Co-Targeting the Dysregulated Ocular and Cochlear Blood Flow via Ophthalmic Nerve Stimulation for the Treatment of Type 2 Usher Syndrome: Prospective Case Series

Background/Objectives: Dysregulated ocular and cochlear blood flow are proposed pathways in the pathogenesis of type 2 Usher syndrome (USH2). This study aimed to evaluate the safety and preliminary efficacy of ophthalmic nerve stimulation (ONS) combined with intravenous ascorbic acid (AA) in patients with USH2. Methods: Nine participants with USH2 were enrolled in a prospective, open-label, interventional case series. All participants received daily ONS combined with intravenous AA over a two-week period. The primary endpoint was the 6-month change in self-reported scotopic function, assessed using the 10-item Low luminance questionnaire (LLQ-10; 0–100 scale). Responders were defined as participants demonstrating a ≥25-point increase in LLQ-10 score. Secondary outcomes included changes in best-corrected visual acuity (BCVA), contrast sensitivity (CS), and subjective hearing function. Results: ONS-based therapy resulted in a significant improvement in LLQ-10 scotopic scores at 6 months (mean change: +42.1 ± 11.3 points, p = 0.0001), with seven of nine participants (77.8%) classified as responders. Clinically meaningful improvements in BCVA (≥0.2 logMAR) and CS (≥0.3 log units) were observed in 22.2% of tested eyes. Additionally, subjective hearing improvement was reported by one-third (33.3%) of participants. No severe adverse events were reported. Conclusions: ONS combined with AA demonstrated safety and yielded significant subjective improvements in night vision quality among patients with USH2, alongside minor improvements in visual acuity, contrast sensitivity, and hearing in a subset of participants. Controlled trials incorporating objective scotopic and audiometric testing are warranted.