Hypertransmission Defects Predict GA Formation

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In a pair of studies, researchers at the Bascom Palmer Eye Institute in Miami have confirmed that persistent hypertransmission defects (hyperTDs)—defined as those with a greatest linear dimension of 250 μm or more—can serve as an independent risk factor for the progression of drusen to geographic atrophy (GA) in dry age-related macu­lar degeneration (AMD).^1,2

On OCT, hyperTDs appear as bright regions due to increased light trans­mission into the choroid where the retinal pigment epithelium (RPE) is attenuated or absent. Previous research has found that hyperTDs could be seen during the progression from intermedi­ate AMD to late-stage AMD.

EVIDENCE. (1) A hyperTD shows as a bright lesion on en face OCT (yellow arrow). (2) Corresponding OCT B-scan shows the increased choroidal hypertransmission (yellow arrow). (3) Nascent GA (blue arrow), identified on OCT B-scan.

En face SD-OCT. Using en face spec­tral-domain OCT, the researchers eval­uated 81 patients (157 eyes). Thirty-nine hyperTDs were documented in 22 patients (27 eyes) and classified as either persistent (26 lesions) or transient (13 lesions) over a three-year period. The presence of the lesions was confirmed on corresponding OCT B-scans.¹

The hyperTDs (≥250 μm) were associated with nascent GA, the analysis found. Because of the high negative predictive value (≥94%), the research­ers concluded that these persistent hyperTDs could be used as a stand-alone precursor for the progression from intermediate AMD to GA.

En face SS-OCT. In a larger study, the researchers found that a persistent hyperTD significantly increases the risk of developing GA in eyes with interme­diate AMD.²

For this study, the researchers used en face swept-source OCT to assess 134 patients (190 eyes). All told, 73 eyes had at least one hyperTD at baseline or fol­low-up. However, those with hyperTDs >250 μm (n = 31) were more likely to progress to GA than were those with smaller lesions (n = 42). Overall, the researchers estimated, the risk of devel­oping GA increased by 80-fold once a hyperTD >250 μm appeared.

Next steps. The Bascom Palmer researchers are planning a treatment trial to slow disease progression in eyes with intermediate AMD, using the appearance of persistent hyperTDs as the clinical trial endpoint, said Philip J. Rosenfeld, MD, PhD, coauthor of both studies. They’ve also developed and trained a machine learning algorithm that can detect hyperTDs on en face images.

High praise for en face OCT. Dr. Rosenfeld credits the Classification of Atrophy Meeting (CAM) group, an international team of AMD and retinal imaging experts, for emphasizing the importance of OCT over autofluores­cence imaging for diagnosing GA.

“I love the simplicity of the meth­od,” Dr. Rosenfeld said. “En face OCT imaging is the most accurate and efficient way to diagnose and monitor disease progression in dry AMD when compared with other imaging mo­dalities. There’s no need to use color fundus imaging, autofluorescence im­aging, or infrared reflectance imaging to detect the earliest formation and subsequent growth of GA. We can do it all with a single OCT raster scan.”

—Miriam Karmel

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1 Shi et al. Ophthalmol Retina. 2021;5(12):1214-1225.

2 Laiginhas R et al. Am J Ophthalmol. Published online Nov. 13, 2021.

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Relevant financial disclosures: Dr. Rosenfeld—Apellis: C,O; Bayer: C; Carl Zeiss: C,S; BoehringerIngelheim: C; Chengdu Kanghong Biotech: C; Gyroscope Therapeutics: S; OcuDyne: C,O; Ocunexus (inflammX): C; Regeneron: C; Stealth BioTherapeutics: S; Unity Biotechnology: C; Valitor: O; Verana Health: O.

For full disclosures and the disclosure key, see below.

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