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Sample records for macular telangiectasia mactel

  1. Swept Source OCT Angiography of Neovascular Macular Telangiectasia Type 2

    Science.gov (United States)

    Zhang, Qinqin; Wang, Ruikang K.; Chen, Chieh-Li; Legarreta, Andrew D.; Durbin, Mary K.; An, Lin; Sharma, Utkarsh; Stetson, Paul F.; Legarreta, John E.; Roisman, Luiz; Gregori, Giovanni; Rosenfeld, Philip J.

    2015-01-01

    Objective To image subretinal neovascularization in proliferative macular telangiectasia type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG). Study Design Patients with MacTel2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1050nm swept-source OCT (SS-OCT) prototype system. The OMAG algorithm generated en face flow images from three retinal layers, as well as the region bounded by the outer retina and Bruch’s membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared to images from fluorescein angiography (FA) and indocyanine green angiography (ICGA). Results Three eyes with neovascular MacTel2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch’s membrane. OMAG images identified these abnormal vessels better than FA and were comparable to the images obtained using ICGA. In all three cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the two cases with ICGA imaging. In one case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, as well as the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex. Conclusions OMAG imaging provided detailed, depth-resolved information about subretinal neovascularization in MacTel2 eyes demonstrating superiority to FA imaging and similarities to ICGA imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy. PMID:26457402

  2. Multimodality imaging in macular telangiectasia 2: A clue to its pathogenesis

    Directory of Open Access Journals (Sweden)

    Lihteh Wu

    2015-01-01

    Full Text Available Macular telangiectasia type 2 also known as idiopathic perifoveal telangiectasia and juxtafoveolar retinal telangiectasis type 2A is an acquired bilateral neurodegenerative macular disease that manifests itself during the fifth or sixth decades of life. It is characterized by minimal dilatation of the parafoveal capillaries with graying of the retinal area involved, a lack of lipid exudation, right-angled retinal venules, refractile deposits in the superficial retina, hyperplasia of the retinal pigment epithelium, foveal atrophy, and subretinal neovascularization (SRNV. Our understanding of the disease has paralleled advances in multimodality imaging of the fundus. Optical coherence tomography (OCT images typically demonstrate the presence of intraretinal hyporeflective spaces that are usually not related to retinal thickening or fluorescein leakage. The typical fluorescein angiographic (FA finding is a deep intraretinal hyperfluorescent staining in the temporal parafoveal area. With time, the staining may involve the whole parafoveal area but does not extend to the center of the fovea. Long-term prognosis for central vision is poor, because of the development of SRNV or macular atrophy. Its pathogenesis remains unclear but multimodality imaging with FA, spectral domain OCT, adaptive optics, confocal blue reflectance and short wave fundus autofluorescence implicate Müller cells and macular pigment. Currently, there is no known treatment for this condition.

  3. Correlations Between Macular, Skin, and Serum Carotenoids

    Science.gov (United States)

    Conrady, Christopher D.; Bell, James P.; Besch, Brian M.; Gorusupudi, Aruna; Farnsworth, Kelliann; Ermakov, Igor; Sharifzadeh, Mohsen; Ermakova, Maia; Gellermann, Werner; Bernstein, Paul S.

    2017-01-01

    Purpose Ocular and systemic measurement and imaging of the macular carotenoids lutein and zeaxanthin have been employed extensively as potential biomarkers of AMD risk. In this study, we systematically compare dual wavelength retinal autofluorescence imaging (AFI) of macular pigment with skin resonance Raman spectroscopy (RRS) and serum carotenoid levels in a clinic-based population. Methods Eighty-eight patients were recruited from retina and general ophthalmology practices from a tertiary referral center and excluded only if they did not have all three modalities tested, had a diagnosis of macular telangiectasia (MacTel) or Stargardt disease, or had poor AFI image quality. Skin, macular, and serum carotenoid levels were measured by RRS, AFI, and HPLC, respectively. Results Skin RRS measurements and serum zeaxanthin concentrations correlated most strongly with AFI macular pigment volume under the curve (MPVUC) measurements up to 9° eccentricity relative to MPVUC or rotationally averaged macular pigment optical density (MPOD) measurements at smaller eccentricities. These measurements were reproducible and not significantly affected by cataracts. We also found that these techniques could readily identify subjects taking oral carotenoid-containing supplements. Conclusions Larger macular pigment volume AFI and skin RRS measurements are noninvasive, objective, and reliable methods to assess ocular and systemic carotenoid levels. They are an attractive alternative to psychophysical and optical methods that measure MPOD at a limited number of eccentricities. Consequently, skin RRS and MPVUC at 9° are both reasonable biomarkers of macular carotenoid status that could be readily adapted to research and clinical settings. PMID:28728169

  4. Ataxia - telangiectasia

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    ... this page: //medlineplus.gov/ency/article/001394.htm Ataxia - telangiectasia To use the sharing features on this page, please enable JavaScript. Ataxia-telangiectasia is a rare childhood disease. It affects ...

  5. Ataxia Telangiectasia

    Science.gov (United States)

    Ataxia-telangiectasia (A-T) is a rare, inherited disease. It affects the nervous system, immune system, and ... young children, usually before age 5. They include Ataxia - trouble coordinating movements Poor balance Slurred speech Tiny, ...

  6. Treating telangiectasias: my method.

    Science.gov (United States)

    Ferrara, F; Ferrara, G

    2013-04-01

    The authors propose a new classification of telangiectasias: conditions involving demonstrated reflux are classified as type A telangiectasias; clustered, spider telangiectasias not related to reflux and with vein diameters of >0.2 mm are classified as type B, while isolated telangiectatic veins of ≤0.2 mm diameter are classed as type C. This histological and pathophysiological approach is the basis for the Authors' Multi-Therapy Treatment Protocol (MTT). The treatment regimen provides for initial treatment of type A telangiectasias with just conventional reflux sclerotherapy, followed three weeks later by treatment of type B telangiectasias with 0.25-0.5% polidocanol foam, associated with both external compression and tumescent vasoconstriction (START technique). This is then followed after a further three months by dermal stimulation with mesoglycan (LIDS technique) to reinforce the district underlying the type C telangiectasias. The MTT Protocol was used on 63 patients (125 limbs). A 12-month follow-up showed the treatment regimen to provide better aesthetic and functional results than classical sclerotherapy, with few adverse effects and greater patient satisfaction.

  7. Genetics Home Reference: ataxia-telangiectasia

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions ataxia-telangiectasia ataxia-telangiectasia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Ataxia-telangiectasia is a rare inherited disorder that affects ...

  8. Ataxia-telangiectasia

    Directory of Open Access Journals (Sweden)

    Nelson Pires Ferreira

    1966-09-01

    Full Text Available São apresentados os casos de dois irmãos com ataxia-telangiectasia, estudados sob os pontos de vista clínico, eletrencefalográfico, liquórico e encefalográfico. O autor resume os achados de diversos autores e chama a atenção para a regressão parcial da síndrome cerebelar em ambos os pacientes, fato ainda não referido na literatura.

  9. What Is Ataxia-Telangiectasia?

    Science.gov (United States)

    ... About A-T Research Fundraising About Us About Ataxia-telangiectasia About A-T » WHAT IS A- ... develop slurred or distorted speech, and swallowing problems. Ataxia... The onset of this ataxia marks the beginning ...

  10. Hashimoto thyroiditis associated with ataxia telangiectasia.

    Science.gov (United States)

    Patiroglu, Turkan; Gungor, Hatice Eke; Unal, Ekrem; Kurtoglu, Selim; Yikilmaz, Ali; Patiroglu, Tahir

    2012-01-01

    Ataxia telangiectasia is a rare genetic disease characterized by neurological manifestations, infections, and cancers. In addition to these cardinal features, different autoimmune diseases can be seen in patients with ataxia telangiectasia. Although there were reports of positive autoimmune thyroid antibodies associated with ataxia telangiectasia, to our knowledge, we report the first cases of nodular Hashimoto thyroiditis in two patients with ataxia telangiectasia in the English medical literature. These cases illustrate that despite the rarity of nodular Hashimoto thyroiditis associated with ataxia telangiectasia, physicians should be aware of this possibility. Furthermore, thyroid examination of patient with ataxia telangiectasia is recommended for early diagnosis.

  11. Pigmentos maculares Macular pigments

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    Renata Canovas

    2009-12-01

    Full Text Available A luteína e a zeaxantina são pigmentos amarelos que se localizam na mácula. Devido à sua localização, diminuem e filtram a quantidade de luz principalmente azul que chega aos fotorreceptores, atuam como antioxidantes e podem melhorar a qualidade visual. Esta é uma revisão do seu mecanismo de incorporação, ação, possíveis aplicações e conhecimento científico a respeito.Lutein and Zeaxanthin are yellow pigments located at the macula. Because of your location macular pigments decrease and filter the amount of blue light that reach photoreceptors, protect the outer retina from oxidative stress and may improve the vision quality. This is a review regarding incorporation mechanism, function and knowledge update.

  12. Ataxia-telangiectasia: recommendations for multidisciplinary treatment

    NARCIS (Netherlands)

    Os, N.J.H. van; Haaxma, C.A.; Flier, M. van der; Merkus, P.J.F.M.; Deuren, M. van; Groot, I.J.M. de; Loeffen, J.; Warrenburg, B.P.C. van de; Willemsen, M.A.A.P.

    2017-01-01

    Ataxia-telangiectasia is a rare, neurodegenerative, and multisystem disease, characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient's n

  13. What Is Macular Edema?

    Medline Plus

    Full Text Available ... Español Eye Health / Eye Health A-Z Macular Edema Sections What Is Macular Edema? What Causes Macular ... Edema Diagnosis Macular Edema Treatment What Is Macular Edema? Dec. 01, 2010 Macular edema is swelling or ...

  14. Survival probability in ataxia telangiectasia

    Science.gov (United States)

    Crawford, T O; Skolasky, R L; Fernandez, R; Rosquist, K J; Lederman, H M

    2006-01-01

    Ataxia telangiectasia is a rare, multiorgan neurodegenerative disorder with enhanced vulnerability to cancer and infection. Median survival in two large cohorts of patients with this disease, one prospective and one retrospective, is 25 and 19 years, with a wide range. Life expectancy does not correlate well with severity of neurological impairment. PMID:16790721

  15. Cerebral abnormalities in adults with ataxia-telangiectasia

    National Research Council Canada - National Science Library

    Lin, D D M; Barker, P B; Lederman, H M; Crawford, T O

    2014-01-01

    Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular...

  16. [From gene to disease; ataxia telangiectasia

    NARCIS (Netherlands)

    Broeks, A.; Veer, L.J. van 't; Ottenheim, C.; Hiel, J.A.P.; Kleijer, W.J.; Weemaes, C.M.R.

    2003-01-01

    Ataxia telangiectasia (AT) is an autosomal recessive disorder characterised by cerebellar ataxia, telangiectasia, immune defects, and a predisposition to malignancy. Chromosomal breakage is a feature. AT cells are abnormally sensitive to cell kill by ionising radiation and abnormally resistant to in

  17. Ataxia-Telangiectasia (A-T)

    Science.gov (United States)

    Ataxia-Telangiectasia (A-T) What is ataxia-telangiectasia (A-T)? A-T is a hereditary progressive neurodegenerative disorder that begins in early childhood. ... nervous system. What are the symptoms of A-T? An affected child usually begins to show signs ...

  18. Macular Diplopia.

    Science.gov (United States)

    Shippman, Sara; Cohen, Kenneth R; Heiser, Larissa

    2015-01-01

    Maculopathies affect point-to-point foveal correspondence causing diplopia. The effect that the maculopathies have on the interaction of central sensory fusion and peripheral fusion are different than the usual understanding of treatment for diplopia. This paper reviews the pathophysiology of macular diplopia, describes the binocular pathology causing the diplopia, discusses the clinical evaluation, and reviews the present treatments including some newer treatment techniques.

  19. Ataxia-telangiectasia: recommendations for multidisciplinary treatment.

    Science.gov (United States)

    van Os, Nienke J H; Haaxma, Charlotte A; van der Flier, Michiel; Merkus, Peter J F M; van Deuren, Marcel; de Groot, Imelda J M; Loeffen, Jan; van de Warrenburg, Bart P C; Willemsen, Michèl A A P

    2017-07-01

    Ataxia-telangiectasia is a rare, neurodegenerative, and multisystem disease, characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient's needs. Besides the classic ataxia-telangiectasia phenotype, a variant phenotype exists with partly overlapping but some distinctive disease characteristics. This guideline summarizes frequently encountered medical problems in the disease course of patients with classic and variant ataxia-telangiectasia, in the domains of neurology, immunology and infectious diseases, pulmonology, anaesthetic and perioperative risk, oncology, endocrinology, and nutrition. Furthermore, it provides a practical guide with evidence- and expert-based recommendations for the follow-up and treatment of all these different clinical topics. © 2017 Mac Keith Press.

  20. Splenic Involvement in Hereditary Hemorrhagic Telangiectasia

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    Susumu Takamatsu

    2016-01-01

    Full Text Available A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

  1. Telangiectasia in aluminium workers: a follow up.

    OpenAIRE

    Thériault, G.; Gingras, S.; Provencher, S

    1984-01-01

    A five step investigation was carried out to gain a better understanding of the morbidity that accompanied the development of telangiectasia on aluminium workers and to find its cause. Fifty workers with multiple telangiectasia when matched with normal controls showed the same amount of illness except that evidence of ischaemia on the ECG was found in nine cases and one control. The cases did not show an excess of abnormal biochemical tests. The basic histopathological lesion affected the sur...

  2. Cognitive phenotype in ataxia-telangiectasia.

    Science.gov (United States)

    Hoche, Franziska; Frankenberg, Emily; Rambow, Jennifer; Theis, Marius; Harding, Jessica Ann; Qirshi, Mayyada; Seidel, Kay; Barbosa-Sicard, Eduardo; Porto, Luciana; Schmahmann, Jeremy D; Kieslich, Matthias

    2014-09-01

    Pediatric cerebrocerebellar neurodegenerative disorders such as ataxia-telangiectasia (AT) have not been examined in detail for neuropsychologic changes. Such studies may contribute to the further understanding of ataxia-telangiectasia and to the role of the cerebrocerebellar system in the development of cognitive function in childhood. Twenty-two patients with the classic phenotype of ataxia-telangiectasia were grouped into early stage cerebellar disease (group AT-I) versus late stage cerebrocerebellar disease (group AT-II) and examined for neurocognitive features. Results were compared with those of healthy control subjects and with standard norms. Patients in AT-I group scored low average compared with standard norms on all tests and were impaired compared with healthy control subjects for verbal intelligence quotient (P ataxia-telangiectasia present early, coinciding with cerebellar pathology and are characteristic of the cerebellar cognitive affective syndrome. Widespread and deeper cognitive deficits manifest in later stages of ataxia-telangiectasia when additional noncerebellar pathology develops. These results are the first indications of distinct cerebellar and extracerebellar and/or subcortical contributions to the range of cognitive domains affected in ataxia-telangiectasia and need to be confirmed in future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Novel ATM mutations with ataxia-telangiectasia.

    Science.gov (United States)

    Liu, Xiao-Li; Wang, Tian; Huang, Xiao-Jun; Zhou, Hai-Yan; Luan, Xing-Hua; Shen, Jun-Yi; Chen, Sheng-Di; Cao, Li

    2016-01-12

    Ataxia telangiectasia is an autosomal recessive multisystem disorder characterized by progressive cerebellar ataxia with onset in childhood, oculocutaneous telangiectasia, increased serum alpha-fetoprotein, immunodeficiency, chromosomal instability, and radiation hypersensitivity. Ataxia-telangiectasia mutated gene (ATM) is one of the known genes to be associated with ataxia telangiectasia. We reported the clinical and genetic findings of three early-onset Chinese patients who demonstrated ataxia, oculomotor apraxia, choreoathetosis, myoclonus and telangiectasia of eyes. Sequence analysis of ATM revealed two known nonsense mutations c.8287C>T and c.9139C>T in the siblings. Though the siblings carried the same mutations, they showed different clinical features involving strephenopodia, exotropia, torsion dystonia, myoclonus and extrapyramidal impairments. The other patient was compound heterozygotes for ATM: c.8911C>T and c.7141_7151delAATGGAAAAAT, both of which were not reported previously and not found in 200 control chromosomes. This study widens the spectrum of mutations and phenotypes in ataxia telangiectasia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Bladder Wall Telangiectasia in a Patient with Ataxia-Telangiectasia and How to Manage?

    Directory of Open Access Journals (Sweden)

    Fatma Deniz Aygün

    2015-01-01

    Full Text Available Ataxia-telangiectasia (A-T is a rare neurodegenerative, inherited disease causing severe morbidity. Oculocutaneous telangiectasias are almost constant findings among the affected cases as telangiectasia is considered the main clinical finding for diagnosis. Vascular abnormalities in organs have been reported infrequently but bladder wall telangiectasias are extremely rare. We aimed to report recurrent hemorrhage from bladder wall telangiectasia in a 9-year-old boy with A-T who had received intravenous cyclophosphamide for non-Hodgkin’s lymphoma. Since A-T patients are known to be more susceptible to chemical agents, we suggested that possibly cyclophosphamide was the drug which induced bladder wall injury in this patient.

  5. What Is Macular Edema?

    Medline Plus

    Full Text Available ... Pediatric Ophthalmology Education Center Oculofacial Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center Global Ophthalmology Guide Eye ... What Is Macular Edema? Dec. 01, 2010 Macular ...

  6. Ataxia-telangiectasia: future prospects

    Directory of Open Access Journals (Sweden)

    Chaudhary MW

    2014-09-01

    Full Text Available Mohammed Wajid Chaudhary, Raidah Saleem Al-Baradie Pediatric Neurology, Neurosciences Centre, King Fahad Specialist Hospital, Dammam, Kingdom of Saudi Arabia Abstract: Ataxia-telangiectasia (A-T is an autosomal recessive multi-system disorder caused by mutation in the ataxia-telangiectasia mutated gene (ATM. ATM is a large serine/threonine protein kinase, a member of the phosphoinositide 3-kinase-related protein kinase (PIKK family whose best-studied function is as master controller of signal transduction for the DNA damage response (DDR in the event of double strand breaks (DSBs. The DDR rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell-cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence. DSBs can be generated by exposure to ionizing radiation (IR or various chemical compounds, such as topoisomerase inhibitors, or can be part of programmed generation and repair of DSBs via cellular enzymes needed for the generation of the antibody repertoire as well as the maturation of germ cells. AT patients have immunodeficiency, and are sterile with gonadal dysgenesis as a result of defect in meiotic recombination. In the cells of nervous system ATM has additional role in vesicle dynamics as well as in the maintenance of the epigenetic code of histone modifications. Moderate levels of ATM are associated with prolonged lifespan through resistance to oxidative stress. ATM inhibitors are being viewed as potential radiosensitizers as part of cancer radiotherapy. Though there is no cure for the disease at present, glucocorticoids have been shown to induce alternate splicing site in the gene for ATM partly restoring its activity, but their most effective timing in the disease natural history is not yet known. Gene therapy is promising but large size of the gene makes it technically difficult

  7. Neuropathology in classical and variant ataxia-telangiectasia.

    NARCIS (Netherlands)

    Verhagen, M.M.M.; Martin, J.J.; Deuren, M. van; Ceuterick-de Groote, C.; Weemaes, C.M.R.; Kremer, B.; Taylor, M.A.; Willemsen, M.A.A.P.; Lammens, M.M.Y.

    2012-01-01

    Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated alpha-fetoprotein levels. Some patients, classified as variant A-T, exhibit a milder clinical course. In the latter patients extrapyramidal symptoms

  8. What Is Macular Edema?

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    Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Macular Edema ... Edema Treatment What Is Macular Edema? Leer en Español: ¿Qué Es un Edema Macular? Dec. 01, 2010 ...

  9. Wet Macular Degeneration

    Science.gov (United States)

    ... macular degeneration Overview By Mayo Clinic Staff Wet macular degeneration is a chronic eye disease that causes blurred vision or a blind spot in your visual field. It's generally caused by abnormal blood vessels that leak fluid or blood into ... macular degeneration is one of two types of age-related ...

  10. Molecular pathology of ataxia telangiectasia

    Science.gov (United States)

    Taylor, A M R; Byrd, P J

    2005-01-01

    Ataxia telangiectasia (A-T) is one of a group of autosomal recessive cerebellar ataxias. Presentation is usually by the age of 2 years and ataxia of both upper and lower limbs develops, such that by early teenage most patients require a wheelchair for mobility. Speech and eye movement are also affected. Other important features are t(7;14) translocations, immunodeficiency, a high serum α fetoprotein concentration, growth retardation, telangiectasia—most noticeably on the bulbar conjunctiva—and a very high risk of developing a lymphoid tumour. Patients also show an increased sensitivity to ionising radiation. The classic form of A-T results from the presence of two truncating ATM mutations, leading to total loss of the ATM protein, a protein kinase. Importantly, A-T shows clinical heterogeneity, including milder forms where neurological progression may be slower or of later onset. In these cases there is a correlation between the preservation of neurological function, decreased radiosensitivity, and the degree of retained ATM protein kinase activity. Considerable scope remains for understanding the progress of the disorder in relation to the types of ATM mutation present. PMID:16189143

  11. [Macular serpiginous choroiditis complicated by macular hole].

    Science.gov (United States)

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    Macular serpiginouschoroiditis is a rare variant of serpiginous choroiditis characterized by a severe recurrent inflammation of both central choroid and retinal pigment epithelium. Visual prognosis is severe due to subsequent distruction of retinal structures. Permanent central visual loss is the consequence of retinal pigment epithelium hyper or hypoplasia and/or subretinal neovascularization leading to fibrous scarring. This article reports the unusual case of rapid development of a macular hole soon after the onset of characteristic clinical features. Despite anti-inflammatory treatment and successful macular hole surgery the visual function remained significantly impaired by secondary central retinal pigment epithelium changes.

  12. Cerebral abnormalities in adults with ataxia-telangiectasia.

    Science.gov (United States)

    Lin, D D M; Barker, P B; Lederman, H M; Crawford, T O

    2014-01-01

    Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.

  13. Conjunctival Telangiectasia in a Patient with Ataxia Telangiectasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Özge Pınar Akarsu

    2012-01-01

    Full Text Available The purpose of this paper is to report a 7-year-old patient who developed bilateral conjunctival hyperemia while being under treatment of pneumonia in Pediatric Infectious Diseases Clinic at Sisli Etfal Training and Research Hospital. Ophthalmological examination revealed bilateral conjunctival telangiectasias which were thought to be the ophthalmologic sign of ataxia telangiectasia after considering the other clinical findings, laboratory and imaging results, and family history. (Turk J Oph thal mol 2012; 42: 75-7

  14. Differentiating full thickness macular holes from impending macular holes and macular pseudoholes

    OpenAIRE

    Tsujikawa, M; Ohji, M; Fujikado, T.; Saito, Y.; Motokura, M.; Ishimoto, I.; Tano, Y.

    1997-01-01

    AIMS—The reliability of scanning laser ophthalmoscope (SLO) microperimetry in differentiating full thickness macular holes from macular pseudoholes and impending macular holes was evaluated.
METHODS—106 eyes with the clinical diagnosis of full thickness macular holes, macular pseudoholes, and impending (stage 1) macular holes were examined for the presence of deep or relative scotoma using SLO microperimetry. The relation between these scotomas and the clinical diagnosis was studied.
RESULTS—...

  15. What Is Macular Edema?

    Medline Plus

    Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Macular Edema ... for Thinning Retina Mar 10, 2014 Leer en Español: ¿Qué Es un Edema Macular? Find an Ophthalmologist ...

  16. Telangiectasia in aluminium workers: a follow up.

    Science.gov (United States)

    Thériault, G; Gingras, S; Provencher, S

    1984-08-01

    A five step investigation was carried out to gain a better understanding of the morbidity that accompanied the development of telangiectasia on aluminium workers and to find its cause. Fifty workers with multiple telangiectasia when matched with normal controls showed the same amount of illness except that evidence of ischaemia on the ECG was found in nine cases and one control. The cases did not show an excess of abnormal biochemical tests. The basic histopathological lesion affected the surrounding tissue rather than the vessels themselves. Working in the current environment and wearing masks seems to protect young workers from developing the lesions. The Soderberg and not the prebake process was associated with the lesions; the causative agent is probably a gas that contains both hydrocarbons and fluoride components emitted from the electrolytic reactors.

  17. Eye movements in ataxia-telangiectasia.

    Science.gov (United States)

    Baloh, R W; Yee, R D; Boder, E

    1978-11-01

    The spectrum of eye movement disorders in six patients with ataxia-telangiectasia at different stages of progression was assessed quantitatively by electrooculography. All patients demonstrated abnormalities of voluntary and involuntary saccades. The youngest and least involved patient had significantly increased reaction times of voluntary saccades, but normal accuracy and velocity. The other patients demonstrated increased reaction times and marked hypometria of horizontal and vertical voluntary saccades. Saccade velocity remained normal. Vestibular and optokinetic fast components (involuntary saccades) had normal amplitude and velocity but the eyes deviated tonically in the direction of the slow component. We conclude that patients with ataxia-telangiectasia have a defect in the initiation of voluntary and involuntary saccades in the earliest stages. These findings are distinctly different from those in other familial cerebellar atrophy syndromes.

  18. Uterine tumors in ataxia-telangiectasia.

    Science.gov (United States)

    Gatti, R A; Nieberg, R; Boder, E

    1989-02-01

    Roughly one-third of patients with ataxia-telangiectasia (AT) develop malignant tumors, usually of lymphoid origin. AT patients also exhibit progeric changes. We describe three patients, between the ages of 27 and 32 years, with uterine tumors: one with a frank leiomyosarcoma and chronic T-cell leukemia, one with a multilobulated leiomyoma of uncertain malignant potential, and one with an unremarkable leiomyoma. Thus, the spectrum of tumors in AT patients beyond adolescence includes nonlymphoid malignancies and precocious, benign leiomyomas.

  19. Clinical variability in ataxia-telangiectasia.

    Science.gov (United States)

    Lohmann, Ebba; Krüger, Stefanie; Hauser, Ann-Kathrin; Hanagasi, Hasmet; Guven, Gamze; Erginel-Unaltuna, Nihan; Biskup, Saskia; Gasser, Thomas

    2015-07-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive inherited disease characterized by progressive childhood-onset cerebellar ataxia, oculomotor apraxia, choreoathetosis and telangiectasias of the conjunctivae. Further symptoms may be immunodeficiency and frequent infections, and an increased risk of malignancy. As well as this classic manifestation, several other non-classic forms exist, including milder or incomplete A-T phenotypes caused by homozygous or compound heterozygous mutations in the ATM gene. Recently, ATM mutations have been found in 13 Canadian Mennonites with early-onset, isolated, predominantly cervical dystonia, in a French family with generalized dystonia and in an Indian family with dopa-responsive cervical dystonia. In this article, we will describe a Turkish family with three affected sibs. Their phenotypes range from pure cervical dystonia associated with hand tremor to truncal and more generalized dystonic postures. Exome sequencing has revealed the potentially pathogenic compound heterozygous variants p.V2716A and p.G301VfsX19 in the ATM gene. The variants segregated perfectly with the phenotypes within the family. Both mutations detected in ATM have been shown to be pathogenic, and the α-fetoprotein, a marker of ataxia telangiectasia, was found to be increased. This report supports recent literature showing that ATM mutations are not exclusively associated with A-T but may also cause a more, even intra-familial variable phenotype in particular in association with dystonia.

  20. Cystoid macular edema

    Directory of Open Access Journals (Sweden)

    Tryfon G Rotsos

    2008-10-01

    Full Text Available Tryfon G Rotsos1, Marilita M Moschos21Medical Retina Service, Moorfields Eye Hospital, London, UK; 2Department of Ophthalmology, University of Athens, GreeceAbstract: We review the epidemiology, pathophysiology, and etiology of cystoid macular edema (CME. Inflammatory, diabetic, post-cataract, and macular edema due to age-related macular degeneration is described. The role of chronic inflammation and hypoxia and direct macular traction is evaluated in each case according to different views from the literature. The different diagnostic methods for evaluating the edema are described. Special attention is given to fluoroangiography and the most modern methods of macula examination, such as ocular coherence tomography and multifocal electroretinography. Finally, we discuss the treatment of cystoid macular edema in relation to its etiology. In this chapter we briefly refer to the therapeutic value of laser treatment especially in diabetic maculopathy or vitrectomy in some selected cases. Our paper is focused mainly on recent therapeutic treatment with intravitreal injection of triamcinolone acetonide and anti-VEGF factors like bevacizumab (Avastin, ranibizumab (Lucentis, pegaptamid (Macugen, and others. The goal of this paper is to review the current status of this treatment for macular edema due to diabetic maculopathy, central retinal vein occlusion and post-cataract surgery. For this reason the results of recent multicenter clinical trials are quoted, as also our experience on the use of intravitreal injections of anti-VEGF factors and we discuss its value in clinical practice.Keywords: cystoid macular edema, anti-VEGF, fluoroangiography, OCT, multifocal electroretinography

  1. Neuropathology in classical and variant ataxia-telangiectasia

    NARCIS (Netherlands)

    Verhagen, Mijke M. M.; Martin, Jean-Jacques; van Deuren, Marcel; Groote, Chantal Ceuterick-de; Weemaes, Corry M. R.; Kremer, Berry H. P. H.; Taylor, Malcolm A. R.; Willemsen, Michel A. A. P.; Lammens, Martin

    2012-01-01

    Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated a-fetoprotein levels. Some patients, classified as variant A-T, exhibit a milder clinical course. In the latter patients extrapyramidal symptoms, in

  2. Neuropathology in classical and variant ataxia-telangiectasia

    NARCIS (Netherlands)

    Verhagen, Mijke M. M.; Martin, Jean-Jacques; van Deuren, Marcel; Groote, Chantal Ceuterick-de; Weemaes, Corry M. R.; Kremer, Berry H. P. H.; Taylor, Malcolm A. R.; Willemsen, Michel A. A. P.; Lammens, Martin

    2012-01-01

    Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated a-fetoprotein levels. Some patients, classified as variant A-T, exhibit a milder clinical course. In the latter patients extrapyramidal symptoms, in

  3. Cerebral abscesses among Danish patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Tørring, P M; Nissen, H;

    2013-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess.......Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess....

  4. What Is Macular Edema?

    Medline Plus

    Full Text Available ... health and preserving your vision. Privacy Policy Related Studies Show Zika Virus May Cause More Serious Eye Damage in Babies Than Thought May 31, 2016 Study Compares Eylea, Lucentis and Avastin for Diabetic Macular ...

  5. What Is Macular Edema?

    Medline Plus

    Full Text Available ... or recognize a face. Macular edema develops when blood vessels in the retina are leaking fluids. The macula ... Your Laser Pointer Dangerous Enough to Cause Eye Injury? Dec 20, 2013 Study Finds Tablets Help People ...

  6. Cataracts and macular degeneration.

    Science.gov (United States)

    Shoch, D

    1979-09-01

    The intraocular lens restores general vision and some degree of independence and mobility to patients with dense cataracts and macular degeneration. The patient, however, must be repeatedly warned that fine central vision, particularly reading, will not be possible after the surgery. An aphakic spectacle leaves such patients a narrow band of vision when superimposed over the macular lesion, and contact lenses are too small for the patient to manage insertion without help.

  7. A case of Mac Tel 2 with an unusual sub macular vitelliform lesion.

    Science.gov (United States)

    Lekha, T; Sarwate, Nikit; Sarwate, Renuka

    2015-01-01

    Observational case report describing the clinical, FFA, OCT and mfERG findings in an elderly female patient with atypical features of macular telangiectasia (Mac Tel 2) RESULTS: A 71-year-old lady was detected to have characteristic features of Mac Tel 2 in the left eye (LE) and a yellowish sub macular vitelliform like lesion in the right eye (RE). FFA showed ill defined hyper fluorescence in the RE and telangiectasia and parafoveal leakage typical of Mac Tel 2 in the LE. On OCT RE had hyper reflective clump of echoes subfoveally with an intact RPE and LE had foveal thinning with hypo reflective intraretinal cavities. mfERG responses were normal in the RE and reduced in the LE. During the course of 3 years LE showed natural progression while RE remained unchanged. Structural and functional evaluation of an unusual sub macular vitelliform lesion seen in association with Mac Tel 2 and its course over a period of 3 years is described. The differentiating features of this lesion from adult onset foveomacular vitelliform dystrophy (AFMD) are discussed.

  8. X-82 to Treat Age-related Macular Degeneration

    Science.gov (United States)

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  9. Mitochondrial dysfunction in ataxia-telangiectasia.

    Science.gov (United States)

    Valentin-Vega, Yasmine A; Maclean, Kirsteen H; Tait-Mulder, Jacqueline; Milasta, Sandra; Steeves, Meredith; Dorsey, Frank C; Cleveland, John L; Green, Douglas R; Kastan, Michael B

    2012-02-09

    Ataxia-telangiectasia mutated (ATM) plays a central role in DNA damage responses, and its loss leads to development of T-cell malignancies. Here, we show that ATM loss also leads to intrinsic mitochondrial abnormalities in thymocytes, including elevated reactive oxygen species, increased aberrant mitochondria, high cellular respiratory capacity, and decreased mitophagy. A fraction of ATM protein is localized in mitochondria, and it is rapidly activated by mitochondrial dysfunction. Unexpectedly, allelic loss of the autophagy regulator Beclin-1 significantly delayed tumor development in ATM-null mice. This effect was not associated with rescue of DNA damage signaling but rather with a significant reversal of the mitochondrial abnormalities. These data support a model in which ATM plays direct roles in modulating mitochondrial homeostasis and suggest that mitochondrial dysfunction and associated increases in mitochondrial reactive oxygen species contribute to the cancer-prone phenotype observed in organisms lacking ATM. Thus, ataxia-telangiectasia should be considered, at least in part, as a mitochondrial disease.

  10. Ataxia-telangiectasia: Immunodeficiency and survival.

    Science.gov (United States)

    van Os, Nienke J H; Jansen, Anne F M; van Deuren, Marcel; Haraldsson, Asgeir; van Driel, Nieke T M; Etzioni, Amos; van der Flier, Michiel; Haaxma, Charlotte A; Morio, Tomohiro; Rawat, Amit; Schoenaker, Michiel H D; Soresina, Annarosa; Taylor, Alexander M R; van de Warrenburg, Bart P C; Weemaes, Corry M R; Roeleveld, Nel; Willemsen, Michèl A A P

    2017-05-01

    Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0-17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1-5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7-36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Bilateral maculopathy in a patient with ataxia telangiectasia.

    Science.gov (United States)

    Gioia, Lauren V; Bonsall, Dean; Moffett, Kathryn; Leys, Monique

    2016-02-01

    We report a case of toxoplasmosis with bilateral maculopathy in a 7-year-old boy diagnosed with ataxia telangiectasia (AT) at age 6. AT manifests as ataxia, apraxia, telangiectasia, and dysarthria. Common ophthalmologic findings in AT include fine conjunctival telangiectasia. Patients also suffer from recurrent sinopulmonary infections; however, serious opportunistic infection is rarely diagnosed. At 8 years of age he developed disseminated Toxoplasma gondii (toxoplasmosis) infection and meningoencephalitis. This ophthalmologic finding and the subsequent toxoplasmosis meningoencephalitis have not been previously reported in AT. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  12. Differentiating full thickness macular holes from impending macular holes and macular pseudoholes

    Science.gov (United States)

    Tsujikawa, M.; Ohji, M.; Fujikado, T.; Saito, Y.; Motokura, M.; Ishimoto, I.; Tano, Y.

    1997-01-01

    AIMS—The reliability of scanning laser ophthalmoscope (SLO) microperimetry in differentiating full thickness macular holes from macular pseudoholes and impending macular holes was evaluated.
METHODS—106 eyes with the clinical diagnosis of full thickness macular holes, macular pseudoholes, and impending (stage 1) macular holes were examined for the presence of deep or relative scotoma using SLO microperimetry. The relation between these scotomas and the clinical diagnosis was studied.
RESULTS—Deep and relative scotomas were detected in all 57 eyes with clinically defined full thickness macular holes. In contrast, among 49 eyes diagnosed with macular pseudoholes or impending macular holes, no deep and only one relative scotoma was observed. The sensitivity of the presence of a deep scotoma as an indicator of the clinical diagnosis of a full thickness macular hole was 100% (57 of 57), and the specificity was 100% (49 of 49). The sensitivity of the presence of a relative scotoma was 100% (57 of 57) and the specificity was 98.0% (48 of 49).
CONCLUSION—With SLO microperimetry, full thickness macular holes can be precisely and objectively distinguished from other conditions that mimic macular holes.

 PMID:9059244

  13. Occult Macular Dystrophy

    Directory of Open Access Journals (Sweden)

    Işıl Sayman Muslubaş

    2016-04-01

    Full Text Available Occult macular dystrophy is an inherited macular dystrophy characterized by a progressive decline of bilateral visual acuity with normal fundus appearance, fluorescein angiogram and full-field electroretinogram. This case report presents a 20-year-old female patient with bilateral progressive decline of visual acuity for six years. Her visual acuity was 3-4/10 in both eyes. Anterior segment and fundus examination, fluorescein angiogram and full-field electroretinogram were normal. She could read all Ishihara pseudoisochromatic plates. Fundus autofluorescence imaging was normal. There was a mild central hyporeflectance on fundus infrared reflectance imaging in both eyes. Reduced foveal thickness and alterations of the photoreceptor inner and outer segment junction were observed by optical coherence tomography in both eyes. Central scotoma was also found by microperimetry and reduced central response was revealed by multifocal electroretinogram in both eyes. These findings are consistent with the clinical characteristics of occult macular dystrophy

  14. Efficacy of Intravitreal Bevacizumab in Treatment of Proliferative Type 2 Idiopathic Juxtafoveal Telangiectasia

    Directory of Open Access Journals (Sweden)

    Ökkeş Baz

    2017-06-01

    Full Text Available Objectives: To evaluate the effectiveness of intravitreal bevacizumab (IVB in patients with subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia. Materials and Methods: Ten eyes of 10 patients were included in this retrospective study. All cases were treated with IVB (1.25 mg bevacizumab. Visual acuity and slit-lamp anterior and posterior segment examinations were performed at each visit. Central macular thickness (CMT and intraretinal/subretinal fluid were evaluated via spectral domain optical coherence tomography (OCT. Loss of a line in visual acuity chart and presence of fluid on OCT were defined as criteria for repeated treatment. Results: The mean age of patients was 66.0±7.0 years (56-75. The mean follow-up time was 54.7±16.0 month (24-72. The mean BCVA was 0.62±0.35 (0.00-1.00 logMAR at baseline and 0.54±0.35 (0.00-1.00 logMAR at final exam (p=0.03. The mean CMT was 251±25.4 µm at baseline and 239±39.3 µm at final exam (p=0.01. Patients received an average of 1.7±1.0 IVB injections during follow-up. At baseline, all cases had intraretinal/subretinal fluid. There was no fluid at final examination of all cases. Conclusion: IVB treatment may be effective in the treatment of subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.

  15. Diabetic Macular Edema

    Science.gov (United States)

    Lobo, Conceição; Pires, Isabel; Cunha-Vaz, José

    The optical coherence tomography (OCT), a noninvasive and noncontact diagnostic method, was introduced in 1995 for imaging macular diseases. In diabetic macular edema (DME), OCT scans show hyporeflectivity, due to intraretinal and/or subretinal fluid accumulation, related to inner and/or outer blood-retinal barrier breakdown. OCT tomograms may also reveal the presence of hard exudates, as hyperreflective spots with a shadow, in the outer retinal layers, among others. In conclusion, OCT is a particularly valuable diagnostic tool in DME, helpful both in the diagnosis and follow-up procedure.

  16. Complementation analysis of ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Jaspers, N.G.; Painter, R.B.; Paterson, M.C.; Kidson, C.; Inoue, T.

    1985-01-01

    In a number of laboratories genetic analysis of ataxia-telangiectasia (AT) has been performed by studying the expression of the AT phenotype in fused somatic cells or mixtures of cell-free extracts from different patients. Complementation of the defective response to ionizing radiation was observed frequently, considering four different parameters for radiosensitivity in AT. The combined results from studies on cultured fibroblasts or lymphoblastoid cells from 17 unrelated families revealed the presence of at least four and possibly nine complementation groups. These findings suggest that there is an extensive genetic heterogeneity in AT. More extensive studies are needed for an integration of these data and to provide a set of genetically characterized cell strains for future research of the AT genetic defect.

  17. Pulmonary hypertension in hereditary haemorrhagic telangiectasia

    Institute of Scientific and Technical Information of China (English)

    Veronique; MM; Vorselaars; Sebastiaan; Velthuis; Repke; J; Snijder; Jan; Albert; Vos; Johannes; J; Mager; Martijn; C; Post

    2015-01-01

    Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.

  18. Predominance of null mutations in ataxia-telangiectasia

    NARCIS (Netherlands)

    S. Gilad (Shlomit); R. Khosravi (Rami); D. Shkedy (Dganit); G. Uziel; Y. Ziv (Yael); K. Savitsky (Kinneret); G. Rotman (Galit); S. Smith (Sarah); T. Chessa (Antonio); T.J. Jorgensen (Timothy); R. Harnik (Reli); M. Frydman (Moshe); O. Sanal (Ozden); S. Portnoi (Sima); Z. Goldwicz (Zipora); N.G.J. Jaspers (Nicolaas); A. Gatti (Arianna); G.M. Lenoir (Gilbert); M.F. Lavin (Martin); K. Tatsumi (Kouichi); M. Wegner (Michael); Y. Shiloh (Yosef); A. Bar-Shira (Anat)

    1996-01-01

    textabstractAtaxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative

  19. Quality of life in patients with hereditary haemorrhagic telangiectasia (HHT)

    National Research Council Canada - National Science Library

    Zarrabeitia, Roberto; Fariñas-Álvarez, Concepción; Santibáñez, Miguel; Señaris, Blanca; Fontalba, Ana; Botella, Luisa María; Parra, José Antonio

    2017-01-01

    ... hemorrhagic telangiectasia (HHT), a rare disease in which epistaxis is a cardinal symptom. Purpose To assess the quality of life in a population of Spanish patients with HHT and compare it with the general population...

  20. "ATM Gene Mutations Detection in Iranian Ataxia-Telangiectasia Patients "

    OpenAIRE

    Toshio MiyawakiMohammad Hossein Sanati; Behnaz Bayat; Ahmad Aleyasin; Hasti Atashi Shirazi; "Anna Isaian; Abolhassan Farhoudi; Mostafa Moin

    2004-01-01

    Ataxia-Telangiectasia (AT) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, radiation sensitivity and cancer predisposition. The ATM gene on human chromosome 11q22.3 has recently been identified as the gene responsible for ataxia-telangiectasia (AT). The gene mutated in AT, which has been designated as the ATM gene, encodes a large protein kinase with a PI-3 kinase-related domain. More than 100 mutations are broadly distributed throughout the ATM gene. T...

  1. Dominant cystoid macular dystrophy

    NARCIS (Netherlands)

    Saksens, N.T.M.; Huet, R.A.C. van; Lith-Verhoeven, J.J. van; Hollander, A.I. den; Hoyng, C.B.; Boon, C.J.

    2015-01-01

    OBJECTIVE: To describe the clinical characteristics and long-term follow-up in patients with autosomal dominant cystoid macular dystrophy (DCMD). DESIGN: Retrospective case series. PARTICIPANTS: Ninety-seven patients with DCMD. METHODS: Extensive ophthalmic examination, including visual acuity (VA),

  2. What Is Macular Edema?

    Medline Plus

    Full Text Available ... may be mild to severe, but in many cases, your peripheral (side) vision remains. Macular edema is often a complication of diabetic retinopathy , and is the most common form of vision loss for people with ... Related Studies Show Zika Virus May Cause More Serious Eye ...

  3. [Pathopshysiological mechanisms in macular edema].

    Science.gov (United States)

    Turlea, Cristian; Zolog, Ileana; Blăjan, Codruta; Roşca, C; Turlea, Magdalena; Munteanu, Mihnea; Boruga, Ovidiu

    2014-01-01

    The treatment of diabetic macular edema has known a fast development in the last 5 years where the transition from laser monotherapy to intravitreal pharmacotherapy is becoming standard practice. Intravitreal injections therapy is in a continuous development with promising positive results. The use of intratvitreal devices in the treatment of macular edema of vascular cause has become a viable alternative also in treating diabetic macular edema. Several clinical studies have revealed the superiority of intravitreal treatment versus laser monotherapy. This article is evaluating and reviewing present and future treatments used to combat diabetic macular edema. [corrected].

  4. Unusual and severe disease course in a child with ataxia-telangiectasia.

    NARCIS (Netherlands)

    Meyts, I.; Weemaes, C.M.R.; Wolf-Peeters, C. de; Proesmans, M.; Renard, M.; Uyttebroeck, A.; Boeck, K. de

    2003-01-01

    Ataxia-telangiectasia (AT) is an autosomal recessive syndrome of combined immunodeficiency. Hallmarks of the disease comprise progressive cerebellar ataxia, oculocutaneous telangiectasia, cancer susceptibility and variable humoral and cellular immunodeficiency. We describe a patient with AT presenti

  5. Unusual and severe disease course in a child with ataxia-telangiectasia.

    NARCIS (Netherlands)

    Meyts, I.; Weemaes, C.M.R.; Wolf-Peeters, C. de; Proesmans, M.; Renard, M.; Uyttebroeck, A.; Boeck, K. de

    2003-01-01

    Ataxia-telangiectasia (AT) is an autosomal recessive syndrome of combined immunodeficiency. Hallmarks of the disease comprise progressive cerebellar ataxia, oculocutaneous telangiectasia, cancer susceptibility and variable humoral and cellular immunodeficiency. We describe a patient with AT presenti

  6. [Mosaic forms of ataxia-telangiectasia].

    Science.gov (United States)

    Kuranova, M L; Pleskach, N M; Ledashcheva, T A; Mikhel'son, V M; Spivak, I M

    2014-01-01

    Ataxia-telangiectasia (AT) is a severe hereditary autosomal recessive neurodegenerative disease associated with accelerated aging and caused by mutation in both alleles of atm gene. This gene encodes a key protein of cell response to DNA damage--an ATM protein kinase. Normally, upon formation of DNA double strand breaks ATM is autophosphorylated and its active form phospho-ATM (P-ATM) appears. Here we describe a mosaic form of AT in which cells of the same patient with normal atm gene demonstrated the accumulation of P-ATM in response to DNA double-strand breaks-inducing factors whereas in cells bearing a mutant form of atm P-ATM was not detected. The epigenetic markers such as histone deacetylases SIRT1 and SIRT6, and trimethylated forms of histone H3 - H3K9me3 and H3K27me3--were studied in the nuclei of primary fibroblasts derived from patients with different forms of AT and the increase of SIRT6 level was revealed.

  7. Ataxia telangiectasia: presentation and diagnostic delay.

    Science.gov (United States)

    Devaney, Rebecca; Pasalodos, Sara; Suri, Mohnish; Bush, Andy; Bhatt, Jayesh M

    2017-04-01

    Ataxia telangiectasia (A-T) is a rare progressive, multisystem genetic disease. Families of children with ultra-rare diseases often experience significant diagnostic delays. We reviewed the diagnostic process for A-T in order to identify causes of delay in an attempt to facilitate earlier identification of A-T in the future. A retrospective case note review of 79 children at the National Paediatric A-T clinic seen since May 2009. Data were collected on the nature and age of initial symptoms, the age at first presentation, measurement of alpha feto-protein (AFP) and age of genetic diagnostic confirmation. At presentation, 71 children (90%) had ataxia. The median presentation delay (from first parental concern to presentation) was 8 months (range 0-118 months), and the median diagnostic delay (genetic confirmation of diagnosis) was 12 months (range 1-109 months). There are significant delays in presentation and diagnostic confirmation of A-T. A greater awareness of A-T and early measurement of AFP may help to improve this. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Síndrome de Ataxia-Telangiectasia

    Directory of Open Access Journals (Sweden)

    Amauri Batista da Silva

    1971-06-01

    Full Text Available A ataxia-telangiectasia, doença de Mme. Louis-Bar, é caracterizada pela associação de ataxia cerebelar progressiva, em geral com início na primeira infância, telangiectasas óculo-cutâneas, movimentos coreoatetósicos, tendência a infecções repetidas do sistema respiratório, retardo estaturo-ponderal, demenciação. São mais ou menos freqüentes os tumores do sistema reticuloendotelial. A doença é geralmente familiar, transmitida por genes recessivos, autossômicos, não ligados ao sexo. A alteração bioquímica mais encontrada consiste na diminuição ou ausência completa da fração A das gamaglobulinas, bem como na perturbação das reações de hipersensibilidade retardada. Os AA. relatam o estudo clínico, biológico e pneumencefalográfico de uma criança de 3 anos de idade, apresentando essa enfermidade desde os 18 meses de vida, sem antecedentes familiares.

  9. Ataxia-telangiectasia. (Clinical and immunological aspects).

    Science.gov (United States)

    Boder, E; Sedgwick, R P

    1970-01-01

    This syndrome was defined by the authors in 1947. Earlier publications of similar disease descriptions were by Syllaba and Henner (1926), Louis-Bar (1941). The authors at present have a stock of 253 cases. The cardinal symptoms of this phakomatosis are: Cerebellar ataxia which begin in infancy and take a slowly progressive course. In the late stages free walking and standing are no longer possible. Progressive atactic speech disorders, cerebellar atrophy in the pneumoencephalogram. Slowly progressing symmetrical skin and mucosal telangiectasia in the face and especially on the conjunctivae at the age of 3 to 6 years. Relapsing sinopulmonary infections with a tendency toward the development of bronchiectases. Apraxia of eye movements. Atrophy of facial skin and premature graying of hair. Recessively hereditary disorder with a high familial manifestation. This syndrome combines the spinocerebellar degeneration, phakomatoses, and infantile dementia processes. Such other conditions as abnormity or absence of thymus, reduction in gamma globulins, amino-aciduria, autosomal-recessive inheritance suggest a genetically determined "error of metabolism".

  10. Ataxia-telangiectasia presenting with a novel immunodeficiency.

    Science.gov (United States)

    Perreault, Sébastien; Bernard, Geneviève; Lortie, Anne; Le Deist, Françoise; Decaluwe, Hélène

    2012-05-01

    Ataxia-telangiectasia is a rare autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, and variable degrees of immunodeficiency. Immunologic evaluations of affected patients often reveal anomalies of humoral and cell-mediated immunity. We describe a case of ataxia-telangiectasia with an atypical immunodeficiency and a novel mutation in the ATM gene. The patient presented at age 3 years with a perineal cellulitis associated with profound neutropenia and T-cell lymphopenia. Serum immunoglobulin levels and antibody titers were normal. Neurologic evaluation revealed minimal hypotonia and wide-based gait, without other signs of cerebellar dysfunction. The alpha-fetoprotein level was elevated, and molecular genetic testing confirmed the diagnosis of ataxia-telangiectasia, uncovering a novel ATM gene mutation c.3931C>T (p.Gln1311X) in exon 28. This patient presents a unique immunologic pattern with normal immunoglobulin levels, significant lymphopenia, and profound neutropenia. The diagnosis of ataxia-telangiectasia should be considered in children presenting with gait disorder and immunologic defects, regardless of subtype and severity. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Macular pigment and fixation after macular translocation surgery

    NARCIS (Netherlands)

    Reinhard, Jens; Kanis, Martijn J.; Berendschot, Tos T. J. M.; Schoen, Christiane; Gelisken, Faik; Trauzettel-Klosinski, Susanne; Bartz-Schmidt, Karl U.; Zrenner, Eberhart

    2010-01-01

    Background After full macular translocation (MT) surgery with 3608 retinotomy, the fovea is rarely identifiable. Our aim was to verify the position of the fovea, to determine how patients fixate after MT and to examine distribution and optical density of macular pigment ( MP). Methods 9 patients aft

  12. Hereditary haemorrhagic telangiectasia: a cause of preventable morbidity and mortality.

    LENUS (Irish Health Repository)

    Brady, A P

    2012-01-31

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition whose effects are mediated through deficient blood vessel formation and regeneration, with multisystem involvement. Patients are usually aware of resulting skin telangiectasia and epistaxis, but are also exposed to dangers posed by occult vascular malformations in other organs. About 15-35% of HHT patients have pulmonary AVMs (PAVMs), 10% have cerebral AVMs (CAVMs), 25-33% suffer significant GI blood loss from GI tract telangiectasia, and an unknown but high percentage have liver involvement. In total, 10% of affected individuals die prematurely or suffer major disability from HHT, largely because of bleeding from CAVMs and PAVMs, or paradoxical embolization through PAVMs. Screening for and early intervention to treat occult PAVMs and CAVMs can largely eliminate these risks, and should be undertaken in a specialist centre. The National HHT Center in The Mercy University Hospital in Cork is the referral centre for HHT screening in Ireland.

  13. Results of an electronic mail survey on hormones and telangiectasias.

    Science.gov (United States)

    Ricci, Stefano

    2005-02-01

    The relationship between the development of telangiectasias and hormonal intake has not been well studied and is empirically managed by phlebologists. To understand the behavior of the international phlebologic community regarding the treatment of leg telangiectasia in patients taking oral contraceptives or receiving postmenopausal hormone replacement therapy. Simple questions concerning the causal effects of hormones, their influence on treatment, and general behavior were asked by an electronic mail questionnaire sent to 131 phlebologists in my personal database. The 61 answers received show the existence of two opposite "parties" concerning the influence of hormones on telangiectasia: cause and treatment. Opposite opinions without any scientific basis underline the ignorance surrounding a subject that concerns 50% of our patients.

  14. Genetics Home Reference: age-related macular degeneration

    Science.gov (United States)

    ... Resources (3 links) BrightFocus Foundation: Macular Degeneration Treatment Macular Degeneration Partnership: Low Vision Rehabilitation Prevent Blindness America: Age-Related Macular Degeneration (AMD) ...

  15. Hereditary benign telangiectasia without family history in China

    Institute of Scientific and Technical Information of China (English)

    CAI Lin; SUN Qing-miao; ZANG Dong-jie; ZHANG Jian-zhong

    2011-01-01

    A case of hereditary benign telangiectasia without family history was reported. A 39-year-old woman presented with small and tiny telangiectases on the face, neck, upper trunk and forearms at birth. The numbers and sizes of the lesions increased gradually and she had no hemorrhagic diathesis and systemic diseases. No similar patients were found in her family. Upon physical examination, telangiectases were found on the face, neck, upper trunk and forearms; and a telangiectatic erythema was found on the right forearm 25 mm ×40 mm in size. Histopathology examination showed a normal epidermis and dilation of the capillaries at upper dermis. Hereditary benign telangiectasia without family history was diagnosed.

  16. [Pathogenic Genes of A Hereditary Hemorrhagic Telangiectasia Pedigree].

    Science.gov (United States)

    Cheng, Xiao-Hui; Tu, Chuan-Qing; Sun, Shun-Chang; Li, Jan-Yun; Zhang, Xu-Yan; Wang, Dian-Wen; Huang, Can

    2015-08-01

    To identify the mutation of ENG and ALK1 genes in a hereditary hemorrhagic telangiectasia pedigree. 14 exons of ENG gene and 9 exons of ALK1 gene in 11 menbers of this pedigree 4 generation were amplified by reverse transcription-polymerase chain reaction (RT-PCR), the PCR products were screened by direct sequencing. A nonsense mutation c.447G > A was found in exon 4 of ENG gen of the pedigreee, resulting in change of Trp 149 into Stop, while no gene mutation was found in ALK1 gene. The hereditary hemorrhagic telangiectasia in this pedigree is caused by the nonsense mutation c.447G > A in ENG gene.

  17. Non-foveal macular holes after PPV for macular pucker

    Directory of Open Access Journals (Sweden)

    Abo EL Enin Mostafa

    2010-01-01

    Full Text Available Purpose: To describe six patients (six eyes who developed an eccentric macular hole after surgery for idiopathic epimacular proliferation. Materials and Methods: Review of records from six patients who developed eccentric macular holes postoperatively following vitrectomy in 107 consecutive cases with peeling of the epimacular proliferation and internal limiting membrane (ILM from June 2004 to January 2009, Results: Eccentric macular holes were developed from nine days to eight months (mean, 3.1 months after epimacular proliferation peeling. The ILM was peeled in addition to the epimacular proliferation in five of the six cases. Of the six eccentric macular holes, four were located temporal to the fovea, one was located superior to the fovea, and one was located nasal to the fovea. Final visual acuities after a mean follow-up period of 17.3 months were 20/20 in two eyes, 20/25 in one eye, 20/40 in two eyes, and 5/200 in one eye. The eye with the eccentric macular hole nasal to the fovea had the poorest final visual acuity of 5/200. Conclusion: Eccentric macular holes occurring after vitrectomy to remove epimacular proliferation is an uncommon postoperative finding. Various explanations have been suggested for the etiology of these holes, but there is no consensus. We suggested that the ILM tear should be initiated with a diamond dusted knife to reduce the likelihood of injury to the underlying Muller cells that may contribute to the formation of eccentric macular holes.

