Table 1.
Summary of Available Articles Describing the Application of Photobiomodulation for Age-Related Macular Degeneration. Subjects, Eyes, Wavelength Treated, Device Used, Dose and Delivery Parameters as Well as Results of the Studies are Presented
| First Author* (Trial Name, NCT) | Year | Design | Subjects (No.) | Eyes (No.) | λ (nm) | Device | Dose and Delivery Parameters | Results |
|---|---|---|---|---|---|---|---|---|
| Begum24 | 2013 | – | 29 CFH knockout mice | 39 | 670 | LED Light Source (C.H. Electronics, UK) | 20 mW/cm2 for 720 sec daily for 12 days | Altered morphology of macrophages marked by IBA-1, increased COX expression, 50% reduction of C3 in outer retina, reduced GFAP and vimentin. |
| Calaza19 | 2015 | - | 44 CFH knockout and 44 C57BL/6 mice | 176 | 670 | Unspecified | 40 mW/cm2 for 90 sec daily for 5 days | ATP decline is reversed, but HSP60 (indicator of IR light effect) expression unchanged at 2.4 and 8 month time points. |
| Kokkinopoulos26 | 2013 | - | 46 C57BL/6 mice | 92 | 670 | WARP10 LED Device (Barneveld,WI) | 40 mW/cm2 for 90 sec five times spaced every 35 hours | Shifting C3b from outer retina to RPE-BM interface reduced inflammation (calcitonin, Complement C3d, TNF) and increased mitochondrial polarization. |
| Rutar20 | 2012 | - | 9 Sprague-Dawley rats | 18 | 670 | WARP75 LED Device (Barneveld, WI) | 50 mW/cm2 for 180 sec daily over 5 days | Decreased immunoreactivity (4-hydroxynonenal protein), decreased complement expression C3,C4, reduced C3 deposition in ONL. |
| Ivandic40 | 2008 | Prospective trial | 203 patients with dry/wet AMD and VA ≤ 20/20 | 348 | 780 | Custom Device | 7.5 mW/cm2 for two 40 sec treatments over 2 weeks | At 3 and 6 months, both cataract and no-cataract patients had improvement in visual acuity; prevalence of metamorphopsia, scotoma, dyschromatopsia were reduced. In patients with wet AMD, edema and bleeding improved. |
| Merry41 (TORPA I) | 2012 | Prospective Interventional Case Series | 9 subjects with dry AMD, 50 or older, VA 20/200-20/20 | 18 | 670 | WARP10 LED Device (Barneveld,WI) | 50–80 mW/cm2 for eighteen 88 sec treatments over 6 weeks | At 12 months, improved visual acuity by ETDRS chart and contrast sensitivity. No change in fixation stability. Raw data not provided |
| 790 | Gentlewaves (Light bioscience, VA) | 6 mW/cm2 for eighteen 35 sec treatments over 6 weeks | ||||||
| Merry42 (TORPA 2, NCT02725762) | 2017 | Prospective Interventional Case Series | 24 subjects with AREDS Stages 2–4, ≥ 50 years of age, VA ≥20/200 | 42 | 670 | WARP10 LED Device (Barneveld, WI) | 50–80 mW/cm2 for nine 88 sec treatments over 2 weeks | At 3 months, 5.14 letter improvement, 0.16 units contrast sensitivity, drusen volume decrease by 0.024 mm3 and central drusen thickness decreased by mean of 3.78 microns. Stable retinal thickness and retinal volume |
| 590 | Gentlewaves (Light bioscience, VA) | 4 mW/cm2 for nine 35 sec treatments over 2 weeks | ||||||
| 790 | Gentlewaves (Light bioscience, VA) | 0.6 mW/cm2 for nine 35 sec treatments over 2 weeks | ||||||
| Markowitz43 (LIGHTSITE I, NCT02725762) | 2019 | Randomized, sham controlled, single center study | 30 subjects with AREDS Stage 2–4 with VA 20/200-20/40 | 46 | 590 | Valeda Light Delivery System (Lumithera, WA) | 5 mW/cm2 for nine 250 sec treatments over 4 weeks after baseline; repeated at 24 weeks. | 50% of PBT subjects improved by 5 letters (vs 13.6%) at 1 month, improved contrast sensitivity, improved fixation stability, improved quality of life, at 12 months, 70% of study eyes had reduction in drusen volume vs 100% of sham eyes showing increase in drusen volume |
