Progression of geographic atrophy in age-related macular degeneration imaged with spectral domain optical coherence tomography

Abstract

Purpose: To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral domain optical coherence tomography (SD-OCT) fundus image.

Design: Prospective, longitudinal, natural history study.

Participants: Eighty-six eyes of 64 patients with ≥6 months of follow-up.

Methods: Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA). The areas of GA identified on the SD-OCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored.

Main outcome measures: Enlargement rate of GA.

Results: At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59 mm(2) (1.8 disc areas [DA]). The mean follow-up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square root scale (ICC = 0.996). Intergrader differences were not an important source of variability in lesion size measurement (ICC = 0.999, 0.997). On average, the ER of GA per year was 1.2 mm(2) (0.47 DA; range, 0.01-3.62 mm(2)/year). The ER correlated with the initial area of GA (r = 0.45; P<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the ER (0.28 mm/yr) was not correlated with baseline size (r = -0.09; P = 0.40). In this cohort of lesions, no correlation was found between ER and length of follow-up. Square root transformation of the data helped to facilitate sample size estimates for controlled clinical trials involving GA.

Conclusions: The SD-OCT fundus image can be used to visualize and quantify GA. Advantages of this approach include the convenience and assurance of using a single imaging technique that permits simultaneous visualization of GA along with the loss of photoreceptors and the retinal pigment epithelium that should correlate with the loss of visual function.

Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Reproducibility of Lesion Size Measurements A. Average of repeated lesion area measurements from multiple scans obtained from each eye plotted against their standard deviations. B. Average of the square root of repeated lesion area measurements from multiple scans obtained from each eye plotted against their standard deviations.

Figure 2

Bland-Altman Plots of Lesion Size Measurements from Two Graders A. The agreement between lesion area measurements performed by two graders at baseline and last follow-up displayed using Bland Altman plots. Solid line depicts the average difference between two graders. Dashed lines depict the Bland-Altman limits of agreement. The coefficient of variation was 7.7%. B. The agreement between the square root of lesion area measurements performed by two graders at baseline and last follow-up displayed using Bland Altman plots. Solid line depicts the average difference between two graders. Dashed lines depict the Bland-Altman limits of agreement. The coefficient of variation was 3.2%.

Figure 3

Relationship between Enlargement Rate and Baseline Lesion Size A. Scatter plot showing the enlargement rate as a function of baseline lesion area. B. Scatter plot showing the enlargement rate based on the square root of the lesion area measurements as a function of the square root of the baseline lesion area.

Figure 4

Relationship between Enlargement Rate and Length of Follow-up A. Scatter plot showing the relationship between the enlargement rate of lesion area and years of follow-up. B. Scatter plot showing the relationship between the enlargement rate of the square root of lesion area and years of follow-up.

Figure 5

Unifocal area of geographic atrophy (GA) as seen by fundus photography (A,F), fundus camera-based autofluorescence* (B,G), and OCT fundus imaging (C, H) at baseline (A-E) and at the end of a 14 month follow-up period (F-J). The boundaries of GA were manually outlined on the OCT fundus image at baseline (D) and at the end of the follow up period (I). Areas of GA were calculated as 7.6 mm2 (E) and 10.09 mm2 (J). Frames E and J show a clear growth in the area of GA over time. This difference was used to calculate the yearly enlargement rate (2.17 mm2/year). On a square root scale the enlargement rate was 0.36 mm/year. *Topcon TRC-501X color fundus camera (Topcon Medical Systems, Oakland, NJ) with filters by Spectrotech, Inc. (Saugus, MA) having an excitation bandpass filter centered at a wavelength of 580 nm and a barrier bandpass filter centered at a wavelength of 695 nm.

Figure 6

Large multifocal area of geographic atrophy (GA) as seen by fundus photography (A,F), fundus camera-based autofluorescence* (B,G), and OCT fundus imaging (C,H) at baseline (A-E) and at the end of a 12 month follow-up period (F-J). The boundaries of GA were manually outlined on the OCT fundus image at baseline (D) and at the end of the follow up period (I). Areas of GA were calculated as 6.88 mm2 (E) and 9.20mm2 (J). Frames E and J show a clear growth in the area of GA over time. This difference was used to calculate the yearly enlargement rate (2.32 mm2/year). On a square root scale the enlargement rate was 0.41 mm/year. *Topcon TRC-501X color fundus camera (Topcon Medical Systems, Oakland, NJ) with filters by Spectrotech, Inc. (Saugus, MA) having an excitation bandpass filter centered at a wavelength of 580 nm and a barrier bandpass filter centered at a wavelength of 695 nm.