  18. Altered corticomotor-cerebellar integrity in young ataxia telangiectasia patients.

    Science.gov (United States)

    Sahama, Ishani; Sinclair, Kate; Fiori, Simona; Pannek, Kerstin; Lavin, Martin; Rose, Stephen

    2014-09-01

    Magnetic resonance imaging (MRI) research in identifying altered brain structure and function in ataxia-telangiectasia, an autosomal recessive neurodegenerative disorder, is limited. Diffusion-weighted MRI were obtained from 11 ataxia telangiectasia patients (age range, 7-22 years; mean, 12 years) and 11 typically developing age-matched participants (age range, 8-23 years; mean, 13 years). Gray matter volume alterations in patients were compared with those of healthy controls using voxel-based morphometry, whereas tract-based spatial statistics was employed to elucidate white matter microstructure differences between groups. White matter microstructure was probed using quantitative fractional anisotropy and mean diffusivity measures. Reduced gray matter volume in both cerebellar hemispheres and in the precentral-postcentral gyrus in the left cerebral hemisphere was observed in ataxia telangiectasia patients compared with controls (P ataxia telangiectasia patients along with white matter tract degeneration projecting from the cerebellum into corticomotor regions. The lack of cortical involvement may reflect early-stage white matter motor pathway degeneration within young patients. © 2014 International Parkinson and Movement Disorder Society.

  19. ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

    NARCIS (Netherlands)

    Bhatt, J.M.; Bush, A.; Gerven, M.; Nissenkorn, A.; Renke, M.; Yarlett, L.; Taylor, M.; Tonia, T.; Warris, A.; Zielen, S.; Zinna, S.; Merkus, P.J.F.M.

    2015-01-01

    Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immu

  20. Clinical spectrum of ataxia-telangiectasia in adulthood.

    NARCIS (Netherlands)

    Verhagen, M.M.; Abdo, W.; Willemsen, M.A.A.P.; Hogervorst, F.B.L.; Smeets, D.F.C.M.; Hiel, J.A.P.; Brunt, E.R.; Rijn, M.A. van; Majoor Krakauer, D.; Oldenburg, R.A.; Broeks, A.; Last, J.I.; Veer, L.J. van 't; Tijssen, M.A.; Dubois, A.M.; Kremer, H.P.H.; Weemaes, C.M.R.; Taylor, A.M.; Deuren, M. van

    2009-01-01

    OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the

  1. Clinical spectrum of ataxia-telangiectasia in adulthood

    NARCIS (Netherlands)

    Verhagen, M. M. M.; Abdo, W. F.; Willemsen, M. A. A. P.; Hogervorst, F. B. L.; Smeets, D. F. C. M.; Hiel, J. A. P.; Brunt, E. R.; van Rijn, M. A.; Krakauer, D. Majoor; Oldenburg, R. A.; Broeks, A.; Last, J. I.; van't Veer, L. J.; Tijssen, M. A. J.; Dubois, A. M. I.; Kremer, H. P. H.; Weemaes, C. M. R.; Taylor, A. M. R.; van Deuren, M.

    2009-01-01

    Objective: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. Methods: Retrospective analysis of the

  2. Clinical spectrum of ataxia-telangiectasia in adulthood.

    NARCIS (Netherlands)

    Verhagen, M.M.; Abdo, W.; Willemsen, M.A.A.P.; Hogervorst, F.B.L.; Smeets, D.F.C.M.; Hiel, J.A.P.; Brunt, E.R.; Rijn, M.A. van; Majoor Krakauer, D.; Oldenburg, R.A.; Broeks, A.; Last, J.I.; Veer, L.J. van 't; Tijssen, M.A.; Dubois, A.M.; Kremer, H.P.H.; Weemaes, C.M.R.; Taylor, A.M.; Deuren, M. van

    2009-01-01

    OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the

  3. Clinical spectrum of ataxia-telangiectasia in adulthood

    NARCIS (Netherlands)

    Verhagen, M M M; Abdo, W F; Willemsen, M A A P; Hogervorst, F B L; Smeets, D F C M; Hiel, J A P; Brunt, E R; van Rijn, M A; Majoor Krakauer, D; Oldenburg, R A; Broeks, A; Last, J I; van't Veer, L J; Tijssen, M A J; Dubois, A M I; Kremer, H P H; Weemaes, C M R; Taylor, A M R; van Deuren, M

    2009-01-01

    OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the

  4. Clinical spectrum of ataxia-telangiectasia in adulthood

    NARCIS (Netherlands)

    Verhagen, M M M; Abdo, W F; Willemsen, M A A P; Hogervorst, F B L; Smeets, D F C M; Hiel, J A P; Brunt, E R; van Rijn, M A; Majoor Krakauer, D; Oldenburg, R A; Broeks, A; Last, J I; van't Veer, L J; Tijssen, M A J; Dubois, A M I; Kremer, H P H; Weemaes, C M R; Taylor, A M R; van Deuren, M

    2009-01-01

    OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the

  5. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Kjeldsen, J

    2000-01-01

    Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population....

  6. Disorders of Upper Limb Movements in Ataxia-Telangiectasia.

    Directory of Open Access Journals (Sweden)

    Aasef G Shaikh

    Full Text Available Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task, while arms were outstretched (postural task, and at rest. Almost all ataxia-telangiectasia subjects (79/80 had abnormal involuntary movements, such as rhythmic oscillations (tremor, slow drifts (dystonia or athetosis, and isolated rapid movements (dystonic jerks or myoclonus. All patients with involuntary movements had both kinetic and postural tremor, while 48 (61% also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia.

  7. Age-Related Macular Degeneration

    Science.gov (United States)

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  8. Telangiectasia nevoide unilateral adquirida em homem hígido Acquired unilateral nevoid telangiectasia in a healthy men

    Directory of Open Access Journals (Sweden)

    Juliana Merheb Jordão

    2010-12-01

    Full Text Available A Telangiectasia Nevoide Unilateral é uma dermatose vascular rara, caracterizada por áreas de telangiectasia superficial, em uma distribuição linear unilateral, descrita, em 1899, por Zeisler e Blaschko. Diversas teorias foram desenvolvidas para explicar sua etiopatogenia, sendo a provável (e a mais fundamentada a relação com elevação dos níveis de estrogênio. Há duas formas: a congênita e a adquirida. Esta, geralmente, se relaciona a hepatopatias, em pacientes do sexo masculino. Em homens hígidos, a ocorrência da forma adquirida é rara, com poucos relatos na literatura, sendo sua causa desconhecida. Este trabalho tem como objetivo relatar um caso de telangiectasia nevoide unilateral adquirida em homem jovem, sem comorbidades, alterações clínicas e/ou laboratoriais sugestivas de hiperestrogenismo.Unilateral nevoid telangiectasia is a rare vascular dermatosis, characterized by areas of superficial telangiectases distributed in a linear unilateral pattern. It was described in 1899 by Zeisler and Blascko. Several theories where developed in order to explain its etiopathogenesis. The most widely accepted is the one which establishes its probable association with an increase in the estrogen levels. There are two types: congenital and acquired. The latter is associated with hepatopathies in male patients. The acquired form is rarely observed in healthy men, with a few cases reported in the medical literature, and its etiology is unknown. This study reports the case of a healthy young man with acquired unilateral nevoid telangiectasia, without any comorbidities, clinical and /or laboratory findings indicative of hyperestrogenism.

  9. Current status in diabetic macular edema treatments

    National Research Council Canada - National Science Library

    Pedro Romero-Aroca

    2013-01-01

    ... status.The photocoagulation laser is currently restricted to focal macular edema in some countries,but due the high cost of intravitreal drugs,the use of laser treatment for focal and diffuse diabetic macular edema(DME...

  10. Facts about Age-Related Macular Degeneration

    Science.gov (United States)

    ... Degeneration (AMD) > Facts About Age-Related Macular Degeneration Facts About Age-Related Macular Degeneration This information was ... an Eye Care Professional Last Reviewed: September 2015 Fact Sheet Blurb The National Eye Institute (NEI) is ...

  11. Variation in Telangiectasia Predisposing Genes Is Associated With Overall Radiation Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Tanteles, George A. [Department of Genetics, University of Leicester, Leicester (United Kingdom); Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester (United Kingdom); Murray, Robert J.S. [Department of Genetics, University of Leicester, Leicester (United Kingdom); Mills, Jamie [Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester (United Kingdom); Barwell, Julian [Department of Genetics, University of Leicester, Leicester (United Kingdom); Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester (United Kingdom); Chakraborti, Prabir [Department of Clinical Oncology, Derby Hospitals NHS Foundation Trust, Derby (United Kingdom); Chan, Steve [Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham (United Kingdom); Cheung, Kwok-Leung [Division of Breast Surgery, University of Nottingham, Nottingham (United Kingdom); Ennis, Dawn [Department of Clinical Oncology, Derby Hospitals NHS Foundation Trust, Derby (United Kingdom); Khurshid, Nazish [Department of Genetics, University of Leicester, Leicester (United Kingdom); Lambert, Kelly [Department of Breast Surgery, University Hospitals of Leicester, Glenfield Hospital, Leicester (United Kingdom); Machhar, Rohan; Meisuria, Mitul [Department of Genetics, University of Leicester, Leicester (United Kingdom); Osman, Ahmed; Peat, Irene [Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester (United Kingdom); Sahota, Harjinder [Department of Genetics, University of Leicester, Leicester (United Kingdom); Woodings, Pamela [Department of Clinical Oncology, Derby Hospitals NHS Foundation Trust, Derby (United Kingdom); Talbot, Christopher J., E-mail: cjt14@le.ac.uk [Department of Genetics, University of Leicester, Leicester (United Kingdom); and others

    2012-11-15

    Purpose: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. Methods and Materials: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were within the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. Results: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. Conclusions: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects.

  12. UNILATERAL RETINAL VASCULAR MALFORMATION IN HEREDITARY HEMORRHAGIC TELANGIECTASIA

    Directory of Open Access Journals (Sweden)

    Ananth Bhandary

    2014-07-01

    Full Text Available Hereditary hemorrhagic telangeiectasia (HHT is an autosomal dominant genetic disorder that leads to vascular malformations. It was first recognized in the 19th century as a familial disorder with abnormal vascular structures causing bleeding from the nose and gastrointestinal tract. HHT is characterized by telangiectatic lesions of the nose, lips, lungs, brain, and spinal cord. The reported incidence in Europe and Japan is between 1:5000 and 1:8000; but is widely variable in other regions. It is seen more frequently in whites. Ocular involvement has been reported in patients with HHT. Although conjunctival telangiectasia is the most common manifestation, rarely intraocular vascular lesions such as retinal telangiectasia and arteriovenous malformations in the retina, are seen. We describe a patient with HHT who had an abnormal unilateral retinal vascular abnormality along with tortuous conjunctival vasculature in the other eye, which has not been reported till date

  13. 14th International Workshop on Ataxia-Telangiectasia ATW2012.

    Science.gov (United States)

    Pandita, Tej K

    2012-10-01

    The fourteenth international Ataxia-Telangiectasia Workshop 2012 (ATW2012) (www.atw2012.com) on ataxia-telangiectasia (AT) and the role of the ataxia telangiectasia mutated (ATM) gene in DNA repair, neurological disease, cancer and related topics was held from February 07 to 11, 2012 in Delhi, India. The international ATW2012 meeting reported the latest advances in ATM research as well as potential therapeutic treatments for A-T. The meeting was attended by a productive mix of scientists, ranging from those prominent in the initial characterization of the underlying genetic defect to young scientists just entering the field. In broad terms, three main themes were discussed at the meeting: first, a wealth of new details emerged on DNA damage signaling/repair mechanisms for which ATM is a critical element; secondly, important functions for ATM in previously unrelated cellular pathways were identified; and thirdly, new physiological effects and potential therapeutic treatments related to A-T were presented. This report summarizes below a sampling of the many interesting results from the meeting. Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  14. Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.

    Science.gov (United States)

    Huang, Yu; Yang, Lu; Wang, Jianchun; Yang, Fan; Xiao, Ying; Xia, Rongjun; Yuan, Xianhou; Yan, Mingshan

    2013-09-01

    Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized mainly by progressive cerebellar ataxia, oculocutaneous telangiectasia, and immunodeficiency. This disease is caused by mutations of the ataxia telangiectasia mutated (Atm) gene. More than 500 Atm mutations that are responsible for A-T have been identified so far. However, there have been very few A-T cases reported in China, and only two Chinese A-T patients have undergone Atm gene analysis. In order to systemically investigate A-T in China and map their Atm mutation spectrum, we recruited eight Chinese A-T patients from six unrelated families nationwide. Using direct sequencing of genomic DNA and the multiplex ligation-dependent probe amplification, we identified twelve pathogenic Atm mutations, including one missense, four nonsense, five frameshift, one splicing, and one large genomic deletion. All the Atm mutations we identified were novel, and no homozygous mutation and founder-effect mutation were found. These results suggest that Atm mutations in Chinese populations are diverse and distinct largely from those in other ethnic areas.

  15. Ataxia-telangiectasia: some historic, clinical and pathologic observations.

    Science.gov (United States)

    Boder, E

    1975-01-01

    Although an isolated clinical case report was published in 1926 and another in 1941, ataxia-telangiectasia (A-T) was not established as a distinct entity until 1957, when it was first delineated clinicopathologically. Susceptibility to sinopulmonary infection was identified as the main cause of death and as the third major component of the syndrome; its heredofamilial nature was documented, and it was designated "ataxia-telangiectasia." In a later review of 101 published cases, lymphoreticular malignancy emerged as the second most frequent cause of death. Although the thymus was found to be absent in the first reported autopsy in 1957 and the serum IgA deficiency was first recorded in 1961, A-T was not established as an immunodeficiency disease until 1963. Thymic abnormality and dysgammaglobulinemia explain the 2 main causes of death, sinopulmonary and neoplastic, but the immunodeficiency is probably not the central defect. It does not appear to explain either of the 2 main clinical diagnostic keys, the ataxia and the telangiectasia, or any of the other seemingly unrealted multisystemic facets of this complex disorder. Some of our most provocative long-term clinical observations and recent pathologic findings in our series of 9 autopsies are discussed.

  16. Nonalcoholic Steatohepatitis in a Patient with Ataxia-Telangiectasia

    Directory of Open Access Journals (Sweden)

    Trinidad Caballero

    2014-01-01

    Full Text Available Ataxia-telangiectasia (A-T is a rare disease characterized by neurodegenerative alterations, telangiectasia, primary immunodeficiency, extreme sensitivity to radiation, and susceptibility to neoplasms. A-T patients have inactivation of ataxia-telangiectasia-mutated (ATM protein, which controls DNA double-strand break repair and is involved in oxidative stress response, among other functions; dysfunctional control of reactive oxygen species may be responsible for many of the clinical manifestations of this disease. To the best of our knowledge, hepatic lesions of steatohepatitis have not previously been reported in A-T patients. The present study reports the case of a 22-year-old man diagnosed with A-T at the age of 6 years who was referred to our Digestive Disease Unit with a three-year history of hyperlipidemia and liver test alterations. Core liver biopsy showed similar lesions to those observed in nonalcoholic steatohepatitis. Immunohistochemical staining disclosed the absence of ATM protein in hepatocyte nuclei. We suggest that the liver injury may be mainly attributable to the oxidative stress associated with ATM protein deficiency, although other factors may have made a contribution. We propose the inclusion of A-T among the causes of nonalcoholic steatohepatitis, which may respond to antioxidant therapy.

  17. [Age related macular degeneration].

    Science.gov (United States)

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  18. Different treatment modalities for choroidal neovascularization in two eyes of one patient with bilateral type 2A parafoveal telangiectasia

    Directory of Open Access Journals (Sweden)

    Vivek Dave

    2013-01-01

    Full Text Available A 60-year-old diabetic man presented with a history of decrease in vision in both eyes since 2 weeks. At presentation, best corrected visual acuity (BCVA in the right eye (RE was 20/30 and that in the left eye (LE was 20/80. The right fundus revealed a grayish reflex, yellowish crystalline deposits and retinal pigment epithelial hyperplasia at the macula. The left fundus showed subretinal fluid and temporal subretinal hemorrhage near a grayish reflex at the macula. A diagnosis in both eyes of idiopathic macular telangiectasia (IMT type 2A with RE stage 4 and LE stage 5, choroidal neovascularization (CNVM was made. The patient was treated with photodynamic therapy (PDT in LE. The visual acuity improved to 20/40 over the next 6 months. At a 4-year follow-up, he developed decreased vision in RE diagnosed as IMT with CNV and was treated with intravitreal ranibizumab. At 6-month follow-up post injection, the vision was 20/40p.

  19. Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study

    Directory of Open Access Journals (Sweden)

    Ishani Sahama

    2015-01-01

    Conclusions: Whole tract analysis of the corticomotor, corticospinal and somatosensory pathways in ataxia telangiectasia showed significant white matter degeneration along the entire length of motor circuits, highlighting that ataxia–telangiectasia gene mutation impacts the cerebellum and multiple other motor circuits in young patients.

  20. Ataxia-telangiectasia - A historical review and a proposal for a new designation: ATM syndrome.

    Science.gov (United States)

    Teive, Hélio A G; Moro, Adriana; Moscovich, Mariana; Arruda, Walter O; Munhoz, Renato P; Raskin, Salmo; Ashizawa, Tetsuo

    2015-08-15

    The authors review ataxia telangiectasia, emphasizing historical aspects, genetic discoveries, and the clinical presentations of the classical and atypical forms. In fact, ataxia telangiectasia represents a multisystem entity with pleomorphic neurological and systemic manifestations. ATM syndrome is proposed as a more adequate designation for this entity. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Ataxia telangiectasia and Nijmegen breakage syndrome : neurological, immunological and genetic aspects

    NARCIS (Netherlands)

    Hiel, J.A.P.

    2004-01-01

    Ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) are rare autosomal recessive conditions caused by mutations in respectively ATM and NBS1. The encoding proteins ATM and nibrin are involved in the processing of DNA damage and maintenance of genomic stability. Ataxia telangiectasia is d

  2. ATAXIA - TELANGIECTASIA – A HISTORICAL REVIEW AND A PROPOSAL FOR A NEW NAME: ATM SYNDROME

    Science.gov (United States)

    Teive, Hélio A. G.; Moro, Adriana; Moscovich, Mariana; Munhoz, Renato P.; Ashizawa, Tetsuo

    2016-01-01

    The authors review ataxia telangiectasia, emphasizing historical aspects, genetic discoveries and the clinical presentations of the classical and atypical forms. Our conclusion is that the term ataxia telangiectasia is a misnomer because it represents a multisystem entity with pleomorphic neurological and systemic manifestations. ATM syndrome is proposed as a more adequate designation for this entity. PMID:26050521

  3. Ataxia-telangiectasia patients presenting with hyper-IgM syndrome.

    NARCIS (Netherlands)

    Noordzij, J.G.; Wulffraat, N.M.; Haraldsson, A.; Meyts, I.; Veer, L.J. van 't; Hogervorst, F.B.L.; Warris, A.; Weemaes, C.M.R.

    2009-01-01

    Ataxia-telangiectasia (A-T) is characterised by progressive neurological abnormalities, oculocutaneous telangiectasias and immunodeficiency (decreased serum IgG subclass and/or IgA levels and lymphopenia). However, 10% of A-T patients present with decreased serum IgG and IgA with normal or raised Ig

  4. Ataxia telangiectasia and Nijmegen breakage syndrome : neurological, immunological and genetic aspects

    NARCIS (Netherlands)

    Hiel, J.A.P.

    2004-01-01

    Ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) are rare autosomal recessive conditions caused by mutations in respectively ATM and NBS1. The encoding proteins ATM and nibrin are involved in the processing of DNA damage and maintenance of genomic stability. Ataxia telangiectasia is d

  5. Benign concentric annular macular dystrophy

    Directory of Open Access Journals (Sweden)

    Luísa Salles de Moura Mendonça

    2015-06-01

    Full Text Available The purpose of the authors is to show clinical findings of a patient with benign concentric annular macular dystrophy, which is an unusual condition, and part of the "bull’s eye" maculopathy differential diagnosis. An ophthalmologic examination with color perception, fluorescein angiography, and ocular electrophysiology was performed.

  6. Mechanisms of Non-canonical Activation of Ataxia Telangiectasia Mutated.

    Science.gov (United States)

    Khoronenkova, S V

    2016-12-01

    ATM is a master regulator of the cellular response to DNA damage. The classical mechanism of ATM activation involves its monomerization in response to DNA double-strand breaks, resulting in ATM-dependent phosphorylation of more than a thousand substrates required for cell cycle progression, DNA repair, and apoptosis. Here, new experimental evidence for non-canonical mechanisms of ATM activation in response to stimuli distinct from DNA double-strand breaks is discussed. It includes cytoskeletal changes, chromatin modifications, RNA-DNA hybrids, and DNA single-strand breaks. Noncanonical ATM activation may be important for the pathology of the multisystemic disease Ataxia Telangiectasia.

  7. Ataxia telangiectasia, Menkes kinky hair disease and neurocutaneous melanosis.

    Science.gov (United States)

    Caccavale, Stefano; Bove, Domenico; Bove, Rocco M; LA Montagna, Maddalena

    2017-02-01

    This article explores three neurocutaneous syndromes (NCSs), i.e. genetic disorders producing developmental abnormalities of the skin and an increased risk of neurological complications. In this review, different aspects of ataxia telangiectasia, Menkes kinky hair disease and neurocutaneous melanosis are examined: clinical features, genetic defect, mutation spectrum, pathogenesis, and neurobiological basis; indications for clinical practice are also provided to the readers. The aim of this review is to stress the importance of cooperation among dermatologists, neurologists and psychiatrists, in order to provide patients suffering from these diseases with timely diagnosis and targeted treatments.

  8. Did Robert Louis Stevenson have hereditary hemorrhagic telangiectasia?

    Science.gov (United States)

    Guttmacher, A E; Callahan, J R

    2000-03-06

    Chronic illness played a major role in the life and literary success of Robert Louis Stevenson. However, the exact nature of his chronic illness remains unclear. It is possible that Stevenson had hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber Syndrome). This would explain his chronic respiratory complaints, recurrent episodes of pulmonary hemorrhage, and his death, at age 44 years, of probable cerebral hemorrhage. It would also explain his mother's hitherto unreported but apparent stroke, at age 38 years. Further support for this hypothesis might come from new details about the health of Stevenson and his relatives or from molecular analysis of tissue specimens remaining from him.

  9. Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene

    Science.gov (United States)

    Staples, E R; McDermott, E M; Reiman, A; Byrd, P J; Ritchie, S; Taylor, A M R; Davies, E G

    2008-01-01

    Immunodeficiency affects over half of all patients with ataxia telangiectasia (A-T) and when present can contribute significantly to morbidity and mortality. A retrospective review of clinical history, immunological findings, ataxia telangiectasia mutated (ATM) enzyme activity and ATM mutation type was conducted on 80 consecutive patients attending the National Clinic for Ataxia Telangiectasia, Nottingham, UK between 1994 and 2006. The aim was to characterize the immunodeficiency in A-T and determine its relationship to the ATM mutations present. Sixty-one patients had mutations resulting in complete loss of ATM kinase activity (group A) and 19 patients had leaky splice or missense mutations resulting in residual kinase activity (group B). There was a significantly higher proportion of patients with recurrent sinopulmonary infections in group A compared with group B (31 of 61 versus four of 19 P = 0·03) and a greater need for prophylactic antibiotics (30 of 61 versus one of 19 P = 0·001). Comparing group A with group B patients, 25 of 46 had undetectable/low immunoglobulin A (IgA) levels compared with none of 19; T cell lymphopenia was found in 28 of 56 compared with one of 18 and B cell lymphopenia in 35 of 55 compared with four of 18 patients (P = 0·00004, 0·001 and 0·003 respectively). Low IgG2 subclass levels and low levels of antibodies to pneumococcal polysaccharide were more common in group A than group B (16 of 27 versus one of 11 P = 0·01; 34/43 versus six of 17 P = 0·002) patients. Ig replacement therapy was required in 10 (12·5%) of the whole cohort, all in group A. In conclusion, A-T patients with no ATM kinase activity had a markedly more severe immunological phenotype than those expressing low levels of ATM activity. PMID:18505428

  10. Navigated macular laser decreases retreatment rate for diabetic macular edema: a comparison with conventional macular laser

    Directory of Open Access Journals (Sweden)

    Neubauer AS

    2013-01-01

    Full Text Available Aljoscha S Neubauer,1,* Julian Langer,1,* Raffael Liegl,1 Christos Haritoglou,1 Armin Wolf,1 Igor Kozak,2 Florian Seidensticker,1 Michael Ulbig,1 William R Freeman,2 Anselm Kampik,1 Marcus Kernt,1 1Ludwig-Maximilians University, Department of Ophthalmology, Munich, Germany; 2Jacobs Retina Center, University of California San Diego, La Jolla, CA, USA*These authors contributed equally to this workBackground: The purpose of this study was to evaluate and compare clinical outcomes and retreatment rates using navigated macular laser versus conventional laser for the treatment of diabetic macular edema (DME.Methods: In this prospective, interventional pilot study, 46 eyes from 46 consecutive patients with DME were allocated to receive macular laser photocoagulation using navigated laser. Best corrected visual acuity and retreatment rate were evaluated for up to 12 months after treatment. The control group was drawn based on chart review of 119 patients treated by conventional laser at the same institutions during the same time period. Propensity score matching was performed with Stata, based on the nearest-neighbor method.Results: Propensity score matching for age, gender, baseline visual acuity, and number of laser spots yielded 28 matched patients for the control group. Visual acuity after navigated macular laser improved from a mean 0.48 ± 0.37 logMAR by a mean +2.9 letters after 3 months, while the control group showed a mean −4.0 letters (P = 0.03. After 6 months, navigated laser maintained a mean visual gain of +3.3 letters, and the conventional laser group showed a slower mean increase to +1.9 letters versus baseline. Using Kaplan-Meier analysis, the laser retreatment rate showed separation of the survival curves after 2 months, with fewer retreatments in the navigated group than in the conventional laser group during the first 8 months (18% versus 31%, respectively, P = 0.02.Conclusion: The short-term results of this pilot study suggest

  11. Precursors of Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Linneberg, Allan; Larsen, Michael

    2013-01-01

    by questionnaire. Digital grayscale fundus photographs were recorded in red-free illumination and graded for the presence of macular drusen >63µm in either eye and the presence of 20 or more small, hard macular drusen as a mean of both eyes. RESULTS: Macular drusen >63µm were associated with the level of physical...... macular drusen per eye. These findings support that a physically active, heart-healthy lifestyle prevents the earliest manifestation of AMD.......PURPOSE: To investigate associations of small, hard macular drusen and larger macular drusen with obesity-related risk factors. METHODS: Cross-sectional study of 888 subjects aged 30-60 years characterized using anthropometric measurements and blood sample analyses. Physical activity was assessed...

  12. Myoclonic axial jerks for diagnosing atypical evolution of ataxia telangiectasia.

    Science.gov (United States)

    Nakayama, Tojo; Sato, Yuko; Uematsu, Mitsugu; Takagi, Masatoshi; Hasegawa, Setsuko; Kumada, Satoko; Kikuchi, Atsuo; Hino-Fukuyo, Naomi; Sasahara, Yoji; Haginoya, Kazuhiro; Kure, Shigeo

    2015-03-01

    Ataxia telangiectasia (A-T) is a common inherited cause of early childhood-onset ataxia, distinguished by progressive cerebellum malfunction, capillary vessel extension, and immunodeficiency. The diagnosis of A-T is sometimes difficult to establish in patients with atypical clinical evolution. We experienced a pediatric 12-years-old female patient, who was finally diagnosed with classic A-T, demonstrating progressive dystonic-myoclonic axial jerks with ataxia as a predominant clinical feature. Oculocutaneous telangiectasias and immune status were unremarkable. Her myoclonic jerks were spontaneous or stimulus-sensitive, and partially ameliorated by levodopa treatment, but the ataxia was slowly progressive. A laboratory examination showed moderate atrophy of the vermis and cerebellum on brain magnetic resonance imaging, elevated serum alpha fetoprotein (AFP) levels, and total absence of A-T mutated (ATM) protein activity. We subsequently confirmed compound heterozygous truncating mutations of the ATM gene in this patient. Our findings highlight the importance of recognizing dystonic-myoclonic jerks as one of the extrapyramidal signs of classic A-T. Measurement of AFP levels should be considered in patients with unexplained myoclonic jerk movements with ataxia in whom definitive diagnoses are not identified. Physicians should be aware that there are cases where typical findings of A-T may not be fulfilled. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  13. Longitudinal analysis of the neurological features of ataxia-telangiectasia.

    Science.gov (United States)

    Jackson, Thomas J; Chow, Gabriel; Suri, Mohnish; Byrd, Philip; Taylor, Malcolm R; Whitehouse, William P

    2016-07-01

    To assess the relationship between genotype and neurological progression in ataxia-telangiectasia (A-T). Clinical and laboratory data were extracted retrospectively from the records of patients attending the UK National Ataxia-Telangiectasia Clinic. Neurological assessments were performed using the A-T Index (Crawford Score) and the A-T Neurological Examination Scale Toolkit (A-T NEST). Variables influencing phenotype were identified by using an information-theoretic approach starting from a maximal model to generate estimates of coefficients for each variable. Per-individual progression was assessed for patients with three or more clinic attendances. The genotype could be determined for 125/135 patients. Crawford and A-T NEST scores were well correlated. For both scoring systems the estimated coefficients were significantly positive for Age x kinase activity but not Age x protein expression. Unlike the per-genotype analysis, the individual progression of neurological scores in the 34 patients that attended on three or more occasions was not smooth and linear (and in some cases improved over time). Residual kinase activity confers a milder phenotype but there is no difference between kinase-dead and protein-null genotypes. The non-linear progression of individual patients' neurological scores may reflect biological complexity, day-to-day variability, limitations of the assessment methods or a combination of all three. © 2016 Mac Keith Press.

  14. Newborn screening for SCID identifies patients with ataxia telangiectasia.

    Science.gov (United States)

    Mallott, Jacob; Kwan, Antonia; Church, Joseph; Gonzalez-Espinosa, Diana; Lorey, Fred; Tang, Ling Fung; Sunderam, Uma; Rana, Sadhna; Srinivasan, Rajgopal; Brenner, Steven E; Puck, Jennifer

    2013-04-01

    Severe combined immunodeficiency (SCID) is characterized by failure of T lymphocyte development and absent or very low T cell receptor excision circles (TRECs), DNA byproducts of T cell maturation. Newborn screening for TRECs to identify SCID is now performed in several states using PCR of DNA from universally collected dried blood spots (DBS). In addition to infants with typical SCID, TREC screening identifies infants with T lymphocytopenia who appear healthy and in whom a SCID diagnosis cannot be confirmed. Deep sequencing was employed to find causes of T lymphocytopenia in such infants. Whole exome sequencing and analysis were performed in infants and their parents. Upon finding deleterious mutations in the ataxia telangiectasia mutated (ATM) gene, we confirmed the diagnosis of ataxia telangiectasia (AT) in two infants and then tested archival newborn DBS of additional AT patients for TREC copy number. Exome sequencing and analysis led to 2 unsuspected gene diagnoses of AT. Of 13 older AT patients for whom newborn DBS had been stored, 7 samples tested positive for SCID under the criteria of California's newborn screening program. AT children with low neonatal TRECs had low CD4 T cell counts subsequently detected (R = 0.64). T lymphocytopenia in newborns can be a feature of AT, as revealed by TREC screening and exome sequencing. Although there is no current cure for the progressive neurological impairment of AT, early detection permits avoidance of infectious complications, while providing information for families regarding reproductive recurrence risks and increased cancer risks in patients and carriers.

  15. Molecular defects in Moroccan patients with ataxia-telangiectasia.

    Science.gov (United States)

    Jeddane, L; Ailal, F; Dubois-d'Enghien, C; Abidi, O; Benhsaien, I; Kili, A; Chaouki, S; Kriouile, Y; El Hafidi, N; Fadil, H; Abilkassem, R; Rada, N; Bousfiha, A A; Barakat, A; Stoppa-Lyonnet, D; Bellaoui, H

    2013-06-01

    Ataxia-telangiectasia (AT) is a rare autosomal recessive disease, affecting neurologic and immune system. Numerous mutations are described in the ATM gene in several populations. However, in Morocco, few data are available concerning this condition. Our main goal is to determine clinical, immunological, and molecular presentation of Moroccan patients with AT. We screened 27 patients, out of 22 unrelated families, for ATM gene mutations. All our patients showed ataxia, ocular telangiectasia, and immunodeficiency, as well as elevated serum alphafetoprotein levels. Mean age at diagnosis was 5.51 years, and consanguinity rate was 81.8 %. Mean age at onset was 2.02 years, and mean time to diagnosis was 3.68 years. We found 14 different mutations in 19 unrelated families, of which 7 were not reported. Our results showed that c.5644C>T mutation was the most common in our series. However, further studies are required to demonstrate a founder effects on ATM gene in Moroccan patients, who showed mutational heterogeneity otherwise. Our data indicate that direct sequencing of coding exons is sufficient for a high detection rate in ATM in Moroccan population.

  16. Circulatory contributors to the phenotype in hereditary hemorrhagic telangiectasia

    Directory of Open Access Journals (Sweden)

    Claire L Shovlin

    2015-04-01

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is mechanistically and therapeutically challenging, not only because of the molecular and cellular perturbations that generate vascular abnormalities, but also the modifications to circulatory physiology that result, and are likely to exacerbate vascular injury. First, most HHT patients have visceral arteriovenous malformations (AVMs. Significant visceral AVMs reduce the systemic vascular resistance: supra-normal cardiac outputs are required to maintain arterial blood pressure, and may result in significant pulmonary venous hypertension. Secondly, bleeding from nasal and gastrointestinal telangiectasia leads to iron losses of such magnitude that in most cases, diet is insufficient to meet the ‘hemorrhage adjusted iron requirement.’ Resultant iron deficiency restricts erythropoiesis, leading to anemia and further increases in cardiac output. Low iron levels are also associated with venous and arterial thromboses, elevated Factor VIII, and increased platelet aggregation to circulating 5HT (serotonin. Third, recent data highlight that reduced oxygenation of blood due to pulmonary AVMs results in a graded erythrocytotic response to maintain arterial oxygen content, and higher stroke volumes and/or heart rates to maintain oxygen delivery. Finally, HHT-independent factors such as diet, pregnancy, sepsis and other intercurrent illnesses also influence vascular structures, hemorrhage, and iron handling in HHT patients. These considerations emphasize the complexity of mechanisms that impact on vascular structures in HHT, and also offer opportunities for targeted therapeutic approaches.

  17. [Therapeutic approach in persistent diabetic macular edema].

    Science.gov (United States)

    Brănişteanu, Daniel; Moraru, Andreea

    2014-01-01

    Terminology of persistent diabetic macular edema has been initially reserved to cases unresponsive to conventional laser photocoagulation according to ETDRS criteria. While knowledge about pathophysiology of macular edema evolved and new drugs became available, the terminology of persistent diabetic macular edema expanded to include resistance to most current therapies. The purpose of this paper is to review medical and surgical options in the treatment of such difficult cases according to literature data and personal experience.

  18. Cystoid Macular Edema in Bietti's Crystalline Retinopathy

    Directory of Open Access Journals (Sweden)

    Ali Osman Saatci

    2014-01-01

    Full Text Available A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD. Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME. Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole.

  19. Macular Degeneration Prevention and Risk Factors

    Science.gov (United States)

    ... Grant Terms & Conditions Patent & Intellectual Property Policy For Current Awardees FAQs Our Funding Philosophy ... Alzheimer’s Disease Research Macular Degeneration Research National Glaucoma Research ...

  20. [Pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  1. Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report

    OpenAIRE

    Antoccia Antonio; Ferrari Francesca; Angelino Giulia; Scarselli Alessia; Folgori Laura; Chessa Luciana; Finocchi Andrea

    2010-01-01

    Abstract Ataxia-telangiectasia (A-T) is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM) gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children. We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively wi...

  2. ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

    Directory of Open Access Journals (Sweden)

    Jayesh M. Bhatt

    2015-12-01

    Full Text Available Ataxia telangiectasia (A-T is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.

  3. ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia.

    Science.gov (United States)

    Bhatt, Jayesh M; Bush, Andrew; van Gerven, Marjo; Nissenkorn, Andreea; Renke, Michael; Yarlett, Lian; Taylor, Malcolm; Tonia, Thomy; Warris, Adilia; Zielen, Stefan; Zinna, Shairbanu; Merkus, Peter J F M

    2015-12-01

    Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document. Copyright ©ERS 2015.

  4. Efficiency of laser treatment in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Jørgensen, Gita; Lange, Bibi; Wanscher, Jens Højberg

    2011-01-01

    Earlier studies have shown the effect of laser treatment on epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). At the present time, only very few prospective trials have been performed, and many studies are based on patients' subjective assessment of the severity of epistaxis....... This prospective study measures the objective effect of laser treatment in HHT patients with mild to moderate epistaxis. We introduce an objective measure to assess the severity of epistaxis: the bleeding time (BT). Before and after treatment, the quality of life, as measured by the patient, was assessed...... and compared to normative data. In 30 patients, we measured the BT before laser treatment 1.5 and 6.5 months after treatment. The Short form 36 (SF-36), a validated health questionnaire, was completed before and 6.5 months after treatment. Compared to preoperative value, BT was significantly reduced 1.5 and 6...

  5. Octreotide acetate in dominant cystoid macular dystrophy.

    NARCIS (Netherlands)

    Hogewind, B.F.T.; Pieters, G.; Hoyng, C.B.

    2008-01-01

    PURPOSE: Dominant cystoid macular degeneration (DCMD) is an autosomal dominant trait of cystoid macular edema with poor visual prognosis. Until now, no efficient treatments for DCMD have been reported. The authors evaluated a somatostatin-analogue (octreotide acetate) as treatment for DCMD. METHODS:

  6. Cutaneous granulomas in ataxia telangiectasia and other primary immunodeficiencies: Reflection of inappropriate immune regulation?

    NARCIS (Netherlands)

    L.Y.T. Chiam (L. Y T); M.M.M. Verhagen (Mijke); A. Haraldsson (Ásgeir); N.M. Wulffraat (Nico); G.J.A. Driessen (Gertjan); M.G. Netea (Mihai); C.M.R. Weemaes (Corry); M.M.B. Seyger (Marieke); M. van Deuren (Marcel)

    2011-01-01

    textabstractBackground: Non-infective cutaneous granulomas with unknown pathogenesis occur in various primary immunodeficiencies (PIDs) including ataxia telangiectasia (A-T). Objective: To find a common immunological denominator in these cutaneous granulomas. Methods: The dermatological and immunolo

  7. Ataxia-Telangiectasia Presenting as Cerebral Palsy and Recurrent Wheezing: A Case Report.

    Science.gov (United States)

    Navratil, Marta; Đuranović, Vlasta; Nogalo, Boro; Švigir, Alen; Dumbović Dubravčić, Iva; Turkalj, Mirjana

    2015-09-18

    Ataxia-telangiectasia (A-T) is an autosomal recessive disease that consists of progressive cerebellar ataxia, variable immunodeficiency, sinopulmonary infections, oculocutaneous telangiectasia, radiosensitivity, early aging, and increased incidence of cancer. We report the case of an 8-year-old boy affected by A-T. At 12 months of age, he had a waddling gait, with his upper body leaning forward. Dystonic/dyskinetic cerebral palsy was diagnosed at the age of 3 years. At age 6 he was diagnosed with asthma based on recurrent wheezing episodes. A-T was confirmed at the age 8 years on the basis of clinical signs and laboratory findings (increased alpha fetoprotein--AFP, immunodeficiency, undetectable ataxia-telangiectasia mutated (ATM) protein on immunoblotting, and identification A-T mutation, 5932G>T). The clinical and immunological presentation of ataxia-telangiectasia (A-T) is very heterogeneous and diagnostically challenging, especially at an early age, leading to frequent misdiagnosis.

  8. Hereditary haemorrhagic telangiectasia: a population-based study of prevalence and mortality in Danish patients

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Vase, P; Green, A

    1999-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early d...

  9. Pulmonary arteriovenous malformations: screening procedures and pulmonary angiography in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Oxhøj, H; Andersen, P E

    1999-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited disease with a high prevalence of pulmonary arteriovenous malformations (PAVMs). The first symptom of HHT may be stroke or fatal hemoptysis associated with the presence of PAVM....

  10. Effect of macular hole volume on postoperative central macular thickness

    Directory of Open Access Journals (Sweden)

    Taylan Ozturk

    2016-06-01

    Full Text Available ABSTRACT Purpose: To evaluate the association between macular hole volume (MHV and postoperative central macular thickness (CMT using spectral-domain optical coherence tomography (SD-OCT. Methods: Thirty-three eyes of 30 patients with a large full-thickness idiopathic macular hole with or without vitreomacular traction who underwent surgical intervention were included in this cross-sectional study. Complete ophthalmological examination, including SD-OCT, was performed for all participants during the pre- and postoperative visits. MHV was preoperatively measured using SD-OCT, which captured the widest cross-sectional image of the hole. For normal distribution analysis of the data, the Kolmogorov-Smirnov test was performed, and for statistical analyses, chi-square, Student's t-test, Mann-Whitney U test, and Pearson's correlation coefficient test were performed. Results: Mean preoperative best-corrected visual acuity (BCVA and MHV were found to be 0.99 ± 0.36 (range, 0.3-2.0 logMAR and 0.139 ± 0.076 (range, 0.004-0.318 mm3, respectively. Mean follow-up was 16.3 ± 14.3 (range, 3-50 months. No statistical correlations were found between MHV and postoperative BCVA (p=0.588 and between MHV and disease recurrence (p=0.544. A weak negative correlation existed between MHV and final CMT scores (p=0.04, r=-0.383. Conclusions: Greater MHV was found to be weakly associated with lower postoperative CMT scores.

  11. Keratoconus in Patients with Macular Stromal Dystrophy.

    Science.gov (United States)

    Kosrirukvongs, Panida; Ngowyutagon, Panotsom; Booranapong, Wipawee

    2016-01-01

    To show the association between keratoconus and macular dystrophy. All patients with macular dystrophy and associated clinical findings leading to a diagnosis of keratoconus by corneal topography were retrospectively reviewed during a 10-year period. Uncorrected and best-corrected visual acuity, automated refraction, manifest refraction, corneal thickness, and corneal curvature by corneal topography were evaluated Three patients with macular dystrophy exhibiting decreased vision, multifocal white dense deposits, and haze surrounding the deposits in the corneal stroma were evaluated. All had a steep corneal curvature of >47 diopters and a thin cornea consistent with keratoconus. Penetrating keratoplasty was performed in one patient with severely decreased vision. Macular dystrophy was diagnosed based on an Alcian blue-stained pathological specimen. Keratoconus may develop as a result of changes associated with macular dystrophy. Therefore, patients with severely decreased vision should be evaluated for keratoconus to ensure proper management.

  12. Combined therapy for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Saba Al Rashaed

    2013-01-01

    Full Text Available Diabetic macular edema (DME is the main cause of visual impairment in diabetic patients. Macular edema within 1 disk diameter of the fovea is present in 9% of the diabetic population. The management of DME is complex and often multiple treatment approaches are needed. This review demonstrates the benefits of intravitreal triamcinolone, bevacizumab and ranibizumab as adjunctive therapy to macular laser treatment in DME. The published results indicate that intravitreal injections of these agents may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present. Therefore, pharmacotherapy could complement focal/grid laser photocoagulation in the management of DME. For this review, we performed a literature search and summarized recent findings regarding combined therapy for DME.

  13. Hereditary hemorrhagic telangiectasia with oral manifestations. Report of periodontal treatment in two cases.

    Science.gov (United States)

    Austin, G B; Quart, A M; Novak, B

    1981-03-01

    The periodontal conditions of two patients with hereditary hemorrhagic telangiectasia were successfully treated by a two-phase plan. The first phase of treatment eliminated inflammation from local etiologic factors by removing plaque and plaque-retaining factors. The second phase eliminated the residual anatomic defects of periodontal disease. Gingival bleeding has been indicated as a symptomatic factor of hereditary hemorrhagic telangiectasia, but such bleeding is more likely the result of periodontal inflammation.

  14. Dexamethasone partially rescues ataxia telangiectasia-mutated (ATM) deficiency in ataxia telangiectasia by promoting a shortened protein variant retaining kinase activity.

    Science.gov (United States)

    Menotta, Michele; Biagiotti, Sara; Bianchi, Marzia; Chessa, Luciana; Magnani, Mauro

    2012-11-30

    Ataxia telangiectasia (AT) is a rare genetic disease, still incurable, resulting from biallelic mutations in the ataxia telangiectasia-mutated (ATM) gene. Recently, short term treatment with glucocorticoid analogues improved neurological symptoms characteristic of this syndrome. Nevertheless, the molecular mechanism involved in glucocorticoid action in AT patients is not yet known. Here we describe, for the first time in mammalian cells, a short direct repeat-mediated noncanonical splicing event induced by dexamethasone, which leads to the skipping of mutations upstream of nucleotide residue 8450 of ATM coding sequence. The resulting transcript provides an alternative ORF translated in a new ATM variant with the complete kinase domain. This miniATM variant was also highlighted in lymphoblastoid cell lines from AT patients and was shown to be likely active. In conclusion, dexamethasone treatment may partly restore ATM activity in ataxia telangiectasia cells by a new molecular mechanism that overcomes most of the mutations so far described within this gene.

  15. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions.

  16. Automatic detection of basal cell carcinoma using telangiectasia analysis in dermoscopy skin lesion images.

    Science.gov (United States)

    Cheng, Beibei; Erdos, David; Stanley, Ronald J; Stoecker, William V; Calcara, David A; Gómez, David D

    2011-08-01

    Telangiectasia, dilated blood vessels near the surface of the skin of small, varying diameter, are critical dermoscopy structures used in the detection of basal cell carcinoma (BCC). Distinguishing these vessels from other telangiectasia, that are commonly found in sun-damaged skin, is challenging. Image analysis techniques are investigated to find vessels structures in BCC automatically. The primary screen for vessels uses an optimized local color drop technique. A noise filter is developed to eliminate false-positive structures, primarily bubbles, hair, and blotch and ulcer edges. From the telangiectasia mask containing candidate vessel-like structures, shape, size and normalized count features are computed to facilitate the discrimination of benign skin lesions from BCCs with telangiectasia. Experimental results yielded a diagnostic accuracy as high as 96.7% using a neural network classifier for a data set of 59 BCCs and 152 benign lesions for skin lesion discrimination based on features computed from the telangiectasia masks. In current clinical practice, it is possible to find smaller BCCs by dermoscopy than by clinical inspection. Although almost all of these small BCCs have telangiectasia, they can be short and thin. Normalization of lengths and areas helps to detect these smaller BCCs. © 2011 John Wiley & Sons A/S.

  17. Terapia alternativa para microvarizes e telangiectasias com uso de agulha Alternative therapy for microvarices and telangiectasias with use of needle

    Directory of Open Access Journals (Sweden)

    Raimundo Rosendo de Oliveira

    2007-03-01

    Full Text Available CONTEXTO: O desenvolvimento de terapia alternativa à convencional para a destruição de microvarizes e telangiectasias sem o uso de produtos químicos tem como objetivo reduzir os efeitos colaterais, faz uso de agulha para lise mecânica dos vasos e tem como modelo experimental galinhas da linhagem Lohmann Brown. OBJETIVO: Elaborar uma nova técnica, desenvolvendo um tratamento alternativo, sem uso de produtos químicos, objetivando a redução dos efeitos colaterais. MÉTODOS: Foram utilizadas 30 galinhas da linhagem Lohmann Brown, sendo que 15 foram submetidas ao método convencional de tratamento de microvarizes e telangiectasias (grupo-controle e as outras 15 receberam o tratamento experimental proposto (grupo experimental. O grupo experimental foi tratado com agulha de lise vascular, percorrendo todo o trajeto dos vasos escolhidos em punções escalonadas até que todo o vaso ser atingido. O grupo-controle foi tratado com oleato de monoetanolamina e glicose a 50%, puncionando-se o vaso com agulha 13 x 3 mm e injetando-se, em média, 0,3 mL da solução em cada vaso. RESULTADOS: Dos 50 vasos tratados no grupo experimental, dois apresentaram recidiva total, cinco apresentaram recidiva parcial, e 43 apresentaram destruição (lise satisfatória; enquanto que, no grupo-controle, dos 51 vasos tratados, quatro apresentaram recidiva total, 12, recidiva parcial, 22, destruição satisfatória, e em 13 ocorreu endurecimento de trajeto. CONCLUSÃO: O presente estudo demonstrou que o método experimental proposto, com uso de agulha de lise vascular, possui mais eficiência no tratamento de microvarizes se comparado com o método convencional, devido à redução das recidivas e à ausência de hipercromia de trajeto endurecido.BACKGROUND: The development of an alternative to the conventional therapy for microvarices and telangiectasias without using chemical products aims at reducing side effects, using a needle for mechanical lysis of vessels. It

  18. Edema macular diabético Diabetic macular edema

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    J. Andonegui

    2008-01-01

    Full Text Available El edema macular diabético representa la primera causa de pérdida visual en los pacientes con diabetes mellitus. Su complejidad, unida a la aparición de nuevos métodos de diagnóstico así como de novedosas alternativas de tratamiento, hace que el enfoque de esta enfermedad suponga un importante reto para el oftalmólogo. A lo largo de este artículo se describen su patofisiología, manifestaciones clínicas, clasificación, diagnóstico y tratamiento, haciendo especial énfasis en los nuevos métodos diagnósticos y en las diferentes opciones terapéuticas.Diabetic macular edema is the principal cause of visual loss in patients with diabetes mellitus. Its complexity, together with the appearance of new methods of diagnosis and new alternatives for treatment, mean that the approach to this disease is an important challenge for ophthalmologists. This article describes its pathophysiology, clinical manifestations, classification, diagnosis and treatment, with special emphasis on the new diagnostic methods and on the different therapeutic options.

  19. Update on treatments of diabetic macular edema

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-lu; LIU Kun; XU Xun

    2009-01-01

    Objective To review the update research progress about the treatment of diabetic macular edema and to give helpful guidelines in the treatment of diabetic macular edema based on available evidence to date.Data sources A literature search of all English articles was performed on the online electronic PubMed database dated 1984 to 2009. The keywords searched included: macular edema, therapy, laser coagulation, intravitreal triamcinolone acetonide, vascular endothelial growth factor inhibitor, protein kinase C inhibitor and Pars plana vitrectomy. After finding relevant articles within these search limits, a manual search was conducted through the references from these articles.Study selection Original articles and critical reviews were reviewed and selected to address the stated purpose.Results To date, demonstrated means to reduce the risk of vision loss from diabetic macular edema include focal/grid laser photocoagulation and improved metabolic control. Emerging pharmacologic therapies (intravitreal triamcinolone acetonide, vascular endothelial growth factor inhibitors and protein kinase C beta-isoform inhibitors) and Pars plana vitrectomy have shown early promise in the treatment of diabetic macular edema.Conclusions As there has been extensive development in multiple treatments of diabetic macular edema, choice of the most suitable treatment for specific patients becomes important. Combination therapy of laser, pharmacological and surgical treatment modalities may offer an alternative to treatment of diabetic macular edema.

  20. Cystoid macular edema after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Khetan Vikas

    2009-01-01

    Full Text Available We report a case of cystoid macular edema in a patient who underwent bone marrow transplant for aplastic anemia. After having ruled out all the other causes of cystoid macular edema, we concluded that it was secondary to the bone marrow transplant. The patient had mild visual impairment and did not recover the lost vision. In this case report, we describe in detail the clinical presentation, follow-up, and course of medication that this patient had. It is an illustrated case report of cystoid macular edema after bone marrow transplant with mild visual impairment and no recovery.

  1. Consistency of ocular coherence tomography fast macular thickness mapping in diabetic diffuse macular edema

    Energy Technology Data Exchange (ETDEWEB)

    Saraiva, Fabio Petersen; Costa, Patricia Grativol; Inomata, Daniela Lumi; Melo, Carlos Sergio Nascimento; Helal Junior, John; Nakashima, Yoshitaka [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. de Oftalmologia]. E-mail: fabiopetersen@yahoo.com.br

    2007-07-01

    Objectives: To investigate optical coherence tomography consistency on foveal thickness, foveal volume, and macular volume measurements in patients with and without diffuse diabetic macular edema. Introduction: Optical coherence tomography represents an objective technique that provides cross-sectional tomographs of retinal structure in vivo. However, it is expected that poor fixation ability, as seen in diabetic macular edema, could alter its results. Several authors have discussed the reproducibility of optical coherence tomography, but only a few have addressed the topic with respect to diabetic maculopathy. Methods: The study recruited diabetic patients without clinically evident retinopathy (control group) and with diffuse macular edema (case group). Only one eye of each patient was evaluated. Five consecutive fast macular scans were taken using Ocular Coherence Tomography 3; the 6 mm macular map was chosen. The consistency in measurements of foveal thickness, foveal volume, and total macular volume for both groups was evaluated using the Pearson's coefficient of variation. The T-test for independent samples was used in order to compare measurements of both groups. Results: Each group consisted of 20 patients. All measurements had a coefficient of variation less than 10%. The most consistent parameter for both groups was the total macular volume. Discussion: Consistency in measurement is a mainstay of any test. A test is unreliable if its measurements can not be correctly repeated. We found a good index of consistency, even considering patients with an unstable gaze. Conclusions: Optical coherence tomography is a consistent method for diabetic subjects with diffuse macular edema. (author)

  2. Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts.

    Science.gov (United States)

    Kim, Min-Hyun; Kim, Aryung; Yu, Ji Hoon; Lim, Joo Weon; Kim, Hyeyoung

    2014-05-01

    To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. The cells were cultured with or without glutamine or GSH. ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and

  3. Ataxia telangiectasia: more variation at clinical and cellular levels.

    Science.gov (United States)

    Taylor, A M R; Lam, Z; Last, J I; Byrd, P J

    2015-03-01

    Ataxia telangiectasia (A-T) is a rare recessively inherited disorder resulting in a progressive neurological decline. It is caused by biallelic mutation of the ATM gene that encodes a 370 kDa serine/threonine protein kinase responsible for phosphorylating many target proteins. ATM is activated by auto(trans)phosphorylation in response to DNA double strand breaks and leads to the activation of cell cycle checkpoints and either DNA repair or apoptosis as part of the cellular response to DNA damage. The allelic heterogeneity in A-T is striking. While the majority of mutations are truncating, leading to instability and loss of the ATM protein from the allele, a significant proportion of patients carry one of a small number of mutations that are either missense or leaky splice site mutations resulting in retention of some ATM with activity. The allelic heterogeneity in ATM, therefore, results in an equally striking clinical heterogeneity. There is also locus heterogeneity because mutation of the MRE11 gene can cause an obvious A-T like disorder both clinically and also at the cellular level and mutation of the RNF168 gene results in a much milder clinical phenotype, neurologically, with the major clinical feature being an immunological defect. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Treatment of essential telangiectasia: effects of increasing concentrations of polidocanol.

    Science.gov (United States)

    Norris, M J; Carlin, M C; Ratz, J L

    1989-04-01

    A double-blind, double-paired comparison study was performed to evaluate the effects of increasing concentrations of polidocanol in the sclerotherapy of essential telangiectasias of the legs. Polidocanol 0.25%, 0.50%, 0.75%, and 1.0% were compared with regard to clinical effectiveness, safety, and patient acceptance. All dosages were well tolerated by the patients. There were no allergic reactions to polidocanol and no cases of superficial ulceration nor necrosis. Among those whose veins cleared, there was little difference in time to clearing for the four concentrations, which averaged three to four treatment sessions. No statistically significant differences existed among the four dosages with respect to level of improvement, itching, or neovascularization. Polidocanol 0.75% and 1.0%, however, caused more side effects noted by patients and induced more hyperpigmentation than did the lower concentrations. Polidocanol 0.25% yielded the lowest percentage of patients whose veins cleared. The 0.50% solution was the most effective concentration for total overall clearing of the types of vessels treated in this study. From this information it appears that 0.50% polidocanol may be the sclerosing agent of choice.

