Diagnostic yield of an inherited retinal disease gene panel in retinopathy of unknown origin

Abstract

Evaluating the presence of class 3, 4 and 5 genetic variants in inherited retinal disease (IRD) genes in patients with retinopathy of unknown origin (RUO). Multicentric retrospective study of RUO cases diagnosed between January 2012 and February 2022. General and ophthalmological history, complete ophthalmological examination, anti-retinal antibodies and IRD gene panel results were analyzed in every patient. Four RUO categories were defined: non-paraneoplastic autoimmune retinopathy (npAIR), unilateral pigmentary retinopathy (UPR), asymmetrical pigmentary retinopathy (APR) and acute zonal occult outer retinopathy (AZOOR). We included 12 patients (9 females) across these four RUO categories. Mean age at inclusion was 45.6 years (20 – 68 years). Seven patients demonstrated class 3 variants in IRD genes. Of these, 2 also demonstrated class 5 variants in other IRD genes. The remaining 5 patients had negative panel results. IRD gene panel analysis allowed diagnosis refinement in 1 (8.3%) npAIR patient in our RUO cohort. When considering the npAIR subpopulation only, a higher diagnostic yield of 20% (1/5 patients) was achieved. Every suspected npAIR patient should benefit from gene panel testing in order not to overlook undiagnosed IRDs. In contrast, UPR, APR and AZOOR subpopulations did not benefit from genetic analysis in this study.