Table 1.
Clinical studies evaluating photobiomodulation in ophthalmology.
| Article (First Author, year) |
Study Quality* | Indication | Sample Size^ | λ (nm) and Dose (J/cm2 and/or mW/cm2)^ | PBM Specifications and Tx Design^ | Key Findings |
|---|---|---|---|---|---|---|
| Franceschelli S. et al., 2024 (62) | 1 | Severe Dry AMD | 60 subjects PBM group: 33 subjects (50 eyes) Control group: 27 subjects (28 eyes) |
630 nm (15 μW; 2.5 μJ/cm²) Control: No LED |
Frequency: PBM Tx 10x for 10 minutes/2 weeks; Assessments conducted after 10th Tx | • Improved VA • Improved microperimetry (mean sensitivity) • No structural change via OCT or safety concerns |
| Zhou W. et al., 2024 (64) | 1 | Myopia | 200 subjects (50 subjects for each group) | 650 nm: 3 interventional levels tested - 0.37 ± 0.02 mW; 0.60 ± 0.2 mW; 1.20 mW Control: SVS only |
Frequency: PBM Tx 2x per day for 3 minutes with at least a 4-hour interval between sessions for 6 months | • No progression of myopia • Reduction in SER progression • Reduced AL • Increased SFCT • No AEs |
| Zhou L. et al., 2023 (65) | 1 | Myopia | Two consecutive cohorts of 50 subjects PBM group: 25 subjects Control group: 25 subjects |
650 nm ± 10 nm (0.35 ± 0.02 mW/cm2); illumination of approximately 400 lux (LD-A, Jilin Londa Optoelectronics Technology) Control: SVS only |
Frequency: PBM Tx 2x per day for 3 minutes with at least a 4-hour interval between sessions for 12 months | • Stabilization of myopia progression • Reduced AL • Reduction in SER progression • No significant change in CCP, ACD, and SFCT • Most common AE included immediate, and reversible, vision loss due to flash blindness or afterimage • No severe, systemic, or other AE related to grades of ocular diseases |
| Boyer D. et al., 2023 (50) | 1 | Dry AMD | 100 subjects (144 eyes) PBM group: 93 eyes Control group: 54 eyes |
590 nm (5 mW/cm2); 660 nm output (65 mW/cm2); 850 nm (8 mW/cm2) Control: 10-100x reduction in 590 nm and 660 nm, removal of 850 nm [Valeda Light Delivery System, LumiThera, Inc] |
Frequency: PBM Tx series 3x per week/3-4 weeks at BL; repeated Tx series at 4, 8, 12, 16, and 20 months | • Improved VA • No increase in drusen volume • Reduced new onset of GA • 4 ocular-specific AEs considered related to the Tx (none led to study discontinuation and were mild or moderate in intensity); No SAE considered related to Tx; no signs of phototoxicity or structural damage via OCT |
| Burton B. et al., 2023 (51) | 1 | Dry AMD | 44 subjects (53 eyes) PBM group: 29 eyes Control group: 15 eyes |
590 nm (5 mW/cm2); 660 nm output (65 mW/cm2); 850 nm (8 mW/cm2) Control: 10-100x reduction in 590 nm and 660 nm, removal of 850 nm [Valeda Light Delivery System, LumiThera, Inc] |
Frequency: PBM Tx series 3x per week/3-4 weeks at BL; repeated Tx series at 4 and 8 months | • Improved VA • No increase in drusen volume • Reduced new onset of GA • No safety concerns or signs of phototoxicity observed |
| Kim JE. et al., 2022 (66) | 1 | DME | 135 subjects PBM group: 69 subjects Control group: 66 subjects |
670 nm Control: Broad spectrum white light |
Frequency: PBM Tx 2x daily for 90 seconds for 4 months | • Reduced central subfield thickness and VA letter loss compared to control • 8 AEs possibly related to PBM device; 2 AEs possibly related to control device; No serious AEs |
| Jiang Y. et al., 2021 (67) | 1 | Myopia | 264 subjects PBM group (plus SVS): 119 subjects Control group (SVS only): 145 subjects |
650 nm (1600 lux and a power of 0.29 mW for a 4-mm pupil) [Eyerising, Suzhou Xuanjia Optoelectronics Technology] Control: SVS only |
Frequency: PBM Tx 2x per day for 3 minutes with at least a 4-hour interval between sessions, 5 days per week, for 12 months | • Reduction in myopia progression • Reduced axial length • Reduction in SER progression • No severe AEs or structural damage to photosensory layer observed by OCT |
| Xiong F. et al., 2021 (68) |
1 | Myopia | 229 subjects PBM group: 74 subjects (74 eyes) OK lens Group: 81 subjects (81 eyes) Vision distance spectacle Group: 74 subjects (74 eyes) |
