and slightly decreased (54.7±4.9 diopters after surgery (P=0.085. Mean best-corrected visual acuity was 0.55±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery (P=0.879. The endothelial cell density was 2706.4±201.6 cells/mm2 before treatment, and slightly decreased (2641.2±218.2 cells/mm2 at last fellow up (P=0.002. CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.

Characteristic of entire corneal topography and tomography for the detection of sub-clinical keratoconus with Zernike polynomials using Pentacam.

Science.gov (United States)

Xu, Zhe; Li, Weibo; Jiang, Jun; Zhuang, Xiran; Chen, Wei; Peng, Mei; Wang, Jianhua; Lu, Fan; Shen, Meixiao; Wang, Yuanyuan

2017-11-28

The study aimed to characterize the entire corneal topography and tomography for the detection of sub-clinical keratoconus (KC) with a Zernike application method. Normal subjects (n = 147; 147 eyes), sub-clinical KC patients (n = 77; 77 eyes), and KC patients (n = 139; 139 eyes) were imaged with the Pentacam HR system. The entire corneal data of pachymetry and elevation of both the anterior and posterior surfaces were exported from the Pentacam HR software. Zernike polynomials fitting was used to quantify the 3D distribution of the corneal thickness and surface elevation. The root mean square (RMS) values for each order and the total high-order irregularity were calculated. Multimeric discriminant functions combined with individual indices were built using linear step discriminant analysis. Receiver operating characteristic curves determined the diagnostic accuracy (area under the curve, AUC). The 3rd-order RMS of the posterior surface (AUC: 0.928) obtained the highest discriminating capability in sub-clinical KC eyes. The multimeric function, which consisted of the Zernike fitting indices of corneal posterior elevation, showed the highest discriminant ability (AUC: 0.951). Indices generated from the elevation of posterior surface and thickness measurements over the entire cornea using the Zernike method based on the Pentacam HR system were able to identify very early KC.

Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease.

Science.gov (United States)

Kovács, Illés; Luna, Carolina; Quirce, Susana; Mizerska, Kamila; Callejo, Gerard; Riestra, Ana; Fernández-Sánchez, Laura; Meseguer, Victor M; Cuenca, Nicolás; Merayo-Lloves, Jesús; Acosta, M Carmen; Gasull, Xavier; Belmonte, Carlos; Gallar, Juana

2016-02-01

Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 μM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED.

A review of corneal diameter, curvature and thickness values and influencing factors*

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K. P. Mashige

2013-12-01

Full Text Available The cornea is an important ocular structure involved in the mediation of visual perception. It is the principal refractive surface of the eye and vision can be significantly affected by relatively small changes in its structure and parameters. Measurement of corneal parameters is important in the diagnosis and management of ocular diseasessuch as keratoconus and glaucoma, and also in the fitting of contact lenses or with refractive surgery such as Laser-Assisted in situ Keratomileusis(LASIK and photorefractive keratectomy (PRK. The human corneal diameter, anterior curvature and centre thickness as well as factors influencing them are reviewed in this article. This review will be useful to eye care professionals who routinely measure these parameters when fitting contact lenses and assessing, diagnosing as well as managing corneal and other ocular conditions. (S Afr Optom 2013 72(4 185-194

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?

Science.gov (United States)

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.

Automated Decision Tree Classification of Corneal Shape

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Twa, Michael D.; Parthasarathy, Srinivasan; Roberts, Cynthia; Mahmoud, Ashraf M.; Raasch, Thomas W.; Bullimore, Mark A.

2011-01-01

Purpose The volume and complexity of data produced during videokeratography examinations present a challenge of interpretation. As a consequence, results are often analyzed qualitatively by subjective pattern recognition or reduced to comparisons of summary indices. We describe the application of decision tree induction, an automated machine learning classification method, to discriminate between normal and keratoconic corneal shapes in an objective and quantitative way. We then compared this method with other known classification methods. Methods The corneal surface was modeled with a seventh-order Zernike polynomial for 132 normal eyes of 92 subjects and 112 eyes of 71 subjects diagnosed with keratoconus. A decision tree classifier was induced using the C4.5 algorithm, and its classification performance was compared with the modified Rabinowitz–McDonnell index, Schwiegerling’s Z3 index (Z3), Keratoconus Prediction Index (KPI), KISA%, and Cone Location and Magnitude Index using recommended classification thresholds for each method. We also evaluated the area under the receiver operator characteristic (ROC) curve for each classification method. Results Our decision tree classifier performed equal to or better than the other classifiers tested: accuracy was 92% and the area under the ROC curve was 0.97. Our decision tree classifier reduced the information needed to distinguish between normal and keratoconus eyes using four of 36 Zernike polynomial coefficients. The four surface features selected as classification attributes by the decision tree method were inferior elevation, greater sagittal depth, oblique toricity, and trefoil. Conclusions Automated decision tree classification of corneal shape through Zernike polynomials is an accurate quantitative method of classification that is interpretable and can be generated from any instrument platform capable of raw elevation data output. This method of pattern classification is extendable to other classification

Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF effects

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Jeffrey S. Fedan

2013-10-01

Full Text Available In asthmatic patients, inhalation of hyperosmolar saline or D-mannitol (D-M elicits bronchoconstriction, but in healthy subjects exercise causes bronchodilation. Hyperventilation causes drying of airway surface liquid (ASL and increases its osmolarity. Hyperosmolar challenge of airway epithelium releases epithelium-derived relaxing factor (EpDRF, which relaxes the airway smooth muscle. This pathway could be involved in exercise-induced bronchodilation. Little is known of ASL hyperosmolarity effects on epithelial function. We investigated the effects of osmolar challenge maneuvers on dispersed and adherent guinea-pig tracheal epithelial cells to examine the hypothesis that EpDRF-mediated relaxation is associated with epithelial cell shrinkage. Enzymatically-dispersed cells shrank when challenged with ≥10 mOsM added D M, urea or NaCl with a concentration-dependence that mimics relaxation of the of isolated, perfused tracheas (IPT. Cells shrank when incubated in isosmolar N-methyl-D-glucamine (NMDG chloride, Na gluconate (Glu, NMDG-Glu, K-Glu and K2SO4, and swelled in isosmolar KBr and KCl. However, isosmolar challenge is not a strong stimulus of relaxation in IPTs. In previous studies amiloride and 4,4' diisothiocyano 2,2' stilbenedisulfonic acid (DIDS inhibited relaxation of IPT to hyperosmolar challenge, but had little effect on shrinkage of dispersed cells. Confocal microscopy in tracheal segments showed that adherent epithelium is refractory to low hyperosmolar concentrations that induce dispersed cell shrinkage and relaxation of IPT. Except for gadolinium and erythro 9 (2 hydroxy 3 nonyladenine (EHNA, actin and microtubule inhibitors and membrane permeabilizing agents did not affect on ion transport by adherent epithelium or shrinkage responses of dispersed cells. Our studies dissociate relaxation of IPT from cell shrinkage after hyperosmolar challenge of airway epithelium .

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.

Establishment of functioning human corneal endothelial cell line with high growth potential.

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Tadashi Yokoi

Full Text Available Hexagonal-shaped human corneal endothelial cells (HCEC form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na(+- and K(+-dependent ATPase (Na(+/K(+-ATPase. Because HCEC proliferative activity is low in vivo, once HCEC are damaged and their numbers decrease, the cornea begins to show opacity due to overhydration, resulting in loss of vision. HCEC cell cycle arrest occurs at the G1 phase and is partly regulated by cyclin-dependent kinase inhibitors (CKIs in the Rb pathway (p16-CDK4/CyclinD1-pRb. In this study, we tried to activate proliferation of HCEC by inhibiting CKIs. Retroviral transduction was used to generate two new HCEC lines: transduced human corneal endothelial cell by human papillomavirus type E6/E7 (THCEC (E6/E7 and transduced human corneal endothelial cell by Cdk4R24C/CyclinD1 (THCEH (Cyclin. Reverse transcriptase polymerase chain reaction analysis of gene expression revealed little difference between THCEC (E6/E7, THCEH (Cyclin and non-transduced HCEC, but cell cycle-related genes were up-regulated in THCEC (E6/E7 and THCEH (Cyclin. THCEH (Cyclin expressed intercellular molecules including ZO-1 and N-cadherin and showed similar Na(+/K(+-ATPase pump function to HCEC, which was not demonstrated in THCEC (E6/E7. This study shows that HCEC cell cycle activation can be achieved by inhibiting CKIs even while maintaining critical pump function and morphology.

