Photobiomodulation in Retina Diseases
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Medical Therapy
Description
Photobiomodulation (PBM) is a non-invasive therapy that employs specific wavelengths of light, typically red and near-infrared (590–850 nm), to stimulate mitochondrial activity, improve cellular energy production, modulate inflammation, and promote retinal neuroprotection without causing thermal or photochemical damage. (1) Initially used for wound healing and pain management, PBM has emerged as a promising approach for slowing or modifying the progression of various retinal diseases. (2)
Patient Selection
Indications
Age-Related Macular Degeneration (AMD)
Dry AMD is the most extensively studied retinal condition in photobiomodulation, particularly in its early and intermediate stages. The rationale for PBM in AMD stems from its ability to reduce oxidative stress, improve mitochondrial function, and support the metabolic needs of the RPE. (3)
The multicenter, randomized, double-masked LIGHTSITE II clinical trial examined the safety and efficacy of PBM therapy in intermediate non-exudative AMD patients. The study used the LumiThera Valeda® Light Delivery System to deliver multiwavelength PBM (590, 660, and 850 nm) or sham treatments three times per week for 3–4 weeks, repeated at baseline, 4 months, and 8 months (a total of 27 treatments). Patients were required to have a BCVA between 20/32 and 20/100 and no central geographic atrophy (GA) within 500 μm of the fovea. PBM-treated eyes had a statistically significant improvement in BCVA at 9 months, gaining 4 letters (p = 0.02) compared to 0.5 letters in the sham group. With an average gain of 4 letters (p = 0.02), PBM-treated eyes demonstrated a statistically significant improvement in BCVA at 9 months, while the sham group's gain was non-significant at 0.5 letters. 35.3% of the eyes (n = 29) that received all 27 treatments showed an improvement of at least five letters. The volume of drusen progressively increased in sham-injected eyes, while it was relatively constant in PBM-treated eyes. Despite the progression of GA lesions in both groups, PBM-treated eyes revealed a 20% less progression over a 10-month visit interval, suggesting potentially disease-modifying effects. There were no safety concerns or signs of phototoxic effects. (4)
The Valeda Light Delivery System was used in the LIGHTSITE III study to assess PBM therapy in patients with dry AMD. In this randomized, sham-controlled study, PBM was administered in treatment cycles every four months, involving 100 participants and 148 eyes. At 13 months, the PBM group had a lower rate of new-onset geographic atrophy (p = 0.024) and a significantly higher improvement in BCVA than the sham group (+2.4 letters, p = 0.02). There were no significant safety concerns, and the therapy was well tolerated. (5)
On November 4, 2024, the FDA authorized Valeda, making it the first non-invasive treatment authorized by the FDA for use in treating dry AMD. (6)
Diabetic Retinopathy (DR)
PBM has demonstrated its potential in DR for treating the significant processes involved in DR, such as oxidant stress/inflammation and vascular leakage. Several preclinical studies have demonstrated that PBM protects the blood-retinal barrier, downregulates the expression of VEGF, reduces leukostasis, and modulates the activation of Müller cells and microglia, thereby preserving retinal structure (7, 8). PBM with low-energy red light (670 nm) has also been reported to attenuate oxidative stress and inflammation in diabetic macular edema (DME). Shen et al. observed a considerable decrease in foveal thickness 2–6 months following 5 weeks of 18 J/cm² of a 670 nm laser in DME patients (9). Similarly, Tang ang Herda et al. reported that daily PBM treatment was associated with a reduction in focal retinal thickening in patients with non-center-involving DME, with no treatment-related adverse effects observed. (10). While human data remain limited, these findings imply that PBM might be a beneficial adjuvant treatment in non-proliferative or early stages of DR and DME, with extension to larger clinical trials warranted.
Retinitis Pigmentosa (RP)
Progressive photoreceptor cell death is a key feature of inherited retinal degenerations, such as RP, and is often associated with oxidative stress and mitochondrial pathology. The neuroprotective processes may be related to the enhancement of mitochondrial resilience, reduction in apoptosis of photoreceptor cells, and action on the expression of neurotrophic factors such as BDNF. (11) P23H transgenic rats, which carry a rhodopsin mutation that imitates human RP, were treated with daily 670 nm red light (9 J/cm²) to promote improved mitochondrial function, less oxidative damage, and preservation of photoreceptors and remaining retinal function (12). Additional studies using 830 nm PBM (4.5 J/cm²) confirmed improvements in ERG responses and retinal structure, supporting its effect on mitochondrial homeostasis . (13) Clinically, a patient with very advanced RP had recovery of visual acuity and visual fields following 780 nm PBM, and this improvement was sustained and retreatment-responsive over the years (14). These results suggest that PBM may be an effective supplementary treatment for RP, particularly in maintaining residual retinal function.