650 nm (2 ± 0:5mW) [Ya Kun Optoelectronic] Controls: OK lens; Vision distance spectacles |
Frequency: PBM Tx 2x per day for 3 minutes with at least a 4-hour interval between sessions, for 6 months | • Reduction in myopia progression • Reduced AL • Reduction in SER progression • Increased SFCT |
| Markowitz S. et al., 2020 (49) | 1 | Dry AMD | 30 subjects (46 eyes) PBM group: 24 eyes Control group: 22 eyes |
590 nm (5 mW/cm2); 660 nm output (65 mW/cm2); 850 nm (8 mW/cm2) Control: 10-100x reduction in 590 nm and 660 nm, removal of 850 nm [Valeda Light Delivery System, LumiThera Inc.] |
Frequency: PBM Tx series 3x per week/3 weeks at BL; PBM Tx series repeated at 6 months, 12-month study duration | • Improved VA • Improved contrast sensitivity • Improved QoL • Improved microperimetry (fixation stability) • Reduced central drusen volume • Reduced central drusen thickness • No AEs related to Tx |
| Kent AL. et al., 2020 (69) | 1 | ROP | 86 subjects (neonates) PBM group: 45 subjects Control group: 41 subjects |
670 nm (9 J/cm2) Control: No light |
Frequency: Full body PBM Tx daily until 34 weeks of age or transfer | • No difference in severity of ROP or requirement for laser treatment • Improved survival rates • No AEs |
| Koev K. et al., 2017 (70) | 2 | AMD | 55 subjects (109 eyes) PBM group: 66 eyes Control group: 44 eyes |
633 nm (He-Ne Laser continuous emission at 0.1 mW/cm2) Control: Mock Tx |
Frequency: PBM Tx 6x for three minutes once every other day for 5 years | • Improved VA • Improved VA optotypes • Reduced metamorphopsis and scotomas • In nAMD, reduced edema and bleeding |
| Ivandic BT, & Ivandic T., 2012 (71) | 2 | Amblyopia | 178 subjects (231 eyes) PBM group: 211 eyes Control group: 20 eyes |
780 nm (292 Hz, 1:1 duty cycle, AVG power 7.5mW; 3mm2) Control: No light; audible signal every 10s |
Frequency: PBM Tx 4x/2 weeks | • Improved VA • Increased m-VEP amplitude • No local or systemic AEs |
| Ivandic BT, & Ivandic T., 2008 (72) | 2 | AMD | 203 subjects (348 eyes) PBM group: 328 eyes Control group: 20 eyes |
780 nm (292 Hz, 1:1 duty cycle, AVG power 7.5mW; 3mm2) Control: No light; audible signal every 10s |
Frequency: PBM Tx 4x/2 weeks | • Improved VA (in eyes with and without cataracts) which was maintained for 3-36 months • Reduced metamorphopsia, scotoma, and dyschromatopsia • Reduced edema and bleeding in nAMD • No AEs |
| Tang J. et al., 2014 (73) | 3 | DME | 4 subjects (8 eyes) PBM group: 4 eyes Control group: 4 eyes |
670 nm (50-80 mW/cm2) [WARP 10, Quantum Devices] Control: Fellow eye |
Frequency: PBM Tx 2x daily/2-9 months | • Reduced macular edema • Reduced focal retinal thickness • No AEs |
| Benlahbib M. et al., 2023 (53) | 4 | AMD | 20 Eyes | 590 nm (5 mW/cm2); 660 nm output (65 mW/cm2); 850 nm (8 mW/cm2) [Valeda Light Delivery System, LumiThera, Inc] | Frequency: PBM Tx 2x per week/5 weeks | • Improved VA • Reduced retinal sensitivity • Increased fixation stability • Reduced drusen volume • Reduced drusen thickness • Increased GA lesion area • Improved QoL • 2 AEs reported: A rupture of drusenoid pigment epithelial detachment 6 months post-PBM Tx and vitreous floaters |
| Kaymak H. et al., 2023 (47) | 4 | DME | 18 subjects (28 eyes) |
590 nm (5 mW/cm2); 660 nm output (65 mW/cm2); 850 nm (8 mW/cm2) [Valeda Light Delivery System, LumiThera, Inc] | Frequency: PBM Tx series 3x per week/3-4 weeks | • Reduction in CRT • Resolution of inner retinal fluid and hard exudates • Improved DRSS scores • Improved QoL • Maintained VA • No ocular or systemic AEs |
| Le HM. et al., 2022 (74) | 4 | Reticular Pseudodrusen (RPD) | 5 subjects (5 eyes) |
590 nm (5 mW/cm2); 660 nm output (65 mW/cm2); 850 nm (8 mW/cm2) [Valeda Light Delivery System, LumiThera, Inc] | Frequency: PBM Tx 2x/week for 6 weeks | • Changes in RPD distribution: Reduced number of stage 3 RPD with accompanying increase in number of stage 1 RPD • Maintained VA • No AEs |
| Casson RJ. et al., 2022 (75) | 4 | RP | 12 Subjects (12 eyes) |