Confocal microscopy and electrophysiological study of single patient corneal endothelium cell cultures

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Tatini, Francesca; Rossi, Francesca; Coppi, Elisabetta; Magni, Giada; Fusco, Irene; Menabuoni, Luca; Pedata, Felicita; Pugliese, Anna Maria; Pini, Roberto

2016-04-01

The characterization of the ion channels in corneal endothelial cells and the elucidation of their involvement in corneal pathologies would lead to the identification of new molecular target for pharmacological treatments and to the clarification of corneal physiology. The corneal endothelium is an amitotic cell monolayer with a major role in preserving corneal transparency and in regulating the water and solute flux across the posterior surface of the cornea. Although endothelial cells are non-excitable, they express a range of ion channels, such as voltage-dependent Na+ channels and K+ channels, L-type Ca2 channels and many others. Interestingly, purinergic receptors have been linked to a variety of conditions within the eye but their presence in the endothelium and their role in its pathophysiology is still uncertain. In this study, we were able to extract endothelial cells from single human corneas, thus obtaining primary cultures that represent the peculiarity of each donor. Corneas were from tissues not suitable for transplant in patients. We characterized the endothelial cells by confocal microscopy, both within the intact cornea and in the primary endothelial cells cultures. We also studied the functional role of the purinergic system (adenosine, ATP and their receptors) by means of electrophysiological recordings. The experiments were performed by patch clamp recordings and confocal time-lapse microscopy and our results indicate that the application of purinergic compounds modulates the amplitude of outward currents in the isolated endothelial cells. These findings may lead to the proposal of new therapies for endothelium-related corneal diseases.

Small-Molecule Induction Promotes Corneal Epithelial Cell Differentiation from Human Induced Pluripotent Stem Cells

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Alexandra Mikhailova

2014-02-01

Full Text Available Human induced pluripotent stem cells (hiPSCs offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.

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.

Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

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Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

2011-01-01

Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

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.

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.

Corneal Nerve Regeneration after Self-Retained Cryopreserved Amniotic Membrane in Dry Eye Disease

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Thomas John

2017-01-01

Full Text Available Purpose. To evaluate the efficacy of self-retained cryopreserved amniotic membrane (CAM in promoting corneal nerve regeneration and improving corneal sensitivity in dry eye disease (DED. Methods. In this prospective randomized clinical trial, subjects with DED were randomized to receive CAM (study group or conventional maximum treatment (control. Changes in signs and symptoms, corneal sensitivity, topography, and in vivo confocal microscopy (IVCM were evaluated at baseline, 1 month, and 3 months. Results. Twenty subjects (age 66.9 ± 8.9 were enrolled and 17 completed all follow-up visits. Signs and symptoms were significantly improved in the study group yet remained constant in the control. IVCM showed a significant increase in corneal nerve density in the study group (12,241 ± 5083 μm/mm2 at baseline, 16,364 ± 3734 μm/mm2 at 1 month, and 18,827 ± 5453 μm/mm2 at 3 months, p=0.015 but was unchanged in the control. This improvement was accompanied with a significant increase in corneal sensitivity (3.25 ± 0.6 cm at baseline, 5.2 ± 0.5 cm at 1 month, and 5.6 ± 0.4 cm at 3 months, p<0.001 and corneal topography only in the study group. Conclusions. Self-retained CAM is a promising therapy for corneal nerve regeneration and accelerated recovery of the ocular surface health in patients with DED. The study is registered at clinicaltrials.gov with trial identifier: NCT02764814.

Endoscopy-guided vitreoretinal surgery following penetrating corneal injury: a case report

