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 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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Financial support included The Joseph Albert Hekimian Fund (MSS), Andreas C. Dracopoulos Professorship (MSS), Andreas C. Dracopoulos and Daniel Finkelstein M.D. Rising Professorship in Ophthalmology (JJD), Wilmer Eye Institute Retina Rising Professorship (IA). The sponsor or funding organization had no role in the design or conduct of this research.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Johns Hopkins University gave ethical approval for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Footnotes

↵a Joint-first authorship

Financial Support: The Joseph Albert Hekimian Fund (MSS), Andreas C. Dracopoulos Professorship (MSS), Andreas C. Dracopoulos and Daniel Finkelstein M.D. Rising Professorship in Ophthalmology (JJD), Wilmer Eye Institute Retina Rising Professorship (IA). The sponsor or funding organization had no role in the design or conduct of this research.

Conflict of Interest: No conflicting relationship exists for any author.

Data Availability

All data produced in the present study are available upon reasonable request to the authors

Abbreviations and AcronymsACMGAmerican College of Medical Genetics and GenomicsarRPautosomal recessive retinitis pigmentosaBCVAbest-corrected visual acuityBESTBest disease (e.g. Bestrophinopathy & Best vitelliform macular dystrophy)CDcone dystrophyCIconfidence intervalCLIAClinical Laboratory Improvement AmendmentsCRDcone-rod dystrophyFDAFood and Drug AdministrationFFBFoundation Fighting BlindnessGEDgenetic eye disorderGEDiGenetic Eye Disease CenterHIPAAHealth Insurance Portability and Accountability ActHLEHispanic or Latino ethnicityIRDinherited retinal diseaseIQRinterquartile rangeLASSOleast absolute shrinkage and selection operatorlogMARlogarithm of the Minimum Angle of ResolutionL-ORDlate-onset retinal degenerationNIHNational Institutes of HealthOCAoculocutaneous albinismONoptic neuropathyORodds ratioPDpattern dystrophyP/LPpathogenic or likely pathogenicRPretinitis pigmentosaRPEretinal pigment epitheliumSTGDStargardt diseaseUSHUsher syndromeU.S.United StatesVUSvariant of uncertain significance