Macular Morphology and Visual Acuity in Year Five of the Comparison of Age-related Macular Degeneration Treatments Trials

Abstract

Purpose: To evaluate associations of morphologic features with 5-year visual acuity (VA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

Design: Cohort study within a randomized clinical trial.

Participants: Participants in CATT.

Methods: Eyes with age-related macular degeneration-associated choroidal neovascularization (CNV) and VA between 20/25 and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or bevacizumab and to 3 dosing regimens for 2 years and was at the ophthalmologists' discretion thereafter.

Main outcome measures: Visual acuity, thickness and morphologic features on OCT, and lesion size and foveal composition on fundus photography (FP) and fluorescein angiography (FA).

Results: Visual acuity and image gradings were available for 523 of 914 participants (57%) alive at 5 years. At 5 years, 60% of eyes had intraretinal fluid (IRF), 38% had subretinal fluid (SRF), 36% had subretinal pigment epithelium (RPE) fluid, and 66% had subretinal hyper-reflective material (SHRM). Mean (standard deviation) foveal center thickness was 148 μm (99) for retina, 5 μm (21) for SRF, 125 μm (107) for subretinal tissue complex, 11 μm (33) for SHRM, and 103 μm (95) for RPE + RPE elevation. The SHRM, thinner retina, greater CNV lesion area, and foveal center pathology (all P < 0.001) and IRF (P < 0.05) were independently associated with worse VA. Adjusted mean VA letters were 62 for no pathology in the foveal center; 61 for CNV, fluid, or hemorrhage; 65 for non-geographic atrophy (GA); 64 for nonfibrotic scar; 53 for GA; and 56 for fibrotic scar. Incidence or worsening of 8 pathologic features (foveal GA, foveal scar, foveal CNV, SHRM, foveal IRF, retinal thinning, CNV lesion area, and GA area) between years 2 and 5 was independently associated with greater loss of VA from years 2 to 5 and VA loss from baseline to year 5.

Conclusions: Associations between VA and morphologic features previously identified through year 1 were maintained or strengthened at year 5. New foveal scar, CNV, intraretinal fluid, SHRM and retinal thinning, development or worsening of foveal GA, and increased lesion size are important contributors to the VA decline from years 2 to 5. A significant need to develop therapies to address these adverse pathologic features remains.

Trial registration: ClinicalTrials.gov NCT00593450.

Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Flow chart for analysis cohort

Figure 2.. Correlation of retinal fluid on OCT with visual acuity.

A) Visual acuity vs. any fluid. B) Visual acuity vs. intraretinal fluid. C) Visual acuity vs sub-retinal fluid. D) Visual acuity vs. sub-RPE fluid.

Figure 3.. Visual acuity with thickness measurements on OCT at baseline, and years 1, 2, and 5.

A) Visual acuity vs. total thickness. B) Visual acuity vs. retinal thickness. C) Visual acuity vs sub-retinal fluid thickness. D) Visual acuity vs. sub-retinal tissue complex thickness.

Figure 4.

Pathology in the foveal center at A) Baseline, B) Year 1, C) Year 2, D) Year 5

Figure 5.. Mean visual acuity over time among eyes without morphological features vs. eyes with at least one new adverse morphological features developed between year 2 to year 5.

The adverse features included the following: foveal GA; foveal scar, foveal CNV, SHRM at 1 mm center, foveal intraretinal fluid, and retinal thinning, each that developed after year 2; area of CNV lesion increased by >2 mm2 between year 2 and Year 5; change of GA area >2mm2 between year 2 and Year 5.

Figure 6.. Mean visual acuity over time by groups of eyes defined based on number of new adverse morphological features developed between year 2 to year 5.

The adverse features were the same as those described in Figure 5, and included foveal GA; foveal scar, foveal CNV, SHRM at 1 mm center, foveal intraretinal fluid, and retinal thinning, each that developed after year 2; area of CNV lesion increased by >2 mm2 between year 2 and Year 5; change of GA area >2mm2 between year 2 and Year 5.

Figure 7.

Visual acuity over time with and without foveal GA and fibrosis