Anatomic and functional retinal changes in female carriers of pathogenic variants in RPGR gene

Abstract

Purpose : To investigate morpho-functional retinal correlation in female carriers with mutations in RPGR gene

Methods : The current study included 25 female carriers of mutations in RPGR gene from 17 separate families. They underwent: best visual corrected acuity (BCVA), anterior segment biomicroscopy, fundus examination, color fundus imaging, Fundus Autofluorescence (FAF), Semi-automatic Kinetic Visual Field (SKVF), Spectral-Domain Optical Coherence Tomography (SD-OCT), and full-field Electroretinography (ERG).

Results : At a mean age of 49.9±15,8 years, BCVA ranged from -0.2 logMAR to hand motion (0.4 ± 0.5 logMar). About half of the carriers (12/25, 48.0%) were asymptomatic. The most frequent symptom was night blindness, referred by 11 carriers (44.0%). Most female carriers (14/25, 56%) were myopic. We graded fundus appearance according to Grover (2000): Grade 0 (normal) was observed in 19 eyes, Grade 1 (Tapetal-like retinal reflex without any pigmentary retinal changes) in 9, Grade 2 (Regional peripheral pigmentary changes) in 7 and Grade 3 (3 or more quadrants of bone spicule-like pigment or extensive peripheral areas of atrophy) in 15 eyes. Most subjects had normal OCT findings; however, five showed a disruption of the ellipsoid zone. ERG showed nondetectable responses in 4 subjects and a rod cone pattern in 12 subjects. Applying FAF grading proposed by Nanda (2018), Normal pattern was observed in 12 eyes, Radial pattern in 14, Focal pigmentary pattern in 10 and Male pattern in 14 eyes. We observed Radial and Focal patterns even in absence of fundus alterations in 9 eyes and 1 eye, respectively. Statistical analysis comparing FAF patterns showed that the Male pattern was associated with significantly (p-value<0.01) worse BCVA, more restricted SKVF (I4e and V4e stimulus size), reduced ERG responses, and thinner CRT. Furthermore, eyes with Radial and Focal pigmentary patterns were significantly (p-value<0.01) associated with both restricted SKVF (I4e size) and reduced ERG amplitude compared to normal FAF pattern.

Conclusions : This study confirms the wide variability of the phenotype spectrum of mutation carriers in the RPGR gene, showing the usefulness of autofluorescence images in highlighting retinal alterations even in subjects with normal fundus appearance. Moreover, it enables to identify carriers with a severe phenotype, who could benefit from gene therapy.

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