Photobiomodulation therapy as a new hope therapy for retinitis pigmentosa: a systematic review

Alberta, Ivana Beatrice; Amelia, Yufilia Suci; Stefanie, Airina

doi:10.37039/1982.8551.20240023

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Review Article • Rev. bras.oftalmol. 83 • 2024 • https://doi.org/10.37039/1982.8551.20240023 copy

Photobiomodulation therapy as a new hope therapy for retinitis pigmentosa: a systematic review

Terapia de fotobiomodulação como nova terapia de esperança para retinite pigmentosa: uma revisão sistemática

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Retinitis pigmentosa is one of the leading causes of hereditary blindness in developed countries and unfortunately there is currently no cure. Photobiomodulation therapy can penetrate the retina and optic nerve and restore the function of damaged mitochondria as an intracellular target. This study is proposed to review and analyze photobiomodulation as a strategy that has the potential to be a new hope therapy and non-invasive treatment for retinitis pigmentosa in the long term. PubMed^® and Google Scholar were used to perform a systematic review of photobiomodulation as a therapy for retinitis pigmentosa. Using PRISMA 2020 Guidelines, we include seven studies in this review. The inclusion criteria for each study were as follows: the study documented the use of photobiomodulation therapy for retinitis pigmentosa, was conducted in human eyes or animals’ eye, its full text was in English, and it published in the last 10 years. We anticipated that most studies would be experimental design, we evaluated the quality of eligible studies using relevant items from the ROBINS-I, which is the recommended tool to evaluate experimental study. There is a clinical improvement in visual acuity and visual fields. Further eye examination showed functional and outer nuclear layer preservation, decline waveforms of electroretinogram slower than control, disruption of retinal pigment epithelium, and preserved photoreceptor nuclei twice thicker than control (p < 0.05). Photobiomodulation also increases retinal mitochondrial function and maintains mitochondrial redox state, revealing significant recovery of photoreceptors’ cell function. Photobiomodulation showed significant change in clinical improvement, mitochondrial repair, and retinal layer thickening; thus, photobiomodulation can be a new hope for therapeutic strategies for retinitis pigmentosa. Several studies only have a few participants, so it does not provide a long-term outcome in retinitis pigmentosa.

Keywords:
Retinitis; Retinitis pigmentosa; Photobiomodulation therapy; Low-level light therapy

No	Entry	Filter	Total Findings
1	((((("phototherapy"[MeSH Terms]) OR ("Low Level Light Therapy"[Text Word])) OR ("Low-Level Laser Therapy"[Text Word])) OR ("Laser Phototherapy"[Text Word])) OR ("Light Therapy"[Text Word])) OR (Photobiomodulation Therapy)	None	5,828
2	(("Retinitis Pigmentosa"[MeSH Terms]) OR ("Retinal Degeneration"[Text Word])) OR ("Retinal Diseases"[Text Word])	None	5,084
3	S1 AND S2	none	234
4	S1 AND S2	Last ten years and full text	61

No	Entry	Filter	Total Findings
1	"low-level light therapy laser" OR therapy "photobiomodulation" AND "Retinitis Pigmentosa"	None	322
2	"low-level light therapy laser" OR therapy "photobiomodulation" AND "Retinitis Pigmentosa"	Last ten years	280

