Suprachoroidal Injection of Wharton’s Jelly-Derived Mesenchymal StemCells in Inherited Retinal Diseases: A Prospective Exploratory Single-Arm Study

Inherited retinal diseases (IRDs) are progressive disorders characterized by photoreceptor and reti-nal pigment epithelium dysfunction, for which effective disease-modifying treatments remain lim-ited. Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) may exert neuroprotective and immunomodulatory effects through paracrine mechanisms. The suprachoroidal route may provide targeted delivery toward the choroid–retinal pigment epithelium–outer retinal interface while avoiding direct subretinal transplantation. This study evaluated preliminary structural, functional, electrophysiological, and safety outcomes 45 days after suprachoroidal administration of WJ-MSCs in patients with IRDs. This prospective, open-label, single-arm exploratory clinical study was con-ducted at Universidade Santo Amaro, Brazil. Ten patients with genetically and multimodally con-firmed IRDs were recruited in June 2026 and followed for 45 days. Eligible participants had no pre-vious ocular treatment and best-corrected visual acuity (BCVA) ≤20/30. Human umbilical cord-derived WJ-MSCs were administered as a single suprachoroidal injection at a dose of 1 × 10⁶ cells in 0.1 mL per treated eye, without additional study-specific in vitro expansion after preparation of the cryopreserved product. BCVA, intraocular pressure (IOP), central foveal thickness (CFT), automated visual-field mean deviation (MD) and pattern standard deviation (PSD), and electro-retinographic (ERG) parameters were assessed at baseline and day 45. Paired Student’s t-tests and Wilcoxon signed-rank tests were performed using Python 3.12.3 and SciPy 1.17.1. Both eyes were included in the analysis, with recognition of within-patient correlation. Mean BCVA improved from 0.849 ± 0.750 to 0.740 ± 0.718 logMAR, corresponding to a mean change of −0.109 logMAR, without statistical significance by either the paired t-test (p = 0.1003) or Wilcoxon test (p = 0.0904). Mean IOP changed from 15.6 ± 2.56 to 16.1 ± 3.28 mmHg, without significant difference. CFT increased from 226.8 ± 108.2 to 275.8 ± 178.4 μm; this difference was significant by the Wilcoxon test (p = 0.0313), but not by the paired t-test (p = 0.0619). Visual-field MD improved from −20.86 ± 8.87 to −19.09 ± 9.47 dB, with significant differences by both the paired t-test (p = 0.0082) and Wilcoxon test (p = 0.0042), whereas PSD remained stable. At the group level, none of the eight ERG parameters showed a sig-nificant change by paired t-test. The Wilcoxon analysis identified a difference only in 30-Hz flicker P1 latency (p = 0.0195), which was not confirmed by the paired t-test. Using an exploratory 30% test–retest variability threshold, Patient 10 demonstrated improvement trends in 7 of 8 ERG parameters, whereas Patients 4 and 9 showed predominantly declining patterns. No ocular inflammatory, infec-tious, or clinically significant treatment-related pressure events were observed during the 45-day follow-up. These preliminary findings indicate that suprachoroidal administration of WJ-MSCs was feasible and was not associated with major ocular safety events during the 45-day observation pe-riod. The observed improvement in visual-field MD warrants further investigation but should be interpreted cautiously given the single-arm design, small sample size, heterogeneous diagnoses, mixed perimetric protocols, potential inter-eye correlation, and marked individual-level variability. The absence of consistent group-level ERG improvement and the CFT increase observed in one par-ticipant further emphasizes the exploratory nature of these findings. Larger controlled studies with standardized functional endpoints, validated ERG repeatability criteria, patient-level mixed-effects analyses, and longer follow-up are required to determine whether the observed functional changes represent a treatment-related biological effect. The study support further controlled investigation of the suprachoroidal route as a targeted strategy for inherited retinal diseases.