  5. Anti-angiogenic therapeutic strategies in hereditary hemorrhagic telangiectasia

    Directory of Open Access Journals (Sweden)

    Daniela S. Ardelean

    2015-02-01

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant vascular dysplastic disorder, characterized by recurrent nosebleeds (epistaxis, multiple telangiectases and arteriovenous malformations (AVMs in major organs. Mutations in Endoglin (ENG or CD105 and Activin receptor-like kinase 1 (ACVRL1 or ALK1 genes of the TGF-β superfamily receptors are responsible for HHT1 and HHT2 respectively and account for the majority of HHT cases. Haploinsufficiency in ENG and ALK1 is recognized at the underlying cause of HHT. However, the mechanisms responsible for the predisposition to and generation of AVMs, the hallmark of this disease, are poorly understood. Recent data suggest that dysregulated angiogenesis contributes to the pathogenesis of HHT and that the vascular endothelial growth factor, VEGF, may be implicated in this disease, by modulating the angiogenic balance in the affected tissues. Hence, anti-angiogenic therapies that target the abnormal vessels and restore the angiogenic balance are candidates for treatment of HHT. Here we review the experimental evidence for dysregulated angiogenesis in HHT, the anti-angiogenic therapeutic strategies used in animal models and some patients with HHT and the potential benefit of the anti-angiogenic treatment for ameliorating this severe, progressive vascular disease.

  6. Molecular basis of ataxia telangiectasia and related diseases

    Institute of Scientific and Technical Information of China (English)

    Lindsay G BALL; Wei XIAO

    2005-01-01

    Ataxia telangiectasia (AT) is a rare human disease characterized by extreme cellular sensitivity to radiation and a predisposition to cancer, with a hallmark of onset in early childhood. Several human diseases also share similar symptoms with AT albeit with different degrees of severity and different associated disorders. While all AT patients contain mutations in the AT-mutated gene (ATM), most other ATlike disorders are defective in genes encoding an MRN protein complex consisting of Mre11, Rad50 and Nbs1. Both ATM and MRN function as cellular sensors to DNA double-strand breaks, which lead to the recruitment and phosphorylation of an array of substrate proteins involved in DNA repair, apoptosis and cell-cycle checkpoints, as well as gene regulation, translation initiation and telomere maintenance. ATM is a member of the family of phosphatidylinositol 3-kinase-like protein kinases (PIKK), and the discovery of many ATM substrates provides the underlying mechanisms of heterologous symptoms among AT patients. This review article focuses on recent findings related to the initial recognition of doublestrand breaks by ATM and MRN, as well as a DNA-dependent protein kinase complex consisting of the heterodimer Ku70/Ku80 and its catalytic subunit DNAPKcs, another member of PIKK. This possible interaction suggests that a much greater complex is involved in sensing, transducing and co-ordinating cellular events in response to genome instability.

  7. Research on Potential Biomarkers in Hereditary Haemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Luisa Maria Botella

    2015-03-01

    Full Text Available Hereditary Hemorrhagic Telangiectasia (HHT is a genetically heterogeneous disorder, involving mutations in two predominant genes known as Endoglin (ENG; HHT1 and Activin receptor like kinase 1 (ACVRL1/ALK1; HHT2, as well as in some less frequent genes, such as MADH4/SMAD4 (JP-HHT or BMP9/GDF2 (HHT5. The diagnosis of HHT patients currently remains at the clinical level, according to the Curaçao criteria, whereas the molecular diagnosis is used to confirm or rule out suspected HHT cases, especially when a well characterized index case is present in the family or in an isolated population. Unfortunately, many suspected patients do not present a clear HHT diagnosis or do not show pathogenic mutations in HHT genes, prompting the need to investigate additional biomarkers of the disease. Here, several HHT biomarkers and novel methodological approaches developed during the last years will be reviewed. On one hand, products detected in plasma or serum samples: soluble proteins (VEGF, TGF-β1, soluble endoglin, angiopoietin-2 and microRNA variants (miR-27a, miR-205, miR-210. On the other hand, differential HHT gene expression fingerprinting, Next Generation Sequencing (NGS of a panel of genes involved in HHT, and infrared spectroscopy combined with Artificial Neural Network (ANN patterns will also be reviewed. All these biomarkers might help to improve and refine HHT diagnosis by distinguishing from the non-HHT population.

  8. Chromosome aberrations in ataxia telangiectasia cells exposed to heavy ions

    Science.gov (United States)

    Kawata, T.; Cucinotta, F.; George, K.; Wu, H.; Shigematsu, N.; Furusawa, Y.; Uno, T.; Isobe, K.; Ito, H.

    Understanding of biological effects of heavy ions is important to assess healt h risk in space. One of the most important issues may be to take into account individual susceptibility. Ataxia telangiectasia (A-T) cells are known to exhibit abnormal responses to radiations but the mechanism of hyper radiosensitivity of A-T still remains unknown. We report chromosome aberrations in normal human fibroblasts and AT fibroblasts exposed to low- and high-LET radiations. A chemical-induced premature chromosome condensation (PCC) technique combined with chromosome- painting technique was applied to score chromosome aberrations in G2/M-phase cells. Following gamma irradiation, GM02052 cells were approximately 5 times more sensitive to g-rays than AG1522 cells. GM02052 cells had a much higher frequency of deletions and misrejoining than AG1522 cells. When the frequency of complex type aberrations was compared, GM02052 cells showed more than 10 times higher frequency than AG1522 cells. The results will be compared with those obtained from high-LET irradiations.

  9. Evaluation and Management of Pulmonary Disease in Ataxia-Telangiectasia

    Science.gov (United States)

    McGrath-Morrow, Sharon A.; Gower, W. Adam; Rothblum-Oviatt, Cynthia; Brody, Alan S.; Langston, Claire; Fan, Leland L.; Lefton-Greif, Maureen A.; Crawford, Thomas O.; Troche, Michelle; Sandlund, John T; Auwaerter, Paul G.; Easley, Blaine; Loughlin, Gerald M.; Carroll, John L.; Lederman, Howard M.

    2014-01-01

    Summary Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, resulting in faulty repair of breakages in double-stranded DNA. The clinical phenotype is complex, and is characterized by neurologic abnormalities, immunodeficiencies, susceptibility to malignancies, recurrent sinopulmonary infections, and cutaneous abnormalities. Lung disease is common in patients with A-T and often progresses with age and neurological decline. Diseases of the respiratory system cause significant morbidity and are a frequent cause of death in the A-T population. Lung disease in this population is thought to exhibit features of one or more of the following phenotypes: recurrent sinopulmonary infections with bronchiectasis, interstitial lung disease, and lung disease associated with neurological abnormalities. Here, we review available evidence and present expert opinion on the diagnosis, evaluation, and management of lung disease in A-T, as discussed in a recent multidisciplinary workshop. Although more data are emerging on this unique population, many recommendations are made based on similarities to other more well-studied diseases. Gaps in current knowledge and areas for future research in the field of pulmonary disease in A-T are also outlined. PMID:20583220

  10. 5'UTR mutations of ENG cause hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Damjanovich, Kristy; Langa, Carmen; Blanco, Francisco J; McDonald, Jamie; Botella, Luisa M; Bernabeu, Carmelo; Wooderchak-Donahue, Whitney; Stevenson, David A; Bayrak-Toydemir, Pinar

    2011-12-22

    Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder characterized by epistaxis, arteriovenous malformations, and telangiectases. The majority of the patients have a mutation in the coding region of the activin A receptor type II-like 1 (ACVRL1) or Endoglin (ENG) gene. However, in approximately 15% of cases, sequencing analysis and deletion/duplication testing fail to identify mutations in the coding regions of these genes. Knowing its vital role in transcription and translation control, we were prompted to investigate the 5'untranslated region (UTR) of ENG. We sequenced the 5'UTR of ENG for 154 HHT patients without mutations in ENG or ACVRL1 coding regions. We found a mutation (c.-127C > T), which is predicted to affect translation initiation and alter the reading frame of endoglin. This mutation was found in a family with linkage to the ENG, as well as in three other patients, one of which had an affected sibling with the same mutation. In vitro expression studies showed that a construct with the c.-127C > T mutation alters the translation and decreases the level of the endoglin protein. In addition, a c.-9G > A mutation was found in three patients, one of whom was homozygous for this mutation. Expression studies showed decreased protein levels suggesting that the c.-9G > A is a hypomorphic mutation. Our results emphasize the need for the inclusion of the 5'UTR region of ENG in clinical testing for HHT.

  11. Hereditary hemorrhagic telangiectasia: two distinct ENG deletions in one family.

    Science.gov (United States)

    Wooderchak, W; Gedge, F; McDonald, M; Krautscheid, P; Wang, X; Malkiewicz, J; Bukjiok, C J; Lewis, T; Bayrak-Toydemir, P

    2010-11-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by aberrant vascular development. Mutations in endoglin (ENG) or activin A receptor type II-like 1 (ACVRL1) account for around 90% of HHT patients, 10% of those are large deletions or duplications. We report here the first observation of two distinct, large ENG deletions segregating in one pedigree. An ENG exon 4-7 deletion was observed in a patient with HHT. This deletion was identified in several affected family members. However, some affected family members had an ENG exon 3 deletion instead. These deletions were detected by multiplex ligation-dependent probe amplification and confirmed by mRNA sequencing and an oligo-CGH array. Linkage analysis revealed that one individual with the exon 3 deletion inherited the same chromosome from his mother who has the exon 4-7 deletion. This finding has important clinical implications because it shows that targeted family-specific mutation analysis for exon deletions could have led to the misdiagnosis of some affected family members. © 2010 John Wiley & Sons A/S.

  12. Neurodegeneration in ataxia-telangiectasia is caused by horror autotoxicus.

    Science.gov (United States)

    Kuljis, R O; Aguila, M C

    1999-05-01

    Ataxia-telangiectasia (A-T) is a pleiotropic, multi-system disorder with manifestations that include immune deficiency, sensitivity to ionizing radiation and neoplasms. Many of these manifestations are understood in principle since the identification in A-T patients of mutations in a gene encoding a protein kinase that plays a key role in signaling and repair of DNA damage. However, the cause of the neurodegeneration that afflicts patients with A-T for at least a decade before they succumb to overwhelming infections or malignancy remains mysterious. Based on our work in a mouse model of A-T and previous evidence of extra-neural autoimmune disorders in A-T, we postulate that the neurodegenerative process in A-T is not due to a function for A-T mutated (ATM) essential for the postnatal brain, but to an autoimmune process (hence 'horror autotoxicus', Paul Ehrlich's term for autoimmune disorder). This hypothetical mechanism may be analogous to that in the so-called 'paraneoplastic' neurodegenerative syndromes in patients with various malignancies. Thus, alterations in the balance between cellular and humoral immunity in A-T probably result in autoantibodies to cerebral epitopes shared with cells of the immune system. This hypothesis has important implications for the understanding and development of effective palliative and even preventative strategies for A-T, and probably for other so far relentlessly progressive neurodegenerative disorders.

  13. Mutation study of Spanish patients with Hereditary Hemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Blanco Francisco J

    2008-08-01

    Full Text Available Abstract Background Hereditary Hemorrhagic Telangiectasia (HHT is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG or activin receptor-like kinase-1 (ALK1, ACVRL1 genes. Methods Here, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT. Results We identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model. Conclusion Overall, ALK1 mutations (HHT2 were predominant over ENG mutations (HHT1 in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy, but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.

  14. What Is Age-Related Macular Degeneration?

    Science.gov (United States)

    ... Qué es la degeneración macular relacionada con la edad? Find an Ophthalmologist Advanced Search Ask an Ophthalmologist ... Privacy Policy Terms of Service For Advertisers For Media Ophthalmology Job Center © American Academy of Ophthalmology 2017 ...

  15. Combination Therapy for Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Dinah Zur

    2012-01-01

    Full Text Available Diabetic macular edema is a main reason for visual loss in diabetic patients. Until recent years, macular laser photocoagulation was the only available therapy. The awareness that inflammation is an important factor in the pathogenetic process of DME gave reason for intravitreal treatment with corticosteroids. The introduction of anti-VEGF drugs brought a revolutionary change in the treatment of DME. This paper will review the important clinical trials with an emphasis on combination therapies.

  16. Cystoid Macular Edema in Bietti's Crystalline Retinopathy

    OpenAIRE

    Ali Osman Saatci; Hasan Can Doruk; Aylin Yaman

    2014-01-01

    A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD in...

  17. Assessment of impaired coordination between respiration and deglutition in children and young adults with ataxia telangiectasia.

    Science.gov (United States)

    Lefton-Greif, Maureen A; Perlman, Adrienne L; He, Xuming; Lederman, Howard M; Crawford, Thomas O

    2016-10-01

    This cross-sectional investigation aimed to assess the value of non-invasive measures of temporal respiratory-swallow coupling in individuals with ataxic swallowing. Twenty participants (11 males, 9 females; range 9-21y) with ataxia telangiectasia were presented with water and pudding boluses. Their 193 swallows were compared with 2200 swallows from 82 age-matched healthy controls. The two components of airway protection during swallowing that were analyzed were: direction of peri-deglutitive airflow and duration of deglutitive inhibition of respiratory airflow (DIORA). Safe expiratory patterns of peri-deglutitive airflow occurred significantly less often in participants with ataxia telangiectasia than in age-matched control participants (younger pataxia telangiectasia (p=0.234). With age, mean duration of DIORA decreased in controls (pataxia telangiectasia (p=0.164). Non-invasive quantitative measures of respiratory-swallow coupling capture temporal relationships that plausibly contribute to airway compromise from dysphagia. Changes in respiratory-swallow coupling observed with advancing age in control participants were not seen in participants with ataxia telangiectasia. Measures of perturbations may herald swallowing problems prior to development of pulmonary and nutritional sequelae. © 2016 Mac Keith Press.

  18. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD...... a fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  19. Long-pulsed dye laser vs. intense pulsed light for the treatment of facial telangiectasias: a randomized controlled trial

    DEFF Research Database (Denmark)

    Nymann, Peter; Hedelund, Lene; Haedersdal, M

    2010-01-01

    This study aims to compare the efficacy and adverse effects of long-pulsed dye laser (LPDL) and intense pulsed light (IPL) in the treatment of facial telangiectasias.......This study aims to compare the efficacy and adverse effects of long-pulsed dye laser (LPDL) and intense pulsed light (IPL) in the treatment of facial telangiectasias....

  20. Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT)

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Oxhøj, H; Andersen, P E;

    2000-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease. HHT is characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs) and neurological symptoms.......Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease. HHT is characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs) and neurological symptoms....

  1. Macular morphology and visual acuity after macular hole surgery with or without internal limiting membrane peeling

    DEFF Research Database (Denmark)

    Christensen, U.C.; Kroyer, K.; Sander, B.

    2010-01-01

    Aim: To examine postoperative macular morphology and visual outcome after 12 months in relation to internal limiting membrane (ILM) peeling versus no peeling, indocyanine green (ICG) staining and re-operation in eyes that achieved macular hole closure after surgery. Methods: Seventy-four eyes wit...

  2. Multi-drugs resistant acne rosacea in a child affected by Ataxia-Telangiectasia: successful treatment with Isotretinoin.

    Science.gov (United States)

    Cantarutti, Nicoletta; Claps, Alessia; Angelino, Giulia; Chessa, Luciana; Callea, Francesco; El Hachem, May; Diociaiuti, Andrea; Finocchi, Andrea

    2015-03-28

    Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.

  3. Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report

    Directory of Open Access Journals (Sweden)

    Antoccia Antonio

    2010-04-01

    Full Text Available Abstract Ataxia-telangiectasia (A-T is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children. We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively with extensive cutaneous granulomatosis and severe combined immunodeficiency, without neurological abnormalities, at the time of diagnosis. This case clearly emphasizes the variable presentation of A-T syndrome and highlights the difficulties in the early diagnosis of A-T. A-T should be considered in children with evidence of combined humoral and cellular immunodeficiency associated with unexplained skin granulomatous lesions, even in the absence of the classic features of this syndrome.

  4. Novel compound heterozygous mutations in a child with Ataxia-Telangiectasia showing unrelated cerebellar disorders.

    Science.gov (United States)

    Piane, Maria; Molinaro, Anna; Soresina, Annarosa; Costa, Silvia; Maffeis, Marianna; Germani, Aldo; Pinelli, Lorenzo; Meschini, Roberta; Plebani, Alessandro; Chessa, Luciana; Micheli, Roberto

    2016-12-15

    We report the case of a 6-year-old female patient with Ataxia Telangiectasia, an extremely rare condition, who developed in addition a left cerebellar astrocytoma and a right cerebellar infarction, considered as two independent events. Children with AT have an increased risk of developing cancer, but only few cases of glioma are reported and, at our knowledge, no other case of unrelated cerebellar glioma and cerebellar infarction in with the same AT patient have been described. The molecular analysis of ATM (Ataxia Telangiectasia Mutated) gene showed that the patient is compound heterozygote for two previously unreported mutations: c.3291delC (p.Phe1097fs) at exon 25 and c.8198A>C (p.Gln2733Pro) at exon 58. The role of the identified ATM gene mutations in the pathogenesis of Ataxia Telangiectasia and the coexisting cerebellar disorders is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Bladder wall telangiectasis causing life-threatening haematuria in ataxia-telangiectasia: a new observation.

    Science.gov (United States)

    Cohen, Jonathan M; Cuckow, Peter; Davies, E Graham

    2008-05-01

    We report two cases of life-threatening haemorrhage from bladder telangiectasia in children with ataxia-telangiectasia (A-T) who had been treated for lymphoma earlier in life. Whilst oculocutaneous telangiectasiae are an almost universal finding in this syndrome, bladder wall telangiectasis has not been reported previously. Both teenagers presented with recurrent severe haematuria due to extensive bladder telangiectasis. Recurrent haemorrhage was controlled with cystoscopic diathermy treatment. As A-T is a DNA repair disorder, it is possible that chemotherapy-mediated damage to the bladder mucosa prompted the development of clinically significant telangiectasis in these patients. We advocate early cystoscopy for A-T patients who develop haematuria to investigate the cause, and cystodiathermy to pre-emptively treat developing lesions prior to haemodynamically significant haemorrhage.

  6. Orofacial hereditary haemorrhagic telangiectasia: high power diode laser in early and advanced lesion treatment

    Science.gov (United States)

    Tempesta, Angela; Franco, Simonetta; Miccoli, Simona; Suppressa, Patrizia; De Falco, Vincenzo; Crincoli, Vito; Lacaita, Mariagrazia; Giuliani, Michele; Favia, Gianfranco

    2014-01-01

    Hereditary Haemorrhagic Telangiectasia (HHT) is a muco-cutaneous inherited disease. Symptoms are epistaxis, visceral arterio-venous malformations, multiple muco-cutaneous telangiectasia with the risk of number increasing enlargement, bleeding, and super-infection. The aim of this work is to show the dual Diode Laser efficacy in preventive treatment of Early Lesions (EL < 2mm) and therapeutic treatment of Advanced Lesions (AL < 2mm). 21 patients affected by HHT with 822 muco-cutaneous telangiectatic nodules have been treated in several sessions with local anaesthesia and cooling of treated sites. EL preventive treatment consists of single Laser impulse (fibre 320) in ultrapulsed mode (2 mm single point spot). AL therapeutic treatment consists of repeated Laser impulses in pulsed mode (on 200ms / off 400ms). According to the results, Diode Laser used in pulsed and ultra-pulsed mode is very effective as noninvasive treatment both in early and advanced oral and perioral telangiectasia.

  7. Injeção intravítrea de triancinolona no tratamento da telangiectasia retiniana justafoveolar idiopática Intravitreal triamcinolone injection in the treatment of idiopathic juxtafoveal telangiectasis

    Directory of Open Access Journals (Sweden)

    Otacílio Oliveira Maia Júnior

    2006-12-01

    Full Text Available Relato de caso de um paciente com telangiectasia justafoveal idiopática (TJI tipo 1A, no olho direito, submetido a 4 mg de triancinolona intravítrea. O resultado foi avaliado por meio da acuidade visual e da tomografia de coerência óptica. A acuidade visual e a espessura retiniana macular medida na tomografia de coerência óptica, antes da injeção intravítrea de triancinolona, foram respectivamente de 20/100 e 569 µm e, após três semanas do tratamento foram de 20/60 e 371 µm e na sexta semana de 20/100 e 614 µm. A estabilização da parede vascular obtida com injeção intravítrea de triancinolona proporciona melhora transitória da visão e do edema macular em olhos com TJI-1A. Não foi demonstrada nenhuma ajuda permanente à fotocoagulação prévia.Case report of one idiopathic juxtafoveal telangiectasis (IJT 1A patient whose right eye was treated with a 4 mg intravitreal triamcinolone acetonide injection. The outcome was evaluated by visual acuity and optic coherence tomography. The visual acuity and the caliper retinal thickness before triamcinolone injection were respectively 20/100 and 569 µm, and 20/60 and 371 µm after three weeks and 20/100 and 614 µm after six week of follow-up. The stabilization of the vascular wall due to the intravitreal triamcinolone injection leads to a transitory improvement in vision and reduction in macular edema in the TJI 1A eyes. No permanent help by the photocoagulation could be shown.

  8. Pulmonary Function in Children and Young Adults With Ataxia Telangiectasia

    Science.gov (United States)

    McGrath-Morrow, Sharon A.; Lederman, Howard M.; Aherrera, Angela D.; Lefton-Greif, Maureen A.; Crawford, Thomas O.; Ryan, Timothy; Wright, Jennifer; Collaco, Joseph M.

    2015-01-01

    Summary Background Pulmonary disease contributes to significant morbidity and mortality in people with ataxia telangiectasia (A-T). To determine the association between age and lung function in children and young adults with A-T and to identify factors associated with decreased lung function, pulmonary function tests were performed in 100 consecutive people with A-T. Methods Children and adults ranging from 6 to 29 years of age and with the diagnosis of A-T were recruited, and underwent pulmonary function tests. Results The mean forced vital capacity % predicted (FVC %) in the population was 56.6 ± 20.0. Males and females between 6 and 10 years of age had similar pulmonary function. Older females were found to have significantly lower FVCs % than both older males (P < 0.02) and younger females (P < 0.001). The use of supplemental gamma globulin was associated with significantly lower FVC %. A modest correlation was found between higher radiation-induced chromosomal breakage and lower FVC % in males. No significant change in FVC % was found in a subset of subjects (n = 25) who underwent pulmonary function testing on two or more occasions over an average of 2 years. Conclusion In children and young adults with A-T, older females and people who required supplemental gamma globulin had significantly lower lung function by cross-sectional analysis. Stable lung function is possible over a 2-year period. Recognition of groups who are at higher risk for lower pulmonary function may help direct care and improve clinical outcomes in people with A-T. PMID:23401357

  9. Growth and nutrition in children with ataxia telangiectasia.

    Science.gov (United States)

    Stewart, Emma; Prayle, Andrew P; Tooke, Alison; Pasalodos, Sara; Suri, Mohnish; Bush, Andy; Bhatt, Jayesh M

    2016-12-01

    Ataxia telangiectasia (A-T) is a rare multisystem disease with high early mortality from lung disease and cancer. Nutritional failure adversely impacts outcomes in many respiratory diseases. Several factors influence nutrition in children with A-T. We hypothesised that children with A-T have progressive growth failure and that early gastrostomy tube feeding (percutaneous endoscopic gastrostomy, PEG) is a favourable management option with good nutritional outcomes. Data were collected prospectively on weight, height and body mass index (BMI) at the national paediatric A-T clinic. Adequacy and safety of oral intake was assessed. Nutritional advice was given at each multidisciplinary review. 101 children (51 girls) had 222 measurements (32 once, 32 twice, 24 thrice) between 2009 and 2016. Median (IQR) age was 9.3 (6.4 to 13.1) years. Mean (SD) weight, height and BMI Z-scores were respectively -1 (1.6), -1.2 (1.2) and -0.4 (1.4). 35/101 children had weight Z-scores below -2 on at least one occasion. Weight, height and BMI Z-scores declined over time. Decline was most obvious after 8 years of age. 14/101 (14%) children had a PEG, with longitudinal data available for 12. In a nested case control study, there was a trend for improvement in weight in those with a PEG (p=0.10). Patients with A-T decline in growth over time. There is an urgent need for new strategies, including an understanding of why growth falters. We suggest early proactive consideration of PEG from age 8 years onwards to prevent progressive growth failure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia.

    Science.gov (United States)

    Méneret, Aurélie; Ahmar-Beaugendre, Yara; Rieunier, Guillaume; Mahlaoui, Nizar; Gaymard, Bertrand; Apartis, Emmanuelle; Tranchant, Christine; Rivaud-Péchoux, Sophie; Degos, Bertrand; Benyahia, Baya; Suarez, Felipe; Maisonobe, Thierry; Koenig, Michel; Durr, Alexandra; Stern, Marc-Henri; Dubois d'Enghien, Catherine; Fischer, Alain; Vidailhet, Marie; Stoppa-Lyonnet, Dominique; Grabli, David; Anheim, Mathieu

    2014-09-16

    To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders. A total of 14 consecutive adults with A-T were included at 2 tertiary adult movement disorders centers and compared to 53 typical patients with A-T. Clinical evaluation, neurophysiologic and video-oculographic recording, imaging, laboratory investigations, and ATM analysis were performed. In comparison with typical A-T cases, our patients demonstrated later mean age at onset (6.1 vs 2.5 years, p ataxia in 71% and dysarthria and dystonia in 14% each. All patients displayed movement disorders, among which dystonia and subcortical myoclonus were the most common (86%), followed by tremor (43%). Video-oculographic recordings revealed mostly dysmetric saccades and 46% of patients had normal latencies (i.e., no oculomotor apraxia) and velocities. The α-fetoprotein (AFP) level was normal in 7%, chromosomal instability was found in 29% (vs 100% of typical patients, p = 0.0006), and immunoglobulin deficiency was found in 29% (vs 69%, p = 0.057). All patients exhibited 2 ATM mutations, including at least 1 missense mutation in 79% of them (vs 36%, p = 0.0067). There is great variability of phenotype and severity in A-T, including a wide spectrum of movement disorders. Karyotype and repeated AFP level assessments should be performed in adults with unexplained movement disorders as valuable clues towards the diagnosis. In case of a compatible phenotype, A-T should be considered even if age at onset is late and progression is slow. © 2014 American Academy of Neurology.

  11. Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia.

    Science.gov (United States)

    Sharma, Nilesh K; Lebedeva, Maria; Thomas, Terace; Kovalenko, Olga A; Stumpf, Jeffrey D; Shadel, Gerald S; Santos, Janine H

    2014-01-01

    Ataxia Telangiectasia (A-T) is a progressive childhood disorder characterized most notably by cerebellar degeneration and predisposition to cancer. A-T is caused by mutations in the kinase ATM, a master regulator of the DNA double-strand break response. In addition to DNA-damage signaling defects, A-T cells display mitochondrial dysfunction that is thought to contribute to A-T pathogenesis. However, the molecular mechanism leading to mitochondrial dysfunction in A-T remains unclear. Here, we show that lack of ATM leads to reduced mitochondrial DNA (mtDNA) integrity and mitochondrial dysfunction, which are associated to defective mtDNA repair. While protein levels of mtDNA repair proteins are essentially normal, in the absence of ATM levels specifically of DNA ligase III (Lig3), the only DNA ligase working in mitochondria is reduced. The reduction of Lig3 is observed in different A-T patient cells, in brain and pre-B cells derived from ATM knockout mice as well as upon transient or stable knockdown of ATM. Furthermore, pharmacological inhibition of Lig3 in wild type cells phenocopies the mtDNA repair defects observed in A-T patient cells. As targeted deletion of LIG3 in the central nervous system causes debilitating ataxia in mice, reduced Lig3 protein levels and the consequent mtDNA repair defect may contribute to A-T neurodegeneration. A-T is thus the first disease characterized by diminished Lig3. Published by Elsevier B.V.

  12. Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Liana Zucco

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant vascular disorder. Circulating angiogenic cells (CACs play an important role in vascular repair and regeneration. This study was designed to examine the function of CACs derived from patients with HHT. Peripheral blood mononuclear cells (PBMNCs isolated from patients with HHT and age- and gender-matched healthy volunteers were assessed for expression of CD34, CD133 and VEGF receptor 2 by flow cytometry. PBMNCs were cultured to procure early outgrowth CACs. Development of endothelial cell (EC phenotype in CACs was analyzed by fluorescence microscopy. CAC apoptosis was assayed with Annexin V staining, and CAC migration assessed by a modified Boyden chamber assay. mRNA expression of endoglin (ENG, activin receptor-like kinase-1 (ACVLR1 or ALK1 and endothelial nitric oxide synthase (eNOS in CACs was measured by real time RT-PCR. The percentage of CD34+ cells in PBMNCs from HHT patients was significantly higher than in PBMNCs of healthy controls. CACs derived from patients with HHT not only showed a significant reduction in EC-selective surface markers following 7-day culture, but also a significant increase in the rate of basal apoptosis and blunted migration in response to vascular endothelial growth factor and stromal cell-derived factor-1. CACs from HHT patients expressed significantly lower levels of ENG, ALK1 and eNOS mRNAs. In conclusion, CACs from patients with HHT exhibited various functional impairments, suggesting a reduced regenerative capacity of CACs to repair the vascular lesions seen in HHT patients.

  13. Ataxia-telangiectasia and wilms tumor: reduced treatment but early relapse.

    Science.gov (United States)

    Pérez-Villena, Ana; Cormenzana, María; de Prada, Inmaculada; Pérez-Martínez, Antonio; Aleo, Esther

    2013-05-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, a high incidence of lymphoreticular tumors, and an increased sensitivity to chemoradiotherapy-induced DNA damage. The appropriate cancer therapy remains unknown because of high toxicity rates with full-dose conventional protocols. We present a patient with A-T and nephroblastoma, who received an adapted treatment regimen. To our knowledge this is the second report on nephroblastoma in a patient with A-T but the first with confirmed premortem studies. Although the patient tolerated the chemotherapy regimen well, the patient relapsed and died a year after initial diagnosis.

  14. Macular edema in uveitis with emphasis on ocular sarcoidosis

    NARCIS (Netherlands)

    Norel, J. van

    2015-01-01

    This thesis investigates the accumulation of fluid in the yellow spot (macular edema) in ocular inflammation (uveitis). Macular edema may result in definitive loss of vision.Two methods of imaging of macular edema are fluorescein angiography (FA) and optical coherence tomography (OCT). The first met

  15. Management of macular epiretinal membrane by vitrectomy and intravitreal triamcinolone

    Directory of Open Access Journals (Sweden)

    Dhananjay Shukla

    2014-01-01

    Full Text Available A patient underwent successful vitrectomy for macular epiretinal membrane with anatomical and functional improvement. 10 weeks later, there was a recurrence of macular edema with corresponding visual decline. An intravitreal injection of triamcinolone acetonide not only restored the macular anatomy but also improved the visual outcome beyond that achieved after surgery.

  16. Macular edema in uveitis with emphasis on ocular sarcoidosis

    NARCIS (Netherlands)

    Norel, J. van

    2015-01-01

    This thesis investigates the accumulation of fluid in the yellow spot (macular edema) in ocular inflammation (uveitis). Macular edema may result in definitive loss of vision.Two methods of imaging of macular edema are fluorescein angiography (FA) and optical coherence tomography (OCT). The first met

  17. Surgical treatment of lamellar macular holes.

    Science.gov (United States)

    Michalewska, Zofia; Michalewski, Janusz; Odrobina, Dominik; Pikulski, Zbigniew; Cisiecki, Sławomir; Dziegielewski, Krzysztof; Nawrocki, Jerzy

    2010-10-01

    The aim of this study is to present functional and anatomical results of pars plana vitrectomy without gas tamponade in lamellar macular holes. Additionally, the study determines factors influencing final outcome. Twenty-six eyes of 26 patients with lamellar macular hole were diagnosed using spectral domain optical coherence tomography (SD-OCT). The diameters of the lamellar defects were measured. Pars plana vitrectomy with epiretinal membrane (ERM) removal and internal limiting membrane (ILM) peeling without endotamponade followed. Follow-up examinations were conducted with SD-OCT for a period of 12 months after surgery. The following factors were examined: maximum and minimum diameter of the lamellar defect, maximum diameter of the disruption of the photoreceptors, representing the photoreceptor layer, central macular thickness, paracentral macular thickness 1000 microm from the centre of the fovea, and maximum paracentral retinal thickness. Retina thickness was measured manually from the inner retina surface to the upper line of retinal pigment epithelium. Prior to surgery, mean visual acuity was 0.2. Twelve months after surgery, the mean visual acuity was 0.51. Lower visual acuity was observed in patients with photoreceptor layer defects localized under the fovea. Epiretinal membranes and complete or partial posterior hyaloid detachment were observed in all cases. The size of the lamellar defect had no influence on final visual acuity. The results obtained show that intraocular gas tamponade is not a crucial step in achieving closure and visual improvement in lamellar macular holes.

  18. Intravitreal triamcinolone for diffuse diabetic macular oedema.

    LENUS (Irish Health Repository)

    Gibran, S K

    2012-02-03

    AIM: To evaluate the efficacy of intravitreal triamcinolone (IVTA) for the treatment of diffuse diabetic macular oedema (DME) refractory to conventional argon macular laser therapy. METHODS: A prospective, consecutive, and noncomparative case series was undertaken involving 38 eyes of 38 patients with refractory DME. Triamcinolone acetonide (4 mg) in 0.1 ml was injected intravitreally. LogMar visual acuity (VA) and macular thickness measured by ocular coherence tomography (OCT) were assessed preoperatively and postoperatively at 1, 3, and 6 months. RESULTS: All patients completed 6 months of follow up. VA (mean+\\/-SD) improved from 0.905+\\/-0.23 to 0.605+\\/-0.28, 0.555+\\/-0.29, and 0.730+\\/-0.30 at 1, 3, and 6 months, respectively. Macular thickness baseline (mean+\\/-SD) on OCT was 418.7+\\/-104.2 microm and this decreased to 276.9+\\/-72.6 microm, 250.6+\\/-53.1 microm, and 308.8+\\/-87.3 microm at 1, 3, and 6 months, respectively. CONCLUSIONS: IVTA may be a potential temporary treatment for refractory DME. It is effective in decreasing macular thickness and improving VA but the effect lasts approximately for 6 months in the majority of patients. Further investigations are required to establish the safety of IVTA for the treatment of DME.

  19. Corticosteroid Treatment in Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Burcu Nurözler Tabakcı

    2017-06-01

    Full Text Available Diabetic macular edema is the most common cause of visual impairment in patients with diabetes mellitus. The pathogenesis of macular edema is complex and multifactorial. For many years, laser photocoagulation has been considered the standard therapy for the treatment of diabetic macular edema; however, few patients achieve significant improvements in visual acuity. Today the intravitreal administration of anti-inflammatory or anti-angiogenic agents together with the use of laser photocoagulation represents the standard of care for the treatment of this complication. The intravitreal route of administration minimizes the systemic side effects of corticosteroids. Steroid-related ocular side effects are elevated intraocular pressure and cataract, while injection-related complications include endophthalmitis, vitreous hemorrhage, and retinal detachment. In order to reduce the risks and complications, intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated injections for the management of diabetic macular edema. In this review, the efficacy, safety, and therapeutic potential of intravitreal corticosteroids in diabetic macular edema are discussed with a review of recent literature.

  20. [Sighting dominance in patients with macular disease].

    Science.gov (United States)

    Akaza, Eriko; Fujita, Kyoko; Shimada, Hiroyuki; Yuzawa, Mitsuko

    2007-04-01

    To study sighting dominance by comparing macular disease patients undergoing surgical treatment with controls. We studied visual acuity and sighting dominance in 92 macular disease patients, 27 of whom were assessed for both outcomes. We also studied visual acuity and sighting dominance in 412 controls. Sighting dominance was evaluated using the hole-in-card test. Among the controls, 70% showed right sighting dominance, and 30%, left sighting dominance. On the other hand, in patients with macular disease, right sighting dominance was demonstrated in 51%, and left in 49%; that is, 24% showed sighting dominance of the affected eye and 76%, of the fellow eye. During follow-up, sighting dominance of three of the 27 macular disease patients shifted from the affected eye to the fellow eye, which showed improvement in visual acuity. This study raises the possibility of sighting dominance shifting in patients with macular disease. There were differences among cases in the timing of the shift in sighting dominance, indicating that visual acuity may not be the only factor influencing sighting dominance. Further study is needed to confirm the factors contributing to sighting dominance.

  1. Spontaneously resolving macular cyst in an infant

    Directory of Open Access Journals (Sweden)

    Anuradha Ganesh

    2013-01-01

    Full Text Available The purpose of this study is to describe transient macular cysts in an infant and correlate their occurrence with normal development events. A newborn Caucasian girl presented with a protruding corneal mass in her left eye at birth. She underwent a complete ophthalmic examination. A keratinized staphylomatous malformation involving the entire cornea and precluding further visualization of the anterior and posterior segment was observed in the left eye. Spectral domain optical coherence tomography (SD-OCT of the right eye performed when the child was approximately 6-week-old had revealed an unexpected finding of macular cysts involving the inner nuclear and outer retinal layers. Corneal transplant in the left eye was performed a month later. Ocular examination under anesthesia just prior to surgery revealed normal intraocular pressure, anterior segment and retina in the right eye. SD-OCT was normal in both eyes and showed complete resolution of the cysts in the right eye. The patient had not been on any medications at that time. Although clinical retinal examination might be unremarkable, SD-OCT may reveal cystic spaces in the macula. In the absence of conditions known to be associated with macular edema, transient macular cysts may arise due to a developmental incompetence of the blood-retinal barrier or may represent transient spaces created during normal migration of retinal cells. Further study is warranted to delineate the entity of transient macular cysts in infancy.

  2. Long-term changes of macular retinal thickness after idiopathic macular hole surgery

    Directory of Open Access Journals (Sweden)

    Yan Yang

    2014-12-01

    Full Text Available AIM:To determine the changes of regional macular retinal thickness(RTwith spectral domain optical coherence tomography(SD-OCTafter successful pars plana vitrectomy(PPVsurgery with inner limiting membrane(ILMpeeling in patients with idiopathic macular hole.METHODS:A non-randomized retrospective case study on 17 patients(17 eyeswho were hospitalized between March 1, 2011 and June 30, 2013. All 17 eyes had been diagnosed with idiopathic macular hole and thereafter underwent 25G-PPV surgeries performed by the same surgeon with ILM peeling and short-term gas tamponade. In the 6mo-plus follow-up after surgery, these eyes were found to have successful closure in the macular hole. The macular RT of the nine areas in the Early Treatment Diabetic Retinopathy Study was measured by SD-OCT. All patients were applied by SD-OCT with linear scan of the macular. At least four examinations on the operated eye were conducted in contrast to the other normal eye: before the surgery, 3~5wk after the surgery(stage A, 2~3mo after the surgery(stage B, and >6mo after the surgery(stage C.RESULTS:In stage A, the macular RT of operated eyes in the areas of C, IS, II, IN, OS, OI, ON(263.00±39.48, 313.92±18.35, 311.00±18.02, 335.67±19.91, 280.83±33.74, 269.92±23.32, 307.00±28.40were significantly thicker than the corresponding areas of the normal fellow eyes(220.51±23.94, 292.08±21.93, 282.50±20.30, 288.33±20.76, 251.25±17.60, 247.75±21.48, 265.17±24.76μm(PP>0.01. In Stage B, the macular RT in the areas of II, IN, OS(335.67±19.20,319.75±19.20, 273.50±16.89μmwere significantly thicker than the corresponding areas of the normal fellow eyes(286.33±20.46, 293.42±17.64, 252.50±16.32μm(PP> 0.01. In Stage C, the macular RT of operated eyes with the areas of IN(321.17±19.71μmwere significantly thicker than the corresponding areas of the normal fellow eyes(296.25±19.57μm(PP>0.01. Moreover, the macular RT of operated eyes in the areas of ON, IT(307.00±28

  3. Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study.

    Science.gov (United States)

    Sahama, Ishani; Sinclair, Kate; Fiori, Simona; Doecke, James; Pannek, Kerstin; Reid, Lee; Lavin, Martin; Rose, Stephen

    2015-01-01

    Our understanding of the effect of ataxia-telangiectasia mutated gene mutations on brain structure and function is limited. In this study, white matter motor pathway integrity was investigated in ataxia telangiectasia patients using diffusion MRI and probabilistic tractography. Diffusion MRI were obtained from 12 patients (age range: 7-22 years, mean: 12 years) and 12 typically developing age matched participants (age range 8-23 years, mean: 13 years). White matter fiber tracking and whole tract statistical analyses were used to assess quantitative fractional anisotropy and mean diffusivity differences along the cortico-ponto-cerebellar, cerebellar-thalamo-cortical, somatosensory and lateral corticospinal tract length in patients using a linear mixed effects model. White matter tract streamline number and apparent fiber density in patient and control tracts were also assessed. Reduced fractional anisotropy along all analyzed patient tracts were observed (p ataxia telangiectasia showed significant white matter degeneration along the entire length of motor circuits, highlighting that ataxia-telangiectasia gene mutation impacts the cerebellum and multiple other motor circuits in young patients.

  4. Chemo- and radiosensitivity testing in a patient with ataxia telangiectasia and Hodgkin disease

    NARCIS (Netherlands)

    Tamminga, RYJ; Dolsma, WV; Leeuw, JA; Kampinga, HH

    2002-01-01

    Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersensitivity to radiation and chemotherapy. Most patients die, due to toxicity or rarely, to progressive disease. The authors report on a 9-year-old girl with stage IIA HD and AT She was treated with a tailor

  5. Tumor suppressor ataxia telangiectasia mutated functions downstream of TGF-β1 in orchestrating profibrotic responses

    NARCIS (Netherlands)

    Overstreet, Jessica M; Samarakoon, Rohan; Cardona-Grau, Diana; Goldschmeding, Roel|info:eu-repo/dai/nl/102376069; Higgins, Paul J

    2015-01-01

    Effective therapy to prevent organ fibrosis, which is associated with more than half of all mortalities, remains elusive. Involvement of tumor suppressor ataxia telangiectasia mutated (ATM) in the TGF-β1 pathway related to renal fibrosis is largely unknown. ATM activation (pATM(Ser1981)) increased 4

  6. Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia.

    Science.gov (United States)

    Exley, Andrew Robert; Buckenham, Samantha; Hodges, Elizabeth; Hallam, Robert; Byrd, Phil; Last, James; Trinder, Claire; Harris, Susan; Screaton, Nicholas; Williams, Anthony P; Taylor, A Malcolm R; Shneerson, John M

    2011-07-01

    ATM kinase modulates pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age. We address this paradox in a molecularly characterised sequential adult cohort with classical and mild variant ataxia telangiectasia. Immunodeficiency has the characteristics of premature ageing across multiple cellular and molecular immune parameters. This immune ageing occurs without previous CMV infection. Age predicts immunodeficiency in genetically homogeneous ataxia telangiectasia, and in comparison with controls, calendar age is exceeded by immunological age defined by thymic naïve CD4+ T cell levels. Applying ataxia telangiectasia as a model of immune ageing, pneumococcal vaccine responses, characteristically deficient in physiological ageing, are predicted by thymic naïve CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naïve CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Nano-Mechanical Characterization of Ataxia Telangiectasia Cells Treated with Dexamethasone.

    Science.gov (United States)

    Menotta, Michele; Biagiotti, Sara; Bartolini, Giulia; Marzia, Bianchi; Orazi, Sara; Germani, Aldo; Chessa, Luciana; Magnani, Mauro

    2017-03-01

    Ataxia telangiectasia is a rare genetic disease and no therapy is currently available. Glucocorticoid analogues have been shown to improve the neurological symptoms of treated patients. In the present study ataxia telangiectasia and wild type cells were used as a cellular model and treated with dexamethasone. The cells were subsequently investigated for membrane and whole cell mechanical properties by atomic force microscopy. In addition, cytoskeleton protein dynamics and nuclear shapes were assayed by fluorescence microscopy, while western blots were used to assess actin and tubulin content. At the macro level, dexamethasone directly modified the cell shape, Young's modulus and cytoskeleton protein dynamics. At the nano level, the roughness of the cell surface and the local nano-mechanical proprieties were found to be affected by Dexa. Our results show that ataxia telangiectasia and wild type cells are affected by Dexa, although there are dissimilarities in some macro-level and nano-level features between the tested cell lines. The Young's modulus of the cells appears to depend mainly on nuclear shape, with a slight contribution from the tested cytoskeleton proteins. The current study proposes that dexamethasone influences ataxia telangiectasia cell membranes contents, cell components and cell shape.

  8. The critically ill patient with ataxia-telangiectasia: a case series.

    Science.gov (United States)

    Lockman, Justin L; Iskander, Andrew J; Bembea, Melania; Crawford, Thomas O; Lederman, Howard M; McGrath-Morrow, Sharon; Easley, R Blaine

    2012-03-01

    To describe the presentation, clinical course, and outcomes of critically ill patients with ataxia-telangiectasia. Retrospective case series. Adult and pediatric intensive care units at an urban tertiary academic center. Seven consecutive patients with confirmed diagnosis of ataxia-telangiectasia had nine intensive care admissions between January 1995 and December 2009. None. Mean age at time of admission 15.9 yrs (median, 13.9 yrs; range, 7.3-33.9 yrs). Mean duration of intensive care unit stay was 17 days (median, 9 days; range, 2-39 days). The most common admitting diagnosis was respiratory distress (six of seven patients). There was no difference in ventilator settings or duration of intensive care unit stay between survivors and nonsurvivors (p > .05). Forty-three percent (three of seven patients) survived to intensive care unit discharge with a 3-yr survival that was 14% (one of seven patients). Critically ill patients with ataxia-telangiectasia have complex, multisystem diseases. In this case series, the most common intensive care unit admission diagnosis was respiratory failure. Suspected or confirmed bacterial infections were prevalent. Neuropathologic autopsy findings were similar to those previously reported. Special considerations for the critical care of patients with ataxia-telangiectasia are discussed.

  9. Cognitive and speech-language performance in children with ataxia telangiectasia

    NARCIS (Netherlands)

    Vinck, Anja; Verhagen, Mijke M. M.; van Gerven, Marjo; de Groot, Imelda J. M.; Weemaes, Corry M. R.; Maassen, Ben A. M.; Willemsen, Michel A. A. P.

    2011-01-01

    Objective: To describe cognitive and speech-language functioning of patients with ataxia-telangiectasia (A-T) in relation to their deteriorating (oculo)motor function. Design: Observational case series. Methods: Cognitive functioning, language, speech and oral-motor functioning were examined in eigh

  10. Whole-exome sequence analysis of ataxia telangiectasia-like phenotype.

    Science.gov (United States)

    Hasegawa, Setsuko; Imai, Kohsuke; Yoshida, Kenichi; Okuno, Yusuke; Muramatsu, Hideki; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Kojima, Seiji; Ogawa, Seishi; Morio, Tomohiro; Mizutani, Shuki; Takagi, Masatoshi

    2014-05-15

    A number of diseases exhibit neurodegeneration with/without additional symptoms such as immunodeficiency, increased cancer risk, and microcephalus. Ataxia telangiectasia and Nijmegen breakage syndrome, for example, develop as a result of mutations in genes involved in the DNA damage response. However, such diseases can be difficult to diagnose as they are only rarely encountered by physicians. To overcome this challenge, nine patients with symptoms that resemble those of ataxia telangiectasia, including neurodegeneration, hypogammaglobulinemia, telangiectasia, and/or elevated serum α-fetoprotein, were subjected to whole-exome sequencing (WES) to identify the causative mutations. Molecular diagnosis was achieved in two patients: one displayed CD40 ligand (CD40LG) deficiency, while a second showed a homozygous SIL1 mutation, which has been linked to Marinesco-Sjögren syndrome (MSS). Typical features of CD40LG deficiency and MSS are distinct from the symptoms usually seen in ataxia telangiectasia. These dissociations between phenotype and genotype make it difficult to achieve molecular diagnosis of orphan diseases. Whole-exome sequencing analyses will assist in the molecular diagnosis of such cases and allow the identification of genotypes that would not be expected from the phenotype. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Identification of ATM mutations in Korean siblings with ataxia-telangiectasia.

    Science.gov (United States)

    Huh, Hee Jae; Cho, Kyoo-Ho; Lee, Ji Eun; Kwon, Min-Jung; Ki, Chang-Seok; Lee, Phil Hyu

    2013-05-01

    Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder. It is characterized by early-onset, progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, conjunctival telangiectasias, immunodeficiency, and an increased risk of malignancy. Although A-T is known to be the most common cause of progressive cerebellar ataxia in childhood, there have been no confirmed cases in Korea. We report the clinical and genetic findings of Korean siblings who presented with limb and truncal ataxia, oculomotor apraxia, choreoathetosis, and telangiectasias of the eyes. Sequence analysis of the ataxia-telangiectasia mutated (ATM) gene revealed a known missense mutation (c.8546G>C; p.Arg2849Pro) and a novel intronic variant of intron 17 (c.2639-19_2639-7del13). Reverse-transcription PCR and sequencing analysis revealed that the c.2639-19_2639-7del13 variant causes a splicing aberration that potentiates skipping exon 18. Because A-T is quite rare in Korea, the diagnosis of A-T in Korean patients can be delayed. We recommend that a diagnosis of A-T should be suspected in Korean patients exhibiting the clinical features of A-T.

  12. Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia.

    Science.gov (United States)

    Li, Jiali; Chen, Jianmin; Ricupero, Christopher L; Hart, Ronald P; Schwartz, Melanie S; Kusnecov, Alexander; Herrup, Karl

    2012-05-01

    Ataxia telangiectasia is a neurodegenerative disease caused by mutation of the Atm gene. Here we report that ataxia telangiectasia mutated (ATM) deficiency causes nuclear accumulation of histone deacetylase 4 (HDAC4) in neurons and promotes neurodegeneration. Nuclear HDAC4 binds to chromatin, as well as to myocyte enhancer factor 2A (MEF2A) and cAMP-responsive element binding protein (CREB), leading to histone deacetylation and altered neuronal gene expression. Blocking either HDAC4 activity or its nuclear accumulation blunts these neurodegenerative changes and rescues several behavioral abnormalities of ATM-deficient mice. Full rescue of the neurodegeneration, however, also requires the presence of HDAC4 in the cytoplasm, suggesting that the ataxia telangiectasia phenotype results both from a loss of cytoplasmic HDAC4 as well as its nuclear accumulation. To remain cytoplasmic, HDAC4 must be phosphorylated. The activity of the HDAC4 phosphatase, protein phosphatase 2A (PP2A), is downregulated by ATM-mediated phosphorylation. In ATM deficiency, enhanced PP2A activity leads to HDAC4 dephosphorylation and the nuclear accumulation of HDAC4. Our results define a crucial role of the cellular localization of HDAC4 in the events leading to ataxia telangiectasia neurodegeneration.

  13. Treatment of Laryngeal Telangiectatic Lesions in a Patient Diagnosed with Hereditary Haemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, Anette Drøhse; Printz, Trine; Slot Mehlum, Camilla;

    2015-01-01

    Abstract We here present a case concerning a 69 year old female patient with Hereditary Haemorrhagic Telangiectasia (HHT). She was suffering from hoarseness due to a telangiectatic lesion on the right vocal cord. The lesion was treated with laser and the voice improved markedly, which is document...

  14. Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia.

    NARCIS (Netherlands)

    Hiel, J.A.P.; Engelen, B.G.M. van; Weemaes, C.M.R.; Broeks, A.; Verrips, A.; Laak, H.J. ter; Vingerhoets, H.M.; Heuvel, L.P.W.J. van den; Lammens, M.M.Y.; Gabreëls, F.J.M.; Last, J.I.; Taylor, A.M.R.

    2006-01-01

    The authors report four adult-onset ataxia telangiectasia (AT) patients belonging to two families lacking pronounced cerebellar ataxia but displaying distal spinal muscular atrophy. AT was proven by genetic studies showing ATM mutations and a reduced level of ATM. ATM activity, as measured by phosph

  15. Cognitive and speech-language performance in children with ataxia telangiectasia

    NARCIS (Netherlands)

    Vinck, Anja; Verhagen, Mijke M. M.; van Gerven, Marjo; de Groot, Imelda J. M.; Weemaes, Corry M. R.; Maassen, Ben A. M.; Willemsen, Michel A. A. P.

    2011-01-01

    Objective: To describe cognitive and speech-language functioning of patients with ataxia-telangiectasia (A-T) in relation to their deteriorating (oculo)motor function. Design: Observational case series. Methods: Cognitive functioning, language, speech and oral-motor functioning were examined in eigh

  16. Cognitive and speech-language performance in children with ataxia telangiectasia

    NARCIS (Netherlands)

    Vinck, A.; Verhagen, M.M.; Gerven, M.; Groot, I.J.M. de; Weemaes, C.M.R.; Maassen, B.A.M.; Willemsen, M.A.A.P.

    2011-01-01

    OBJECTIVE: To describe cognitive and speech-language functioning of patients with ataxia-telangiectasia (A-T) in relation to their deteriorating (oculo)motor function. DESIGN: Observational case series. METHODS: Cognitive functioning, language, speech and oral-motor functioning were examined in eigh

  17. Screening for macular disorders: the optometrist's perspective

    Directory of Open Access Journals (Sweden)

    Elsner AE

    2015-03-01

    Full Text Available Ann E Elsner, Brett J King School of Optometry, Indiana University, Bloomington, IN, USA Abstract: Macular screening services can take many forms, offering a variety of roles for optometrists. The need for screening has been demonstrated in industrialized and developing nations alike. Populations of particular interest for macular screening services include individuals at high risk for diabetes, not just diagnosed diabetics, since a significant proportion of those with diabetes do not realize it. Individuals who know they have diabetes are frequently not examined at the recommended intervals. Related populations include patients with a high likelihood of retinal vascular disease and high blood pressure. A second population is older individuals, who are at risk for age-related macular degeneration and degenerative myopia, key causes of vision loss depending upon geographic location and ethnicity. Images showing the complexity of lesions from diabetic retinopathy, age-related macular degeneration, and degenerative myopia illustrate the challenges of screening and classification. A third population to be screened is the large pediatric one. While many children are at risk for developing myopia, which could lead to high myopia, the risk of myopia and retinal damage is far more common in individuals who had low birth weight or premature birth. A variety of types of screening instrumentation are discussed in terms of practicality of use and cost. The technical challenges in populations with dark eyes, small pupils, and poor anterior-segment media are discussed. We discuss the wealth of screening strategies, from permanent sites with trained staff and expert graders to planned campaigns that target specific populations. Successful screening systems include instrumentation that is used within its limits, feedback and supervision during screening and grading, and clear pathways for referral for a complete examination or treatment. Keywords: vision

  18. [New aspects in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  19. The Electrophysiology in Idiopathic Senile Macular Hole

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    Of 12 patients with idiopathic senile full- thickness macular hole, 3 had bilateral involvement, 9 had monocular macular hole. Flash ERG and pattern VEP were performed in the bilateral eyes of all patients. The abnormal rate of the pattern VEP was 93.3% when we used 15' checkboard stimulus, the changes of the VEP appeared as delayed latencies, reduced amplitudes or malformation of P100. The abnormal rate of the flash ERG was 53.3%, showing primary characteristics of reduced amplitudes of cone response b...

  20. Precursors of age-related macular degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Toft, Ulla; Linneberg, Allan;

    2016-01-01

    PURPOSE: To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in complement factor H (CFHY402H) and ARMS2/LOC387715. METHODS: Cross......: In this cross-sectional study, a higher intake of vitamin A increased the risk of macular drusen >63 μm in subjects with CFHY402H. The study supports that vitamin A may be a risk factor for early AMD....

  1. Angiographically Documented Macular Ischemia after Single Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion.

    Science.gov (United States)

    Lee, Kyou Ho; Kang, Eui Chun; Koh, Hyoung Jun

    2017-05-01

    This report describes a case of angiographically documented foveal avascular zone (FAZ) enlargement after a single intravitreal injection of bevacizumab for macular edema secondary to central retinal vein occlusion (CRVO). A 71-year-old female was treated with an intravitreal bevacizumab injection for macular edema following CRVO. Despite successfully decreased edema one month after injection, the postinjection best-corrected visual acuity immediately decreased from 20/40 to 20/1000 (Snellen equivalent). The FAZ area increased from 0.37 mm² to 3.11 mm² (8.4-fold increase). While intravitreal anti-vascular endothelial growth factor is effective and should be considered as a first-line treatment for macular edema secondary to CRVO, it may aggravate macular ischemia. © Copyright: Yonsei University College of Medicine 2017.

  2. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    OpenAIRE

    Lai, Timothy Y. Y.; Fong

    2013-01-01

    Angie HC Fong,1 Timothy YY Lai1,2 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong; 22010 Retina and Macula Centre, Tsimshatsui, Kowloon, Hong Kong Abstract: Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially o...