Central Serous Chorioretinopathy (CSCR)
PBM is being recognized as an option for chronic CSCR that affects inflammation, oxidative stress, and choroidal regulation. One case report with multi-wavelength PBM (Valeda®: 590 nm, 660 nm, and 850 nm) demonstrated a rapid resorption of subretinal fluid and an increase in BCVA from 55 to 80 ETDRS letters after only 3 treatments with stable visual acuities up to 1 year after a second treatment cycle. Although not yet confirmed by randomized controlled studies, this clinical case report suggests the possibility that PBM may be used therapeutically for the CSCR by modulating the inflammatory process, the oxidative stress, and the choroidal circulation, factors involved in the perpetuation of the disease. (15)
Pathological Myopia
PBM appears to be a potentially non-invasive intervention to prevent the development of myopia in children. Several randomized controlled trials (RCT) have shown that repeated exposure to low-level red light can induce a significant inhibition of axial elongation, as well as delay the progress of spherical equivalent refraction. (16, 17) A recent RCT involving 188 children showed that twice-daily photobiomodulation therapy over 12 months significantly reduced axial length growth compared to controls (–0.06 mm vs +0.34 mm, p < 0.001), with 53.3% of treated participants experiencing axial shortening greater than 0.05 mm. The mean change in spherical equivalent refraction was +0.11 D in the treatment group and –0.75 D in the control group. At the same time, no significant differences were observed in subfoveal choroidal thickness, anterior chamber depth, or corneal power. (18). While the exact mechanisms remain under investigation, PBM may act through mitochondrial stimulation, improved choroidal perfusion, and modulation of retinal dopamine signalling (19). As high myopia carries a substantial risk of complications such as retinal detachment, choroidal neovascularization, and degenerative changes, PBM presents a potential early intervention strategy to reduce long-term visual morbidity.
Other Potential Indications
Emerging applications of PBM include retinopathy of prematurity, Stargardt disease, and Leber’s hereditary optic neuropathy. In these conditions, PBM’s potential neuroprotective and anti-inflammatory properties are of interest (20). However, these uses remain experimental, and there is currently insufficient evidence to support routine clinical use.
Contraindications
PBM is contraindicated in patients with known photosensitivity disorders, such as epilepsy triggered by light stimuli or severe photophobia associated with migraine. It should also be avoided in individuals taking photosensitizing medications, due to the potential for exaggerated tissue response to light exposure. Active intraocular infection or uncontrolled ocular inflammation represents another contraindication, as the inflammatory process may be exacerbated or confound treatment effects. Additionally, PBM is not recommended in the immediate postoperative period following ocular surgery; treatment should be deferred until the patient is clinically stable and cleared by an ophthalmologist. (21)
Clinical Pharmacology
PBM exerts its biological effects through absorbing low-level red or near-infrared light—typically within the 630 to 1000 nm range—by intracellular chromophores. The central enzyme in the mitochondrial respiratory chain, cytochrome c oxidase (CcO), is the primary target. Photon absorption by CcO displaces nitric oxide, which can inhibit mitochondrial respiration under cellular stress, thereby restoring efficient oxidative phosphorylation (22, 23). This results in an increase of adenosine triphosphate (ATP) levels and promotes cellular energy. Concurrently, PBM modulates reactive oxygen species (ROS) production, which may contribute to redox balance, and stimulates transcription factors, including NF-κB and AP-1, that control the expression of cellular survival, repair, and inflammation mediator genes (23).
PBM also exerts significant anti-inflammatory effects. It has been shown to reduce pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, while modulating microglial activation and upregulating anti-inflammatory and neuroprotective factors (24). These effects are particularly relevant in retinal diseases such as age-related macular degeneration and diabetic retinopathy, where low-grade, chronic inflammation contributes to disease progression (3, 25).
In terms of neuroprotection, PBM efficiently protects the retinal cell architecture by preventing apoptosis in photoreceptors and RPE. It also upregulates neurotrophic factor expression, including brain-derived neurotrophic factor (BDNF) and improves mitochondrial activity under metabolic stress. (11). In animal model studies, PBM has been shown to confer remarkable vascular benefits such as increasing retinal blood flow, preserving blood-retinal barrier integrity, and reducing vascular leakage, particularly in diabetic subjects. (25). The sum of all these effects renders PBM an interesting therapeutic tool for several retinal diseases.
Warnings/Precautions
General
Treatment should be performed only with approved PBM devices and parameters validated for ocular use. Avoid excessive cumulative dosing beyond studied fluence ranges (0.01–10 J/cm²).
Information for Patients
PBM is painless, non-invasive, and typically requires no dilation or anaesthesia. Multiple sessions are usually necessary; effects are gradual and may require maintenance cycles.
Drug Interactions
PBM can potentially increase sensitivity in patients taking photosensitizing drugs (e.g., certain antibiotics, amiodarone, psoralens).
