Proteomics-based approach for differentiation of age-related macular degeneration sub-types

Purpose:Age-related macular degeneration (AMD) is one of the leading causes of irreversible central vision loss in the elderly population. The current study aims to find non-invasive prognostic biomarkers in the urine specimens of the AMD patients.Methods:Peripheral blood and urine samples were collected from 23 controls and 61 AMD patients. Genomic DNA was extracted from the buffy coat of peripheral blood. Allele specific PCR was used to assay SNPs in complement factor H (CFH), complement component 3 (C3). Comparative proteomic analysis of urine samples from early AMD, choroidal neovascular membrane (CNVM), geographic atrophy (GA), and healthy controls was performed using isobaric labelling followed by mass spectrometry. Validation was performed using enzyme-linked immunosorbent assay (ELISA).Results:Comparative proteomic analysis of urine samples identified 751 proteins, of which 383 proteins were found to be differentially expressed in various groups of AMD patients. Gene ontology classification of differentially expressed proteins revealed the majority of them were involved in catalytic functions and binding activities. Pathway analysis showed cell adhesion molecule pathways (CAMs), Complement and coagulation cascades, to be significantly deregulated in AMD. Upon validation by ELISA, SERPINA-1 (Alpha1 antitrypsin), TIMP-1 (Tissue inhibitor of matrix metaloprotease-1), APOA-1 (Apolipoprotein A-1) were significantly over-expressed in AMD (n = 61) patients compared to controls (n = 23). A logistic model of APOA-1 in combination with CFH and C3 polymorphisms predicted the risk of developing AMD with 82% accuracy.Conclusion:This study gives us a preliminary data on non-invasive predictive biomarkers for AMD, which can be further validated in a large cohort and translated for diagnostic use.     

Impact of glaucoma on visual functioning in indians

Purpose. To evaluate the impact of glaucoma on visual functioning in Indians. Methods. Patients attending the glaucoma service who had undergone a comprehensive glaucoma evaluation were recruited. Better mean deviation (MD, using Humphrey Field Analyzer program 24-2) between two eyes was used to classify participants into mild, moderate, and severe visual field (VF) loss groups. Participants were administered the Glaucoma Quality of Life-15 (GQL-15) questionnaire. Rasch analysis was used to validate the GQL-15 and its four subscales. Linear regression was used to determine associations between GQL-15 scores and VF loss after adjusting for sociodemographic variables. Results. A total of 198 patients (mean age ± SD, 59.8 ± 12.3 years; 67% male) were recruited. Participants with severe VF loss (39%) followed by mild loss (35%) comprised the largest group. Rasch analysis resulted in a 10-item reliable and valid questionnaire: the Glaucoma Activity Limitation-10 (GAL-10). Although a single subscale, "peripheral vision," met requirements of the Rasch model, it could not be preserved in the GAL-10. In multivariate analyses, the middle-income group (compared with higher income) and severe VF-loss (compared with mild VF-loss) participants reported significantly poorer functioning on GAL-10 ([β = 0.84; 95% confidence interval (CI), 0.16-1.52; P = 0.02] and [β = 1.19; 95% CI, 0.61-1.78; P < 0.000], respectively). None of these associations were, however, clinically significant. Conclusions. Glaucoma patients in India, especially those with severe VF loss, face significant challenges in performing daily tasks and in mobility. It is important to prevent progression such that activity limitation is minimized in glaucoma patients.     

Evaluation of blotchy pigments in the anterior chamber angle as a sign of angle closure

Background:

Blotchy pigments in the anterior chamber (AC) angle are considered diagnostic of primary angle closure (PAC). But there are no reports either on the prevalence of blotchy pigments in AC angles or the validity of this sign.

Aims:

To determine the prevalence of blotchy pigments in AC angles and to evaluate their relationship with glaucomatous optic neuropathy (GON) in eyes with occludable angles.

Setting and Design:

Cross-sectional, comparative study.

Materials and Methods:

Gonioscopy was performed in 1001 eyes of 526 subjects (245 eyes of 148 consecutive, occludable angle subjects and 756 eyes of 378 non-consecutive, open angle subjects), above 35 years of age. Quadrant-wise location of blotchy pigments was documented.

Statistical Analysis:

Odds of blotchy pigments in occludable angles against that in open angles were evaluated. Relationship of GON with blotchy pigments in occludable angle eyes was evaluated using a multivariate model.

Results:

Prevalence of blotchy pigments in occludable angles was 28.6% (95% CI, 22.9-34.3) and in open angles was 4.7% (95% CI, 3.2-6.3). Blotchy pigments were more frequently seen in inferior (16%) and superior quadrants (15%) of occludable angles, and inferior quadrant of open angles (4%). Odds of superior quadrant blotchy pigments in occludable angles were 33 times that in open angles. GON was seen in 107 occludable angle eyes. Blotchy pigments were not significantly associated with GON (odds ratio = 0.5; P = 0.1).

Conclusions:

Blotchy pigments were seen in 28.6% of occludable angle eyes and 4.7% of open angles eyes. Presence of blotchy pigments in the superior quadrant is more common in occludable angles. Presence of GON in occludable angle eyes was not associated with blotchy pigments.     

“Venous congestion” as a cause of subcortical white matter T2 hypointensity on magnetic resonance images

Subcortical T2 hypointensity is an uncommon finding seen in very limited conditions such as multiple sclerosis, Sturge-Weber syndrome, and meningitis. Some of the conditions such as moyamoya disease, severe ischemic-anoxic insults, early cortical ischemia, and infarcts are of “arterial origin.” We describe two conditions in which “venous congestion” plays a major role in T2 hypointensity — cerebral venous sinus thrombosis (CVST) and dural arteriovenous fistula (dAVF). The third case is a case of meningitis, showing T2 hypointensity as well, and can be explained by the “venous congestion” hypothesis. The same hypothesis can explain few of the other conditions causing subcortical T2 hypointensity.