  3. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration

    OpenAIRE

    Akuffo, Kwadwo Owusu; Nolan, John M.; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2016-01-01

    Purpose To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). Methods 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disa...

  4. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    OpenAIRE

    Fong, Angie HC; Lai, Timothy YY

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, mon...

  5. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    OpenAIRE

    Das, Undurti N

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies sug...

  6. Serous macular detachment, yellow macular deposits, and prominent middle limiting membrane in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Dogan B

    2015-04-01

    Full Text Available Berna Dogan,1 Muhammet Kazim Erol,1 Devrim Toslak,1 Deniz Turgut Coban,1 Mehmet Bulut,1 Ayse Cengiz,1 Esin Sogutlu Sari2 1Antalya Training and Research Hospital, Eye Clinic, Antalya, Turkey; 2Balikesir University Medicine Faculty, Eye Clinic, Balikesir, Turkey Abstract: Bone marrow-derived multiple myeloma is a type of plasma cell tumor that may be associated with ocular complications. A 52-year-old male patient was admitted to our eye clinic with the complaint of sudden visual loss and a visual acuity of 20/50 in the right eye and 20/800 in the left eye. Fundus examination revealed common flame-shaped hemorrhages, venous dilatation and tortuosity, Roth spots, serous macular detachment, and yellow macular deposits in both eyes. Evaluation with fundus fluorescein angiography, fundus autofluorescence, and spectral-domain optical coherence tomography resulted in suspicion of hyperviscosity retinopathy and referral to the hematology clinic. After hematology consultation confirmed a diagnosis of multiple myeloma, chemotherapy and plasmapheresis were initiated. Four months after presentation, best-corrected visual acuity was 20/20 in both eyes and improvement in hyperviscosity retinopathy, serous macular detachment, and yellow macular deposits was observed. Keywords: serous macular detachment, yellow macular deposit, prominent middle limiting membrane, multiple myeloma

  7. Macular thickness and volume in the elderly

    DEFF Research Database (Denmark)

    Subhi, Yousif; Forshaw, Thomas; Sørensen, Torben Lykke

    2016-01-01

    manifests in the macula of the elderly focusing on clinical relevant measures that are thicknesses and volumes of different macular areas. Ageing seems to increase center point foveal thickness. Ageing does not seem to change the center subfield thickness significantly. Ageing decreases the inner and outer...

  8. Driving and Age-Related Macular Degeneration

    Science.gov (United States)

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  9. Current status in diabetic macular edema treatments

    Institute of Scientific and Technical Information of China (English)

    Pedro; Romero-Aroca

    2013-01-01

    Diabetes is a serious chronic condition,which increase the risk of cardiovascular diseases,kidney failure and nerve damage leading to amputation.Furthermore the ocular complications include diabetic macular edema,is the leading cause of blindness among adults in the industrialized countries.Today,blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy.The treatment should include an optimized control of glycemia,arterial tension,lipids and renal status.The photocoagulation laser is currently restricted to focal macular edema in some countries,but due the high cost of intravitreal drugs,the use of laser treatment for focal and diffuse diabetic macular edema(DME),can be valid as gold standard in many countries.The intravitreal anti vascular endothelial growth factor drugs(ranibizumab and bevacizumab),are indicated in the treatment of all types of DME,but the correct protocol for administration should be defined for the different Retina Scientific Societies.The corticosteroids for diffuse DME,has a place in pseudophakic patients,but its complications restricted the use of these drugs for some patients.Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.

  10. Macular Amyloidosis and Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Yalda Nahidi

    2016-01-01

    Full Text Available Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group. There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8% and control (23.8% groups (P=0.08. Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis.

  11. Depression in Age-Related Macular Degeneration

    Science.gov (United States)

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  12. SMRT compounds abrogate cellular phenotypes of ataxia telangiectasia in neural derivatives of patient-specific hiPSCs.

    Science.gov (United States)

    Lee, Peiyee; Martin, Nathan T; Nakamura, Kotoka; Azghadi, Soheila; Amiri, Mandana; Ben-David, Uri; Perlman, Susan; Gatti, Richard A; Hu, Hailiang; Lowry, William E

    2013-01-01

    Ataxia telangiectasia is a devastating neurodegenerative disease caused primarily by loss of function mutations in ATM, a hierarchical DNA repair gene and tumour suppressor. So far, murine models of ataxia telangiectasia have failed to accurately recapitulate many aspects of the disease, most notably, the progressive cerebellar ataxia. Here we present a model of human ataxia telangiectasia using induced pluripotent stem cells, and show that small molecule read-through compounds, designed to induce read-through of mRNA around premature termination codons, restore ATM activity and improve the response to DNA damage. This platform allows for efficient screening of novel compounds, identification of target and off-target effects, and preclinical testing on relevant cell types for the pathogenic dissection and treatment of ataxia telangiectasia.

  13. “A DNA Damage Response (DDR) –independent Role for the Ataxia-Telangiectasia Mutated (ATM) Gene Product"

    OpenAIRE

    Palazzo, Luca

    2010-01-01

    Ataxia-Telangiectasia (A-T) is a recessive hereditary syndrome characterized by cerebellar degeneration, telangiectasia, precocious aging, immunodeficiency, cancer predisposition and insulin-resistant diabetes. A-T is caused by defects in Ataxia-Telagiectasia Mutated (Atm) gene. Atm encodes a ser/thr kinase (ATM) of the PI3 kinase family that plays a crucial role in the DNA damage response (DDR). Although some A-T features are easily explained by defects in DDR, others, like precocious aging,...

  14. Hereditary hemorrhagic telangiectasia: a rare cause of long-lasting abdominal distension in an 8-year-old boy

    Institute of Scientific and Technical Information of China (English)

    陈雷铃; 郎诗明; 胡廷泽; 钟麟; 李俊杰

    2002-01-01

    @@ Abdominal distension is a common complaint encountered in pediatric surgery. In most cases, Hirschsprung's disease is the most common cause associated with abdominal distension in older children. Hereditary hemorrhagic telangiectasia is a rare disease which commonly presents with hemorrhage and anemia. We treated an 8-year-old boy with long lasting intractable abdominal distension associated with hereditary hemorrhagic telangiectasia. Clinicopathologic features of this rare entity are discussed with emphasis on its pathogenesis and diagnosis.

  15. Microperimetry and optical coherence tomography in a case of traumatic macular hole and associated macular detachment with spontaneous resolution

    Directory of Open Access Journals (Sweden)

    Lalit Aalok

    2012-01-01

    Full Text Available The association of macular detachment with posttraumatic macular hole is a known but rare occurrence. Spontaneously occurring resolution of the detachment and closure of the macular hole has been reported only once in the literature. We describe a similar rare event in a young male, the documentation of which was done serially by microperimetry (MP and optical coherence tomography (OCT. A 17-year-old male presented with a decrease in vision following a closed globe injury to the left eye. A coexisting macular hole and macular detachment were detected in the affected eye. Serial follow-up with OCT and MP documented complete resolution of the macular hole and the macular detachment within 1 week of presentation. The case highlights that spontaneous resolution of traumatic macular hole and related macular detachment may occur and a waiting period is advisable before undertaking any corrective surgical procedure. The pathophysiologic mechanisms of causation and the resolution of posttraumatic macular hole-related retinal detachment are discussed.

  16. Gastric outlet obstruction due to adenocarcinoma in a patient with Ataxia-Telangiectasia syndrome: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Hammond Sue

    2009-03-01

    Full Text Available Abstract Background Ataxia-Telangiectasia syndrome is characterized by progressive cerebellar dysfunction, conjuctival and cutaneous telangiectasias, severe immune deficiencies, premature aging and predisposition to cancer. Clinical and radiographic evaluation for malignancy in ataxia-telangiectasia patients is usually atypical, leading to delays in diagnosis. Case presentation We report the case of a 20 year old ataxia-telangiectasia patient with gastric adenocarcinoma that presented as complete gastric outlet obstruction. Conclusion A literature search of adenocarcinoma associated with ataxia-telangiectasia revealed 6 cases. All patients presented with non-specific gastrointestinal complaints suggestive of ulcer disease. Although there was no correlation between immunoglobulin levels and development of gastric adenocarcinoma, the presence of chronic gastritis and intestinal metaplasia seem to lead to the development of gastric adenocarcinoma. One should consider adenocarcinoma in any patient with ataxia-telangiectasia who presents with non-specific gastrointestinal complaints, since this can lead to earlier diagnosis.

  17. Effect of change in macular birefringence imaging protocol on retinal nerve fiber layer thickness parameters using GDx VCC in eyes with macular lesions.

    Science.gov (United States)

    Dada, Tanuj; Tinwala, Sana I; Dave, Vivek; Agarwal, Anand; Sharma, Reetika; Wadhwani, Meenakshi

    2014-08-01

    This study evaluates the effect of two macular birefringence protocols (bow-tie retardation and irregular macular scan) using GDx VCC on the retinal nerve fiber layer (RNFL) thickness parameters in normal eyes and eyes with macular lesions. In eyes with macular lesions, the standard protocol led to significant overestimation of RNFL thickness which was normalized using the irregular macular pattern protocol. In eyes with normal macula, absolute RNFL thickness values were higher in irregular macular pattern protocols with the difference being statistically significant for all parameters except for inferior average thickness. This has implications for monitoring glaucoma patients who develop macular lesions during the course of their follow-up.

  18. Accurate diagnostics of ataxia-telangiectasia cellular phenotype by employing in vitro lymphocyte radiosensitivity testing

    Directory of Open Access Journals (Sweden)

    Vujić Dragana S.

    2013-01-01

    Full Text Available In this paper we present the data of lymphocyte radiosensitivity testing used for characterization of radiosensitive cellular phenotype and diagnostics of ataxia-telangiectasia disease. We point out the advantage of lymphocyte micronucleus test (CBMN over other cellular tests for assessment of radiosensitivity: the first advantage of CBMN is that primary patient cells are used (less than 1 ml, the second one is that the results of testing are obtained within 3 days and there is no need for establishing a patient-derived cell line, which requires additional time and application of more expensive methods. The third advantage of CBMN method is that it gives information about proliferative ability of cells, which can recognize dysfunctional ataxia-telangiectasia mutated protein. The results are fast and accurate in diagnostics of ataxia-telagiectasia diseases.

  19. Patient's evaluation of argon laser therapy of port wine stain, decorative tattoo, and essential telangiectasia.

    Science.gov (United States)

    Dixon, J A; Rotering, R H; Huether, S E

    1984-01-01

    One hundred fourteen patients were studied to assess their perception of the results of argon laser therapy for port wine stains (PWS), tattoos, or essential telangiectasia of legs. At least 1 yr following treatment patients were surveyed using a 30-item mail questionnaire. A 91% response rate was achieved. The findings indicate that patients with PWS and tattoo treated with argon laser are moderately satisfied with the results and 85% of them would have treatment again. Laser therapy of these lesions should be continued. Treatment results of essential telangiectasia of the legs are disappointing and only 49% of patients would have treatment again. Discontinuance of argon laser therapy using the described techniques is recommended.

  20. Accurate diagnostics of ataxia-telangiectasia cellular phenotype by employing in vitro lymphocyte radiosensitivity testing

    OpenAIRE

    Vujić Dragana S.; Petrović Sandra Ž.; Leskovac Andreja R.; Joksić Ivana D.; Filipović Jelena G.; Valenta-Šobot Ana P.

    2013-01-01

    In this paper we present the data of lymphocyte radiosensitivity testing used for characterization of radiosensitive cellular phenotype and diagnostics of ataxia-telangiectasia disease. We point out the advantage of lymphocyte micronucleus test (CBMN) over other cellular tests for assessment of radiosensitivity: the first advantage of CBMN is that primary patient cells are used (less than 1 ml), the second one is that the results of testing are obtained within 3 days and there is no nee...

  1. Dexamethasone improves redox state in ataxia telangiectasia cells by promoting an NRF2-mediated antioxidant response.

    Science.gov (United States)

    Biagiotti, Sara; Menotta, Michele; Orazi, Sara; Spapperi, Chiara; Brundu, Serena; Fraternale, Alessandra; Bianchi, Marzia; Rossi, Luigia; Chessa, Luciana; Magnani, Mauro

    2016-11-01

    Ataxia telangiectasia (A-T) is a rare incurable neurodegenerative disease caused by biallelic mutations in the gene for ataxia-telangiectasia mutated (ATM). The lack of a functional ATM kinase leads to a pleiotropic phenotype, and oxidative stress is considered to have a crucial role in the complex physiopathology. Recently, steroids have been shown to reduce the neurological symptoms of the disease, although the molecular mechanism of this effect is largely unknown. In the present study, we have demonstrated that dexamethasone treatment of A-T lymphoblastoid cells increases the content of two of the most abundant antioxidants [glutathione (GSH) and NADPH] by up to 30%. Dexamethasone promoted the nuclear accumulation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 to drive expression of antioxidant pathways involved in GSH synthesis and NADPH production. The latter effect was via glucose 6-phosphate dehydrogenase activation, as confirmed by increased enzyme activity and enhancement of the pentose phosphate pathway rate. This evidence indicates that glucocorticoids are able to potentiate antioxidant defenses to counteract oxidative stress in ataxia telangiectasia, and also reveals an unexpected role for dexamethasone in redox homeostasis and cellular antioxidant activity. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  2. Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites

    Science.gov (United States)

    Raymond, D.; Stoessl, A.J.; Hobson, D.; Nakamura, T.; Pullman, S.; Lefton, D.; Okun, M.S.; Uitti, R.; Sachdev, R.; Stanley, K.; San Luciano, M.; Hagenah, J.; Gatti, R.; Ozelius, L.J.; Bressman, S.B.

    2012-01-01

    Objective: To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. Methods: Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. Result: Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p ataxia on examination, and absence of ocular telangiectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. Conclusion: Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia. PMID:22345219

  3. Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong; Kim, Min Ju; Park, Sang-Min; Ryu, Junghyun; Ahn, Jin Seop; Heo, Soon Young; Kang, Jee Hyun; Choi, You Jung [Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan (Korea, Republic of); Choi, Seong-Jun [Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of); Shim, Hosup, E-mail: shim@dku.edu [Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan (Korea, Republic of); Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of); Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of)

    2014-10-03

    Highlights: • ATM gene-targeted pigs were produced by somatic cell nuclear transfer. • A novel large animal model for ataxia telangiectasia was developed. • The new model may provide an alternative to the mouse model. - Abstract: Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.

  4. Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

    Science.gov (United States)

    Shimada, Yoshiaki; Horiguchi, Masayuki

    2016-01-01

    ABSTRACT Leber hereditary optic neuropathy (LHON) causes visual loss, predominantly in healthy young men. We recently examined a patient who previously had bilateral macular holes and subsequently developed LHON at 74 years of age. Although his central scotomas were initially attributed to the macular holes, his visual acuity declined following an initial improvement after operative closure of the macular holes; thus, other diagnoses, including LHON, were considered. Furthermore, macular optical coherence tomography (OCT) images remained unchanged in this time. A mitochondrial genetic analysis identified a 11778G→A mutation. From this case, we propose that LHON remains in the differential diagnosis even in older patients, as has previously been reported. PMID:27335507

  5. Ataxia-Telangiectasia and RAD3-Related and Ataxia-Telangiectasia-Mutated Proteins in Epithelial Ovarian Carcinoma: Their Expression and Clinical Significance.

    Science.gov (United States)

    Lee, Banghyun; Lee, Hee Jin; Cho, Hye-Yon; Suh, Dong Hoon; Kim, Kidong; No, Jae Hong; Kim, Haeryoung; Kim, Yong-Beom

    2015-07-01

    The expression patterns of the key DNA damage response-related proteins, ataxia-telangiectasia and tfiih/ner complex atp-dependent 5'-3' dna helicase subunit rad3 (RAD3)-related (ATR) and ataxia-telangiectasia-mutated (ATM) proteins in ovarian cancer are not well-known. This study aimed to evaluate the expressions of ATR and ATM proteins, and to investigate their clinical significance in epithelial ovarian carcinoma (EOC). The expressions of nuclear/cytoplasmic Ser428-phosphorylated ATR (p-ATR) and Ser1981-phosphorylated ATM (p-ATM) were evaluated by immunohistochemistry in 100 patients with EOC. The clinical significances of p-ATR and p-ATM protein expression were evaluated in terms of tumor progression and survival. Low expression of cytoplasmic p-ATR was significantly associated with advanced stage, serous histology, large residual mass, and high preoperative serum CA125 level. Univariate survival analysis revealed that low expression of cytoplasmic p-ATR protein was significantly associated with poor disease-free survival and poor overall survival. Our study demonstrates that cytoplasmic ATR protein might serve as a prognostic biomarker for patients with EOC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Management of pseudophakic cystoid macular edema.

    Science.gov (United States)

    Guo, Suqin; Patel, Shriji; Baumrind, Ben; Johnson, Keegan; Levinsohn, Daniel; Marcus, Edward; Tannen, Brad; Roy, Monique; Bhagat, Neelakshi; Zarbin, Marco

    2015-01-01

    Pseudophakic cystoid macular edema (PCME) is a common complication following cataract surgery. Acute PCME may resolve spontaneously, but some patients will develop chronic macular edema that affects vision and is difficult to treat. This disease was described more than 50 years ago, and there are multiple options for clinical management. We discuss mechanisms, clinical efficacy, and adverse effects of these treatment modalities. Topical non-steroidal anti-inflammatory agents and corticosteroids are widely used and, when combined, may have a synergistic effect. Intravitreal corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) agents have shown promise when topical medications either fail or have had limited effects. Randomized clinical studies evaluating anti-VEGF agents are needed to fully evaluate benefits and risks. When PCME is either refractory to medical therapy or is associated with significant vitreous involvement, pars plana vitrectomy has been shown to improve outcomes, though it is associated with additional risks.

  7. [Treatment of retinal detachment with macular hole].

    Science.gov (United States)

    Pikulski, Z; Nawrocki, J; Dziegielewski, K

    1993-01-01

    The methods and results of surgery in 6 cases of retinal detachment with macular hole are presented. In all 6 cases pars plana vitrectomy was performed, in 4 with subsequent SF6 and in 2 with silicone oil tamponade. Retinal attachment was achieved in 4 eyes. Visual acuity 1/50-2/50 was found after surgery in 5 cases. The follow-up ranged from 6 to 9 months.

  8. Immunology of age related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Kijlstra Aize; Yang Peizeng

    2011-01-01

    @@ Age-related macular degeneration(AMD)is the most important cause of blindness in persons over 55 years of age in the Western world.In view of the increasing life expectancy we can assume that the problem will increase dramatically over the coming decades unless preventive or therapeutic measures are developed.Towards this goal many groups all over the world have performed epidemiological studies to identify potential risk factors for AMD.

  9. Depression in Age-Related Macular Degeneration

    OpenAIRE

    Casten,Robin; Rovner,Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depressio...

  10. Rehabilitation Approaches in Macular Degeneration Patients

    OpenAIRE

    Maniglia, Marcello; Benoit R Cottereau; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient’s quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in...

  11. Animal models of age related macular degeneration

    OpenAIRE

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  12. Current Treatments of Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Wei-Chun Chan

    2011-12-01

    Full Text Available Diabetic macular edema (DME is a major cause of visual impairment in diabetic patients. Laser photocoagulation is the standard management strategy for macular edema, but its results remain unsatisfactory. Several clinical trials of new treatment modalities for DME have been conducted over the past 10 years. We performed a literature search of English articles, published between 2000 and 2010, by using the PubMed database. The keywords searched included “diabetic macular edema and treatment” with limits set to include only clinical trials and review articles, over 50 articles were reviewed. Among the newer treatment modalities reviewed, therapy with anti-vascular endothelial growth factor (VEGF antibodies showed significantly better efficacy, with level I evidence. However, multiple injections were required to maintain its efficacy. Therefore, the associated complications and cost implications are the major limitations of this treatment. Several combinations of different modalities have been evaluated in the literature, but none are more efficacious than monotherapy with anti-VEGF antibodies. Since DME is a multifactorial disease, further studies involving combinations of modalities or new treatments modalities may be needed to reduce the number of injections required or improve the visual outcomes in case of DME.

  13. Visual hallucinations in patients with macular degeneration.

    Science.gov (United States)

    Holroyd, S; Rabins, P V; Finkelstein, D; Nicholson, M C; Chase, G A; Wisniewski, S C

    1992-12-01

    This study was undertaken to determine the prevalence of visual hallucinations in patients with macular degeneration, describe such hallucinations phenomenologically, and possibly determine factors predisposing to their development. Using a case-control design, the authors screened 100 consecutive patients with age-related macular degeneration for visual hallucinations. Each patient with visual hallucinations was matched to the next three patients without hallucinations. The patients and comparison subjects were compared in terms of scores on the Beck Depression Inventory, Eysenck Personality Questionnaire, Telephone Interview for Cognitive Status, and a structured questionnaire including demographic characteristics, family history, and medical and psychiatric history. Ophthalmologic data were obtained by chart review. Of the 100 patients, 13 experienced visual hallucinations. Four variables were significantly associated with having hallucinations: living alone, lower cognition score, history of stroke, and bilaterally worse visual acuity. Hallucinations were not associated with family or personal history of psychiatric disorder or with personality traits. In 11 (84.6%) of the 13 patients, the hallucinations had begun in association with an acute change in vision. These results indicate that visual hallucinations are prevalent among patients with macular degeneration. They appear unrelated to primary psychiatric disorder. The predisposing factors of bilaterally worse vision and living alone support an association with sensory deprivation, while history of stroke and worse cognition support a decreased cortical inhibition theory.

  14. Acute effect of pure oxygen breathing on diabetic macular edema

    DEFF Research Database (Denmark)

    Vinten, Carl Martin; La Cour, Morten; Lund-Andersen, Henrik

    2012-01-01

    Purpose. A small-scale pilot study of the pathophysiology of diabetic macular edema (DME) was made by assessing concomitant changes in macular volume (MV), mean arterial blood pressure (MABP), intraocular pressure (IOP), retinal artery diameter (RAD), and retinal vein diameter (RVD) in response t...

  15. Interocular agreement in melanin and macular pigment optical density.

    NARCIS (Netherlands)

    Kanis, M.J.; Berendschot, T.T.J.M.; van Norren, D.

    2007-01-01

    Macular pigment (MP) and melanin possibly protect the macular area by absorbing blue light and acting as antioxidants. Because little is known about the interocular correlation of melanin, we determined its optical density (MOD) in both eyes of healthy subjects using fundus reflectometry. The measur

  16. Spontaneous closure of macular hole following blunt trauma

    Directory of Open Access Journals (Sweden)

    Clovis Arcoverde Freitas-Neto

    2016-01-01

    Full Text Available Ocular trauma can result in macular hole and it can lead to complete loss of central vision. We are reporting a case of traumatic macular hole associated with retinal hemorrhages and choroidal ruptures with spontaneous resolution and total vision recovery.

  17. Acute effect of pure oxygen breathing on diabetic macular edema

    DEFF Research Database (Denmark)

    Vinten, Carl Martin; La Cour, Morten; Lund-Andersen, Henrik;

    2012-01-01

    Purpose. A small-scale pilot study of the pathophysiology of diabetic macular edema (DME) was made by assessing concomitant changes in macular volume (MV), mean arterial blood pressure (MABP), intraocular pressure (IOP), retinal artery diameter (RAD), and retinal vein diameter (RVD) in response...

  18. Quantification of metamorphopsia in patients with macular hole

    DEFF Research Database (Denmark)

    Kroyer, K.; Christensen, U.; Larsen, M.;

    2008-01-01

    .001). CONCLUSIONS. The level of metamorphopsia declined as a function of eccentricity and affected the central 10 of visual field. Macular hole size had an independent effect on interocular disparity. These results confirm reports that visuospatial distortion in the presence of macular hole is primarily the result...

  19. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde;

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  20. Acetazolamide for cystoid macular oedema in Bietti crystalline retinal dystrophy.

    Science.gov (United States)

    Broadhead, Geoffrey K; Chang, Andrew A

    2014-04-01

    Bietti crystalline retinal dystrophy is a rare, inherited disorder whose hallmark is the presence of retinal crystal deposits associated with later chorioretinal degeneration. This condition may rarely be complicated by the development of cystoid macular oedema leading to rapid visual decline. Currently, treatment options for this complication of Bietti dystrophy are limited and the visual prognosis is poor. Here, we present a case of cystoid macular oedema associated with Bietti dystrophy that was successfully diagnosed using multimodal imaging techniques including optical coherence tomography and fluorescein angiography. These modalities confirmed the diagnosis of macular oedema and excluded other possible causes of oedema such as choroidal neovascularisation. In this patient, cystoid macular oedema was resolved with oral acetazolamide therapy, a treatment that has not been previously reported in this context. Acetazolamide treatment resulted in oedema resolution and improvement in visual function, and can be considered a therapeutic option for other patients with Bietti dystrophy who develop cystoid macular oedema.

  1. Effect of macular photocoagulation on visual acuity of Omani patients with clinically significant macular edema

    Directory of Open Access Journals (Sweden)

    Zafar A Zaidi

    2009-01-01

    Full Text Available Background: The aim of this study was to determine the effect of macular laser treatment on the visual acuity (VA of Omani diabetic patients with clinically significant macular edema (CSME. Visual outcome was also correlated with duration and control of diabetes and presence or absence of hypertension and hyperlipidemia. Materials and Methods: This is a retrospective noncomparative cohort study involving 101 eyes of 72 Omani diabetic patients. Change in VA was determined using Snellen′s VA chart. The mean duration of follow-up was approximately 21 months (range, 16-24 months. Results: 29.7% of the patients maintained their vision, 35.6% showed improvement, whereas 34.7% showed a decrease in their vision. Positive visual outcome showed a statistically significant direct relationship with tight control of diabetes and absence of hypertension and an inverse relationship with the duration of diabetes. Presence of hyperlipedemia did not show a statistically significant relationship with positive visual outcome. However, it showed a trend to better visual outcome in the absence of hyperlipedemia. Peak incidence of macular edema was seen at the age of 52.3 years. Conclusion: Macular photocoagulation was found to be an effective method of treatment for CSME among Omani diabetic patients, which has resulted in a positive visual outcome in 65.3% of the patients (stable and improved vision. Effective control of diabetes, duration of diabetes, and hypertension are the factors which influence the postlaser visual outcome.

  2. Visual loss related to macular subretinal fluid and cystoid macular edema in HIV-related optic neuropathy

    DEFF Research Database (Denmark)

    Gautier, David; Rabier, Valérie; Jallet, Ghislaine;

    2012-01-01

    Optic nerve involvement may occur in various infectious diseases, but is rarely reported after infection by the human immunodeficiency virus (HIV). We report the atypical case of a 38-year-old patient in whom the presenting features of HIV infection were due to a bilateral optic neuropathy associ...... associated with macular subretinal fluid and cystoid macular edema, which responded well to antiretroviral therapy....

  3. Efficacy of intravitreal ranibizumab injection combined with macular grid photocoagulation for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Hu-Lin Jiang

    2014-07-01

    Full Text Available AIM:To evaluate the clinical efficacy of intravitreal injection of ranibizumab combined with macular grid photocoagulation for diabetic macular edema(DME.METHODS:Totally 60 eyes(60 patientswith DME were randomly divided into 2 groups: 30 eyes of simple injection group underwent intravitreal injection of ranibizumab, and 30 eyes of combined treatment group underwent intravitreal injection of ranibizumab and macular grid photocoagulation 1wk later. The best corrected visual acuity(BCVA, central macular thickness(CMTmeasured by optical coherence tomography(OCTand postoperative complications were observed.RESULTS:In simple injection group, the BCVA after operation were separately 0.390±0.075(4wk, 0.367±0.088(8wkand 0.319±0.064(12wk,the CMT after operation were separately 221.63±112.34μm(4wk, 337.73±99.56μm(8wkand 432.92±100.46μm(12wk, which were much better than pre-operation. But during follow-up, the BCVA presented down trend and the CMT was on the rise slowly. In combined treatment group, the BCVA after operation were separately 0.385±0.036(4wk, 0.382±0.079(8wkand 0.377±0.097(12wk,the CMT after operation were separately 249.77±106.55μm(4wk, 270.40±92.88μm(8wkand 275.84±97.34μm(12wk, which were satisfactory and steady during follow-up, better than simple injection group(PCONCLUSION:Intravitreal injection of ranibizumab can effectively improve visual acuity and decrease central foveal thickness for patients with DME, combining with macular grid photocoagulation can ensure therapeutic effects steady and permanent.

  4. The macular mapping test: a reliability study

    Directory of Open Access Journals (Sweden)

    Davies Leon N

    2005-08-01

    Full Text Available Abstract Background Age-related macular degeneration (ARMD is the leading cause of visual disability in people over 60 years of age in the developed world. The success of treatment deteriorates with increased latency of diagnosis. The purpose of this study was to determine the reliability of the macular mapping test (MMT, and to investigate its potential as a screening tool. Methods The study population comprised of 31 healthy eyes of 31 participants. To assess reliability, four macular mapping test (MMT measurements were taken in two sessions separated by one hour by two practitioners, with reversal of order in the second session. MMT readings were also taken from 17 age-related maculopathy (ARM, and 12 AMD affected eyes. Results For the normal cohort, average MMT scores ranged from 85.5 to 100.0 MMT points. Scores ranged from 79.0 to 99.0 for the ARM group and from 9.0 to 92.0 for the AMD group. MMT scores were reliable to within ± 7.0 points. The difference between AMD affected eyes and controls (z = 3.761, p = Conclusion The reliability data shows that a change of 14 points or more is required to indicate a clinically significant change. This value is required for use of the MMT as an outcome measure in clinical trials. Although there was no difference between MMT scores from ARM affected eyes and controls, the MMT has the advantage over the Amsler grid in that it uses a letter target, has a peripheral fixation aid, and it provides a numerical score. This score could be beneficial in office and home monitoring of AMD progression, as well as an outcome measure in clinical research.

  5. Outcomes of chronic macular hole surgical repair

    Directory of Open Access Journals (Sweden)

    Shripaad Y Shukla

    2014-01-01

    Full Text Available Purpose: To report visual and anatomic outcomes of chronic macular hole surgery, with analysis of pre-operative OCT-based hole size and post-operative closure type. Settings and Design: An IRB-approved, retrospective case series of 26 eyes of 24 patients who underwent surgery for stage 3 or 4 idiopathic chronic macular holes at a tertiary care referral center. Statistical Analysis: Student′s t-test. Results: Nineteen of 26 eyes (73% had visual improvement after surgery on most recent exam. Twenty-one of 26 eyes (81% achieved anatomic closure; 16 of 26 eyes (62% achieved type 1, and five of 26 eyes (19% achieved type 2 closure. Post-operative LogMAR VA for type 1 closure holes (0.49 was significantly greater than for type 2 closure and open holes (1.26, P < 0.003 and 1.10, P < 0.005, respectively, despite similar pre-operative VA (P = 0.51 and 0.68, respectively. Mean pre-operative hole diameter for eyes with type 1 closure, type 2 closure, and holes that remained open were 554, 929, and 1205 microns, respectively. Mean pre-operative hole diameter was significantly larger in eyes that remained open as compared to eyes with type 1 closure (P = 0.015. Conclusion: Vitrectomy to repair chronic macular holes can improve vision and achieve long-term closure. Holes of greater than 3.4 years duration were associated with a greater incidence of remaining open and type 2 closure. Larger holes (mean diameter of 1205 microns were more likely to remain open after repair.

  6. Forward subtractive libraries containing genes transactivated by dexamethasone in ataxia-telangiectasia lymphoblastoid cells.

    Science.gov (United States)

    Biagiotti, Sara; Menotta, Michele; Giacomini, Elisa; Radici, Lucia; Bianchi, Marzia; Bozzao, Cristina; Chessa, Luciana; Magnani, Mauro

    2014-07-01

    Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder caused by biallelic mutations in the Ataxia Telangiectasia-mutated gene. A-T shows a complex phenotype ranging from early-onset progressive neurodegeneration to immunodeficiencies, high incidence of infections, and tumors. Unfortunately, no therapy is up to now available for treating this condition. Recently, the short term treatment of ataxia-telangiectasia patients with glucocorticoids was shown to improve their neurological symptoms and possibly reverse cerebellar atrophy. Thus, corticosteroids represent an attractive approach for the treatment of this neurodegenerative disease. However, the molecular mechanism involved in glucocorticoid action in A-T is yet unknown. The aim of our work is to construct cDNA libraries containing those genes which are transactivated by the glucocorticoid analogue, dexamethasone, in A-T human cells. For this purpose, suppression subtractive hybridization has been performed on ATM-null lymphoblastoid cell transcriptome extracted following drug administration. Annotation of whole genes contained in the libraries has been obtained by coupling subtractive hybridization with microarray analysis. Positive transcripts have been validated by quantitative PCR. Through in silico analyses, identified genes have been classified on the basis of the pathway in which they are involved, being able to address signaling required for dexamethasone action. Most of the induced transcripts are involved in metabolic processes and regulation of cellular processes. Our results can help to unravel the mechanism of glucocorticoid action in the reversion of A-T phenotype. Moreover, the induction of a specific region of the ATM transcript has been identified as putative biomarker predictive of dexamethasone efficacy on ataxic patients.

  7. Ataxia-telangiectasia in the south of Tunisia: A study of 11 cases.

    Science.gov (United States)

    Sfaihi, Lamia; Stoppa Lyonnet, Dominique; Ben Ameur, Salma; Dubois D'enghien, Catherine; Kamoun, Thouraya; Barbouch, Mohamed Ridha; Hachicha, Mongia

    2015-01-01

    Ataxia-telangiectasia (A-T) is a multisystem disorder characterized by progressive neurologic impairment, variable immunodeficiency, impaired organ maturation, X-ray hypersensitivity, oculocutaneous telangiectasia, and a predisposition to malignancy. We performed this study in order to describe clinical, immunological and molecular features of patients with AT followed in the south of Tunisia Methods: we performed a retrospective study (1996-2012) in the south of Tunisia about all cases of A-T in order to describe their clinical, immunological and molecular features. 11 cases of AT were found. The mean age at onset of symptoms was 20 months with extremes varying from 3 months to 4 years. The median time to diagnosis was 3.6 years (range: 0-12 years).The main clinical feature of cerebellar syndrome, ataxia, was present at diagnosis in 8 patients and occurred at mean ages of 2.8 years. Ocular telangiectasia occurred at a mean age of 3.9 years (extremes: 3 months and 7 years). Recurrent sino-pulmonary infections that affected 7 children occurred at the mean age of 4.3 years. The most common humoral immune abnormality was serum IgA deficiency. Lymphopenia was found in 7 cases and lack of CD4 T in 6 cases. Cytogenetic analyses showed chromosomal instability in all children and a translocation (7-14) in two patients. A molecular diagnosis established in 6 patients from 4 families showed 5 different mutations of ATM gene. After an average decline of 5 years and 6 months, 7 patients died of severe pulmonary infection. Among them, 3 were ATM mutated. Morbidity and mortality among patients with A- T are associated with ATM genotype.

  8. Inmunodeficiencia con ataxia telangiectasia: presentación de 4 casos

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    Ma. Victoria Guntiñas Zamora

    2004-03-01

    Full Text Available Se presentan 4 pacientes con síntomas y signos propios de una inmunodeficiencia con ataxia telangiectasia, tanto desde el punto de vista clínico como de los marcadores serológicos y celulares. En todos los casos la ataxia se evidenció cuando los pacientes comenzaron a caminar, las telangiectasias tuvieron una aparición más tardía y las infecciones fueron manifiestas desde edades muy tempranas. Los defectos inmunológicos fueron heterogéneos, tanto de células B como T. Todos los pacientes se encuentran actualmente bajo tratamiento inmunoestimulante a pesar de lo cual mantienen cuadros infecciosos frecuentes. La enfermedad neurológica progresa. Se recomienda el seguimiento estrecho de los casos por la posible aparición de complicaciones graves como enfermedad pulmonar crónica o neoplasias linforreticulares4 patients with symptoms and signs typical of an immunodeficiency with ataxia telangiectasia from the clinical point of view and from the point of view of the serological and cellular markers are presented. In all the cases, ataxia was confirmed when the patients began to walk. Telangiectasies had a later appearance and the infections manifested at very early ages. The immunological defects of B and T cells were heterogeneous. The patients maintain infectious pictures despite being under immunostimulating treatment. The neurological disease is in progress. It is recommended the close follow-up of the cases due to the possible emergence of severe complications, such as chronic pulmonary disease or lymphoreticular neoplasias.

  9. [Age-related macular degeneration (AMD)].

    Science.gov (United States)

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  10. Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Kjeldsen, A.D.; Ousager, L.B.

    2012-01-01

    Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817......-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal...

  11. Transcatheter closure of a pulmonary arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Parker, Christopher; Rousan, Talla A; Abu-Fadel, Mazen

    2015-07-01

    Pulmonary arteriovenous malformations (PAVM) are rare pulmonary vascular anomalies. Over 50 % of the cases are associated with hereditary hemorrhagic telangiectasia or Osler-Weber-Rendu Syndrome. Untreated PAVMs progressively enlarge and can cause significant right-to-left shunting. Surgical- and catheter-based approaches have been used in the management of PAVM. We report a case of a 74-year-old man who presented with dyspnea and hypoxia and was found to have a large right-sided PAVM. He underwent percutaneous closure of the PAVM with an Amplatzer device with significant improvement of his symptoms.

  12. Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability.

    Science.gov (United States)

    Fukawatase, Yoshihiro; Toyoda, Masashi; Okamura, Kohji; Nakamura, Ken-ichi; Nakabayashi, Kazuhiko; Takada, Shuji; Yamazaki-Inoue, Mayu; Masuda, Akira; Nasu, Michiyo; Hata, Kenichiro; Hanaoka, Kazunori; Higuchi, Akon; Takubo, Kaiyo; Umezawa, Akihiro

    2014-06-27

    Ataxia telangiectasia is a neurodegenerative inherited disease with chromosomal instability and hypersensitivity to ionizing radiation. iPS cells lacking ATM (AT-iPS cells) exhibited hypersensitivity to X-ray irradiation, one of the characteristics of the disease. While parental ataxia telangiectasia cells exhibited significant chromosomal abnormalities, AT-iPS cells did not show any chromosomal instability in vitro for at least 80 passages (560 days). Whole exome analysis also showed a comparable nucleotide substitution rate in AT-iPS cells. Taken together, these data show that ATM is involved in protection from irradiation-induced cell death.

  13. Early neonatal complications from pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: case report and review of the literature.

    Science.gov (United States)

    Gludovacz, Karoy; Vlasselaer, Jozef; Mesens, Tinne; Van Holsbeke, Caroline; Van Robays, Johan; Gyselaers, Wilfried

    2012-08-01

    Hereditary hemorrhagic telangiectasia (HHT) is a rare but life-threatening disease characterized by multi system telangiectasias and arteriovenous malformations (AVM). Complications in adults have been reported extensively, but neonatal (NN) complications have only been published in incidental case reports. In this paper, we present a literature review on NN pulmonary AVM related to HHT, following our own experience with a NN death due to this disease. As prenatal diagnosis of pulmonary AVM is feasible, we recommend that a family history of HHT should be an indication for expertise prenatal anomaly scanning, in order to organise optimal NN support at birth.

  14. Update on corticosteroids for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Schwartz SG

    2016-09-01

    Full Text Available Stephen G Schwartz,1 Ingrid U Scott,2,3 Michael W Stewart,4 Harry W Flynn Jr1 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 2Department of Ophthalmology, 3Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, 4Department of Ophthalmology, Mayo Clinic Florida, Jacksonville, FL, USA Abstract: Diabetic macular edema (DME remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME. Keywords: diabetic macular edema, vascular endothelial growth factor, triamcinolone acetonide, dexamethasone, fluocinolone acetonide, randomized clinical trial

  15. Acute Macular Neuroretinopathy Associated With Chikungunya Fever.

    Science.gov (United States)

    Pang, Claudine E; Navajas, Eduardo V; Warner, Simon J; Heisler, Morgan; Sarunic, Marinko V

    2016-06-01

    A 47-year-old man with recent travel to the Caribbean was admitted with acute febrileillness associated with arthralgia and skin rash followed by sudden onset of bilateral visual field defects. Funduscopy revealed subtle bilateral paracentral dark lesions nasal to the fovea best seen on near infrared imaging as hyporeflective, wedge-shaped, paracentral macular lesions. Spectral-domain optical coherence tomography (SD-OCT) through the lesions revealed hyperreflective bands at the level of the outer plexiform layer and outer nuclear layer (ONL), with concomitant attenuation of the underlying external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Neither fluorescein angiography nor speckle variance OCT angiography (sv-OCTA) showed any defects in retinal circulation. Work up revealed positive Immunoglobulin M for Chikungunya virus (CHIKV). Six months later, the patient had persistent scotomas, although reduced in size. SD-OCT showed subtle ONL thinning and restoration of the ELM, although EZ and IZ remained disrupted. Chikungunya fever may manifest as bilateral acute macular neuroretinopathy (AMN). Clinicians should be aware of possible systemic associations of AMN. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:596-599.]. Copyright 2016, SLACK Incorporated.

  16. [Physiopathology of macular edema in central vein occlusion].

    Science.gov (United States)

    Stanca, Horia T; Manea, Georgiana

    2012-01-01

    Retinal Vein Occlusions are vascular diseases affecting the Central Retinal Vein and its branches causing decreased retinal drainage resulting in significant clinical and functional pathological changes. RVO determines the increase of vascular permeability, with edema and hemorrhage and development of collateral vessels in a few weeks. Among the serious consequences of venous occlusion is the installation of macular edema to which depends long-term visual prognosis. Macular Edema is the accumulation of intraretinal serous fluid in the macular area caused by the breakdown of blood-retinal barrier.

  17. Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions.

    Science.gov (United States)

    Ambrose, Mark; Gatti, Richard A

    2013-05-16

    In 1988, the gene responsible for the autosomal recessive disease ataxia- telangiectasia (A-T) was localized to 11q22.3-23.1. It was eventually cloned in 1995. Many independent laboratories have since demonstrated that in replicating cells, ataxia telangiectasia mutated (ATM) is predominantly a nuclear protein that is involved in the early recognition and response to double-stranded DNA breaks. ATM is a high-molecular-weight PI3K-family kinase. ATM also plays many important cytoplasmic roles where it phosphorylates hundreds of protein substrates that activate and coordinate cell-signaling pathways involved in cell-cycle checkpoints, nuclear localization, gene transcription and expression, the response to oxidative stress, apoptosis, nonsense-mediated decay, and others. Appreciating these roles helps to provide new insights into the diverse clinical phenotypes exhibited by A-T patients-children and adults alike-which include neurodegeneration, high cancer risk, adverse reactions to radiation and chemotherapy, pulmonary failure, immunodeficiency, glucose transporter aberrations, insulin-resistant diabetogenic responses, and distinct chromosomal and chromatin changes. An exciting recent development is the ATM-dependent pathology encountered in mitochondria, leading to inefficient respiration and energy metabolism and the excessive generation of free radicals that themselves create life-threatening DNA lesions that must be repaired within minutes to minimize individual cell losses.

  18. Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia.

    Science.gov (United States)

    Byrd, P J; Srinivasan, V; Last, J I; Smith, A; Biggs, P; Carney, E F; Exley, A; Abson, C; Stewart, G S; Izatt, L; Taylor, A M

    2012-01-17

    Severe early and late radiation reaction to radiotherapy is extremely rare in breast cancer patients. Such a reaction prompted an investigation into a 44-year-old mother (patient A-T213). A neurological examination was performed and blood lymphocytes and skin fibroblasts were assessed for radiosensitivity chromosomally and by colony-forming assay. The ATM gene was sequenced and ATM mutations modelled by site-directed mutagenesis. The ATM kinase activity was also assessed. Patient A-T213 was normally ambulant with no ataxia and minimal other neurological features. T lymphocytes and skin fibroblasts were unusually radiosensitive, although less sensitive than in classical ataxia telangiectasia (A-T). A lymphoblastoid cell line and skin fibroblasts expressed ATM protein with some retained kinase activity. One missense ATM mutation c.8672G>A (p.Gly2891Asp) and a c.1A>G substitution were identified. In the modelling system, the p.Gly2891Asp mutant protein was expressed and shown to have residual ATM kinase activity. Patient A-T213 has a milder form of A-T with biallelic ATM mutations, which may have contributed to breast cancer development, and certainly caused the severe radiation reaction. Ataxia telangiectasia should be investigated as a potential cause of untoward severe early and late radiation reactions in breast cancer patients.

  19. Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer.

    Science.gov (United States)

    Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong; Kim, Min Ju; Park, Sang-Min; Ryu, Junghyun; Ahn, Jin Seop; Heo, Soon Young; Kang, Jee Hyun; Choi, You Jung; Choi, Seong-Jun; Shim, Hosup

    2014-10-03

    Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Class switch recombination process in ataxia telangiectasia patients with elevated serum levels of IgM.

    Science.gov (United States)

    Mohammadinejad, Payam; Abolhassani, Hassan; Aghamohammadi, Asghar; Pourhamdi, Shabnam; Ghosh, Sujal; Sadeghi, Bamdad; Nasiri Kalmarzi, Rasoul; Durandy, Anne; Borkhardt, Arndt

    2015-01-01

    Ataxia telangiectasia (AT) is a rare primary immunodeficiency disorder with various clinical manifestations. Increased serum levels of IgM and recurrent infections, mainly sinopulmonary infections, can be the presenting feature in a number of AT patients and may be initially misdiagnosed as hyper-IgM (HIgM) syndrome. This study was designed to investigate class switch recombination (CSR) as a critical mechanism in B lymphocytes' maturation to produce different isotypes of antibody in response to antigen stimulation in AT cases with HIgM presentation. Quantitative IgE production after stimulation by IL-4 and CD40L was considered as an indicator for CSR function. We also compared their results with sex and age matched AT patients without HIgM presentation. We report four AT patients with recurrent infections during infancy and high serum levels of IgM. Laboratory evaluations revealed defective CSR while none of the three AT patients without HIgM presentation had a defect in the CSR process. The characterized defect in AT is a mutation in the ataxia telangiectasia mutated (ATM) gene. This gene may result in CSR defects due to impaired DNA break repair. A special association between AT and HIgM may indicate a new subgroup of AT patients according to their clinical phenotype and CSR condition.

  1. p53 centrosomal localization diagnoses ataxia-telangiectasia homozygotes and heterozygotes.

    Science.gov (United States)

    Prodosmo, Andrea; De Amicis, Andrea; Nisticò, Cecilia; Gabriele, Mario; Di Rocco, Giuliana; Monteonofrio, Laura; Piane, Maria; Cundari, Enrico; Chessa, Luciana; Soddu, Silvia

    2013-03-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder characterized by radiosensitivity, genomic instability, and predisposition to cancer. A-T is caused by biallelic mutations in the ataxia-telangiectasia mutated (ATM) gene, but heterozygous carriers, though apparently healthy, are believed to be at increased risk for cancer and more sensitive to ionizing radiation than the general population. Despite progress in functional and sequencing-based assays, no straightforward, rapid, and inexpensive test is available for the identification of A-T homozygotes and heterozygotes, which is essential for diagnosis, genetic counseling, and carrier prediction. The oncosuppressor p53 prevents genomic instability and centrosomal amplification. During mitosis, p53 localizes at the centrosome in an ATM-dependent manner. We capitalized on the latter finding and established a simple, fast, minimally invasive, reliable, and inexpensive test to determine mutant ATM zygosity. The percentage of mitotic lymphoblasts or PBMCs bearing p53 centrosomal localization clearly discriminated among healthy donors (>75%), A-T heterozygotes (40%-56%), and A-T homozygotes (<30%). The test is specific for A-T, independent of the type of ATM mutations, and recognized tumor-associated ATM polymorphisms. In a preliminary study, our test confirmed that ATM is a breast cancer susceptibility gene. These data open the possibility of cost-effective, early diagnosis of A-T homozygotes and large-scale screenings for heterozygotes.

  2. NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease.

    Science.gov (United States)

    Weyemi, Urbain; Redon, Christophe E; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R; Bonner, Michael Y; Arbiser, Jack L; Bonner, William M

    2015-02-17

    Ataxia telangiectasia (A-T), a rare autosomal recessive disorder characterized by progressive cerebellar degeneration and a greatly increased incidence of cancer among other symptoms, is caused by a defective or missing ataxia telangiectasia mutated (ATM) gene. The ATM protein has roles in DNA repair and in the regulation of reactive oxygen species (ROS). Here, we provide, to our knowledge, the first evidence that NADPH oxidase 4 (NOX4) is involved in manifesting A-T disease. We showed that NOX4 expression levels are higher in A-T cells, and that ATM inhibition leads to increased NOX4 expression in normal cells. A-T cells exhibit elevated levels of oxidative DNA damage, DNA double-strand breaks and replicative senescence, all of which are partially abrogated by down-regulation of NOX4 with siRNA. Sections of degenerating cerebelli from A-T patients revealed elevated NOX4 levels. ATM-null mice exhibit A-T disease but they die from cancer before the neurological symptoms are manifested. Injecting Atm-null mice with fulvene-5, a specific inhibitor of NOX4 and NADPH oxidase 2 (NOX2), decreased their elevated cancer incidence to that of the controls. We conclude that, in A-T disease in humans and mice, NOX4 may be critical mediator and targeting it will open up new avenues for therapeutic intervention in neurodegeneration.

  3. Analysis of Residual DSBs in Ataxia-Telangiectasia Lymphoblast Cells Initiating Apoptosis

    Directory of Open Access Journals (Sweden)

    Teresa Anglada

    2016-01-01

    Full Text Available In order to examine the relationship between accumulation of residual DNA double-strand breaks (DSBs and cell death, we have used a control and an ATM (Ataxia-Telangiectasia Mutated defective cell line, as Ataxia-Telangiectasia (AT cells tend to accumulate residual DSBs at long times after damage infliction. After irradiation, AT cells showed checkpoint impairment and a fraction of cells displayed an abnormal centrosome number and tetraploid DNA content, and this fraction increased along with apoptosis rates. At all times analyzed, AT cells displayed a significantly higher rate of radiation-induced apoptosis than normal cells. Besides apoptosis, 70–85% of the AT viable cells (TUNEL-negative carried ≥10 γH2AX foci/cell, while only 12–27% of normal cells did. The fraction of AT and normal cells undergoing early and late apoptosis were isolated by flow cytometry and residual DSBs were concretely scored in these populations. Half of the γH2AX-positive AT cells undergoing early apoptosis carried ≥10 γH2AX foci/cell and this fraction increased to 75% in late apoptosis. The results suggest that retention of DNA damage-induced γH2AX foci is an indicative of lethal DNA damage, as cells undergoing apoptosis are those accumulating more DSBs. Scoring of residual γH2AX foci might function as a predictive tool to assess radiation-induced apoptosis.

  4. Acute lymphoblastic leukemia in early childhood as the presenting sign of ataxia-telangiectasia variant.

    Science.gov (United States)

    Bielorai, Bella; Fisher, Tamar; Waldman, Dalia; Lerenthal, Yaniv; Nissenkorn, Andreea; Tohami, Tali; Marek, Dina; Amariglio, Ninette; Toren, Amos

    2013-09-01

    Ataxia-telangiectasia (A-T), an autosomal recessive disorder is characterized by progressive neurodegeneration, immunodeficiency, sensitivity to ionizing radiation, and predisposition to cancer, especially to lymphoid malignancies. A-T variant is characterized by a milder clinical phenotype and is caused by missense or leaky splice site mutations that produce residual ataxia telangiectasia mutated (ATM) kinase activity. Lymphoid malignancy can precede the diagnosis of A-T, particularly in young children with mild neurological symptoms. We studied a consanguineous family with four A-T variant patients, three of them developed T-ALL at a young age before the diagnosis of A-T was established. ATM mutation analysis detected two new missense mutations both within exon 12: c.1514T>C and c.1547T>C. All four patients are homozygous for the two mutations, while their parents are heterozygous for the mutations. ATM protein level was low in all patients and the response to the radiomimetic agent, neocarzinostatin, was reduced. Leukemic presentation in a young age in three members of consanguineous family led to the identification of a new missense mutation in the ATM gene. The diagnosis of A-T or A-T variant should be considered in children with neurological abnormalities who develop T-ALL at a young age.

  5. Clinical course of two Italian siblings with ataxia-telangiectasia-like disorder.

    Science.gov (United States)

    Palmeri, Silvia; Rufa, Alessandra; Pucci, Barbara; Santarnecchi, Emiliano; Malandrini, Alessandro; Stromillo, Maria Laura; Mandalà, Marco; Rosini, Francesca; De Stefano, Nicola; Federico, Antonio

    2013-08-01

    Ataxia-telangiectasia-like disorder (ATLD) due to mutations in the MRE11 gene is a very rare autosomal recessive disease, described so far in only 20 patients. Little is known about the onset of the first symptoms or the clinical course of the disease. The present report contributes to the diagnosis of ATLD and its prognosis at onset. We report 30 years of clinical and ophthalmic observations and the results of quantitative magnetic resonance (MR), MR spectroscopy (proton magnetic resonance spectroscopic imaging) and neuropsychological assessment in the first Italian siblings identified with ATLD. Although the disease had early onset and the clinical picture was initially severe, suggesting ataxia-telangiectasia, neurological impairment, ocular motor apraxia and neuropsychological tests showed very slow deterioration in adult age. The patients developed eye and head motor strategies to compensate ocular motor apraxia. MR measurements and MR spectroscopy disclosed widespread neuronal and axonal involvement. ATLD should be considered in patients with ocular apraxia and ataxia in infancy. The long follow-up provided insights into clinical outcome, with functional neuroimaging studies shedding light on the pathogenetic mechanisms of this rare disease.

  6. A patient-derived olfactory stem cell disease model for ataxia-telangiectasia.

    Science.gov (United States)

    Stewart, Romal; Kozlov, Sergei; Matigian, Nicholas; Wali, Gautam; Gatei, Magtouf; Sutharsan, Ratneswary; Bellette, Bernadette; Wraith-Kijas, Amanda; Cochrane, Julie; Coulthard, Mark; Perry, Chris; Sinclair, Kate; Mackay-Sim, Alan; Lavin, Martin F

    2013-06-15

    The autosomal recessive disorder ataxia-telangiectasia (A-T) is characterized by genome instability, cancer predisposition and neurodegeneration. Although the role of ataxia-telangiectasia mutated (ATM) protein, the protein defective in this syndrome, is well described in the response to DNA damage, its role in protecting the nervous system is less clear. We describe the establishment and characterization of patient-specific stem cells that have the potential to address this shortcoming. Olfactory neurosphere (ONS)-derived cells were generated from A-T patients, which expressed stem cell markers and exhibited A-T molecular and cellular characteristics that included hypersensitivity to radiation, defective radiation-induced signaling and cell cycle checkpoint defects. Introduction of full-length ATM cDNA into these cells corrected defects in the A-T cellular phenotype. Gene expression profiling and pathway analysis revealed defects in multiple cell signaling pathways associated with ATM function, with cell cycle, cell death and DNA damage response pathways being the most significantly dysregulated. A-T ONS cells were also capable of differentiating into neural progenitors, but they were defective in neurite formation, number of neurites and length of these neurites. Thus, ONS cells are a patient-derived neural stem cell model that recapitulate the phenotype of A-T, do not require genetic reprogramming, have the capacity to differentiate into neurons and have potential to delineate the neurological defect in these patients.

  7. A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease.

    Science.gov (United States)

    Beraldi, Rosanna; Chan, Chun-Hung; Rogers, Christopher S; Kovács, Attila D; Meyerholz, David K; Trantzas, Constantin; Lambertz, Allyn M; Darbro, Benjamin W; Weber, Krystal L; White, Katherine A M; Rheeden, Richard V; Kruer, Michael C; Dacken, Brian A; Wang, Xiao-Jun; Davis, Bryan T; Rohret, Judy A; Struzynski, Jason T; Rohret, Frank A; Weimer, Jill M; Pearce, David A

    2015-11-15

    Ataxia telangiectasia (AT) is a progressive multisystem disorder caused by mutations in the AT-mutated (ATM) gene. AT is a neurodegenerative disease primarily characterized by cerebellar degeneration in children leading to motor impairment. The disease progresses with other clinical manifestations including oculocutaneous telangiectasia, immune disorders, increased susceptibly to cancer and respiratory infections. Although genetic investigations and physiological models have established the linkage of ATM with AT onset, the mechanisms linking ATM to neurodegeneration remain undetermined, hindering therapeutic development. Several murine models of AT have been successfully generated showing some of the clinical manifestations of the disease, however they do not fully recapitulate the hallmark neurological phenotype, thus highlighting the need for a more suitable animal model. We engineered a novel porcine model of AT to better phenocopy the disease and bridge the gap between human and current animal models. The initial characterization of AT pigs revealed early cerebellar lesions including loss of Purkinje cells (PCs) and altered cytoarchitecture suggesting a developmental etiology for AT and could advocate for early therapies for AT patients. In addition, similar to patients, AT pigs show growth retardation and develop motor deficit phenotypes. By using the porcine system to model human AT, we established the first animal model showing PC loss and motor features of the human disease. The novel AT pig provides new opportunities to unmask functions and roles of ATM in AT disease and in physiological conditions.

