Over the past decade, researchers have explored new therapeutic strategies to address the underlying cellular damage associated with dry age-related macular degeneration (dry AMD). One emerging treatment is photobiomodulation therapy (PBMT), also known as low-level light therapy (LLLT). This non-invasive treatment uses specific wavelengths of light to stimulate cellular processes within the retina, potentially improving retinal metabolism and slowing disease progression. PBMT has attracted growing interest in ophthalmology because it targets the metabolic and inflammatory pathways that contribute to retinal degeneration. In this article, Dr Nisha Sachdev, one of the first Australian ophthalmologists to use PBM to treat dry eye disease and meibomian cysts, explores its use for the treatment of dry AMD, including its mechanisms of action, the clinical evidence, treatment protocols, and future potential.

• Reduced oxygen and nutrient delivery to retinal tissues,

One of the earliest clinical signs of dry AMD is the appearance of drusen, small yellow deposits of lipids and proteins that accumulate between the retina and the underlying retinal pigment epithelium (RPE).

• Chronic inflammation,

• Increased oxidative stress, and

Several pathological processes occur with AMD formation:

• Impaired mitochondrial function.

In more advanced stages, dry AMD may lead to geographic atrophy – the irreversible chronic loss of the RPE, photoreceptors, and choriocapillaris.

• Degeneration of the retinal pigment epithelium (RPE),

• Damage to photoreceptor cells,

Dr Nis

ha Sachdev

WRITER

CURRENT TREATMENT LIMITATIONS Unlike neovascular AMD, which is treated with anti-VEGF injections, treatment options for dry AMD remain exceptionally limited.

The most widely recommended intervention is nutritional supplementation, based on findings from large clinical studies (such as AREDS) showing that certain formulations of antioxidants, vitamins, and minerals may reduce the risk of progression from intermediate to advanced AMD. information read the article on page 73.

However, these supplements do not reverse retinal damage; their primary benefit is in slowing disease progression. Similarly, newly-approved intravitreal injections for geographic atrophic AMD have been shown to slow progression.

Because of these limitations, researchers have increasingly focused on therapies that address the cellular mechanisms underlying retinal degeneration. Photobiomodulation therapy is one such approach that aims to improve retinal cell metabolism, resulting in a reduction in drusen.

WHAT IS PHOTOBIOMODULATION THERAPY? The concept of photobiomodulation is not entirely new. Light-based therapies have been studied for decades in fields such as dermatology, wound healing, neurology, and musculoskeletal medicine.

In eye health, it has been utilised for dry eye disease, as previously discussed. recently, researchers have investigated its potential benefits for retinal diseases.

PBMT uses low-intensity light at specific wavelengths to stimulate biological processes in cells and tissues. Unlike high-energy lasers used in surgical procedures, PBMT delivers light at levels that do not cause thermal damage or tissue destruction.

The therapy typically uses wavelengths within the visible red and near-infrared spectrum, generally ranging from approximately 590 to 850 nanometers. These wavelengths are able to penetrate biological tissues and interact with cellular components that influence metabolism and signalling pathways.

For use in dry AMD, PBM devices deliver controlled light exposure to the retina with delivery via a mask. Treatments are usually administered in the clinical setting and the therapy is non-invasive, painless, atraumatic, and relatively quick (Figure 1).

BIOLOGICAL MECHANISMS OF PMB FOR DRY AMD Photobiomodulation therapy, in the setting of AMD, works by influencing several cellular processes that are known to contribute to retinal degeneration. The primary target is the mitochondria, which are responsible for producing energy within cells.

Enhancement of Mitochondrial Function One of the most widely accepted mechanisms of PBMT involves stimulation of cytochrome c oxidase, an enzyme in the mitochondrial respiratory chain. When this enzyme absorbs light in the red or near-infrared spectrum, it enhances the efficiency of mitochondrial energy production.

This leads to increased synthesis of adenosine triphosphate (ATP), the molecule that fuels many cellular functions. This allows retinal cells to maintain normal metabolic activity and resist degenerative changes.

Reduction of Oxidative Stress Oxidative stress is a key factor in the development of dry AMD. It occurs when the production of harmful reactive oxygen species exceeds the body’s ability to neutralise them.

Photobiomodulation therapy has been shown to:

One important observation from clinical trials is that patients with early to intermediate stages of dry AMD tend to respond more favourably than those with end stage or advanced geographic atrophy.

By decreasing oxidative stress, PBM therapy may help protect retinal pigment epithelial cells and photoreceptors from damage.

Anti-Inflammatory Effects Chronic inflammation plays a significant role in the progression of AMD. Inflammatory mediators and immune responses can contribute to retinal cell injury and degeneration. Studies suggest that PBMT may regulate inflammatory signalling pathways, resulting in reduced production of inflammatory molecules and improved cellular homeostasis within the retina.

It is important to note that responses can vary between individuals, and not all patients experience the same degree of improvement.

TREATMENT PROCEDURE AND PROTOCOLS Photobiomodulation therapy is typically performed using specialised ophthalmic devices designed to deliver precise wavelengths of light to the retina.

Improved Blood Flow and Tissue Oxygenation Some research indicates that photobiomodulation may enhance microcirculation in retinal tissues. Improved blood flow helps deliver oxygen and nutrients to metabolically active cells, supporting retinal health.

Although treatment protocols may vary depending on the device and clinical study design, common features include:

Promotion of Cellular Repair and Survival PBMT can also activate protective cellular signalling pathways that promote cell survival, reduce apoptosis (programmed cell death), and support tissue repair.

Together, these mechanisms may help create a more favourable environment for retinal cells, potentially slowing or stabilising degenerative changes associated with dry AMD.

During the procedure, patients sit comfortably while the device directs controlled light exposure toward the eyes. The treatment is painless and generally well tolerated.

THE CLINICAL EVIDENCE Several clinical trials and pilot studies have evaluated the use of PBMT in patients with dry AMD. While research is still evolving, many studies have reported encouraging outcomes. Some key findings from clinical investigations include:

In many studies, patients received multiple treatment sessions over several weeks. Improvements in visual function were sometimes observed shortly after treatment, and maintained for several months.

• Potential neuroprotective benefits: By improving cellular metabolism and reducing oxidative stress, PBMT may help protect