Light Therapy Boosts Vision and Slows AMD Progression Over 2 Years

Dry age-related macular degeneration (AMD) is the leading cause of vision loss in older adults, yet until recently no approved therapy existed for its intermediate stage. Photobiomodulation (PBM) — the application of specific light wavelengths to stimulate mitochondrial function and cellular repair — has emerged as a candidate intervention given that retinal tissue is among the most metabolically active in the body and mitochondrial dysfunction is central to AMD pathogenesis.

LIGHTSITE III was a double-masked, randomized, sham-controlled, multicenter, 24-month trial enrolling 100 subjects (148 eyes) across 10 U.S. centers. Participants were aged 50+ with intermediate dry AMD (drusen ≥63 µm) and baseline BCVA of 50–75 ETDRS letters. They were randomized 2:1 to active PBM (Valeda Light Delivery System; 590, 660, and 850 nm wavelengths) or sham (greatly attenuated 590/660 nm, no 850 nm). Six treatment series of nine sessions each were administered every four months over 24 months. Co-primary endpoints were BCVA change from baseline at months 13 and 21, with month 24 serving as a follow-up visit three months after the final treatment.

The trial met its pre-specified primary efficacy endpoint: at month 21, PBM-treated eyes demonstrated a mean gain of +6.2 ETDRS letters versus sham (P=0.0036). Clinically meaningful response rates were substantial — 61.5% of PBM eyes gained ≥5 letters, 23.1% gained ≥10 letters, and 4.4% gained ≥15 letters. Secondary outcomes including low-luminance BCVA, contrast sensitivity, reading ability, color vision, and vision-related quality of life (VFQ-25) all showed favorable trends favoring PBM. Anatomically, progression to geographic atrophy (GA) at month 24 occurred in only 6.8% of PBM-treated eyes compared with 24.0% of sham eyes — a statistically and clinically significant 72% relative risk reduction (P=0.007), suggesting genuine disease-modifying potential rather than purely symptomatic benefit.

The safety profile was excellent throughout the 24-month period. No signs of phototoxicity, retinal damage, or serious ocular adverse events attributable to PBM were reported. Baseline cataracts, age, eye laterality, and worse-eye status did not significantly influence outcomes, broadening the potential applicable patient population. Groups were well-balanced at baseline for age and BCVA. Statistical analysis employed linear mixed-effects models with multiple imputation to handle missing data, adding methodological rigor.

These results build on prior LIGHTSITE I and II data and represent the longest and largest controlled PBM trial in dry AMD to date. The convergence of functional improvement and anatomical disease modification positions multiwavelength PBM as a meaningful therapeutic advance. Caveats include the relatively small sample size, predominantly White patient population, industry sponsorship, and the fact that GA incidence was a descriptive (not multiplicity-controlled) secondary endpoint. Nonetheless, LIGHTSITE III provides compelling evidence that PBM may become an important, non-invasive treatment option for patients with intermediate dry AMD.