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Original Investigation
May 7, 2020

Characterization of Drusen and Hyperreflective Foci as Biomarkers for Disease Progression in Age-Related Macular Degeneration Using Artificial Intelligence in Optical Coherence Tomography

Author Affiliations
  • 1Christian Doppler Laboratory for Ophthalmic Image Analysis, Department of Ophthalmology, Medical University of Vienna, Vienna, Austria
JAMA Ophthalmol. 2020;138(7):740-747. doi:10.1001/jamaophthalmol.2020.1376
Key Points

Question  Are there characteristic morphologic patterns on optical coherence tomography in eyes with age-related macular degeneration that develop macular atrophy and macular neovascularization?

Findings  In this cohort study of 8529 optical coherence tomographic volumes of 512 patients, eyes progressing to advanced age-related macular degeneration had higher drusen and hyperreflective foci volume and an accelerated increase in drusen volume and hyperreflective foci activity.

Meaning  Drusen and hyperreflective foci distribution, time course, and volumes may differ among distinct progression pathways in patients with age-related macular degeneration.


Importance  The morphologic changes and their pathognomonic distribution in progressing age-related macular degeneration (AMD) are not well understood.

Objectives  To characterize the pathognomonic distribution and time course of morphologic patterns in AMD and to quantify changes distinctive for progression to macular neovascularization (MNV) and macular atrophy (MA).

Design, Setting, and Participants  This cohort study included optical coherence tomography (OCT) volumes from study participants with early or intermediate AMD in the fellow eye in the HARBOR (A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration) trial. Patients underwent imaging monthly for 2 years (July 1, 2009, to August 31, 2012) following a standardized protocol. Data analysis was performed from June 1, 2018, to January 21, 2020.

Main Outcomes and Measures  To obtain topographic correspondence between patients and over time, all scans were mapped into a joint reference frame. The time of progression to MNV and MA was established, and drusen volumes and hyperreflective foci (HRF) volumes were automatically segmented in 3 dimensions using validated artificial intelligence algorithms. Topographically resolved population means of these markers were constructed by averaging quantified drusen and HRF maps in the patient subgroups.

Results  Of 1097 patients enrolled in HARBOR, 518 (mean [SD] age, 78.1 [8.2] years; 309 [59.7%] female) had early or intermediate AMD in the fellow eye at baseline. During the 24-month follow-up period, 135 (26%) eyes developed MNV, 50 eyes (10%) developed MA, and 333 (64%) eyes did not progress to advanced AMD. Drusen and HRF had distinct topographic patterns. Mean drusen thickness at the fovea was 29.6 μm (95% CI, 20.2-39.0 μm) for eyes progressing to MNV, 17.2 μm (95% CI, 9.8-24.6 μm) for eyes progressing to MA, and 17.1 μm (95% CI, 12.5-21.7 μm) for eyes without disease progression. At 0.5-mm eccentricity, mean drusen thickness was 25.8 μm (95% CI, 19.1-32.5 μm) for eyes progressing to MNV, 21.7 μm (95% CI, 14.6-28.8 μm) for eyes progressing to MA, and 14.4 μm (95% CI, 11.2-17.6 μm) for eyes without disease progression. The mean HRF thickness at the foveal center was 0.072 μm (95% CI, 0-0.152 μm) for eyes progressing to MNV, 0.059 μm (95% CI, 0-0.126 μm) for eyes progressing to MA, and 0.044 μm (95% CI, 0.007-0.081) for eyes without disease progression. At 0.5-mm eccentricity, the largest mean HRF thickness was seen in eyes progressing to MA (0.227 μm; 95% CI, 0.104-0.349 μm) followed by eyes progressing to MNV (0.161 μm; 95% CI, 0.101-0.221 μm) and eyes without disease progression (0.085 μm; 95% CI, 0.058-0.112 μm).

Conclusions and Relevance  In this study, drusen and HRF represented imaging biomarkers of disease progression in AMD, demonstrating distinct topographic patterns over time that differed between eyes progressing to MNV, eyes progressing to MA, or eyes without disease progression. Automated localization and precise quantification of these factors may help to develop reliable methods of predicting future disease progression.

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