Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration

Abstract

Purpose: Appearance of geographic atrophy (GA) on color photography (CP) is preceded by specific features on spectral-domain optical coherence tomography (SD OCT). We aimed to build SD OCT-based risk assessment models for 5-year new onset of GA and central GA on CP.

Design: Prospective, longitudinal study.

Participants: Age-Related Eye Disease Study 2 Ancillary SD OCT study participants with age-related macular degeneration (AMD) with bilateral large drusen or noncentral GA and at least 1 eye without advanced disease (n = 317).

Methods: For 1 eye per participant, qualitative and quantitative SD OCT variables were derived from standardized grading and semiautomated segmentation, respectively, at baseline. Up to 7 years later, annual outcomes were extracted and analyzed to fit multivariate logistic regression models and build a risk calculator.

Main outcome measures: New onset of CP-visible GA and central GA.

Results: Over a follow-up median of 4.0 years and among 292 AMD eyes (without advanced disease at baseline) with complete outcome data, 46 (15.8%) developed central GA. Among 265 eyes without any GA on baseline CP, 70 (26.4%) developed CP-visible GA. Final multivariate models were adjusted for age. In the model for GA, the independent predicting SD OCT factors (P < 0.001-0.03) were: hyperreflective foci and retinal pigment epithelium (RPE) layer atrophy or absence, followed by choroid thickness in absence of subretinal drusenoid deposits, photoreceptor outer segment loss, RPE drusen complex volume, and RPE drusen complex abnormal thinning volume. For central GA, the factors (P < 0.001) were RPE drusen complex abnormal thinning volume, intraretinal fluid or cystoid spaces, hyperreflective foci, and RPE layer atrophy or absence. The models yielded a calculator that computes the probabilities of CP-visible, new-onset GA and central GA after 1 to 5 years.

Conclusions: For AMD eyes with large drusen and no advanced disease, we built a novel risk assessment model-based on age and SD OCT segmentation, drusen characteristics, and retinal pathology-for progression to CP-visible GA over up to 5 years. This calculator may simplify SD OCT grading and with future validation has a promising role as a clinical prognostic tool.

Trial registration: ClinicalTrials.gov NCT00734487.

Figure 1

AREDS2 Ancillary SDOCT Study Participants and Selection of Groups At Risk of New-Onset Central Geographic Atrophy (N=292), and New-Onset Geographic Atrophy (GA) (N=265). AREDS2 = Age-Related Eye Disease Study 2, SDOCT = spectral domain optical coherence tomography, GA = geographic atrophy, AMD = age-related macular degeneration, CP = color photography. ^a On color photography (CP), 25 eyes of 25 participants with no Advanced AMD (per AREDS2 definition) were excluded due to insufficient CP data on follow-up: 14 lost to follow-up before 1 year + 11 with CP ungradable for GA on follow-up visits. ^b One eye per participant.

Figure 2

Preview of the SDOCT-based Risk Calculator ^a for New-Onset ^b of Central GA and of GA. The upper panel corresponds to the risk calculation for a participant in the AREDS2 Ancillary SDOCT study with no GA on baseline color photography. The lower panel is for a hypothetical patient with similar findings, except without RPE layer Atrophy or absence on SDOCT. SDOCT = spectral domain optical coherence tomography, GA = geographic atrophy, AREDS2 = Age-Related Eye Disease Study 2. ^a This calculator is a research tool, not validated, and not intended for clinical use. Actual outcome is shown in figure 3. ^b New-onset of atrophy on color fundus photography.

Figure 3

AREDS2 Ancillary SDOCT Study imaging from the eye from example in Figure 2. Top row: baseline imaging. (a) Color fundus photography at baseline shows large drusen but no geographic atrophy. (b) Baseline SDOCT B-scan at location of green line in (a) showing hyperreflective foci (green arrowheads) and RPE layer Atrophy or absence on OCT (blue arrow). (c) Baseline map of abnormal thickness of RPE drusen complex (OCT Drusen in orange/red, RPE drusen complex Abnormal Thinning in blue). Green line shows location of B-scan in (b). Bottom row: follow-up imaging (chronologic from left to right). Color fundus photography from years 1, 2, 3, and 4 respectively in (d), (e), (f), and (g). In this eye, new onset of GA on color photography (red arrow) occurred in year 4 (g). The participant underwent cataract surgery between years 3 (f) and 4 (g), which explains the improvement in the focus and crispness of the photo (g). AREDS2 = Age-Related Eye Disease Study 2, SDOCT = spectral domain optical coherence tomography, AMD = age-related macular degeneration, RPE = retinal pigment epithelium, GA = geographic atrophy.

Equation 1

System of Equations for the Risk Calculator for New-Onset Central GA and New-Onset GA on Color Fundus Photography after x Years.