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

Abstract

Objective: To describe changes in visual acuity (VA) and macular morphology at 5 years in eyes with non-fibrotic scars (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. NFS 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 (CNV). Follow-up images were assessed for changes in and around the NFS. Main outcome measures: Changes in pigmentation, VA, development of fibrotic scar (FS), non-geographic (NGA) and geographic atrophy (GA), retinal fluid on optical coherent tomography, and fluorescein leakage.

Hyperreflective material as a biomarker in neovascular age-related macular degeneration

“…However, we believe it is paramount to make a distinction between fibrotic scar and nonfibrotic scar. While fibrotic scar development negatively affects the visual outcomes [32][33][34][35], nonfibrotic scars that develop during the first year of treatment appear to be associated with better functional outcomes during follow-up [42]. We also observed that HRM thickness at the initiation of treatment may be an indicator of the scar evolution [23], since thicker HRM has been associated with the development of fibrotic scar [42].…”

Anti–Vascular Endothelial Growth Factor Use and Atrophy in Neovascular Age-Related Macular Degeneration

“…In addition, it is difficult to determine whether prognostic factors truly affect atrophy. For example, atrophy incidence was lower in patients with a nonfibrotic scar than in those with no scar 23 ; however, this observation could be a result of the inability of atrophy to develop in these areas. Furthermore, patient populations in randomized controlled trials do not necessarily reflect real-world patients.…”

“…17 Nonfibrotic scar in year 1 was associated with an increased GA incidence at years 2 and 5. 23 Poor baseline VA was associated with an increased risk of development of GA by 5 years. 22 Additional factors associated with a higher incident GA risk at 5 years were older age, hypercholesterolemia, increasing MNV lesion size, RAP lesion, fellow eye GA, and intraretinal fluid.…”

“…Population: patients who completed the 5-yr follow-up; GA at 1 yr: 13%; GA at 2 yrs: 18%; GA at 5 yrs: 39% Population: patients who completed the 5-yr follow-up (n ¼ 112); overall GA growth rate: 0.29 mm/yr Daniel et al (2018) 23 Eyes with nonfibrotic scar identified at 1 yr in CATT (N ¼ 39)…”

Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

“…In spite of the efficacy, some cases still showed poor vision outcomes after long-term anti-VEGF therapy. Moreover, several clinical trials also reported that GA developed in neovascular AMD patients after continual treatment with ranibizumab or bevacizumab [ 70 , 71 , 72 , 73 ]. One study even showed that the cumulative incidence of GA increased from the first (12%) to the fifth year (38%) of treatment.…”