Improvement in Dry Age-Related Macular Degeneration with Photobiomodulation

Age-related macular degeneration (AMD) affects nearly 200 million people worldwide and remains a leading cause of visual impairment and blindness in the aging population [1]. The number of patients with AMD is expected to rise to 288 million by the year 2040 [1]. Hallmarks of dry AMD include the progressive accumulation of drusen under the retinal pigment epithelium (RPE) and photoreceptor degeneration resulting in irreversible vision loss [1‒6]. Interventions to slow the progression of AMD are currently limited to antioxidant supplementation [7‒9]. Though C3 and C5 complement inhibitors have shown promise in slowing the progression of geographic atrophy [10, 11], they have not been shown to improve visual outcomes and carry risks, most notably of conversion to neovascular AMD [12].

More recently, photobiomodulation has emerged as a potential adjunct treatment regimen for several degenerative diseases [13‒16]. It involves the application of light in the red to near-infrared (NIR) spectrum at 650–1,300 nm [17, 18], which is thought to promote tissue repair through multiple proposed mechanisms including increased mitochondrial function and modulation of inflammatory pathways [19]. Clinical trials of photobiomodulation with specialized devices for dry AMD have found improvements in visual acuity with reduction in or stabilization of drusen volume [20‒22]. In addition, a reduction in the incidence of geographic atrophy was noted in Lightsite III [22]. We present a case of dramatic improvement in drusen volume and visual acuity in a patient diagnosed with dry AMD with daily home treatment of a widely available photobiomodulation system alongside longstanding use of AREDS-2 supplements. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000543971).

A 73-year-old Caucasian male initially diagnosed with dry AMD was seen in consultation in October 2023. He was healthy and did not have any risk factors such as hypertension, dyslipidemia, diabetes or cardiovascular disease. He was a non-smoker. There were no reports of previous ocular comorbidities or surgeries. He had been adherent to a daily regimen of AREDS-2 vitamin supplementation since diagnosis. At the first consultation, his visual acuity was 20/25 OD and 20/30-1 OS, with significant soft confluent drusen burden and large drusenoid pigment epithelial detachments bilaterally (Fig. 1). Drusen area was quantified from optical coherence tomography (OCT) images using CellProfiler [23].

The patient began Joovv (JOOVV Inc., Minneapolis-St. Paul MN, USA) photobiomodulation with wavelengths between 660 nm–850 nm [24] as an adjunct treatment consisting of the following daily protocol alongside regular AREDS-2 supplementation (at two feet distance from device):

• 3 min of red-light exposure to the eye with eyes closed without glasses

• 5 min of red-light exposure to the upper body, including both front and back

• 5 min of red-light exposure to the lower body, including both front and back

After 8 months of consistent photobiomodulation therapy, visual acuity improved to 20/20 OS and remained stable at 20/25 OD. Preservation of the RPE and outer retina without signs of geographic atrophy was observed on OCT (shown in Fig. 2). Analysis of OCT cross-sectional scans showed that the total drusen reduced in number, average area (75%), and total area (58%) OD, while a complete 100% resolution of drusen was observed OS (Table 1). Structurally, fundus imaging demonstrated drastic reduction in drusen burden after photobiomodulation (Fig. 3).

In this case report, we highlight the potential disease course-altering effects of implementing photobiomodulation in an elderly patient diagnosed with dry AMD, a condition with no definitive cure to date. The consistent use of Joovv photobiomodulation for 8 months was associated with reduction in macular drusen deposits with structural and functional improvement, as evidenced by both imaging modalities of OCT and fundus photography. This was consistent with other existing studies employing photobiomodulation therapy for dry AMD, which has demonstrated post-treatment drusen volume reduction and visual acuity improvement [20, 22, 25‒27]. To our knowledge, this is the first case report highlighting the efficacy of the Joovv photobiomodulation system in treating dry AMD. Previous studies have evaluated the effectiveness of another photobiomodulation device, the Valeda Light Delivery System (Lumithera, WA, USA) [20‒22, 27, 28] consisting of wavelengths of 590 nm (yellow), 660 nm (red), and 850 nm (NIR), in patients with dry AMD. Our patient’s age falls within the range of those treated with Valeda system, and similar clinical outcomes were observed, such as improvements in visual acuity, preservation of the RPE, and reductions in macular drusen. However, notable discrepancies in methodology and the extent of anatomical changes were observed between the studies. For instance, the Joovv system used by our patient delivers higher wavelengths than the Valeda system, in the red to NIR range (660 nm–850 nm) and was administered daily for 8 months. In contrast, the Valeda system provided 9 treatment sessions repeated every 3 weeks over a longer period. The consistent use of long-wavelength light stimulus may explain the unique findings from our patient, in particular the significant drusen reductions in both eyes after only 8 months of therapy as compared to 13 months in the Lightsite III trial [22]. Remarkably, our patient’s left eye even showed complete resolution in terms of total number and drusen area. Moreover, other techniques for photobiomodulation therapy in dry AMD, including the combined WARP10 (Barneveld, WI, USA) and Gentlewaves (Light bioscience, Virginia, USA) system [26], as well as custom systems with fixed wavelengths [25], have also demonstrated similar findings of improved visual acuity and reduced drusen, while using different wavelengths and treatment schedules.

