Valeria Nagy

Trombophilic screening for nonarteritic anterior ischemic optic neuropathy

BackgroundNonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic infarction of the optic nerve head, frequently leading to sudden, mostly irreversible loss of vision. In this study blood thrombophilic factors, as well as cardiovascular risk factors were investigated for their relevance to this pathology. Trombophilic risk factors so far not evaluated were included in the study.Patients and methods37 NAION patients (4 with sequential second eye involvement) and 81 matched control subjects were examined. From blood, protein C, protein S, antithrombin, von Willebrand antigen levels (vWFAg), and factor V (Leiden) mutation, factor VIIIC level, plasminogen activity, lipoprotein (a) and fibrinogen levels, and presence of anticardiolipin antibodies were investigated. Possibly relevant pathologies [e.g. diabetes mellitus (DM), hypertension, and ischemic heart disease] were also registered.ResultsElevated Lp(a) and vWFAg levels, DM, F V (Leiden), hypercholesterolemia, and hyperfibinogenemia proved to be significant risk factors associated with NAION. Forward stepwise logistic regression analysis revealed that high Lp(a), DM, and FV (Leiden) were the main predictive components, with odds ratios 16.88 (p=0.012), 5.78 (p=0.022) and 4.44 (p=0.033), respectively.ConclusionsBased on our results it appears that thrombophilia is likely to contribute to the development of NAION besides vascular damage due to the presence of cardiovascular risk factors. Further data are needed, however, to justify the suggested use of secondary prophylaxis using anticoagulant/antiplatelet therapy.

Tear fluid proteomics multimarkers for diabetic retinopathy screening

BackgroundThe aim of the project was to develop a novel method for diabetic retinopathy screening based on the examination of tear fluid biomarker changes. In order to evaluate the usability of protein biomarkers for pre-screening purposes several different approaches were used, including machine learning algorithms.MethodsAll persons involved in the study had diabetes. Diabetic retinopathy (DR) was diagnosed by capturing 7-field fundus images, evaluated by two independent ophthalmologists. 165 eyes were examined (from 119 patients), 55 were diagnosed healthy and 110 images showed signs of DR. Tear samples were taken from all eyes and state-of-the-art nano-HPLC coupled ESI-MS/MS mass spectrometry protein identification was performed on all samples. Applicability of protein biomarkers was evaluated by six different optimally parameterized machine learning algorithms: Support Vector Machine, Recursive Partitioning, Random Forest, Naive Bayes, Logistic Regression, K-Nearest Neighbor.ResultsOut of the six investigated machine learning algorithms the result of Recursive Partitioning proved to be the most accurate. The performance of the system realizing the above algorithm reached 74% sensitivity and 48% specificity.ConclusionsProtein biomarkers selected and classified with machine learning algorithms alone are at present not recommended for screening purposes because of low specificity and sensitivity values. This tool can be potentially used to improve the results of image processing methods as a complementary tool in automatic or semiautomatic systems.

Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and Tear Fluid Proteomics Biomarkers

Background. It is estimated that 347 million people suffer from diabetes mellitus (DM), and almost 5 million are blind due to diabetic retinopathy (DR). The progression of DR can be slowed down with early diagnosis and treatment. Therefore our aim was to develop a novel automated method for DR screening. Methods. 52 patients with diabetes mellitus were enrolled into the project. Of all patients, 39 had signs of DR. Digital retina images and tear fluid samples were taken from each eye. The results from the tear fluid proteomics analysis and from digital microaneurysm (MA) detection on fundus images were used as the input of a machine learning system. Results. MA detection method alone resulted in 0.84 sensitivity and 0.81 specificity. Using the proteomics data for analysis 0.87 sensitivity and 0.68 specificity values were achieved. The combined data analysis integrated the features of the proteomics data along with the number of detected MAs in the associated image and achieved sensitivity/specificity values of 0.93/0.78. Conclusions. As the two different types of data represent independent and complementary information on the outcome, the combined model resulted in a reliable screening method that is comparable to the requirements of DR screening programs applied in clinical routine.

Hepatitis C virus presumably associated bilateral consecutive anterior ischemic optic neuropathy

Purpose To report a case of bilateral nonarteritic anterior ischemic optic neuropathy (NAION) in a hepatitis C (HCV) infected patient and demonstrate the relationship between HCV and the development of NAION. Methods Case report. Results A 43-year-old woman with chronic HCV infection and long-term euthyroid autoimmune thyroiditis suddenly lost vision in her right eye, and 6 months later in her left eye, due to NAION. Slightly elevated levels of aminotransferases suggested liver infection activity. Anti-HCV antibody was detected; the genotype of the virus was 1b and the viral RNA level was 1.8 × 106 IU/mL. Liver biopsy proved chronic active hepatitis (Ishak score grading: 7, staging: 2). Except for the elevated levels of antithyroid antibodies and a weak antinuclear factor, the detailed laboratory examinations (thrombophilia, cryoglobulin, anticardiolipin antibodies, co-infections) revealed no other abnormalities; a causative relationship between the underlying chronic hepatitis C and bilateral NAION therefore seems probable. The patient was treated with pegylated interferon and ribavirin for 1 year and a sustained viral remission could be achieved. Her vision has neither improved nor deteriorated further. Conclusions This appears to be the first reported case of bilateral NAION presumably caused by HCV infection.

