Spectral-domain optical coherence tomography characteristics of intermediate age-related macular degeneration

Abstract

Purpose: Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading.

Design: Prospective cross-sectional study.

Participants: We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD.

Methods: Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ≥1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility.

Main outcome measures: We assessed SD-OCT characteristics at baseline.

Results: In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy.

Conclusions: Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Trial registration: ClinicalTrials.gov NCT00734487.

Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Study eye designation and age-related macular degeneration (AMD) categorization of both eyes from 345 participants by color fundus photography grading. *One of the 314 eyes could not be graded.

Figure 2

Examples of spectral-domain optical coherence tomography morphology in study eyes with age-related macular degeneration (AMD). All of these eyes had been graded as category 3 AMD (nonadvanced) on color fundus photographs. The spectral-domain optical coherence tomography morphology terms are defined in Table 1 (available at http://aaojournal.org). To reduce the noise in linear B-scan images, varying numbers of B-scans were summed using Image J software. A, Vitreomacular attachment (arrow). B, Epiretinal membrane (upward arrow) and focal high reflectivity over druse (downward arrow) within the outer retina and distinct from normal variation in retinal reflectivity. C, Intraretinal cystoid structure. D, Subretinal fluid over large contiguous drusen (arrows). E, Subretinal pathology that likely represents choroidal neovascularization with overlying intraretinal fluid (cystoid edema). F, A broad area of retinal pigment epithelial atrophy (geographic atrophy) extends through the fovea with overlying photoreceptor loss and increase in reflectivity of the underlying choroid. G, Subretinal fluid at the foveal center. H, Photoreceptor layer thinning over drusen (left druse, with arrow).

Figure 3

Spectral-domain optical coherence tomography drusen morphology and retinal morphology related to drusen. The morphology terms are defined in Table 1. To reduce the noise in linear B-scan images, varying numbers of B-scans were summed using Image J software. A, B, Drusen with low reflectivity. C, D, Mid-reflective drusen. Photoreceptor layer thinning overlying the drusen is indicated by the arrows. E, Highly reflective druse. F, Stage 2 subretinal reticular drusenoid deposits are characterized as drusen. G–I. Drusen with cores. G, The low reflective core (wide arrow) is within a mid-reflective drusen with overlying hyperreflective focus (narrow arrow). H, Hyperreflective focus within a mid-reflective druse. I, Low-reflective druse with a core.

Figure 4

Prevalence of spectral-domain optical coherence tomography retinal pathologies and drusen characteristics among the 313 category 3 age-related macular degeneration (AMD) study eyes.

Figure 5

Effect of age on visual acuity among 313 category 3 age-related macular degeneration (AMD) study eyes and 122 control eyes. The box outlines the interquartile range (25th–75th percentiles), and whiskers extend to the most extreme data point within 1.5 times the length of interquartile range. Values beyond 1.5 times the interquartile range were considered outliers (circles). The mean Early Treatment Diabetic Retinopathy Study value is shown as a diamond within each box, and a horizontal line represents the median.

Figure 6

Effect of foveal pathologies on visual acuity among 313 category 3 age-related macular degeneration (AMD) study eyes. The mean visual acuity score (adjusted for age) was higher among eyes without foveal pathology than among eyes with foveal pathologies. This difference was significant (P<0.02) in all subgroups except eyes with foveal vitreomacular attachment (VMA; P = 0.1278). Among eyes containing foveal pathology, the subgroup with the highest Early Treatment of Diabetic Retinopathy Study score was eyes with foveal drusen, although the Early Treatment Diabetic Retinopathy Study score was still significantly decreased compared with controls (P = 0.009). Eyes containing foveal subretinal fluid and foveal retinal pigment epithelium atrophy or absence had the poorest visual acuities, significantly lower than eyes without foveal pathology (P<0.0001 and P = 0.0002, respectively). When compared with no foveal lesion, there was no difference for VMA. In light of multiple comparisons, there is likely no difference for epiretinal membrane and drusen, but there was a difference in the others: intraretinal cysts, P = 0.002; subretinal fluid, P≤0.0001; other subretinal lesion, P = 0.002; and atrophy, P = 0.0002. The box outlines the interquartile range (25th–75th percentiles), and whiskers extend to the most extreme data point within 1.5 times the length of interquartile range. Values beyond 1.5 times the interquartile range were considered outliers (circles). Diamonds represent the mean Early Treatment of Diabetic Retinopathy Study value (adjusted for age), and the horizontal line within the box indicates the median. Additionally, analysis of variance assumptions of normality and equal variances were violated among eyes with foveal vitreomacular attachment, subretinal fluid, drusen, and retinal pigment epithelium atrophy or absence. The analysis of variance model is robust if the sample size is large (as in the case of eyes with foveal drusen), but results may be biased among subgroups with a small number of eyes (e.g., vitreomacular attachment).