INTRODUCTION
Light as medicine may seem like a new concept, but scientists have known since at least the late 1800s that certain wavelengths of light in prescribed doses can be used to heal the tissue [1,2]. For the eye and vision care community, light is being used as Intense Pulsed Light Therapy (IPL) for dry eye, red-light treatment of myopia control, and optometric (Syntonic) phototherapy (OP) for treating visual conditions such as strabismus, amblyopia, and photo-sensitivity following brain trauma.
Photobiomodulation (PBM) is the current term being used to describe light therapy that is non-thermal and utilizes non-ionizing radiation in the visible and near-infrared spectrum. It was formerly called low-level laser (light) therapy or LLLT. Visible light being used and studied is primarily long wavelength red light or short-wavelength blue light (Fig. 1). Light as medicine is now considered a safe and effective tool and is playing an ever-increasing role in both eye health and general health. The newest information, as referenced in each section, is showing light’s importance for treatment of dry eye, age-related macular degeneration (AMD), post-cataract surgery, migraine headaches, cognitive enhancement, brain injury, Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases.
Some Key Takeaways:
AMD and Red-Light Therapy (Red light) – More recently, Samuel Markowitz, MD, and colleagues led a controlled study on the use of red-light therapy for dry ARMD and found significant acuity improvement in 50% of the patients along with improvement in contrast sensitivity, drusen volume, and central drusen thickness with no adverse effects being reported in the treatment group.
MYOPIA AND RED-LIGHT THERAPY (Red light)- Slowing myopia progression has become important as we now know that even low levels of myopia increase the risk for glaucoma, macular degeneration, and retinal detachment. Mechanisms for red light suppressing myopia progression suggest that narrow band long wavelength light promotes hyperopia by retarding axial elongation, decreasing elongation of the vitreous chamber, and increasing choroidal thickness [22]. In addition, it has been found that bright light suppresses form-deprivation myopia development by activating dopamine D1 receptor signaling in the retina.
Low-level red-light therapy, therefore, is an emerging treatment for slowing myopia progression. In 2022 alone, a number of studies demonstrated positive effects of red-light therapy in reducing myopia, reducing axial length, and being well-tolerated with no adverse effects.
Yu Jiang and colleagues used a home-based desktop light therapy device to administer red light of 650 nm wavelength at an illuminance level of approximately 1600 lux and a power of 0.29 mW for a 4-mm pupil. Treatment was done under parental supervision for 3 minutes per session, twice daily with a minimum interval of 4 hours between sessions. The treatment was administered 5 days per week. Subjects in the experimental group had far less myopic progression and axial length change than the control group that received sham therapy. They reported a mean spherical equivalent refraction change over 6 months of -0.2D, and average axial length change of 0.13 mm in the treatment
group versus a refraction change of -0.79D and axial length growth of 0.38 mm in the control group. Results of a 6-month follow-up showed additional positive results; 16% of subjects had reduced myopia and 25% showed reductions in axial length. The therapy was well-tolerated with no adverse effects being reported by test subjects [24].
Jiang Y, Zhu Z, Tan X, et al. Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children. Ophthalmology 2022;129(5):509–19.
In another study, Jing Dong and colleagues administered repeated low-level red-light therapy to a group of Chinese children. They also used a desktop redlight device with the experimental group receiving 100% light power and the sham group receiving 10% of the device’s power. Treatment was done at home, and they followed a similar schedule of 3-minute sessions twice daily with an interval of at least 4 hours between sessions. Cycloplegic refraction and axial length (AL) were measured at baseline and 6 months. Children in the treatment group had less myopia progression and axial elongation compared to the sham control group. At the final visit, distance visual loss was statistically significantly greater for children with myopia in the sham device group than for those in the red-light therapy group. Visual acuity testing demonstrated a change of 0.076 +/- 0.189 logMAR for the treatment group compared to -0.002 +/-0.172 logMAR for the sham treatment group (P=0.013). Mean spherical equivalent refraction change over 6 months was 0.06D in the treatment group and -0.11D in the sham device control group. The average AL growth was less 0.02 mm in the treatment group compared with 0.13 mm in the sham control group. The treatment was well-tolerated, and no adverse effects were reported.
In a recent literature review [26], it was found that while current recognized treatments for myopia including low-dose atropine, orthokeratology, and defocus-incorporated multiple segment spectacle lenses are 30% to 60% effective in delaying the onset of or progression of myopia, they are not strong enough to restrain AL growth. Lei Zhou and colleagues [27] were able to show that PBM therapy modestly decreases AL for myopia control. In addition, recent studies of red-light irradiation were found to induce hyperopia, therefore, red-light therapy may be a powerful tool in myopia prevention and control. In the literature review, it was noted that red light may be a safe treatment given its protective effect on both the cornea and retina.
