Refractive Error in Inherited Retinal Disease: A review of Findings from Three Academic Centers.

Abstract

Purpose : The prevalence of ametropia in inherited retinal dystrophies (IRDs) and its genetic associations is poorly studied. We aim to address this knowledge gap by performing a retrospective cross-sectional study of ametropia in a cohort of IRD patients reviewed at three academic ophthalmology referral centers.

Methods : Cases were included from the dystrophy clinics of the Shiley Eye Institute, University of California San Diego, Casey Eye Institute, Oregon Health and Science University and Children Hospital of Los Angeles. Patients were included with clinically and molecularly confirmed IRD. Data reviewed included age, gender, disease phenotype and genotype, best corrected visual acuity, objective, and subjective refraction. Distributions and mean spherical equivalent (SE) were calculated for causal genes. The Analysis of SE was conducted through Linear Mixed Effects modeling, with a random intercept to account for intercorrelated subject eyes. Statistical analyses were performed using the R statistical software (R Version 4.2.2).

Results : In total 768 patients were included, 412 (54%) were males, mean age was 34.9 years (33.4, 36.4). Of these, 669 patients (1307 eyes) had refractive data, 388 patients (58%) (696 eyes, 53%) were ametropic (Fig. 1). Investigating genes associated with myopia (Fig. 2), RP1 (n=34, 2.2%) had the highest odds ratio of myopia (3.466, P=0.002; SD=2.4); followed by RPGR (n=104, 6.8%)(1.933, P=0.006; SD=4.47); and ABCA4 (n= 150, 9.8%)(1.494, P=0.05; SD=2.36). For genes associated with hyperopia (Fig.2), CRB1 (n= 22, 1.4%) had the highest odds ratio of hyperopia (8.678 P<0.001; SD=4.1); followed by BEST1 (n= 46, 3%)(8.172, P<0.001; SD=3.15); and RS1 (n= 26, 1.7%)(6.539, P<0.001; SD=2.62). n=number of eyes, 2 eyes per subject was used for SE analysis when available.

Conclusions : Ametropia was commonly seen in IRD patients. The pattern of error of refraction varied widely by causal gene. Our findings confirm previous reports that some genes, such as RP1 were associated with myopia, as well as other genes such as CRB1 were associated with hypermetropia. However, the genes identified require further validation in larger cohorts and are candidates for more in-depth investigation in functional studies of refractive error.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1: Overall prevalence of Ametropia.

 

Figure 2: Box plot of Mean SER by Causal Gene