  8. Hereditary hemorrhagic telangiectasia with bilateral pulmonary vascular malformations: A case report

    Directory of Open Access Journals (Sweden)

    Lončarević Olivera

    2016-01-01

    Full Text Available Introduction. Hereditary hemorrhagic telangiectasia (HHT also known as Osler-Weber-Rendu syndrome is an autosomal dominant disease that occurs due to vascular dysplasia associated with the disorder in the signaling pathway of transforming growth factor β (TGF-β. The clinical consequence is a disorder of blood vessels in multiple organ systems with the existence of telangiectasia which causes dilation of capillaries and veins, are present from birth and are localized on the skin and mucosa of the mouth, respiratory, gastrointestinal and urinary tract. They can make a rupture with consequent serious bleeding that can end up with fatal outcome. Since there is a disruption of blood vessels of more than one organic system, the diagnosis is very complex and requires a multidisciplinary approach. Case report. We reported a 40-year-old female patient with a long-time evolution of problems, who was diagnosed and treated at the Clinic for Lung Diseases of the Military Medical Academy in Belgrade, Serbia, because of bilaterally pulmonary arteriovenous malformations associated with HHT. Embolization was performed in two acts, followed with normalization of clinical, radiological and functional findings with the cessation of hemoptysis, effort intolerance with a significant improvement of the quality of life. Conclusion. HHT is a rare dominant inherited multisystem disease that requires multidisciplinary approach to diagnosis and treatment. Embolization is the method of choice in the treatment of arteriovenous malformations with minor adverse effects and very satisfying therapeutic effect.

  9. Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia.

    Science.gov (United States)

    Carranza, Diana; Vega, Ana Karina; Torres-Rusillo, Sara; Montero, Enrique; Martinez, Luis Javier; Santamaría, Manuel; Santos, Juan Luis; Molina, Ignacio J

    2017-03-01

    Ataxia-telangiectasia is a multisystemic disease with severe neurological affectation, immunodeficiency and telangiectasia. The disorder is caused by alterations in the ATM gene, whose size and complexity make molecular diagnosis difficult. We designed a target-enrichment next-generation sequencing strategy to characterize 28 patients from several regions of Spain. This approach allowed us to identify gene variants affecting function in 54 out of the 56 alleles analyzed, although the two unresolved alleles belong to brothers. We found 28 ATM gene mutations, of which 10 have not been reported. A total of 171 gene variants not affecting function were also found, of which 22 are reported to predispose to disease. Interestingly, all Roma (Spanish Gypsies) patients are homozygous for the same mutation and share the H3 ATM haplotype, which is strong evidence of a founder effect in this population. In addition, we generated a panel of 27 primary T cell lines from A-T patients, which revealed significant expression of ATM in two patients and traces of the protein in nine more. None of them retained residual ATM activity, and almost all T cell lines show increased or intermediate radiosensitivity.

  10. Ondine's curse with accompanying trigeminal and glossopharyngeal neuralgia secondary to medullary telangiectasia.

    Science.gov (United States)

    Kapnadak, Siddhartha G; Mikolaenko, Ivan; Enfield, Kyle; Gress, Daryl R; Nathan, Barnett R

    2010-06-01

    Central hypoventilation syndrome ("Ondine's Curse") is an infrequent disorder that can lead to serious acute or chronic health consequences. This syndrome, especially in adults, is rare, and even less frequent in the absence of clear pathogenic lesions on MRI. In addition, we are not aware of any previously reported cases with associated cranial nerve neuralgias. We describe a patient with baseline trigeminal and glossopharyngeal neuralgia, admitted with episodes of severe hypoventilatory failure of central origin, consistent with "Ondine's Curse". After evaluation, she was found to have a medullary capillary telangiectasia, thought to be the causative lesion, and which could explain her complete neurologic and hypoventilatory syndrome. The patient was treated with placement of a diaphragmatic pacing system, which has been effective thus far. This case illustrates the need for investigation of centrally mediated apnea, especially when co-occurring cranial nerve neuralgia is present and cardiopulmonary evaluation is negative. It provides an example of capillary telangiectasia as the causative lesion, one that to our knowledge has not been reported before. Placement of a diaphragmatic pacing system was warranted and became lifesaving as the patient was deemed to be severely incapacitated by chronic ventilatory insufficiency.

  11. Clinical and tomographic aspects of macular microholes; Aspectos clinicos e tomograficos dos microburacos maculares

    Energy Technology Data Exchange (ETDEWEB)

    Novelli, Fernando Jose de [Hospital de Olhos Sadalla Amin Ghanem, Joinville, SC (Brazil)], e-mail: Fernando.novelli@gmail.com; Maia Junior, Otacilio de Oliveira [Fundacao Monte Tabor, Salvador, BA (Brazil). Hospital Sao Rafael; Nobrega, Mario Junqueira [Universidade da Regiao de Joinville (UNIVILLE), Joinville, SC (Brazil); Garrido Neto, Theodomiro [Universidade do Estado do Amazonas (UEA), Manaus, AM (Brazil); Takahashi, Walter Yukihiko [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. de Oftalmologia

    2009-07-01

    Purpose: To describe the clinical aspects and evaluate optical coherence tomography of macular microholes. Methods: Seven patients were assessed (8 eyes) with microholes of the macula. All patients underwent complete eye examination, fundus photography, fluorescent angiography and OCT-3 imaging. Results: Ages ranged from 26 to 69 years. Six patients were female (85.7%) and five of them had microhole in the right eye. The presenting symptom was decrease in visual acuity (71.3%) and central scotoma in (14.3%). Five eyes (71.4%) had no defects shown by fluorescent angiography. A defect in the outer retina was demonstrated in all eyes on optical coherence tomography. The lesions were nonprogressive. Conclusion: Macular microholes are small lamellar defects in the outer retina. The condition is nonprogressive, generally unilateral and compatible with good visual acuity. Fundus biomicroscopy associated with an optical coherence tomography are the main elements in the diagnosis and study of this pathology. (author)

  12. LASER PHOTOCOAGULATION IN DIABETIC MACULAR EDEMA: EFFECTS ON VISUAL ACUITY AND MACULAR EDEMA

    Directory of Open Access Journals (Sweden)

    M.H. Dehghan

    1999-06-01

    Full Text Available Due to the importance of clinically significant macular edema in diabetic patients, this study is aimed to determine if laser photocoagulation is effective in the treatment of clinically significant diabetic macular edema. In addition, the effects of risk factors arc surveyed* This is an existing data study considering patients with clinically significant diabetic macular edema, treated with argon-green laser photocoagulation in Labbafinejad hospital, department of lasertherapy, from 1995 to 1997. in 60 (42.6% eyes the treatment method was focal, in 22 (15.6% eyes grid, and in 59 (41.84 modified grid laser photocoagulation was performed. The results are based upon deterioration of visual acuity, occurance of moderate visual loss and improvement or persistence of CSME. We studied 114 eyes from 87 patients. Two years after initial treatment, visual acuity improved in 19.1% of eyes, unchanged in 9.5% and worsened in 71.4% of eyes. After this period the rate of moderate visual loss was 28.6% and CSME was improved in 23.8% of eyes. According to our study, baseline visual acuity and retinopathy severity were two important intervening factors in response to lasertherapy. Comparing our results with natural course of diabetic macular edema, indicates that in assessing visual outcome laser photocoagulation is an effective modality in treatment of CSME, but it is not effective in maintaining or improving visual acuity, which is due to patients delay in visiting ophthalmologists and paying not enough attention to follow-up visits.

  13. Assessment of Macular Sensitivity and Fixation Stability by MP-1 Microperimetry in Diabetic Macular Edema

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    Tuncay Küsbeci

    2012-12-01

    Full Text Available Pur po se: To evaluate macular light sensitivity and fixation stability in subjects with clinically significant macular edema (CSME related to diabetes mellitus. Ma te ri al and Met hod: Thirty eyes of 22 patients with CSME, as defined by Early Treatment Diabetic Retinopathy Study, and 32 eyes of 32 healthy subjects were enrolled in this study. Microperimetry was performed with the Micro Perimeter MP-1 in both groups. The mean retinal sensitivities at central 4°, at central 12° and at central 20° were measured. The mean extent of preferred retinal locus (PRL, fixation stability and fixation location were calculated using fixation test in MP-1 microperimeter. Statistical analysis was performed using student t-test and chisquare test. Re sults: The mean best-corrected visual acuity (BCVA was significantly lower in the CSME group than the control group (p<0.001. The mean retinal sensitivities at central 4°, 12° and 20° areas were significantly lower in the CSME group compared to the control group (p<0.001, for each central degrees. In subjects with CSME, fixation stability was detected as stable in 8 (26.7% eyes, relatively unstable in 21 (70% eyes and unstable in 1 (3.3% eye. Significant decrease was found in fixation stability and fixation location scores in eyes with CSME compared to control subjects (p<0.001. The difference of mean extent in PRL between the groups was statistically significant (p<0.001. Dis cus si on: The macular light sensitivity and fixation stability are affected in patients with CSME. MP-1 micropeimetry might be helpful to evaluate the extent of PRL and useful for evaluation of severity and progression of diabetic macular edema. (Turk J Ophthalmol 2012; 42: 310-5

  14. Coroidite serpiginosa macular: relato de caso Macular serpiginous choroiditis: case report

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    Michel Klejnberg

    2009-10-01

    Full Text Available A coroidite serpiginosa é uma doença rara, que pode causar perda visual irreversível quando a mácula é atingida. Este artigo relata um caso de coroidite serpiginosa com acometimento macular isolado, submetido a tratamento com injeções subtenoniana e intravítrea de triancinolona. Os aspectos clínicos e diagnósticos diferenciais desta doença ocular são discutidos, assim como, os achados de angiografia fluoresceínica e tomografia de coerência óptica de alta resolução.Serpiginous choroiditis is a rare ocular inflammatory disease that can lead to permanent vision loss due to macular involvement. This article reports a case of a patient with macular serpiginous choroiditis submitted to subtenon and intravitreal triamcinolone injections. The clinical aspects and differential diagnosis of this ocular disease, including fluorescein angiogram and high-resolution optical coherence tomography are discussed.

  15. Endoglin, a TGF-β binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1

    NARCIS (Netherlands)

    K.A. McAllister (K.); K.M. Grogg (K.); D.W. Johnson (D.); C.J. Gallione (C.); P.J. Baldwin (Peter); C.E. Jackson (C.); E.A. Helmbold (E.); D.S. Markel (D.); W. McKinnon; J.R. Murrell (Jill); J.A. McCormick (James); M.A. Pericak-Vance (Margaret); P. Heutink (Peter); B.A. Oostra (Ben); T. Haitjema (T.); C.J.J. Westerman (C. J J); M.E. Porteous (Mary); A.E. Guttmacher (A.); M. Letarte (M.); D.A. Marchuk (D.)

    1994-01-01

    textabstractHereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent haemorrhage. Linkage for some families has been established to chromosome 9q33−q34. In the present study, endoglin, a transforming growth factor

  16. Small-molecule inhibitors of Ataxia Telangiectasia and Rad3 related kinase (ATR) sensitize lymphoma cells to UVA radiation

    DEFF Research Database (Denmark)

    Biskup, Edyta; Naym, David Gram; Gniadecki, Robert

    2016-01-01

    and require more aggressive therapies. OBJECTIVE: The aim of this project was to investigate whether inhibition of Ataxia Telangiectasia and Rad3 related kinase (ATR) may enhance efficacy of phototherapy. METHODS: CTCL cell lines (MyLa2000, SeAx and Mac2a) served as in vitro cell models. ATR and Chk1 were...

  17. T-cell ALL in ataxia telangiectasia cured with only 7 weeks of anti-leukemic therapy

    DEFF Research Database (Denmark)

    Hersby, Ditte S; Sehested, Astrid; Kristensen, Kim

    2015-01-01

    -fetoprotein was 20- to 30-fold elevated, and genetic analysis confirmed the diagnosis of ataxia telangiectasia. Despite receiving only 7 weeks of anti-leukemic therapy, she has stayed in first remission now 8 years after the diagnosis. We speculate that this could be because of increased chemosensitivity of ATM...

  18. Quantification of retinal layer thickness changes in acute macular neuroretinopathy

    DEFF Research Database (Denmark)

    Munk, Marion R; Beck, Marco; Kolb, Simone

    2017-01-01

    PURPOSE: To quantitatively evaluate retinal layer thickness changes in acute macular neuroretinopathy (AMN). METHODS: AMN areas were identified using near-infrared reflectance (NIR) images. Intraretinal layer segmentation using Heidelberg software was performed. The inbuilt ETDRS -grid was moved ...

  19. Prognostic significance of delayed structural recovery after macular hole surgery

    DEFF Research Database (Denmark)

    Christensen, Ulrik C; Krøyer, Kristian; Sander, Birgit

    2009-01-01

    PURPOSE: To assess the prognostic significance for visual function of persistent subfoveal fluid and persistent photoreceptor layer discontinuity in eyes in which hole closure had been obtained 3 months after macular hole surgery. DESIGN: Ancillary study of subjects enrolled in a randomized...... clinical trial. PARTICIPANTS: Participants were recruited from a randomized clinical trial evaluating internal limiting membrane (ILM) peeling in macular hole surgery. The study included 74 eyes in which a contiguous retinal surface or a full attachment with a flat neuroretinal rim had been reestablished...... OUTCOME MEASURES: Postoperative foveal configuration and foveal photoreceptor layer discontinuity diameter 3 months after macular hole surgery. RESULTS: Persistent subfoveal fluid 3 months after macular hole surgery, which was found in 36.5% of eyes, was not associated with a significantly different BCVA...

  20. Macular surgery using intraoperative spectral domain optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Mohammad Riazi-Esfahani

    2015-01-01

    Conclusion: Intraoperative SD-OCT is a useful imaging technique which provides vitreoretinal surgeons with rapid awareness of changes in macular anatomy during surgery and may therefore result in better anatomical and visual outcomes.

  1. Successful treatment of pseudophakic cystoid macular edema with intravitreal bevacizumab.

    Science.gov (United States)

    Barone, Antonio; Prascina, Francesco; Russo, Vincenzo; Iaculli, Cristiana; Primavera, Vito; Querques, Giuseppe; Stella, Andrea; Delle Noci, Nicola

    2008-07-01

    A 67-year-old woman developed refractory pseudophakic cystoid macular edema (CME) after uneventful phacoemulsification. Three months after an intravitreal injection of bevacizumab (1.25 mg), the CME was completely resolved, with resultant improvement in visual acuity.

  2. Disappearance of diabetic macular hard exudates after hemodialysis introduction.

    Directory of Open Access Journals (Sweden)

    Matsuo,Toshihiko

    2006-06-01

    Full Text Available

    We report herein the disappearance of macular hard exudates after the introduction of hemodialysis in diabetic patients. A 62-year-old woman and a 52-year-old man with diabetes mellitus showed hard exudates in the macula of the left eyes. Both patients had previously undergone panretinal photocoagulation in both eyes. During the follow-up, hemodialysis was introduced for deteriorating chronic renal failure caused by diabetic nephropathy. Half a year later, macular hard exudates in the left eyes disappeared dramatically in both patients, but the visual acuity remained the same. No additional laser treatment was done during the observation period. Hemodialysis is considered to have accelerated the resolution of macular hard exudates in both patients. The deposition of macular hard exudates in diabetic patients is due in part to concurrent poor renal function.

  3. Acute macular edema following intracorporeal prostaglandin injection for erectile dysfunction

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    Asahi MG

    2015-07-01

    Full Text Available Masumi G Asahi, Calvin Chou, Ron P Gallemore Retina Macula Institute, Torrance, CA, USA Purpose: We aimed to describe the first case of macular edema following intracorporeal injection of alprostadil, a prostaglandin E1. Methods: This was a retrospective case report followed with optical coherence tomography, fundus photos, and fluorescein angiography images. Results: A patient developed bilateral cystoid macular edema following intracorporeal injection of alprostadil, a prostaglandin E1 for treatment of erectile dysfunction. The edema resolved following treatment with nonsteroidal anti-inflammatory drugs (NSAIDs and corticosteroids, with subsequent recovery in visual acuity. Discussion: Systemic prostaglandin administration can cause macular edema and vision loss, indicating that elevated systemic prostaglandin levels may affect visual function. This has potential implications for other systemic disorders and treatments that could affect macular function. Keywords: alprostadil, inflammation

  4. Multiple extra macular branch retinal vein occlusions in hyperhomocysteinemia

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    Abhijit Diwakar Gore

    2014-01-01

    Full Text Available Hyperhomocysteinemia is a well-known modifiable risk factor for thromboembolism. Retinal vascular occlusion in patients having hyperhomocysteinemia is a known entity, particularly in young patients. However, multiple extra macular branch retinal vein occlusion (BRVO is a rare condition, which can be a presentation of this disease. We present a patient who had multiple extra macular BRVO; on complete systemic workup, he was found to have raised homocysteine levels.

  5. Simple Raman Instrument for in Vivo Detection of Macular Pigments

    OpenAIRE

    Ermakov, Igor V.; Ermakova, Maia R.; Gellermann, Werner

    2005-01-01

    Raman spectroscopy holds promise as a novel noninvasive technology for the quantification of the macular pigments (MP) lutein and zeaxanthin. These compounds, which are members of the carotenoid family, are thought to prevent or delay the onset of age-related macular degeneration, the leading cause of irreversible blindness in the elderly. It is highly likely that they achieve this protection through their function as optical filters and/or antioxidants. Using resonant excitation in the visib...

  6. Pathology of Macular Foveoschisis Associated with Degenerative Myopia

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    Johnny Tang

    2010-01-01

    Full Text Available This is a clinicopathological paper on the histologic findings in myopia-associated macular foveoschisis. The findings on ophthalmic pathological study of a 73-year-old woman with high myopia are reviewed. Multiple retinoschisis cavities involving both the macula and retinal periphery were disclosed. Our paper offers tissue evidence and supports recent ocular coherence tomography reports of eyes with high myopia and associated macular foveoschisis.

  7. [Depression in Patients with Age-Related Macular Degeneration].

    Science.gov (United States)

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  8. CKD Increases the Risk of Age-Related Macular Degeneration

    OpenAIRE

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-01-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerul...

  9. Visual function of the idiopathic macular hole

    Directory of Open Access Journals (Sweden)

    Jian-Tao Ren

    2015-02-01

    Full Text Available The idiopathic macular hole(IMHis research priority associated with the regenerate quickly of vitrectomy. The unaided visual acuity and the best corrected visual acuity is partial for the visual acuity of the patient with IMH.The mechanism and clinical significance of modern visual function measurements associated with IMH, including contrast sensitivity, visual field, multifocal electroretinogram, and stereoscopic vision, have been introduced. These measurements could be of great value in early diagnosis of IMH, assessment of surgical indication and evaluation of visual performance after vitrectomy. They would also be helpful to the analysis of postoperative impaired visual function and its management. Having an adequate understanding of the contents and significance of visual function is helpful to the improvement of IMH surgery techniques and postoperative visual acuity.

  10. [Macular surgery in a new point of view].

    Science.gov (United States)

    Branişteanu, D; Moraru, Andreea

    2014-01-01

    To reveal the differences in anatomical and functional results following standard 20-gauge vitrectomy and modern transconjunctival sutureless vitrectomy in macular surface pathology. Retrospective, interventional, comparative evaluation of macular pathology cases operated by standard 20-gauge vitrectomy and transconjunctival 23 G sutureless vitrectomy. In evaluation were included a comparable number of epiretinal membranes (both idiopathic and secondary) and stage 3 and 4 macular holes. A postoperative anatomical and functional analysis was performed and also the incidence of pre-and postoperative complications was noted. Transconjunctival sutureless vitrectomy was associated with a shorter operating time and quicker anatomical and functional results. If in epiretinal membranes there was no significant difference in final results, in macular holes anatomical and functional results were better with sutureless vitrectomy. These results confirm the efficacy and safety of both surgical procedures in macular surface pathology. Better anatomical and functional results in macular holes and quicker functional rehabilitation in all cases promote sutureless vitrectomy as new standard procedure in these cases.

  11. Optic Coherence Tomography of Idiopathic Macular Epiretinal Membranes

    Institute of Scientific and Technical Information of China (English)

    Xing Liu; Yunlan Ling; Jingjing Huang; Xiaoping Zheng

    2002-01-01

    bjectives: To study the characteristics of optical coherence tomography (OCT)inopathic macular epiretinal membranes (IMEM) and the relationship between thethickness offovea and the vision of affected eyes.Methods:A total of 67 cases (73 eyes) with clinical diagnosis of IMEM using direct,indirect ophthalmoscope, three mirror contact lens, fundus color photography or fundusfluorescein angiography (FFA)were examined with OCTResults: Epiretinal membranes (ERMs) with macular edema were found in 32 eyes,proliferative ERMs in 20 eyes, ERMs with macular pseudoholes in 14 eyes and ERMswith laminar macular holes in 7 eyes. Based on OCT, the ERMs were clearly andpartially seperated from the retinal (27 eyes, 38.36% ), the retinal thickness of thefovea was the thickest in the proliferative ERMs and the thinnest in the ERMs withlaminar macular holes. The statistical analysis showed there was a negative correlationbetween the thickness of fovea and visual acuity ( r = - 0. 454, P = 0. 000).Conclusion:There were four types of images of OCT in IMEM: ERMs with macularedema, proliferative ERMs, ERMs with macular pseudohole and ERMs with laminarmacular hole; and the thicker the fovea under the OCT, the poorer the vision acuity in the affected eyes with ERMs.

  12. Clinical Observation on Juvenile Macular Hole without Trauma and Hypermyopia

    Institute of Scientific and Technical Information of China (English)

    Tieying Zhao; Qingshan Chen; Ming Li; Xunqing Gu; Rulong Gao; Feng Wen

    2005-01-01

    Purpose: To investigate the clinical characteristics of juvenile macular hole without trauma and hypermyopia, and research the mechanism of macular hole.Methods: Sixty-seven patients less than 40 years of age were studied retrospectively from June 1998 to March 2003. Five cases (7 eyes) aged from 22 to 38 years were reported and the clinical characteristics that had macular hole without trauma or hypermyopia were summed up.Results: There was 1 male and 4 females with visual acuity from 0.08 to 0.8. The images of optical coherence tomography (OCT) showed full thickness macular hole in 5 patients (7 eyes), and the diameters were from 87 to 1043 μm. Among them, 2 cases were combined with retina pigmentosa; 1 case with binocular Coat's disease; 1 case had bilateral macular hole combined with Eagles' disease; 1 case was combined with 2-2.5PD old retinochoroidal lesion under middle-peripheral fundus, and 1.5 PD retinal pigment epithelium (RPE) defect on the optical disk.Conclusion: The juvenile macular hole without trauma and hypermyopia combined the different retina vascular damages and the RPE defects.

  13. CKD increases the risk of age-related macular degeneration.

    Science.gov (United States)

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-04-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.

  14. Peripapillary and Macular Choroidal Thickness in Glaucoma

    Directory of Open Access Journals (Sweden)

    Hamid Hosseini

    2014-01-01

    Full Text Available Purpose: To compare choroidal thickness (CT between individuals with and without glaucomatous damage and to explore the association of peripapillary and submacular CT with glaucoma severity using spectral domain optical coherence tomography (SD-OCT. Methods: Ninety-one eyes of 20 normal subjects and 43 glaucoma patients from the UCLA SD-OCT Imaging Study were enrolled. Imaging was performed using Cirrus HDOCT. Choroidal thickness was measured at four predetermined points in the macular and peripapillary regions, and compared between glaucoma and control groups before and after adjusting for potential confounding variables. Results: The average (± standard deviation mean deviation (MD on visual fields was −0.3 (±2.0 dB in controls and −3.5 (±3.5 dB in glaucoma patients. Age, axial length and their interaction were the most significant factors affecting CT on multivariate analysis. Adjusted average CT (corrected for age, axial length, their interaction, gender and lens status however, was not different between glaucoma patients and the control group (P=0.083 except in the temporal parafoveal region (P=0.037; nor was choroidal thickness related to glaucoma severity (r=−0.187, P=0.176 for correlation with MD, r=−0.151, P=0.275 for correlation with average nerve fiber layer thickness. Conclusions: Choroidal thickness of the macular and peripapillary regions is not decreased in glaucoma. Anatomical measurements with SD-OCT do not support the possible influence of the choroid on the pathophysiology of glaucoma.

  15. Perceptual learning in patients with macular degeneration

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    Tina ePlank

    2014-10-01

    Full Text Available Patients with age-related macular degeneration (AMD or hereditary macular dystrophies (JMD rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT at their preferred retinal locus (PRL used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later took part in three functional magnetic resonance imaging (fMRI sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p=.001 in the stimulus onset asynchrony (SOA between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p=.014. The following trends were observed: (i Improvement in Vernier acuity for an eccentric line-bisection task; (ii positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r=0.531; (iii positive correlation between the increase in task performance and initial fixation stability (r=0.730. The first two trends were non-significant, whereas the third trend was significant at p=.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.

  16. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  17. Treatment of idiopathic macular hole with silicone oil tamponade

    Directory of Open Access Journals (Sweden)

    Ivanovska-Adjievska B

    2012-09-01

    Full Text Available Biljana Ivanovska-Adjievska,1 Salih Boskurt,1 Faruk Semiz,1 Hakan Yuzer,1 Vesna Dimovska-Jordanova21European Eye Hospital, Skopje, Macedonia, 2Clinic for Eye Diseases, University "St Cyril and Methodius", Skopje, MacedoniaPurpose: We analyzed the anatomical and visual outcomes after surgical treatment of idiopathic macular holes with pars plana vitrectomy, internal limiting membrane (ILM peeling using Brilliant Blue dye, and silicone oil tamponade without postoperative posturing.Methods: This was a retrospective interventional study of 10 eyes in eight patients who underwent surgical treatment of idiopathic macular holes using pars plana vitrectomy, ILM peeling using Brilliant Blue dye, and silicone oil tamponade without postoperative posturing. The preoperative staging of macular holes and postoperative anatomic outcomes were assessed using spectral-domain optical coherence tomography.Results: All patients were women with a mean age of 66.86 ± 4.8 years. In two patients, bilateral macular holes were present and both eyes were operated on. Stage 2 macular hole was diagnosed in three eyes, three eyes had stage 3, and four eyes had stage 4 macular holes. Anatomical success and closure of the macular hole was achieved in nine eyes (90% after one operation. In one eye, the macular hole was closed after reoperation. The preoperative mean best-corrected visual acuity (BCVA was 0.15 decimal units (0.8 logMAR units. Until the end of the follow-up period, BCVA was 0.25 decimal units (0.6 logMAR units. Visual acuity was improved in seven patients (70%. In two patients (20%, visual acuity remained at the same level, and in one eye (10%, visual acuity decreased. Postoperatively, all patients reported a significant reduction of metamorphopsia.Conclusion: Initial results after 20G pars plana vitrectomy with peeling of the ILM, use of dye (Brilliant Blue, and tamponade with silicone oil without postoperative posturing gave good anatomical and functional

  18. Ataxia Telangiectasia

    Science.gov (United States)

    ... Translational Research Research at NINDS Focus on Research Alzheimer's & Related Dementias Bioengineering Epilepsy Health Disparities Neural Interfaces Parkinson's Disease Spinal Cord Injury Stem Cells Traumatic Brain Injury Trans-Agency Activities Interagency Research ...

  19. Ataxia Telangiectasia

    Science.gov (United States)

    ... Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  20. Ataxia-telangiectasia (A-T): An emerging dimension of premature ageing.

    Science.gov (United States)

    Shiloh, Yosef; Lederman, Howard M

    2017-01-01

    A-T is a prototype genome instability syndrome and a multifaceted disease. A-T leads to neurodegeneration - primarily cerebellar atrophy, immunodeficiency, oculocutaneous telangiectasia (dilated blood vessels), vestigial thymus and gonads, endocrine abnormalities, cancer predisposition and varying sensitivity to DNA damaging agents, particularly those that induce DNA double-strand breaks. With the recent increase in life expectancy of A-T patients, the premature ageing component of this disease is gaining greater awareness. The complex A-T phenotype reflects the ever growing number of functions assigned to the protein encoded by the responsible gene - the homeostatic protein kinase, ATM. The quest to thoroughly understand the complex A-T phenotype may reveal yet elusive ATM functions. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia.

    Science.gov (United States)

    Eickmeier, Olaf; Kim, Su Youn; Herrmann, Eva; Döring, Constanze; Duecker, Ruth; Voss, Sandra; Wehner, Sibylle; Hölscher, Christoph; Pietzner, Julia; Zielen, Stefan; Schubert, Ralf

    2014-05-29

    Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death. We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm(-/-)). ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm(-/-) mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed. Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.

  2. Management of Individuals With a Mutation in the Ataxia Telangiectasia Mutated Gene.

    Science.gov (United States)

    Mahon, Suzanne M

    2016-01-01

    Advances in genetic testing have led to the identification of multiple genes associated with a hereditary risk for developing breast and other cancers. One such gene is the ataxia telangiectasia mutated (ATM) gene, which is available on many genetic panels offered to individuals with suspected hereditary risk. Genetic testing can often lead to improved understanding and clarification of risk for developing cancer, as well as allow affected individuals to make informed choices about management, including the adoption of primary prevention strategies and more aggressive screening than typically recommended in the general population. This article provides an overview of the role of mutations in the ATM gene in developing malignancies, along with emerging research on treatment implications based on genetic testing results.
.

  3. Cell and Molecular Biology of Ataxia Telangiectasia Heterozygous Human Mammary Epithelial Cells Irradiated in Culture

    Science.gov (United States)

    Richmond, Robert C.

    2001-01-01

    Autologous isolates of cell types from obligate heterozygotes with the autosomal disorder ataxia-telangiectasia (A-T)were used to begin a tissue culture model for assessing pathways of radiation-induced cancer formation in this target tissue. This was done by establishing cultures of stromal fibroblasts and long-term growth human mammary epithelial cells (HMEC) in standard 2-dimensional tissue culture in order to establish expression of markers detailing early steps of carcinogenesis. The presumptive breast cancer susceptibility of A-T heterozygotes as a sequel to damage caused by ionizing radiation provided reason to study expression of markers in irradiated HMEC. Findings from our study with HMEC have included determination of differences in specific protein expression amongst growth phase (e.g., log vs stationary) and growth progression (e.g., pass 7 vs pass 9), as well as differences in morphologic markers within populations of irradiated HMEC (e.g., development of multinucleated cells).

  4. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Møller, T R; Brusgaard, K

    2005-01-01

    BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically...... heterogeneous disorder involving at least two loci; HHT 1 mapping to chromosome 9 q 34.1 (ENG) and HHT 2 mapping to chromosome 12 q 31 (ALK-1). OBJECTIVE: To evaluate and describe the diversity of clinical manifestations in a Danish population of HHT patients with known HHT 1 or HHT 2 subtype. DESIGN......: Prospective clinical examination with genetic evaluation and follow-up. SETTING: Investigation centre was Odense University Hospital. All HHT patients in the County of Fyn were included. METHODS: HHT family members were invited to a clinical examination including registration of HHT manifestations, screening...

  5. Stable radioresistance in ataxia-telangiectasia cells containing DNA from normal human cells

    Energy Technology Data Exchange (ETDEWEB)

    Kapp, L.N.; Painter, R.B. (California Univ., San Francisco, CA (USA). Lab. of Radiobiology)

    1989-11-01

    SV40-transformed ataxia-telangiectasia (AT) cells were transfected with a cosmid containing a normal human DNA library and selectable marker, the neo gene, which endows successfully transformed mammalian cells with resistance to the antibiotic G418. Cells from this line were irradiated with 50 Gy of X-rays and fused with non-transfected AT cells. Among the G418-resistant colonies recovered was one stably resistant to radiation. Resistance to ionizing radiation of both primary transfectant line and its fusion derivative was intermediate between that of AT cells and normal cells, as assayed by colony-forming ability and measurement of radiation-induced G{sub 2} chromatic aberrations; both cell lines retained AT-like radioresistant DNA synthesis. Results suggest that, because radioresistance in transfected cells was not as great as in normal human cells, two hallmarks of AT, radiosensitivity and radioresistant DNA synthesis, may still be the result of a single defective AT gene. (author).

  6. Optical coherence tomography imaging of telangiectasias during intense pulsed light treatment

    DEFF Research Database (Denmark)

    Ring, Hans Christian; Mogensen, Mette; Banzhaf, Christina

    2013-01-01

    Vascular malformations commonly occur in the facial region, and can be associated with significant stigma and embarrassment. Studies have shown that even recommended light-based treatments do not always result in complete clearance. This indicates the need for more accurate pre-treatment assessment...... and minutes after IPL treatment. OCT images of the telangiectasias before treatment were displayed as hyporeflective/signal poor bands clearly demarcated from the surrounding tissue. Minutes after treatment, OCT images demonstrated two different reactions. (1) Narrow hyperreflective bands surrounding...... the vessels, which may indicate edema or insufficient coagulation. (2) Hyperreflective signals within the lumen of the vessels, compatible with the expected irreversible microthrombus formation in the vessels. OCT imaging is capable of real-time assessment of tissue damage during light and laser treatment...

  7. Cell and Molecular Biology of Ataxia Telangiectasia Heterozygous Human Mammary Epithelial Cells Irradiated in Culture

    Science.gov (United States)

    Richmond, Robert C.

    2001-01-01

    Autologous isolates of cell types from obligate heterozygotes with the autosomal disorder ataxia-telangiectasia (A-T)were used to begin a tissue culture model for assessing pathways of radiation-induced cancer formation in this target tissue. This was done by establishing cultures of stromal fibroblasts and long-term growth human mammary epithelial cells (HMEC) in standard 2-dimensional tissue culture in order to establish expression of markers detailing early steps of carcinogenesis. The presumptive breast cancer susceptibility of A-T heterozygotes as a sequel to damage caused by ionizing radiation provided reason to study expression of markers in irradiated HMEC. Findings from our study with HMEC have included determination of differences in specific protein expression amongst growth phase (e.g., log vs stationary) and growth progression (e.g., pass 7 vs pass 9), as well as differences in morphologic markers within populations of irradiated HMEC (e.g., development of multinucleated cells).

  8. Chemo- and radiosensitivity testing in a patient with ataxia telangiectasia and Hodgkin disease.

    Science.gov (United States)

    Tamminga, R Y J; Dolsma, W V; Leeuw, J A; Kampinga, H H

    2002-01-01

    Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersensitivity to radiation and chemotherapy. Most patients die, due to toxicity or, rarely, to progressive disease. The authors report on a 9-year-old girl with stage IIA HD and AT She was treated with a tailored combined modality approach. No unacceptable toxicity was found, but the girl died of a relapse outside the irradiation field. In comparison with fibroblasts of non-AT patients, the fibroblasts of the patient were 3 times as sensitive for radiotherapy but just 1.2 times as sensitive for doxorubicin. A good correlation was shown between in vitro radio- and chemosensitivity testing and the observed clinical toxicity. The authors suggest, therefore, treating AT patients as much as possible according to standard protocols by adjusting the radiotherapy delivery and the chemotherapy regimen to individual doses derived from in vitro radio- and chemosensitivity testing.

  9. A randomized trial of oral betamethasone to reduce ataxia symptoms in ataxia telangiectasia.

    Science.gov (United States)

    Zannolli, Raffaella; Buoni, Sabrina; Betti, Gianni; Salvucci, Sara; Plebani, Alessandro; Soresina, Annarosa; Pietrogrande, Maria C; Martino, Silvana; Leuzzi, Vincenzo; Finocchi, Andrea; Micheli, Roberto; Rossi, Livia Nicoletta; Brusco, Alfredo; Misiani, Filippo; Fois, Alberto; Hayek, Joseph; Kelly, Colleen; Chessa, Luciana

    2012-09-01

    No controlled studies exist regarding the pharmaceutical reduction of ataxia symptoms in ataxia telangiectasia (A-T). In a multicenter, double-blind, randomized, placebo-controlled crossover trial, oral betamethasone (BETA) and placebo were compared in terms of their reduction of ataxia symptoms as assessed with the International Cooperative Ataxia Rating Scale (ICARS). In this study of 13 A-T children, betamethasone reduced the ICARS total score by a median of 13 points in the intent-to-treat population and 16 points in the per-protocol population (ie, median percent decreases of ataxia symptoms of 28% and 31%, respectively). In conclusion, Oral betamethasone could be a promising therapy to relieve ataxia symptoms in A-T patients; however, long-term effectiveness and safety must be established. (Current Controlled Trials, number ISRCTN08774933.) Copyright © 2012 Movement Disorder Society.

  10. Hereditary Haemorrhagic Telangiectasia with Thrombocytopenia - A Rare Association with an Atypical Presentation

    Directory of Open Access Journals (Sweden)

    Padmakumar R

    2015-04-01

    Full Text Available Hereditary Haemorrhagic Telangiectasia (Osler-Rendu-Weber disease is a rare autosomal dominant disorder commonly a ecting small vessels of skin and mucosa. It is usually misdiagnosed because of its atypical presentation. This disease frequently presents as epistaxis, GI bleed and visceral arterio venous malformations. Patient may present with stroke or migraine but presentation due to predominant respiratory symptoms may occur in the presence of pulmonary A-V stula. We present a 9 yr old male with dyspnoea on exertion and cyanosis and clubbing. He had a past history of intracerebral bleed with thrombocytopenia and he was being treated as ITP. Contrast echo revealed ndings suggestive of pulmonary arterio venous stula which led to subsequent investigations and retrospective evaluation and hence achieving the final diagnosis.

  11. Ataxia-telangiectasia: Linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome

    NARCIS (Netherlands)

    Y. Ziv (Yael); M. Frydman (Moshe); E.M. Lange (Ethan); N. Zelnik (N.); G. Rotman (Galit); C. Julier (C.); N.G.J. Jaspers (Nicolaas); E. Dagan (Efrat); D. Abeliovicz (Dvorah); H. Dar (H.); Z. Borochowitz (Z.); M. Lathrop (Mark); A. Gatti (Arianna); Y. Shiloh (Yosef)

    1992-01-01

    textabstractAtaxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by t

  12. Ataxia-telangiectasia: Linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome

    NARCIS (Netherlands)

    Y. Ziv (Yael); M. Frydman (Moshe); E.M. Lange (Ethan); N. Zelnik (N.); G. Rotman (Galit); C. Julier (C.); N.G.J. Jaspers (Nicolaas); E. Dagan (Efrat); D. Abeliovicz (Dvorah); H. Dar (H.); Z. Borochowitz (Z.); M. Lathrop (Mark); A. Gatti (Arianna); Y. Shiloh (Yosef)

    1992-01-01

    textabstractAtaxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by t

  13. Experience of the Irish National Centre for hereditary haemorrhagic telangiectasia 2003-2008.

    LENUS (Irish Health Repository)

    Ni Bhuachalla, C F

    2012-01-31

    Hereditary haemorrhagic telangiectasia (HHT) is a group of autosomal dominant disorders of vascular structure. The Irish National Centre for HHT at the Mercy University Hospital, Cork, Ireland was founded in 2003. From 2003 to 2008, screening of 164 patients with contrast echocardiography, thoracic computerised tomography (CT) and cerebral magnetic resonance imaging (MRI) has identified 88 patients with definite HHT, 72 (82%) of whom had epistaxis, 70 (80%) had telangiectasia and 81 (92%) had a first-degree relative with HHT. We sought to describe the manifestations of HHT in an Irish population and to determine differences between internationally reported data. The HHT patient database was analysed to describe demographics, clinical manifestations and interventional procedures performed in all referred patients. Contrast echocardiography and\\/or CT were performed in 86 patients with definite HHT, identifying 27 patients (31%) with pulmonary arteriovenous malformations (pAVMs). Nineteen patients with single or multiple pAVMs had 28 embolisation procedures performed, with 1-6 pAVMs embolised per procedure. Cerebral MRI was performed in 78 (89%) patients and 2 (2.3%) had cerebral arteriovenous malformations (cAVMs). HHT prevalence is thought to be 1 in 2500-8000, suggesting that there are many undiagnosed cases in Irish patients. Internationally published data suggest a prevalence of 15-35% for pAVMs and 10-23% for cAVMs in patients with HHT. While the prevalence of pAVMs in our group is consistent with these data, the prevalence of cAVMs is considerably lower, suggesting that Irish patients with HHT may differ genotypically and phenotypically from those in other countries.

  14. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype.

    Science.gov (United States)

    Micol, Romain; Ben Slama, Lilia; Suarez, Felipe; Le Mignot, Loïc; Beauté, Julien; Mahlaoui, Nizar; Dubois d'Enghien, Catherine; Laugé, Anthony; Hall, Janet; Couturier, Jérôme; Vallée, Louis; Delobel, Bruno; Rivier, François; Nguyen, Karine; Billette de Villemeur, Thierry; Stephan, Jean-Louis; Bordigoni, Pierre; Bertrand, Yves; Aladjidi, Nathalie; Pedespan, Jean-Michel; Thomas, Caroline; Pellier, Isabelle; Koenig, Michel; Hermine, Olivier; Picard, Capucine; Moshous, Despina; Neven, Bénédicte; Lanternier, Fanny; Blanche, Stéphane; Tardieu, Marc; Debré, Marianne; Fischer, Alain; Stoppa-Lyonnet, Dominique

    2011-08-01

    Ataxia-telangiectasia (A-T) is a rare genetic disease caused by germline biallelic mutations in the ataxia-telangiectasia mutated gene (ATM) that result in partial or complete loss of ATM expression or activity. The course of the disease is characterized by neurologic manifestations, infections, and cancers. We studied A-T progression and investigated whether manifestations were associated with the ATM genotype. We performed a retrospective cohort study in France of 240 patients with A-T born from 1954 to 2005 and analyzed ATM mutations in 184 patients, along with neurologic manifestations, infections, and cancers. Among patients with A-T, the Kaplan-Meier 20-year survival rate was 53.4%; the prognosis for these patients has not changed since 1954. Life expectancy was lower among patients with mutations in ATM that caused total loss of expression or function of the gene product (null mutations) compared with that seen in patients with hypomorphic mutations because of earlier onset of cancer (mainly hematologic malignancies). Cancer (hazard ratio, 2.7; 95% CI, 1.6-4.5) and respiratory tract infections (hazard ratio, 2.3; 95% CI, 1.4-3.8) were independently associated with mortality. Cancer (hazard ratio, 5.8; 95% CI, 2.9-11.6) was a major risk factor for mortality among patients with null mutations, whereas respiratory tract infections (hazard ratio, 4.1; 95% CI, 1.8-9.1) were the leading cause of death among patients with hypomorphic mutations. Morbidity and mortality among patients with A-T are associated with ATM genotype. This information could improve our prognostic ability and lead to adapted therapeutic strategies. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Mutation of ataxia-telangiectasia mutated is associated with dysfunctional glutathione homeostasis in cerebellar astroglia.

    Science.gov (United States)

    Campbell, Andrew; Bushman, Jared; Munger, Joshua; Noble, Mark; Pröschel, Christoph; Mayer-Pröschel, Margot

    2016-02-01

    Astroglial dysfunction plays an important role in neurodegenerative diseases otherwise attributed to neuronal loss of function. Here we focus on the role of astroglia in ataxia-telangiectasia (A-T), a disease caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. A hallmark of A-T pathology is progressive loss of cerebellar neurons, but the mechanisms that impact neuronal survival are unclear. We now provide a possible mechanism by which A-T astroglia affect the survival of cerebellar neurons. As astroglial functions are difficult to study in an in vivo setting, particularly in the cerebellum where these cells are intertwined with the far more numerous neurons, we conducted in vitro coculture experiments that allow for the generation and pharmacological manipulation of purified cell populations. Our analyses revealed that cerebellar astroglia isolated from Atm mutant mice show decreased expression of the cystine/glutamate exchanger subunit xCT, glutathione (GSH) reductase, and glutathione-S-transferase. We also found decreased levels of intercellular and secreted GSH in A-T astroglia. Metabolic labeling of l-cystine, the major precursor for GSH, revealed that a key component of the defect in A-T astroglia is an impaired ability to import this rate-limiting precursor for the production of GSH. This impairment resulted in suboptimal extracellular GSH supply, which in turn impaired survival of cerebellar neurons. We show that by circumventing the xCT-dependent import of L-cystine through addition of N-acetyl-L-cysteine (NAC) as an alternative cysteine source, we were able to restore GSH levels in A-T mutant astroglia providing a possible future avenue for targeted therapeutic intervention. © 2015 Wiley Periodicals, Inc.

  16. Immune deficiency in Ataxia-Telangiectasia: a longitudinal study of 44 patients.

    Science.gov (United States)

    Chopra, C; Davies, G; Taylor, M; Anderson, M; Bainbridge, S; Tighe, P; McDermott, E M

    2014-05-01

    Ataxia-Telangiectasia (A-T) is a genetic condition leading to neurological defects and immune deficiency. The nature of the immune deficiency is highly variable, and in some cases causes significant morbidity and mortality due to recurrent sinopulmonary infections. Although the neurological defects in A-T are progressive, the natural history of the immune deficiency in A-T has not been evaluated formally. In this study we analyse the clinical history and immunological data in 44 patients with A-T who attended the National Ataxia-Telangiectasia clinic in Nottingham between 2001 and 2011. Using patient medical records and Nottingham University Hospitals (NUH) National Health Service Trust medical IT systems, data regarding clinical history, use of immunoglobulin replacement therapy, total immunoglobulin levels, specific antibody levels and lymphocyte subset counts were obtained. T cell receptor spectratyping results in some patients were already available and, where possible, repeat blood samples were collected for analysis. This study shows that subtle quantitative changes in certain immunological parameters such as lymphocyte subset counts may occur in patients with A-T over time. However, in general, for the majority of patients the severity of immune deficiency (both clinically and in terms of immunological blood markers) does not seem to deteriorate significantly with time. This finding serves to inform the long-term management of this cohort of patients because, if recurrent respiratory tract infections present later in life, then other contributory factors (e.g. cough/swallowing difficulties, underlying lung disease) should be investigated aggressively. Our findings also offer some form of reassurance for parents of children with A-T, which is otherwise a progressively severely debilitating condition. © 2014 British Society for Immunology.

  17. Hereditary hemorrhagic telangiectasia and pregnancy: potential adverse events and pregnancy outcomes

    Directory of Open Access Journals (Sweden)

    Bari O

    2017-05-01

    Full Text Available Omar Bari,1 Philip R Cohen2 1School of Medicine, University of California San Diego, La Jolla, CA, USA; 2Department of Dermatology, University of California San Diego, La Jolla, CA, USA Abstract: Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant condition with a prevalence of ~1 in 5,000 individuals. The pathophysiology of this condition centers on the lack of capillary beds between arterioles and venules, leading to direct contact between these vessels. This results in telangiectases on characteristic locations such as the face, fingers, mouth, and nasal mucosa. Visceral arteriovenous malformations (AVMs are also observed in many patients, and these are most commonly seen in the brain, gastrointestinal tract, and lungs. Liver AVMs are present in many patients with HHT, though these individuals are usually asymptomatic; however, liver AVMs may lead to serious complications, such as high output cardiac failure. Diagnosis of HHT hinges upon fulfilling three out of four criteria: family history of the condition, mucocutaneous telangiectases, spontaneous and recurrent episodes of epistaxis, and visceral AVMs. Management is guided by international consensus guidelines and targets patients’ specific AVMs. Prognosis is good, though severe complications including hemorrhage and paradoxical emboli are possible. Novel therapeutics are being explored in clinical trials; bevacizumab and pazopanib inhibit angiogenesis, while thalidomide bolsters blood vessel maturation. Pregnancy in patients with HHT is considered high risk. While the majority of pregnancies proceed normally, severe complications have been reported in some women with HHT; these include heart failure, intracranial hemorrhage, pulmonary hemorrhage, and stroke. Such complications occur most often in the second and third trimesters when maternal changes such as peripheral vasodilation and increased cardiac output are at their maximum. Awareness of the diagnosis of HHT has

  18. Single night postoperative prone posturing in idiopathic macular hole surgery.

    LENUS (Irish Health Repository)

    2012-02-01

    Purpose. To evaluate the role of postoperative prone posturing for a single night in the outcome of trans pars plana vitrectomy (TPPV) with internal limiting membrane (ILM) peel and 20% perfluoroethane (C2F6) internal tamponade for idiopathic macular hole. Methods. This prospective trial enrolled 14 eyes in 14 consecutive patients with idiopathic macular hole. All eyes underwent TPPV with vision blue assisted ILM peeling with and without phacoemulsification and intraocular lens (IOL) for macular hole. Intraocular gas tamponade (20% C2F6) was used in all cases with postoperative face-down posturing overnight and without specific posturing afterwards. LogMAR visual acuity, appearance by slit-lamp biomicroscopy, and ocular coherence tomography (OCT) scans were compared preoperatively and postoperatively to assess outcome. Results. Among 14 eyes recruited, all eyes were phakic; 50% of patients underwent concurrent phacoemulsification with IOL. The macular holes were categorized preoperatively by OCT appearance, 4 (28.57%) were stage 2, 7 (50%) were stage 3, and 3 (21.43%) were stage 4. Mean macular hole size was 0.35 disk diameters. Symptoms of macular hole had been present for an average of 6.5 months. All holes (100%) were closed 3 and 6 months postoperatively. Mean visual acuity (logMAR) was improved to 0.61 at 3 months and was stable at 6 months after the surgery. None of the eyes had worse vision postoperatively. Conclusions. Vitrectomy with ILM peeling and 20% C2F6 gas with a brief postoperative 1 night prone posturing regimen is a reasonable approach to achieve anatomic closure in idiopathic macular hole. Concurrent cataract extraction did not alter outcomes and was not associated with any additional complications.

  19. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Fong AH

    2013-04-01

    Full Text Available Angie HC Fong,1 Timothy YY Lai1,2 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong; 22010 Retina and Macula Centre, Tsimshatsui, Kowloon, Hong Kong Abstract: Neovascular age-related macular degeneration (AMD and diabetic macular edema (DME are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various

  20. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  1. Decreased fixation stability of the preferred retinal location in juvenile macular degeneration

    NARCIS (Netherlands)

    Bethlehem, Richard A I; Dumoulin, Serge O.; Dalmaijer, Edwin S.; Smit, Miranda; Berendschot, Tos T J M; Nijboer, Tanja C W; Van Der Stigchel, Stefan

    2014-01-01

    Macular degeneration is the main cause for diminished visual acuity in the elderly. The juvenile form of macular degeneration has equally detrimental consequences on foveal vision. To compensate for loss of foveal vision most patients with macular degeneration adopt an eccentric preferred retinal lo

  2. Intravitreal gas injection for the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    McHugh D

    2011-10-01

    Full Text Available Dominic McHugh, Bhaskar Gupta, Manzar Saeed King's College Hospital, Denmark Hill, London, England, UK Purpose: This study investigates the efficacy of an intravitreal gas injection in inducing a posterior vitreous detachment (PVD in patients with clinically significant diabetic macular edema refractory to laser therapy. Methods: A local ethics committee-approved technique of an intravitreal injection of pure perfluoropropane gas (C3F8 was performed for all participants. After a period of prone positioning, the patients underwent regular and detailed clinical review. Main outcome measures: The induction of a PVD, change in macular thickness, change in visual acuity. Results: A PVD was induced in all five eyes with subsequent signs of reduction in macular thickness and resolution of exudates. Mean visual improvement was 11 ETDRS (Early Treatment Diabetic Retinopathy Study letters (range 4–21. Apart from a transient vitreous hemorrhage in one eye, there were no significant treatment-related complications. Conclusion: The induction of a PVD by pneumatic retinopexy appears to have a significant influence on diabetic macular edema in eyes which have not successfully responded to macular laser therapy. A randomized clinical trial is justified on the basis of the initial promising data. Keywords: optical coherence tomography, OCT, posterior vitreous detachment, perfluoropropane

  3. Imaging study of lymphoreticular tumor development in ataxia-telangiectasia and Nijmegen breakage syndrome; Estudio por imagen del desarrollo de tumores linforreticulares en la ataxia telangiectasia y el sindrome de Nijmegen

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Leon, M. I.; Ceres-Ruiz, L.; Cuesta, M. A.; Garcia-Martin, F. J. [Hospital Materno-Infantil C.H.U. Carlos Haya. Malaga (Spain)

    2003-07-01

    Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is an autosomal recessive illness characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency combined with susceptibility to sinopulmonary infections and high incidence of neoplastic development. Nijmegen breakage syndrome (NBS) is a variant of AT, is also an autosomal recessive illness that presents cerebellar ataxia, as well as combined immunodeficiency and a tendency toward tumor development. Contrary to Louis-Bar syndrome, it doesn't present telangiectasia and exhibits a characteristics phenotype (short stature, bird-like face and microcephaly). Both entities are classified as syndrome of chromosomal instability or chromosomal fragility, a group which also includes Bloom syndrome and Fanconi anemia. All of these show an increase in the frequency of neoplastic pathologies, mainly lymphoid tumors. We present three patients,two with AT and one with NBS, who developed different lymphoma types in the course of the illness. We highlight the most outstanding aspects from a clinical-radiological point of view. (Author) 17 refs.

  4. Hereditary haemorrhagic telangiectasia treated by pulsed neodymium:yttrium-aluminium-garnet (Nd:YAG) laser (1,064 nm).

    Science.gov (United States)

    Werner, A; Bäumler, W; Zietz, S; Kühnel, T; Hohenleutner, U; Landthaler, M

    2008-10-01

    Hereditary haemorrhagic telangiectasia (HHT) is a familial, autosomal, dominant, multi-system, vascular, dysplasia. Besides repetitive epistaxis, cutaneous eruptive macules and nodules lead to recurring bleeding and cosmetic problems. We report on a pilot study of four cases of HHT in which cutaneous lesions were treated with a pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (1,064 nm). Pulsed Nd:YAG laser treatment, without anaesthesia, was performed several times on eruptive angiomas on palmar and facial skin. Lesions on fingers and face mostly showed very good, or even complete, clearing after the first laser treatment. Several macules required multiple treatment; only a few lesions showed no effect. Pulsed Nd:YAG laser therapy (1,064 nm) appears to be an effective and safe treatment option for hereditary haemorrhagic telangiectasia on the skin of face and extremities.

  5. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions.

    Science.gov (United States)

    Das, Undurti N

    2016-10-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD.

  6. New Computer Simulations of Macular Neural Functioning

    Science.gov (United States)

    Ross, Muriel D.; Doshay, D.; Linton, S.; Parnas, B.; Montgomery, K.; Chimento, T.

    1994-01-01

    We use high performance graphics workstations and supercomputers to study the functional significance of the three-dimensional (3-D) organization of gravity sensors. These sensors have a prototypic architecture foreshadowing more complex systems. Scaled-down simulations run on a Silicon Graphics workstation and scaled-up, 3-D versions run on a Cray Y-MP supercomputer. A semi-automated method of reconstruction of neural tissue from serial sections studied in a transmission electron microscope has been developed to eliminate tedious conventional photography. The reconstructions use a mesh as a step in generating a neural surface for visualization. Two meshes are required to model calyx surfaces. The meshes are connected and the resulting prisms represent the cytoplasm and the bounding membranes. A finite volume analysis method is employed to simulate voltage changes along the calyx in response to synapse activation on the calyx or on calyceal processes. The finite volume method insures that charge is conserved at the calyx-process junction. These and other models indicate that efferent processes act as voltage followers, and that the morphology of some afferent processes affects their functioning. In a final application, morphological information is symbolically represented in three dimensions in a computer. The possible functioning of the connectivities is tested using mathematical interpretations of physiological parameters taken from the literature. Symbolic, 3-D simulations are in progress to probe the functional significance of the connectivities. This research is expected to advance computer-based studies of macular functioning and of synaptic plasticity.

  7. Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory

    Directory of Open Access Journals (Sweden)

    Pedro Romero-Aroca

    2016-01-01

    Full Text Available Diabetic macular edema (DME can cause blindness in diabetic patients suffering from diabetic retinopathy (DR. DM parameters controls (glycemia, arterial tension, and lipids are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug.

  8. Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory

    Science.gov (United States)

    Baget-Bernaldiz, Marc; Pareja-Rios, Alicia; Lopez-Galvez, Maribel; Navarro-Gil, Raul; Verges, Raquel

    2016-01-01

    Diabetic macular edema (DME) can cause blindness in diabetic patients suffering from diabetic retinopathy (DR). DM parameters controls (glycemia, arterial tension, and lipids) are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF) is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug.

