Development and Course of Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials

Abstract

Purpose: To describe risk factors for scar formation and changes to fibrotic scar through 5 years in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

Design: Multicenter, prospective cohort study.

Participants: A total of 1061 subjects in CATT.

Methods: Color photographic and fluorescein angiographic images from baseline and 1, 2, and 5 years were evaluated. Incidence of scar formation was estimated with Kaplan-Meier curves. Risk factors were assessed with Cox regression models.

Main outcome measures: Scar formation, fibrotic scar area, and macular atrophy associated with fibrotic scar ("atrophy").

Results: Cumulative proportion of eyes with scar was 32%, 46%, and 56% at years 1, 2, and 5, respectively. Baseline factors associated with increased risk (adjusted hazards ratio [aHR] and 95% confidence interval [CI]) were classic choroidal neovascularization (CNV) (aHR, 4.49; 95% CI, 3.34-6.04) versus occult, hemorrhage >1 disc area (DA) (aHR, 2.28; 95% CI, 1.49-3.47) versus no hemorrhage, retinal thickness >212 μm (aHR, 2.58; 95% CI, 1.69-3.94) versus <120 μm, subretinal tissue complex thickness >275 μm (aHR, 2.64; 95% CI, 1.81-3.84) versus ≤75 μm, subretinal fluid thickness >25 μm (aHR, 1.31; 95% CI, 0.97-1.75) versus no fluid, visual acuity (VA) in fellow eye 20/20 (aHR, 1.72; 95% CI, 1.25-2.36) versus 20/50 or worse, retinal pigment epithelium elevation absence (aHR, 1.71; 95% CI, 1.21-2.41), and subretinal hyperreflective material (aHR, 1.72; 95% CI, 1.25-2.36). Among 68 eyes that developed fibrotic scar at year 1, VA decreased by a mean of additional 13 letters between years 1 and 5. Mean scar area was 1.2, 1.2, and 1.9 DA at 1, 2, and 5 years, respectively. Atrophy was present in 18%, 24%, and 54% of these eyes at years 1, 2, and 5, respectively; the mean areas were 1.6, 2.0, and 3.1 DA, respectively. Atrophy replaced fibrotic scar in 8 eyes at year 5. There was no significant correlation between scar growth and atrophy growth. The rate of growth for both was similar between the clinical trial and observation periods.

Conclusions: Several morphologic features, including classic CNV and large hemorrhage, are associated with scar formation. Rate of new scar formation declined after 2 years. Most fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.

Trial registration: ClinicalTrials.gov NCT00593450.

Figure 1

Color images of fibrotic scar and macular atrophy associated with fibrotic scar (atrophy) A: Stable Fibrotic Scar: A1 shows a fibrotic scar that has developed at year 1 (black arrow). It remains stable at Year 2 and 5. There is hyperpigmentation on the scar (Green arrow) B Scar increasing in size: B1 shows a fibrotic scar that shows no change in area from Year 1 (B1) to year 2 (B2) but has a larger area in year 5 (B3) when there is growth superiorly (black arrow). There is also pigmentation on the scar (Green arrow) at year 5 C Scar with Peripheral Macular Atrophy: C1 shows a fibrotic scar at year 1 that undergoes thinning at year 2 (B3 Black arrow) with an area of macular atrophy associated with fibrotic scar (atrophy) surrounding it in year 5 (B3 Green arrow). Increased hyperpigmentation is also seen at year 5 (B3 Blue arrow). D Macular Atrophy Associated with Fibrotic scar: D1 shows a thick round fibrotic scar at year 1 (Black arrow). In year 5 the superior part of the fibrotic scar has been replaced by macular atrophy (D3 Blue arrow) E. Scar completely replaced by macular atrophy: E1 shows a fibrotic scar (Black arrow) that develops atrophy in year 2 (E2 Blue arrow) and eventually at year 5 the area of the fibrotic scar is replaced by an expanding macular atrophy (E3 Blue arrow).

Figure 3

Kaplan Meier graph showing the cumulative incidence of scar through 5 years

Figure 4

Box plot of fibrotic scar in Disc Areas over time among 68 eyes with fibrotic scar at year 1

Figure 5

Box plot of macular atrophy associated with fibrotic scar (atrophy) in Disc Areas at 1, 2 and 5 years among 68 eyes with fibrotic scar at year 1

Figure 6

Bar diagram of percentage of eyes with fibrotic scar pigmentation in year 1, 2 and 5 among 68 eyes with fibrotic scar at year 1.