Cone Structure and Function in RPGR- and USH2A-Associated Retinal Degeneration

center dot PURPOSE: To compare cone structure and function be-tween RPGR-and USH2A-associated retinal degenera-tion.center dot DESIGN: Retrospective, observational, cross-sectional study.center dot METHODS: This multicenter study included 13 eyes (9 participants) with RPGR-related X-linked retinitis pigmentosa (RPGR), 15 eyes (10 participants) with USH2A-related Usher syndrome type 2 (USH2), 16 eyes (9 participants) with USH2A-related autosomal reces-sive retinitis pigmentosa (ARRP), and 7 normal eyes (6 participants). Structural measures included cone spacing and density from adaptive optics scanning laser ophthal-moscopy and photoreceptor inner segment (IS), outer segment (OS), and outer nuclear layer (ONL) thickness from optical coherence tomography (OCT) images. OCT angiography images were used to study choriocapillaris flow deficit percent (CCFD). Cone function was assessed by fundus-guided microperimetry. Measures were com-pared at designated regions using analysis of variance with pairwise comparisons among disease groups, adjusted for disease duration and eccentricity.center dot RESULTS: OCT segmentation revealed shorter OS and IS, with reduced ONL thickness in RPGR compared to normal (OS: P < .001, IS: P = .001, ONL: P = .005), USH2 (OS: P = .01, IS: P = .03, ONL: P = .03), or ARRP (OS: P = .001, ONL: P = .03). Increased cone spacing was observed in both RPGR ( P = .03) and USH2 compared with normal ( P = .048). The mean CCFD in RPGR was greater than in USH2 ( P = .02). Mi-croperimetry demonstrated below-normal regional sensi-tivity in RPGR ( P = .004), USH2 ( P = .02), and ARRP ( P = .009), without significant intergroup differences.center dot CONCLUSIONS: Outer retinal structure and chori-ocapillaris perfusion were more abnormal in RPGR-than USH2A-related retinal degenerations, whereas there were no significant differences in below-normal regional sensitivity between each rod-cone degeneration associated with variants in these 2 genes expressed at the photoreceptor-connecting cilium. (Am J Ophthalmol 2023;250: 1-11.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ))