The US Food and Drug Administration (FDA) has approved photobiomodulation (PBM) for intermediate AMD, bringing our specialty into a new era of options for earlier stage atrophic age-related macular degeneration (AMD). The LIGHTSITE III trial met its 13-month prespecified primary endpoint, demonstrating significant improvement in best-corrected visual acuity (BCVA) for enrolled intermediate AMD patients compared to a sham group, with benefits sustained for up to 24 months.¹

Mechanism of Action

The mechanism of action is novel, with the suggested efficacy derived from targeting mitochondria with 3 wavelengths of light (590 nm, 660 nm, and 850 nm), reducing oxidative stress, and positively affecting adenosine triphosphate production.² It is important that PBM is differentiated from “red light therapy,” because there are multiple wavelengths utilized in approved ophthalmic PBM, and these are distinct from several “red light” sources promoted to patients and clinicians. The validity of the results of the small registration trial needs to be studied in the real world and in larger data sets, but the design of LIGHTSITE III supported the efficacy and safety of PBM, which led to its commercialization in 2026.

A new way to administer treatment for AMD, PBM is noninvasive, does not require dilation or anesthesia, and has a relatively short duration at under 5 minutes per eye. The treatment has coverage from our regional Medicare carrier for on-label use, so access is improving in our market. There is a mixture of coverage in July 2026 for commercial and Medicare Advantage carriers, and patients require prior authorization or can elect self-pay if they are commercial or Medicare Advantage patients.

Incorporating Photobiomodulation Into Practice

Our practice was the first in a large suburban market to implement PBM as an option for our patients. We have 7 physicians, 7 practice locations, and a research facility. We elected to place the first PBM machine in a single location so we could optimize flow before considering more diffuse practice-wide integration. On-label PBM is a time-intensive option for patients on an individual basis, because the regimen is 9 treatments over approximately 1 month. Although the treatment time is short, adherence to multiple treatment sessions requires a significant commitment. Treatments can be repeated approximately every 4 months from the inception of the first treatment. Per the LIGHTSITE III protocol, there is no definitive endpoint to the exposures.

Patient selection for PBM is crucial, because the LIGHTSITE III trial only studied a specific population. The therapy is intended to serve patients who are not candidates for complement-modulating geographic atrophy (GA) therapies and is not intended to treat patients with concomitant neovascular AMD.³ The target population is essentially the same group of patients identified anatomically who would benefit from AREDS therapy but also have some vision loss, because only patients with 20/32 to 20/100 visual acuity were studied in the registration trial. Our typical early PBM patients have a relatively high drusen load. PBM can be considered a bridge therapy for patients with vision loss but without significant/central GA nor neovascularization. Importantly, there was a suggestion in the registration data set that patients who received PBM had a lower incidence of new GA lesions, although the progression of GA was not a prespecified endpoint in LIGHTSITE III. Importantly, there was consistency of safety in LIGHTSITE I through III, which emphasizes that PBM seems to be a low-risk offering to patients.³

When patients elect to undergo PBM at our clinic, they are scheduled for all 9 of their PBM appointments and then for a dilated examination with imaging 4 months after the first PBM appointment. It is crucial that there is appropriate documentation on the medical record of both the on-label diagnosis and visual acuity if the PBM is going to be submitted for third-party reimbursement. The patient will discuss the outcome of the PBM series with their referring MD at the 4-month follow-up and will elect whether to continue with additional treatment series.

The PBM machine is small. We placed our first device into an existing imaging room and placed a divider in that space. The machine requires a technician, who seats and aligns the patient, and a physician or an advanced-practice provider to administer the treatment. The device itself is straightforward to align and treat patients with, and there is an easy-to-use interface with touch-screen controls. Setup and treatment administration is not fussy.

Due to the high frequency of the PBM visits—up to 2 to 3 per week per patient—we put the PBM patients into their own schedule to make the visits short and efficient. We dedicate a single technician to PBM patients when volume demands; our technicians are cross-trained in PBM, so many of them can fill this role. PBM patients are asked if they are having any new vision problems on presentation to the clinic for their scheduled treatments. If they are not, they are brought to the PBM machine for treatment without undergoing visual acuity testing, intraocular pressure measurement, or pupillary dilation. The physician present in the clinic that day administers treatment, regardless of which physician in our practice referred the patient for PBM.

Challenges in Practice

The biggest limitation we have with PBM so far is clinical uncertainty regarding long-term benefits as well as the lack of a clear benchmark for stopping treatment. As a community, we need to collect real-world data to see if the treatment mirrors the registration experience, and we can aggregate imaging data to see if there are beneficial short or long-term structural changes after PBM treatment in a larger population. As with most new therapies, we can make clinical decisions with incomplete information and adjust our decision algorithm as we learn more. With PBM, we can make these decisions with confidence that there is little risk of harm.

Conclusion

We are happy with our PBM experience so far, and our referring optometrists and ophthalmologists, as well as our patients, are grateful to have access to this option. It is too soon to assess whether there is a real-world impact that mirrors the significant vision gains in the LIGHTSITE III trial. We are optimistic that we will see some subjective and objective benefits of PBM in the clinic, and we are proud to lead the way in our community with this treatment option.

References

1. Study of photobiomodulation to treat dry age-related macular degeneration (LIGHTSITE III). Clinicaltrials.gov identifier: NCT04065490. Updated February 5, 2021. https://clinicaltrials.gov/study/NCT04065490

2. Sadda SR. Photobiomodulation for age-related macular degeneration. JAMA Ophthalmol. 2025;143(3):195–196. doi:10.1001/jamaophthalmol.2025.0077

3. Boyer D, Hu A, Warrow D, et al. LIGHTSITE III: 13-month efficacy and safety evaluation of multiwavelength photobiomodulation in nonexudative (dry) age-related macular degeneration using the Lumithera Valeda light delivery system. Retina. 2024 Mar 1;44(3):487-497. doi:10.1097/IAE.0000000000003980

David A. Eichenbaum, MD, is the director of research at the Retina Vitreous Associates of Florida and a collaborative associate professor at the University of South Florida’s Morsani College of Medicine. He is also a fellow of the American Society of Retina Specialists. Dr. Eichenbaum is a consultant for Alcon.