  9. Animal models of age related macular degeneration.

    Science.gov (United States)

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  10. Thalidomide Effects in Patients with Hereditary Hemorrhagic Telangiectasia During Therapeutic Treatment and in Fli-EGFP Transgenic Zebrafish Model

    Institute of Scientific and Technical Information of China (English)

    Hong-Ling Peng; Yi-Fang Yi; Shun-Ke Zhou; Si-Si Xie; Guang-Sen Zhang

    2015-01-01

    Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis,mucocutaneous telangiectasia, and arteriovenous malformations.The efficacy of traditional treatments for HHT is very limited.The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.Methods: HHT was diagnosed according to Shovlin criteria.Five HHT patients were treated with thalidomide (100 mg/d).The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide.The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis.Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.Results: The average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P =0.009).The "telangiectatic spot" on the tongue almost vanished;CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation.The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy.The plasma VEGF protein expression was down-regulated in HHT patients.Conclusions: Thalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients.It also leads to vascular remodeling in the zebrafish model.

  11. Early change of central macular thickness after intravitreous triamcinolone or bevacizumab in diabetic macular edema or retinal vein occlusion.

    Science.gov (United States)

    Sonoda, Yasushi; Arimura, Noboru; Shimura, Masahiko; Sakamoto, Taiji

    2011-02-01

    To evaluate the immediate changes after intravitreous triamcinolone acetonide or intravitreous bevacizumab in diabetic macular edema (DME). A nonrandomized interventional study. Type 2 diabetic patients were included. Intravitreous triamcinolone acetonide (4 mg) was injected for 22 eyes with DME and IVB (1.25 mg) for 18 eyes with DME. The early time-dependent changes of central macular thickness were evaluated by optical coherence tomography before and from 1 hour to 1 month after intervention. Intravitreous bevacizumab was also tested in patients with retinal vein occlusion as a control of non-DME. Visual acuity was also examined. Compared with the baseline, central macular thickness of eyes with DME decreased significantly 1 hour after intravitreous triamcinolone acetonide (P central macular thickness was observed significantly from 3 hours after IVB in retinal vein occlusion (P retinal vein occlusion than DME after IVB. Visual acuity improved significantly in DME with intravitreous triamcinolone acetonide or IVB at 1 month (P retinal vein occlusion. Although no conclusion can be drawn, immediate decrease in central macular thickness after intravitreous triamcinolone acetonide might indicate the possible involvement of a nongenomic pathway of triamcinolone acetonide action.

  12. Cystoid Macular Edema Induced by Low Doses of Nicotinic Acid

    Directory of Open Access Journals (Sweden)

    Daniela Domanico

    2013-01-01

    Full Text Available Cystoid macular edema (CME is a condition that involves the macula, causing painless vision loss. In this paper, we report a case of niacin-induced bilateral cystoid macular edema (CME in a middle-age woman taking low dose of niacin (18 mg of nicotinic acid. Optical coherence tomography (OCT showed retinal thickening and cystoid spaces in both eyes, whereas fluorescein angiography (FA; HRA 2, Heidelberg Engineering revealed the absence of fluorescein leakage also in later phases. Four weeks after discontinuation of therapy there were a complete disappearance of macular edema at funduscopic examination and an improvement of visual acuity in both eyes. Furthermore OCT showed a normal retinal profile in both eyes. In our opinion considering the wide availability of niacin, medical monitoring and periodical examination should be considered during niacin administration. To our knowledge, this is the first report in the literature that described the very low-dose niacin-induced bilateral niacin maculopathy.

  13. Age-related macular degeneration: current treatment and future options.

    Science.gov (United States)

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  14. Hypergonadotropic hypogonadism and hypersegmented neutrophils in a patient with ataxia-telangiectasia-like disorder: potential diagnostic clues?

    Science.gov (United States)

    Yoshida, Takeshi; Awaya, Tomonari; Shibata, Minoru; Kato, Takeo; Numabe, Hironao; Kobayashi, Junya; Komatsu, Kenshi; Heike, Toshio

    2014-07-01

    Ataxia-telangiectasia-like disorder (ATLD) is a rare autosomal recessive disorder, and has symptoms similar to ataxia-telangiectasia (AT). ATLD is caused by mutations in the MRE11 gene, involved in DNA double-strand break repair (DSBR). In contrast to AT, ATLD patients lack key clinical features, such as telangiectasia or immunodeficiency, and are therefore difficult to be diagnosed. We report a female ATLD patient presenting with hypergonadotropic hypogonadism and hypersegmented neutrophils, previously undescribed features in this disorder, and potential diagnostic clues to differentiate ATLD from other conditions. The patient showed slowly progressive cerebellar ataxia from 2 years of age, and MRI revealed atrophy of the cerebellum, oculomotor apraxia, mild cognitive impairment, writing dystonia, hypergonadotropic hypogonadism with primary amenorrhea, and hypersegmented neutrophils. Western blot assay demonstrated total loss of MRE11 and reduction of ATM-dependent phosphorylation; thus, we diagnosed ATLD. Genetically, a novel missense mutation (c.140C>T) was detected in the MRE11 gene, but no other mutation was found in the patient. Our presenting patient suggests that impaired DSBR may be associated with hypergonadotropic hypogonadism and neutrophil hypersegmentation. In conclusion, when assessing patients with ataxia of unknown cause, ATLD should be considered, and the gonadal state and peripheral blood smear samples evaluated. © 2014 Wiley Periodicals, Inc.

  15. Surgical outcomes of inverted internal limiting membrane flap technique for large macular hole

    Directory of Open Access Journals (Sweden)

    Prabhushanker Mahalingam

    2013-01-01

    Full Text Available We are presenting the initial results of inverted internal limiting membrane (ILM flap technique for large macular hole. Five eyes of five patients with large diameter macular hole (>700 μm were selected. All patients underwent inverted ILM flap technique for macular hole. Anatomical closure and functional success were achieved in all patients. There was no loss of best-corrected visual acuity in any of the patients. Inverted ILM flap technique in macular hole surgery seems to have a better hole closure rates, especially in large diameter macular holes. Larger case series is required to assess the efficacy and safety of this technique.

  16. Macular hard exudates and scar formation after laser photocoagulation in retinopathy of prematurity.

    Science.gov (United States)

    Epstein, Ilan J; Aziz, Hassan A; Young, Ryan C; Berrocal, Audina M

    2013-07-02

    The authors report the formation of hard exudates and macular scarring after laser photocoagulation therapy in patients with retinopathy of prematurity (ROP). Two premature neonates, the first born at 24 weeks and the second at 25 weeks gestational age, were diagnosed as having ROP that necessitated laser photocoagulation treatment at 32 and 36 weeks, respectively. Subretinal fluid and macular hard exudation developed in both patients that eventually caused bilateral macular scarring. Subretinal macular fluid with hard exudation could lead to macular scar formation in neonates with ROP after laser photocoagulation that could significantly affect the visual prognosis in preterm infants. Copyright 2013, SLACK Incorporated.

  17. Spontaneous resolution of macular edema after silicone oil removal

    Directory of Open Access Journals (Sweden)

    Eyyup Karahan

    2014-12-01

    Full Text Available AIM:To investigate the macular changes in eyes filled with silicone oil (SO and course of these changes after SO removal.METHODS:A retrospective optical coherence tomography scan review was conducted for twenty-four patients who underwent uncomplicated pars plana vitrectomy with SO tamponade for complex retinal detachments were detected with optical coherence tomography before, and one week, one month and three months after SO removal.RESULTS:Mean duration of SO tamponade was 3.6±1.0mo (range:3-7mo. Cystoid macular edema (CME was detected in 3 eyes before SO removal. Submacular fluid was represented in 1 eye before silicone SO removal. Resolution of CME and submacular fluid was achieved 1mo after SO removal in all eyes. Mean best corrected visual acuity (BCVA was 1.15±0.65 (range, hand movement to 0.2 before SO removal in the eyes without macular changes. After SO removal, the mean BCVA values at 1wk and 1 and 3mo, and 0.82±0.23, 0.76±0.21, and 0.70±0.19, all of which were significantly better than baseline (P=0.030, 0.017, 0.006 respectively. In the eyes with macular CME and subretinal fluid the mean BCVA was significantly improved at 3mo after SO removal compared with baseline (P=0.037.CONCLUSION:Decreased visual acuity in eyes filled with SO could be caused by macular complications due to SO. CME and subretinal fluid may resolve without any additional macular surgery after SO removal.

  18. New developments in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Lyndon da Cruz

    2008-09-01

    Full Text Available The World Health Organization (WHO estimates that over 3 million people (9% of global blindness are blinded by age-related macular degeneration (AMD. AMD affects people over the age of 55. There are two main types of AMD, dry and wet. In dry AMD, patients slowly lose vision through progressive atrophy of the macular tissue. Wet, or exudative, AMD, is associated with new blood vessels called subretinal neovascular membranes (or SRNVM and affected patients lose vision more rapidly due to fluid leakage and haemorrhage at the macula.

  19. Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images

    OpenAIRE

    Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

    2016-01-01

    Non-lethal macular diseases greatly impact patients’ life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Corr...

  20. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Bassam R Ali

    Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

  1. Volcano like pattern in optical coherence tomography in chronic diabetic macular edema.

    Science.gov (United States)

    Pai, Sivakami A; Hussain, Nazimul; Hebri, Sudhira P; Lootah, Afra M; Dekhain, Moza A

    2014-04-01

    In this article we herein report an interesting vitreo-macular interface abnormality associated with chronic diabetic cystoid macular edema. It is an observational case study of three diabetic patients examined in the diabetic clinic. All the patients had proliferative diabetic retinopathy with chronic macular edema. A serial cross sectional OCT examination and tracking of both the longitudinal progression of macular thickening and vitreo-macular interface revealed cystoid macular edema with a characteristic hyperreflective vitreous shadow emerging from the vitreofoveal interface. All the patients had dehiscence of inner retinal layers. This particular morphological feature at the vitreo-foveolar interface, which we name as "volcano sign", has not been described earlier. The probable mechanism of such a finding probably could be due to slow progressive leakage of chronic cytoid fluid into the vitreous with condensation of the overlying vitreous. Vitreo-macular traction followed by posterior vitreous detachment probably would have contributed to such a morphological event.

  2. Treatment of macular degeneration, according to Bangerter.

    Science.gov (United States)

    Teichmann, K D

    1997-10-30

    Age-related macular degeneration (AMD) is a common cause of visual loss among elderly patients. Although some risk factors have been determined, the ultimate cause of the disease is not known. For a long time, therapeutic nihilism has been the rule among ophthalmologists confronted with such patients. Bangerter has not shared this attitude, especially since the time that he incidentally discovered, more than 40 years ago, the beneficial effects of radiotherapy, in discouraging the growth of new vessels at the posterior pole of the eye. A variety of approaches are combined and used by Bangerter in the treatment of the different types of AMD, including retrobulbar injections of either vasodilating medications (in the dry - or atrophic - type) or corticosteroids (in the wet - or exudative - type), general medical measures aimed at improving metabolic and vascular functions such as supplementation with trace elements, antioxidants, and vitamins; ozone therapy; advice to increase physical fitness, improve nutrition, and abstain from smoking; and protection from excessive light exposure. Being convinced of the usefulness of his type of combination treatment, he has always rejected undertaking controlled clinical trials, of only single aspects of the therapy, as unethical and invalid. For this reason, scientific journals have not proven cooperative in several attempts at publishing his results, as collected in retrospective surveys. Recently, however, some of the several approaches combined by Bangerter in treating AMD have been pronounced effective by other investigators. We present here an overview of his treatment approaches, as few people are aware of them, to clear up misconceptions and to set records straight.

  3. Rehabilitation Approaches in Macular Degeneration Patients.

    Science.gov (United States)

    Maniglia, Marcello; Cottereau, Benoit R; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient's quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient's visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients.

  4. Rehabilitation Approaches in Macular Degeneration Patients

    Science.gov (United States)

    Maniglia, Marcello; Cottereau, Benoit R.; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient’s quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient’s visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients. PMID:28082876

  5. Aspectos atuais na fisiopatologia do edema macular diabético Recent aspects on physiopathology of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Mário Martins dos Santos Motta

    2008-02-01

    Full Text Available O edema macular é a principal causa de baixa visual em pacientes diabéticos. Seu mecanismo de formação é complexo e envolve alterações bioquímicas e estruturais. Os autores fazem uma revisão e atualização dos conceitos fisiopatológicos envolvidos na maculopatia diabética.Macular edema is the leading cause of poor vision in diabetic patients.The mechanism of edema formation is complex and involves biochemical and structural changes. The authors review and update the physiopathologic concepts related to diabetic maculopathy.

  6. Health state utilities in patients with diabetic retinopathy, diabetic macular oedema and age-related macular degeneration: a systematic review

    OpenAIRE

    Poku, E.; Brazier, J; Carlton, J; Ferreira, A.

    2013-01-01

    Background\\ud \\ud Health state utility values (HSUVs) are important in the assessment of the cost effectiveness of new interventions. In the case of visual conditions, models generally tend have tended to be built around a set of health states defined by visual acuity (VA). The aim of this review was to assess the impact of VA on HSUVs in patients with diabetic retinopathy, diabetic macular oedema or age-related macular degeneration.\\ud \\ud Methods\\ud \\ud A systematic literature search was un...

  7. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema.

    Science.gov (United States)

    Fong, Angie H C; Lai, Timothy Y Y

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed.

  8. Analysis of macular cone photoreceptors in a case of occult macular dystrophy

    Directory of Open Access Journals (Sweden)

    Tojo N

    2013-05-01

    Full Text Available Naoki Tojo Tomoko Nakamura Hironori Ozaki Miyako Oka Toshihiko Oiwake Atsushi HayashiDepartment of Ophthalmology, University of Toyama, Toyama, JapanPurpose: To investigate changes in cone photoreceptors with adaptive optics (AO fundus imaging and spectral domain optical coherence tomography (SD-OCT in a case of occult macular dystrophy (OMD.Patient and methods: Both eyes of a 42-year-old woman diagnosed with OMD were examined. We used an AO fundus camera to obtain images of cone photoreceptors in the macula of the OMD subject and five healthy control subjects. Correlations between the AO images and the SD-OCT images were examined. Cone photoreceptors in eight areas in the macula of OMD and healthy control subjects were analyzed and compared.Results: SD-OCT showed a loss of the cone outer-segment tips line outside of the fovea in both eyes of the subject with OMD. The left eye with decreased visual acuity showed a discontinuous photoreceptor inner-segment and outer-segment line and cone outer-segment tips line at the fovea in SD-OCT and loss of cone mosaics as a dark spot in the AO image. In panoramic AO images and cone-density maps, less cone density was observed in a ring-like region outside the fovea than in the peripheral retina. In most of the areas examined, the cone densities were lower in the OMD eyes than in the healthy control eyes.Conclusions: Cone densities in the macula of the OMD patient were greatly decreased. AO images were found to be useful to evaluate morphologic changes in cone photoreceptors in patients with OMD.Keywords: occult macular dystrophy, adaptive optics, cone photoreceptor, cone analysis, optical coherence tomography

  9. NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair.

    Science.gov (United States)

    Fang, Evandro Fei; Kassahun, Henok; Croteau, Deborah L; Scheibye-Knudsen, Morten; Marosi, Krisztina; Lu, Huiming; Shamanna, Raghavendra A; Kalyanasundaram, Sumana; Bollineni, Ravi Chand; Wilson, Mark A; Iser, Wendy B; Wollman, Bradley N; Morevati, Marya; Li, Jun; Kerr, Jesse S; Lu, Qiping; Waltz, Tyler B; Tian, Jane; Sinclair, David A; Mattson, Mark P; Nilsen, Hilde; Bohr, Vilhelm A

    2016-10-11

    Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD(+), and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD(+) reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD(+) also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions. Published by Elsevier Inc.

  10. Induced Pluripotent Stem Cells from Ataxia-Telangiectasia Recapitulate the Cellular Phenotype

    Science.gov (United States)

    Nayler, Sam; Gatei, Magtouf; Kozlov, Sergei; Gatti, Richard; Mar, Jessica C.; Wells, Christine A.

    2012-01-01

    Pluripotent stem cells can differentiate into every cell type of the human body. Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) therefore provides an opportunity to gain insight into the molecular and cellular basis of disease. Because the cellular DNA damage response poses a barrier to reprogramming, generation of iPSCs from patients with chromosomal instability syndromes has thus far proven to be difficult. Here we demonstrate that fibroblasts from patients with ataxia-telangiectasia (A-T), a disorder characterized by chromosomal instability, progressive neurodegeneration, high risk of cancer, and immunodeficiency, can be reprogrammed to bona fide iPSCs, albeit at a reduced efficiency. A-T iPSCs display defective radiation-induced signaling, radiosensitivity, and cell cycle checkpoint defects. Bioinformatic analysis of gene expression in the A-T iPSCs identifies abnormalities in DNA damage signaling pathways, as well as changes in mitochondrial and pentose phosphate pathways. A-T iPSCs can be differentiated into functional neurons and thus represent a suitable model system to investigate A-T-associated neurodegeneration. Collectively, our data show that iPSCs can be generated from a chromosomal instability syndrome and that these cells can be used to discover early developmental consequences of ATM deficiency, such as altered mitochondrial function, that may be relevant to A-T pathogenesis and amenable to therapeutic intervention. PMID:23197857

  11. Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia.

    Science.gov (United States)

    Worth, Paul F; Srinivasan, Venkataramanan; Smith, Anna; Last, James I; Wootton, Laura L; Biggs, Paul M; Davies, Nicholas P; Carney, Ellen F; Byrd, Philip J; Taylor, A Malcolm R

    2013-04-01

    The major clinical feature of ataxia telangiectasia (A-T) is severe progressive neurodegeneration with onset in infancy. This classical A-T phenotype is caused by biallelic null mutations in the ATM gene, leading to the absence of ATM protein and increased cellular radiosensitivity. We report an unusual case of A-T in a 41-year-old mother, A-T210, who had very mild neurological symptoms despite complete loss of ATM protein. A neurological examination was performed, cellular radiosensitivity was assessed, and the ATM gene was sequenced. Skin fibroblasts and a lymphoblastoid cell line (LCL) were assayed for ATM protein expression and kinase activity. Patient A-T210 showed mild chorea, dystonia, and gait ataxia, walked independently, and drove a car. LCL and skin fibroblasts were radiosensitive and did not express ATM protein. Two ATM-null mutations were identified. The severe neurodegeneration resulting from loss of ATM can be mitigated in some circumstances. Copyright © 2012 Movement Disorders Society.

  12. The appropriateness of the mouse model for ataxia-telangiectasia: neurological defects but no neurodegeneration.

    Science.gov (United States)

    Lavin, Martin F

    2013-08-01

    Patients with ataxia-telangiectasia (A-T) are characterised by genome instability, cancer predisposition and a progressive neurodegeneration. A number of model systems have been developed for A-T but none recapitulate all the phenotype. The majority of these models have been generated in mice. While Atm deficient mouse models exhibit much of the phenotype described in patients with A-T, the broad consensus is that they do not display the most debilitating aspect of A-T, i.e. neurodegeneration. Cerebellar atrophy is one of the neuronal characteristics of A-T patients due to defects in neuronal development and progressive loss of Purkinje and granule cells. This is not evident in Atm-deficient mutants but there are multiple reports on neurological abnormalities in these mice. The focus of this review is to evaluate the appropriateness of Atm mutant mouse models for A-T, particularly with reference to neurological abnormalities and how they might relate to neurodegeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Development of global rating instruments for pediatric patients with ataxia telangiectasia.

    Science.gov (United States)

    Nissenkorn, Andreea; Borgohain, Rupam; Micheli, Roberto; Leuzzi, Vincenzo; Hegde, Anaita Udwadia; Mridula, Kandadai Rukmini; Molinaro, Anna; D'Agnano, Daniela; Yareeda, Sireesha; Ben-Zeev, Bruria

    2016-01-01

    Ataxia telangiectasia (AT) is a neurodegenerative disorder with cerebellar and extrapyramidal features. Interventional and epidemiological studies in AT should rely on specific scales which encompass the specific neurological features, as well the early progressive course and the subsequent plateau. The aim of this study was to build a scale of the CGI type (Clinical Global Impression) which is disease specific, as well as to check the feasibility of the ICARS scale for ataxia in this population. We recruited 63 patients with ataxia, aged 10.76 ± 3.2 years, followed at 6 international AT centers, 49 of them (77.8%) with classical AT. All patients were evaluated for ataxia with ICARS scale. In patients with AT, two CGI scales were scored, unstructured as structured for which separate anchors were provided. Mean ICARS score was 44.7 ± 20.52, and it's severity positively correlated with age (Spearman correlation, r = 0.46, p ataxia can be reliably measured in children with AT by using ICARS. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  14. Novel mutations in ataxia telangiectasia and AOA2 associated with prolonged survival.

    Science.gov (United States)

    Davis, Marie Y; Keene, C Dirk; Swanson, Phillip D; Sheehy, Conor; Bird, Thomas D

    2013-12-15

    Ataxia telangiectasia (AT) and ataxia oculomotor apraxia type 2 (AOA2) are autosomal recessive ataxias caused by mutations in genes involved in maintaining DNA integrity. Lifespan in AT is greatly shortened (20s-30s) due to increased susceptibility to malignancies (leukemia/lymphoma). Lifespan in AOA2 is uncertain. We describe a woman with variant AT with two novel mutations in ATM (IVS14+2T>G and 5825C>T, p.A1942V) who died at age 48 with pancreatic adenocarcinoma. Her mutations are associated with an unusually long life for AT and with a cancer rarely associated with that disease. We also describe two siblings with AOA2, heterozygous for two novel mutations in senataxin (3 bp deletion c.343-345 and 1398T>G, p.I466M) who have survived into their 70s, allowing us to characterize the longitudinal course of AOA2. In contrast to AT, we show that persons with AOA2 can experience a prolonged lifespan with considerable motor disability. Published by Elsevier B.V.

  15. Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia.

    Science.gov (United States)

    Voss, Sandra; Pietzner, Julia; Hoche, Franziska; Taylor, Alexander Malcolm R; Last, James I; Schubert, Ralf; Zielen, Stefan

    2014-06-01

    Ataxia telangiectasia (A-T) is a devastating human recessive disorder characterised by progressive cerebellar ataxia, immunodeficiency, genetic instability, and cancer susceptibility. In addition, many patients suffer from growth failure. We analyzed growth and IGF-1/BP3 levels of 24 A-T-patients compared with an age-matched group of healthy controls (n = 36). Ten (41.7%) A-T patients and none of healthy controls had an IGF-1 level below the 3rd percentile for age. The growth hormone (GH) stimulation tests revealed a severe GH deficiency with no increase of >5 ng/ml in six of the ten A-T patients. The IGF-1 generation tests revealed normal increases in IGF-1 values in all patients. Our results show that a disturbance in the GH/IGF-1 axis was present in 58.3% of A-T patients. Low levels of GH were the result of reduced central GH secretion. GH treatment may be a therapeutic option for A-T patients with severe growth failure.

  16. Treatment of acute leukemia in children with ataxia telangiectasia (A-T).

    Science.gov (United States)

    Schoenaker, M H D; Suarez, F; Szczepanski, T; Mahlaoui, N; Loeffen, J L

    2016-12-01

    Early onset ataxia telangiectasia (A-T) is a neurodegenerative DNA-instability disorder, which presents early in childhood. Hallmarks of A-T are progressive ataxia and a dramatic increased risk of developing malignancies (25%), especially of hematological origin. In children these malignancies mainly concern aggressive Non-Hodgkin lymphoma, acute leukemias and Hodgkin lymphoma. Of the acute leukemias, T-cell lymphoblastic leukemia (T-ALL) is by far the most common. Since patients with A-T experience increased toxicity to radio- and chemotherapeutic treatment, the optimal treatment strategy of acute leukemia remains subject of debate. Review of literature of treatment of T-ALL in patients with A-T (n = 18) showed that many patients are not diagnosed with A-T at time of presentation of T-ALL. This implicates that physicians must be aware of symptoms of A-T in young patients presenting with T-ALL. Complete remission rates are high following upfront modified as well as unmodified treatment strategies. Treatment of ALL in children with A-T is feasible and should be performed. Definitive treatment strategy must be determined by shared decision making with patient, caretakers and medical team. Future prospective studies are needed to elucidate optimal treatment strategy. Copyright © 2016. Published by Elsevier Masson SAS.

  17. EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia.

    Science.gov (United States)

    Li, Jiali; Hart, Ronald P; Mallimo, Elyse M; Swerdel, Mavis R; Kusnecov, Alexander W; Herrup, Karl

    2013-12-01

    The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. We previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; we now report that increased trimethylation of histone H3 on Lys27 (H3K27me3) mediated by polycomb repressive complex 2 (PRC2) is also important in the A-T phenotype. Enhancer of zeste homolog 2 (EZH2), a core catalytic component of PRC2, is a new ATM kinase target, and ATM-mediated phosphorylation of EZH2 on Ser734 reduces protein stability. Thus, PRC2 formation is elevated along with H3K27me3 in ATM deficiency. Chromatin immunoprecipitation and sequencing showed an increase in H3K27me3 'marks' and a dramatic shift in their location. The change of H3K27me3 chromatin-binding pattern is directly related to cell cycle reentry and cell death of ATM-deficient neurons. Lentiviral knockdown of EZH2 rescued Purkinje cell degeneration and behavioral abnormalities in Atm(-/-) mice, demonstrating that EZH2 hyperactivity is another key factor in A-T neurodegeneration.

  18. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  19. Identification of 4 ataxia telangiectasia cell lines hypersensitive to. gamma. -irradiation but not to hydrogen peroxide

    Energy Technology Data Exchange (ETDEWEB)

    Cantoni, O.; Sestili, P.; Santoro, M.P.; Tannoia, M.C.; Cattabeni, F. (Universita degli Studi di Urbino (Italy). Istituto di Farmacologia e Farmacognosia and Centro di Farmacologia Oncologia Sperimentale); Novelli, G.; Dallapiccola, B. (Universit degli Studi di Urbino (Italy). Cattedra di Genetica); Fiorilli, M. (Universita di Roma ' La Sapienze' (Italy). Cattedra di Allergologia e Immunologia Clinica)

    1989-09-01

    The effct of hydrogen peroxide on the rate of semi-conservative DNA synthesis in ataxia telangiectasia (AT) and normal human lymphoblastoid cells was investigated. The rate of DNA synthesis in AT cells was not depressed to a lesser extent than in normal cells, as might have been expected since H{sub 2O2} is a radiomimetic agent. On the contrary, 4 AT cell lines displayed a higher sensitivity to the inhibitory effect of H{sub 2O2} on DNA synthesis than 2 normal cell lines. Comparable levels of cytotoxicity were detected in cell vaibility studies. Furthermore, neither the level of DNA breakage produced by H{sub 2O2}, nor the rate of repair of these lesions was signigicantly different in normal and AT cells. Together, these results indicate that the AT cell lines utilized in this study are not hypersensitive to the oxidant. It is suggested that H-2-O-2 may not induce lethality via the direct ation of the hydroxyl radical (OH). (Author). 20 refs.; 3 figs.; 1 tab.

  20. Impaired recovery and mutagenic SOS-like responses in ataxia telangiectasia cells

    Energy Technology Data Exchange (ETDEWEB)

    Hilgers, G. (Universite Libre de Bruxelles (Belgium) Rijksuniversiteit Leiden (Netherlands)); Abrahams, P.J. (Rijksuniversiteit Leiden (Netherlands)); Chen, Y.Q. (Universite Libre de Bruxelles (Belgium)); Schouten, R. (Rijksuniversiteit Leiden (Netherlands)); Cornelis, J.J. (Universite Libre de Bruxelles (Belgium) Institut Pasteur, 75 - Paris (France)); Lowe, J.E. (Sussex Univ., Brighton (UK)); Eb, A.J. van der (Rijksuniversiteit Leiden (Netherlands)); Rommelaere, J. (Universite Libre de Bruxelles (Belgium) Institut Pasteur, 75 - Paris (France))

    1989-01-01

    Radiosensitive fibroblasts from patients with ataxia telangiectasia (AT) were studied for their proficiency in two putative eukaryotic SOS-like responses, namely the enhanced reactivation (ER) and enhanced mutagenesis of damaged viruses infecting pre-irradiated versus mock-treated cells. A previous report indicated that, unlike normal human cells, a line of AT fibroblasts (AT5BIVA) could not be induced to express ER of damaged parvovirus H-1, a single-stranded DNA virus, by UV- or X-irradiation. In the present study, AT5BIVA fibroblasts were also distinguished from normal cells by the inability of the former to achieve enhanced mutagenesis of damaged H-1 virus upon cell UV-irradiation. In contrast, dose-response and time-course experiments revealed normal levels of ER of Herpes simplex virus 1, a double-stranded DNA virus, in X- or UV-irradiated AT5BIVA cells. Taken together, these data point to a possible deficiency of AT cells in a conditioned mutagenic process that contributes to a greater extent to the recovery of damaged single-stranded than double-stranded DNA. Such a defect may concern the replication of damaged DNA or the generation of signals promoting the latter process and may be related to the lack of radiation-induced delay that is typical of AT cell DNA synthesis. (author).

  1. Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks.

    Science.gov (United States)

    Sordet, Olivier; Redon, Christophe E; Guirouilh-Barbat, Josée; Smith, Susan; Solier, Stéphanie; Douarre, Céline; Conti, Chiara; Nakamura, Asako J; Das, Benu B; Nicolas, Estelle; Kohn, Kurt W; Bonner, William M; Pommier, Yves

    2009-08-01

    Ataxia telangiectasia mutated (ATM), the deficiency of which causes a severe neurodegenerative disease, is a crucial mediator for the DNA damage response (DDR). As neurons have high rates of transcription that require topoisomerase I (TOP1), we investigated whether TOP1 cleavage complexes (TOP1cc)-which are potent transcription-blocking lesions-also produce transcription-dependent DNA double-strand breaks (DSBs) with ATM activation. We show the induction of DSBs and DDR activation in post-mitotic primary neurons and lymphocytes treated with camptothecin, with the induction of nuclear DDR foci containing activated ATM, gamma-H2AX (phosphorylated histone H2AX), activated CHK2 (checkpoint kinase 2), MDC1 (mediator of DNA damage checkpoint 1) and 53BP1 (p53 binding protein 1). The DSB-ATM-DDR pathway was suppressed by inhibiting transcription and gamma-H2AX signals were reduced by RNase H1 transfection, which removes transcription-mediated R-loops. Thus, we propose that Top1cc produce transcription arrests with R-loop formation and generate DSBs that activate ATM in post-mitotic cells.

  2. Control of cell respiration by nitric oxide in Ataxia Telangiectasia lymphoblastoid cells.

    Science.gov (United States)

    Masci, Alessandra; Mastronicola, Daniela; Arese, Marzia; Piane, Maria; De Amicis, Andrea; Blanck, Thomas J J; Chessa, Luciana; Sarti, Paolo

    2008-01-01

    Ataxia Telangiectasia (AT) patients are particularly sensitive to oxidative-nitrosative stress. Nitric oxide (NO) controls mitochondrial respiration via the reversible inhibition of complex IV. The mitochondrial response to NO of AT lymphoblastoid cells was investigated. Cells isolated from three patients and three intrafamilial healthy controls were selected showing within each group a normal diploid karyotype and homogeneous telomere length. Different complex IV NO-inhibition patterns were induced by varying the electron flux through the respiratory chain, using exogenous cell membrane permeable electron donors. Under conditions of high electron flux the mitochondrial NO inhibition of respiration was greater in AT than in control cells (P< or =0.05). This property appears peculiar to AT, and correlates well to the higher concentration of cytochrome c detected in the AT cells. This finding is discussed on the basis of the proposed mechanism of reaction of NO with complex IV. It is suggested that the peculiar response of AT mitochondria to NO stress may be relevant to the mitochondrial metabolism of AT patients.

  3. Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.

    Science.gov (United States)

    Lin, Zi-Li; Kim, Nam-Hyung

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes.

  4. Chromosome instability and oxidative stress markers in patients with ataxia telangiectasia and their parents.

    Science.gov (United States)

    Ludwig, Luciane Bitelo; Valiati, Victor Hugo; Palazzo, Roberta Passos; Jardim, Laura Bannach; da Rosa, Darlan Pase; Bona, Silvia; Rodrigues, Graziela; Marroni, Norma Possa; Prá, Daniel; Maluf, Sharbel Weidner

    2013-01-01

    Ataxia telangiectasia (AT) is a rare neurodegenerative disorder, inherited in an autosomal recessive manner. Total blood samples were collected from 20 patients with AT, 13 parents of patients, and 17 healthy volunteers. This study aimed at evaluating the frequency of chromosomal breaks in spontaneous cultures, induced by bleomycin and ionizing radiation, and further evaluated the rates of oxidative stress in AT patients and in their parents, compared to a control group. Three cell cultures were performed to each individual: the first culture did not receive induction to chromosomal instability, the second was exposed to bleomycin, and the last culture was exposed to ionizing radiation. To evaluate the rates of oxidative stress, the markers superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid (TBARS) were utilized. Significant differences were observed between the three kinds of culture treatments (spontaneous, bleomycin, and radiation induced) and the breaks and chromosomal aberrations in the different groups. The oxidative stress showed no significant differences between the markers. This study showed that techniques of chromosomal instability after the induction of ionizing radiation and bleomycin are efficient in the identification of syndrome patients, with the ionizing radiation being the most effective.

  5. The role of the neuro-astro-vascular unit in the etiology of Ataxia Telangiectasia

    Directory of Open Access Journals (Sweden)

    Leenoy eMeshulam

    2012-09-01

    Full Text Available The growing recognition that brain pathologies do not affect neurons only but rather are, to a large extent, pathologies of glial cells as well as of the vasculature opens to new perspectives in our understanding of genetic disorders of the CNS. To validate the role of the neuron-glial-vascular unit in the etiology of genome instability disorders, we report about cell death and morphological aspects of neuro-glia networks and the associated vasculature in a mouse model of Ataxia Telangiectasia (A-T, a human genetic disorder that induces severe motor impairment. We found that AT-mutated protein deficiency was consistent with aberrant astrocytic morphology and alterations of the vasculature, often accompanied by reactive gliosis. Interestingly similar findings could also be reported in the case of other genetic disorders. These observations bolster the notion that astrocyte-specific pathologies, hampered vascularization and astrocyte-endothelium interactions in the CNS could play a crucial role in the etiology of genome instability brain disorders and could underlie neurodegeneration.

  6. A single ataxia telangiectasia gene with a product similar to PI-3 kinase

    Energy Technology Data Exchange (ETDEWEB)

    Savitsky, K.; Bar-Shira, A.; Gilad, S.; Rotman, G.; Ziv, Y.; Vanagaite, L.; Smith, S.; Uziel, T.; Sfez, S.; Ashkenazi, M. [Tel Aviv Univ. (Israel)] [and others

    1995-06-23

    A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3{prime} kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer. 54 refs., 5 figs., 1 tab.

  7. Arteriovenous malformations in hereditary haemorrhagic telangiectasia: looking beyond ALK1-NOTCH interactions.

    Science.gov (United States)

    Peacock, Hanna M; Caolo, Vincenza; Jones, Elizabeth A V

    2016-02-01

    Hereditary haemorrhagic telangiectasia (HHT) is characterized by the development of arteriovenous malformations--enlarged shunts allowing arterial flow to bypass capillaries and enter directly into veins. HHT is caused by mutations in ALK1 or Endoglin; however, the majority of arteriovenous malformations are idiopathic and arise spontaneously. Idiopathic arteriovenous malformations differ from those due to loss of ALK1 in terms of both location and disease progression. Furthermore, while arteriovenous malformations in HHT and Alk1 knockout models have decreased NOTCH signalling, some idiopathic arteriovenous malformations have increased NOTCH signalling. The pathogenesis of these lesions also differs, with loss of ALK1 causing expansion of the shunt through proliferation, and NOTCH gain of function inducing initial shunt enlargement by cellular hypertrophy. Hence, we propose that idiopathic arteriovenous malformations are distinct from those of HHT. In this review, we explore the role of ALK1-NOTCH interactions in the development of arteriovenous malformations and examine a possible role of two signalling pathways downstream of ALK1, TMEM100 and IDs, in the development of arteriovenous malformations in HHT. A nuanced understanding of the precise molecular mechanisms underlying idiopathic and HHT-associated arteriovenous malformations will allow for development of targeted treatments for these lesions.

  8. Macular laser photocoagulation guided by spectral-domain optical coherence tomography versus fluorescein angiography for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Gallego-Pinazo R

    2011-05-01

    Full Text Available Roberto Gallego-Pinazo1,2, Ana Marina Suelves-Cogollos1, Rosa Dolz-Marco1, J Fernando Arevalo3, Salvador García-Delpech1, J Luis Mullor4, Manuel Díaz-Llopis1,2,51Department of Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain; 3Retina and Vitreous Service, Clinical Ophthalmology Center, Caracas, Venezuela; 4Unit of Experimental Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 5University of Valencia, Faculty of Medicine, Valencia, SpainBackground: The aim of this study was to compare the efficacy of spectral-domain optical coherence tomography (SD-OCT and fluorescein angiography (FA in the guidance of macular laser photocoagulation for diabetic macular edema.Methods: This was a prospective interventional clinical comparative pilot study. Forty eyes from 24 consecutive patients with diabetic macular edema were allocated to receive laser photocoagulation guided by SD-OCT or FA. Best-corrected visual acuity (BCVA, central macular thickness, and retinal volume were assessed at baseline and two months after treatment.Results: Subjects treated using FA-guided laser improved BCVA from the logarithm of the minimum angle of resolution (logMAR 0.52 ± 0.2 to 0.37 ± 0.2 (P < 0.001, and decreased mean central macular thickness from 397.25 ± 139.1 to 333.50 ± 105.7 µm (P < 0.001 and retinal volume from 12.61 ± 1.6 to 10.94 ± 1.4 mm3 (P < 0.001. Subjects treated using SD-OCT guided laser had improved BCVA from 0.48 ± 0.2 to 0.33 ± 0.2 logMAR (P < 0.001, and decreased mean central macular thickness from 425.90 ± 149.6 to 353.4 ± 140 µm (P < 0.001 and retinal volume from 12.38 ± 2.1 to 11.53 ± 1.1 mm3 (P < 0.001. No significant differences between the groups were found in two-month BCVA (P = 0.505, two-month central macular thickness (P = 0.660, or two-month retinal volume (P = 0.582.Conclusion: The short-term results of this pilot study

  9. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  10. Inverted Internal Limiting Membrane Flap For Large Traumatic Macular Holes.

    Science.gov (United States)

    Abou Shousha, Mohsen Ahmed

    2016-01-01

    The aim of the study was to assess the role of inverted internal limiting membrane flap as a treatment option for large traumatic macular holes.This is a prospective noncomparative study in which 12 eyes with large traumatic macular holes (basal diameter of 1300-2800 μm) since 3 to 6 months were subjected to standard 23-gauge vitrectomy with removal of the posterior hyaloid, brilliant blue G (BBG)-assisted internal limiting membrane peeling in a circular fashion keeping it attached to the edge of the hole to create a flap. At the end of the surgery, air fluid exchange was done with inversion of the internal limiting membrane flap inside the macular hole using the soft tipped cannula and sulfur hexafluoride 20% as tamponade. The main follow-up measures are the best corrected visual acuity and the optical coherence tomography for 6 to 9 months.All the included eyes had a closed hole from the first week postoperative and along the follow-up period (6-9 months). The best corrected visual acuity improved from 20/2000 to 20/200 with a median of 20/400 preoperatively to 20/400 to 20/50 with a median of 20/100 at the end of follow-up period.Inverted internal limiting membrane flap is a good adjuvant to standard vitrectomy in the management of large traumatic macular holes that led to the 100% closure rate and improvement of best corrected visual acuity.

  11. The Experience of Age-Related Macular Degeneration

    Science.gov (United States)

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  12. Non-invasive in vivo measurement of macular carotenoids

    Science.gov (United States)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2009-01-01

    A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.

  13. Assessing Errors Inherent in OCT-Derived Macular Thickness Maps

    Directory of Open Access Journals (Sweden)

    Daniel Odell

    2011-01-01

    Full Text Available SD-OCT has become an essential tool for evaluating macular pathology; however several aspects of data collection and analysis affect the accuracy of retinal thickness measurements. Here we evaluated sampling density, scan centering, and axial length compensation as factors affecting the accuracy of macular thickness maps. Forty-three patients with various retinal pathologies and 113 normal subjects were imaged using Cirrus HD-OCT. Reduced B-scan density was associated with increased interpolation error in ETDRS macular thickness plots. Correcting for individual differences in axial length revealed modest errors in retinal thickness maps, while more pronounced errors were observed when the ETDRS plot was not positioned at the center of the fovea (which can occur as a result of errant fixation. Cumulative error can exceed hundreds of microns, even under “ideal observer” conditions. This preventable error is particularly relevant when attempting to compare macular thickness maps to normative databases or measuring the area or volume of retinal features.

  14. Complement factor d in age-related macular degeneration

    NARCIS (Netherlands)

    Stanton, C.M.; Yates, J.R.W.; Hollander, A.I. den; Seddon, J.M.; Swaroop, A.; Stambolian, D.; Fauser, S.; Hoyng, C.B.; Yu, Y.; Atsuhiro, K.; Branham, K.; Othman, M.; Chen, W.; Kortvely, E.; Chalmers, K.; Hayward, C.; Moore, A.T.; Dhillon, B.; Ueffing, M.; Wright, A.F.

    2011-01-01

    Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by

  15. Resultado funcional e índice macular em portadores de buraco macular submetidos à cirurgia com remoção da membrana limitante interna Functional outcome and macular index in macular hole patients who underwent surgery with internal limiting membrane removal

    Directory of Open Access Journals (Sweden)

    José Ricardo Diniz

    2008-04-01

    Full Text Available OBJETIVOS: Avaliar o resultado funcional e o índice macular dos portadores de buraco macular submetidos à cirurgia com remoção da membrana limitante interna. MÉTODOS: Quinze olhos de 15 pacientes com buraco macular estágios 2, 3 e 4 foram incluídos no estudo. Todos foram submetidos à cirurgia de buraco macular convencional com remoção da membrana limitante interna corada pelo azul de tripan. Melhor acuidade visual com correção e cortes transversais medidos por tomografia de coerência óptica (OCT foram avaliados no pré- e pós-operatório. O índice macular (razão entre a altura e base do buraco macular foi calculado e correlacionado com o diâmetro mínimo do buraco macular e o ganho de acuidade visual pós-operatória. RESULTADOS: Obteve-se fechamento do buraco macular em todos pacientes operados. Em 86,7%, houve ganho de pelo menos três linhas de visão. O índice macular demonstrou correlação negativa significante com o diâmetro mínimo (r=0,811. Não foi observada correlação significante entre o índice macular e o ganho de acuidade visual pós-operatória (r=0,351. CONCLUSÃO: Os resultados funcionais na cirurgia do buraco macular com remoção da membrana limitante interna foram bons neste grupo de pacientes. O índice macular demonstrou ser compatível com a configuração espacial do buraco macular, porém não foi preditor de resultados visuais.PURPOSE: To evaluate the functional outcome and macular index in patients with macular hole who underwent surgery with internal limiting membrane removal. METHODS: Fifteen eyes of 15 patients with idiopathic macular hole stages 2, 3 or 4 were enrolled in this study. All patients underwent conventional macular hole surgery with trypan blue staining to remove the internal limiting membrane. The best-corrected visual acuity and cross-sectional images of macular hole measured by optical coherence tomography (OCT were evaluated pre- and postoperatively. The macular hole index

  16. Intraoperative Changes in Idiopathic Macular Holes by Spectral-Domain Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Atsushi Hayashi

    2011-05-01

    Full Text Available Purpose: To examine anatomical changes in idiopathic macular holes during surgery using handheld spectral-domain optical coherence tomography (SD-OCT. Methods: Five eyes of 5 patients who underwent surgery for the repair of idiopathic macular holes were examined. The surgery included standard 25-gauge, 3-port pars plana vitrectomy, removal of the internal limiting membrane (ILM, fluid-air exchange, and 20% sulfur hexafluoride tamponade. Intraoperative SD-OCT images of the macular holes were obtained after ILM removal and under fluid-air exchange using a handheld SD-OCT. From SD-OCT images, the macular hole base diameter (MHBD was measured and compared. Results: All macular holes were successfully closed after the primary surgery. The mean MHBD under fluid-air exchange was significantly smaller than the mean MHBD after ILM removal and the preoperative mean MHBD. In 1 eye with a stage 3 macular hole, SD-OCT images revealed that the inner edges of the macular hole touched each other under fluid-air exchange. Conclusion: Fluid-air exchange significantly reduced MHBD during surgery to repair macular holes. Fluid-air exchange may be an important step for macular hole closure as it reduces the base diameter of the macular hole.

  17. Optimal management of idiopathic macular holes

    Directory of Open Access Journals (Sweden)

    Madi HA

    2016-01-01

    Full Text Available Haifa A Madi,1,* Ibrahim Masri,1,* David H Steel1,2 1Sunderland Eye Infirmary, Sunderland, 2Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle, UK *These authors contributed equally to this work Abstract: This review evaluates the current surgical options for the management of idiopathic macular holes (IMHs, including vitrectomy, ocriplasmin (OCP, and expansile gas use, and discusses key background information to inform the choice of treatment. An evidence-based approach to selecting the best treatment option for the individual patient based on IMH characteristics and patient-specific factors is suggested. For holes without vitreomacular attachment (VMA, vitrectomy is the only option with three key surgical variables: whether to peel the inner limiting membrane (ILM, the type of tamponade agent to be used, and the requirement for postoperative face-down posturing. There is a general consensus that ILM peeling improves primary anatomical hole closure rate; however, in small holes (<250 µm, it is uncertain whether peeling is always required. It has been increasingly recognized that long-acting gas and face-down positioning are not always necessary in patients with small- and medium-sized holes, but large (>400 µm and chronic holes (>1-year history are usually treated with long-acting gas and posturing. Several studies on posturing and gas choice were carried out in combination with ILM peeling, which may also influence the gas and posturing requirement. Combined phacovitrectomy appears to offer more rapid visual recovery without affecting the long-term outcomes of vitrectomy for IMH. OCP is licensed for use in patients with small- or medium-sized holes and VMA. A greater success rate in using OCP has been reported in smaller holes, but further predictive factors for its success are needed to refine its use. It is important to counsel patients realistically regarding the rates of success with

  18. Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularisation and age-related macular degeneration

    Science.gov (United States)

    Takeuchi, K; Kachi, S; Iwata, E; Ishikawa, K; Terasaki, H

    2012-01-01

    Purpose To evaluate the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularisation (mCNV). Methods The medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes) were reviewed. Overall, 40 patients, 17 mCNV and 23 AMD, were followed for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit. Results In the 23 AMD eyes followed for ≥5 years, the mean preoperative BCVA was 1.149±0.105 logMAR units, which significantly improved to 0.69±0.06 logMAR units at 1 year (P142 logMAR units on their final examination. The area of the VF was significantly decreased at 12 months and did not change significantly thereafter. Conclusions Our results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years. PMID:22173070

  19. Lipids, lipid genes, and incident age-related macular degeneration: The three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    R. Klein (Ronald); C.E. Myers (Chelsea); G.H.S. Buitendijk (Gabrielle); E. Rochtchina (Elena); X. Gao (Xiaoyi); P.T.V.M. de Jong (Paulus); T.A. Sivakumaran (Theru); G. Burlutsky (George); R. McKean-Cowdin (Roberta); A. Hofman (Albert); S.K. Iyengar (Sudha); K.E. Lee (Kristine); B.H.Ch. Stricker (Bruno); J.R. Vingerling (Hans); P. Mitchell (Paul); B.E.K. Klein (Barbara); C.C.W. Klaver (Caroline); J.J. Wang (Jie Jin)

    2014-01-01

    textabstractPurpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES),

  20. Lipids, lipid genes, and incident age-related macular degeneration : the three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

    PURPOSE: To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). DESIGN: Meta-analysis. METHODS: setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue

  1. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    OpenAIRE

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

  2. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

    Science.gov (United States)

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-11-13

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

  3. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    Science.gov (United States)

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

  4. Triamcinolona subtenoniana en el edema macular diabético Subtenon triamcinolone in the diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Eddy Mesa Hernández

    2009-12-01

    Full Text Available INTRODUCCIÓN: La prevalencia de la retinopatía diabética está determinada por el tipo de diabetes mellitus y por el tiempo de evolución de la enfermedad. El edema macular es la principal causa de la disminución de la agudeza visual en el paciente diabético. Un diagnóstico precoz y certero de esta enfermedad, unido al establecimiento de un tratamiento adecuado es crucial en el esfuerzo por reducir la incapacidad visual. El propósito de este trabajo fue determinar la efectividad de la triamcinolona subtenoniana como tratamiento del edema macular en un grupo de pacientes diabéticos. MÉTODOS: Se realizó un estudio descriptivo-prospectivo de caso control. La muestra estuvo formada por 30 pacientes diabéticos que fueron atendidos en el Hospital Clínicoquirúrgico "Dr. Miguel Enríquez, desde enero a junio de 2007, con diagnóstico de edema macular diabético que cumplieron con los criterios de inclusión. RESULTADOS: Predominó el sexo femenino, el grupo de edades más frecuentes fue de 55 a 65 años. Se relacionó el tiempo de evolución con la presencia de edema macular, se evidenció una involución de esta patología, así como una mejoría en la agudeza visual después de aplicado el tratamiento y no se presentaron complicaciones graves. CONCLUSIONES: El tratamiento con acetato de triamcinolona por vía subtenoniana posterior es una alternativa efectiva en el tratamiento de el edema macular.INTRODUCTION: Prevalence of diabetic retinopathy is determined by type of diabetes mellitus and the length of development of the disease. Macular edema is the main cause of reduction in visual acuity of the diabetic patient. An early exact diagnosis of the disease together with an adequate treatment is essential to decrease visual disability. The objective of this paper was to evaluate the effectiveness of subtenon triamcinolone as therapy for macular edema in a group of diabetics. METHODS: A prospective descriptive case-control study was

  5. EVALUATION OF MACULAR ISCHEMIA IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION: An Optical Coherence Tomography Angiography Study.

    Science.gov (United States)

    Ghashut, Rima; Muraoka, Yuki; Ooto, Sotaro; Iida, Yuto; Miwa, Yuko; Suzuma, Kiyoshi; Murakami, Tomoaki; Kadomoto, Shin; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2017-06-30

    To quantitatively assess macular perfusion status using optical coherence tomography angiography in eyes with aflibercept-treated central retinal vein occlusion and resolved macular edema and to investigate the impact of macular morphology and perfusion status on visual function. This prospective consecutive case series included 23 patients with central retinal vein occlusion. All patients received intravitreal aflibercept injections before analysis. Visual acuity, macular sensitivity, and the macular nonperfusion area (NPA) were evaluated in eyes without macular edema. The macular NPA was evaluated by optical coherence tomography angiography using 3 mm × 3 mm images of the macula. Foveal ellipsoid zone disruption was also analyzed. The superficial macular NPA measured 4.15 mm ± 0.71 mm (95% confidence interval 3.85-4.46), and the deep macular NPA measured 4.23 mm ± 0.97 mm (95% confidence interval 3.82-4.56). The logarithm of the minimum angle of resolution visual acuity was significantly associated with foveal ellipsoid zone disruption (P = 0.001), the superficial macular NPA (P = 0.015), and the deep macular NPA (P = 0.018). Macular sensitivity correlated negatively with logarithm of the minimum angle of resolution visual acuity (P = 0.007), the superficial macular NPA (P = 0.029), and the deep macular NPA (P = 0.040), but not with the foveal ellipsoid zone disruption (P = 0.435). Optical coherence tomography angiography is a novel technique that enables segmented evaluation of the macular perfusion status in eyes with central retinal vein occlusion and provides visual prognostic information. Enlargement of the macular NPA in the superficial and deep layers was significantly correlated with impaired visual acuity and with decreased macular sensitivity in patients with aflibercept-treated central retinal vein occlusion and resolved macular edema.

  6. Change in macular thickness in a case of refractory diabetic macular edema with dexamethasone intravitreal implant in comparison to intravitreal bevacizumab: A case report

    Directory of Open Access Journals (Sweden)

    Ashish Sharma

    2012-01-01

    Full Text Available We report on the significant improvement of central macular thickness in a case of clinically significant macular edema after dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA, USA. Patient presented to us with persistent clinically significant macular edema (CSME in both eyes. Right eye received dexamethasone implant and left eye received two intravitreal bevacizumab injections 1.25 mg/0.05 mL (Avastin®; Genentech Inc., South San Francisco, CA, USA with an interval of four weeks. After six weeks of follow-up, dexamethasone implant in the right eye showed normal macular thickness whereas persistent macular edema (ME was found even after second intravitreal bevacizumab injection in the left eye.

  7. Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance.

    Science.gov (United States)

    Connelly, P J; Smith, N; Chadwick, R; Exley, A R; Shneerson, J M; Pearson, E R

    2016-03-01

    To investigate glucose and insulin metabolism in participants with ataxia telangiectasia in the absence of a diagnosis of diabetes. A standard oral glucose tolerance test was performed in participants with ataxia telangiectasia (n = 10) and in a control cohort (n = 10). Serial glucose and insulin measurements were taken to permit cohort comparisons of glucose-insulin homeostasis and indices of insulin secretion and sensitivity. During the oral glucose tolerance test, the 2-h glucose (6.75 vs 4.93 mmol/l; P = 0.029), insulin concentrations (285.6 vs 148.5 pmol/l; P = 0.043), incremental area under the curve for glucose (314 vs 161 mmol/l/min; P = 0.036) and incremental area under the curve for insulin (37,720 vs 18,080 pmol/l/min; P = 0.03) were higher in participants with ataxia telangiectasia than in the controls. There were no significant differences between groups in fasting glucose, insulin concentrations or insulinogenic index measurement (0.94 vs 0.95; P = 0.95). The Matsuda index, reflecting whole-body insulin sensitivity, was lower in participants with ataxia telangiectasia (5.96 vs 11.03; P = 0.019) than in control subjects. Mutations in Ataxia Telangiectasia Mutated (ATM) that cause ataxia telangiectasia are associated with elevated glycaemia and low insulin sensitivity in participants without diabetes. This indicates a role of ATM in glucose and insulin metabolic pathways. © 2016 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  8. Ataxia Telangiectasia-Mutated (ATMPolymorphisms and Risk of Lung Cancer in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Ajay A. Myneni

    2017-06-01

    Full Text Available BackgroundThe ataxia telangiectasia-mutated (ATM gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer.MethodsA population-based case–control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases. The two ATM gene SNPs, ATMrs227060 and ATMrs228589 as well as p53 gene SNP, p53rs1042522 were genotyped using Sequenom platform. Unconditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR and 95% confidence intervals (CIs. Adjusted models controlled for age, sex, and smoking status.ResultsThe study showed that TT genotype of ATMrs227060 (aOR = 1.58, 95% CI: 1.06–2.35 and AA genotype of ATMrs228589 were significantly associated with lung cancer (aOR = 1.50, 95% CI: 1.08–2.08 in a recessive model. Additionally, carrying variant genotypes of ATMrs227060 (TT, ATMrs228589 (AA, and p53rs1042522 (CC concomitantly was associated with much higher risk (aOR = 3.68, 95% CI: 1.43–9.45 of lung cancer than carrying variant genotypes of any one of the above three SNPs. We also found multiplicative and additive interaction between tea drinking and ATMrs227060 in association with lung cancer.ConclusionThis study indicates that ATM gene variants might be associated with development of lung cancer in Chinese population. These results need to be validated in larger and different population samples.