First author	Design	Subjects	Eyes (no)	Dose and delivery parameters			Duration	Results
First author	Design	Subjects	Eyes (no)	λ (nm)	power density (mW/cm²)	energy density (J/cm²)	Duration	Results
Gopalakrishnan et al.(¹1 Gopalakrishnan S, Mehrvar S, Maleki S, Schmitt H, Summerfelt P, Dubis AM, et al. Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa. Sci Rep. 2020 Dec;10(1):20382.)	Experimental study	P23H rats	N/A	830	25	4,5	Once a day in 15 days (5 days on 2 days off)	Preserves the mitochondrial redox state (higher redox ratio, increasing NADH, decreasing FAD), preserving retinal structure (retinal and ONL thickness), protect photoreceptor cell loss
Kirk et al.(³3 Kirk DK, Gopalakrishnan S, Schmitt H, Abroe B, Stoehr M, Dubis A, et al. Photobiomodulation reduces photoreceptor death and regulates cytoprotection in early states of P23H retinal dystrophy. In: Mechanisms for Low-Light Therapy VIII [Internet]. SPIE; 2013 [cited 2022 Jan 25]. p. 84–93. Available from: https://www.spiedigitallibrary.org/conference-proceedings-of-spie/8569/85690F/Photobiomodulation-reduces-photoreceptor-death-and-regulates-cytoprotection-in-early-states/10.1117/12.981791.full https://www.spiedigitallibrary.org/confe... )	Experimental study	P23H rats	9	670	50	9	Once a day in 5 days for 180 seconds	Increase retinal mitochondrial cytochrome oxidase (in INL and GCL), improve photoreceptors function and reduce photoreceptors cell loss. (TUNEL+ cells in the ONL was reduced 70%), preserve retinal tissue
Kang et al.(⁸8 Kang S, Lorach H, Bhuckory MB, Quan Y, Dalal R, Palanker D. Retinal Laser Therapy Preserves Photoreceptors in a Rodent Model of MERTK-Related Retinitis Pigmentosa. Translational Vision Science & Technology. 2019 Aug 7;8(4):19.)	Experimental study	Rats	30 rats divided into 6 groups (n=5 per group) Fellow eye as control	N/A	40	N/A	Single dose for 15 ms	FA: hyperreflective spots, indicating disruption of the RPE in laser treated areaERG: Waveforms decline slower with time in treated eye than in control eyeB-wave: the laser pattern density of 1.5 d was optimal for functional preservationOCT: ONL preservation in laser-treated eyes until P180 while in control, ONL was not distinguishable after P98mfERG: preservation of ONL only in the treated central retina, whereas little to no ONL was observed in untreated eyeHistology: in treated eye, exhibited the best-preserved photoreceptor layer, up to five rows of photoreceptor nuclei, while in control eye displayed no discernible photoreceptor layer or their nuclei
Lorach et al.(⁹9 Lorach H, Kang S, Dalal R, Bhuckory MB, Quan Y, Palanker D. Long-term Rescue of Photoreceptors in a Rodent Model of Retinitis Pigmentosa Associated with MERTK Mutation. Sci Rep. 2018 Jul 27;8(1):11312.)	Experimental study	Rats	12 eyes (fellow eyes as control)	577	40	N/A	N/A	mfERG: responses only in the laser-treated area, no response in control OCT: delays the loss of photoreceptorsHistology: twice thicker ONL in the laser-treated area (p < 0.05)B-wave: amplitudes were higher in the laser-treated eyes than control
Ivandic et al.(¹³13 Ivandic BT, Ivandic T. Low-Level Laser Therapy Improves Vision in a Patient with Retinitis Pigmentosa. Photomedicine and Laser Surgery. 2014 Mar;32(3):181–4.)	Case report	RP patient	2	780	N/A	0,4	2 times per w for 2 weeks (for 40 s each)	Increased visual acuity from 20/50 at baseline to 20/20 in each eye (uncorrected)No adverse effect was noted
Ghanian et al.(¹²12 Ghanian Z, Maleki S, Gopalakrishnan S, Sepehr R, Eells JT, Ranji M. Optical imaging of oxidative stress in retinitis pigmentosa (RP) in rodent model. In: Optical Diagnostics and Sensing XIII: Toward Point-of-Care Diagnostics [Internet]. SPIE; 2013 [cited 2022 Jun 15]. p. 138–43. Available from: https://www.spiedigitallibrary.org/conference-proceedings-of-spie/8591/85910S/Optical-imaging-of-oxidative-stress-in-retinitis-pigmentosa-RP-in/10.1117/12.2004843.full https://www.spiedigitallibrary.org/confe... )	Experimental study	P23H rats	12 eyes divided into 3 groups (4 eyes per groups)	670	50	4,5	for 90 sec	Less oxidative stress in mitochondrial respiratory chain (20% increase the NADH RR), which reveals a significant recovery of photoreceptors cell function in retina
	Experimental study	P23H rats	12 eyes divided into 3 groups (4 eyes per groups)	830	25	4,5	for 180 sec
Gkotsi et al.(¹⁴14 Gkotsi D, Begum R, Salt T, Lascaratos G, Hogg C, Chau KY, et al. Recharging mitochondrial batteries in old eyes. Near infra-red increases ATP. Experimental Eye Research. 2014 May 1;122:50–3.)	Experimental study	rats	79	670	40	N/A	7 times spaced evenly over 84 hours, for 90 seconds	ATP is increased significantly by 670 nm exposure, associated with increased COX and reduced acrolein expression

