Localised cone density and retinal sensitivity changes in female carriers of RPGR mutations

Abstract

Purpose : Heterozygous RPGR mutations may cause progressive photoreceptor degeneration in female carriers. In this single-center, retrospective, observational study, we assessed retinal structure and function in female carriers of RPGR mutations.

Methods : Adaptive optics (AO) imaging and microperimetry (MAIA) were performed in female carriers of RPGR mutations. Cone density (CD) at 1.4° (4 loci/eye) and 3.2° (8 loci/eye) from the foveal center, and point-wise sensitivity (PWS) at 68 loci spanning central 20° (the 10-2 test grid) were analysed (Figure 1). Normality of measured values was defined against 10 (AO cohort) and 25 (MAIA cohort) age-matched healthy controls: normal < 1 SD, moderate defect 1–2 SD and severe defect > 2 SD from the normal average.

Results : AO and MAIA data were available in 8 and 12 patients, respectively. CD at 1.4° and 3.2° eccentricities showed severe defect in at least 2 locations in 4/8 and 5/8 patients, respectively (overall 38 locations at both eccentricities across the cohort). Severe PWS defect at 1.4° and 3.2° eccentricities was observed in at least 2 locations in 3/12 and 4/12 patients, respectively. Overall, PWS was normal in 25/38 (66%) loci with severe CD defect within the central 3.2° across the cohort (Figure 2). In addition, PWS showed at least moderate defect in ≥ 10/68 loci in 9/12 patients.

Conclusions : AO imaging and microperimetry detected localised defects in cone mosaic and retinal sensitivity in RPGR mutation carriers. Severe cone loss in locations with normal PWS in the parafoveal region suggests that structural damage preceded functional loss in this cohort.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1. Locations of cone density (CD) and pointwise sensitivity (PWS) measurements. Solid circles show the locations of MAIA 10-2 grid (N = 68 locations). CD measurement was performed on solid points located within the dotted area. Horizontal and vertical axes show the distance to foveal center (for CD) or preferred retinal locus (for PWS) in degree units. The circle located at the center represents 0, 0 coordinate.

 

Figure 2. Pointwise sensitivity (PWS) map (A, E), cone density (CD) map (B, F), PWS deviation map (C, G) and CD deviation map (D, H) in a 36 y/o (A-D) and a 26 y/o (E-H) patient. Deviation maps were calculated based on average and standard deviation (SD) in age-matched healthy controls. Severe CD defect (D) despite normal PWS (C) was noted in the parafoveal region in both patients.