Disease and Participant-Related Correlates of Genetic Testing Completion for Hereditary Eye Disorders in a Cohort of over 1400 Patients

Abstract Objective To identify clinical and demographic predictors of genetic testing (GT) completion and diagnostic yield among patients with genetic eye disorders (GED) at a large U.S. tertiary academic center. Design Retrospective cohort study. Participants Patients with clinically diagnosed GEDs evaluated at the Wilmer Eye Institute’s Genetic Eye Disease (GEDi) Center between 2002 and 2025. Methods Demographic, clinical, and GT data were extracted. Bivariate analyses and multivariable logistic regression identified factors associated with GT completion and molecular diagnosis. Subgroup analyses examined racial disparities between Black, non-Hispanic White, and Other race participants. Main Outcome Measures Proportion of patients completing GT, molecular diagnostic yield, and clinical/demographic predictors of each. Results Of 1466 participants (median age at presentation 44 years, symptom onset 28 years; median follow-up 6 years), 74% (1088) completed genetic testing, with a likely molecular diagnosis achieved in 62%, inconclusive results in 22%, and no diagnosis in 16%. GT completion was more likely among younger participants with earlier symptom onset, and longer follow-up. Likely molecular diagnosis was more likely in participants with earlier symptom onset, worse visual acuity (VA), male sex, and syndromic or X-linked phenotypes. Black and Other race participants had significantly lower odds of completing GT (Black: OR [95% CI] 0.40 [0.30-0.53]; Other: 0.57 [0.36-0.92]) and receiving a likely molecular diagnosis (Black: 0.37 [0.26-0.51]; Other: 0.58 [0.35-0.98]), and consistently exhibited worse VA at both baseline and follow-up. Notably, among Black and Other race participants, disparities in GT completion and visual outcomes persisted despite equivalent or shorter time from presentation to GT completion, suggesting barriers arise independently of delays in care engagement. We identified 118 causative genes among participants with likely molecular diagnoses, with ABCA4 , USH2A , PRPH2 , RHO , and BEST1 accounting for 47% of cases. Conclusions This is the largest single-center GED genetic testing cohort reported in the U.S. and reveals significant disparities in GT completion and yield by race, age, sex, and disease-level factors. Our findings underscore the need to expand early access to GT, diversify genomic databases, and address systemic barriers to ensure equity in GED diagnosis, clinical trial access, and delivery of emerging therapies.