670 nm (25 mW/cm2 or 100 mW/cm2) | Frequency: PBM 2x weekly for 8 weeks | • Improved VA • Cone-derived photopic flicker responses were almost completely abolished • No change in ERG amplitude • No AEs |
| Scalinci SZ. et al., 2022 (76) | 4 | Stargardt Disease | 45 Subjects (90 eyes) |
650 nm (10 Hz) | Frequency: PBM Tx 2x daily/5 days/week for 12 months | • Improved VA • Improved pERG • Improved microperimetry |
| Siqueira RC. et al., 2021 (77) | 4 | AMD | 10 Subjects | 670 nm (50-80 mW/cm2) [WARP 10, Quantum Devices] |
Frequency: PBM Tx 9x | • Improved VA • Improved visual field function • No change or abnormalities in OCT, ERG, FR and AF • No AEs |
| Shen W. et al., 2020 (78) | 4 | Center-involving DME | 21 Subjects | 670 nm laser (3 interventional levels tested - 25, 100 or 200 mW/cm2) | Frequency: PBM Tx 12x/5 weeks | • Dose dependent reduction in central macular thickness • No AEs |
| Grewal MK. et al., 2020 (79) | 4 | AMD and normal ageing | 31 Subjects with iAMD; 11 Subjects aged 55 years or above with normal retina | 670 nm (40 mW/cm2 or 4.8J/cm2) | Frequency: PBM Tx for 2 minutes daily for 12 months | • In normal ageing, an improvement in scotopic thresholds in the group with no AMD • No significant improvement in any functional or structural changes • No effect on intermediate AMD • No serious AEs related to the device |
| Merry G. et al., 2017 (48) | 4 | Dry AMD | 22 Subjects (42 Eyes) |
670 nm (50-80 mW/cm2) [WARP 10, Quantum Devices] 590 nm (4 mW/cm2); 790 nm (0.6 mW/cm2) [Gentlewaves, Light Bioscience] |
Frequency: PBM treatment series 9x/3 weeks | • Improved VA • Improved contrast sensitivity • Reduced central drusen volume • Reduced central drusen thickness • No AEs |
| Kent AL. et al., 2015 (80) | 4 | ROP | 28 Subjects (56 eyes) |
670 nm (9 J/cm2) | Frequency: PBM Tx for 15 minutes daily from ≤ 48 hours post-birth until 34 weeks postmenstrual age | • No skin burns or other documented AEs • No safety concerns |
| Sachdev A., 2024 (52) |
5 | CSCR | 1 Subject (1 eye) | 590 nm (5 mW/cm2); 660 nm output (65 mW/cm2); 850 nm (8 mW/cm2) [Valeda Light Delivery System, LumiThera, Inc] | Frequency: PBM Tx series 3x per week/3 weeks; PBM Tx series repeated at 6 months | • Improved VA • Resolution of edema |
| Ahadi M. et al., 2022 (81) | 5 | DME | 1 Subject (2 eyes) |
670 nm (50-80 mW/cm2) [WARP 10, Quantum Devices] |
Frequency: PBM Tx 1x daily for month 1; 3x/week for month 2; 1x/week for month 3; 1x/month afterwards | • Improved VA • Resolution of macular edema • At 16 months follow-up, VA remained stable and OCT showed no evidence of recurrence of edema |
| Ivandic BT, and Ivandic T., 2014 (82) | 5 | RP | 1 Subject | 780 nm (292 Hz, 1:1 duty cycle, AVG power 10mW; 3mm2) | Frequency: PBM Tx 2x/2 weeks | • Improved VA |
*Study Quality Assessment Designations:1: Prospective, randomized, controlled study; 2: Prospective, non-randomized, controlled; 3: Retrospective, controlled study; 4: Prospective or retrospective uncontrolled study (e.g., Observational study); 5: Case report(s) with small sample size. ^PBM specifications and study design taken from published reports where described. Number of subjects and number of eyes provided where available. AE, adverse event; AF, autofluorescence; AL, axial length; AMD, age-related macular degeneration; ACD, anterior chamber depth; BL, baseline; CCP, central corneal refractive power; CRT, central retinal thickness; DME, diabetic macular edema; DRSS, diabetic retinopathy severity scale; ERG, electroretinography; FR, fluorescence retinography; GA, geographic atrophy; IPL, intense pulsed laser; m-VEP, multifocal visual evoked potential; nAMD, neovascular age-related macular degeneration; nm, nanomolar; OCT, optical coherence tomography; pERG, pattern electroretinography; PBM, photobiomodulation; QoL, quality of life; ROP, Retinopathy of prematurity; RPD, reticular pseduodrusen; SER, spherical equivalent of refraction; SFCT, subfoveal choroidal thickness; Tx, treatment; VA, visual acuity.