Carcinogenesis/Mutagenesis/Impairment of Fertility
No evidence from current studies suggests carcinogenic or mutagenic risks at therapeutic doses for ocular PBM.
Pregnancy
No controlled studies in pregnant women; use only if the potential benefit outweighs risks.
Nursing Mothers
No adverse effects on breastfed infants reported; systemic exposure is negligible.
Pediatric Use
Increasing evidence supports safety and efficacy in myopia control in children; long-term safety is still under investigation.
Adverse Reactions
Transient photophobia, mild visual disturbances, or ocular discomfort (rare). No significant retinal or systemic side effects were reported in clinical trials.
Overdosage
Excessive fluence or inappropriate wavelength may cause retinal stress; follow manufacturer protocols strictly.
Dosage and Administration
Device and Light Parameters
PBM is provided by non-invasive LED-based equipment which emits low-power red or near-infrared light in the 590–850 nm band. These wavelengths are chosen to closely correspond to the absorption peaks of mitochondrial chromophores, including CCO, which is also thought to be the central component of the cellular bioenergetic response (23). The light is incoherent and non-thermal and was optimally designed to give retinal tissue a boost without eliciting photochemical or thermal responses. Single-wavelength and multi-wavelength-based systems have been developed that use a wide range of peak wavelengths for targeting retinal layers and cellular constituents (20).
Treatment Setting and Procedure
PBM is performed on an outpatient basis, and no pharmacological pretreatment is necessary. Depending on the system, patients can be seated at a slit-lamp–mounted PBM unit or placed under a stationary LED panel (20). Treatment is painless, non-invasive, and does not necessitate pupil dilation or topical anaesthesia. The author has the patients fixate on a central target during treatment to achieve the proper macular exposure. The instrument is arranged to provide homogeneous lighting of the posterior pole. Its ease and tolerance of use allow repeated applications, also in elderly or frail patients (26).
Session Duration and Frequency
Each PBM session typically lasts 90 seconds and a few minutes per eye. Treatment protocols vary depending on the specific device and clinical indication, but most regimens recommend two to three sessions per week over three to five weeks, for a total of nine to fifteen sessions per treatment cycle (27). Maintenance treatments may be scheduled every three to six months in chronic conditions such as dry age-related macular degeneration, based on disease stability and clinician assessment (28).
Dosing and Safety
The therapeutic dose of light is administered at low fluence rates, generally at 0.01 to 10 J/cm², which is far below the extent required to create thermal damage (28). This dosing regimen should be able to trigger cellular effects while maintaining retinal safety. Studies conducted by different groups have demonstrated that PBM is safe and well-tolerated in clinical environments, and no significant deleterious ocular or systemic side effects have been reported (12). Nevertheless, PBM is not recommended in photosensitivity disorders (epilepsy, migraine) or for those taking photosensitizing medications. (21)
How Supplied
PBM is delivered via LED-based devices (single or multi-wavelength) designed for ocular use (e.g., Valeda® Light Delivery System). (21)
Patient’s Instructions for Use
Attend all scheduled sessions for optimal effect. Maintain fixation on the central target during treatment.
References
(1) Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys. 2017;4(3):337-361. doi:10.3934/biophy.2017.3.337
(2) Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2012;40(2):516-533. doi:10.1007/s10439-011-0454-7
(3) Merry GF, Munk MR, Dotson RS, Walker MG, Devenyi RG. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration. Acta Ophthalmol. 2017;95(4):e270-e277. doi:10.1111/aos.13354
(4) Boyer, D. S., Goldbaum, M., Khanani, A. M., Patnaik, J. L., Regillo, C. D., Rhoades, W. R., Kaiser, P. K., & Moinuddin, O. (2023). Multicenter, double-masked, randomized clinical trial evaluating the safety and efficacy of multiwavelength photobiomodulation for dry age-related macular degeneration: LIGHTSITE II Study. Ophthalmology and Therapy, 12(2), 953–968. https://doi.org/10.1007/s40123-022-00640-6
(5) Boyer, D. S., Kaiser, P. K., Regillo, C. D., Rhoades, W. R., & Slakter, J. S. (2024). 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the LumiThera Valeda Light Delivery System: LIGHTSITE III Study. Retina, 44(3), 487–497. https://doi.org/10.1097/IAE.0000000000003980
(6) U.S. Food and Drug Administration. (2024). FDA authorizes marketing of Valeda Light Delivery System for treatment of patients with dry AMD. Retrieved from https://www.fda.gov/medical-devices
(7) Opazo G, Tapia F, Díaz A, Vielma AH, Schmachtenberg O. Prolonged Photobiomodulation with Deep Red Light Mitigates Incipient Retinal Deterioration in a Mouse Model of Type 2 Diabetes. Int J Mol Sci. 2024;25(22):12128. Published 2024 Nov 12. doi:10.3390/ijms252212128
(8) Cheng Y, Du Y, Liu H, Tang J, Veenstra A, Kern TS. Photobiomodulation Inhibits Long-term Structural and Functional Lesions of Diabetic Retinopathy. Diabetes. 2018;67(2):291-298. doi:10.2337/db17-0803
(9) Janis T Eells, Sandeep Gopalakrishnan, Thomas B Connor, Kimberly Stepien, Joseph Carroll, Vesper Williams, Krissa Packard, Judy E Kim; 670 nm Photobiomodulation as a Therapy for Diabetic Macular Edema: A Pilot Study . Invest. Ophthalmol. Vis. Sci. 2017;58(8):932.
