Age-related Macular Degeneration, or AMD, is a name familiar to many, and unfortunately, it stands as a primary cause of significant sight loss, particularly amongst older adults in the developed world. Specifically, the 'dry' form of AMD poses a considerable challenge because, currently, options to effectively treat it are quite limited. This leaves many people grappling with the condition's gradual impact on their central vision, which is crucial for tasks like reading, recognising faces, and driving.

Understanding dry amd and current challenges

The macula is a small but vital part of the retina at the back of the eye, responsible for sharp, detailed central vision. In dry AMD, this area gradually deteriorates. One of the early signs is the appearance of drusen – small yellow deposits of lipids and proteins that accumulate under the retina. As the condition progresses, the light-sensitive cells in the macula can thin and break down (a process called geographic atrophy in its advanced stages), leading to blurred vision or a dim spot in the centre of the visual field.

For years, the main advice for people diagnosed with early to intermediate dry AMD has centred around lifestyle adjustments and specific nutritional supplements. Formulations based on the Age-Related Eye Disease Studies (AREDS and AREDS2) – containing vitamins C and E, lutein, zeaxanthin, zinc, and copper – have been shown to potentially slow the progression to advanced AMD for some individuals. However, these supplements are not a cure, nor do they reverse existing damage. They represent a way to potentially manage risk, rather than a direct treatment for the underlying cellular changes.

This lack of direct treatment options for the majority of dry AMD stages (especially before it becomes advanced geographic atrophy, for which some treatments are emerging but have limitations) creates a significant unmet need. People diagnosed with the condition, and the eye care professionals supporting them, are keenly interested in any research exploring new ways to intervene earlier and perhaps slow down the degenerative process. This is where the investigation into therapies like photobiomodulation comes into the picture.

Introducing photobiomodulation therapy

Against the backdrop of limited options for dry AMD, researchers are exploring different approaches. One area gaining attention is photobiomodulation therapy (PBM), sometimes referred to as low-level light therapy (LLLT). This isn't about using bright lights for illumination; instead, it involves applying specific wavelengths of low-intensity light to biological tissues. The core idea is that particular colours, or wavelengths, of light energy can be absorbed by cells and trigger beneficial responses within them.

What is photobiomodulation therapy for dry AMD? In essence, it's the application of this light therapy concept specifically targeting the cellular processes thought to be involved in the development and progression of dry AMD. The hope is that by delivering controlled doses of specific light wavelengths to the eye, it might be possible to stimulate cellular repair mechanisms, improve cell function, reduce inflammation, and potentially protect the cells of the macula from further degeneration.

This approach is distinct from surgical interventions or drug injections. It's fundamentally about using light energy to try and positively influence cell behaviour at a microscopic level within the retina. It represents a shift towards exploring non-invasive methods that could potentially help manage the condition. The research in this area is looking into whether this targeted light application can offer a way to intervene in the disease process itself.

How light therapy is thought to work for dry amd

The central question is: How does light therapy potentially help dry AMD? The proposed mechanisms are based on how specific light wavelengths interact with components inside our cells, particularly the mitochondria. Mitochondria are often called the 'powerhouses' of the cell because they are responsible for generating most of the cell's energy supply in the form of adenosine triphosphate (ATP).

Retinal cells, especially the photoreceptors (rods and cones) and the retinal pigment epithelium (RPE) cells that support them, have very high energy demands. In AMD, it's believed that mitochondrial function can become impaired, leading to reduced energy production, increased oxidative stress (an imbalance between damaging free radicals and antioxidants), inflammation, and eventually cell death – all factors contributing to the disease's progression.

Photobiomodulation research suggests that certain wavelengths of light can be absorbed by molecules within the mitochondria (specifically, a component called cytochrome c oxidase). This absorption is thought to kick-start a cascade of events:

• Boosting energy production: The light energy may help restore mitochondrial function, leading to increased ATP production. More energy could help stressed retinal cells function better and potentially resist degeneration.
• Reducing inflammation: Chronic inflammation is known to play a role in AMD. Some studies suggest PBM might help modulate inflammatory pathways, potentially dampening down the damaging inflammatory responses in the retina.
• Combating oxidative stress: By improving mitochondrial health, PBM might also help cells better manage oxidative stress, reducing the damage caused by free radicals.
• Promoting cell survival: By addressing energy deficits, inflammation, and oxidative stress, the therapy might inhibit pathways that lead to programmed cell death (apoptosis), thus helping to preserve retinal cells.

The research often focuses on specific wavelengths, as different colours of light appear to have different primary effects based on the available information:

• Red light (around 630 nm): This wavelength seems particularly effective at targeting mitochondria to boost ATP production, enhance metabolic activity, and potentially inhibit inflammation and cell death.
• Yellow light (around 590 nm): This wavelength is being investigated for its potential role in reducing the expression of vascular endothelial growth factor (VEGF). While VEGF is strongly associated with the 'wet' form of AMD (characterised by abnormal blood vessel growth), modulating factors involved in blood vessel formation might also have relevance in the complex environment of dry AMD.

The overall hypothesis is that by using a combination of these specific light wavelengths, delivered in controlled doses, PBM could help improve the health and resilience of retinal cells affected by the dry AMD process, potentially slowing down the disease's progression.

Early research and potential findings

Interest in photobiomodulation for dry AMD has moved beyond theoretical mechanisms into clinical investigation. What do early studies suggest about light therapy for dry AMD? It's crucial to emphasise that this is still an area of active research, and the findings reported so far are generally from initial or ongoing trials. They provide early indications rather than definitive proof of long-term effectiveness.