Bilateral Central Retinal Vein Occlusion Caused By Malignant Hypertension in a Young Patient

Central retinal vein occlusion (CRVO) occurring simultaneously in both eyes is a rare condition, in such cases usually associated with severe systemic disease. Overall, only 10% of all CRVO patients are younger than 40 years. A relatively young patient reported with simultaneous bilateral CRVO associated with chronic kidney disease and malignant hypertension. A case of a 35-year-old male patient presented with the complaint of decreased vision in both eyes. Ophthalmic examination revealed bilateral CRVO. Chronic kidney disease leading to malignant hypertension and hyperviscosity was diagnosed as the underlying cause. Clinical support and medical therapy effectively controlled the hypertension, leading to improvement of both the systemic and ocular changes. To the best of our knowledge, this is the first case report of simultaneous bilateral CRVO in a young patient associated with chronic renal failure and malignant hypertension. Primary care providers, either ophthalmologists or physicians, need to consider both common and atypical risk factors for retinal vein occlusion, in order to prevent further ocular morbidity and systemic complications.

Thrombophilic screening in retinal artery occlusion patients.

Background Retinal artery occlusion (RAO) is an ischemic vascular damage of the retina, which frequently leads to sudden, mostly irreversible loss of vision. In this study, blood thrombophilic factors as well as cardiovascular risk factors were investigated for their relevance to this pathology. Thrombophilic risk factors so far not evaluated were included in the study. Patients and methods 28 RAO patients and 81 matched control subjects were examined. From blood samples, protein C, protein S, antithrombinopathy, and factor V (Leiden) mutation (FV), factor II gene polymorphism, factor VIIIC level, plasminogen activity, lipoprotein(a) and fibrinogen levels, hyperhomocysteinemia and presence of anticardiolipin – antiphospholipid antibodies were investigated. Possibly relevant pathologies such as diabetes mellitus, hypertension, and ischemic heart disease were also registered. Statistical analysis by logistic regression was performed with 95% confidence intervals. Results In the group of patients with RAO only the incidence of hypertension (OR: 3.33, 95% CI: 1.30–9.70, p = 0.014) as an average risk factor showed significant difference, but thrombophilic factors such as hyperfibrinogenemia (OR: 2.9, 95% CI: 1.29–6.57, p = 0.010) and the presence of FV (Leiden mutation) (OR: 3.9, 95% CI: 1.43–10.96, p = 0.008) increased the chances of developing this disease. Conclusions Our results support the assumption that thrombophilia may contribute to the development of RAO besides vascular damage due to the presence of cardiovascular risk factors. Further studies are needed, however, to justify the possible use of secondary prophylaxis in form of anticoagulant/antiplatelet therapy.

Analysis of optic disc damage by optical coherence tomography in terms of therapy in non-arteritic anterior ischemic optic neuropathy.

This study aimed to assess the relationship between the rate of nerve fiber loss in non-arteritic anterior ischemic optic neuropathy (NAION) and time delay before therapy. Total 24 patients received the same treatment within or after 2wk (early and late groups). There were significantly lower level of destruction of nerve fibers (P=0.0014) and significantly better visual field sensitivity (P=0.039) in early group. The results indicate that therapy should be started within 2wk. The degree of ischemic damage due to NAION correlates well with retinal nerve fiber layer thickness and the ischemia-induced decrease in visual field sensitivity.

Vascular endothelial growth factor levels in tears of patients with retinal vein occlusion

PurposeWe measured vascular endothelial growth factor (VEGF) levels in tear fluid and serum in patients with retinal vein occlusion (RVO).Patients and methodsEight patients with RVO due to secondary macular oedema were examined. VEGF levels were measured by enzyme-linked immunosorbent assay. All patients had a full ophthalmic examination (visual acuity, slit lamp biomicroscopy, perimetry, and fluorescein angiography). Central retinal thickness (CRT) was examined using optical coherence tomography (OCT). Tear and serum samples were collected and examinations were performed at diagnosis and 1 and 4 weeks later.ResultsVEGF levels in the tears of RVO eyes were significantly higher than in fellow eyes at diagnosis and after both 1 and 4 weeks (paired t test, p1 = 0.01, p2 = 0.02, p3 = 0.006). We found a weak but significant positive correlation between VEGF levels in tear fluid and serum of patients with RVO (r = 0.21), while this correlation tended to be stronger between the fellow eyes and serum levels (r = 0.33).ConclusionTo the best of our knowledge, we are the first to report an increased level of VEGF in the tear fluid of patients with RVO. Alterations of VEGF levels in tears may be useful for determining stages of RVO. This non-invasive and objective method may also be helpful for estimating the severity of macular oedema and efficacy of treatment.

Curbside Consultation in Neuro-Ophthalmology—49 Clinical Questions. Eds: Andrew G. Lee, Paul W. Brazis and Lanning B. Kline. ISBN: 978-1-55642-840-1 SLACK Incorporated

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