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

Purpose: To compare cone structure and function between RPGR- and USH2A-associated retinal degeneration.

Design: Retrospective, observational, cross-sectional study.

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 recessive retinitis pigmentosa (ARRP), and 7 normal eyes (6 participants). Structural measures included cone spacing and density from adaptive optics scanning laser ophthalmoscopy 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 compared at designated regions using analysis of variance with pairwise comparisons among disease groups, adjusted for disease duration and eccentricity.

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). Microperimetry demonstrated below-normal regional sensitivity in RPGR (P = .004), USH2 (P = .02), and ARRP (P = .009), without significant intergroup differences.

Conclusions: Outer retinal structure and choriocapillaris 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.