Early onset cone photoreceptor degeneration as a risk factor for high myopia in RPGR-retinal dystrophy

Abstract

Purpose : High myopia is a feature of several inherited retinal dystrophies, including X-linked retinitis pigmentosa (XLRP) which is characterised by early onset, centripetal photoreceptor degeneration and rapid progression to blindness by the fourth decade. Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene cause over 70% of XLRP cases. It presents phenotypic variability, but the rod-cone phenotype predominates and reduced glutamylation of RPGR protein is a risk factor for the cone dystrophy phenotype. This retrospective study evaluates trends in myopia in patients with RPGR-retinal dystrophy.

Methods : Data from 14 phakic male patients were collected from a single centre and analysed. This included visual acuity, refractive error, axial length, self-reported onset of spectacle use and nyctalopia, clinical phenotype and genotype. A linear mixed model determined the influence of axial length on refractive error.

Results : Mean ETDRS letter score was 67 and 61 for cone-rod and rod-cone phenotypes respectively. The median (interquartile range) refractive error was –10.31 DS [4.81] and –3.06 DS [4.38]. A significant negative correlation was found between spherical equivalent refractive error and axial length (p=0.031), indicating axial myopia in this cohort. Phenotyping identified two categories: cone-rod (n=5) and rod-cone degeneration (n=9). High axial myopia showed preponderance in cone-rod degenerations. Median self-reported onset of nyctalopia was age 20 and 8.5 in cone-rod and rod-cone degenerations respectively, and onset of spectacle use was age 5 for both phenotypes. Two outliers were examined in a case series discussion. These outliers were a severe rod-cone phenotype with high myopia and a slow progressing cone-rod phenotype with low myopia.

Conclusions : Trends within this RPGR-retinal dystrophy cohort suggest that if cone photoreceptor degeneration occurs during the critical development period, there is a predisposition to higher myopia. A novel myopigenic factor is proposed; image degradation primarily due to cone photoreceptor dysfunction may act as a stimulus to drive myopia development in early childhood. Further controlled studies are required to ascertain the clinical significance of these associations.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Figure 1. Violin plot distribution of spherical equivalent refractive error (DS) in cone-rod and rod-cone RPGR-retinal dystrophy