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Motoko Kawashima

2010-08-01

Full Text Available Motoko Kawashima1, Shinichi Kawashima2, Murat Dogru1,3, Makoto Inoue4, Jun Shimazaki1,51Department of Ophthalmology, Tokyo Dental College, Chiba, Japan; 2Department of Ophthalmology, International University of Health and Welfare, Tokyo, Japan; 3Department of Ocular Surface and Visual Optics, Keio University School of Medicine, Tokyo, Japan; 4Kyorin Eye Center, Tokyo, Japan; 5Department of Ophthalmology, Keio University School of Medicine, Tokyo, JapanIntroduction: Severe ocular trauma requires emergency surgery, and a fresh corneal graft may not always be available. We describe a case of perforating eye injury with corneal ­opacity, suspected endophthalmitis, and an intraocular foreign body. The patient was successfully treated with a two-step procedure comprising endoscopy-guided vitrectomy followed by corneal transplantation. This surgical technique offers a good option to vitrectomy with simultaneous keratoplasty in emergency cases where no graft is immediately available and there is the ­possibility of infection due to the presence of a foreign body.Case presentation: A 55-year-old Japanese woman was referred to our hospital with a ­perforating corneal and lens injury sustained with a muddy ferrous rod. Primary corneal sutures and lensectomy were performed immediately. Vitreoretinal surgery was required due to ­suspected endophthalmitis, vitreous hemorrhage, retinal detachment, dialysis and necrosis of the peripheral retina. Instead of conventional vitrectomy, endoscopy-guided vitreous surgery was performed with the Solid Fiber Catheter AS-611 (FiberTech, Tokyo, Japan due to the presence of corneal opacity and the unavailability of a donor cornea. The retina was successfully attached with the aid of a silicon oil tamponade. Following removal of the silicon oil at 3 months after surgery, penetrating keratoplasty and intraocular lens implantation with ciliary sulcus suture fixation were performed. At 6 months after penetrating

Glycosaminoglycans are involved in pathogen adherence to corneal epithelial cells differently for Gram-positive and Gram-negative bacteria

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Beatriz García

2016-11-01

Full Text Available The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies.

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

Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes.

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Justin D Mallet

Full Text Available Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD and pyrimidine (6-4 pyrimidone photoproducts (6-4PP. These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced.

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...

Progenitor Epithelium

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Marty-Santos, Leilani

2015-01-01

Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

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.

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

Impression cytology in the evaluation of ocular surface tumors: review article

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Jeison de Nadai Barros

2015-04-01

Full Text Available Impression cytology (IC has been widely used as a method for evaluating the ocular surface and superficial cells layers in the diagnosis and follow-up after treatment of several ocular surface tumors of both epithelial and melanocytic origin. Information regarding this can be found in the English-language literature since 1992. Using either cellulose acetate or Biopore membranes for specimen collection, a high correlation has been found between IC and tissue histology. Compared with exfoliative cytology with spatula, IC is less traumatic to the patient’s eye, provides a precise location of the area being studied, and allows accurate observation of the cells the way they exist in vivo. The additional advantage of IC is the preservation of limbal stem cells responsible for continuous corneal epithelium renewal; these can be affected after incisional or excisional biopsy at the corneoscleral limbus, which is the most frequent site of appearance of tumors in the stratified epithelium. Treatment for ocular surface squamous neoplasia has historically included surgery, but nonsurgical interventions have also been adopted. Hence, in certain cases, ophthalmologists may prefer interventions less invasive than surgical biopsy such as of impression cytology for both initial diagnosis and therapeutic monitoring of treatment for ocular surface lesions. Nevertheless, it should be considered that IC may be less helpful if the results conflict with the clinical picture or if the clinical diagnosis is uncertain and results are negative. In such cases, surgical biopsy is required for accurate diagnosis. The purpose of this review is to examine the published literature on the utilization of IC for the diagnosis and management of ocular surface tumors and to discuss the requirement for further investigation on the subject.

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.

Comparison of Central Corneal Thickness Measured by Standard Ultrasound Pachymetry, Corneal Topography, Tono-Pachymetry and Anterior Segment Optical Coherence Tomography.

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González-Pérez, Javier; Queiruga Piñeiro, Juan; Sánchez García, Ángelx; González Méijome, José Manuel

2018-04-10

To compare central corneal thickness (CCT) measured by standard ultrasound pachymetry (USP), and three non-contact devices in healthy eyes. A cross-sectional study of CCT measurement in 52 eyes of 52 healthy volunteers was done by a single examiner at Ocular Surface and Contact Lens Laboratory. Three consecutive measurements were done by standard USP, non-contact tono-pachymeter, Pentacam corneal topographer, and Anterior Segment Optical Coherence Tomography (AS-OCT). The mean values were used for assessment. The results were compared using multivariate ANOVA, linear regression, and Pearson correlation. Agreement among the devices was analyzed using mean differences and Bland-Altman analysis with 95% limits of agreement (LoA). Finally, reliability was analyzed using intraclass correlation coefficient (ICC). Mean CCT by ultrasound pachymeter, tono-pachymeter, corneal topographer and AS-OCT were 558.9 ± 31.2 µm, 525.8 ± 43.1 µm, 550.4 ± 30.5 µm, and 545.9 ± 30.5 µm respectively. There was a significant positive correlation between AS-OCT and USP (Pearson correlation = 0.957, p device, and USP. Mean CCT among USP, Pentacam and AS-OCT were comparable and had significant linear correlations. In clinical practice, these three modalities could be interchangeable in healthy patients.

