12-month outcomes of photobiomodulation in dry age-related macular degeneration: a prospective multicentre randomised double-masked controlled clinical trial

BACKGROUND: Dry age-related macular degeneration (dAMD) is the leading cause of irreversible vision loss in older adults, with no approved treatment to modify progression in early and intermediate stages. Photobiomodulation (PBM), which targets mitochondrial dysfunction and retinal inflammation, has shown promise in early studies. This study aims to evaluate the anatomical and functional efficacy of PBM in eyes with early and intermediate dAMD. METHODS: In this 12-month, multicentre, randomised double-masked controlled trial, 138 eyes from 78 patients with early or intermediate dAMD were included. The primary outcome was change in mean drusen volume (MDV) from baseline to 12 months. Secondary outcomes included change in best-corrected visual acuity (BCVA) and adverse events. Multilevel mixed-effects regression was used to analyse treatment-time interactions. RESULTS: MDV decreased significantly in the PBM group (-0.03±0.05 mm³) while increased in the sham group (+0.02 ± 0.04 mm³; p<0.001) at 12 months. The PBM group also showed a significant improvement in BCVA (+1.31 ± 6.7 letters) compared with a decline in the sham group (-2.62±7.1 letters), yielding a between-group difference of +3.75 letters (95% CI 1.16 to 6.34; p=0.0001). Female sex and higher Age-Related Eye Disease Study (AREDS) category were associated with MDV increase over time (p=0.030 and p=0.003; respectively), while older age was associated with MDV reduction (p=0.049). Four eyes in the sham group developed macular neovascularisation, compared with none in the PBM group (p=0.044), while one eye in the PBM group developed geographic atrophy (p=1.00). No cases of retinal phototoxicity were observed. CONCLUSION: PBM significantly reduced drusen burden and improved visual function in early and intermediate dAMD over 12 months, with an excellent safety profile. These findings support PBM as a promising therapeutic option for patients with non-neovascular age-related macular degeneration, despite further studies with longer follow-up are needed to confirm the role of PBM in potentially slowing the natural course of the disease.