01.09.2015
New studies on the treatment of eye diseases with PBM cause a sensation. PBM has been investigated as a therapy for age-related macular degeneration.
In the past two years studies on an area of application of LLLT have been published that was previously absolutely taboo. Direct irradiation of the eye had been considered the ultimate contraindication since the beginning of LLLT. Now this taboo has been broken, and there are signs in research that eye diseases may become significant indications of LLLT in the future.
Human case studies on the treatment of dry AMD (age-related macula degeneration), diabetic retinopathy, retinitis pigmentosa, and on controlling retinal blood flow, as well as animal studies on the treatment of retinopathy of prematurity, AMD, and generally of damage to the photoreceptors, among other ailments, promise to hold great potential for LLLT in the treatment of eye diseases.
THE MOST IMPORTANT INDICATION: AMD
One of the most important eye diseases is age-related macula degeneration (AMD). Due to the increase in life expectancy, AMD is expected to rise considerably over the next few decades. AMD is the main reason for blindness in the elderly in the industrial nations. It is considered non-treatable, but its course can be delayed by adapting a healthy lifestyle and the intake of antioxidants and such substances as lutein and zeaxanthin (AREDS 2 ? Age-Related Eye Disease Study 2).
There are two types of AMD: wet AMD (also called neovascular or exudative AMD) and atrophic, dry AMD (also called geographic atrophy or GA-AMD AMD). The former is responsible for 90% and the latter for 10% of serious visual impairments. Wet AMD is characterized by choroidal neovascularization (the formation of new vessels in the choroid, the vascular layer of the eye that is located between the retina and the sclera). Dry AMD is characterized by an atrophy of the retinal pigment epithelium and a degeneration of the photoreceptors in the deeper layers. Dry AMD is believed to be caused by inflammations, oxidative stress, and genetic disposition.
Inhibition of VEGF (vascular endothelial growth factor) in order to curb angiogenesis by way of repeated, cost-intensive intravitreal injections (anti-VEGF therapy), which carry the risk of inflammation and retinal detachment, is regarded as the gold standard in the treatment of wet AMD. No therapy exists for dry AMD.
Since the pathogenesis of AMD has been largely deciphered today, therapeutic approaches which can influence the underlying mechanisms are the most promising. Being a safe, affordable, and highly controllable therapy, LLLT has therefore attracted a good deal of attention over the past few years as a method for treating eye diseases. Due to its photomodulatory effects on all kinds of metabolic processes which are also involved in the development of AMD, it is assumed that it holds great potential for the treatment of AMD and other eye diseases.
The causes of macula degeneration are age-related mutations of the mitochondrial DNA, which reduce the synthesis of ATP and lead to oxidative stress, inflammation, and degeneration, among other consequences. Inflammation is a general characteristic of the ageing process. It occurs in the old retina and particularly age-related macula degeneration (AMD) and promotes the pathological formation of new vessels, the main symptom of wet AMD.
It is a primary as well as secondary effect of photobiomodulation through LLLT that it promotes the cell's reactions to inflammations, stress, and apoptosis.
The effects that may be expected when treating eye diseases include, among others:
? Inhibition of retinal neovascularization
? Reduction of HIF-1 (hypoxia-induced factor 1), a marker for the formation of VEGF which has been activated by hypoxia (anti-VEGF therapy)
? Reduction of oxidative stress in the external retina and the retinal pigment epithelium
? Modulation of gene expression and cytokine release
? Regulation of inflammation reactions in the case of transmural microtraumas
When administered in a proper dose, LLLT can trigger a cascade of biochemical and biophysical cell mechanisms in connection with the formation of high-energy molecules, such as ATP, and the ability of receptors to function properly. The latter modulate the entire metabolism at the cell and tissue level, and are needed for the complex system of signal transmission. Some laser therapists ascribe to LLLT the potential of a monotherapy for many diseases of the eye.
STUDY RESULTS
Only scattered case studies involving humans have been performed, while animal models have been able to clearly demonstrate the potential of LLLT in the treatment of eye diseases.
Animal studies
The results of the animal studies are, among others:
? Increase in cytochrome c oxidase (COX), an enzyme of the respiratory chain which regulates oxidative phosphorylation
? Reduction of inflammation markers (e.g. inflammation-enhancing complement factor C3) in the external retina
? Reduction of retinal stress makers, such as vimetin and GFAP (glial fibrillary acidic protein)
? Increase of the membrane potential in aged eyes
? Significant ATP increase
? Reduction of free radicals (markers for oxidative stress) such as acrolein expression
? Increase in neuroprotective factors
? Regulation of genes and ncRNA (non-coding RNA genes) which are involved in neuroprotective processes
? Improvement of the photo receptor functions
? Increase in activated microglia
Case studies involving humans
The results of the human case studies are, among others:
? Reduction of diabetic oedemas and a thickening of the retina
? Normalization of visual fields
? Improvement of visual acuity
? Improvement of contrast vision
? Improvement of fixation stability
? Increase in blood flow speed in the arteria ophthalmica
Case study of dry AMD
A prospective case study of nine patients with dry AMD and the application of near infrared and yellow LLLT by Graham Merry et al. (2012) found significantly positive treatment results with respect to visual acuity, contrast vision, and fixation stability.
In each treatment, the test persons were irradiated using two different laser units and three different wavelengths (1st device: 670 nm / 4?7.68 J/cm²; 2nd device: 590 nm and 790 nm / 0.1 J/cm²).
The results were documented immediately following the LLLT and again after four, six, and twelve months. The improvements remained at a significant level even after twelve months, with the exception of visual acuity, which began to deteriorate again in some test persons after approximately four months. In patients whose visual acuity deteriorates drastically within a short time, it might make sense to follow up with repeat treatments in four-month intervals.
Case study of diabetic retinopathy
In the case study by Tang J et al. (2014), four patients with type 2 diabetes and a diabetic macula oedema were treated with red and near infrared LLLT on the eye over a period of up to nine months. In all patients, one eye was lasered while the other eye remained untreated as "control". LLLT led to a significant reduction of focal retinal thickening in the treated eyes.
Case study of retinitis pigmentosa
Even though only an individual case study, this documentation of a therapy of retinitis pigmentosa with LLLT over a period of seven years at the University of Heidelberg (Ivandic BT and Ivandic T 2014) is one of the most interesting publications we have found:
The patient suffered from an advanced case of retinitis pigmentosa (hereditary or toxic destruction of the photoreceptors) with night blindness, dyschromatopsia, and failing vision. The visual field was reduced to a central residual of five degrees, and the optic nerve had atrophied. After just four treatments, visual acuity improved, and the field of vision became normal, with the exception of a medium, peripheral scotoma. Following a relapse after five years, the patient was again lasered four times, which was equally successful. Over the next two years, 17 additional treatments were performed as needed in order to maintain the success that had been achieved.
The authors conclude that LLLT can improve and maintain the visual faculty and contribute towards slowing down the loss of eyesight.
The retina was lasered directly on its entire surface with an extremely low dose (transscleral LLLT). Laser light with a wavelength of 780 nm (infrared laser) was used at a dose of 0.4 J (equalling a power density of 0.33 W/cm2 for 40 sec). The laser light was not applied in the continuous wave mode but with a frequency of 292 Hz, which equals Nogier frequency A.
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