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.

Cationic Gelatin Nanoparticles for Drug Delivery to the Ocular Surface: In Vitro and In Vivo Evaluation

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Ching-Li Tseng

2013-01-01

Full Text Available To develop an effective ocular drug delivery carrier, we prepared two different charged gelatin nanoparticles (GPs and evaluated particle size, surface charge, and morphology. The in vitro biocompatibility of GPs was assessed using human corneal epithelium (HCE cells and in vivo safety by administering them as eye drops to New Zealand rabbits. The GPs prepared using type A gelatin were positively charged (GP(+, +33 mV; size, 180.6±45.7 nm. Water-soluble tetrazolium salt (WST-1 assay showed that both GPs were nontoxic to HCE cells. The fluorescence intensity of HCE cells cultured with cationic GPs conjugated with a fluorescent dye was higher than that of the anionic GP-treated HCE cells. In vivo examination showed no serious irritation to the rabbit eyes. Furthermore, corneal thickness and ocular pressure in the eyes of the treated rabbits were similar to those in the eyes of normal rabbits. Microscopic examination of corneal cryosections showed widely distributed fluorescent nanocarriers, from the anterior to the posterior part of the cornea of the GP(+ group, and higher fluorescence intensity in the GP(+ group was also observed. In conclusion, GPs as cationic colloidal carriers were efficiently adsorbed on the negatively charged cornea without irritating the eyes of the rabbits and can be retained in the cornea for a longer time. Thus, GPs(+ have a great potential as vehicles for ocular drug delivery.

A Comparative Study of Vertebrate Corneal Structure: The Evolution of a Refractive Lens.

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Winkler, Moritz; Shoa, Golroxan; Tran, Stephanie T; Xie, Yilu; Thomasy, Sarah; Raghunathan, Vijay K; Murphy, Christopher; Brown, Donald J; Jester, James V

2015-04-01

Although corneal curvature plays an important role in determining the refractive power of the vertebrate eye, the mechanisms controlling corneal shape remain largely unknown. To address this question, we performed a comparative study of vertebrate corneal structure to identify potential evolutionarily based changes that correlate with the development of a corneal refractive lens. Nonlinear optical (NLO) imaging of second-harmonic-generated (SHG) signals was used to image collagen and three-dimensionally reconstruct the lamellar organization in corneas from different vertebrate clades. Second-harmonic-generated images taken normal to the corneal surface showed that corneal collagen in all nonmammalian vertebrates was organized into sheets (fish and amphibians) or ribbons (reptiles and birds) extending from limbus to limbus that were oriented nearly orthogonal (ranging from 77.7°-88.2°) to their neighbors. The slight angular offset (2°-13°) created a rotational pattern that continued throughout the full thickness in fish and amphibians and to the very posterior layers in reptiles and birds. Interactions between lamellae were limited to "sutural" fibers in cartilaginous fish, and occasional lamellar branching in fish and amphibians. There was a marked increase in lamellar branching in higher vertebrates, such that birds ≫ reptiles > amphibians > fish. By contrast, mammalian corneas showed a nearly random collagen fiber organization with no orthogonal, chiral pattern. Our data indicate that nonmammalian vertebrate corneas share a common orthogonal collagen structural organization that shows increased lamellar branching in higher vertebrate species. Importantly, mammalian corneas showed a different structural organization, suggesting a divergent evolutionary background.

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.

Structure and development of the saccular sensory epithelium in ...

African Journals Online (AJOL)

Structure and development of the saccular sensory epithelium in relation to otolith growth in the perch Perca fluviatilis (Telostei) ... Electron microscopy indicated: 1) The apical surface of each hair cell is covered with a ciliary bundle which varies in length in different epithelial regions. Each bundle is formed from a long ...

