Phenotypic Distinctions Between EYS- and USH2A-Associated Retinitis Pigmentosa in an Asian Population.

Abstract

Purpose: This study compares clinical characteristics of retinitis pigmentosa (RP) associated with mutations in the EYS and USH2A genes in a Southeast Asian cohort.

Methods: Prospective single-center study of families with EYS- or USH2A-associated RP seen at the Singapore National Eye Centre. Comprehensive ophthalmic evaluations, multimodal imaging, genetic testing, and longitudinal follow-up identified clinically useful differentiating features between the two genotypes.

Results: A total of 300 families with RP were enrolled, with EYS- and USH2A-associated RP, accounting for 24.7% of all probands and 50.7% of solved or likely solved cases. USH2A cases were predominantly nonsyndromic RP (75%). EYS-associated RP was more severe in functional and structural outcomes, and patients were more myopic than USH2A (SE -3.31 vs. -0.69; P < 0.0001). EYS RP displayed peripapillary nasal sparing on autofluorescence imaging more frequently than USH2A (57.6% vs. 26.7%; P = 0.006), whereas USH2A cases more often had a parafoveal ring (73.3% vs. 30.3%; P = 0.0002). Multiple logistic regression identified diagnostic features with 83.2% accuracy in distinguishing between EYS and USH2A, validated in a second unrelated clinical cohort.

Conclusions: EYS- and USH2A-associated RP have overlapping clinical presentations but can often be distinguished based on a constellation of phenotypic features including disease onset and severity, refractive error, and fundus autofluorescence. These diagnostic features may support a more effective diagnostic strategy for these common forms of RP.

Translational relevance: Distinct clinical features differentiating EYS- and USH2A-associated RP provide valuable diagnostic tools that may inform personalized management and facilitate targeted interventions in clinical practice.