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BACKGROUND: Photobiomodulation therapy (PBMT)-a noninvasive therapeutic strategy-employs low-level red or near-infrared light to regulate cellular bioenergetics, reduce oxidative stress, and modulate inflammation. It has demonstrated therapeutic potential for several ophthalmic diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa, and dry eye disease. However, the clinical evidence remains fragmented due to heterogeneity in study designs, treatment parameters, and outcome measures. Moreover, existing reviews are largely confined to single diseases. Robust, prespecified assessments that standardize disease-specific endpoints and only explore shared physiological measures across conditions remain scarce. METHODS: The protocol is registered in the PROSPERO database. This review will follow the PRISMA guidelines; randomized controlled trials and comparative nonrandomized clinical studies involving PBMT interventions for any clinically diagnosed ophthalmic disease will be included. Eligible comparators will include sham treatment, no treatment, or standard care, and outcomes will be primarily analyzed at the disease-specific level, with endpoints including best-corrected visual acuity, drusen volume, intraocular pressure, and diabetic retinopathy severity. Selected shared physiological or functional outcomes (e.g., electroretinogram amplitude, tear cytokine concentrations, and optical coherence tomography measurements of retinal structure) will be examined in a secondary exploratory framework to provide hypothesis-generating insights across conditions. Databases-including PubMed, Embase, Cochrane Library, Web of Science, and Scopus-will be searched for articles published up to July 31, 2025. Two reviewers will independently select studies, extract data, and assess risk of bias. Random-effects models will be used for the meta-analysis, and heterogeneity will be explored through prespecified subgroup (disease type, wavelength, irradiance, fluence, session duration, treatment frequency) and exploratory meta-regression analyses. DISCUSSION: This review will provide pooled effect estimates for PBMT based on clinical outcomes across ophthalmic diseases. These will be stratified by intervention parameters and outcome types (disease-specific and shared physiological/biomarker-based). Rather than aiming to determine optimal treatment strategies, the findings are intended to provide exploratory insights and generate hypotheses for future clinical research. The study will synthesize clinical evidence regarding the effect of PBMT on ophthalmic diseases, highlighting methodological considerations to guide the design of future trials and serve as an exploratory framework for understanding potential multidisease and multioutcome perspectives. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420251033569.
Choy et al. (Thu,) studied this question.