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

Objective: To identify clinical and demographic predictors of genetic testing completion and diagnostic yield among patients with genetic eye disorders (GEDs) at a large US tertiary academic center. Design: A retrospective cohort study. Participants: Patients with clinically diagnosed GEDs evaluated at the Wilmer Eye Institute’s Genetic Eye Disease Center between 2002 and 2025. Methods: Demographic, clinical, and genetic testing data were extracted. Bivariate analyses and multivariable logistic regression identified factors associated with genetic testing 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 genetic testing, 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%. Genetic testing 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, male sex, and syndromic or X-linked phenotypes. Black and Other race participants had significantly lower odds of completing genetic testing (Black: odds ratio [95% confidence interval] 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 visual acuity at both baseline and follow-up. Notably, among Black and Other race participants, disparities in genetic testing completion and visual outcomes persisted despite equivalent or shorter time from presentation to genetic testing 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 United States and reveals significant disparities in genetic testing completion and yield by race, age, sex, and disease-level factors. Our findings underscore the need to expand early access to genetic testing, diversify genomic databases, and address systemic barriers to ensure equity in GED diagnosis, clinical trial access, and delivery of emerging therapies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.