Macular Atrophy Occurs Late in AMD Progression, Study Suggests

Rosa Dolz-Marco, MD, PhD

A new study determined that, although imaging methods like fundus autoflorescence (FAF) and optical coherence tomography (OCT) can determine characteristics of disease presence and progression in age-related macular degeneration (AMD) by identifying signs of macular atrophy (MA), there may be signs of AMD development occurring prior to evidence of MA that are detectable on the cellular level.

Led by Rosa Dolz-Marco, MD, PhD, of the Vitreous Retina Macula Consultants, investigators found that MA may be evidence of late-stage disease progression, and that more research is needed into earlier anatomic endpoints.

Although investigators noted that detailed outer retinal morphology is "readily visible on high-quality OCT" there is still a large range of retinal pigment epithelium (RPE) morphology in patients with advanced AMD.

“The termination of the continuous RPE layer provides an inexact boundary for analyzing atrophy progression,” Dolz-Marco and colleagues wrote.

A more concise measure of atrophy progression could be found in the curved line formed by the descent of the external limiting membrane (ELM) toward the Bruch membrane (BrM), according to the study, which could provide a clearer delimitation of RPE and photoreceptor atrophy on the histological level.

The case study focused on the right eye of a 98 year old female patient with advanced MA caused by AMD and related open-angle glaucoma who was treated over an 11-year period at the Vitreous Retina Macula Consultants of New York. Investigators compared in vivo eye-tracked cross-sectional OCT scans of the study eye performed 8 and 13 months prior to the patient's death and to cellular postmortem analysis of the study eye in order to determine the effectiveness of OCT in determining retinal thickness and extent of retinal damage in comparison to OCT-tracked histology for subcellular resolution across the macula.

Dolz-Marco and colleagues report that the studied eye exhibited a “collapsed acquired vitelliform deposit and, seen only upon histology, a type 1 neovascularization, sub-RPE hematoma, and intraretinal fluid.”

The researchers also found basal linear deposit, basal laminar deposit ( BLamD), and subretinal drusenoid deposits which supported the diagnosis of macular atrophy secondary to AMD and exhibited multiple AMD features not explained by normal aging.

Investigators noted there was evidence of AMD progression to macular atrophy observed between the 8- and 13- month visits with disruption or disappearance of the RPE layer and persistence of BLamD across the atrophic area. They added that ELM was not visible in areas of atrophy, but was throughout non-atrophic areas.

Dolz-Marco and colleagues wrote that their data suggested that RPE and ELM morphology may have prognostic value, and that detection of the ELM descent to determine shape and thickening of BLamD toward the ELM descent may serve as an earlier sign of macular degeneration than atrophy itself.

“How atrophy is detected impacts its clinical relevance, and diagnostic technologies to date have revealed only some of the challenges to treatments targeting atrophy in AMD," investigators wrote.

The study, "The Border of Macular Atrophy in Age-Related Macular Degeneration: A Clinicopathologic Correlation" was published in the American Journal of Ophthalmology.