Disease and Participant-Related Correlates of Genetic Testing Completion for Hereditary Eye Disorders in a Cohort of Over 1800 Patients
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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 1809 participants (median age at presentation 44 years, symptom onset 28 years; median follow-up 5.2 years), 72% (1296) completed genetic testing, with a molecular diagnosis achieved in 63%, inconclusive results in 21%, and no diagnosis in 16%. GT completion was more likely among younger participants with earlier symptom onset, longer follow-up, and worse visual acuity (VA). Molecular diagnosis was more likely in participants with earlier symptom onset, worse 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] 0.48 [0.37-0.63]; Other: 0.52 [0.35-0.78]) and receiving a molecular diagnosis (Black: 0.39 [0.28-0.54]; Other: 0.62 [0.38-0.99]), and consistently exhibited worse VA at both baseline and follow-up. Notably, Black and Other race participants presented at significantly younger ages than White participants, and disparities in GT completion and visual outcomes persisted despite equivalent or shorter time from presentation to GT, suggesting barriers arise independently of delays in care engagement. Among solved cases, 132 causative genes were identified; ABCA4 , USH2A , PRPH2 , RHO , and BEST1 accounted for 45% of molecular diagnoses.
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.
