Potential new therapy for aniridia-related keratopathy: a collagen scaffold containing limbal epithelial and stromal stem cells

Researchers in the UK have developed a new treatment approach for aniridia-related keratopathy (ARK), a rare genetic ocular disease, namely, a collagen scaffold that delivers limbal epithelial stem cells and stromal stem cells to the area affected by ARK. The treatment resulted in improved ocular surface scores and visual acuities. They reported their results in JAMA Ophthalmology.¹

The collagen scaffold, the Real Architecture for 3D Tissues–Ocular Surface (RAFT-OS) transplant, combines limbal epithelial and stromal cell transplant. In their nonrandomized clinical trial, the investigators evaluated the safety and feasibility of its use in adults with advanced ARK. The study was led by senior author Sajjad Ahmad, MBBS, PhD. He and the rest of the investigative team are from Moorfields Eye Hospital NHS Foundation Trust, and the UCL Institute of Ophthalmology, University College London, both in London.

The investigators describe ARK as a progressive sight-threatening corneal disorder resulting from PAX6 haploinsufficiency in congenital aniridia. The characteristics include limbal stem cell deficiency, conjunctivalization, subepithelial fibrosis, and recurrent epithelial breakdown that result in chronic surface instability and visual impairment. Currently, limited treatment options exist for these patients.

The search for an effective, sustained treatment is based on the fact that conventional management of this disease is challenging. Ahmad and colleagues explained that penetrating keratoplasty often fails because host pathology recurs in donor tissue, and existing ocular surface reconstruction approaches, such as keratolimbal allograft and allogeneic cultivated limbal epithelial stem cell transplant, have variable durability, with epithelial-only approaches often attenuating beyond 12 to 24 months.2

ARK study design

This single-arm, open-label, phase 1, nonrandomized clinical trial (NCT05044598) was conducted at a tertiary referral center in London. Adults with congenital aniridia and advanced ARK underwent RAFT-OS transplantation in one eye; the fellow eyes were untreated and served as controls.

The primary end points of the evaluation of the RAFT-OS construct were safety and ocular surface normalization at 3 and 12 months, based on assessment using the Ocular Surface Score (OSS). The secondary outcomes included the Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA) and patient-reported outcomes using the Visual Function Questionnaire and the 36-Item Short Form Survey.

What did the evaluation of the implant find?

The study included nine patients (3 women; mean age ± standard deviation, 50.6 ± 11.6 years) who had been followed for 12 months.

The RAFT-OS transplant, according to the authors, was associated with a mean Ocular Surface Score reduction of 3.6 points at 3 months, with partial maintenance of this reduction at 12 months and no substantial safety concerns compared with untreated fellow eyes.

Regarding safety, one early serious adverse event developed that prompted a change in the manufacturing protocol; no other major RAFT-OS-related safety events occurred. A persistent epithelial defect developed in two patients

In the treated eyes, the mean baseline OSSs at baseline and 3 and 12 months were, respectively, 9.4 ± 1.9, 5.9 ± 2.4, and 6.7 ± 2.4. In the untreated fellow eyes, the mean OSSs at the three time points were, respectively, 8.4 ± 2.7, 8.4 ± 2.4, and 8.0 ± 2.5.

The mean logarithm of the minimum angle of resolution BCVAs in the treated eyes at baseline and 12 months were, respectively, 2.23 ± 0.16 (Snellen equivalent, <20/1,600) and 1.77 ± 0.67 (20/1,280). The values in the untreated fellow eyes were, respectively, 1.47 ± 0.71 (20/640) and 1.44 ± 0.75 (20/640).

Based on the results, the investigators concluded, “The 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.”

Ahmad commented, “This treatment has proved effective for a previously untreatable progressive condition leading to sight loss. We are now looking to take this forward to a larger clinical trial, with a view to this being accepted as an NHS treatment.”

References
1. Kaye AE, Morgan L, Shah R, et al. Combined limbal epithelial and stromal cell transplant for aniridia-related keratopathy: a nonrandomized clinical trial. JAMA Ophthalmol. 2026; published online July23, 2026. doi: 10.1001/jamaophthalmol.2026.2701

2. Funderburgh ML, Du Y, Mann MM, SundarRaj N, Funderburgh JL. PAX6 expression identifies progenitor cells for corneal keratocytes. FASEB J. 2005;19:1371-3. doi: 10.1096/fj.04-2770fje