One notable piece of research mentioned in the context of devices being developed is the LightWave I clinical trial, which includes the 'Drusen Study'. This study was designed as a double-blind, randomised controlled trial – a robust methodology where neither the participants nor the researchers directly involved in assessment know who receives the active treatment and who receives a placebo or sham treatment. This helps to minimise bias.

The study reportedly involved over 150 eyes diagnosed with dry AMD (specifically targeting AREDS 3 and lower classifications, indicating earlier stages of the disease) and followed them over a period of time. Six-month results have been published or presented, suggesting some encouraging signs:

• Slowing of drusen progression: The data indicated that eyes receiving the light therapy showed a slower progression or accumulation of drusen compared to the control group. As drusen are a key indicator of AMD progression, slowing their development could be significant.
• Improvement in visual acuity: The results also suggested an improvement in best-corrected visual acuity (BCVA) for some participants in the treatment group. Specifically, an improvement of five or more letters on the LOGMAR eye chart (a standard measure of vision) was noted. While seemingly small, even modest improvements in visual acuity can make a difference to a person's daily life.
• Outer retinal changes: Some research, potentially linked to these trials, has also looked at changes in the deeper layers of the eye using advanced imaging. Findings hinted at possible improvements in blood flow in the choriocapillaris (a critical blood vessel layer supplying the outer retina) and some positive structural changes (remodeling) in the outer retinal layers following PBM therapy.

These early findings are generating interest because they suggest that photobiomodulation might not only slow down the anatomical progression of the disease (as measured by drusen) but could also potentially lead to functional improvements in vision for some patients with early to intermediate dry AMD.

However, it's vital to maintain perspective. These are short-term results (six months) from studies that are often part of larger, ongoing longitudinal trials. Longer-term data is needed to see if these effects are sustained, whether they translate into meaningful delays in progression to advanced AMD, and to fully understand the safety profile over extended periods. While promising, these results need to be replicated in larger, independent studies before PBM can be considered a standard, proven treatment.

The treatment process explained

Based on the descriptions of the technology being used in clinical trials, the application of photobiomodulation therapy for dry AMD appears relatively straightforward and non-invasive. Unlike injections or surgery, the treatment involves directing light towards the eyes using a specially designed device.

Typically, this involves the patient wearing a mask that covers the eyes. This mask contains light-emitting elements (likely LEDs) precisely calibrated to deliver the specific wavelengths of light being studied – primarily red and yellow light in the context of the AMD research discussed.

The treatment process might look something like this:

1. Assessment: An eye care professional would first confirm the diagnosis and stage of dry AMD to determine if the patient fits the criteria being used in the trials or for the approved use of the device (if it gains wider regulatory clearance).
2. Treatment Sessions: The patient would undergo a series of treatment sessions, likely in a clinical setting. During each session, they would wear the light-emitting mask for a set duration. The device delivers the programmed sequence and intensity of red and yellow light.
3. Treatment Schedule: The exact number and frequency of sessions would depend on the specific protocol being followed. The research mentioned suggests an initial course of treatment perhaps followed by assessment and potential follow-up treatments later (e.g., a six-month follow-up was mentioned in the context of the Drusen Study).
4. Non-Invasive Nature: A key aspect is that the process is non-invasive. No needles, no incisions. The patient simply wears the mask while the light is delivered. This generally makes it a comfortable and well-tolerated procedure.

Some practices using similar technology for other conditions, like dry eye disease, might set up dedicated clinics or specific appointment slots to deliver these light therapy treatments, as they require specific equipment and a set amount of time per session. The development for AMD suggests a similar model might be adopted if the therapy becomes more established.

What is the current status?

It's important to understand where photobiomodulation therapy for dry AMD currently stands. While the underlying science and early clinical results are generating excitement, this is still very much a developing area. It is not yet a routine, widely available standard treatment offered by most opticians or ophthalmologists for dry AMD.

The technology, such as the specific devices used in the LightWave I trial, has gained clearance or approval in some regions for treating dry AMD based on the initial data. This means regulatory bodies have assessed the available evidence and deemed it sufficient to allow the device to be marketed and used for this specific purpose, under certain conditions. In the UK and Ireland, for instance, distribution of devices like the one developed by Espansione Group is beginning via established healthcare equipment suppliers like Topcon.

However, regulatory clearance is not the same as universal adoption or endorsement by all clinical bodies as a first-line treatment. It signifies that the technology has met certain safety and efficacy standards based on the submitted data, often focusing on specific patient groups (like those with earlier stages of dry AMD, such as AREDS 3 or lower).

Many eye care professionals will likely wait for more extensive, long-term data and independent verification before widely incorporating this therapy into their practice. Ongoing research, including the longer-term follow-up from studies like LightWave I, will be crucial in determining the true place of photobiomodulation dry AMD treatment within the broader landscape of AMD care.

The potential for a non-invasive therapy that could slow the progression of dry AMD is certainly appealing, especially given the current lack of options. Research into light therapy AMD and low-level light therapy eye applications continues to evolve. While the journey from promising research to standard clinical practice can take time, the exploration of dry AMD treatment research like photobiomodulation offers hope for better management strategies in the future, potentially contributing to slowing AMD progression for many individuals.

Exploring photobiomodulation: A potential new direction for dry AMD research
1. Espansione Group – LightWave I / DRUSEN Study 6-month results (press release) 2. Independent PBM4AMD clinical study (Eye, 2024) – DOI 10.1038/s41433-024-03326-4 3. 2024 systematic review & meta-analysis (BMC Retina & Vitreous) – DOI 10.1186/s40942-024-00569-x