What is Photobiomodulation?
Photobiomodulation (PBM), also known as low-level light therapy (LLLT), is a non-invasive therapeutic procedure that uses specific wavelengths of light in the red spectrum to stimulate biological processes at the cellular level. The procedure uses low-energy light that generates no heat and does not damage tissue.
The foundations of PBM were discovered in the 1960s by Endre Mester in Hungary, when he observed that low-energy laser light accelerates wound healing. Since then, the understanding of the underlying mechanisms has deepened considerably. Today, PBM is used in various medical fields, including pain therapy, wound healing, and neurology. In the USA, a PBM device (Valeda, LumiThera) was cleared by the FDA for the treatment of dry AMD for the first time in 2025. In Europe, PBM devices for AMD therapy are still in clinical trials.
The Central Mechanism of Action
The key to understanding PBM lies in the mitochondria – the powerhouses of our cells. Within the mitochondria is the enzyme cytochrome c oxidase (CCO), also known as Complex IV of the electron transport chain. This enzyme is the primary photoacceptor for PBM: it absorbs photons in the red and near-infrared range and converts light energy into cellular energy.
In patients with age-related macular degeneration, the mitochondrial function in the cells of the macula – particularly in the retinal pigment epithelium (RPE) and photoreceptors – is impaired. Nitric oxide (NO) binds to CCO and inhibits its activity, leading to reduced ATP production and increased oxidative stress. PBM releases NO from CCO, reactivates the electron transport chain, and restores normal cell function.
The PBM Effect Cascade
Primary Effects (immediate):
- •Release of NO from cytochrome c oxidase
- •Increase in mitochondrial membrane potential
- •Increase in ATP synthesis by up to 50%
- •Modulation of reactive oxygen species (ROS)
Secondary Effects (hours/days):
- •Activation of transcription factors (NF-κB, AP-1)
- •Upregulation of antioxidant enzymes
- •Reduction of pro-inflammatory cytokines
- •Promotion of cell regeneration and repair
How Photobiomodulation Works
Explained in five steps: How low-energy light works at the cellular level and regenerates the retina in dry AMD.
Wavelength 670 nm
Light energy reaches the retina
Light with a wavelength of 670 nm in the red spectrum penetrates the eye and reaches the photoreceptors and retinal pigment epithelium (RPE) in the macula. According to current research, the 670 nm wavelength is considered the most effective for retinal photobiomodulation, as it is optimally absorbed by cytochrome c oxidase.
Current Findings from the Scientific Community
At the meeting of the Rhineland-Westphalian Ophthalmologists on 07.02.2026 in Bochum, the current scientific status of photobiomodulation was presented in a dialogue session. The results so far show that PBM is safe and demonstrates significant effects in clinical trials. (view program).
What do the current study results mean for patients?
Expert lecture: Study results and their significance
In the pivotal LIGHTSITE III study, which led to FDA clearance in the USA, treated eyes showed a statistically significant improvement in vision. Critics noted that the average gain was "only" 2.4 letters on the eye chart. But vision loss does not progress linearly: you can have already lost 90% of the cones in the fovea and still achieve passable visual performance. Translating the letter gain to the number of retinal cells, this corresponds to saving approximately 50,000 cones – a decisive gain in quality of life.
PBM currently still faces hurdles in healthcare delivery
Expert lecture: Current hurdles with PBM
Previous PBM devices require patients to visit an ophthalmology practice multiple times at short intervals for therapy. Additionally, the treatment is expensive for many patients. For many elderly patients, this effort is considerable, and without consistent application, the positive effect is lost. Currently, a new device is being discussed in research that could positively influence this. With a home device, patients can perform the treatment simply and safely themselves. The device is not yet available on the market or approved outside of studies. The currently ongoing MACULIGHT study at several renowned German university hospitals is investigating the efficacy and safety of this home device.
Summary of Current Findings
1.PBM shows two decisive advantages in studies: improvement of visual acuity and slowing of geographic atrophy.
2.With correct application, no significant risks are known – neither acceleration of the disease nor conversion to wet AMD.
3.Home devices could decisively improve therapy adherence and make PBM accessible to a broad patient group.
Why PBM Works for Dry AMD
Dry AMD is fundamentally a mitochondrial disease. The cells of the macula – particularly the retinal pigment epithelium (RPE) and photoreceptors – are among the most metabolically active cells in the human body. They require enormous amounts of energy (ATP) to maintain their function: the daily breakdown and renewal of photoreceptor outer segments, the transport of nutrients and waste products, and protection against oxidative stress.
With increasing age, mitochondrial efficiency decreases. The mitochondria in RPE cells produce less ATP while simultaneously generating more reactive oxygen species (ROS). This vicious cycle of energy deficiency and oxidative stress leads to the accumulation of lipofuscin and drusen – the characteristic deposits of AMD.
PBM targets precisely this point: by stimulating cytochrome c oxidase – particularly with light at 670 nm wavelength, which according to current studies is considered the most effective – mitochondrial function is restored, ATP production is increased, and the cell's antioxidant defense mechanisms are activated. This can break the vicious cycle and allow the cells to regenerate.
The Biphasic Dose-Response Principle
PBM follows the Arndt-Schulz law: too little light has no effect, the optimal dose maximally stimulates the cells, and too much light can be inhibitory. The therapeutic parameters – wavelength, power density, irradiation duration, and total dose – must therefore be precisely coordinated.
The parameters used in clinical studies typically involve a power density of 50–100 mW/cm² and a treatment duration of 3–5 minutes per session. Current research results suggest that the 670 nm wavelength is particularly effective, as it is optimally absorbed by cytochrome c oxidase and offers the highest tissue penetration with maximum energy absorption.
Scientific Foundation
The efficacy of photobiomodulation for AMD is supported by a growing number of clinical trials, meta-analyses, and basic research. In January 2025, the FDA in the USA cleared PBM as the first non-invasive treatment for dry AMD. Further clinical trials are ongoing in Europe.
letters BCVA improvement (LIGHTSITE III)
First clearance in the USA (2025)
years of clinical research on PBM for AMD
LIGHTSITE III – Pivotal Trial
Multicenter, double-blind, sham-controlled study with 100 patients. Treated eyes showed an improvement of +5 letters (BCVA) after 13 months. Basis for FDA clearance of the Valeda Light Delivery System (LumiThera).
LIGHTSITE IIIB – Long-term Extension
Extension of LIGHTSITE III over 4.5 years. Sustained visual improvement and excellent safety profile with continued PBM treatment.
LIGHTSITE II – Randomized Trial
48 patients, double-blind, sham-controlled. Significant improvement in BCVA by 4+ letters and reduction in drusen volume.
LIGHTSITE I – Pilot Study
First clinical study with 30 patients. Double-blind, sham-controlled. Significant improvement in visual acuity after PBM treatment.