Refractive Error in Inherited Retinal Disease

Abstract

Purpose: Inherited retinal dystrophies (IRDs) lead to significant vision impairment. Refractive errors (REs) are also associated with vision impairment and an increased risk of ocular comorbidities and may compound impairment caused by IRDs. Identifying the pattern of RE in IRDs may assist in better management of patients with IRD and provide insights into understanding genetic associations with RE. The aim of this study was to investigate the patterns of RE in patients with IRD from three academic ophthalmology referral centers.

Design: Retrospective multicenter cohort study.

Methods: Chart review of clinically and molecularly confirmed IRD cases seen at the University of California San Diego, Oregon Health and Science University, and Children's Hospital Los Angeles. Data retrieved included patient demographics, disease phenotype, genotype, best-corrected visual acuity, objective, and/or subjective refraction.

Results: A total of 1942 patients' notes were reviewed. Of these, 634 patients (1255 eyes) had refractive data. For genes associated with myopia, NYX (n = 14 [1%]) was associated with the highest spherical equivalent RE of myopia (mean -9.26 diopters [D] [95% CI -11.867 to -6.651], P < .001) followed by IMPG2 (n = 16 [1.1%]) (mean -4.062 D [95% CI -6.254 to -1.871], P = .002), then RPGR (n = 104 [7.2%]) (mean -2.664 D [95% CI -3.618 to -1.710], P = .016) and for genes associated with hyperopia, BEST1 (n = 38 [2.6%]) had the highest spherical equivalent RE for hyperopia (mean 2.996 D [95% CI 1.830-4.162], P < .001) followed by RS1 (n = 26 [1.8%]) (mean 2.562 D [95% CI 1.454-3.671], P < .001), then CNGA3 (n = 28 [1.9%]) (mean 0.603 D [95% CI -0.48 to 1.686], P = .009). Overall, patients with IRD were significantly more myopic than age-matched control participants.

Conclusion: By combining genetic testing with refraction data from a large cohort of patients, we identify IRD genes associated with myopia and hyperopia. However, we find that the pattern of ametropia varies widely not only by gene but also within a gene cohort. The genes identified to be associated with RE are candidates for further in-depth investigation to understand their functional role in RE.