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Light therapy in retinal vascular disease

Ricci LH

Department of Ophthalmology, School of Medicine, Laureate International Universities, São Paulo (SP), Brazil

E-mail : aa

Gonçalves ICD

Department of Ophthalmology, School of Medicine, Laureate International Universities, São Paulo (SP), Brazil

Andrade GC

Department of Ophthalmology and Visual Sciences-Federal University of São Paulo (UNIFESP), São Paulo (SP), Brazil

Ferraz CA

Department of Ophthalmology, School of Medicine, Laureate International Universities, São Paulo (SP), Brazil
Department of Ophthalmology and Visual Sciences-Federal University of São Paulo (UNIFESP), São Paulo (SP), Brazil

DOI: 10.15761/PMRR.1000160

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Abstract

Objectives: To describe and appraise the latest reports on light devices currently used for the treatment of diabetic retinopathy and age-related macular degeneration.

Methods: The present review was conducted using four national and international databases - PubMed, Scielo, Medline and Cochrane. Initial set of clinical or experimental trials was screened based on title and abstracts, followed by full text analysis and critical review.

Results: Five main articles were included. Each report’s methods and results are described in table 1. Light-mask appears to be effective in the treatment of diabetic retinopathy and diabetic macular edema. A recent trial is being conducted to evaluate its efficacy in early age-related macular degeneration, although no results are available yet.

Table 1: Depicts the latest and current trials concerning the use of a light device during sleep and the effect on progression of diabetic retinopathy, diabetic macular edema and early AMD.

Studies

Retinal disease

Light device

Results

Arden, et al. (2010) [16]

Diabetic maculopathy

 

 

Trans-lid retinal illumination

 

 

 

12 patients enrolled in a 3 month-period. Reduction in tritan thresholds and the incidence of hemorrhage and microaneurysms (p=0.03).

Arden, et al. (2011) [17]

 

 

Diabetic maculopathy

 

 

 

Sleep mask (505 nm)

 

 

 

 

 

34 patients enrolled in a 6 month-period. Regression of macular edema (p=0.01) and improvement of visual acuity, achromatic contrast sensitivity, and microperimetric thresholds.

Sivaprasad, et al. (2014) [18]

 

Non-central diabetic maculopathy

 

 

Sleep mask (PolyPhotonix Medical Ltd)

 

 

Results are still not available.

 

 

McKeague, et al. (2014) [14]

 

Early AMD

 

 

Sleep mask (PolyPhotonix Medical Ltd)

 

Results are still not available.

 

 

Sahni, et al. (2017) [11]

 

Diabetic maculopathy

 

Sleep mask (PolyPhotonix Medical Ltd)

 

46 patients enrolled in 4 month-period (1 month for recovery). Beneficial effect on OCT CST (p=0.001) and OCT maxCT (p=0.05). Psychological wellbeing worsened in all groups (p=<0.05).

 

Conclusion: Based on recent latest clinical trials, light-mask shows promising results in the treatment of diabetic retinopathy and diabetic macular edema. 

Key words

Light-mask; Diabetic macular edema; Rods; Retinal hypoxia; Dark adaptation

Introduction

The outer retina is an avascular layer that is predominantly composed by photoreceptors. Its vascular supply depends on simple diffusion, relying in the integrity of choroidal circulation [1].

Rods are highly metabolic active [2,3], consuming the most oxygen delivered to the retina. In bright light, oxygen consumption decreases due to a drop in the energy required by these cells [4]. In contrast, cones seem to consume the same amount of O2 as it would in dark environments, and energy requirement is minimally affect by differences is luminosity.

Light is a novel, simple approach that may be used to alter retinal hypoxia [5,6], which is a major component in retinal vascular diseases such as diabetes and age-related macular degeneration (AMD). Evidences show that inner segment hypoxia is sufficient to trigger microvascular changes [7], which may be further enhanced by choroidal vasculopathy, an early feature of systemic vascular diseases, such as diabetes [8].

In this review, the authors will present the latest evidence on how light can affect vascular integrity and disease progression based on recent experimental and clinical trials.

Methods

A retrospective, descriptive review of current models using light devices to prevent nocturnal retinal hypoxia was conducted, based on recent clinical trials available in literature. Four national and international databases were consulted (PubMed, Scielo, Medline, and Cochrane). An initial screen yielded a total of twenty three articles, each meeting at least one of the following criteria:
(1) retinal changes in diabetes mellitus and age-related macular degeneration,
(2) light-masks for the treatment of retinal hypoxia, and
(3) rod metabolism.
After secondary analysis, only 5 clinical trials were considered to meet two or three of the above criteria. These were included in this review.

