Microperimetry Sensitivity Changes at the Functional Transition Zone and at the EZ Margins in X-Linked Retinitis Pigmentosa Treated With Gene Therapy.

Purpose: To evaluate the structure-function relationship between the photoreceptor ellipsoid zone (EZ) and functional transition zone (FTZ) in X-linked retinitis pigmentosa (XLRP) eyes treated with gene therapy.

Methods: In a post-hoc analysis of the Skyline trial, baseline OCT volumes were segmented to generate an en-face map of intact EZ, and after registration with microperimetry (MP) image, the transformed EZ map was used to delineate the EZ margin. FTZ was defined by microperimetry absolute scotomatous points. Non-scotomatous loci adjacent to FTZ, and inside the EZ margin, were analyzed. We quantified the percentage of loci with ≥7 dB sensitivity improvements over 12 months and the average treatment effect (ATE; difference in mean sensitivity change between treated and untreated eyes).

Results: Twenty-four eyes (12 treated, 12 untreated; seven high-dose, five low-dose) were analyzed. Baseline distance to the EZ margin did not correlate with loci achieving ≥7 dB improvement at month 12 in either dose group. High-dose eyes showed a higher mean percentage of loci with ≥7 dB improvement than untreated eyes for the entire grid, but not on regional analysis. High-dose subjects also showed higher ATE than untreated eyes in all retinal zones.

Conclusions: High-dose AAV-RPGR gene therapy was associated with improved MP outcomes and greater ATE inside FTZ and intact EZ; however, loci with ≥7 dB improvement did not correlate with baseline EZ margin distance, highlighting challenges in prespecifying localized ≥7 dB changes.

Translational relevance: Identifying and selecting retinal regions that are likely to show sensitivity improvements may benefit future clinical trials of ocular gene therapy.