Optimizing Patient Selection for Panel-Based Molecular Diagnosis in Inherited Retinal Disease: A Health Economics-Oriented Taiwanese Cohort Study.

PURPOSE: To determine whether the clinical characteristics of IRD patients are associated with the positive molecular diagnosis.

METHODS

This multi-center cross-sectional study analyzed 492 IRD patients in Taiwan enrolled between January 2018 and May 2022. Patients with clinical IRD suspicion aged between 0 and 96 years with no previous genetic diagnosis were enrolled.

RESULTS

Among the 492 patients recruited, 274 (55.7%) received a molecular diagnosis. The mean age at first visit was 49.5 years, and 245 patients (49.8%) were male. Positive genetic results were observed in 67 of 72 patients (93.1%) with onset age < 10 years, compared with 18 of 28 (64.3%) in those with onset age ≥ 50 years. Positive results were also more common in patients with a positive IRD family history, 136 of 162 (84.0%), compared with those without a family history, 138 of 179 (77.1%). In addition, patients with a previous genetic diagnosis in one family member had a higher diagnostic yield. In univariate analysis, male sex (OR 1.83; p < .01), age of onset 0-9 years (OR 3.00; p < .01), a positive IRD family history (OR 4.18; p < .05), and a previous genetic diagnosis in one family member (OR 4.24; p < .001) were associated with higher odds of a positive result. For worse-seeing-eye BCVA, diagnostic yield ranged from 68.6% in patients with normal vision to 87.5% in those with moderate visual impairment and 85.1% in those with no light perception. In the multivariate model, only worse-seeing-eye logMAR BCVA > 2.0 remained independently associated with positive testing (OR 4.80; p < .001). No negative predictors of panel-based molecular diagnosis were identified.

CONCLUSION

We discovered key patient-level demographic and clinical factors associated with increased odds of obtaining a molecular diagnosis. This study supports further evaluations of clinical characteristics that can improve the cost-benefit of panel-based genetic testing for IRD, paving the way for efficient genetic diagnostics and identifying high-risk panel-undiagnosable patients to pursue more advanced sequencing platforms.