Non-damaging Retinal Laser Therapy for Prophylaxis of Age-Related Macular Degeneration

Principal Investigator: Steven Sanislo
Scientific Advisor: Daniel Palanker
Stanford Ophthalmic Reading Center (STARC): Theodore Leng, Director
Co-investigators:
Byers Eye Institute at Stanford: Darius Moshfeghi, Peter Karth
Federal University de Rio Grande de Sol (Porto Alegre, Brazil): Daniel Lavinsky
Kangwon National University, Korea: Seungjun Lee

            Age Related Macular Degeneration (AMD) is the leading cause of blindness and visual disability among patients exceeding 60 years of age in developed countries. AMD symptoms begin with appearance of drusen (shown in the image) in patients with normal visual acuity, and may advance to loss of the retinal pigment epithelium (RPE) cells and photoreceptors, called geographic atrophy, or to development of subfoveal choroidal neovascularization (CNV), disciform scarring and eventually loss of central vision [1]. Fortunately, neovascular (so called “wet”) AMD can be effectively treated by suppressing neovascularization pharmacologically, thereby maintaining good visual acuity for extended period of time. However, there is still no treatment for dry AMD other than slowing disease progression with vitamin supplementation, and patients inevitably progress to advanced disease and associated visual loss.
            Several clinical trials have been conducted to test the effect of laser photocoagulation on reabsorption of drusen in the macula [2]. The assumption was that phagocytic cells or macrophages clearing the laser-induced debris in the retina, RPE and choroid could also reduce or eliminate the drusen. In these studies, photocoagulation induced significant reduction of drusen over time. However, it also slightly increased the incidence of CNV and geographic atrophy, albeit not statistically significant [3]. This increase could be related to the damage of Bruch’s membrane by conventional photocoagulation, consequently inducing CNV. This hypothesis is supported by the fact that “subthreshold” laser treatments of the drusen resulted in their reduction with much fewer side effects than with conventional visible burns: 10% of eyes treated with visible burns developed CNV within 3 months of treatment, while no such CNV was reported for “subthreshold” treatment. Despite the drusen reduction, the “subthreshold” laser treatment did not slow the progression to geographic atrophy or to CNV, compared to observation in this trial. This might be due to very small number (a few tens) of laser spots applied to the macula. Our approach might rectify this deficiency by applying much higher density of the treatment: up to 400 non-damaging spots.
            We have developed the titration protocol, called EndPoint Management, for PASCAL laser, which ensures that in every patient the pulse energy is within the range of clinical response, but below damage threshold [4]. This protocol, recently tested in a pilot clinical trial, demonstrated its safety and efficacy in treatment of Central Serous Retinopathy [5], with excellent tissue response to the treatment, even after multiple retreatments. The same laser parameters will be applied for treatment of the central macula in patients with early AMD to prevent drusen growth and advancement of the disease into geographic atrophy or neovascularization.

References

1.             Gangnon, R.E., et al. JAMA Ophthalmol 133, 125-132 (2015).
2.             Complications of Age-Related Macular Degeneration Prevention Trial Research, G. Ophthalmology 113, 1974-1986 (2006).
3.             Owens, S.L., et al. Eye (Lond) 17, 623-627 (2003).
4.             Lavinsky, D., et al. Retina 34, 87-97 (2014).
5.             Lavinsky, D. & Palanker, D. Retina 35, 213-222 (2015).