Researchers Tackle AMD with Hyperthermia

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Researchers Tackle AMD with Hyperthermia

Researchers at Aalto University have introduced an innovative hyperthermia-based intervention designed to halt the progression of early-stage dry age-related macular degeneration (AMD). Published in Nature Communications, the study targets the age-related decline in retinal cellular protective mechanisms, which exacerbates oxidative stress in the fundus, leading to protein misfolding, aggregation, and drusen accumulation—a hallmark of dry AMD.

The technique employs controlled heating of the retinal pigment epithelium (RPE) and photoreceptor layers using near-infrared (NIR) light, elevating tissue temperature by a few degrees while maintaining sub-45°C thresholds to prevent thermal injury. A key advancement is the integration of real-time thermometry with NIR delivery, enabling precise dosimetry and minimizing risks to delicate ocular structures.

At the cellular level, this mild hyperthermia leverages endogenous repair pathways. It upregulates heat shock proteins (HSPs) to chaperone and refold misfolded proteins, preventing aggregation. When refolding fails, it enhances proteasomal degradation into amino acids. For established aggregates, the therapy induces autophagy—encapsulating damaged proteins in autophagosomes for lysosomal degradation, akin to cellular waste clearance (notably, the discovery of autophagy earned Yoshinori Ohsumi the 2016 Nobel Prize in Physiology or Medicine).

Preclinical efficacy was demonstrated in murine and porcine models, where repeated heat shocks activated HSP expression and enhanced autophagic flux, resulting in reduced drusen-like deposits without adverse effects. Human phase 1 trials, commencing in Finland in early 2026, will prioritize safety assessment, followed by efficacy evaluations to optimize treatment frequency, as protective responses wane within days post-exposure.

To facilitate translation, the team founded Maculaser, a startup focused on commercializing this noninvasive modality. This approach holds promise as an adjunct or alternative to current anti-VEGF therapies, potentially preserving vision in at-risk patients by addressing upstream pathophysiology.

My Two Cents

We have another treatment option in the pipeline for macular degeneration! This comes after recent approvals for photobiomodulation, complement inhibition, and various second-generation anti-VEGF therapies. As someone who has a strong family history of macular degeneration (both my grandfather and father), this recent research fascinates me almost as much as dry eye research does! Clinically, I have been encouraging my practice to consider a low-level light therapy machine from Optometric Aesthetics for my dry eye patients, and it’s interesting to consider similar therapeutic approaches for our AMD patients. Not only does this seem to be the golden age of dry eye therapies, but also AMD treatments! At a recent conference, Sarah Terlesky, OD, showed me some incredible images of the macula of patients who were treated with photobiomodulation, and I was blown away!

OUTSIDE THE LANE

Get Your Vitamin D3!

A recent study presented at the 2025 American Heart Association’s scientific sessions highlights the potential cardioprotective role of vitamin D3 supplementation in post-myocardial infarction (MI) patients, which may have broader systemic implications relevant to ophthalmologists managing patients with comorbidities. Conducted by Intermountain Health in Salt Lake City, Utah, the TARGET-D trial—a large, randomized clinical trial—involved 630 patients who had suffered an acute MI within the prior month. Notably, 85% of participants exhibited insufficient vitamin D3 levels at baseline, a deficiency affecting up to two-thirds of the global population due to reduced sun exposure from modern lifestyles.

Patients were divided into two groups: one receiving targeted vitamin D3 supplementation to achieve serum levels above 40 ng/mL, and a control group that received no intervention. Initial doses often reached 5,000 IU daily—far exceeding the standard 600 IU to 800 IU recommendation for adults—to normalize levels (typically 30-50 ng/mL). Over the follow-up period, 107 major cardiac events occurred among the cohort. Remarkably, the treatment group experienced a 50% reduction in recurrent MI risk compared with controls, with no reported adverse effects from higher dosing.

Lead researcher Heidi May, PhD, emphasized the need for further validation, but noted vitamin D’s established link to a reduced risk of coronary artery disease, heart failure, and stroke. Interventional cardiologist Bradley Serwer, MD, reinforced that prior observational data have correlated low vitamin D levels with heightened cardiovascular risks, although earlier trials using suboptimal doses failed to show benefits.

For ophthalmologists, this underscores vitamin D's multifaceted role in systemic health. Vitamin D deficiency is implicated in ocular conditions such as dry eye syndrome, AMD, and uveitis, often co-occurring with cardiovascular disease due to shared risk factors like aging and metabolic syndrome. Patients who are post-MI may present in ophthalmic clinics with vascular retinopathies or glaucoma exacerbated by inflammation. Recommending vitamin D screening and supplementation could enhance holistic care, potentially mitigating both cardiac recurrence and ocular complications. While the study focused on high-risk cardiac patients, its findings suggest benefits may extend to lower-risk groups, warranting interdisciplinary discussions. Further research is needed to explore direct ophthalmic outcomes; however, normalizing vitamin D levels appears to be a low-risk strategy for overall patient optimization.

My Two Cents

Vitamin D is a hot topic in eye care, with Bausch + Lomb promoting its benefits for dry eye patients in its newest supplement, Blink-NutriTears, as well as research on its benefits for reducing proinflammatory cytokines in the retina and uvea, which could reduce the risk and severity of uveitis. We are considering reformulating the Dry Eye Drink at some point to add ingredients, such as vitamin D3, that have recently been shown to aid in the treatment of ocular surface disease.

CAN YOU RELATE

This past weekend, I was at the MODLive conference in Austin, Texas. This special meeting is one of my absolute favorites, as it’s a much smaller and more intimate gathering of doctors. The meeting has almost become a family gathering each year, with many of us having enough time during after-hours events and between sessions to catch up with each other’s lives and professional updates. In addition, attendees can ask questions during the lectures and spend a substantial amount of time after each session questioning the lecturers about how their message relates to their own clinical experiences.

Some of my personal highlights included watching Kyle Klute, OD, from Nebraska, guide the audience through the wonderful trends in eye care during his thought-provoking session, as well as hearing from one of our profession’s rising stars, Ada Noh, OD, describe her journey through eye care. She spoke about the burnout that many of us feel and how she was able to find her niche as a world-class and highly sought-after specialist in dry eye care. Her talk had me ready to run out of the conference room and immediately see patients. It’s moments like Dr. Noh’s talk that make meetings so special. It’s not only the education and what we learn, but also how the lecturers make us feel, which is so special! That’s the takeaway this week. The best continuing medical education events not only help us learn new material but also motivate us professionally.  Make your CE hours count and find meetings and events that truly resonate with you!

QUOTE OF THE WEEK

“Zig Ziglar taught me that ‘your attitude, not your aptitude, will determine your altitude.’ I still quote him in every stump speech I’ve ever given.”

– Bill Clinton