GA Case Compendium: Identifying High-Risk Biomarkers for

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Case Presentation

A 70-year-old asymptomatic man presented for a routine examination. He reported having cataract surgery 2 years prior and his medical history was remarkable for hypertension, dyslipidemia, and heart disease post coronary artery stenting. He denied current or past tobacco use and had no family history of age-related macular degeneration (AMD). His medications included lisinopril, atorvastatin, clopidogrel, hydroxyzine, 81 mg aspirin, and a daily multivitamin. BCVA was 20/20 in both the right and left eyes on initial exam.

Ophthalmoscopy revealed multiple drusen subtypes bilaterally including large soft drusen, reticular pseuodrusen (RPD) or subretinal drusenoid deposits (SDD), and several whitish/glistening appearing reflective or calcific drusen (Figures 1 and 2). Of importance to the case, both RPD and reflective drusen are high-risk features for progression to GA.^1-3 Furthermore, hyperpigmentary retinal pigment epithelium (RPE) changes were present in the left eye.

With cross-sectional OCT, bright hyperreflective linear sub-retinal RPE plaques resting on Bruch membrane were noted bilaterally and corresponded clinically with reflective/calcific drusen (Figures 1 and 2, yellow arrows). Also present on the right eye OCT were drusen with dark, hyporeflective cores (Figure 1, teal arrows) as well as a soft drusen with underlying intermittent choroidal hyperreflectivity (sub-RPE hyperreflective columns) suggestive of compromised integrity of the RPE at the apex of the druse (Figure 1, pink arrows).

Baseline OCT imaging of the left eye revealed intraretinal hyperreflective foci overlying a large soft druse and corresponded clinically with hyperpigmentary changes (Figure 2, teal arrows). Extensive RPD were present throughout the macula, appearing as nodular, hyper-reflective deposits resting on the anterior RPE surface within the subretinal space (Figure 2, red arrows). In addition, an incipient or impending GA lesion was present in the inferior parafovea: OCT imaging features of this lesion included an underlying vertical column of choroidal hypertransmission, "V" shaped subsidence or sinking of the outer plexiform layer (OPL), and a pair of hyporeflective wedges that bordered an area of photoreceptor, RPE and external limiting membrane (ELM) attenuation/loss (Figure 2).¹

Summary/Clinical Take-Home

Early detection and timely referral of GA are vital to slow progression and maintain central vision for as long as possible. Awareness of risk factors and intentional examination strategies including imaging such as OCT allows for maximal patient outcomes.

GA from AMD often progresses quickly, resulting in irreversible structural damage and vision loss. Therefore, early detection and timely referral are vital to slow expansion and maximize patient outcomes by delaying central involvement for as long as possible. Early GA detection starts with identifying patients at high-risk for progression and performing multimodal imaging, especially OCT and FAF, since these technologies highlight subclinical pathology. OCT assessment in particular provides powerful prognostic value because it provides high-resolution, detailed images of the individual retinal layers that allows us to detect high-risk biomarkers for progression and visualize the earliest atrophic lesions before they become clinically apparent.

1. Jaffe GJ, Chakravarthy U, Freund KB, et al. Imaging features associated with progression to geographic atrophy in age-related macular degeneration: classification of atrophy meeting report 5. Ophthalmol Retina. 2021;5(9):855-867.
2. Rabiolo A, Sacconi R, Cicinelli MV, et al. Spotlight on reticular pseudodrusen. Clin Ophthalmol. 2017;11:1707-1718.
3. Liu J, Laiginhas R, Shen M, et al. Multimodal imaging and en face OCT detection of calcified drusen in eyes with age-related macular degeneration. Ophthalmol Sci. 2022;2(2):100162.
4. Biarnés M, Arias L, Alonso J, et al. Increased fundus autofluorescence and progression of geographic atrophy secondary to age-related macular degeneration: The GAIN study. Am J Ophthalmol. 2015;160(2):345-353.e5.
5. Holz FG, Bindewald-Wittich A, Fleckenstein M, et al.; FAM-Study Group. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am J Ophthalmol. 2007;143(3):463-72.

Carolyn Majcher, OD, FAAO, FORS

- Director, Residency Programs and Associate Professor, Northeastern State University Oklahoma College of Optometry, Tahlequah, Oklahoma

- Chief, Broward Eye Care Institute, Fort Lauderdale, Florida

- majcher@nsuok.edu

- Financial disclosures: Consultant (Topcon); Speaker and Consultant (Apellis Pharmaceuticals, Astellas, Zeiss, Regeneron Pharmaceuticals)

ABOUT THIS SERIES

Newly available treatment options for geographic atrophy (GA) have the potential to change the prognosis for long-term eye health. However, their newness also raises important practical questions, including about who should be referred and when. The Geographic Atrophy Clinical Case Compendium was developed, with guidance from Carolyn E. Majcher, OD, FAAO, FORS, and Julie Rodman, OD, MSc, FAAO, to demonstrate real-world patient encounters and the impact of treatment on the clinical course.

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