Results and Discussion

The idea to prevent retinal hypoxia using light therapy during sleep has been promising, although there is little evidence to support it. In 2008, Okawa, et al. [4] showed that mice retinal oxygen consumption is decreased approximately by half in the presence of bright light. On the contrary, using diabetic mice in a 12-week period, Kur, et al. [9] showed that a 12:12 hour light-adapted photocycle (30 lux during day, and 3 lux during night) did not prevent the progression of neuronal and glial abnormalities when compared to control group (30 lux during day, and 0 lux during night). However, the authors postulate that a 12 week period may have been insufficient to detect positive effects with this intervention, although some studies described below report positive results during the same period of intervention. 

Sahni, et al. [10] evaluated the use of a light-mask (504 nm wavelength, 80 cd/m², for 8 hours nightly) in two different age-groups with healthy participants compared to a third group, composed by patients with diabetic macular edema. Several parameters were evaluated after a three month period, including psychological assessment. Intolerance to light and sleep disturbance were reported, which caused a withdrawal of 6 patients. However, in those with macular edema, there was a reduction of optical coherence tomography mean central subfield thickness (OCT CST; p=0.001) and mean thickness of OCT subfield with maximal pathology (OCT maxST; p=0.05) at months 3 and 4, as well as cyst resolution/reduction in 67% of patients.

Even though sleep and psychological wellbeing were compromised, the authors reported no major safety precaution. Further, the rise in PO2 with this approach does not seem to harm the rods, even in prolonged periods of illumination [11].

Noctura 400® (PolyPhotonix Medical Ltd, Sedgefield, UK) is a light-mask recently developed for the treatment of diabetic retinopathy and diabetic macular edema, and is currently being (or have been) used in large clinical trials, with promising results. It consists in a light-emitting diode placed inside a fabric mask, originally intended for a 12 week period during night-time sleep [12]. Although there is a focus on diabetes, a recent protocol [13] has been developed for patients with early AMD, and is currently in progress. Vascular compromise in patients with AMD may correlate to the thickness of Bruch’s membrane, which further impair oxygen diffusion to the outer segment [14]. A newer version, Noctura 500, has been designed for wet AMD. Currently, however, no evidence is available for its use in this disease.

The adoption of a light-mask may also have an impact on health care cost. Patients with proliferative diabetic retinopathy typically require costly treatments, such as laser photocoagulation or repeated sessions of intra-ocular anti-vascular endothelial growth factor (anti-VEGF). Light therapy may potentially replace these options in the future (Table 1) [10,13,15-17]. 

Conclusion

Latest clinical trials seem to favor effect of low-level night-time light therapy in patients with diabetic maculopathy, non-central diabetic maculopathy and early AMD. To our knowledge, this was the first review on this subject, concerning the newest experimental protocols of light therapy. The approach of this review is to organize the information needed for future research.

Acknowledgement

The authors declare no conflict of interest.

No financial support was required for the development of this article.

