Purpose: The aim of the study was to investigate annual structural and functional results, and their correlation with inheritance pattern of retinitis pigmentosa (RP) patients who were treated with Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs).
Material and methods: This prospective, sequential, open-label phase-3 clinical study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology, between April 2019 and May 2020. The study included 34 eyes from 32 retinitis pigmentosa patients of various genotypes who were enrolled in the stem cells clinical trial. The patients were followed for 12 months after the WJ-MSCs transplantation into subtenon space and evaluated with consecutive examinations. Genetic mutations were investigated using a retinitis pigmentosa panel sequencing method consisting of 90 genes. All patients underwent a complete routine ophthalmic examination with best corrected visual acuity, optical coherence tomography angiography, visual field, and full-field electroretinography. Quantitative data obtained from baseline (T0), 6th month (T1), and 12th month (T2) examinations were compared.
Results: According to timepoints at T0, T1, and T2: The mean outer retinal thickness was 100.3 μm, 119.1 μm, and 118.0 μm, respectively (p = 0.01; T0 < T1, T2). The mean horizontal ellipsoid zone width were 2.65 mm, 2.70 mm, and 2.69 mm respectively (p = 0.01; T0 < T1, T2). The mean best corrected visual acuity (BCVA) were 70.5 letters, 80.6 letters, and 79.9 letters, respectively (p = 0.01; T0 < T1, T2). The mean fundus perimetry deviation index (FPDI) was 8.0%, 11.4%, and 11.6%, respectively (p = 0.01; T0 < T1, T2). The mean full-field flicker ERG parameters at T0, T1, and T2: amplitudes were 2.4 mV, 5.0 mV, and 4.6 mV, respectively (p = 0.01; T0 < T1, T2). Implicit time were 43.3 ms, 37.9 ms, and 38.6 ms, respectively (p = 0.01; T0 > T1, T2). According to inheritance pattern, BCVA, FPDI, ERG amplitude, and implicit time data improved significantly in autosomal dominant (AD) and in autosomal recessive (AR) RP at 1 year follow-up (pAD = 0.01, pAR = 0.01; pAD = pAR > pX-linked). No ocular or systemic adverse events related to the surgical methods and/or WJ-MSCs were observed during the 1 year follow-up period.
Conclusion: Subtenon transplantation of WJ-MSCs was found to be effective and safe in the treatment of RP during the first year, similar to the sixth month's results. In autosomal dominant and autosomal recessive inheritance of RP, regardless of the genetic mutations, subtenon administration of WJ-MSCs can be considered an effective and safe option without any adverse effect for slowing or stopping the disease progression.
Trial registration: ClinicalTrials.gov, NCT04224207 . Registered 8 January 2020.
Keywords: Autosomal dominant; Autosomal recessive; Genotype; Retinitis pigmentosa; Stem cell; Wharton jelly.