New approaches for detecting and treating age-related macular degeneration (AMD) are needed, according to a study published in Experimental Eye Research. This includes assessing choriocapillaris flow deficits via optical coherence tomography-angiography (OCTA), performing gene therapies, and targeting the retinal pigment epithelium (RPE), choroid, and choriocapillaris in early AMD treatments.  

Researchers have identified the choroid and choriocapillaris as sites of pathology in early AMD and suggest interventions at these locations. According to donor eye studies, early AMD is associated with a loss of choriocapillaris density and worsens with disease progression to geographic atrophy (GA). Vascular dropout occurs primarily in the microvasculature of the choriocapillaris, with no effect on outer choroid density in eyes with AMD. Choriocapillaris dropout also correlates with drusen density. Mean vascular density is significantly lower beneath the drusen than adjacent to it. 

The complement membrane attack complex (MAC) selectively accumulates in the choriocapillaris with age and is more abundant in the choroid of patients with the AMD high-risk CFH genotype. It is also associated with the basal surface of the RPE adjacent to Bruch’s membrane. Choriocapillaris exposure to MAC over a lifetime may make it more vulnerable to damage and loss over time, contributing to further AMD-related pathological changes like drusen. Researchers assert that SS-OCTA can detect these choriocapillaris flow deficits associated with aging.


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Investigators argue that future AMD therapies should consider targeting pathologies within the choroid and choriocapillaris. They suggest subretinal gene delivery, suprachoroidal administration of both gene vectors and small molecules, and  lipophilic drug and prodrug administration via episcleral delivery. 

Researchers highlight the importance of new imaging methods in assessing choroidal parameters in patients with AMD and state, “the development of OCT-A as a critical imaging tool to interrogate the choriocapillaris and choroid will be important to our understanding of how these retinal vascular compartments contribute to the progression of AMD.”

Reference

Csaky K, Curcio CA, Mullins RF, et al. New approaches to the treatment of age-related macular degeneration (AMD). Exp Eye Res. Published online May 30, 2022. doi:10.1016/j.exer.2022.109134