Abstract
Purpose :
Ametropia has been associated with Inherited Retinal Dystrophies (IRDs). However, the prevalence of ametropia in IRDs and its genetic associations is poorly studied. We aim to address this knowledge gap by studying refractive error in a cohort of IRD patients at an academic ophthalmology referral center.
Methods :
We performed a single center cross-sectional retrospective study of cases identified from the IRD database of the Shiley Eye Institute, University of California San Diego, containing all patients seen in the dystrophy clinic. Patients were included with clinical and molecular confirmed IRD. Demographic and clinical data retrieved from medical records included age, gender, disease phenotype, best corrected visual acuity, objective and subjective refraction. Distributions and mean spherical equivalent (SE) were calculated for causal genes. Analysis of SE was conducted on a per subject eye level through Linear Mixed Effects modeling. Statistical analyses were performed using R statistical software (R Version 3.6.3).
Results :
The database contained 571 patients with IRD. We represent 162 patients with clinical and molecular confirmed IRD, 82 (51%) were males, mean age was 37.6 years (SD +/-2.4). Of these, 112 patients had refractive data, 61 (54%) were ametropic (Fig. 1). Investigating genes associated with myopia, RPGR (n=10, 6%) had the highest odds ratio of myopia 403.43 (P<0.02; SE 1.90 D [SD 34.20]); followed by NYX (n=3, 2%)(78.02, P<0.04; SE 2.59 D [SD 46.62]); and ABCA4 (n= 15, 9%)(54.60, P<0.03; SE 2.92 D [SD 52.56]). For genes associated with hyperopia, NMNAT-1 (n= 3, 2%) had the highest odds ratio of hyperopia 971.57 (P<0.001; SE 2.81 D [SD 50.58]); followed by AIPL1 (n= 2, 1%)(405.45, P<0.001; SE 2.92 D [SD 52.56]); and CNGB3 (n= 3, 2%)(40.04, P<0.001; SE 3.17 D [SD 57.06]). n=number of subjects, 2 eyes per subject was used for SE analysis.
Conclusions :
Ametropia was commonly seen in IRD patients and appears similarly prevalent as in the unaffected US population which contrasts previous reports. The pattern of error of refraction varied widely by causal gene. Our findings confirm previous reports in some genes such as myopia associated with NYX. However, in our cohort, AIPL1 variants were associated with hyperopia contrasting with previous reports of myopia. Genes identified require further validation in larger cohorts but are candidates for more in-depth investigation in functional studies of refractive error.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.