Introduction

Age-related macular degeneration cases continue to grow due both to the aging population and to better diagnostic abilities. Those numbers will steadily climb as the global prevalence of the disease is estimated to reach 288 million by 2040.1 Seeing as age-related macular degeneration is the leading cause of legal blindness in older Americans, finding efficacious treatments is more important now than ever.

Of the 2 types, dry age-related macular degeneration affects up to 90% of patients with the condition. Once detected, the clinician should first determine the stage (early, intermediate, or advanced), which is important to assess appropriate actions to be taken along with the clinical follow-up schedule.

Identifying the intermediate stage allows the practitioner to institute science-based methods to decrease the risk of progression. However, this micronutrient supplementation may only delay progression for 20% to 25% of patients.2 Additionally, dietary changes can likely play a role at any stage, but especially at the intermediate level. A particularly noteworthy diet to consider is the Mediterranean diet, which has been highlighted in numerous studies and publications for its potential health benefits.3

Unfortunately, despite these interventions, those with intermediate age-related macular degeneration are at risk for progression to the advanced stage. Visual function tends to decline before visual acuity.4 And once geographic atrophy develops, it takes only 2.5 years for central visual function to decline.5 Unfortunately, all patients with age-related macular degeneration will progress.

But what if there was an opportunity to either treat this degenerative disease earlier, prior to loss of functional vision, or at other stages? Enter photobiomodulation.

Age-related macular degeneration shows dysfunction of mitochondria, which contributes to the development and progression of the disease. The primary mechanism of action is regulation of mitochondrial activity, which is associated with cell survival otherwise impacted by the aging processes.6,7 With degenerative disease, it is imperative to intervene earlier before progression results in cellular apoptosis and irreversible structural loss. Photobiomodulation is a treatment that uses visible or near-infrared light directed to the eye and adnexa area to produce a beneficial cellular effect. Based on the positive results of LIGHTSITE III clinical trial results, the US Food and Drug Administration in 2024 authorized photobiomodulation with the Valeda Light Delivery System for the treatment of nonexudative or dry age-related macular degeneration.

The LIGHTSITE III randomized clinical trial evaluated multiwavelength photobiomodulation therapy for dry age-related macular degeneration using the Valeda device. Eligible subjects were aged at least 50 years, had a diagnosis of age-related macular degeneration defined by the presence of drusen and/or nonsubfoveal geographic atrophy, and had best-corrected visual acuity scores per the Early Treatment Diabetic Retinopathy Study between 50 and 75 letters (converted to Snellen equivalence of 20/32 to 20/100). The clinical classification of age-related macular degeneration followed the Beckman categorization.8 Subjects were excluded from the trial if they had a history of choroidal neovascularization, central subfoveal geographical atrophy, or coexisting significant retinal disease.9

A total of 100 subjects (148 eyes) were randomized (2:1 photobiomodulation versus sham). Treatment for the photobiomodulation group consisted of exposure to 3 wavelengths: yellow (590 nm), red (660 nm), and near infrared (850 nm). The researchers divided the treatment into 4 phases, which resulted in a total time of under 5 minutes per eye. They delivered the 590-nm and 850-nm wavelengths in a pulsed manner through an open eyelid for 35 seconds (phase 1 and 3). The 660-nm wavelength, however, was delivered continuously through a closed eyelid for 90 seconds (phase 2 and 4).

The sham group, on the other hand, received a 50- and 100-times reduced exposure to the 590-nm and 660-nm wavelengths, respectively. Researchers omitted the 850-nm wavelength. Treatment or sham was delivered in a series of 9 sessions over a 3- to 5-week period every 4 months over a duration of 24 months.

At month 13 (4 series of treatments), the average change in baseline best-corrected visual acuity was an increase of 5.4 letters in the photobiomodulation-treated eyes and 3.0 letters in the sham-treated eyes. Table 1 lists the specific breakdown for letters gained. In addition, the sham-treated eyes showed a 2-fold decrease in best-corrected letter count, and more sham-treated eyes had an increased number of eyes with a more than 10 letter loss at each visit compared with photobiomodulation-treated eyes.10

Table 1.Letters Gained for the Treatment and Sham Groups in the LIGHTSITE III Trial
LIGHTSITE III >5 Letter Gain >10 Letter Gain >15 Letter Gain
Treatment ~55% 26.4% 5.5%
Sham 40.8% 14.9% 1.9%

Anatomically, macular drusen volume decreased in the photobiomodulation-treated eyes versus an increase in macular drusen volume for the sham-treated group, which also saw progression to confluent drusen and pigment epithelial detachments. In addition, patients treated with photobiomodulation had a statistically significant decrease in new onset of geographic atrophy (1.1%) versus the sham-treatment (10%).10

Given the results, LIGHTSITE III provides a prospective, randomized, controlled clinical trial showing improved anatomical and clinical outcomes in patients with early/intermediate dry age-related macular degeneration following photobiomodulation therapy. Photobiomodulation-treated eyes were more likely to have increased best-corrected visual acuity, reduced volume of drusen, and a lower onset of new geographical atrophy lesions, with no signs of phototoxicity. This demonstrates a disease modifying effect of therapy and a favorable safety profile.