N-Isopropylacrylamide-co-glycidylmethacrylate as a Thermoresponsive Substrate for Corneal Endothelial Cell Sheet Engineering

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Bernadette K. Madathil

2014-01-01

Full Text Available Endothelial keratoplasty is a recent shift in the surgical treatment of corneal endothelial dystrophies, where the dysfunctional endothelium is replaced whilst retaining the unaffected corneal layers. To overcome the limitation of donor corneal shortage, alternative use of tissue engineered constructs is being researched. Tissue constructs with intact extracellular matrix are generated using stimuli responsive polymers. In this study we evaluated the feasibility of using the thermoresponsive poly(N-isopropylacrylamide-co-glycidylmethacrylate polymer as a culture surface to harvest viable corneal endothelial cell sheets. Incubation below the lower critical solution temperature of the polymer allowed the detachment of the intact endothelial cell sheet. Phase contrast and scanning electron microscopy revealed the intact architecture, cobble stone morphology, and cell-to-cell contact in the retrieved cell sheet. Strong extracellular matrix deposition was also observed. The RT-PCR analysis confirmed functionally active endothelial cells in the cell sheet as evidenced by the positive expression of aquaporin 1, collagen IV, Na+-K+ ATPase, and FLK-1. Na+-K+ ATPase protein expression was also visualized by immunofluorescence staining. These results suggest that the in-house developed thermoresponsive culture dish is a suitable substrate for the generation of intact corneal endothelial cell sheet towards transplantation for endothelial keratoplasty.

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.

Measurement of the thickness of the bronchial epithelium

International Nuclear Information System (INIS)

Bowden, D.H.; Baldwin, F.

1989-02-01

Cancer of the lung in uranium miners is thought to be related to the inhalation of gaseous radon daughters which become attached to molecules of water vapour or to dust particles. Since, the depth of tissue penetration by alpha particles is short, the thickness of the epithelium that lines the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the present study were: 1) to measure the thickness of human bronchial epithelium; 2) to determine the distribution and depth of the nuclei of basal cells in the bronchial epithelium; and 3) to compare these parameters in groups of smokers and non-smokers. Twenty-nine surgically removed specimens of the lung were examined (26 smokers, 3 non-smokers). The specimens were fixed and prepared for examination by light and electron microscopy. Blocks of tissue were oriented so that the maximum number of bronchi were cut in cross-section; measurements included bronchi of all sizes from bronchial generations (1≥ 9.01 mm) diameter to the smallest bronchioles, generations 7 - 16 (0.26 - 2.0 mm). Comparison of measurements in smokers and non-smokers show no significant differences, so that the 29 cases are considered to represent a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness. Of more importance are the figures relating to the distance from the cell surface to the underlying nucleus. Here too, with the exception of goblet cells, the measurements are significantly smaller in generations 7 - 16 than in generation 1

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 ...

Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo.

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Rajiv R Mohan

Full Text Available Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5 impedes corneal neovascularization (CNV in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 µl; 5×10(12 vg/ml application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and CD31 immunoblotting. Real-time PCR quantified mRNA expression of pro- and anti-angiogenic genes. Corneal health in live animals was monitored with clinical, slit-lamp and optical coherence tomography biomicroscopic examinations. Selective decorin delivery into stroma showed significant 52% (p<0.05, 66% (p<0.001, and 63% (p<0.01 reduction at early (day 5, mid (day 10, and late (day 14 stages of CNV in decorin-delivered rabbit corneas compared to control (no decorin delivered corneas in morphometric analysis. The H&E staining, lectin, collagen type IV, CD31 immunostaining (57-65, p<0.5, and CD31 immunoblotting (62-67%, p<0.05 supported morphometric findings. Quantitative PCR studies demonstrated decorin gene therapy down-regulated expression of VEGF, MCP1 and angiopoietin (pro-angiogenic and up-regulated PEDF (anti-angiogenic genes. The clinical, biomicroscopy and transmission electron microscopy studies revealed that AAV5-mediated decorin gene therapy is safe for the cornea. Tissue-targeted AAV5-mediated decorin gene therapy decreases CNV with no major side effects, and could potentially be used for treating patients.

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.

Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

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Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale

2018-04-01

To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.

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

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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 Structure of Urethral Epithelium in Merinos Lambs

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Vasile RUS

2018-05-01

Full Text Available The aim of this study was to investigate by histological techniques the structure of urethral epithelium in lambs. In this study, we harvested several fragments (prostatic, membranous and cavernous from urethra from 5 merino’s lambs of 3 months old. The first anatomical segment, the prostatic urethra, is lined by a urinary epithelium. The intermediary layer of this epithelium is formed of 5-6 rows of oval cells. The second segment of urethra has the same type of epithelium but the intermediary layer is formed of 6-7 rows of oval cells. In the last anatomical segment, the penile urethra, the epithelium is the same, but the intermediary layer has 3-4 rows of oval cells. In lambs, the urethra is lined by urinary epithelium. The urethral epithelium does not have the same thickness in all segments. The thinner epithelium it is in the cavernous urethra, the ticker is the membranous urethra.