  9. Quantitative evaluation of brain involvement in ataxia telangiectasia by diffusion weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Firat, Ahmet Kemal [Inonu University Medical Faculty, Turgut Ozal Medical Center, Department of Radiology, Malatya 44280 (Turkey); Karakas, Hakki Muammer [Inonu University Medical Faculty, Turgut Ozal Medical Center, Department of Radiology, Malatya 44280 (Turkey)]. E-mail: hkarakas@inonu.edu.tr; Firat, Yezdan [Inonu University Medical Faculty, Turgut Ozal Medical Center, Department of Otorhinolaryngology, Malatya (Turkey); Yakinci, Cengiz [Inonu University Medical Faculty, Turgut Ozal Medical Center, Department of Pediatrics, Malatya (Turkey)

    2005-11-01

    Objective: To evaluate the value of diffusion weighted imaging (DWI) in diagnosing ataxia telangiectasia (AT) and to investigate the spatial distribution of cerebral microstructural changes caused by the disease. Methods: Six AT patients (9-13 years) and nine healthy control subjects were examined on 1.5 T scanner. In addition to conventional MR images, DWI were performed with a fat suppressed, multishot spin echo EPI sequence using B values of 0, 500 and 1000 s/mm{sup 2}. Mean ADC values were measured from 16 different supra and infratentorial location. The difference between controls and AT patients regarding ADC values, and the accuracy, sensitivity and specificity of them in discrimination were analyzed with t-tests, logistic regression analysis, ANOVA and ROC curves. Results: Conventional images of the controls were normal. In AT patients, the only conventional MR abnormality was cerebellar atrophy. The difference between both groups regarding mean ADC values was not significant for any of the cerebral structures. In contrary to cerebrum, cerebellar mean ADC values of patients and controls were statistically different (p < 0.011-0.0001). Patients and controls were classified with 100% accuracy using ADC values of cerebellar white matter and cortex together (p < 0.016). The cut-off ADC value (0.699 mm{sup 2}/s) for middle cerebellar cortex had produced highest (100%) sensitivity and specificity. There was a difference between superior, middle and inferior cerebellar cortex regarding ADC values (p < 0.026). Superior cerebellar cortex (0.987 {+-} 0.1956 mm{sup 2}/s) had higher ADC values than the middle and inferior cerebellar cortex. Conclusion: DWI provides a supplementary and objective imaging finding in AT. This finding is highly accurate in the radiological discrimination of healthy subjects and AT. Our findings also implicate that AT causes a diffuse atrophy and mostly affects superior part of the cortex.

  10. Safety and caregiver satisfaction with gastrostomy in patients with Ataxia Telangiectasia

    Science.gov (United States)

    2011-01-01

    Background Ataxia Telangiectasia (A-T) is a rare monogenetic neurodegenerative disease with pulmonary, nutritional, and dysphagic complications. Gastrostomy tube (GT) feedings are commonly recommended to manage these co-morbidities. In general, outcomes of GT placement in patients with progressive diseases that develop during childhood are not well characterized. The primary purposes of this study were to determine whether GT placement in patients with A-T would be tolerated and associated with caregiver satisfaction. Methods We completed a retrospective review of 175 patients who visited the A-T Children's Center at Johns Hopkins Hospital from 2001 through 2008, and identified 28 patients with A-T (19 males, 9 females) who underwent GT placement for non-palliative reasons. Information was obtained from medical records, interviews with primary health care providers, and 24 (83%) caregivers of patients with GT's who responded to survey requests. Results Twenty-five (89%) patients tolerated GT placement and were a median of 5.0 (0.4-12.6) years post GT placement at the time of this investigation. Three (11%) patients died within one month of GT placement. In comparison to patients who tolerated GT placement, patients with early mortality were older when GT's were placed (median 24.9 vs. 12.3 years, p = 0.006) and had developed a combination of dysphagia, nutritional, and respiratory problems. Caregivers of patients tolerating GT placement reported significant improvements in mealtime satisfaction and participation in daily activities. Conclusions GT placement can be well tolerated and associated with easier mealtimes in patients with A-T when feeding tubes are placed at young ages. Patients with childhood onset of disorders with predictable progression of the disease process and impaired swallowing may benefit from early versus late placement of feeding tubes. PMID:21569628

  11. Disturbed B and T cell homeostasis and neogenesis in patients with ataxia telangiectasia.

    Science.gov (United States)

    Kraus, Matan; Lev, Atar; Simon, Amos J; Levran, Inbal; Nissenkorn, Andrea; Levi, Yonit B; Berkun, Yackov; Efrati, Ori; Amariglio, Ninette; Rechavi, Gideon; Somech, Raz

    2014-07-01

    Ataxia telangiectasia (AT) is a rare genetic, multi-system disorder characterized by neurodegeneration, chromosome instability, B and T cell immunodeficiency and a predisposition to cancer. We examined immunologic parameters reflecting cell development and proliferation and their relevancy to the clinical phenotype in affected individuals. AT patients from the AT National Clinic in Israel underwent immunological investigation. Their T and B cell workup included lymphocyte subset counts, immunoglobulin levels, responses to mitogenic stimulations, TCR-Vβ families and BCR immunoglobulin heavy chain spectratyping, TCR rearrangement excision circles (TRECs) and Kappa-deleting recombination excision circles (KRECs). Thirty-seven AT patients (median age 12.7 years, range 4.2-25.1) were evaluated. CD20 B and CD3 T lymphocytes were decreased in 67 % and 64 % of the patients, respectively, while only 33 % of the patients had reduced lymphoproliferative responses. Almost all AT patients displayed extremely low TRECs and KRECs levels, irrespective of their age. Those levels were correlated to one another and to the amounts of CD3+ and CD20+ cells, respectively. Abnormal TCR-Vβ repertoires were found with different degrees of clonality or reduced expression in these AT patients. There was no clear clustering of expansions to specific TCR-Vβ genes. PCR spectratyping analysis of the FR2 IgH BCR gene rearrangements in peripheral blood was abnormal in 50 % of the patients. The immunodeficiency associated with AT is combined, remains low over time and not progressive. It is characterized by low TREC and KREC copies suggestive of abnormal T and B cell neogenesis.

  12. Nucleotide sequence analysis of a candidate gene for ataxia-telangiectasia group D (ATDC)

    Energy Technology Data Exchange (ETDEWEB)

    Leonhardt, E.A.; Kapp, L.N.; Young, B.R.; Murnane, J.P. (Univ. of California, San Francisco, CA (United States))

    1994-01-01

    A radioresistant cell clone (1B3) was previously isolated after transfection of an ataxia-telangiectasia (AT) group D cell line with a human cosmid library. A cosmid rescued from the integration site in 1B3 contained human DNA from chromosome position 11q23, the same region shown by both genetic linkage and chromosome transfer to contain the genes for AT complementation groups A/B, C, and D. A gene within the cosmid (ATDC) was found to produce mRNAs of different sizes. A cDNA for one of the most abundant mRNAs (3.0 kb) was isolated from a HeLa cell library. In the present study, the authors sequenced the 3.0-kb cDNA and the surrounding intron DNA in the cosmids. They used polymerase chain reaction, with primers in the introns, to confirm the number of exons and to analyze DNA from AT group D cells for mutations within this gene. Although no mutations were found, they do not rule out the possibility that mutations may be present within the regulatory sequences or coding sequences found in other mRNAs specific for this gene. From the sequence analysis, they found that the ATDC gene product is one of a group of proteins that share multiple zinc finger motifs and an adjacent leucine zipper motif. These proteins have been proposed to form homo- or hetero-dimers involved in nucleic acid binding, consistent with the fact that many of these proteins appear to be transcriptional regulatory factors involved in carcinogenesis and/or differentiation. The likelihood that the ATDC gene product is involved in transcriptional regulation could explain the pleiomorphic characteristics of AT, including abnormal cell cycle regulation. 36 refs., 5 figs., 2 tabs.

  13. Emerging roles of BMP9 and BMP10 in hereditary hemorrhagic telangiectasia

    Directory of Open Access Journals (Sweden)

    Emmanuelle eTillet

    2015-01-01

    Full Text Available Rendu-Osler-Weber syndrome, also known as hereditary hemorrhagic telangiectasia (HHT, is an autosomal dominant vascular disorder. Three genes are causally related to HHT: the ENG gene encoding endoglin, a co-receptor of the TGFß family (HHT1, the ACVRL1 gene encoding ALK1 (activin receptor-like kinase 1, a type I receptor of the TGFß family (HHT2, and the SMAD4 gene, encoding a transcription factor critical for this signaling pathway. Bone morphogenetic proteins (BMPs are growth factors of the TGFß family. Among them, BMP9 and BMP10 have been shown to bind directly with high affinity to ALK1 and endoglin, and BMP9 mutations have recently been linked to a vascular-anomaly syndrome that has phenotypic overlap with HHT. BMP9 and BMP10 are both circulating cytokines in blood, and the current working model is that BMP9 and BMP10 maintain a quiescent endothelial state that is dependent on the level of ALK1/endoglin activation on endothelial cells. In accordance with this model, to explain the etiology of HHT we hypothesize that a deficient BMP9/BMP10/ALK1/endoglin pathway may lead to re-activation of angiogenesis or a greater sensitivity to an angiogenic stimulus. Resulting endothelial hyperproliferation and hypermigration may lead to vasodilatation and formation of arteriovenous malformation (AVM. HHT would thus result from a defect in the angiogenic balance. This review will focus on the emerging role played by BMP9 and BMP10 in the development of this disease and the therapeutic approaches that this opens.

  14. Hepatic artery embolization for treatment of patients with hereditary hemorrhagic telangiectasia and symptomatic hepatic vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Chavan, Ajay [Hannover Medical School, Department of Diagnostic Radiology, Hannover (Germany); Klinikum Oldenburg, Department of Radiology and Nuclear Medicine, Oldenburg (Germany); Caselitz, Martin; Wagner, Siegfried; Manns, Michael [Hannover Medical School, Department of Gastroenterology and Hepatology, Hannover (Germany); Gratz, Karl-Friedrich [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Lotz, Joachim; Kirchhoff, Timm; Galanski, Michael [Hannover Medical School, Department of Diagnostic Radiology, Hannover (Germany); Piso, Plinio [Hannover Medical School, Department of Abdominal and Transplantation Surgery, Hannover (Germany)

    2004-11-01

    At present there is no established therapy for treating patients with hereditary hemorrhagic telangiectasia (HHT) and symptomatic hepatic involvement. We present the results of a prospective study with 15 consecutive patients who were treated with staged hepatic artery embolization (HAE). Branches of the hepatic artery were selectively catheterized and embolized in stages using polyvinyl alcohol particles (PVA) and platinum microcoils or steel macrocoils. Prophylactic antibiotics, analgesics and anti-emetics were administered after every embolization. Clinical symptomatology and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 28 months; range 10-136 months). Five patients had abdominal pain and four patients had symptoms of portal hypertension. The cardiac output was raised in all patients, with cardiac failure being present in 11 patients. After treatment, pain resolved in all five patients, and portal hypertension improved in two of the four patients. The mean cardiac output decreased significantly (P<0.001) from 12.57{+-}3.27 l/min pre-treatment to 8.36{+-}2.60 l/min at the end of follow-up. Symptoms arising from cardiac failure resolved or improved markedly in all but one patient. Cholangitis and/or cholecystitis occurred in three patients of whom two required a cholecystectomy. One patient with pre-existent hepatic cirrhosis died as a complication of the procedure. Staged HAE yields long-term relief of clinical symptoms in patients with HHT and hepatic involvement. Patients with pre-existing hepatic cirrhosis may be poor candidates for HAE. (orig.)

  15. Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia.

    Science.gov (United States)

    Shaikh, Aasef G; Marti, Sarah; Tarnutzer, Alexander A; Palla, Antonella; Crawford, Thomas O; Zee, David S; Straumann, Dominik

    2013-11-01

    Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per- and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.

  16. Heterogeneity of chromosomal breakage levels in epithelial tissue of ataxia-telangiectasia homozygotes and heterozygotes.

    Science.gov (United States)

    Rosin, M P; Ochs, H D; Gatti, R A; Boder, E

    1989-09-01

    The objective of this study was to obtain an estimate of the frequency distribution of spontaneous chromosomal breakage occurring in vivo in oral epithelia of 20 ataxia-telangiectasia patients (A-T homozygotes) and 26 parents (A-T obligate heterozygotes). Samples of exfoliated cells were obtained from each individual by swabbing the oral cavity and preparing air-dried slides. The percentage of exfoliated cells with micronuclei (MEC frequency) was used as an in vivo indicator for the amount of chromosomal breakage occurring in the tissue. As a population group, MEC frequencies of the A-T patients differed significantly from controls (mean for A-T patients, 1.51; for controls, 0.29; P less than 0.01). However, the values observed in individual patients ranged from MEC frequencies 10- to 12-fold above control values, to frequencies overlapping the upper values observed in the controls. Similarly, MEC frequencies observed among the A-T heterozygotes differed significantly from controls (mean for A-T heterozygotes, 1.02, mean for controls, 0.29; P less than 0.01). However, only 16 of the 26 individuals sampled had MEC frequencies greater than 0.5%, the 90th percentile for controls (compared with 16 of the 20 A-T patients examined). Of the A-T patients 11 had been previously assigned to complementation groups on the basis of sensitivity to x-irradiation. Seven of the patients belonged to group A and had MEC frequencies ranging from 0.3% to 1.9% with the remaining patients belonging to group C with MEC frequencies of 0.2% to 0.9%. The data presented in this paper suggest that although levels of spontaneous breakage in epithelial tissues of A-T patients and A-T obligate heterozygotes are often significantly elevated, this is not the case in all individuals.

  17. Contribution of Oxidative stress to Endothelial Dysfunction in Hereditary Hemorrhagic Telangiectasia

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    Mirjana eJerkic

    2015-02-01

    Full Text Available Oxidative stress causes endothelial dysfunction and is implicated in the pathogenesis of cardiovascular diseases. Our studies suggested that reactive oxygen species (ROS play a crucial role in Hereditary Hemorrhagic Telangiectasia (HHT disease, a vascular dysplasia affecting 1 in 5,000-8,000 people. Mutations in endoglin (ENG and activin receptor-like kinase (ACVRL1 genes are responsible for HHT1 and HHT2 and are associated with arteriovenous malformations. Endoglin and ACVRL1 interact with endothelial NO synthase (eNOS and regulate its activation. Mice heterozygous for these genes (Eng+/− and Acvrl1+/- show reduced endoglin or ACVRL1 protein levels in endothelial cells causing eNOS uncoupling, generation of reactive oxygen species (ROS rather than nitric oxide (NO•, leading to impaired NO• mediated vasodilation. ROS production is increased in several organs of Eng+/− and Acvrl1+/− mice, including lungs, liver, and colon, affected in HHT. The major source of increased oxidative stress in these tissues is eNOS-derived ROS and not mitochondrial or NADPH oxidase-dependent ROS. Eng+/− and Acvrl1+/− mice also develop with age signs of pulmonary arterial hypertension (PH attributable to eNOS-derived ROS, which was preventable by antioxidant treatment. To date, only one pilot study has been carried out in HHT patients, and it showed beneficial effects of antioxidant therapy on epistaxis. We suggest that more clinical studies are warranted to investigate whether antioxidants would prevent, delay or attenuate manifestations of disease in individuals with HHT, based on our experimental data in mouse models.

  18. Combination of Anti-VEGF and Laser Photocoagulation for Diabetic Macular Edema: A Review

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    Laura N. Distefano

    2017-01-01

    Full Text Available Diabetic macular edema (DME is the most common cause of vision loss in diabetic patients. Thirty years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS demonstrated that focal/grid laser photocoagulation reduces moderate vision loss from DME by 50% or more; thus, macular photocoagulation became the gold standard treatment for DME. However, with the development of anti-VEGF drugs (bevacizumab, ranibizumab, and aflibercept, better outcomes were obtained in terms of visual acuity gain and decrease in macular thickness in some studies when antiangiogenic drugs were administered in monotherapy. Macular laser therapy may still play an important role as an adjuvant treatment because it is able to improve macular thickness outcomes and reduce the number of injections needed. Here, we review some of the clinical trials that have assessed the efficacy of macular laser treatment, either as part of the treatment protocol or as rescue therapy.

  19. One day wonder: Fast resolution of macular edema following intravitreal ranibizumab in retinal venous occlusions

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    Lalit Verma

    2013-01-01

    Full Text Available Macular edema is a significant cause of vision loss in patients with central retinal vein occlusions and branch retinal vein occlusions. Vascular endothelial growth factor (VEGF appears to be a key factor in the pathogenesis of this disease. Anti-VEGF therapy, such as intravitreal ranibizumab provides an effective treatment against vision-threatening macular edema. We report three patients of retinal vein occlusion with macular edema who demonstrated overnight resolution of macular edema following treatment with intravitreal ranibizumab (0.5 mg. 3D optical coherence tomography (Optovue was used as a tool for comparison of the macular thickness before and after treatment. The significant reductions in the central foveal thickness demonstrated in these patients one night after intravitreal injections could have significant influence on modifying current treatment protocols. Early treatment of macular edema related to retinal venous occlusive disease with anti-VEGF injections could result in faster visual rehabilitation in these patients.

  20. Macular Hole Progression after Intravitreal Bevacizumab for Hemicentral Retinal Vein Occlusion

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    Manish Nagpal

    2011-01-01

    Full Text Available Macular edema secondary to retinal vein occlusion is commonly being treated with off-label intravitreal bevacizumab with good outcomes. A significant reduction in macular edema and improvement in visual acuity is seen following such a treatment with no serious adverse effects. In the reported case, a full-thickness macular hole was noticed one month after intravitreal bevacizumab for macular edema secondary to hemicentral retinal vein occlusion. On a detailed review of the pre- and postoptical coherence tomography scans, it was realized that there was a preexisting stage 2-3 macular hole which was masked by the hemorrhages and edema at the fovea and the macular hole had progressed following the injection.

  1. The relationship between nailfold capillaroscopic assessment and telangiectasia score with severity of peripheral vascular involvement in systemic sclerosis.

    Science.gov (United States)

    Yalcinkaya, Yasemin; Pehlivan, Ozlem; Omma, Ahmet; Alpay, Nilufer; Erer, Burak; Kamali, Sevil; Ocal, Lale; Inanc, Murat

    2015-01-01

    To determine the association of nailfold video-capillaroscopy (NVC) findings and telangiectasia score with digital ulcer (DU) history and severity of peripheral vascular involvement (PVI) in systemic sclerosis (SSc). Fifty-nine SSc patients fulfilling Leroy & Medsger criteria were evaluated including telangiectasia score, disease activity and severity scores. NVC was performed according to qualitative (early, active and late patterns) and semi-quantitative assessments. When DU+ and DU- groups were compared; the mean score of capillary number (CN) was 2.0±0.5 vs. 1.4±0.7 (p<0.001), irregularly enlarged capillaries (IEC) was 1.8±0.6 vs. 1.4±0.7 (p<0.05), microangiopathy evolution score (MES) was 2.5±1.5 vs. 1.8±1.0 (p<0.05) and 'early' pattern was significantly less frequent in DU+ patients (1 vs. 9, p=0.016). The frequency of severe-PVI (Medsger severity score of 2-4) was 22% in females (12/54) and 80% in males (4/5). When severe and non-severe groups were compared; the mean score of CN was 2.1±0.4 vs. 1.5±0.7 (p<0.001), MES was 2.8±1.6 vs. 1.8±1.1 (p<0.05) and 'early' pattern was significantly less frequent in patients with severe PVI (0 vs. 9, p=0.049). The mean values of telangiectasia score were similar between groups. DU history and severe PVI in SSc were associated with capillary loss and microangiopathy. 'Early' NVC pattern was very rare in patients with DU history and was not found in severe PVI. Severe PVI in males was more frequent than females. Telangiectasia scores were not found to be related to PVI. NVC may be a helpful method in the assessment of SSc patients for PVI prognosis, warranting prospective studies.

  2. Term neonate with intracranial hemorrhage and hereditary hemorrhagic telangiectasia: a case report and review of the literature.

    Science.gov (United States)

    Delaney, H M; Rooks, V J; Wolfe, S Q; Sawyer, T L

    2012-08-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs). The disease rarely presents in the neonatal period, primarily manifesting with epistaxis and gastrointestinal bleeding in adulthood. Occasionally, HHT can also present with symptoms related to AVMs in the cerebral, pulmonary or gastrointestinal vasculature. In prior reports, intracranial hemorrhage (ICH) secondary to cerebral AVM in neonates with HHT has been catastrophic and uniformly fatal. Here we report a case of a newborn with HHT and ICH from a suspected AVM who survived with aggressive medical management and surgical intervention, and provide a comprehensive review of the literature on ICH in neonates with HHT.

  3. Effect of intravenous iron supplementation on iron stores in non-anemic iron-deficient patients with hereditary hemorrhagic telangiectasia

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    Torbjörn Karlsson

    2016-03-01

    Full Text Available In hereditary hemorrhagic telangiectasia (HHT, frequent episodes of nasal and gastrointestinal bleeding commonly lead to irondeficiency with or without anemia. In the retrospective study presented here we assessed the iron stores, as determined by analysis of plasma ferritin, during oral and intravenous iron supplementation, respectively, in a population of iron-deficient non-anemic HHT patients who were inadequately iron-repleted by oral supplementation. A switch from oral to intravenous iron supplementation was associated with a significant increase in ferritin in this patient population.

  4. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    Science.gov (United States)

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  5. Macular morphology and response to ranibizumab treatment in patients with wet age-related macular degeneration

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    Dervenis N

    2016-06-01

    Full Text Available Nikolaos Dervenis, Saad Younis Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK Purpose: The purpose of this study was to assess whether specific characteristics of spectral domain optical coherence tomography (SD-OCT affect structural and functional outcomes and number of injections needed in ranibizumab (0.05 mL of 10 mg/mL Lucentis solution-treated wet age-related macular degeneration (AMD patients. Patients and methods: This retrospective case series included 62 newly diagnosed wet AMD patients treated with three monthly intravitreal ranibizumab injections followed by monthly follow-up and pro re nata retreatment. The presence of dome-shaped pigment epithelial detachment (PED, disruption of the retinal pigment epithelium (RPE, and subretinal and intraretinal fluid was associated with changes in Early Treatment of Diabetic Retinopathy Study visual acuity, central macular thickness (CMT, and number of injections needed during the 6-month follow-up. Results: The presence of PED was associated with lower values of CMT at presentation (399 µm [±132 µm] vs 310 µm [±51 µm], P=0.005. The presence of RPE disruption was associated with worse visual acuity in month 6 (0.36 [±0.22] vs 0.61 [0.45], P=0.027 and fewer injections (4.23 [±0.92] vs 3.55 [±0.60], P=0.007. The presence of intraretinal fluid at presentation was associated with worse visual acuity outcomes in month 4 (P=0.045 but not in month 6. Conclusion: The dome-shaped PED was associated with lower CMT at presentation, but it did not affect response to treatment. RPE disruption was associated with worse functional outcomes with fewer injections. Intraretinal fluid at presentation may suggest delayed response to treatment. Individualized SD-OCT analysis could lead to individualized approach to wet AMD patients. SD-OCT can offer imaging biomarkers to assess the prognosis of anti-VEGF treatment in AMD patients. Keywords: AMD, spectral domain optical

  6. Consistency of ocular coherence tomography fast macular thickness mapping in diabetic diffuse macular edema Consistência da tomografia de coerência óptica no edema macular difuso diabético

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    Fábio Petersen Saraiva

    2007-01-01

    Full Text Available OBJECTIVES: To investigate optical coherence tomography consistency on foveal thickness, foveal volume, and macular volume measurements in patients with and without diffuse diabetic macular edema. INTRODUCTION: Optical coherence tomography represents an objective technique that provides cross-sectional tomographs of retinal structure in vivo. However, it is expected that poor fixation ability, as seen in diabetic macular edema, could alter its results. Several authors have discussed the reproducibility of optical coherence tomography, but only a few have addressed the topic with respect to diabetic maculopathy. METHODS: The study recruited diabetic patients without clinically evident retinopathy (control group and with diffuse macular edema (case group. Only one eye of each patient was evaluated. Five consecutive fast macular scans were taken using Ocular Coherence Tomography 3; the 6 mm macular map was chosen. The consistency in measurements of foveal thickness, foveal volume, and total macular volume for both groups was evaluated using the Pearson's coefficient of variation. The T-test for independent samples was used in order to compare measurements of both groups. RESULTS: Each group consisted of 20 patients. All measurements had a coefficient of variation less than 10%. The most consistent parameter for both groups was the total macular volume. DISCUSSION: Consistency in measurement is a mainstay of any test. A test is unreliable if its measurements can not be correctly repeated. We found a good index of consistency, even considering patients with an unstable gaze. CONCLUSIONS: Optical coherence tomography is a consistent method for diabetic subjects with diffuse macular edema.OBJETIVOS: Investigar a consistência das medidas de espessura foveal, volume foveal e volume macular total feitas pela tomografia de coerência óptica em pacientes com e sem edema macular difuso diabético. INTRODUÇÃO: A tomografia de coerência óptica é uma t

  7. Idiopathic horseshoe-like macular tear: a case report

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    Kubota M

    2016-07-01

    Full Text Available Masaomi Kubota,1 Tomohiro Shibata,1 Hisato Gunji,1 Hiroshi Tsuneoka2 1Department of Ophthalmology, The Jikei University School of Medicine Kashiwa Hospital, Chiba, 2Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan Background: Although a few cases with idiopathic horseshoe-like macular tear have been reported, the mechanism remains unknown and a standard treatment has yet to be determined. Objective: To report the outcome for a patient with idiopathic horseshoe-like macular tear who underwent vitreous surgery. Case report: A 65-year-old man with no previous injury or ophthalmic disease presented with abnormal vision in his left eye. Best-corrected visual acuity was 0.8 in the right and 0.3 in the left, and the relative afferent pupillary defect was negative. Ophthalmoscopy revealed a horseshoe-like tear on the temporal side of the macula in the left eye. The tear size was 0.75 disc diameters (DD. Optical coherence tomography showed that the focal retinal detachment reached the fovea. A few days after the first visit, there was no longer adhesion of the flap of the tear to the retina and the tear size had increased to 1.5 DD. The patient underwent vitreous surgery similar to large macular hole surgery, with the tear closure repaired using the inverted internal limiting membrane flap technique with 20% SF6 gas tamponade. Although the tear decreased to 0.5 DD after the surgery, complete closure of the tear was not achieved. Conclusion: While cases with horseshoe-like macular tear following trauma and branch retinal vein occlusion have been reported, to the best of our knowledge, this is the first reported idiopathic case. In the present case, there was expansion of the tear until the patient actually underwent surgery. If vertical vitreous traction indeed plays a role in horseshoe-like macular tears, this will need to be taken into consideration at the time of the vitreous surgery in these types of cases. Keywords

  8. Bilateral macular holes in X-linked retinoschisis: Now the spectrum is wider

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    Manoj Gautam

    2011-01-01

    Full Text Available Bilateral occurrence of macular hole in X-linked retinoschisis is an extremely rare event. Spectral domain optical coherence tomography (OCT findings revealed that formation of a macular hole is secondary to the retinoschisis process alone. Bilateral macular holes should be added to the spectrum of X-linked retinoschisis variations and the retinoschisis process alone should be accounted for their formation.

  9. Severe Macular Edema in Patients with Juvenile Idiopathic Arthritis-Related Uveitis

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    Maria Pia Paroli

    2013-01-01

    unilateral macular edema. OCT revealed massive macular thickening (range from 550 μm to 1214 μm. Conclusions. Macular edema appeared in female adolescent patients in eyes with long-dating CAU submitted to cataract surgery. In such patients, in presence of age-related microvascular changes due to the enhancer effect of sex hormones, cataract extraction should be a factor triggering the retinal complication.

  10. Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration

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    Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi-Chao

    2012-01-01

    Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch’s membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflam...

  11. Degeneração macular relacionada à idade: novas perspectivas Age-related macular degeneration: new perspectives

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    Marcio Bittar Nehemy

    2006-12-01

    Full Text Available A degeneração macular relacionada à idade (DMRI é a principal causa de cegueira legal em indivíduos acima de 50 anos de idade. Embora estudos recentes tenham mostrado que o fator genético é significativo, a patogênese da degeneração macular relacionada à idade permanece obscura, e os fatores de risco não estão ainda completamente estabelecidos. Estudos multicêntricos randomizados, publicados nos últimos anos, demonstraram que uma combinação de vitaminas e minerais é eficaz na redução do risco de desenvolvimento de neovascularização e de progressão para os estágios mais avançados da degeneração macular relacionada à idade. De maneira análoga, a terapia fotodinâmica (PDT e a terapia antiangiogênica também tiveram sua eficácia comprovada no tratamento de membrana neovascular coroideana subfoveal associada à degeneração macular relacionada à idade. Ambas reduzem o risco de perda de visão e, eventualmente, permitem melhora temporária da acuidade visual. Outras modalidades de tratamento, tais como fotocoagulação a laser, remoção cirúrgica da membrana e termoterapia transpupilar (TTT, podem beneficiar apenas um pequeno subgrupo de pacientes. Uma melhor compreensão dos mecanismos fisiopatológicos e dos eventos moleculares nas diversas fases da doença deverão propiciar, em futuro próximo, melhores estratégias para o controle e tratamento da degeneração macular relacionada à idade.Age-related macular degeneration (ARMD is a major source of legal blindness in individuals older than 50 years. Even though recent reports suggest that genetics plays an important role, its pathogenesis remains puzzling and the risk factors for its occurrence are not completely established. Vitamin and mineral supplementation reduced the risk of development of choroidal neovascularization (CNV or progression to the most advanced stages of age-related macular degeneration. Photodynamic therapy (PDT and antiangiogenic therapy

  12. Trombose venosa profunda como complicação da escleroterapia química no tratamento de telangiectasias dos membros inferiores Deep venous thrombosis as complication of chemical sclerotherapy in the treatment of leg telangiectasias

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    Adilson Ferraz Paschôa

    2005-01-01

    Full Text Available Os autores relatam dois casos de escleroterapia de telangiectasias, as quais complicaram com trombose venosa profunda. O primeiro caso foi confirmado por flebografia, e o segundo, por duplex scan. Um paciente, 8 anos após, apresentou uma tromboflebite espontânea de veia safena parva, que resultou em pesquisa de trombofilia positiva para o Fator V Leiden. A outra paciente teve pesquisa de trombofilia negativa. Os relatos de tromboembolismo relacionado à escleroterapia são escassos na literatura. O objetivo do trabalho é alertar para essa possibilidade, valorizando as queixas de dor e edema após a escleroterapia. Havendo suspeita clínica, o duplex scan deve ser realizado.The authors report two cases of sclerotherapy for telangiectasias, which complicated with deep venous thrombosis. The first case was confirmed by phlebography and the second one by duplex scan. One patient, 8 years later, had a spontaneous lesser saphenous vein thrombophlebitis, which resulted in positive thrombophilia investigation for factor V Leiden. The other patient had negative investigation for thrombophilia. There are very few reports on thromboembolism after sclerotherapy in the literature. This study aims to warn against this possibility, valuing the complaints of pain and swollen leg after the sclerotherapy. In case of clinical suspicion, a duplex scan should be performed.

  13. Telangiectasia hemorrágica hereditária: ácido tranexâmico no tratamento de úlcera plantar Hereditary hemorrhagic telangiectasia: tranexamic acid for plantar ulcer

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    Gabriella Corrêa de Albuquerque

    2005-12-01

    Full Text Available Relato de um caso de úlcera plantar por fístula arteriovenosa em paciente portador de telangiectasia hemorrágica hereditária ou doença de Rendu-Osler-Weber tratado com ácido tranexâmico. Este fármaco é utilizado para tratamento de epistaxe, referindo-se o principal achado deste artigo ao uso eficaz desse medicamento na terapia de úlceras plantares hemorrágicas. São descritos os aspectos fisiopatológicos e clínicos da doença e as propriedades antifibrinolíticas do ácido tranexâmico. Este foi bem tolerado e apresentou evidências de eficácia na utilização para controle do sangramento e cicatrização da úlcera.Case report of one patient with Hereditary Hemorrhagic Telangiectasia, also known as Rendu-Osler-Weber syndrome, treated with Tranexamic Acid for arteriovenous plantar ulcer. This drug has proved effective in controlling epistaxis, but the main point of this report is to expose the success use of this medication in the therapy of skin bleeding ulcer. The pathophysiologic and clinical features of the disease are reviewed and also the pharmacological aspects of the antifibrinolytic drugs. This drug was well tolerated by the patient and show evidence of good activity in the bleeding and healed the ulcer.

  14. [Cystoid macular oedema after fingolimod treatment in multiple sclerosis].

    Science.gov (United States)

    Asensio-Sánchez, V M; Trujillo-Guzmán, L; Ramoa-Osorio, R

    2014-03-01

    A woman, treated with immunomodulatory and immunosuppressive drugs for multiple sclerosis, developed macular oedema 4 months after oral fingolimod administration. The patient was previously seen by an ophthalmologist, with a normal anterior segment and funduscopic examination. Four months after the treatment she referred to decreased visual acuity in both eyes. The funduscopic and OCT examination now revealed cystoid macular oedema (CME). Attention to visual changes and periodic funduscopic examinations are an important part of monitoring while using fingolimod. In our patient early recognition and discontinuation of fingolimod did not result in resolution of the CME. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  15. Wearable diagnostic system for age-related macular degeneration.

    Science.gov (United States)

    Mohaghegh, N; Zadeh, E Ghafar; Magierowski, S

    2016-08-01

    This paper presents a novel head-mounted point-of-care diagnostic system for detection and continuous monitoring of Age-related Macular Degeneration (AMD). This wearable embedded open-source platform enables accurate monitoring of AMD by taking advantage of multiple standard graphical interface techniques such as Amsler Grid, Threshold Amsler Grid, Macular Computerized Psychophysical Test and Preferential Hyperacuity Perimeter (PHP). Here, we describe the proposed multi-Grid or so-called NGRID software and elaborate on the hardware prototype. This prototype includes a commercially available Oculus HMD incorporated with a single board computer. As the first step towards a fully integrated wearable system, this paper successfully proves the functionality of head-mounted graphical interface device ready for a live demonstration. Participants can experience this device and take a 10-minute AMD eye-exam. Furthermore, NGRID has been approved and permitted for an in-hospital clinical trial.

  16. Compact single-channel Raman detector for macular pigments

    Science.gov (United States)

    Ermakov, Igor V.; Ermakova, Maia R.; Gellermann, Werner

    2004-07-01

    Raman detection of macular pigments (MP) holds promise as a novel noninvasive technology for the quantification of lutein and zeaxanthin carotenoids, which are thought to prevent or delay the onset of age-related macular degeneration. Using resonant excitation in the visible, we measure the Raman signals that originate from the double-bond stretch vibrations of the p-conjugated carotenoid molecule's carbon backbone. In this paper we describe the construction and performance of a new, compact, and low-cost MP Raman instrument using dielectric, angle-tuned band-pass filters for wavelength selection and single-channel photo-multiplier detection of carotenoid Raman responses. MP concentration measurements are fast and accurate, as seen in experiments with model eyes and living human eyes. The ease and rapidity of Raman MP measurements, the relative simplicity of the instrumentation, the high accuracy of the measurements, and the lack of significant systematic errors should make this technology useful for widespread clinical research.

  17. Fingolimod Associated Bilateral Cystoid Macular Edema—Wait and See?

    Directory of Open Access Journals (Sweden)

    Refik Pul

    2016-12-01

    Full Text Available Fingolimod 0.5-mg once-daily is an approved therapy for patients with relapsing–remitting multiple sclerosis (MS. Several pivotal and real-world studies have demonstrated that fingolimod is associated with the development of macular edema (ME. Herein, we present a case of a diabetic MS patient who developed severe bilateral ME during fingolimod treatment. By means of this case study we provide a detailed review about fingolimod associated macular edema (FAME, its current incidence with or without diabetes mellitus, and previous therapy attempts and outcomes in MS patients. Intravitreal administration of antibodies raised against vascular endothelial growth factor A (VEGF-A has not yet been used in the management of FAME, however, the excellent therapeutic response in our patient may justify the use of anti-VEGF-A agents in combination with cessation of fingolimod to achieve fast resolution of FAME and to prevent visual deficits, particularly in bilateral FAME.

  18. Grid pattern Argon Laser photocoagulation for diabetic diffuse macular edema

    Directory of Open Access Journals (Sweden)

    Karkhane R

    1998-05-01

    Full Text Available Purpose: to determine the effect of Grid pattern laser photocoagulation on diabetic diffuse macular edema with assessment of visual outcome. Patients & Methods: The author reviewed the medical records of 84 eyes of 62 patients with diabetic diffuse macular edema treated with Grid pattern green Argon laser photocoagulation in Farabi Eye Hospital between the years 1992-1995, the follow-up period was 16-48 months (average 24.55±6.42, median 28 mounths. Results: Visual acuity was improved in 11.9%; unchanged in 65.4% and worsened in 22.7% of eyes. Conclusion: In assessing long-term visual outcome, Grid laser photocoagulation is an effective modality in maintaining or improving visual acuity.

  19. Vitrectomy for bilateral macular schisis without apparent optic disc anomalies

    Science.gov (United States)

    Andonegui, José; Maya, José Ramón; Echeverría, Marta; Alcaine, Araceli

    2016-01-01

    A 78-year-old man complained of bilateral visual acuity loss. Optical coherence tomography examination showed bilateral macular schisis with fluid accumulation in the external retinal layers without vitreous traction. Fundus examination and fluorescein angiography were normal in both eyes. Both eyes were treated by phacoemulsification, intraocular lens implantation, and vitrectomy without laser, gas exchange, or retinal fenestration. Slow and progressive fluid resorption and improvement in VA were observed in both eyes. Macular schisis similar to the one associated with optic disc anomalies is a possibility in patients without apparent disc anomalies. Vitrectomy without laser, gas, or retinal fenestration may be a good therapeutic option even in patients with a PVD preoperatively. PMID:27703873

  20. Localized bi-nasal macular edema in optic chiasmal syndrome

    Directory of Open Access Journals (Sweden)

    Alejandro J Lavaque

    2013-01-01

    Full Text Available A 28-year-old healthy male complaining of vision loss in his right eye was discovered to have localized bi-nasal macular edema in the presence of a pituitary adenoma. The presence of a junctional scotoma composed by a central scotoma in the right eye associated with superior temporal quadrantanopia in the fellow eye was seen. The pattern detected in the visual field suggested the presence of an expansive mass at the level of the optic chiasm. Optical coherence tomography findings also revealed subtle macular thickness beyond normal in the superior and nasal quadrants of both maculae. This report illustrates the importance of suspecting a pituitary adenoma in the light of uncharacteristic retinal alterations.

  1. Clinical and histopathological study of primary cutaneous macular amyloidosis

    Directory of Open Access Journals (Sweden)

    Fatima Razvi

    2013-02-01

    Full Text Available Primary cutaneous amyloidosis often presents with pigmentary dystonias of the skin in the form of asymptomatic reticulate hyper-pigmentation or pruritic lichenoid papular lesions. The aim of this study was to evaluate the incidence of primary cutaneous macular amyloidosis and also to find out the possible etiological agents, to correlate their clinical disease with histopathological positivity for amyloid deposition, and to find out the percentage of positive cas-es by special stains. A total of 24 patients attending dermatology out-patient clinic of Princess Esra Hospital, Hyderabad over a pe-riod of 1 year presenting with hyperpigmented skin lesions and clinically diagnosed as macular amyloidosis were taken up for this study.

  2. [Surgical treatment of macular pucker--preliminary report].

    Science.gov (United States)

    Nawrocki, J; Pikulski, Z; Dziegielewski, K

    1993-01-01

    The authors presented preliminary results of pars plana vitrectomy applied in 8 eyes with macular pucker. The aim of the surgery was to remove epiretinal membranes and it was achieved in 7 eyes; in one some fragments of the membrane remained. Visual acuity before surgery ranged from 1/50 to 3/50, after the treatment it was improved in 7 cases, in one being the same as before.

  3. Smoking and Age-Related Macular Degeneration: Review and Update

    Science.gov (United States)

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  4. The role of epigenetics in age-related macular degeneration

    OpenAIRE

    Gemenetzi, M; Lotery, A.J.

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research fo...

  5. Bilateral macular injury caused by a femtosecond laser.

    Science.gov (United States)

    de Juan-Marcos, L; Cañete-Campos, C; Cruz-González, F; López-Corral, A; Hernández-Galilea, E

    2014-11-01

    We describe the case of a 35-year-old man who arrived in the Emergency Department with bilateral macular injury caused by accidental exposure to an industrial femtosecond laser. Workers operating industrial lasers must protect their eyes properly when handling these devices. Otherwise, retina damage may occur which usually is recoverable. However, sometimes this damage causes permanent visual loss. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Binocular Refraction in Patients with Age-Related Macular Degeneration

    OpenAIRE

    Skrbek, Matěj

    2013-01-01

    We’ve been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used ...

  7. Vitreomacular traction and age-related macular degeneration.

    Science.gov (United States)

    Green-Simms, Amy E; Bakri, Sophie J

    2011-05-01

    The interaction between the vitreous and the internal limiting membrane of the retina is important in the pathoetiology of numerous ocular disease processes. Recent studies have focused on the vitreo-retinal interface in the context of age-related macular degeneration (AMD), linking vitreo-retinal adhesion to exudative AMD in particular. This review summarizes our knowledge of vitreous anatomy and recent investigations regarding vitreomacular adhesion and AMD.

  8. Pinpointing the Earliest Defects in Age-Related Macular Degeneration

    OpenAIRE

    Magnusson, Kristinn P; Shan Duan; Haraldur Sigurdsson; Hjorvar Petursson; Zhenglin Yang; Yu Zhao; Bernstein, Paul S.; Jian Ge; Fridbert Jonasson; Einar Stefansson; Gudleif Helgadottir; Norman A Zabriskie; Thorlakur Jonsson; Asgeir Björnsson; Theodora Thorlacius

    2005-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in t...

  9. Stereotactic radiotherapy in neovascular age-related macular degeneration

    OpenAIRE

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address ...

  10. The Burden of Age-Related Macular Degeneration

    OpenAIRE

    Jordana K. Schmier; Mechelle L. Jones; Halpern, Michael T.

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, bo...

  11. Updates in the Management of Diabetic Macular Edema

    OpenAIRE

    Christopher Mathew; Anastasia Yunirakasiwi; Srinivasan Sanjay

    2015-01-01

    Diabetes mellitus is a chronic disease which has multiple effects on different end-organs, including the retina. In this paper, we discuss updates on diabetic macular edema (DME) and the management options. The underlying pathology of DME is the leakage of exudates from retinal microaneurysms, which trigger subsequent inflammatory reactions. Both clinical and imaging techniques are useful in diagnosing, classifying, and gauging the severity of DME. We performed a comprehensive literature sear...

  12. An Immunologic Study on Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    Forty-one patients with age-related macular degeneration(AMD) were detected for serum autoantibodies against normal humanretinal protein by means of Western immunoblot analysis.Twenty-sevenout of the 41 patients showed positive response,with a rate of 66 percent.The positive rate of antiretinal antibody in the AMD patients wassignificantly higher than that in normal controls (18%) and in patients withother retinal diseases (24%) (p<0.0005).These antiretinal antibodies fromthe AMD patients partly reacted...

  13. Geriatric vision loss due to cataracts, macular degeneration, and glaucoma.

    Science.gov (United States)

    Eichenbaum, Joseph W

    2012-01-01

    The major causes of impaired vision in the elderly population of the United States are cataracts, macular degeneration, and open-angle glaucoma. Cataracts and macular degeneration usually reduce central vision, especially reading and near activities, whereas chronic glaucoma characteristically attacks peripheral vision in a silent way, impacting balance, walking, and driving. Untreated, these visual problems lead to issues with regard to taking medications, keeping track of finances and personal information, walking, watching television, and attending the theater, and often create social isolation. Thus, visually impaired individuals enter nursing homes 3 years earlier, have twice the risk of falling, and have 4× the risk of hip fracture. Consequently, many elderly with low vision exercise greater demands on community services. With the prospect of little improvement and sustained visual loss, in the face of poor tolerance of low-vision services and not accepting magnification as the only way to read, clinical depression is common. In many instances, however, early and accurate diagnosis can result in timely treatment and can preserve quality of life. This review will look at current diagnostic and therapeutic considerations. Currently, about 20.5 million people in the United States have cataracts. The number will reach 30 million by 2020. About 1.75 million Americans currently have some form of macular degeneration, and the number is estimated to increase to 2.95 million in 2020. Approximately 2.2 million Americans have glaucoma, and by 2020 that number is estimated to be close to 3.4 million people. It is projected that by 2030 there will be 72.1 million seniors. With some overlap of the above 3 groups conservatively estimated (if you add the 2030 cataract group to the macular degeneration and glaucoma groups), then about 1 in 2 senior individuals by 2030 may have some significant ocular disease, which could account for about 50% of the healthcare budget for the

  14. Present and Possible Therapies for Age-Related Macular Degeneration

    OpenAIRE

    Muhammad Khan; Ketan Agarwal; Mohamed Loutfi; Ahmed Kamal

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment ...

  15. Smoking and Age-Related Macular Degeneration: Review and Update

    Directory of Open Access Journals (Sweden)

    Sara Velilla

    2013-01-01

    Full Text Available Age-related macular degeneration (AMD is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

  16. Early detection of age related macular degeneration: current status

    OpenAIRE

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient’s home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  17. Early detection of age related macular degeneration: current status.

    Science.gov (United States)

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  18. The relationship between nutritional status, vitamin A and zinc levels and oxidative stress in patients with ataxia-telangiectasia.

    Science.gov (United States)

    da Silva, R; dos Santos-Valente, E C; Burim Scomparini, F; Saccardo Sarni, R O; Costa-Carvalho, B T

    2014-01-01

    Ataxia-telangiectasia (A-T) is a rare and degenerative disease that leads to varying degrees of immunodeficiency, oxidative stress, and malnutrition. Vitamin A and zinc are essential for immune function and antioxidant defence. To compare levels of retinol, beta carotene, and zinc in patients with ataxia-telangiectasia and healthy controls. We performed a cross-sectional study with 14 AT patients and 14 healthy controls matched for age and gender. All participants underwent a nutritional and laboratory evaluation comprising concentrations of retinol, beta carotene, serum and erythrocyte zinc, malondialdehyde (MDA), T lymphocyte numbers (CD4(+) and CD8(+)) and immunoglobulin (IgA). The AT patients showed high rates of malnutrition with reduced lean body mass when compared to the control group. However, the concentrations of MDA, retinol, beta carotene, and serum and erythrocyte zinc in AT patients were similar to those of the control group. The retinol levels presented a negative correlation with MDA and positive correlation with IgA serum level. The AT patients assessed showed no change in nutritional status for vitamin A and zinc; however, they presented severe impairment in overall nutritional status observed and correlation between retinol with MDA and IgA. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

  19. Targeted Next-Generation Sequencing Revealed Novel Mutations in Chinese Ataxia Telangiectasia Patients: A Precision Medicine Perspective.

    Science.gov (United States)

    Chen, Zhao; Ye, Wei; Long, Zhe; Ding, Dongxue; Peng, Huirong; Hou, Xuan; Qiu, Rong; Xia, Kun; Tang, Beisha; Jiang, Hong

    2015-01-01

    Ataxia telangiectasia (AT) is an autosomal recessive disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia and immunodeficiency due to mutations in the ATM gene. We performed targeted next-generation sequencing (NGS) on three unrelated patients and identified five disease-causing variants in three probands, including two pairs of heterozygous variants (FAT-1:c.4396C>T/p.R1466X, c.1608-2A>G; FAT-2:c.4412_4413insT/p.L1472Ffs*19, c.8824C>T/p.Q2942X) and one pair of homozygous variants (FAT-3: c.8110T>G/p.C2704G, Hom). With regard to precision medicine for rare genetic diseases, targeted NGS currently enables the rapid and cost-effective identification of causative mutations and is an updated molecular diagnostic tool that merits further optimization. This high-throughput data-based strategy would propel the development of precision diagnostic methods and establish a foundation for precision medicine.

  20. Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline.

    Science.gov (United States)

    van Os, N J H; Roeleveld, N; Weemaes, C M R; Jongmans, M C J; Janssens, G O; Taylor, A M R; Hoogerbrugge, N; Willemsen, M A A P

    2016-08-01

    Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder with immunodeficiency and an increased risk of developing cancer, caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. Logically, blood relatives may also carry a pathogenic ATM mutation. Female carriers of such a mutation have an increased risk of breast cancer. Other health risks for carriers are suspected but have never been studied systematically. Consequently, evidence-based guidelines for carriers are not available yet. We systematically analyzed all literature and found that ATM mutation carriers have a reduced life expectancy because of mortality from cancer and ischemic heart diseases (RR 1.7, 95% CI 1.2-2.4) and an increased risk of developing cancer (RR 1.5, 95% CI 0.9-2.4), in particular breast cancer (RRwomen 3.0, 95% CI 2.1-4.5), and cancers of the digestive tract. Associations between ATM heterozygosity and other health risks have been suggested, but clear evidence is lacking. Based on these results, we propose that all female carriers of 40-50 years of age and female ATM c.7271T>G mutation carriers from 25 years of age onwards be offered intensified surveillance programs for breast cancer. Furthermore, all carriers should be made aware of lifestyle factors that contribute to the development of cardiovascular diseases and diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Targeted Next-Generation Sequencing Revealed Novel Mutations in Chinese Ataxia Telangiectasia Patients: A Precision Medicine Perspective.

    Directory of Open Access Journals (Sweden)

    Zhao Chen

    Full Text Available Ataxia telangiectasia (AT is an autosomal recessive disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia and immunodeficiency due to mutations in the ATM gene. We performed targeted next-generation sequencing (NGS on three unrelated patients and identified five disease-causing variants in three probands, including two pairs of heterozygous variants (FAT-1:c.4396C>T/p.R1466X, c.1608-2A>G; FAT-2:c.4412_4413insT/p.L1472Ffs*19, c.8824C>T/p.Q2942X and one pair of homozygous variants (FAT-3: c.8110T>G/p.C2704G, Hom. With regard to precision medicine for rare genetic diseases, targeted NGS currently enables the rapid and cost-effective identification of causative mutations and is an updated molecular diagnostic tool that merits further optimization. This high-throughput data-based strategy would propel the development of precision diagnostic methods and establish a foundation for precision medicine.

  2. Intraocular lens iris fixation. Clinical and macular OCT outcomes

    Directory of Open Access Journals (Sweden)

    Garcia-Rojas Leonardo

    2012-10-01

    Full Text Available Abstract Background To assess the efficacy, clinical outcomes, visual acuity (VA, incidence of adverse effects, and complications of peripheral iris fixation of 3-piece acrylic IOLs in eyes lacking capsular support. Thirteen patients who underwent implantation and peripheral iris fixation of a 3-piece foldable acrylic PC IOL for aphakia in the absence of capsular support were followed after surgery. Clinical outcomes and macular SD-OCT (Cirrus OCT; Carl Zeiss Meditec, Germany were analyzed. Findings The final CDVA was 20/40 or better in 8 eyes (62%, 20/60 or better in 12 eyes (92%, and one case of 20/80 due to corneal astigmatism and mild persistent edema. No intraoperative complications were reported. There were seven cases of medically controlled ocular hypertension after surgery due to the presence of viscoelastic in the AC. There were no cases of cystoid macular edema, chronic iridocyclitis, IOL subluxation, pigment dispersion, or glaucoma. Macular edema did not develop in any case by means of SD-OCT. Conclusions We think that this technique for iris suture fixation provides safe and effective results. Patients had substantial improvements in UDVA and CDVA. This surgical strategy may be individualized however; age, cornea status, angle structures, iris anatomy, and glaucoma are important considerations in selecting candidates for an appropriate IOL fixation method.

  3. Changes of macular thickness in HIV positive patients using OCT

    Directory of Open Access Journals (Sweden)

    Shang Li

    2014-10-01

    Full Text Available AIM: To assess the changes of macular thickness of acquire immunodeficiency syndrome(AIDSpatients. METHODS: The study based on the data analysis of 38 human immunodeficiency virus(HIVpositive patients(64 eyes. According to CD4 count and whether cytomegalovirus retinitis(CMVRhappened, the patients were divided into 3 groups. Group A included 16 patients(32 eyes, in which CD4 count was 50cells/μL and CMVR did not happen. Group C included 12 patients(12 eyes, in which CD4 count was RESULTS: The mean foveal thicknesses in groups A, B, C and D were 254.03±15.63μm, 263.11±17.12μm, 304.50±50.62μm and 257.64±8.54μm in order. Compared with foveal thickness in each group, there were significant differences in general(F=12.933, P=0.000. The mean foveal thickness in groups CMVR increased, which was of significant difference(P=0.000, compared with other groups.CONCLUSION: CMVR can impair the structure and function of macular, which then seriously affects the visual function of patients. It's helpful to understand the progress and prognosis of CMVR disease by observing macular structure with OCT in early time.

  4. Macular oedema due to letrozole: a first case report.

    Science.gov (United States)

    Moschos, Marilita M; Chatziralli, Irini P; Zagouri, Flora; Zografos, George C

    2012-11-01

    A 72-year-old woman presented with unexplained, progressive, painless visual loss in the right eye during the past six months. At presentation visual acuity (VA) was 3/60 in the right eye and 6/6 in the left eye. Anterior segment examination and intraocular pressures were normal. Dilated fundoscopy revealed significant macular oedema in the right eye and a normal fundus appearance in the left eye. Her medical history was noteworthy for breast ductal carcinoma in situ, for which she had undergone right mastectomy three years earlier. She had not received chemotherapy or radiotherapy but she had been under treatment with letrozole 2.5 mg/day over the past three years. She did not receive any other medication. Optical coherence tomography showed intraretinal fluid and a significant increase in retinal thickness in the foveal and parafoveal areas, while fluorescein angiography detected foveal hyperfluorescence and leakage of the dye in the late phase. Multifocal electroretinogram showed a decreased response in both eyes. In suspicion of letrozole-related retinopathy, the patient was advised to stop the medication. The patient agreed to receive an intravitreal injection of 0.05 ml/0.5 mg ranibizumab. One month later, VA in the right eye was 6/9 and macular oedema had apparently improved. This is the first reported case of letrozole-associated macular oedema treated with intravitreal ranibizumab.

  5. Chromosome Aberrations in Normal and Ataxia-Telangiectasia Cells Exposed to Heavy Ions

    Science.gov (United States)

    Kawata, T.; Ito, H.; Liu, C.; Shigematsu, N.; George, K.; Cucinotta, F. A.

    2007-01-01

    Although cells derived from Ataxia Telangiectasia (AT) patients are known to exhibit abnormal responses to ionizing radiations, its underlying mechanism still remains unclear. Previously, the authors reported that at the same gamma-irradiation dose AT cells show higher frequencies of misrepair and deletions compared to normal human fibroblast cells. In this study, we investigated the effects of heavy ions beams on chromosomal aberrations in normal and AT cells. Normal and AT fibroblast cells arrested at G0/G1 phase were irradiated with 2 Gy of X-rays, 490 MeV/u Silicon (LET 55 keV/m), 500 MeV/u Iron (LET 185 keV/m) and 200 MeV/u Iron (LET 440 keV/m) particles, and then cells were allowed to repair for 24 hours at 37 degrees before subculture. Calyculin-A induced PCC method was employed to collect G2/M chromosomes and whole DNA probes 1 and 3 were used to analyze chromosomal aberrations such as color-junctions, deletions, simple exchanges (incomplete and reciprocal exanges) and complex-type exchanges. The percentages of aberrant cells were higher when normal and AT cells were exposed to heavy ions compared to X-rays, and had a tendency to increase with increasing LET up to 185 keV/m and then decreased at 440 keV/m. When the frequency of color-junctions per cell was compared after X-ray exposure, AT cells had around three times higher frequency of color-junctions (mis-rejoining) than normal cells. However, at 185 keV/m there was no difference in the frequency of color-junctions between two cell lines. It was also found that the frequency of simple exchanges per cell was almost constant in AT cells regardless LET levels, but it was LET dependent for normal cells. Interestingly, the frequency of simple exchanges was higher for AT cells when it was compared at 185 keV/m but AT cells had more complex-type exchanges at the same LET levels. Heavy ions are more efficient in inducing chromosome aberrations in normal and AT cells compared to X-rays, and the aberration types

  6. FVC deterioration, airway obstruction determination, and life span in Ataxia telangiectasia.

    Science.gov (United States)

    Vilozni, Daphna; Lavie, Moran; Sarouk, Ifat; Bar-Aluma, Bat-El; Dagan, Adi; Ashkenazi, Moshe; Ofek, Miryam; Efrati, Ori

    2015-07-01

    Forced vital capacity (FVC) values decrease with progress of the disease in Ataxia telangiectasia (AT). To study the effect of this process on airway obstruction determination and life span in AT. Clinical data and yearly best spirometry maneuvers were collected retrospectively from 37 AT patients (196 spirometry tests) during 5.4 ± 1.8yrs (initial age 4-21 y). Twelve patients were walking (7 of them had recurrent respiratory system infections); 25 subjects were confined to wheelchair, of them 8 patients were towards end-stage lung disease. Spirometry indices included Forced Vital Capacity (FVC), mid-expiratory-flow (FEF25-75), and tidal volume (VT). We calculated FEF25-75/FVC and VT/FVC ratios. FVC declined from 67 ± 8 while walking to 19 ± 6 %predicted values. FEF25-75 values that were elevated (116 ± 23 %predicted) while walking, decreased to 69 ± 27 %predicted at end-stage where 7 patients responded to bronchodilators. VT/FVC ratio was 0.25 ± 0.06 while walking, increased to 0.35 once on wheelchairs, and further increased to 0.57 ± 0.19 at end-stage disease. FEF25-75/FVC ratio was 2.54 ± 0.70 above normal (∼1.0) increasing to 4.16 ± 0.75 at end stage. A sharp elevation was seen in FEF25-75/FVC ratio when FEV1 was still ∼45 %predicted and 2-years prior to death. Having a low baseline-FVC (60% predicted) artificially raises FEF25-75 values, so FEF25-75 of "mild obstruction" values may indicate severe airway obstruction in AT subjects. VT/FVC and FEF25-75/FVC ratios may therefore assist in revealing higher than normal breathing effort. The results further suggest adding VT/FVC and FEF25-75/FVC ratios to pulmonary function assessments in patients with AT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Liver Disease in Pediatric Patients With Ataxia Telangiectasia: A Novel Report.