(10) Tang J, Herda AA, Kern TS. Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema. Br J Ophthalmol. 2014;98(8):1013-1015. doi:10.1136/bjophthalmol-2013-304477
(11) Kim SY, Song MJ, Kim IB, Park TK, Lyu J. Photobiomodulation therapy activates YAP and triggers proliferation and dedifferentiation of Müller glia in mammalian retina. BMB Rep. 2023;56(9):502-507. doi:10.5483/BMBRep.2023-0059
(12) Albarracin R, Natoli R, Rutar M, Valter K, Provis J. 670 nm red light preconditioning supports Müller cell function: evidence from the P23H rat model of retinal degeneration. PLoS One. 2013;8(1):e54373.
(13) Gopalakrishnan S, Natoli R, Valter K, Provis JM. Near infrared light (830 nm) protects retina against oxidative stress in P23H rat model of RP. Exp Eye Res. 2020;189:107857.
(14) Ivandic BT, Ivandic T. Low-level laser therapy improves vision in a patient with retinitis pigmentosa: a case report. Photomed Laser Surg. 2008;26(3):239–242.
(15) Sachdev A. Improvement in Central Serous Chorioretinopathy Following Multiwavelength Photobiomodulation Treatment - Case Report. Ophthalmol Ther. 2024;13(7):2055-2060. doi:10.1007/s40123-024-00963-6
(16) Jiang Y, Zhu Z, Tan X, et al. Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children: A Multicenter Randomized Controlled Trial. Ophthalmology. 2022;129(5):509-519. doi:10.1016/j.ophtha.2021.11.023
(17) Xiong F, Mao T, Liao H, Hu X, Shang L, Yu L, et al. Orthokeratology and low intensity laser therapy for slowing the progression of myopia in children. BioMed Res Int. (2021) 2021:8915867. doi: 10.1155/2021/8915867
(18) Xu Y, Cui L, Kong M, et al. Repeated Low-Level Red Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial. Ophthalmology. 2024;131(11):1314-1323. doi:10.1016/j.ophtha.2024.05.023
(19) Zhu Q, Cao X, Zhang Y, et al. Repeated Low-Level Red-Light Therapy for Controlling Onset and Progression of Myopia-a Review. Int J Med Sci. 2023;20(10):1363-1376. Published 2023 Sep 4. doi:10.7150/ijms.85746
(20) Valter K, Tedford SE, Eells JT and Tedford CE (2024) Photobiomodulation use in ophthalmology – an overview of translational research from bench to bedside. Front. Ophthalmol. 4:1388602. doi: 10.3389/fopht.2024.1388602
(21) U.S. Food and Drug Administration guidance (2025) for PBM devices and LumiThera Valeda® contraindications
(22) Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys. 2017;4(3):337-361. doi:10.3934/biophy.2017.3.337
(23) de Freitas LF, Hamblin MR. Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy. IEEE J Sel Top Quantum Electron. 2016;22(3):7000417. doi:10.1109/JSTQE.2016.2561201
(24) Yang J, Liu X, Elbayoumi T, et al. Anti-inflammatory and neuroprotective effects of photobiomodulation on retinal microglia and Müller cells. Invest Ophthalmol Vis Sci. 2018;59(14):5931–5941.
(25) Tang J, Kern TS. Inflammation in diabetic retinopathy. Prog Retin Eye Res. 2011;30(5):343-358. doi:10.1016/j.preteyeres.2011.05.002
(26) Borrelli E, Coco G, Pellegrini M, et al. Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration. Ophthalmol Ther. 2024;13(11):2855-2868. doi:10.1007/s40123-024-01030-w
(27) Nassisi M, Mainetti C, Paparella GR, et al. Short-term efficacy of photobiomodulation in early and intermediate age-related macular degeneration: the PBM4AMD study. Eye (Lond). 2024;38(18):3467-3472. doi:10.1038/s41433-024-03326-4
(28) Sadda, S. R., et al. (2025). Photobiomodulation for Age‑Related Macular Degeneration. JAMA Ophthalmology.
