Subjects could use AREDS vitamin supplementation however, no change in supplements 1 month before the study and during the study trial was allowed. Subjects were excluded from enrollment with previous/active wet AMD, with a history of epilepsy, with cognitive impairment, other significant retinal disease, or other significant disease. Subjects were eligible for trial enrollment if they had dry AMD and were in Age-Related Eye Disease Study (AREDS) categories 2 to 4 with BCVA scores as determined by the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity chart with a letter score between 50 and 85 (Snellen equivalent of 20/40 to 20/200). The primary goal of this study was to evaluate the efficacy and safety of PBM in subjects with dry AMD using the Valeda Light Delivery System, specifically designed for the ophthalmological use of PBM. The current study further investigates the effects of PBM treatment on subjects with dry AMD in a double-masked, randomized, sham-controlled, parallel group, single-center prospective design. 23, 24 These positive clinical findings coupled with the known mitochondrial-based mode of action of PBM and the underlying pathology associated with AMD highly suggest that PBM treatment could have a therapeutic role in dry AMD, a condition that is characterized by mitochondrial dysfunction, oxidative stress, and inflammation within the RPE cell layer. 20 Most recently, the Toronto and Oak Ridge PBM Studies for Dry Age-Related Macular Degeneration (TORPA I and II) presented evidence for clinical (improvements in best-corrected visual acuity and contrast sensitivity ) and anatomical (reductions in drusen volume) benefits after PBM in patients with dry AMD. No changes in visual acuity were seen in the control group, and there were no reports of any adverse effects among PBM-treated patients. 20– 22 In subjects with AMD, treatment with a laser diode aimed at the macular area improved visual acuity in both subjects with dry and wet AMD.
Ivandic and Ivandic 20 have shown clinical improvements in patients with amblyopia, retinitis pigmentosa, and AMD after treatment with PBM. 15– 19 Limited clinical studies show high potential for the use of PBM in the ocular field. In animal models of ocular injury, PBM has reduced damage or symptoms associated with methanol-toxicity, laser burn, complement factor H knockout inflammatory, bright light damage, retinitis pigmentosa, and diabetic retinopathy. The use of PBM in ocular diseases and disorders has been studied in both preclinical and clinical settings. 10– 13 The beneficial effects of PBM are linked to increases in mitochondrial energy generation through ATP, replication, density, and activity and increases in RNA and protein synthesis. 6– 9 The driving mechanism behind these benefits suggests that the mitochondrial enzyme cytochrome C oxidase is a key photoacceptor of light in the far red to NIR spectral range. Photobiomodulation can be applied to selected tissues to produce beneficial cellular effects leading to improved outcomes at the cellular, systemic, and clinical level in a wide range of disease states. The use of photobiomodulation (PBM), previously termed low-level light therapy, involves targeted use of selected wavelengths of visible light to near infrared (NIR) light (500–1,000 nm) produced by a laser or a noncoherent light source such as light-emitting diodes. The more frequent dry form of AMD has limited treatment options available other than lifestyle changes and the use of vitamin supplements, demonstrating a significant unmet clinical need for alternate treatment plans for an expanding population base. Treatment is available for wet AMD through periodic intravitreal injections of anti–vascular endothelial growth factor compounds. 2 Contributing factors to RPE cell degeneration include mitochondrial dysfunction, oxidative stress, inflammation, and genetic disposition. The advanced late-stage dry form of AMD, which accounts for 80% to 90% of the cases, is characterized by retinal pigment epithelium (RPE) and outer retinal atrophy, whereas only 10% to 20% develop the exudative, wet late-stage form, with choroidal neovascularization (CNV) as a hallmark of respective disease. Progression of AMD is characterized by accumulation of membranous debris, lipofuscin, and extracellular material and complement deposition. The prevalence of AMD is projected to affect 196 million by the year 2020 with an expected growth rate to 288 million in 2040. Disease progression inevitably leads to significant visual dysfunction and serious compromises in quality of life (QoL). Age-related macular degeneration (AMD) is a retinal disease that results in irreversible, severe loss of vision, including legal blindness.