Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration

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• 作者：Malini Veerappan ; BA¹ ; ^{malini.veerappan@dm.duke.edu" class="auth_mail" title="E-mail the corresponding author} ; Abdul-Karim M. El-Hage-Sleiman ; MD¹ ; Vincent Tai ; MS¹ ; Stephanie J. Chiu ; PhD¹ ; Katrina P. Winter ; BS¹ ; Sandra S. Stinnett ; DPH¹ ; Thomas S. Hwang ; MD² ; G. Baker Hubbard III ; MD³ ; Michelle Michelson ; BS¹ ; Randall Gunther ; MS¹ ; Wai T. Wong ; MD ; PhD⁴ ; Emily Y. Chew ; MD⁴ ; Cynthia A. Toth ; MD¹ ; ⁵ ; for the Age-related Eye Disease Study 2 Ancillary Spectral Domain Optical Coherence Tomography Study Group^&lowast ; ; Cynthia A. Toth ; Wai Wong ; Thomas Hwang ; G. Baker Hubbard ; Sunil Srivastava ; Michelle McCall ; Katrina Winter ; Neeru Sarin ; Katherine Hall ; Patti McCollum ; Linda Curtis ; Stefanie Schuman ; Stephanie J. Chiu ; Sina Farsiu ; Vincent Tai ; Monica Sevilla ; Christopher Harrington ; Randall Gunther ; Du Tran-Viet ; Francisco Folgar ; Eric Yuan ; Traci Clemons ; Molly Harrington ; Emily Chew
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：123
• 期：12
• 页码：2554-2570
• 全文大小：2435 K

文摘

Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography–reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)–related features and AMD progression.

Design

Retrospective analysis in a prospective study.

Participants

Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography (SD OCT) study.

Methods

Baseline SD OCT scans of 1 eye per patient were analyzed for the presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm-diameter region around individual ODS and corresponding control region without ODS in the same eye.

Main Outcome Measures

Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs.

Results

Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Among the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline (P < 0.001), (2) development of preatrophic changes at year 2 (P = 0.001–0.01), and (3) development of macular GA (P = 0.005) and preatrophic changes at year 3 (P = 0.002–0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline (P = 0.02–0.03) and (2) development of preatrophy changes at years 2 and 3 within the region (P = 0.008–0.05).

Conclusions

Optical coherence tomography–reflective drusen substructures are optical coherence tomography–based biomarkers of progression to GA, but not to CNV, in eyes with intermediate AMD. Optical coherence tomography–reflective drusen substructures may be a clinical entity helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.