Photobiomodulation activates the mitochondria and modulates the mitochondrial respiratory chain through elevated electron transport and adenosine triphosphate (ATP) production [29‒31]. Enhanced ATP levels are crucial in assisting the RPE and photoreceptors achieve repair and regeneration as they have high metabolic demands requiring lots of cellular energy [32, 33]. Moreover, the use of photobiomodulation has shown promising potential in improving the activities of antioxidant enzymes to combat reactive oxygen species [34, 35], and in regulating pro-inflammatory cytokines to reverse inflammation [34], both of which contribute to AMD disease pathophysiology and progression of the condition [36].

The use of AREDS-2 supplementation alongside photobiomodulation may serve synergistic functions for patients’ retinal health. The AREDS-2 vitamins have been implicated in reducing the risk of progression to more advanced stages of AMD, and provide important nutrients for retinal growth, function and repair. Our patient’s improvement in visual acuity and reduction in macular drusen, especially the complete resolution in the left eye, questions the therapeutic potential of this synergistic relationship, and warrants further studies.

The non-invasive nature of photobiomodulation with a good safety profile [22, 25] suggests that its clinical incorporation could provide patients worldwide with a safe and effective option to add to existing treatment regimen for dry AMD and perhaps other ocular conditions yet to be explored. The availability of portable photobiomodulation systems allows flexibility and can improve patient compliance and usage rate. AMD is very prevalent among the elderly population, and there is currently no definitive treatment to reverse disease progression. Early intervention with photobiomodulation may help preserve vision and ultimately improve the quality of life.

While this report shows promising results of photobiomodulation in 1 patient, larger, controlled studies in the future are warranted to understand and to determine the optimal parameters of photobiomodulation, especially the Joovv therapy system, including long-term safety, efficacy, frequency, duration, and dosage, similar to other pharmaceutical products or biomedical devices. Lastly, exploring photobiomodulation in combination with other treatment regimens, such as AREDS-2 supplementation, may provide valuable information which can contribute toward developing a comprehensive management plan for dry-AMD.

This case report illustrates the improvements in both functional and structural parameters in an elderly patient with dry AMD undergoing daily photobiomodulation treatment. To the best of our knowledge, this was the first time a complete drusen resolution was observed following photobiomodulation treatment. These results suggest the potential of combining photobiomodulation alongside AREDS-2 supplementation into a promising treatment regimen for managing dry AMD and improving quality of life. Our findings here warrant future research studies to confirm this intervention’s efficacy, and to optimize protocols for broader clinical implementation.

We gratefully thank the patient for their contribution to this case report.

The study complies with the guidelines for human studies and was conducted in accordance with the World Health Organization Declaration of Helsinki. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. Research ethics approval was not required for this article as per the University of Toronto Research Ethics Board.

The authors have no conflicts of interest to declare with respect to the research, authorship, and/or publication of this article.

The authors received no financial support for this research, authorship, and/or publication of this case report.

All listed authors meet the International Committee of Medical Journal Editors criteria. Patrick Xiang Ji: writing – original draft, data analysis, review and editing, and conceptualization. Lauren Pickel: writing – original draft, data analysis, and review and editing. Alan R. Berger: writing – review and editing, and supervision. Nirojini Sivachandran: writing – original draft, data analysis, review and editing, conceptualization, supervision, and methodology.

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.