    Science.gov (United States)

    Weiss, Batia; Krauthammer, Alexander; Soudack, Michalle; Lahad, Avishay; Sarouk, Ifat; Somech, Raz; Heimer, Gali; Ben-Zeev, Bruria; Nissenkorn, Andreea

    2016-04-01

    Ataxia telangiectasia (A-T) is a rare genetic multiorgan disease. Although gastrointestinal involvement is known, hepatic involvement in A-T has not been investigated. We aimed to study the hepatic involvement in a large cohort of patients with A-T. A retrospective review of patients, studied from January 1986 to January 2015 at a National A-T Center. Clinical data including demographic, genetic, laboratory, nutritional, radiographic, and histological data were retrieved. Fifty-three patients, 27 (49%) boys, age 14.6 ± 5.2 years (range 5.9-26.1 years), were included. Twenty-three patients (43.4%), age 9.9 ± 5.1 years, had consistently abnormal liver enzymes. The mean enzyme levels were alanine aminotransferase 76.8 ± 73.8 IU/L, aspartate aminotransferase 70 ± 50 IU/L, alkaline phosphatase 331 ± 134 IU/L, and gamma glutamyl transferase 114.7 ± 8 IU/L. Evaluation of other etiology of liver disease was negative. Ultrasonography revealed fatty liver in 9 of them (39%). Liver biopsy was performed in 2 patients, revealing mild-to-moderate steatosis in both, and fibrosis in 1 patient. Progression to advanced liver disease occurred in 2 of 23 (9%) patients within 2 to 5 years. Dyslipidemia was significantly associated with abnormal liver enzymes: 3 of 30 (10%) patients without abnormal liver enzymes versus 10 of 23 (45.5%) patients with abnormal liver enzymes, respectively (P < 0.05, Fisher exact test). No correlation was found between hepatic involvement and HbA1C, sex, presence of malignancy, or type of mutation. Abnormal liver enzymes and fatty liver are common in patients with A-T and may progress to advanced liver disease at a young age. These findings are novel and implicate that patients with A-T with abnormal liver enzymes should be evaluated for the presence of liver disease.

  8. Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Eun-Jung Choi

    Full Text Available Endoglin (ENG is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1. HHT1 patients have a higher prevalence of brain arteriovenous malformation (AVM than the general population and patients with other HHT subtypes. The pathogenesis of brain AVM in HHT1 patients is currently unknown and no specific medical therapy is available to treat patients. Proper animal models are crucial for identifying the underlying mechanisms for brain AVM development and for testing new therapies. However, creating HHT1 brain AVM models has been quite challenging because of difficulties related to deleting Eng-floxed sequence in Eng(2fl/2fl mice. To create an HHT1 brain AVM mouse model, we used several Cre transgenic mouse lines to delete Eng in different cell-types in Eng(2fl/2fl mice: R26CreER (all cell types after tamoxifen treatment, SM22α-Cre (smooth muscle and endothelial cell and LysM-Cre (lysozyme M-positive macrophage. An adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF was injected into the brain to induce focal angiogenesis. We found that SM22α-Cre-mediated Eng deletion in the embryo caused AVMs in the postnatal brain, spinal cord, and intestines. Induction of Eng deletion in adult mice using R26CreER plus local VEGF stimulation induced the brain AVM phenotype. In both models, Eng-null endothelial cells were detected in the brain AVM lesions, and formed mosaicism with wildtype endothelial cells. However, LysM-Cre-mediated Eng deletion in the embryo did not cause AVM in the postnatal brain even after VEGF stimulation. In this study, we report two novel HHT1 brain AVM models that mimic many phenotypes of human brain AVM and can thus be used for studying brain AVM pathogenesis and testing new therapies. Further, our data indicate that macrophage Eng deletion is insufficient and that endothelial Eng homozygous deletion is required for HHT1 brain AVM development.

  9. Brain arteriovenous malformation multiplicity predicts diagnosis of Hereditary Hemorrhagic Telangiectasia: Quantitative assessment

    Science.gov (United States)

    Bharatha, Aditya; Faughnan, Marie E.; Kim, Helen; Pourmohamad, Tony; Krings, Timo; Bayrak-Toydemir, Pinar; Pawlikowska, Ludmila; McCulloch, Charles E.; Lawton, Michael T.; Dowd, Christopher F.; Young, William L.; Terbrugge, Karel G.

    2013-01-01

    Purpose To quantitatively estimate the relationship between multiplicity of brain arteriovenous malformations (bAVMs) and the diagnosis of hereditary hemorrhagic telangiectasia (HHT). Methods We combined databases from two large North American bAVM referral centers, including demographics, clinical presentation and angiographic characteristics, and compared HHT patients with non-HHT patients. Logistic regression analysis was performed to quantify the association between bAVM multiplicity and odds of HHT diagnosis. Sensitivity, specificity, positive and negative predictive value (PPV, NPV), and positive and negative likelihood ratios (LR) were calculated to determine accuracy of bAVM multiplicity for screening HHT. Results Prevalence of HHT was 2.8% in the combined group. bAVM multiplicity was present in 39% of HHT patients and was highly associated with diagnosis of HHT in univariate (OR=83, 95% CI:40–173, P<0.0001) and multivariable (OR=87, 95% CI: 38–195, P<0.001) models, adjusting for age at presentation (P=0.013), non-symptomatic presentation (P=0.029) and cohort site (P=0.021). bAVM multiplicity alone was associated with high specificity (99.2%, 95%CI: 98.7–99.6%) and NPV (98.3%, 95% CI: 97.6–98.8%), and low sensitivity (39.3%, 95% CI: 26.5–53.2%) and PPV (59.5%, 95% CI: 42.1–75.2%). Positive and negative LR was 51 and 0.61, respectively, for diagnosis of HHT. HHT bAVMs were also more often smaller in size (<3 cm), non-eloquent in location and associated with superficial venous drainage, compared to non-HHT bAVMs. Conclusion Multiplicity of bAVMs is highly predictive of the diagnosis of HHT. The presence of multiple bAVMs should alert the clinician to the high probability of HHT and lead to comprehensive investigation for this diagnosis. PMID:22034007

  10. Mutation affecting the proximal promoter of Endoglin as the origin of hereditary hemorrhagic telangiectasia type 1.

    Science.gov (United States)

    Albiñana, Virginia; Zafra, Ma Paz; Colau, Jorge; Zarrabeitia, Roberto; Recio-Poveda, Lucia; Olavarrieta, Leticia; Pérez-Pérez, Julián; Botella, Luisa M

    2017-02-23

    Hereditary hemorrhagic telangiectasia (HHT) is a vascular multi-organ system disorder. Its diagnostic criteria include epistaxis, telangiectases in mucocutaneous sites, arteriovenous malformations (AVMs), and familial inheritance. HHT is transmitted as an autosomal dominant condition, caused in 85% of cases by mutations in either Endoglin (ENG) or Activin receptor-like kinase (ACVRL1/ACVRL1/ALK1) genes. Pathogenic mutations have been described in exons, splice junctions and, in a few cases with ENG mutations, in the proximal promoter, which creates a new ATG start site. However, no mutations affecting transcription regulation have been described to date in HHT, and this type of mutation is rarely identified in the literature on rare diseases. Sequencing data from a family with HHT lead to single nucleotide change, c.-58G > A. The functionality and pathogenicity of this change was analyzed by in vitro mutagenesis, quantitative PCR and Gel shift assay. Student t test was used for statistical significance. A single nucleotide change, c.-58G > A, in the proximal ENG promoter co-segregated with HHT clinical features in an HHT family. This mutation was present in the proband and in 2 other symptomatic members, whereas 2 asymptomatic relatives did not harbor the mutation. Analysis of RNA from activated monocytes from the probands and the healthy brother revealed reduced ENG mRNA expression in the HHT patient (p = 0.005). Site-directed mutagenesis of the ENG promoter resulted in a three-fold decrease in luciferase activity of the mutant c.-58A allele compared to wild type (p = 0.005). Finally, gel shift assay identified a DNA-protein specific complex. The novel ENG c.-58G > A substitution in the ENG promoter co-segregates with HHT symptoms in a family and appears to affect the transcriptional regulation of the gene, resulting in reduced ENG expression. ENG c.-58G > A may therefore be a pathogenic HHT mutation leading to haploinsufficiency of

  11. Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images.

    Science.gov (United States)

    Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

    2016-12-01

    Non-lethal macular diseases greatly impact patients' life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples.

  12. Treatment of EBV-associated nodular sclerosing Hodgkin lymphoma in a patient with ataxia telangiectasia with brentuximab vedotin and reduced COPP plus rituximab.

    Science.gov (United States)

    Meister, Michael T; Voss, Sandra; Schwabe, Dirk

    2015-11-01

    Patients with ataxia telangiectasia (AT) with malignancies face poor prognosis due to increased treatment-related toxicity. Here, we report a 14-year-old male with AT and Hodgkin lymphoma (HL) who received brentuximab vedotin and reduced COPP plus rituximab courses. This treatment resulted in complete remission and showed no severe toxicity. © 2015 Wiley Periodicals, Inc.

  13. An early-onset recessive cerebellar disorder with distal amyotrophy and, in two patients, gross myoclonia: A probable ataxia telangiectasia variant

    NARCIS (Netherlands)

    A.S. de Graaf (A.); G. de Jong (G.); W.J. Kleijer (Wim)

    1995-01-01

    textabstractWe report a family of 4 siblings from a non-consanguineous marriage, presenting with an early onset recessive cerebellar ataxia and progressive distal limb wasting. Ocular or other telangiectasias were absent. There were neither frequent infections nor immunodeficiencies. The two younges

  14. Domoprednate (Stermonid), a topical D-homocorticosteroid, skin atrophy and telangiectasia. A double-blind, randomized comparison with hydrocortisone butyrate, betamethasone valerate, clobetasole propionate and placebo.

    Science.gov (United States)

    Serup, J; Holm, P

    1985-01-01

    Five corticosteroid ointments and placebo were compared in 17 volunteers with regard to their influence on normal skin under occlusive conditions. Each volunteer had six simultaneous applications on the forearms and six on the back. The trial was double-blind and lasted 4 weeks. The ointments were placed in randomized order. The treatments were 0.1 and 0.03% domoprednate, 0.1% hydrocortisone butyrate, 0.1% betamethasone valerate, 0.05% clobetasole propionate and placebo. Skin thickness was measured on days 0, 7, 14, 21 and 28, transepidermal water loss on days 0, 14 and 28, while blood flow and telangiectasias were evaluated only on day 28 at termination of the trial. The skin thickness became significantly reduced on all corticosteroids, but not on placebo; 0.03% domoprednate, however, tended to have an intermediate position between placebo and the other ointments. The transepidermal water loss did not change. Rating of telangiectasia under stereomicroscope showed a significantly lower score after 0.03% domoprednate and placebo as compared to the other ointments. Assessment of telangiectasia by laser-Doppler flowmetry showed a similar tendency. It is concluded that 0.1% domoprednate is comparable to other topical corticosteroids with respect to atrophogeneity and formation of telangiectasia, but the 0.03% concentration seems to result in fewer side effects.

  15. Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation

    DEFF Research Database (Denmark)

    Gatei, Magtouf; Sloper, Katie; Sørensen, Claus Storgaard

    2003-01-01

    In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2...

  16. Ataxia Telangiectasia-Mutated (ATM) kinase activity is regulated by ATP-driven conformational changes in the Mre11/Rad50/Nbs1 (MRN) complex

    NARCIS (Netherlands)

    J.-H. Lee (Ji-Hoon); M.R. Mand (Michael); R.A. Deshpande (Rajashree); E. Kinoshita (Eri); S.-H. Yang (Soo-Hyun); C. Wyman (Claire); T.T. Paull

    2013-01-01

    textabstractThe Ataxia Telangiectasia-Mutated (ATM) protein kinase is recruited to sites of double-strand DNA breaks by the Mre11/Rad50/Nbs1 (MRN) complex, which also facilitates ATM monomerization and activation. MRN exists in at least two distinct conformational states, dependent on ATP binding an

  17. Dexamethasone intravitreal implant in the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Dugel PU

    2015-07-01

    Full Text Available Pravin U Dugel,1,2 Francesco Bandello,3 Anat Loewenstein4 1Retinal Consultants of Arizona, Phoenix, AZ, 2Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 3Department of Ophthalmology, University Vita-Salute Scientific Institute San Raffaele, Milan, Italy; 4Department of Ophthalmology, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Diabetic macular edema (DME resembles a chronic, low-grade inflammatory reaction, and is characterized by blood–retinal barrier (BRB breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048 from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%. Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of

  18. Prevention of visual field defects after macular hole surgery.

    LENUS (Irish Health Repository)

    Cullinane, A B

    2012-02-03

    BACKGROUND\\/AIM: The pathogenesis of visual field loss associated with macular hole surgery is uncertain but a number of explanations have been proposed, the most convincing of which is the effect of peeling of the posterior hyaloid, causing either direct damage to the nerve fibre layer or to its blood supply at the optic nerve head. The purpose of this preliminary prospective study was to determine the incidence of visual field defects following macular hole surgery in cases in which peeling of the posterior hyaloid was confined only to the area of the macula. METHODS: 102 consecutive eyes that had macular hole surgery had preoperative and postoperative visual field examination using a Humphrey\\'s perimeter. A comparison was made between two groups: I, those treated with vitrectomy with complete posterior cortical vitreous peeling; and II, those treated with a vitrectomy with peeling of the posterior hyaloid in the area of the macula but without attempting a complete posterior vitreous detachment. Specifically, no attempt was made to separate the posterior hyaloid from the optic nerve head. Eyes with stage II or III macular holes were operated. Autologous platelet concentrate and non-expansile gas tamponade was used. Patients were postured prone for 1 week. RESULTS: In group I, 22% of patients were found to have visual field defects. In group II, it was possible to separate the posterior hyaloid from the macula without stripping it from the optic nerve head and in these eyes no pattern of postoperative visual field loss emerged. There were no significant vision threatening complications in this group. The difference in the incidence of visual field loss between group I and group II was significant (p=0.02). The anatomical and visual success rates were comparable between both groups. CONCLUSION: The results from this preliminary study suggest that the complication of visual field loss after macular surgery may be reduced if peeling of the posterior hyaloid is

  19. Analisador de espessura retiniana (RTA na avaliação de buraco macular Retinal thickness analyzer (RTA in evaluation of macular hole

    Directory of Open Access Journals (Sweden)

    Márcio Bittar Nehemy

    2001-04-01

    Full Text Available Objetivo: Avaliar os resultados do Analisador de Espessura Retiniana (RTA em olhos com buraco macular e compará-los aos achados da biomicroscopia do segmento posterior, retinografia e fluoresceinografia. Métodos: Foram estudados por meio do analisador de espessura retiniana, biomicroscopia do segmento posterior, retinografia e fluoresceinografia, dez olhos de seis pacientes com diagnóstico de buraco macular. Destes, 8 foram examinados antes de qualquer tratamento, e dois, após o tratamento do buraco macular pela vitrectomia. Resultados: Em dois olhos com diagnóstico de buraco macular pelo exame clínico e outros exames complementares, a opacidade dos meios impediu a análise pelo analisador de espessura retiniana. O corte óptico do analisador de espessura retiniana mostrou concordância com os achados clínicos e com os observados nos oito olhos em que o exame foi possível. O corte topográfico nos dois olhos que apresentavam buraco macular fechado pela cirurgia mostraram espessura foveal média normal, e nos seis olhos com buraco macular não operado, espessura foveal média aumentada. Conclusão: O corte óptico do analisador de espessura retiniana evidenciou o buraco macular, forneceu informações sobre sua largura e profundidade e comprovou o fechamento do buraco após a vitrectomia. O corte topográfico do analisador de espessura retiniana mostrou espessura foveal média normal nos dois casos de fechamento do buraco macular e, espessura foveal média aumentada em todos os seis olhos não operados.Objective: To evaluate the Retinal Thickness Analyzer (RTA findings in eyes with macular hole and compare them to findings of retina and vitreous biomicroscopy, retinography and fluorescein angiography. Methods: The authors studied ten eyes of six patients with the diagnosis of macular hole, using retinal thickness analyzer, retina and vitreous biomicroscopy, retinography and fluorescein angiography. Eight eyes had been examined before any

  20. Retro-Mode Scanning Laser Ophthalmoscopy Planning for Navigated Macular Laser Photocoagulation in Macular Edema

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    Ernest V. Boiko

    2016-01-01

    Full Text Available Purpose. To compare treatment areas and navigated macular laser photocoagulation (MLP plans suggested by retro-mode scanning laser ophthalmoscopy (RM-SLO image versus optical coherence tomography (OCT central retinal thickness map and treatment planning among retina specialists. Methods. Thirty-nine eyes with diabetic or branch retinal vein occlusion-related ME undergoing navigated MLP with navigated photocoagulator had OCT and RM-SLO taken. OCT map and RM-SLO image were imported to the photocoagulator and aligned onto the retina. Two retina specialists placed laser spot marks separately based on OCT and RM-SLO images in a random fashion. The spots placed by each physician were compared between OCT and RM-SLO and among physicians. The areas of retinal edema on OCT and RM-SLO of the same eye were also compared. Results. The average number of laser spots using RM-SLO and OCT template was 189.6±77.4 and 136.6±46.8, respectively, P=0.003. The average area of edema on RM-SLO image was larger than that on OCT map (14.5±3.9 mm2 versus 10.3±2.8 mm2, P=0.005 because of a larger scanning area. There was narrow variability in treatment planning among retina specialists for both RM-SLO (P=0.13 and OCT (P=0.19. Conclusion. The RM-SLO image superimposed onto the fundus of the same eye can be used to guide MLP with narrow variability in treatment planning among retina specialists. The treatment areas suggested by RM-SLO-guided MLP plans for ME were shown to be larger than those suggested by OCT-guided plans.

  1. Retro-Mode Scanning Laser Ophthalmoscopy Planning for Navigated Macular Laser Photocoagulation in Macular Edema.

    Science.gov (United States)

    Boiko, Ernest V; Maltsev, Dmitrii S

    2016-01-01

    Purpose. To compare treatment areas and navigated macular laser photocoagulation (MLP) plans suggested by retro-mode scanning laser ophthalmoscopy (RM-SLO) image versus optical coherence tomography (OCT) central retinal thickness map and treatment planning among retina specialists. Methods. Thirty-nine eyes with diabetic or branch retinal vein occlusion-related ME undergoing navigated MLP with navigated photocoagulator had OCT and RM-SLO taken. OCT map and RM-SLO image were imported to the photocoagulator and aligned onto the retina. Two retina specialists placed laser spot marks separately based on OCT and RM-SLO images in a random fashion. The spots placed by each physician were compared between OCT and RM-SLO and among physicians. The areas of retinal edema on OCT and RM-SLO of the same eye were also compared. Results. The average number of laser spots using RM-SLO and OCT template was 189.6 ± 77.4 and 136.6 ± 46.8, respectively, P = 0.003. The average area of edema on RM-SLO image was larger than that on OCT map (14.5 ± 3.9 mm(2) versus 10.3 ± 2.8 mm(2), P = 0.005) because of a larger scanning area. There was narrow variability in treatment planning among retina specialists for both RM-SLO (P = 0.13) and OCT (P = 0.19). Conclusion. The RM-SLO image superimposed onto the fundus of the same eye can be used to guide MLP with narrow variability in treatment planning among retina specialists. The treatment areas suggested by RM-SLO-guided MLP plans for ME were shown to be larger than those suggested by OCT-guided plans.

  2. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    Science.gov (United States)

    ... related macular degeneration.” Nature Genetics , September 2013. DOI: 10.1038/ng.2758. Seddon JM et al . “Rare variants ... related macular degeneration.” Nature Genetics , September 2013. DOI: 10.1038/ng.2741. Helgason H et al . “A rare ...

  3. Late Closure of a Stage III Idiopathic Macular Hole after Pars Plana Vitrectomy

    Directory of Open Access Journals (Sweden)

    Filiz Afrashi

    2015-12-01

    Full Text Available A 57-year-old female presented to our hospital with decreased vision in her right eye. Detailed ocular examination was performed, and a macular hole was detected in the right eye. The presence of a full-thickness stage III macular hole was confirmed with optical coherence tomography (OCT imaging. Pars plana vitrectomy followed by long-acting gas tamponade (C3F8 was performed as treatment. One month after surgery, clinical examination revealed a persistent macular hole, confirmed by an OCT scan. Although the patient was scheduled for reoperation, the surgery was postponed due to personal reasons of the patient. Surprisingly, after five months, a closure pattern with accompanying epiretinal membrane was observed in the macular hole area. The closure of the macular hole was completed without any further intervention 8 months post-surgery. In cases of unclosed macular hole after the first surgery, if a second surgery cannot be performed, follow-up with OCT recommended due to the possibility of spontaneous closure. However, spontaneous closure of a persistent macular hole following PPV is rare, so early diagnosis and surgical repair of unclosed macular holes must remain the primary goal.

  4. Quality of Life and Health Economic Assessments of Age-Related Macular Degeneration

    OpenAIRE

    Covert, D.; Berdeaux, G; Mitchell, J; Bradley, Clare; Barnes, R.

    2007-01-01

    In this article, we review measures of patient-reported outcomes that can show whether a treatment for age-related macular degeneration also provides patient-perceived benefits. In addition, we look at health economic measurements currently being used to develop cost-effectiveness models for age-related macular degeneration.

  5. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    Science.gov (United States)

    The xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain t...

  6. Macular Effects of Silicone Oil Tamponade: Optical Coherence Tomography Findings During and After Silicone Oil Removal.

    Science.gov (United States)

    Lo, Danielle M; Flaxel, Christina J; Fawzi, Amani A

    2017-01-01

    To investigate retinal morphologic changes during silicone oil tamponade and after its removal using spectral domain OCT (SD-OCT) imaging. Retrospective review of 12 patients who underwent silicone oil tamponade for repair of retinal detachments. Macular OCT scans and volumetric thickness maps were examined qualitatively and quantitatively. Volumetric OCT revealed two distinct patterns during silicone oil: macular thickening (Group A) and macular thinning (Group B). In Group A, mean foveal thickness (507 ± 169 µm vs. 407 ± 163 µm, p = 0.003) and mean macular volume (11.6 ± 2.4 mm(3) vs. 9.9 ± 1.5 mm(3)) were significantly increased during tamponade compared to post-oil removal. Group B had significantly decreased mean foveal thickness (210 ± 38 µm vs. 276 ± 58 µm, p = 0.009) and macular volume (7.3 ± 1.8 mm(3) vs. 8.4 ± 1.8 mm(3)) during tamponade. Importantly, resolution of macular changes occurred without further intervention and was associated with improved visual acuity in both groups. Our series suggests that when faced with unexplained macular edema or macular thinning during tamponade, silicone oil removal alone can achieve resolution of these structural changes.

  7. Influence of ischemia on visual function in patients with branch retinal vein occlusion and macular edema

    Directory of Open Access Journals (Sweden)

    Noma H

    2011-05-01

    Full Text Available Hidetaka Noma¹, Hideharu Funatsu¹, Tatsuya Mimura², Katsunori Shimada³¹Department of Ophthalmology, Yachiyo Medical Center, Tokyo Women's Medical University, Owada-shinden, Chiba, Japan; ²Department of Ophthalmology, University of Tokyo Graduate School of Medicine, Tokyo, Japan; ³Department of Hygiene and Public Health II, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, JapanAbstract: Visual function and retinal morphology were investigated to elucidate the influence of ischemia in patients with branch retinal vein occlusion (BRVO and macular edema. In 41 consecutive patients with BRVO aged 68.9 ± 10.0 years (22 women and 19 men, the area of capillary nonperfusion was measured by fluorescein angiography. Retinal thickness and retinal volume were measured by optical coherence tomography, and mean retinal sensitivity was calculated for each of 9 macular subfields. Mean visual acuity and macular sensitivity within the central subfield were not significantly correlated with the nonperfused area. However, the macular sensitivity within the central 5 subfields and all 9 subfields showed significant negative correlations with the nonperfused area. Also, macular thickness and volume within all 9 subfields were significantly correlated with the nonperfused area. In conclusion, evaluation of both the fovea and the entire macular region may be important in patients with ischemic BRVO.Keywords: branch retinal vein occlusion, macular edema, macular sensitivity, ischemia

  8. The predictive value of optical coherence tomography after grid laser photocoagulation for diffuse diabetic macular oedema

    DEFF Research Database (Denmark)

    Soliman, W.; Sander, B.; Soliman, K.A.E.N.

    2008-01-01

    Purpose: To assess the predictive value of optical coherence tomography (OCT) mapping of retinal thickness and intraretinal morphological changes after macular grid for diffuse diabetic macular oedema (DMO). Methods: We carried out a prospective, non-controlled, case series study, in which 28 con...

  9. Telangiectasia hemorrágica hereditária: resposta hematológica após terapêutica com talidomida

    Directory of Open Access Journals (Sweden)

    Eduardo Ribeiro

    2013-03-01

    Full Text Available A telangiectasia hemorrágica hereditária (THH é uma doença autossómica dominante, que se distingue em dois tipos, devidos a mutações em genes diferentes. É caracterizada por telangiectasias mucocutâneas e viscerais, envolvendo vários órgãos com malformações vasculares. O sintoma comum é a anemia. O diagnóstico clínico é baseado na presença de pelo menos três das quatro principais características clínicas: epistáxis, telangiectasias cutâneas ou mucosas, envolvimento visceral e história familiar. Dependendo das manifestações da doença e da sua gravidade, existem várias formas de tratamento que variam desde terapêutica local, a cirurgia, ou terapêutica farmacológica. Apresentamos o caso de um paciente com THH e anemia por deficiência de ferro grave, dependente de transfusões de sangue frequentes, que teve uma melhoria dramática após terapêutica com a talidomida, sem ocorrência de efeitos colaterais. Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant disease and is distinguished into two types, which are due to mutations in different genes. It is characterized by mucocutaneous and visceral telangiectasia and involves several organs with vascular malformations. The common symptom is anemia. The clinical diagnosis is based on the presence of at least three of four main clinical features: epistaxis, cutaneous or mucosal telangiectases, visceral involvement and a family history. Depending on disease manifestation and it severity, there are several forms of therapy ranging from local therapy, surgery ou drug therapy. Here we describe a dramatic improvement of a patient with HHT and severe iron deficiency anemia, requiring frequent blood transfusion, successfully treated with thalidomide, without side effects.

  10. Etiology and treatment of the inflammatory causes of cystoid macular edema

    Directory of Open Access Journals (Sweden)

    Hyung Cho

    2009-10-01

    Full Text Available Hyung Cho1, Assumpta Madu11Department of Ophthalmology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USAAbstract: Cystoid macular edema in its various forms can be considered one of the leading causes of central vision loss in the developed world. It occurs in a wide variety of pathologic conditions and represents the final common pathway of several basic processes. Therapeutic approaches to cystoid macular edema depend on a clear understanding of its contributing pathophysiologic mechanisms. This review will discuss the mechanism of ocular inflammation in cystoid macular edema with a particular focus on the inflammatory causes: post-operative, uveitic, and after laser procedures. A variety of pharmacologic agents targeting inflammatory molecules have been shown to reduce macular edema and improve visual function. However, the long-term efficacy and safety of most new therapies have yet to be established in controlled clinical trials.Keywords: ocular inflammation, cystoid macular edema, uveitis

  11. Correlation between the optical coherence tomography and electroretinogram in retinal vein occlusion macular edema

    Directory of Open Access Journals (Sweden)

    Ya Xu

    2014-11-01

    Full Text Available AIM: To evaluate the correlation between retinal thickness and photopic flash electroretinogram(ERGparameters(Cone a-wave, Cone b-wave, and 30Hz flickerin patients with central retinal vein occlusion(CRVOand macular edema. METHODS: A total of 25 patients(25 CRVO eyes and 25 unaffected fellow eyeswith CRVO underwent the examination of optical coherence tomography(OCTand photopic falsh ERG. The amplitude and implicit time of the ERG parameters were extracted from the ERG traces. Retinal thicknesses were measured by OCT in nine macular subfields. Then the correlations between ERG parameters and macular morphological parameters were analyzed. RESULTS: The Cone b-wave and 30Hz flicker implicit time were correlated with macular retinal thickness in seven out of nine subfields, excluding the temporal subfields. CONCLUSION: The retinal thickness of the macular edema may be associated with inner retinal function in CRVO patients.

  12. Role of chromatin structure modulation by the histone deacetylase inhibitor trichostatin A on the radio-sensitivity of ataxia telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Meschini, Roberta, E-mail: meschini@unitus.it; Morucci, Elisa; Berni, Andrea; Lopez-Martinez, Wilner; Palitti, Fabrizio

    2015-07-15

    Highlights: • Role of chromatin compaction on chromosomal instability. • Reduced radiation-induced clastogenicity in Ataxia telangiectasia cell lines. • Histone tails hyperacetylation reduces heterochromatin content favouring DSBs repair. - Abstract: At present, a lot is known about biochemical aspects of double strand breaks (DBS) repair but how chromatin structure affects this process and the sensitivity of DNA to DSB induction is still an unresolved question. Ataxia telangiectasia (A-T) patients are characterised by very high sensitivity to DSB-inducing agents such as ionising radiation. This radiosensitivity is revealed with an enhancement of chromosomal instability as a consequence of defective DNA repair for a small fraction of breaks located in the heterochromatin, where they are less accessible. Besides, recently it has been reported that Ataxia Telangiectasia Mutated (ATM) mediated signalling modifies chromatin structure. In order to study the impact of chromatin compaction on the chromosomal instability of A-T cells, the response to trichostatin-A, an histone deacetylase inhibitor, in normal and A-T lymphoblastoid cell lines was investigated testing its effect on chromosomal aberrations, cell cycle progression, DNA damage and repair after exposure to X-rays. The results suggest that the response to both trichostatin-A pre- and continuous treatments is independent of the presence of either functional or mutated ATM protein, as the reduction of chromosomal damage was found also in the wild-type cell line. The presence of trichostatin-A before exposure to X-rays could give rise to prompt DNA repair functioning on chromatin structure already in an open conformation. Differently, trichostatin-A post-treatment causing hyperacetylation of histone tails and reducing the heterochromatic DNA content might diminish the requirement for ATM and favour DSBs repair reducing chromosomal damage only in A-T cells. This fact could suggest that trichostatin-A post

  13. Quantitative assessment of macular thickness in normal subjects and patients with diabetic retinopathy by scanning retinal thickness analyser

    Science.gov (United States)

    Oshima, Y.; Emi, K.; Yamanishi, S.; Motokura, M.

    1999-01-01

    AIMS—To evaluate the scanning retinal thickness analyser (RTA), a novel non-invasive imaging instrument, in diagnosing and quantitatively characterising diabetic macular oedema, and to investigate the relation between central macula thickness measured by RTA and other clinical examinations.
METHODS—Central macular thickness was measured using the RTA in 40 normal subjects and 60 patients with diabetic retinopathy. The reproducibility of the retinal thickness measurements was evaluated by calculating the mean of the inter- and intrasession variations. Central macular thickness was correlated with the results of visual acuity measurements, biomicroscopy, and fluorescein angiography.
RESULTS—Intra- and intersession reproducibility of the RTA in normal subjects was plus or minus 5.2% (16 µm) and plus or minus 6.1% (19 µm), respectively. The mean central macular thickness was 182 (SD 16) µm in normal subjects, 283 (116) µm in diabetic eyes without clinically significant macular oedema (CSMO), and 564 (168) µm in diabetic eyes with CSMO. Central macular thickness was significantly greater (p<0.001) in eyes with diabetic retinopathy than in normal subjects, even when macular thickening did not meet the standard for CSMO (p=0.019) measured by biomicroscopy. Although greater fluorescein leakage at the macula results in greater central macular thickness, only eyes with diffuse leakage had statistically significant macular thickening compared with normal subjects (p=0.022). Central macular thickness measured with the RTA was significantly correlated with the logarithmic converted visual acuity (r2= 0.76) in diabetic eyes.
CONCLUSION—Scanning RTA, which has good reproducibility, might be useful to quantitatively detect and monitor macular thickening in diabetic retinopathy. Central macular thickness was highly correlated with logarithmic converted visual acuity in diabetic macular oedema.

 Keywords: scanning retinal thickness analyser; macular

  14. [Modified technique of autologous transplantation of internal limiting membrane for macular hole].

    Science.gov (United States)

    Hernández-da Mota, Sergio Eustolio; Béjar-Cornejo, Francisco

    Autologous internal limiting membrane transplantation has allowed some cases of macular holes refractory to conventional surgery techniques to be treated. The purpose of this study is to describe the anatomical and functional outcomes of a modification of this technique in a case series of naïve macular hole patients. A consecutive case series study was performed on patients with naïve macular holes with a diameter greater than 600 μ. Best corrected visual acuity, clinical features of the macular area, and optical coherence tomography were recorded before the operation and at the end of follow-up in all patients studied. All patients underwent 23 Ga core vitrectomy, posterior hyaloid separation, and brilliant-blue assisted internal limiting membrane peeling. A small piece of the internal limiting membrane was peeled off to make a free flap, and this was trasplanted and placed inside the macular hole under perfluorocarbon liquids. Air-fluid exchange was performed and SF6 gas was injected at a non-expansile concentration. The study included 5 eyes of 5 patients who underwent internal limiting membrane autograft. The mean age was 50.6 (SD 12.3) years. Four of the 5 cases had macular hole closure. The case where there was no closure of the macular hole was secondary to trauma. There was an improvement in visual acuity in all patients where the closing of the macular hole was achieved at the end of follow-up. In this cases series of macular hole patients, the autologous internal limiting membrane transplantation was associated with an anatomical closure of the macular hole and functional improvement in most of the patients studied. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  15. The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration

    OpenAIRE

    Stringham, J.M; Hammond, BR; Nolan, John,; Wooten, BR; Mammen, A.; Smollen, W

    2008-01-01

    The purpose of this study was to assess the utility and validity of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment optical density (MPOD) in patients with intermediate stages of age-related macular degeneration (AMD). The measurement procedure was optimized to accommodate individual differences in temporal vision related to age, disease, or other factors. The validity criteria were based on the similarity of the spectral absorption curves to ex vivo curv...

  16. Evaluation of Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness after Vitrectomy with Internal Limiting Membrane Peeling for Idiopathic Macular Holes

    Directory of Open Access Journals (Sweden)

    Alfonso L. Sabater

    2014-01-01

    Full Text Available Purpose. To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral-domain optical coherence tomography (SD-OCT. Methods. 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA. Results. No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. Conclusion. SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole.

  17. Evaluation of Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness after Vitrectomy with Internal Limiting Membrane Peeling for Idiopathic Macular Holes

    Science.gov (United States)

    Velázquez-Villoria, Álvaro; Zapata, Miguel A.; Figueroa, Marta S.; Suárez-Leoz, Marta; Arrevola, Luis; Teijeiro, María-Ángeles; García-Layana, Alfredo

    2014-01-01

    Purpose. To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral-domain optical coherence tomography (SD-OCT). Methods. 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA). Results. No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. Conclusion. SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole. PMID:25110679

  18. Radiation Dose-effects on Cell Cycle, Apoptosis, and Marker Expression of Ataxia Telangiectasia-Heterozygous Human Breast Epithelial Cells

    Science.gov (United States)

    Cruz, A.; Bors, K.; Jansen, H.; Richmond, R.

    2003-01-01

    Ataxia-telangiectasia (A-T) is a radiation-sensitive genetic condition. AT-heterozygous human mammary epithelial cells (HMEC) were irradiated using a Cs137 source in order to compare cell cycle, apoptosis, and marker expression responses across 3 radiation doses. No differences in cell cycle and apoptosis were found with any of the radiation doses used (30, 60, and 90 rads) compared with the unirradiated control (0 rad). At the same doses, however, differences were found in marker expression, such as keratin 18 (kl8), keratin 14 (k14), insulin-like growth factor I receptor (IGF-IR), and connexin 43 (cx43). This may indicate that radiation sensitivity in the heterozygous state may be initiated through signal transduction responses.

  19. [Diagnostics of ataxia-telangiectasia by the express-test found on the method of indirect immunofluorescence].

    Science.gov (United States)

    Kuranova, M L; Ledashcheva, T A; Tulush, E K; Beliaev, D L; Zherebtsov, S V; Pleskach, N M; Prokof'eva, V V; Mikhel'son, V M; Spivak, I M

    2013-01-01

    Ataxia-telangiectasia (AT) is a hereditary severe neurodegenerative disease developing, when mutations take place in both alleles of the atm gene, which encodes the key protein of the cellular response to DNA damage (DDR)--ATM proteinkinase. In response to the occurrence of double-strand DNA breaks, the ATM proteinkinase pass the autophosphorylation, and its active form--the phospho-ATM (P-ATM) appears in cells. In the nuclei of cells having the atm gene, P-ATM is revealed, being absent in cells with mutated forms of this gene, by means of the application of the modified method of indirect immunofluorescence. This peculiarity may be applied in the clinic, in order to confirm the diagnosis of AT.

  20. Radiation Dose-effects on Cell Cycle, Apoptosis, and Marker Expression of Ataxia Telangiectasia-Heterozygous Human Breast Epithelial Cells

    Science.gov (United States)

    Cruz, A.; Bors, K.; Jansen, H.; Richmond, R.

    2003-01-01

    Ataxia-telangiectasia (A-T) is a radiation-sensitive genetic condition. AT-heterozygous human mammary epithelial cells (HMEC) were irradiated using a Cs137 source in order to compare cell cycle, apoptosis, and marker expression responses across 3 radiation doses. No differences in cell cycle and apoptosis were found with any of the radiation doses used (30, 60, and 90 rads) compared with the unirradiated control (0 rad). At the same doses, however, differences were found in marker expression, such as keratin 18 (kl8), keratin 14 (k14), insulin-like growth factor I receptor (IGF-IR), and connexin 43 (cx43). This may indicate that radiation sensitivity in the heterozygous state may be initiated through signal transduction responses.

  1. Utility of hard exudates for the screening of macular edema.

    Science.gov (United States)

    Litvin, Taras V; Ozawa, Glen Y; Bresnick, George H; Cuadros, Jorge A; Muller, Matthew S; Elsner, Ann E; Gast, Thomas J

    2014-04-01

    The purpose of this study was to determine whether hard exudates (HEs) within one disc diameter of the foveola is an acceptable criterion for the referral of diabetic patients suspected of clinically significant macular edema (CSME) in a screening setting. One hundred forty-three adults diagnosed as having diabetes mellitus were imaged using a nonmydriatic digital fundus camera at the Alameda County Medical Center in Oakland, CA. Nonstereo fundus images were graded independently for the presence of HE near the center of the macula by two graders according to the EyePACS grading protocol. The patients also received a dilated fundus examination on a separate visit. Clinically significant macular edema was determined during the dilated fundus examination using the criteria set forth by the Early Treatment Diabetic Retinopathy Study. Subsequently, the sensitivity and specificity of HEs within one disc diameter of the foveola in nonstereo digital images used as a surrogate for the detection of CSME diagnosed by live fundus examination were calculated. The mean (±SD) age of 103 patients included in the analysis was 56 ± 17 years. Clinically significant macular edema was diagnosed in 15.5% of eyes during the dilated examination. For the right eyes, the sensitivity of HEs within one disc diameter from the foveola as a surrogate for detecting CSME was 93.8% for each of the graders; the specificity values were 88.5 and 85.1%. For the left eyes, the sensitivity values were 93.8 and 75% for each of the two graders, respectively; the specificity was 87.4% for both graders. This study supports the use of HE within a disc diameter of the center of the macula in nonstereo digital images for CSME detection in a screening setting.

  2. Intravitreal bevacizumab for persistent macular edema with proliferative diabetic retinopathy.

    Science.gov (United States)

    Gulkilik, Gokhan; Taskapili, Muhittin; Kocabora, Selim; Muftuoglu, Gulipek; Demirci, Goktug

    2010-12-01

    To evaluate the effectiveness of an intravitreal bevacizumab injection on retinal neovascularization and diabetic macular edema (DME) refractory to laser photocoagulation therapy. Thirty-four eyes of 22 patients with proliferative diabetic retinopathy and DME refractory to laser photocoagulation therapy received an intravitreal injection of 1.25 mg/0.05 ml of bevazicumab. Changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), regression of neovascularization over time, and correlation between BCVA and CMT were evaluated. Follow-up visits were at weeks 1, 2 and 4 and months 3 and 6. Mean BCVA was significantly better than baseline only at week 2 (P = 0.036). Mean CMT decreased significantly from baseline at weeks 1, 2, and 4 (P = 0.001). At months 3 and 6, mean CMT increased, albeit insignificantly (P = 0.804 and P = 1.0). The decrease in fluorescein leakage was moderate in all eyes at the end of week 1. At week 2, there was total resolution of fluorescein leakage in 24 (70.5%) eyes and moderate resolution in 10 (29.5%) eyes. At the end of month 3, the fluorescein leakage was fully resolved in 5 (14.7%) eyes, moderately resolved in 24 (70.5%) eyes, and was similar to baseline in 5 (14.7%) eyes. At month 6, the fluorescein leakage was fully resolved in 3 (8.8%) eyes, moderately resolved in 20 (58.8%) eyes, and was similar to baseline in 11 (32.4%) eyes. A moderate but insignificant negative correlation was found between visual acuity and CMT (P > 0.05). Persistence or recurrence of neovascular tissue after panretinal photocoagulation may be attributed to the production of vascular endothelial growth factor by the residual ischemic retina, which also results in persistent or recurrent DME despite macular grid photocoagulation.

  3. The role of epigenetics in age-related macular degeneration.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the

  4. Macular hole in Behçet′s disease

    Directory of Open Access Journals (Sweden)

    Hassan Al-Dhibi

    2011-01-01

    Full Text Available Objective: To investigate the clinical features, prevalence, role of surgical intervention and the visual prognosis of macular holes (MH in patients with Behcet′s disease (BD. Materials and Methods: Retrospective study of patients with BD and MH from January 1998 to November 2008. Results: Out of 159 patients, 21 eyes of 17 patients were identified with MH. The mean age was 38.59 (range 23-61 years and the mean follow-up period was 5.1 years (range 13-164 months. The prevalence of MH was 7%. Visual acuity (VA at the time of presentation ranged from 20/70 to hand-motion. Optical coherence tomography (OCT findings revealed intraretinal cysts at the edge of the MH. The mean size of MH was 983.6 um; 52% had elevated edges, 43% had flat edges and only one eye (5% was closed postoperatively. Fluorescein angiography (FA was consistent with macular ischemia in 76% of the cases. Human leukocyte antigen (HLA B51 association was found in 14 of the 15 patients investigated. Six patients (out of 17 underwent pars plana vitrectomy. The final VA on their last follow-up ranged from 20/70 to 2/200. Surgical intervention for MH did not result in any visual improvement as compared to non-operated eyes. One patient lost vision completely due to elevated intraocular pressure post vitrectomy and silicon oil tamponade. Conclusions: MH in patients with BD may lead to significant visual disability. Surgical intervention does not seem to have any potential beneficial effect on the VA, probably due to significant macular ischemia and sequelae from the ocular inflammation.

  5. Characteristics of fundus autofluorescence in cystoid macular edema

    Institute of Scientific and Technical Information of China (English)

    PENG Xi-jia; SU Lan-ping

    2011-01-01

    Background Fundus autofluorescence (FAF) imaging is a fast and noninvasive technique developed over the last decade.The authors utilized fluorescent properties of lipofuscin to study the health and viability of the retinal pigment epithelium (RPE)-photoreceptor complex.Observing the intensity and distribution of FAF of various retinal diseases is helpful for ascertaining diagnosis and evaluating prognosis.In this study,we described the FAF characteristics of cystoid macular edema (CME).Methods Sixty-two patients (70 eyes) with CME were subjected to FAF and fundus fluorescein angiography (FFA) by a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2 (HRA2)).Characteristics of FAF images were compared with FFA images.Results FAF intensity in normal subjects was highest at the posterior pole and dipped at the fovea.All cases of CME showed fluorescein dye accumulated into honeycomb-like spaces in macular and formated a typical petaloid pattern or atypical petaloid pattern in the late phases of the angiography.Sixty-one eyes with CME on FAF images showed mild or moderate hyperautofluorescence petaloid pattern in fovea,the FAF patterns of these CME was perfectly corresponding with shape in their FFA images;nine eyes with CME secondary to exudative age related macular degeneration (AMD) showed expansion of the hypoautofluorescence without petaloid pattern in macula.Conclusion FAF imaging can be used as a new rapid,non-invasive and ancillary technique in the diagnosis of the majority of CME,except for AMD and small part of other fundus diseases.

  6. Role of chromatin structure modulation by the histone deacetylase inhibitor trichostatin A on the radio-sensitivity of ataxia telangiectasia.

    Science.gov (United States)

    Meschini, Roberta; Morucci, Elisa; Berni, Andrea; Lopez-Martinez, Wilner; Palitti, Fabrizio

    2015-07-01

    At present, a lot is known about biochemical aspects of double strand breaks (DBS) repair but how chromatin structure affects this process and the sensitivity of DNA to DSB induction is still an unresolved question. Ataxia telangiectasia (A-T) patients are characterised by very high sensitivity to DSB-inducing agents such as ionising radiation. This radiosensitivity is revealed with an enhancement of chromosomal instability as a consequence of defective DNA repair for a small fraction of breaks located in the heterochromatin, where they are less accessible. Besides, recently it has been reported that Ataxia Telangiectasia Mutated (ATM) mediated signalling modifies chromatin structure. In order to study the impact of chromatin compaction on the chromosomal instability of A-T cells, the response to trichostatin-A, an histone deacetylase inhibitor, in normal and A-T lymphoblastoid cell lines was investigated testing its effect on chromosomal aberrations, cell cycle progression, DNA damage and repair after exposure to X-rays. The results suggest that the response to both trichostatin-A pre- and continuous treatments is independent of the presence of either functional or mutated ATM protein, as the reduction of chromosomal damage was found also in the wild-type cell line. The presence of trichostatin-A before exposure to X-rays could give rise to prompt DNA repair functioning on chromatin structure already in an open conformation. Differently, trichostatin-A post-treatment causing hyperacetylation of histone tails and reducing the heterochromatic DNA content might diminish the requirement for ATM and favour DSBs repair reducing chromosomal damage only in A-T cells. This fact could suggest that trichostatin-A post-treatment is favouring the slow component of DSB repair pathway, the one impaired in absence of a functionally ATM protein. Data obtained suggest a fundamental role of chromatin compaction on chromosomal instability in A-T cells. Copyright © 2015 Elsevier B

  7. Variant ataxia telangiectasia: clinical and molecular findings and evaluation of radiosensitive phenotypes in a patient and relatives.

    Science.gov (United States)

    Claes, Kathleen; Depuydt, Julie; Taylor, A Malcolm R; Last, James I; Baert, Annelot; Schietecatte, Peter; Vandersickel, Veerle; Poppe, Bruce; De Leeneer, Kim; D'Hooghe, Marc; Vral, Anne

    2013-09-01

    Variant ataxia telangiectasia (A-T) may be an underdiagnosed entity. We correlate data from radiosensitivity and kinase assays with clinical and molecular data from a patient with variant A-T and relatives. The coding region of ATM was sequenced. To evaluate the functional effect of the mutations, we performed kinase assays and developed a novel S-G2 micronucleus test. Our patient presented with mild dystonia, moderately dysarthric speech, increased serum α-fetoprotein but no ataxia nor telangiectasias, no nystagmus or oculomotor dyspraxia. She has a severe IgA deficiency, but does not have recurrent infections. She is compound heterozygote for ATM c.8122G>A (p.Asp2708Asn) and c.8851-1G>T, leading to in frame loss of 63 nucleotides at the cDNA level. A trace amount of ATM protein is translated from both alleles. Residual kinase activity is derived only from the p.Asp2708Asn allele. The conventional G0 micronucleus test, based on irradiation of resting lymphocytes, revealed a radiosensitive phenotype for the patient, but not for the heterozygous relatives. As ATM is involved in homologous recombination and G2/M cell cycle checkpoint, we optimized an S-G2 micronucleus assay, allowing to evaluate micronuclei in lymphocytes irradiated in the S and G2 phases. This test showed increased radiosensitivity for both the patient and the heterozygous carriers. Intriguingly, heterozygous carriers of c.8851-1G>T (mutation associated with absence of kinase activity) showed a stronger radiosensitive phenotype with this assay than heterozygous carriers of p.Asp2708Asn (mutation associated with residual kinase activity). The modified S-G2 micronucleus assay provided phenotypic insight into complement the diagnosis of this atypical A-T patient.

  8. Dexamethasone intravitreal implant in the treatment of diabetic macular edema.

    Science.gov (United States)

    Dugel, Pravin U; Bandello, Francesco; Loewenstein, Anat

    2015-01-01

    Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood-retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ≥25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (implant offers a

  9. Future Therapies of Wet Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Makoto Ishikawa

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies.

  10. Preventing depression in age-related macular degeneration.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E; Tasman, William S

    2007-08-01

    Age-related macular degeneration is a prevalent disease of aging that may cause irreversible vision loss, disability, and depression. The latter is rarely recognized or treated in ophthalmologic settings. To determine whether problem-solving treatment can prevent depressive disorders in patients with recent vision loss. Randomized, controlled trial. Outpatient ophthalmology offices in Philadelphia, Pennsylvania. Two hundred six patients aged 65 years or older with recent diagnoses of neovascular age-related macular degeneration in one eye and pre-existing age-related macular degeneration in the fellow eye. Patients were randomly assigned to problem-solving treatment (n = 105) or usual care (n = 101). Problem-solving treatment therapists delivered 6 sessions during 8 weeks in subjects' homes. Outcomes were assessed at 2 months for short-term effects and 6 months for maintenance effects. These included DSM-IV-defined diagnoses of depressive disorders, National Eye Institute Vision Function Questionnaire-17 scores, and rates of relinquishing valued activities. The 2-month incidence rate of depressive disorders in problem-solving-treated subjects was significantly lower than controls (11.6% vs 23.2%, respectively; odds ratio, 0.39; 95% confidence interval, 0.17-0.92; P = .03). Problem-solving treatment also reduced the odds of relinquishing a valued activity (odds ratio, 0.48; 95% confidence interval, 0.25-0.96; P = .04). This effect mediated the relationship between treatment group and depression. By 6 months, most earlier observed benefits had diminished, though problem-solving treatment subjects were less likely to suffer persistent depression (chi2(1,3) = 8.46; P = .04). Problem-solving treatment prevented depressive disorders and loss of valued activities in patients with age-related macular degeneration as a short-term treatment, but these benefits were not maintained over time. Booster or rescue treatments may be necessary to sustain problem-solving treatment

  11. Age-related macular degeneration: Complement in action.

    Science.gov (United States)

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  12. Metamorphopsia assessment before and after vitrectomy for macular hole

    DEFF Research Database (Denmark)

    Krøyer, Kristian; Christensen, Ulrik; la Cour, Morten

    2009-01-01

    PURPOSE: To evaluate the degree of metamorphopsia in 42 patients before and 6 months after vitrectomy for idiopathic unilateral macular hole. METHODS: Semicircular test and reference stimuli of variable diameters were applied in a binocular test that measured interocular size disparity in patients...... after successful hole closure, interocular disparity was practically constant, with a median disparity below 0.1 and no significant effect of eccentricity. Baseline interocular disparities lower than 0.35 degrees at 1 degrees eccentricity were associated with nine EDTRS letters of better visual outcome...

  13. Choroidal and macular thickness changes induced by cataract surgery

    Directory of Open Access Journals (Sweden)

    Falcão MS

    2013-12-01

    Full Text Available Manuel S Falcão,1,2 Nuno M Gonçalves,2 Paulo Freitas-Costa,1,3 João B Beato,2 Amândio Rocha-Sousa,1,2 Ângela Carneiro,1,2 Elisete M Brandão,2 Fernando M Falcão-Reis1,21Department of Sense Organs, Faculty of Medicine, University of Porto, 2Department of Ophthalmology of Hospital de São João, 3Department of Anatomy, Faculty of Medicine, University of Porto, Porto, PortugalBackground: The aim of this study was to evaluate the effect of uneventful phacoemulsification on the morphology and thickness of the macula, the submacular choroid, and the peripapillary choroid.Methods: In 14 eyes from 14 patients, retinal macular thickness, choroidal submacular thickness, and choroidal peripapillary thickness were measured preoperatively and at one week and one month after phacoemulsification using enhanced depth imaging spectral domain optical coherence tomography. Changes in thickness of the different ocular tissues were evaluated.Results: There was a statistically significant increase in mean retinal macular thickness at one month. In horizontal scans, the mean increase was +8.67±6.75 µm (P<0.001, and in vertical scans, the mean increase was +8.80±7.07 µm (P=0.001. However, there were no significant changes in choroidal morphology in the submacular and peripapillary areas one month after surgery. In vertical scans, there was a nonsignificant increase in choroidal thickness (+4.21±20.2 µm; P=0.47 whilst in horizontal scans a nonsignificant decrease was recorded (−9.11±39.59 µm; P=0.41. In peripapillary scans, a nonsignificant increase in mean choroidal thickness was registered (+3.25±11.80 µm; P=0.36.Conclusion: Uncomplicated phacoemulsification induces nonpathologic increases in retinal macular thickness probably due to the inflammatory insult of the surgery; however these changes are not accompanied by significant changes in choroidal thickness. In the posterior segment, the morphologic response to the inflammatory insult of

  14. Vision rehabilitation of persons with age related macular degeneration.

    Science.gov (United States)

    Siemsen, Dennis W; Brown, William L

    2011-05-01

    As the population of the United States ages, there is an increase in the number of persons with age related macular degeneration (ARMD). Even as new prevention and treatment techniques are developed, the vision loss associated with ARMD may lead to loss of independence and quality of life. Low vision is a rehabilitative process designed to improve visual function and restore independence. This paper is a review of the current research related to low vision in the areas of magnification, contrast and illumination, reading, training, driving and outcomes assessment.

  15. Binocular refraction in patients with age-related macular degeneration.

    Science.gov (United States)

    Skrbek, Matej

    2013-04-01

    We've been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used to prismatic correction was spontaneous and non-problematic. Based on these results we expect to find possibly the most effective rehabilitation of vision in patients suffering from ARMD.

  16. Squalamine lactate for exudative age-related macular degeneration.

    Science.gov (United States)

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies.

  17. Practice management of french retinal specialists in diabetic macular edema

    OpenAIRE

    QU-KNAFO, Mo lise

    2015-01-01

    Purpose: To evaluate the practice management of french vitreoretinal (VR) specialists in the treatment of diabetic macular edema (DME)Methods: A 31-item survey investigating real life practice in diagnosis and treatment of DME was mailed to specialists identified from the Société Française d’Ophtalmologie and the Club Francophone des Spécialistes de la Rétine. Answers were analysed anonymously by an online survey software. Results: 95 specialists answered the survey. 25%, 36% and 32% of respo...

  18. Nutritional Modulation of Age-Related Macular Degeneration

    OpenAIRE

    Weikel, Karen A; Taylor, Allen

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 20...

  19. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  20. An unusual complication of blunt ocular trauma: A horseshoe-shaped macular tear with spontaneous closure

    Directory of Open Access Journals (Sweden)

    Umut Karaca

    2014-01-01

    Full Text Available A case of horseshoe-shaped macular tear after blunt trauma with the course of the tear and the relevant findings obtained by spectral-domain optical coherence tomography (SD-OCT is described. A 21-year-old man who had suffered blunt trauma 5 days previously visited our clinic complaining of vision loss in his left eye. Ophthalmic examination and SD-OCT images revealed a horseshoe-shaped macular tear. A month later at the second visit, the macular tear was found to have spontaneously closed. There have been many cases reported previously of the spontaneous closure of traumatic macular holes. A horseshoe-shaped macular tear is an atypical clinical presentation. However, the mechanism of spontaneous closure is hypothetically as same as that for a macular hole. High-resolution images and three-dimensional maps taken with SD-OCT can provide more details on macular diseases and are more useful than time-domain OCT images.