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Photobiomodulation for retinal diseases Table 1 PBM sample delivery protocols from animal model studies PBM delivery device LED array (λ=670nm) LED array (λ=670nm) LED array (λ=670nm) Table 2 PBM sample delivery protocols from clinical trials Concurrent treatment None Twice during the light-damage period None None Daily, 3min each, at 9 J/cm Retinal disease [44] Model of AMD Species SD rats Lewis rats New-born C57BL/6J mice or SD rats Pre-treatment Once daily for 5d prior to light damage, 3min each, energy fluence of 9 J/cm2 Once on the day prior to light damage None None None Mode of PBM application At 2.5 cm distance from the eye Whole-body irradiation At 2.5 cm distance from the eye Mode of disease induction Light damage with 1000 lx for 24h Streptozoto-cin- induced diabetes Oxygen-induced retinal damage over 5d (mice), 18d (rats) Mode of PBM Application Transconjunctival irradiations Through a closed eyelid Appliedtothemaculabyguidingthebeamofthelaserdiodeat 1 cm distance above the eyeball, with the eye in adduction Post-treatment None Once after the light-damage period Once daily for 5d, 3min each, at energy fluence of 9 J/cm2 Once daily for 9wk, 240s Model retinopathy[35] of diabetic 2 each, at 6.0 J/cm energy density None total Model of ROP[53] 2 Model of methanol [33] LED array (λ=670nm) Whole-body irradiation Methanol intoxication 2.5min sessions at 5, 25, and 50h after methanol poisoning, at 4 J/cm2 SD rats λ: Wavelength; AMD: Age-related macular degeneration; SD: Sprague-Dawley; LED: Light-emitting diode; ROP: Retinopathy of prematurity. toxicity None Twice per week for 2wk, 40s, at 0.3 J/cm2 each Twice a day for 2-9mo, 80s each, at 25 J/cm2 total energy density 3-4 sessions over 2wk period, 30s each, at 0.22 J/cm2 each Twice a week for 2wk, 40s, at 0.4 J/cm2 each, repeated 5y later after a relapse Given the promising pre-clinical results and the equally promising first few translations to human patients, we should expect a growth in the field of photobiomodulation applied to treat common retinal conditions such as age-related macular degeneration, retinopathy of prematurity, and diabetic retinopathy, as well as the many orphan disease variants of retinitis pigmentosa and possibly other retinal conditions. Nevertheless, much more work in human subjects as well as in animal models needs to be carried out in order to: 1) better understand the underlying mechanisms of how PBM helps cure and/or prevent retinal damage; 2) establish robust treatment protocols for the various applications; 3) identify and properly address potential harmful effects on the various tissues that get irradiated during PBM treatments. Currently, there are a number of challenges in the field. These include the large variety of potentially treatable ocular conditions and the wide range of treatment protocols being published in terms of wavelength, treatment session duration, and the total number of treatment sessions. These aspects make it harder to pull the available data into Meta-analyses for the purpose of developing standardized treatment guidelines. Also, most None λ PBM delivery (nm) device 780 Semi-conductor laser diode 670 LED array Semi-conductor 780 laser diode two times per week for 2wk. This resulted in VA improvement to 20/20 bilaterally and the regaining of normal visual field outer perimeters, although there remained a residual mid-peripheral circular scotoma. These gains in visual function were retained over the following 5y. However , the patient experienced a relapse at year 5 post-treatment with his visual function decreasing down to the pre-treatment level. A repetition of the 4-session PBM was able to restore the original vision gains and over the following 2y the patient underwent 17 more treatment sessions, on an as needed basis, in order to maintain the same VA. Certainly, a larger study will be necessary to optimize the treatment protocol and gain a deeper understanding of the mechanism involved in the healing of retina succumbing to RP. Nevertheless, this very first report offers hope and will likely serve to spur more studies. Delivery Protocols Being a rather new therapeutic approach for the treatment of retinal conditions, the experimental protocols for PBM delivery vary greatly. To illustrate this diversity, Tables 1 and 2 provide examples of successful regimen in animal model studies and clinical trials, respectively. Type of retinal disease AMD[21] Diabetic retinopathy[22] Amblyopia in adolescents and adults[23] PBM regimen 780 Continuous-wave laser diode RP[57] λ: Wavelength; AMD: Age-related macular degeneration; LED: Light-emitting diode; RP: Retinitis pigmentosa. Transconjunctival illumination of the whole retina 150 CONCLUSIONPDF Image | Photobiomodulation for the treatment of retinal diseases
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