Short- and Long-Term Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Multiwavelength photobiomodulation (PBM) is a novel non-invasive intervention that targets mitochondrial dysfunction in nonexudative (dry) age-related macular degeneration (AMD).This systematic review and meta-analysis aimed to evaluate the short-and long-term efficacy and safety of PBM in patients with dry AMD.A systematic search of major databases (PubMed, Embase, CENTRAL, Scopus, Web of Science) and trial registries was conducted until August 2026.Randomized controlled trials (RCTs) comparing multiwavelength PBM (e.g., 590/660/850 nm) to sham or no treatment were included.Continuous and dichotomous outcomes were pooled using random-effects models with the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment.The risk of bias (Cochrane Risk of Bias 2 (RoB 2)) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation (GRADE)) were systematically evaluated.Ten reports from nine unique studies (four RCTs, one non-randomized comparative study, and four uncontrolled studies) were included.A meta-analysis of four RCTs (365 eyes) revealed a fragile, short-term (< 12 months) improvement in best-corrected visual acuity (BCVA) (mean difference (MD): +1.44 ETDRS letters; 95% confidence interval (CI): 0.12 to 2.76), which lost significance after adjustment for the correlation between the two eyes of the same patient (MD: 1.37; 95% CI: -0.03 to 2.77 at an assumed intraclass correlation of 0.5) and in leave-one-out analyses.However, in a post-hoc analysis, PBM increased the likelihood of a clinically meaningful ≥ 5-letter BCVA gain (risk ratio (RR): 2.77; 95% CI: 2.08-3.68;p = 0.0015), which was unchanged after excluding one trial's full-protocol subgroup (RR: 2.84; 95% CI: 1.86-4.32).Reductions in macular drusen volume (standardized mean difference (SMD): -0.18; p = 0.081) and contrast sensitivity were not statistically significant.One large trial reported a significant reduction in incident geographic atrophy at 24 months (RR: 0.29).PBM demonstrated a favorable safety profile, with no increased risk of ocular adverse events or progression to neovascular AMD.The overall certainty of the evidence was graded as low to very low due to the high risk of bias, small sample sizes, and imprecision.Multiwavelength PBM significantly increased the proportion of patients who achieved categorical visual gains and maintained a favorable safety profile.However, the continuous visual and anatomical benefits are modest and fragile.High-quality, independently funded RCTs with standardized sham controls and long-term follow-ups are warranted to definitively establish the role of PBM in AMD management.