Five-Year Follow-up of Nonfibrotic Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials

Abstract

Purpose: To describe changes in visual acuity (VA) and macular morphologic features at 5 years in eyes with nonfibrotic scar (NFS) identified at 1 year in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

Design: Prospective cohort study within a randomized clinical trial.

Participants: Participants in CATT.

Methods: Participants assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens were released from the clinical trial protocol after 2 years and recalled at 5 years. Nonfibrotic scar was identified on color images at year 1 as flat, small, well-circumscribed areas of pigmentation with varying degrees of central hypopigmentation without exposure of underlying choroidal vessels at the site of baseline choroidal neovascularization. Follow-up images were assessed for changes in and around NFS.

Main outcome measures: Pigmentation changes, VA, development of fibrotic scar (FS), nongeographic atrophy (NGA), geographic atrophy (GA), retinal fluid on OCT, and fluorescein leakage.

Results: Among 474 eyes with images obtained at 1, 2, and 5 years, 39 (8.2%) showed NFS at 1 year with a mean VA of 80 letters (Snellen equivalent, 20/25). Among these eyes, FS developed in 5% at 2 years and 28% at 5 years. Nongeographic atrophy was observed in 34%, 47%, and 65% of eyes at 1, 2, and 5 years, respectively. Geographic atrophy developed in 5% of eyes at 2 years and 21% at 5 years. Among eyes with NFS, FS, or no scar at 1 year, mean VA at 5 years was 73 letters (20/32), 48 letters (20/100), and 62 letters (20/63), respectively. At 5 years, NFS eyes demonstrated less GA, less intraretinal fluid, more subretinal fluid, and less subretinal pigment epithelium fluid (all P < 0.01). Among NFS eyes, mean thickness of the retina, subretinal tissue complex, and total retina did not change across years 1 to 5 (P > 0.50). The proportion of eyes with fluid on OCT also did not change (P = 0.36). Subretinal hyperreflective material disappeared by 5 years in 40% of eyes with NFS.

Conclusions: These results indicate that, on average, eyes with NFS after anti-VEGF treatment have good VA not only at 1 and 2 years, but also through 5 years.

Trial registration: ClinicalTrials.gov NCT00593450.

Conflict of interest statement

Conflict of Interest: No conflicting relationship exists for any other author than described above.

Copyright © 2018 American Academy of Ophthalmology. All rights reserved.

Figures

Figure 1:

Color fundus photograph (CFP) and Fluorescein Angiogram (FA) images of non-fibrotic scar (NFS) in four different CATT subjects: A1 shows a typical NFS at year 1 with hyperpigmentation encircling an area of hypopigmentation on CFP. A2 is the corresponding FA showing an inner hyperfluorescence surrounded by circular hypofluorescence. No changes are seen at year 2 (A3) but part of the pigmentation at 7 o’clock has disappeared in the year 5 CFP (A4). B1 and B2 show a halo of non-geographic atrophy (NGA) surrounding the NFS in year 1. This persists in year 2 (B3) and intensifies into geographic atrophy (GA) at year 5 (B4); C1–C3 show NGA surrounding the NFS at years 1 and 2 with development of a large GA at year 5 (C4) and the disappearance of more than half of the circular hyperpigmentation of the NFS; D1 and D2 show a NFS which develops fibrosis within the hyperpigmented ring at year 2 (D3) that is more pronounced at year 5 (D4). Some amount of fibrosis is also observed superiorly overlying an area of geographic atrophy. White arrow=NGA. Black arrow=GA.

Figure 2:

Color fundus photograph (CFP, left), infrared scanning laser ophthalmoscopic (IR, center) and spectral domain optical coherence tomographic (SDOCT, right) images of non-fibrotic scar (NFS) in three CATT subjects at year 2 and 5. A small pigment encircled NFS is seen at 2 years (A1, B1 and C1) diminishes at year 5 (A4, B4 and C4). Pigmented areas appear bright on the IR images (A2–C2). SDOCT A3 and A6 show compact subretinal hyperreflective material (SHRM, white arrow) over the fibrovascular pigment epithelial detachment (PED) with adjacent subretinal fluid (SRF), however, there is a hyperreflective layer extending from the retinal pigment epithelium (RPE) across part of the inner border of the SHRM (orange arrow). By year 5, the SHRM is now encased in the RPE layer contiguous with the inner border of the PED, subretinal fluid persists with focal sites of greater penetration of OCT signal into the choroid. B1, B2 and B3 show a NFS at 2 years in another study eye along with a similar appearance as in the previous eye (A3) but with an even more prominent region of heaped up hyperreflectivity corresponding to the sites of the dark pigment ring and a second “RPE layer” extending across the SHRM. However the SHRM has either resolved or cannot be distinguished from the layered reflectance in the fibrovascular PED (B6) and the SRF has resolved. In the third example C1–C3, the year 2 compact SHRM (C3) contracts further at year 5 with a more pronounced hyperreflective RPE layer over the lesion (C6).