The therapy may offer novel treatment strategy with unique mechanism, modality for patients diagnosed with dry age-related macular degeneration.
Reviewed by Richard B. Rosen, MD, FACS, FASRS, FARVO
Photobiomodulation is an emerging new technology that is being tested to treat ocular diseases. The treatment applies low levels of light to targeted tissue to decrease inflammation and helps with tissue healing by positively affecting mitochondrial output and improving cellular activity. The technology uses red and infrared light to stimulate beneficial activity in cells—all without the production of heat. This process increases energy production, alters signaling modalities, activates transcription factors, and has cytoprotective properties that kick in during wound healing.
Richard B. Rosen, MD, FACS, FASRS, FARVO, the Belinda and Gerald Pierce Distinguished Professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai, as well as chief of retina service, vice chair of research, and surgeon director at the New York Eye and Ear Infirmary of Mount Sinai Eye Faculty Practice in New York City, reported the interim analysis data from the prospective, randomized, double-masked, multicenter LIGHTSITE III study (NCT04065490) n the safety and efficacy of photobiomodulation in patients with dry age-related macular degeneration (AMD).
Using photobiomodulation, Rosen explained, the primary tissue targets are 2 sites on the cytochrome c oxidase component on the electron transport chain, which stimulates the production of adenosine triphosphate, the primary energy currency of cells. Three wavelengths of light can be applied to the primary targets: (1) 590 nm to inhibit expression of VEGF and remove cellular deposits; (2) 660 nm to promote oxygen binding to cytochrome c oxidase, stimulate metabolic activity, and inhibit inflammation and cellular loss; and (3) 850 nm to drive electron transfer to cytochrome c, stimulate metabolic activity, and inhibit inflammation and cellular loss.
Patients and treatment
A total of 100 patients (68 women, 32 men; 148 eyes) were included. Their visual acuity levels ranged from 20/100 to 20/32. All patients underwent 9 treatments with photobiomodulation or sham over a 3-week period, every 4 months for 24 months. Most patients (99%) were Caucasian the mean age was 75 years, and 86% had taken Age-Related Eye Disease 2 supplements before treatment. The mean time elapsed since diagnosis of dry AMD was 4.9 years. The top-line data showed a statistically significant (P = .02) difference in the changes in the best-corrected visual acuity (BCVA) between the photobiomodulation and sham treatment groups at month 13.
Photobiomodulation therapy resulted in a sustained and improved BCVA, with a mean 5.5-letter increase from the baseline value at month 13, a difference that reached significance (P < .0001). The photobiomodulation group either gained more or lost fewer letters compared with the sham group. The improvements were also significant at months 1, 5, 8, and 12.
Among the patients who had the highest response to photobiomodulation, 55% of eyes treated with active treatment gained 5 or more letters (mean, 9.7 + 0.52 letters), 26.4% of those eyes gained 10 letters or more (mean, 12.8 + 0.54 letters), and 5.5% gained 15 letters or more compared with 1.9% of the sham-treated patients.
The active treatment group also showed an effect on the volume of drusen in the central retina. Rosen pointed out that at month 13, no significant numerical change in central drusen volume was seen compared with baseline in eyes (0.006 mm3) receiving active treatment. In contrast, during the same time interval, compared with baseline, there was an increase in the volume of drusen in the central retina in the sham-treated eyes (0.049 mm3).
Effect on geographic atrophy
Photobiomodulation has had a positive effect on the appearance of atrophic lesions, as new geographic atrophy developed in approximately 10% of the sham-treated eyes compared with 1.1% of the active-treatment eyes. This difference reached significance (P = .025) in the patients with intermediate dry AMD.
Commenting on the analysis, Rosen enumerated the main findings:
The LIGHTSITE III study met the predetermined primary efficacy BCVA end point, with a statistically significant difference in favor of the active group at month 13.
The active-treatment eyes lost approximately half as many BCVA letters compared with the sham-treated eyes.
The sham-treated eyes had an increase in the volume of drusen in the central retina, in contrast to the active-treatment eyes, in which there was no increase in the central drusen. This was consistent with the LIGHTSITE I and II studies and suggests a disease-modifying benefit.
Finally, Rosen pointed out that photobiomodulation treatment with the Valeda Light Delivery Systemhas an excellent safety profile. “The LIGHTSITE III study provides the largest randomized controlled trial data set to date, evaluating the effects of photobiomodulation in dry AMD,” Rosen said. “Photobiomodulation therapy may offer a novel treatment strategy with a unique mechanism and modality for patients with dry AMD.”
Richard B. Rosen, MD, FACS, FASRS, FARVO
Rosen is the Belinda and Gerald Pierce Distinguished Professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai, as well as chief of retina service, vice chair of research, and surgeon director at the New York Eye and Ear Infirmary of Mount Sinai Eye Faculty Practice in New York City. He is a consultant to LumiThera Inc.