| 670 | 65 mW/cm2 for nine 250 sec treatments over 4 weeks after baseline; repeated at 24 weeks. | |||||||
| 850 | 8 mW/cm2 for 250 seconds delivered in 9 treatments over 4 weeks after baseline; repeated at 24 weeks. | |||||||
| LumiThera, Inc.46 (LIGHTSITE II, NCT03878420) | 2019 | Double-masked, sham-controlled, parallel design, prospective multi-site study | 96 participants ≥ 50 years of age with VA 20/100-20/30 and dry AMD | 96 | 590, 660, 850 | Valeda Light Delivery System (Lumithera, WA) | Unspecified | Last update August 2020. Outcomes are BCVA, contrast sensitivity, central drusen volume, central drusen thickness at 9 months |
| LumiThera, Inc.47 (LIGHTSITE III, NCT04065490) | 2019 | Double-masked, sham-controlled, parallel design, prospective multi-site study | 96 participants ≥ 50 years of age with VA 20/100-20/32 and dry AMD | 96 | 590, 660, 850 | Valeda Light Delivery System (Lumithera, WA) | Unspecified | Last Update February 2020. Outcomes are BCVA, contrast sensitivity, central drusen volume, central drusen thickness at 21 months |
| LumiThera, Inc.48 (ELECTROLIGHT, NCT04522999) | 2020 | Open label, prospective pilot study | 15 participants ≥ 50 years of age with VA 20/100-20/32 and dry AMD | 15 | 670 | Valeda Light Delivery System (Lumithera, WA) | 40 mW/cm2 for non ? sec treatments over 3 weeks | Last update January 2021. Outcomes are ERG changes on multifocal ERG, photopic negative response, multi-luminance flicker ERG, and fixed-luminance flicker ERG at 3 months and 6 month safer therapy |
| Grewal19 | 2020 | Randomized, sham controlled, single center pilot study | 42 (12 controls, 30 with intermediate AMD) | 42 | 670 | Custom Device | 40 mW/cm2 for 120 sec daily for 52 weeks | Unaltered rod time intercept, no change in scotopic threshold, no change in visual acuity, no change in photopic ERG, no change in ONL, RPE, RPE-BM complexes |
| Pinelli44 | 2020 | Case Report | 1 patient with dry AMD; unspecified stage | 2 | 590, 660, 850 | Valeda Light Delivery System (Lumithera, WA) | Unspecified mW/cm2 delivered 240 secs daily for 4 weeks | Reduced drusen, improved near/far VA at 1, 3 and 6 months. Subjective vision improvement. Contrast improved from 1.8 to 2.0 |
| Kaymak45 | 2020 | Case Series | 3 patients with intermediate AMD | 4 | 590, 660, 850 | Valeda Light Delivery System (Lumithera, WA) | Unspecified mW/cm2 for ? delivered in 9 sessions over 3 weeks, repeated at 7 months for 4 sessions over 2 weeks | Reduced drusen volume, microperimetry improvements, contrast improvements, subjective improvements in all cases, recordable vision improvement in one case |
Notes: *Or responsible party if no single author listed on clincaltrials.gov. ?Not specified duration of time (N/L) = not listed on clinicaltrials.gov.
Abbreviations: λ, wavelength; CFH, complement factor H; LED, light emitting diode; sec, seconds; ERG, electroretinogram; IBA, ionized calcium binding adaptor molecule 1; COX, cyclooxygenase; GFAP, glial fibrillary acidic protein; ATP, Adenosine Triphosphate; HSP60, heat shock protein 60; RPE-BM, Retinal Pigment Epithelium - Bruch’s Membrane; IR, infrared; AMD, age related macular degeneration; TNF, tumor necrosis factor; ONL, outer nuclear layer; ETDRS, Early Treatment in diabetic Retinopathy Study; AREDS, Age Related Eye Diseases Study; PBT, photobiomodulation therapy; CST, central subfield thickness; VA, visual acuity; ERG, electroretinogram; RPE, retinal pigment epithelium.