Microperimetry Sensitivity Changes at the Functional Transition Zone and at the EZ Margins in X-Linked Retinitis Pigmentosa Treated With Gene Therapy
In brief
High-dose RPGR gene therapy showed greater sensitivity gains across retinal zones
In a post-hoc analysis of 24 eyes, high-dose gene therapy was associated with greater average microperimetry sensitivity gains than no treatment across all retinal zones. The share of locations gaining at least 7 dB was higher only across the full test grid, not in individual regions, and baseline distance from the photoreceptor boundary did not predict gains - limiting how precisely future trials can target responsive areas.
- Journal
- Translational vision science & technology (Q1)
- Published
- 5 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Muhammad Usman Jamil, A Yasin Alibhai, Darin Curtiss, Lucas R De Pretto, Antonio Yaghy, Jungeun Won, et al.
- PMID
- 42847595
- DOI
- 10.1167/tvst.15.10.10
Why clinicians should know about it
- Picked for Ophthalmology (paper of the day, 11 October 2026): Gene therapy RPGR improves microperimetry in XLRP
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.