Finally, data from LIGHTSITE IIIB was just recently discussed at the 2025 American Society of Retina Specialists meeting.11 Interestingly, the patients in this extension study went 20 months since exiting the original trial, meaning they went without photobiomodulation treatment (or sham). Those patients in the original treatment group lost just over 2 letters during the gap, whereas the sham patients lost 5.7 letters. Further, during the 13-month extension, although all patients received photobiomodulation, those in the original treatment group gained further vision, whereas those originally in the sham were able to maintain, but not gain. This shows the benefit to starting treatment earlier rather than later.

Counterpoint (Drs Haynie and Gerson): Are We All on the Same Wavelength About Photobiomodulation?

When the US Food and Drug Administration authorizes a new therapy, physicians are in an obligatory position to understand the clinical data on which the authorization was based so proper counseling of a patient regarding risk and benefits can take place. Ultimately, the patient should decide on whether to pursue or decline therapy. A closer look into photobiomodulation clinical results may give pause to a physician and/or the patient. In addition, one must realize this therapy will create a treatment burden for the patient. The therapy as described consists of 9 sessions over 3 to 5 weeks that is repeated every 4 months, hence adding 27 office visits per year for the patient.

When looking at the clinical trial data, there were a total of 100 participants (148 eyes) included. However, 8 of 34 (23.5%) sham participants and 9 of 64 (14.1%) photobiomodulation participants discontinued the study before the primary end point with no explanation as to why. In addition, the average age of a photobiomodulation participant was 74 years, whereas the sham group was 77 years. Knowing that age-related macular degeneration is an aging disorder, having older participants in the sham group may have had an impact on the results, especially when looking at the percentage of patients that went on to develop geographic atrophy.

Besides age, other factors can signal a risk for geographical atrophy development, namely optical coherence tomography biomarkers. However, these baseline characteristics were not explored or documented for either group. If geographical atrophy biomarkers were more prevalent in the sham group at baseline, then one could hypothesize that the photobiomodulation-treated eyes may not have had a lower incidence of developing geographical atrophy, but rather it was the natural history of the disease. Additionally, although the goal of photobiomodulation treatment is to preserve retinal tissue and improve best-corrected visual acuity, there was a higher incidence of converting to neovascular age-related macular degeneration in the photobiomodulation-treated eyes (5.4%) versus the sham-treated eyes (1.8%).

Although the mild or infrequent adverse ocular events reported to be associated with photobiomodulation were described as mild or infrequent, other concerns have been raised about the delivery of low-intensity, red light therapy that need monitoring. Some describe apparent photoreceptor damage in the fovea in patients treated with photobiomodulation for the slowing of myopia progression. Therefore, photobiomodulation in an aging eye with a diseased retinal pigment epithelium and photoreceptor layer could potentially be more susceptible to damage or insult.

It should also be noted that the Valeda device is US Food and Drug Administration authorized, which is different than US Food and Drug Administration approved. A US Food and Drug Administration–authorized device went through 501(k) submission, and the manufacturer demonstrated that the product is “substantially equivalent” to another similar legally marketed device that has already been approved. US Food and Drug Administration approved means that the manufacturer has submitted a premarket approval application (similar to a new drug application) with robust clinical testing results. Given all of the above, more data may be necessary for physicians to confidently recommend photobiomodulation to patients.

* The counterpoint is based on the following reference:

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

Summary With Editorial Comments

As treatment options for age-related macular degeneration continue to expand, the importance of prompt diagnosis and timely initiation or referral for therapy has never been greater. Patients are becoming increasingly aware of their choices and will expect them to be presented thoughtfully and comprehensively. As a result, primary eyecare will need to serve as a central hub for age-related macular degeneration management, guiding patients through their options and promoting better long-term outcomes.

Although photobiomodulation offers hope as a potential treatment for dry age-related macular degeneration, the current evidence remains insufficient to support confident clinical recommendations. Limitations in trial design and the modest effects observed warrant caution, underscoring the need for more rigorous, transparent, and long-term studies before photobiomodulation can be widely endorsed.

Also, clinicians should be aware of the device’s indications for use.12 Specifically, the Valeda Light Delivery System is intended to provide improved visual acuity in patients with best-corrected visual acuity of 20/32 through 20/70 and who have dry age-related macular degeneration characterized by the following:

  • The presence of at least 3 medium drusen (>63 um and ≤ 125 um in diameter), or large drusen (>125 um in diameter), or noncentral geographical atrophy, AND

  • The absence of neovascular maculopathy or center-involving geographical atrophy

Moving forward, effectively managing patient expectations while navigating emerging therapies will be critical to optimizing care and ensuring patients remain informed and engaged in their treatment journey.

Disclosures

Dr Haynie served as the consultant or on the advisory board for Apellis, Astellas, Notal, MacuHealth, and Orasis. Dr Gerson served on the advisory board of, served as a consultant for, received honoraria from, or served on the speaker’s bureau list for Abbvie, Apellis, Astellas, Bausch Health, Essilor, iCare, Lenz, LKC, Luneau Technologies, Macular Degeneration Association, Notal Vision, Optos, Regeneron, Tarsus, Viatris, and ZeaVision.