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[This article belongs to Volume - 71, Issue - 4]
Published on : 2026-04-17 19:03:42
Article Code: AMJ-17-04-2026-12373
Title : Intravitreal Photoswitch Therapy with KIO-302 in Advanced Retinitis Pigmentosa: A Phase 1/2 Randomized, Controlled Trial
Author(s) : Robert J. Casson, Rajesh Kumar Verma
Abstract :
Background: Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal degenerations with no approved pharmacological therapies for late-stage disease. KIO-302 is a next-generation azobenzene photoswitch designed to restore light sensitivity to surviving retinal ganglion cells (RGCs) in advanced photoreceptor degeneration. We report the first randomized, controlled evaluation of intravitreal KIO-302 in patients with advanced RP.
Methods: In this Phase 1/2, randomized, single-masked, dose-escalation trial conducted at AIIMS New Delhi and Royal Adelaide Hospital, 18 participants with advanced RP (bare light perception [BLP] to count fingers [CF] vision) were randomized (2:1) to receive intravitreal KIO-302 (25 μg or 50 μg) or sham injection. Primary outcomes were safety and tolerability over 180 days. Secondary outcomes included changes in light perception, visual acuity (Berkeley Rudimentary Vision Test [BRVT]), kinetic visual field, functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) responses, and participant-reported outcomes (NEI VFQ-25).
Results: Between March 2023 and December 2024, 18 participants (mean age 64.3 years; 67% male) received treatment. KIO-302 demonstrated an acceptable safety profile with no serious adverse events, dose-limiting toxicities, or drug-related intraocular inflammation. Mild, transient ocular adverse events occurred in 22% of treated eyes (n=4/18), predominantly procedure-related. Exploratory efficacy analyses revealed significant improvements in light perception accuracy (mean increase 42.3% at day 7, 95% CI: 28.4–56.2; P<0.001) and functional vision task performance peaking at days 7–14. fMRI demonstrated stimulus-evoked BOLD signal changes in primary visual cortex (V1) in 78% of participants (n=14/18), with maximal activation at day 2 post-treatment. Quality-of-life scores improved by mean 15.4 points at day 90 (P=0.03 vs sham).
Conclusions: Intravitreal KIO-302 demonstrated favorable safety and preliminary efficacy signals in advanced RP, supporting further development of photoswitch therapy as a gene-agnostic approach for inherited retinal degenerations. These data establish proof-of-mechanism for pharmacological restoration of light sensitivity in degenerated retinas.