Quantitative Autofluorescence Illuminates 2 Geographic Atrophy Pathways in AMD

Quantitative autofluorescence can be used to differentiate the soft drusen and subretinal drusenoid deposit pathways to geographic atrophy in AMD.

Geographic atrophy (GA) appears to occur in 2 different pathways, originating from soft drusen and subretinal drusenoid deposits (SDDs), according to research published in Eye. Lower quantitative autofluorescence (qAF) values reflect a soft drusen pathway, while higher qAF values may indicate the SDD pathway, according to the report. 

Researchers included 18 patients (eyes, 23; mean age, 85 years) with age-related macular degeneration (AMD) and GA who underwent spectral-domain optical coherence tomography (SD-OCT) and quantitative autofluorescence (qAF) imaging in the analysis. The research team selected 52 GA regions-of-interest (ROIs), or clusters of adjacent lesions, and the ROIs were divided into groups based on the dominant intermediate AMD precursors using serial tracked SD-OCT scans. The average follow-up time was 5.5 years (range, 1.2-10 years).

Group 1 lesions (soft drusen/pigment epithelial detachment precursors, 18/52) were isolated and had a lower mean qAF (35.88 units). Group 2 lesions (mixed precursors, 22/52) had intermediate qAF (58.13 units), and group 3 lesions (SDD precursors, 12/52) were multilobular and had significantly higher mean qAF (71.62 units) compared with group 1 and 2 lesions (P <.05), according to the report.   

A significantly higher prevalence of split retinal pigment epithelium and Bruch’s membrane complex was found in SDD-associated GA, suggesting that basal laminar deposits, not drusen-associated lesions, structurally differentiated it from group 1 lesions. 

Quantitative autofluorescence and individual consideration of the two SDD- and drusen-associated pathways might improve the interpretation of research on GA mechanisms, treatments and prognostic factors for disease progression.

“In conclusion, there are potentially two different pathways to GA that are associated with the two characteristic [intermediate] AMD phenotypes of drusen and SDD, and that can be differentiated by the surrogate marker of qAF in their outcomes. The source of the greater autofluorescence in SDD-associated GA appears to be [basal laminar deposits],” according to the researchers. “Quantitative autofluorescence and individual consideration of the two SDD- and drusen-associated pathways might improve the interpretation of research on GA mechanisms, treatments and prognostic factors for disease progression.”

This study was limited by the small sample size.

References:

Wei W, Mazzola M, Otero-Marquez O, et al. Two potentially distinct pathways to geographic atrophy in age-related macular degeneration characterized by quantitative fundus autofluorescence. Eye. Published online January 9, 2023. doi:10.1038/s41433-022-02332-8