Visual and Morphologic Outcomes in Eyes with Hard Exudate in the Comparison of Age-Related Macular Degeneration Treatments Trials

Abstract

Purpose: To compare baseline characteristics, visual acuity (VA) and morphological outcomes between eyes with baseline hard exudates (HE) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factors (anti-VEGF).

Design: Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

Participants: Patients with NVAMD.

Methods: Readers evaluated baseline and follow-up morphology on digital color images, fluorescein angiography (FA), and optical coherence tomography (OCT) in eyes with NVAMD that were randomly assigned to treatment with either ranibizumab or bevacizumab. Ophthalmologists identified HE on color images in the study eye.

Main outcome measures: VA; scar; geographic atrophy; retinal thickness, fluid; and number of anti-VEGF injections.

Results: HE was present in 128 of 1185 (11%) study eyes at baseline, 77% within 1 disc diameter of the foveal center. Patients with study eye HE were more likely female (81% vs 60%; p<0.001) and non-smokers (53% vs 42%; p=0.004). Both groups had similar proportions of hypercholesterolemia and hypertriglyceridemia. At baseline, eyes with HE had worse VA (mean 57 vs 61 letters; p=0.003), larger total lesion size (3.3 vs 2.4 DA; p <0.001), greater total foveal thickness (522µm vs 452µm; p<0.001), more retinal angiomatous proliferation (18% vs 10%; p=0.009) and sub-RPE fluid (65% vs 47%; p<0.001). At 1 year, VA was similar in both groups; more eyes with baseline HE had no fluid (45% vs 29%; p<0.001) and greater reduction in total foveal thickness (-266µm vs -158u; p<0.001). VA at year 2 was similar but retinas of eyes with baseline HE were thinner (267µm vs 299µm; p=0.03) and fewer eyes had sub-retinal fluid (23% vs 36%; p=0.008). HE was present in 19% of eyes at 1 year and 5% of eyes at 2 years. LIPC promoter SNP rs10468017 was not associated with NVAMD HE.

Conclusion: Eyes with HE have larger CNV lesions and more RAP. Their initially thicker retina rapidly becomes thinner on anti-VEGF treatment. HE is not significantly associated with hyperlipidemia. HE at baseline does not significantly influence VA, scar and GA outcomes in eyes with NVAMD treated with anti-VEGF. Few eyes have HE at year 2.

Figure 1

[A] Baseline images. A1=Color image with a small amount of hard exudates (yellow arrow), A2 Fluorescein angiogram showing leakage and A3 Time domain OCT with sub-retinal and sub-RPE fluid (red arrows). [B] Year 1 images. B1 = Color image with increased amounts of hard exudates and B2 Fluorescein angiogram showing leakage. [C] Year 2 images. C1 Color image showing increased amounts of hard exudates and C2 Fluorescein angiogram showing leakage. The top green line in C1 corresponds to the spectralis OCT scan in C3 showing the hard exudates on OCT (red arrows) occupying the lower portion of the inner retina and some hard exudates in the sub-retinal space. The bottom blue line in C1 corresponds to C4 where the spectralis OCT shows sub-RPE lesion and fluid (fibrovascular PED) (red arrow) and intraretinal cystoid spaces (green arrow).

Figure 2

Mean total foveal thickness in µm (retinal thickness plus subretinal fluid and lesion plus RPE and sub RPE fluid and lesion thickness) on OCT through 2 years between the two groups.