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.

Corneal Laceration

Medline Plus

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 ...

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

Science.gov (United States)

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.

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.

Alloimmunity and Tolerance in Corneal Transplantation.

Science.gov (United States)

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.

Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

Science.gov (United States)

Garzotto, D.; De Marchis, S.

2010-10-01

Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

Relative permeability of the endothelium and epithelium of rabbit lungs

International Nuclear Information System (INIS)

Effros, R.M.; Mason, G.R.; Silverman, P.; Hukkanen, J.

1986-01-01

Electron micrographic studies of lungs suggest that the epithelial cells are more tightly joined than the underlying endothelium, and macromolecules penetrate the endothelium more readily than the epithelium. Comparisons of epithelial and endothelial permeability to small molecules have been based upon the relative rates at which solutes traverse the alveolar-capillary barrier in fluid filled lungs and those at which they equilibrate across the capillaries in air-filled lungs. Because the former process is much slower than the latter, it has been concluded that the epithelium is less permeable to small solutes than the endothelium. However this difference may be related to inadequate access of solutes to airway surfaces. In this study, solute losses from the vascular space were compared to those from the airspace in perfused, fluid-filled rabbit lungs. 36 Cl - and 125 I - were lost from air-spaces almost twice as rapidly as 22 Na + . In contrast, the endothelium is equally permeable to 22 Na + and these anions. Loss of 3 H-mannitol from the perfusate resembled that of 22 Na + for about 30 minutes, after which diffusion of 3 H-mannitol into the tissue nearly ceased. These observations suggest that the epithelium is more permselective than the endothelium. By resisting solute and water transport, the epithelium tends to prevent alveolar flooding and confines edema to the interstitium, where it is less likely to interfere with gas exchange

Safety of intracameral injection of gatifloxacin, levofloxacin on corneal endothelial structure and viability.

Science.gov (United States)

Choi, Jin A; Chung, Sung Kun

2009-10-01

To investigate the safety of intracameral injection of gatifloxacin, levofloxacin in a rabbit model as prophylaxis against endophthalmitis. Twenty-four eyes of New Zealand white rabbits were randomly divided into 3 treatment groups: levofloxacin, gatifloxacin, and balanced salt solution (BSS) control groups. After 100 microL of each was injected into the anterior chamber, endothelial toxicity was evaluated by measuring the central corneal thicknesses and the clinical toxicity scores using a slit-lamp at post-procedure days 3 and 7. The percent of dead cells was determined by vital staining with alizarin red and trypan blue at 7 days after injection. Finally, in each group, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed for the evaluation of structural integrity. The toxicity scores were increased at post-procedure days 3 and 7, but the difference among the groups was not statistically significant (P = 0.661, 0.216, respectively). With regard to baseline corneal thickness, only the levofloxacin group exhibited a significant increase from baseline (P = 0.028), whereas the other treatment groups showed no difference from baseline (P = 0.128 in gatifloxacin, 0.161 in BSS group). The mean corneal endothelial damage was 0.81 +/- 0.31% in the levofloxacin group, 0.56 +/- 0.47% in the gatifloxacin group, and 0.53 +/- 0.52% in the BSS group, with no statistically significant difference noted among the groups (P = 0.582). SEM revealed a well-preserved hexagonal endothelial cell mosaic and normal microvilli on the endothelial cell surface in the gatifloxacin and control groups. However, the levofloxacin group showed slightly disintegrated cellular borders. TEM revealed that each group maintained normal intracellular organization, whereas the levofloxacin group exhibited slightly flat cell configuration with irregular folds on the apical cell surface. Intracameral injection of gatifloxacin and levofloxacin was nontoxic in terms of

Aloe vera: an in vitro study of effects on corneal wound closure and collagenase activity.

