Title: Low Level Photo Bio Modulation LL PBM in geographic atrophy: A pivotal randomized single blind study follow up 12 months
Abstract:
Introduction: PhotoBioModulation (PBM) has emerged in recent years as a potential therapeutic approach to counteract the progression of dry Age Related Macular Degeneration (d AMD). Its primary mechanism of action involves the interaction between red light and mitochondrial cytochrome c oxidase, leading to enhanced cellular efficiency, improved mitochondrial respiration, and reduced oxidative stress. However, in the late stages of d AMD and in Geographic Atrophy (GA), conventional PBM protocols may present limitations: the irradiance delivered to the retina can be excessively high, potentially accelerating functional decline rather than mitigating it. We have previously demonstrated that ultra-low irradiance stimulation, delivered through a wearable device Jupiter, emitting 30 nanowatts/cm², can improve short term retinal function (MP and BCVA) without adverse effects.
Aim: To evaluate the efficacy and safety of LL-PBM in advanced forms of d AMD, including GA, and to determine whether this ultra-low irradiance approach can slow the functional deterioration typically observed in these patients.
Materials and Methods: For this preliminary randomized, single blind study, we enrolled 17 patients for a total of 23 eyes. Inclusion criteria: non foveal GA according to the Ferris classification.
- Active group: Treated with a wearable LL-PBM device:
- Induction phase: One 12’ session daily for 10 consecutive days
- Maintenance phase: One 12’ session every other day for 12 months
- Control group: Used an identical but inactive device.
Retinal function was assessed primarily through microperimetry (MP), performed at baseline and after 12 months. Given the variability of structural progression in GA, MP was considered the most reliable functional endpoint to monitor disease evolution.
Statistical analysis:
- Continuous variables were expressed as mean ± SD.
- Within group changes (T0 vs T1) were evaluated using paired t tests.
- Between group differences in mean change (Δ) were assessed using independent samples t tests. A p value < 0.05 was considered statistically significant.
Results: After 12 months of treatment, the active group showed no clinically relevant change in mean retinal sensitivity compared with baseline. In contrast, the placebo group exhibited a mean decrease of approximately 2 dB, consistent with the expected natural progression of GA (p < 0.01). These findings suggest that LL PBM may stabilize retinal function over a 12 month period, whereas untreated eyes continue to decline.
Discussion: The rate of decline in retinal sensitivity during the GA stage is highly variable. Intercurrent events may accelerate functional loss. Published data report an average decline of 1–2 dB per year in untreated GA. In our study, the placebo group showed a mean reduction in retinal sensitivity consistent with the literature. Conversely, the treated group exhibited only minimal variation from baseline, indicating a potential stabilizing effect of LL PBM.
Conclusions:
- LL- PBM does not induce thermal or phototoxic effects on the retinal target tissue.
- No adverse events or treatment related discomfort were reported.
- LL- PBM may slow functional deterioration even in advanced stages of d AMD, including GA.