Reference	Potential for confounding	Eligibility criteria	Intervention	Deviation from intended intervention	Missing data	Measurement of outcomes	Selection in reported result
Gopalakrishnan et al.(¹1 Gopalakrishnan S, Mehrvar S, Maleki S, Schmitt H, Summerfelt P, Dubis AM, et al. Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa. Sci Rep. 2020 Dec;10(1):20382.)	Probably no	Unclear	Yes	No	No	Yes	Yes
Kirk et al.(³3 Kirk DK, Gopalakrishnan S, Schmitt H, Abroe B, Stoehr M, Dubis A, et al. Photobiomodulation reduces photoreceptor death and regulates cytoprotection in early states of P23H retinal dystrophy. In: Mechanisms for Low-Light Therapy VIII [Internet]. SPIE; 2013 [cited 2022 Jan 25]. p. 84–93. Available from: https://www.spiedigitallibrary.org/conference-proceedings-of-spie/8569/85690F/Photobiomodulation-reduces-photoreceptor-death-and-regulates-cytoprotection-in-early-states/10.1117/12.981791.full https://www.spiedigitallibrary.org/confe... )	No	Yes	Yes	No	No	Yes	Yes
Kang et al.(⁸8 Kang S, Lorach H, Bhuckory MB, Quan Y, Dalal R, Palanker D. Retinal Laser Therapy Preserves Photoreceptors in a Rodent Model of MERTK-Related Retinitis Pigmentosa. Translational Vision Science & Technology. 2019 Aug 7;8(4):19.)	Probably no	Yes	Unclear	No	No	Yes	Yes
Lorach et al.(⁹9 Lorach H, Kang S, Dalal R, Bhuckory MB, Quan Y, Palanker D. Long-term Rescue of Photoreceptors in a Rodent Model of Retinitis Pigmentosa Associated with MERTK Mutation. Sci Rep. 2018 Jul 27;8(1):11312.)	Probably no	Yes	Unclear	Probably no	No	Yes	Yes
Ivandic et al.(¹³13 Ivandic BT, Ivandic T. Low-Level Laser Therapy Improves Vision in a Patient with Retinitis Pigmentosa. Photomedicine and Laser Surgery. 2014 Mar;32(3):181–4.)	No	Yes	Yes	Probably no	No	Unclear	Yes
Ghanian et al.(¹²12 Ghanian Z, Maleki S, Gopalakrishnan S, Sepehr R, Eells JT, Ranji M. Optical imaging of oxidative stress in retinitis pigmentosa (RP) in rodent model. In: Optical Diagnostics and Sensing XIII: Toward Point-of-Care Diagnostics [Internet]. SPIE; 2013 [cited 2022 Jun 15]. p. 138–43. Available from: https://www.spiedigitallibrary.org/conference-proceedings-of-spie/8591/85910S/Optical-imaging-of-oxidative-stress-in-retinitis-pigmentosa-RP-in/10.1117/12.2004843.full https://www.spiedigitallibrary.org/confe... )	No	Yes	Yes	No	No	Yes	Yes
Gkotsi et al.(¹⁴14 Gkotsi D, Begum R, Salt T, Lascaratos G, Hogg C, Chau KY, et al. Recharging mitochondrial batteries in old eyes. Near infra-red increases ATP. Experimental Eye Research. 2014 May 1;122:50–3.)	No	Yes	Yes	No	No	Yes	Yes

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[1] Corresponding author: Ivana Beatrice Alberta Jl. Raya Kalirungkut 27/B10, Surabaya E-mail: ivanabeatricealberta@gmail.com