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Curto, Elizabeth M; Labelle, Amber; Chandler, Heather L

2014-11-01

To evaluate the in vitro effects of an aloe vera solution on (i) the viability and wound healing response of corneal cells and (ii) the ability to alter collagenase and gelatinase activities. Primary cultures of corneal epithelial cells and fibroblasts were prepared from grossly normal enucleated canine globes and treated with an aloe solution (doses ranging from 0.0-2 mg/mL). Cellular viability was evaluated using a colorimetric assay. A corneal wound healing model was used to quantify cellular ingrowth across a defect made on the confluent surface. Anticollagenase and antigelatinase activities were evaluated by incubating a bacterial collagenase/gelatinase with aloe solution (doses ranging from 0.0-500 μg/mL) and comparing outcome measures to a general metalloproteinase inhibitor, 1, 10-phenanthroline, and canine serum (doses ranging from 0.0-100%). None of the concentrations of aloe solution tested significantly affected the viability of corneal epithelial cells or fibroblasts. Concentrations ≤175 μg/mL slightly accelerated corneal epithelial cell wound closure; this change was not significant. Concentrations ≥175 μg/mL significantly (P ≤ 0.001) slowed the rate of corneal fibroblast wound closure, while aloe concentrations Aloe solution did not alter the ability for collagenase to degrade gelatin or collagen Type I but increased the ability for collagenase to degrade Type IV collagen. Although additional experiments are required, lower concentrations of aloe solution may be beneficial in healing of superficial corneal wounds to help decrease fibrosis and speed epithelialization. An increase in collagenase activity with aloe vera warrants further testing before considering in vivo studies. © 2014 American College of Veterinary Ophthalmologists.

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.

Barrier properties of cultured retinal pigment epithelium.

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Rizzolo, Lawrence J

2014-09-01

The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health.

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Xiang, Ping; Liu, Rong-Yan; Li, Chao; Gao, Peng; Cui, Xin-Yi; Ma, Lena Q

2017-11-01

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC 50 at 202 μg/mL. A concentration-dependent apoptotic sign was observed in HCECs after exposing to ≥2 μg/mL TDCPP. Endoplasmic reticulum stress induction was evidenced by up-regulation of its biomarker genes (ATF-4, CHOP, BiP, and XBP1). Furthermore, alternation of Bcl-2/Bax expression, mitochondrial membrane potential loss, cellular ATP content decrease, and caspase-3 and -9 activity increase were observed after exposing to 2 or 20 μg/mL TDCPP. Taken together, the data implicated the involvement of endoplasmic reticulum stress in TDCPP-induced HCEC apoptosis, probably mediated by mitochondrial apoptotic pathway. Our findings showed TDCPP exposure induced toxicity to human cornea. Due to TDCPP's presence at high levels in indoor dust, further study is warranted to evaluate its health risk on human corneas. Published by Elsevier Ltd.

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.

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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

Challenges and opportunities for tissue-engineering polarized epithelium.

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Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

2014-02-01

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

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.

Mechanisms of superficial micropunctate corneal staining with sodium fluorescein: the contribution of pooling.

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Bandamwar, Kalika L; Garrett, Qian; Papas, Eric B

2012-04-01

To establish if sodium fluorescein (SFL) dye accumulation within intercellular spaces on the ocular surface contributes to the appearance of superficial punctate corneal staining. Thirteen subjects bilaterally wore PureVision™ lenses that had been pre-soaked in ReNu MultiPlus® multipurpose solution. After 1h of lens wear, corneal staining with SFL was assessed using a standard slit-lamp technique. Participants who presented with bilateral, corneal staining were selected for further evaluation. A randomly selected eye was rinsed with saline three times. Fellow eyes (control) received no rinsing. After each rinse, the appearance of SFL staining was recorded without any further instillation of the dye. To eliminate any confounding effects of staining due to residual fluorescein in the tear menisci, corneal staining was induced in freshly excised, isolated, rabbit eyes by topical administration of 0.001% PHMB and staining, rinsing and grading were performed as above. Nine out of 13 subjects presented with bilateral diffuse corneal staining (mean grade±SD: 2.4±0.7). The mean staining grades in test and control eyes respectively after each of the three rinses were (1) 2.41±0.41, 2.25±0.69 (p=0.9); (2) 2.34±0.79, 2.1±0.83 (p=0.8); and (3) 1.71±0.65, 1.60±0.79 (p=0.6) there was no significant reduction in staining with rinsing (p>0.05) and no difference was observed between test and control eyes at any sampling-point. Similar observations made in ex vivo rabbit eyes replicated these results. Pooling or accumulation of SFL solution within intercellular spaces does not appear to contribute to the appearance of superficial micropunctate corneal staining. Copyright © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.