Combined Limbal Epithelial and Stromal Cell Transplant for Aniridia-Related Keratopathy: A Nonrandomized Clinical Trial

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Abstract

IMPORTANCE: Advanced aniridia-related keratopathy (ARK) is a progressive ocular surface disorder associated with limbal stem cell deficiency and limited effective treatment options. OBJECTIVE: To evaluate the safety, feasibility, and clinical outcomes of Real Architecture for 3D Tissues-Ocular Surface (RAFT-OS), a tissue-engineered collagen scaffold incorporating allogeneic limbal epithelial stem cells and stromal keratocytes, in adults with advanced ARK. DESIGN, SETTING, AND PARTICIPANTS: This single-arm, open-label nonrandomized clinical trial was conducted at a tertiary referral center in London, United Kingdom. Adults with congenital aniridia and advanced ARK underwent RAFT-OS transplant. Untreated fellow eyes served as natural history comparators. Recruitment occurred between February 2022 and April 2024, with final study completion in April 2025. Follow-up was 12 months. Data analysis was performed from May 2025 through February 2026. INTERVENTION: Surgical transplant of a good manufacturing practice-manufactured RAFT-OS construct. MAIN OUTCOMES AND MEASURES: The primary end points were safety and ocular surface normalization at 3 and 12 months, assessed using the Ocular Surface Score (OSS). Secondary outcomes included best-corrected visual acuity (BCVA, via Early Treatment Diabetic Retinopathy Study [ETDRS] acuity charts) and patient-reported outcomes (Visual Function Questionnaire [VFQ-25], 36-Item Short Form Survey [RAND-36]). RESULTS: Nine participants were included (3 female [33%]; mean [SD] age, 50.6 [11.6] years). One early serious adverse event prompted amendment of the manufacturing protocol; no further major RAFT-OS-related safety events occurred. Two participants developed persistent epithelial defects. In treated eyes, mean (SD) OSS was 9.4 (1.9) at baseline, 5.9 (2.4) at 3 months (mean difference from baseline, -3.6; 95% CI, -5.6 to -1.6), and 6.7 (2.4) at 12 months (mean difference, -2.8; 95% CI, -4.5 to -1.0). In untreated fellow eyes, mean (SD) OSS was 8.4 (2.7) at baseline, 8.4 (2.4) at 3 months (mean difference, 0; 95% CI, -2.5 to 2.5), and 8.0 (2.5) at 12 months (mean difference, -0.4; 95% CI, -2.4 to 1.5). Mean (SD) treated eye BCVA was 2.23 (0.16) logMAR (Snellen equivalent, <20/1600) at baseline and 1.77 (0.67) logMAR (20/1280) at 12 months (mean difference, -0.47; 95% CI, -0.97 to 0.04). Mean (SD) fellow eye BCVA was 1.47 (0.71) logMAR (Snellen equivalent, 20/640) at baseline and 1.44 (0.75) logMAR (20/640) at 12 months (mean difference, -0.04; 95% CI, -0.44 to 0.37). CONCLUSIONS AND RELEVANCE: In this 9-participant nonrandomized clinical trial, RAFT-OS transplant was feasible and associated with early ocular surface improvement, partly sustained through 12 months, without substantial safety concerns. Additional controlled studies with longer follow-up are needed to define safety and clinical effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05044598.

Abstract as published, via PubMed.