Victoria Addis

Factors associated with participation by African Americans in a study of the genetics of glaucoma

ABSTRACT Objective: African Americans have been historically underrepresented in research studies. Our aim was to evaluate factors influencing enrollment in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Design: Patients approached to enroll in the POAAGG study were asked to complete a 15-item survey addressing demographic characteristics, knowledge of genetics and glaucoma, and opinions on human research. Survey responses were compared between subjects who enrolled (Enrollers) and did not enroll (Decliners) in the POAAGG study. Results: Enrollers (N = 190) were 3.7 years younger (P = 0.007) and had similar gender, education, and income level to Decliners (N = 117). Knowledge about genetics and glaucoma was similar between groups. Enrollers were more comfortable providing DNA for research studies (93.1% vs 54.1%; P < 0.001) and more likely to have participated in prior studies (P = 0.003) and consider participating in future studies (P < 0.001). Among Decliners, lack of time was the primary reason given for not enrolling. Conclusion: To increase participation of African Americans in genetic research studies, efforts should be made to raise comfort with DNA donation.

Acute Visual Changes in the Elderly

Changes in vision are common complaints among the geriatric population. Causes range from cataracts and glaucoma to cerebral strokes or other systemic diseases. Loss of vision may be the turning point from independence to dependence in an elderly persons life. This article focuses on acute vision changes and provides a systematic, symptom-based approach to the evaluation and diagnosis of these processes. It is important that the primary practitioner or geriatrician recognize and evaluate acute vision changes, determine whether a treatable or reversible condition exists, and know when to refer to an ophthalmologist or neurologist for a complete evaluation and management.

Comparative Effectiveness of Generic Latanoprost Versus Branded Prostaglandin Analogs for Primary Open Angle Glaucoma

ABSTRACT Purpose: The purpose of the study is to determine the comparative effectiveness of generic latanoprost (GL) to its branded (BL) counterpart and other brand-name prostaglandin analogs (bPGAs) in preventing the need for additional therapy in the treatment of primary open angle glaucoma (POAG). Methods: Retrospective cohort study using US commercial medical claims data. All new POAG patients from 2000 to 2015 who initiated treatment with either GL or BL were included. Exclusion occurred for having less than 2 years of time in the plan prior to diagnosis, previous use of glaucoma medications, or any diagnosis of glaucoma other than POAG at any time. Analyses compared GL to BL and also to those who received any branded PGA after 2011 (when the generic became available). Cox proportional hazard regression was used to assess the hazards of filling a prescription for a second IOP-lowering medication or having surgical intervention, individually and either outcome combined. Results: A total of 6317 and 4150 POAG patients were treated with GL and BL, respectively. After 2010, 6317 GL and 3703 brand-name prostaglandin analog (bPGA) POAG patients met criteria for inclusion. After adjustment, compared to BL, the GL conferred a reduced hazard of having a glaucoma procedure performed (hazard ratio [HR] = 0.72, 95% CI: 0.62–0.84, p < 0.001) and the combined outcome (HR = 0.90, 95% CI: 0.83–0.97, p = 0.006) but was not associated with having a second IOP medication (HR = 0.95, 95% CI: 0.87–1.03, p = 0.18). Compared to the bPGAs, however, GL conferred a reduced hazard in each comparison (second IOP medication HR = 0.87, 95% CI: 0.81–0.94, p < 0.001; surgery HR = 0.70, 95% CI: 0.61–0.81, p < 0.001; combined HR = 0.85, 95% CI: 0.79–0.92, p < 0.001). Sensitivity analyses confirmed these findings. Conclusions: GL was no less and possibly more effective in preventing the need for additional intervention than branded PGAs.

The MT-CO1 V83I Polymorphism is a Risk Factor for Primary Open-Angle Glaucoma in African American Men

Purpose We investigate the function of the V83I polymorphism (m.6150G>A, rs879053914) in the mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) gene and its role in African American (AA) primary open-angle glaucoma (POAG). Methods This study used Sanger sequencing (1339 cases, 850 controls), phenotypic characterization of Primary Open-Angle African American Glaucoma Genetics study (POAAGG) cases, a masked chart review of CO1 missense cases (V83I plus M117T, n = 29) versus wild type cases (n = 29), a yeast 2-hybrid (Y2H) cDNA library screen, and quantification of protein–protein interactions by Y2H and ELISA. Results The association of V83I with POAG in AA was highly significant for men (odds ratio [OR] 6.5; 95% confidence interval [CI] 2.0–21.3, P = 0.0001), but not for women (OR 1.1; 95% CI, 0.62–2.00, P = 0.78). POAG cases having CO1 double missense mutation (V83I + M117T, L1c2 haplogroup) had a higher cup-to-disc ratio (0.77 vs. 0.71, P = 0.04) and significantly worse visual function (average pattern standard deviation, 6.5 vs. 4.3, P = 0.009; average mean deviation −10.4 vs. −4.5, P = 0.006) when compared to matched wild type cases (L1b haplogroup). Interaction of the V83I region of CO1 with amyloid beta peptide (Aβ) was confirmed by ELISA assay, and this interaction was abrogated by V83I. A Y2H screen of an adult human brain cDNA library with the V83 region of CO1 as bait retrieved the UBQLN1 gene. Conclusions The V83I polymorphism was associated strongly with POAG in AA men and disrupts Aβ-binding to CO1. This region also interacts with a neuroprotective protein, UBQLN1.

The SCHEIE Visual Field Grading System

Objective No method of grading visual field (VF) defects has been widely accepted throughout the glaucoma community. The SCHEIE (Systematic Classification of Humphrey visual fields-Easy Interpretation and Evaluation) grading system for glaucomatous visual fields was created to convey qualitative and quantitative information regarding visual field defects in an objective, reproducible, and easily applicable manner for research purposes. Methods The SCHEIE grading system is composed of a qualitative and quantitative score. The qualitative score consists of designation in one or more of the following categories: normal, central scotoma, paracentral scotoma, paracentral crescent, temporal quadrant, nasal quadrant, peripheral arcuate defect, expansive arcuate, or altitudinal defect. The quantitative component incorporates the Humphrey visual field index (VFI), location of visual defects for superior and inferior hemifields, and blind spot involvement. Accuracy and speed at grading using the qualitative and quantitative components was calculated for non-physician graders. Results Graders had a median accuracy of 96.67% for their qualitative scores and a median accuracy of 98.75% for their quantitative scores. Graders took a mean of 56 seconds per visual field to assign a qualitative score and 20 seconds per visual field to assign a quantitative score. Conclusion The SCHEIE grading system is a reproducible tool that combines qualitative and quantitative measurements to grade glaucomatous visual field defects. The system aims to standardize clinical staging and to make specific visual field defects more easily identifiable. Specific patterns of visual field loss may also be associated with genetic variants in future genetic analysis.