References

  1. Ciulla TA, Harris A, Kagemann L, Danis RP, Pratt LM, et al. (2002) Choroidal perfusion perturbations in non-neovascular age related macular degeneration. Br J Ophthalmol 86: 209-213. [CrossRef]
  2. Calzia D, Barabino S, Bianchini P, Garbarino G, Oneto M, et al. (2013) New findings in ATP supply in rod outer segments: insights for retinopathies. Biol Cell 105: 345-358. [CrossRef]
  3. Birol G, Wang S, Budzynski E, Wangsa-Wirawan ND, Linsenmeier RA (2007) Oxygen distribution and consumption in the macaque retina. Am J Physiol Heart Circ Physiol 293: H1696–H1704. [CrossRef]
  4. Okawa H, Sampath AP, Laughlin SB, Fain GL (2008) ATP consumption by mammalian rod photoreceptors in darkness and in light. Curr Biol 18: 1917-1921. [CrossRef]
  5. de Gooyer TE, Stevenson KA, Humphries P, Simpson DA, Gardiner TA, et al. (2006) Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration. Invest Ophthalmol Vis Sci 47: 5561-5568. [CrossRef]
  6. Arden GB (2001) The absence of diabetic retinopathy in patients with retinitis pigmentosa: implications for pathophysiology and possible treatment. Br J Ophthalmol 85: 366-370. [CrossRef]
  7. Sivaprasad S, Arden G (2016) Spare the rods and spoil the retina: revisited. Eye (Lond) 30: 189-192. [CrossRef]
  8. Cao J, McLeod S, Merges CA, Lutty GA (1998) Choriocapillaris degeneration and related pathologic changes in human diabetic eyes. Arch Ophthalmol 116: 589-597. [CrossRef]
  9. Kur J, Burian MA, Newman EA (2016) Light adaptation does not prevent early retinal abnormalities in diabetic rats. Sci Rep 6: 21075. [CrossRef]
  10. Sahni JN, Czanner G, Gutu T, Taylor SA, Bennett KM, et al. (2017) Safety and acceptability of an organic light-emitting diode sleep mask as a potential therapy for retinal disease. Eye (Lond) 31: 97-106. [CrossRef]
  11. Yagi T, MacLeish PR (1994) Ionic conductances of monkey solitary cone inner segments. J Neurophysiol 71: 656-665. [CrossRef]
  12. Improving the prevention and treatment of diabetic retinopathy and diabetic macular edema (2017) Special report. Global Business Media.
  13. McKeague C, Margrain TH, Bailey C, Binns AM (2014) Low-level night-time light therapy for age-related macular degeneration (ALight): study protocol for a randomized controlled trial. Trials 15: 246. [CrossRef]
  14. Stefánsson E, Geirsdóttir A, Sigurdsson H (2011) Metabolic physiology in age related macular degeneration. Prog Retin Eye Res 30: 72-80. [CrossRef]
  15. Arden GB, Gunduz MK, Kurtenbach A, Volker M, Zrenner E, et al. (2010) Preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy. Eye (Lond) 24: 1149-1155. [CrossRef]
  16. Arden GB, Jyothi S, Hogg CH, Lee YF, Sivaprasad S (2011) Regression of early diabetic macular oedema is associated with prevention of dark adaptation. Eye (Lond) 25: 1546-1554. [CrossRef]
  17. Sivaprasad S, Arden G, Prevost AT, Crosby-Nwaobi R, Holmes H, et al. (2014) A multicentre phase III randomized controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomized controlled trial. Trials 15: 458. [CrossRef]

Editorial Information

Editor-in-Chief

Martin Grabois
Baylor College of Medicine

Article Type

Research Article

Publication history

Received date: December 05, 2017
Accepted date: December 26, 2017
Published date: December 30, 2017

Copyright

©2017 Ricci LH. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Ricci LH (2017) Light therapy in retinal vascular disease. Phys Med Rehabil Res 2: DOI: 10.15761/PMRR.1000160

Corresponding author

Lucas Holderegger Ricci

Department of Ophthalmology, School of Medicine, Laureate International Universities, São Paulo (SP), Brazil

Table 1: Depicts the latest and current trials concerning the use of a light device during sleep and the effect on progression of diabetic retinopathy, diabetic macular edema and early AMD.

Studies

Retinal disease

Light device

Results

Arden, et al. (2010) [16]

Diabetic maculopathy

 

 

Trans-lid retinal illumination

 

 

 

12 patients enrolled in a 3 month-period. Reduction in tritan thresholds and the incidence of hemorrhage and microaneurysms (p=0.03).

Arden, et al. (2011) [17]

 

 

Diabetic maculopathy

 

 

 

Sleep mask (505 nm)

 

 

 

 

 

34 patients enrolled in a 6 month-period. Regression of macular edema (p=0.01) and improvement of visual acuity, achromatic contrast sensitivity, and microperimetric thresholds.

Sivaprasad, et al. (2014) [18]

 

Non-central diabetic maculopathy

 

 

Sleep mask (PolyPhotonix Medical Ltd)

 

 

Results are still not available.

 

 

McKeague, et al. (2014) [14]

 

Early AMD

 

 

Sleep mask (PolyPhotonix Medical Ltd)

 

Results are still not available.

 

 

Sahni, et al. (2017) [11]

 

Diabetic maculopathy

 

Sleep mask (PolyPhotonix Medical Ltd)

 

46 patients enrolled in 4 month-period (1 month for recovery). Beneficial effect on OCT CST (p=0.001) and OCT maxCT (p=0.05). Psychological wellbeing worsened in all groups (p=<0.05).