Transcranial magnetic stimulation as a novel therapeutic approach for severe retinal degenerative diseases: a pilot study

BACKGROUND: Retinal degenerative diseases, including myopic macular degeneration (MMD) and retinitis pigmentosa (RP), lead to irreversible vision impairment, with limited treatment options. Transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique for rehabilitation, may hold potential for vision restoration. The pilot study explored whether TMS is associated with short-term functional visual improvements in patients with severe retinal degenerative diseases. METHODS: This prospective, non-randomised, parallel-arm pilot study enrolled 98 patients with bilateral severe MMD or RP. Participants received either five consecutive days of theta-burst TMS or conventional conservative care. Primary outcomes were changes in best-corrected visual acuity (BCVA) and visual field from baseline to 4-week follow-up. Contrast sensitivity, macular sensitivity, fixation stability, Visual Function Index-14 (VF-14) and Visual Functioning Questionnaire-25 (VFQ-25) questionnaires were also evaluated. A subset of participants underwent resting-state functional magnetic resonance imaging (fMRI) to explore cortical functional changes. RESULTS: The study analysed 174 eyes from 88 patients (mean age: 60.3±9.1 years; 52% female). Compared with controls, the TMS group showed greater improvements in BCVA (MMD: 0.22±0.28 logarithm of the minimum angle of resolution (logMAR); RP: 0.24±0.21 logMAR) and VF mean defect (MMD: 1.96±2.09 dB; RP: 1.08±1.28 dB). Contrast sensitivity, macular sensitivity and fixation stability also showed short-term gains. Patient-reported outcomes improved in several functional domains. fMRI demonstrated increased activity and functional connectivity in visual-related cortical regions following TMS. CONCLUSIONS: In this exploratory pilot study, TMS treatment was associated with short-term functional visual improvements and cortical modulation in individuals with severe retinal degenerative diseases. These findings are hypothesis-generating and warrant validation through larger, randomised, masked clinical trials with longer follow-up.