Zhou L, Tong L, Li Y, et al. Photobiomodulation therapy retarded axial length growth in children with myopia: evidence from a 12-month randomized controlled trial evidence. Sci Rep 2023;13(1):3321.
Lei Tian and colleagues investigated the efficacy and safety of 650 nm low level red light for myopia control in children. The median 6-month change in AL was _0.06 for the treatment group and 0.14 mm for the control group (P. < 0.001). The median 6-month spherical equivalent refraction was 0.125D for the treatment group and _0.25 for the control group (P. <.001). They concluded that 650 nm low-level red light was an effective and safe treatment. It significantly slowed myopia progression in the children treated, reversed myopia progression in over half the children treated, and no adverse effects were observed.
MIGRAINE HEADACHE AND PAIN REDUCTION (Green light)- Exposing migraine sufferers to a narrow band of green light was found to significantly reduce photophobia and headache severity. This research by Rami Burstein, PhD, of the Harvard Brain Science Initiative was published in 2017.
Burstein R. Reply: Pupil area and photopigment spectral sensitivity are relevant to study of migraine photophobia. Brain 2017;140(1):e3.
Before that, he published findings suggesting that patients’ experience with color and migraine photophobia may originate in cone-driven retinal pathways, then fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. These findings helped to establish the value of green light for migraine [35,36].
Noseda R, Bernstein CA, Nir RR, et al. Migraine photophobia originating in cone-driven retinal pathways. Brain 2016;139(Pt 7):1971–86.
36] Green Light Exposure May Help Reduce Pain and Headaches. Time. Published October 27, 2022 Available at: https://time.com/6225133/green-light-headaches-pain-relief/. Accessed 3 March, 2023.
In a study presented at the 2022 annual meeting of the American Society of Anesthesiologists, Padma Gulur, MBBS, reported that 34 fibromyalgia patients were assigned to wearing either green, blue, or clear lenses for 4 hours per day for 2 weeks. Those wearing the green lenses reduced their reliance on opioids, were four times more likely to report less pain-related anxiety associated with their fibromyalgia, and they did not want to give up their green lenses at the end of the study [37].
- Fibromyalgia: How Green Eyeglasses Can Ease Anxiety. Healthline. Published October 23, 2022. Available at:https://www.healthline.com/health-news/fibromyalgia-how-greeneyeglasses-can-help-ease-pain-related-anxiety. Accessed 3 March, 2023.
BRAIN INJURY AND PHOTOBIOMODULATION (blue and red light)- A recent study of blue light exposure following mild traumatic brain injury (mTBI) provides evidence of the benefits of PBM on functional outcomes following brain injury. Killgore and colleagues provide a well-controlled, double- blind study on the use of blue light treatment. Test subjects received 30- minute pulses of blue light each morning, while control subjects received pulses of amber light. Test subjects showed significant improvements in sleep timing, daytime fatigue, and executive functioning. In addition, MRIs showed increased volume of the posterior thalamus (pulvinar).
A more recent review and meta-analysis of TBI in in vivo mammalian models supports the use of PBMin acute traumatic brain injury. The analysis favored light of 665 nm (red) and 810 nm with no differences found between pulsed or continuous wave light delivery. The review supports antiapoptotic, anti-inflammatory, and pro-proliferative effects, and modulation of cellular metabolism. They concluded that substantial meta-analysis evidence exists for both functional and histological outcomes of traumatic brain injury in in vivo mammalian models [39].
- Killgore WDS, Vanuk JR, Shane BR, et al. A randomized, double-blind, placebo-controlled trial of blue wavelength light exposure on sleep and recovery of brain structure, function, and cognition following mild traumatic brain injury. Neurobiol Dis 2020;134:104679.
[39] Stevens AR, Hadis M, Milward M, et al. Photobiomodulation in Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis. J Neurotrauma 2023;40(3–4):210–27.
SUMMARY
The use of modulated light to treat visual and systemic conditions now is considered a safe and effective tool. Research has changed its mission from if light can heal to how light stimulates healing. Initial research concentrated on the effect of modulated light in mitochondria and the cytochrome c oxidase molecule with its ability to allow the release of nitric oxide and assist the cells in increasing ATP production. Now research is expanding to include many other positive effects for light as medicine. The more recent discovery of intrinsically photosensitive retinal ganglion cells and their connection to hypothalamus support the use of light in the maintenance of health, and the autonomic system balance validates the use of light through the eyes to treat organic and functional vision disorders.
Today, the eye and vision care community has the opportunity to use devices that deliver modulated light through the eyes for macular degeneration, dry eye, myopia control, amblyopia, and other ocular conditions. In addition, we have tools to assist our patients with photosensitivity, migraine headaches, and the sequelae of brain injury.
In the future, there most certainly will be expanded opportunities to use modulated light for Alzheimer’s disease, Parkinson’s disease, and other neuro-degenerative diseases, as well as to prevent or slow ocular conditions resistant to current surgical or drug interventions.
