The junctional zone at the border of areas of geographic atrophy (GA) in eyes with nonneovascular age-related macular degeneration is an important target region for future therapeutic strategies. The goal of this study was to perform a detailed classification and quantitative characterization of the junctional zone using spectral domain optical coherence tomography.
Spectral domain optical coherence tomography volume cube scans (Spectralis OCT, 1024 × 37, Automatic Real Time > 9) were obtained from 15 eyes of 11 patients with GA because of nonneovascular age-related macular degeneration. Volume optical coherence tomography data were imported into previously described validated grading software (3D-OCTOR), and manual segmentation of the retinal pigment epithelium (RPE) and photoreceptor layers was performed on all B-scans (total of 555). Retinal pigment epithelium and photoreceptor defect maps were produced for each case. The borders of the photoreceptor defect area and RPE defect area were delineated individually on separate annotation layers. The two outlines were then superimposed to compare the areas of overlap and nonoverlap. The perimeter of the RPE defect area was calculated by the software in pixels. The superimposed outline of the photoreceptor defect area and the RPE defect area was scrutinized to classify the overlap configuration of the junctional zone into one of three categories: Type 0, exact correspondence between the edge of the RPE defect and photoreceptor defect; Type 1, loss of photoreceptors outside and beyond the edge of the RPE defect; Type 2, preservation of photoreceptors beyond the edge of the RPE defect. The relative proportion of the various border configurations was expressed as a percentage of the perimeter of the RPE defect. Each configuration was then classified into four subgroups according to irregularity of the RPE band and the presence of debris.
Fifteen eyes of 11 patients (mean age: 79.3 ± 4.3 years; range: 79–94 years) were included in this study. Seventeen GA lesions were analyzed. Two hundred and thirty-two B-scans were found to pass through the GA lesions, yielding 612 individual GA borders which were separately analyzed and classified. The mean area of the RPE defect was 4.0 ± 4.4 mm2, which was significantly smaller than that of the photoreceptor defect which measured 4.4 ± 4.1 mm2 (paired t test, P = 0.037). On average, 18.0 ± 9.6% (range, 2.3–36.6%) of the junctional zone was of the Type 0 configuration, 57.3 ± 19.0% (range, 21.3–96.8%) was Type 1, and 24.7 ± 18.0% (range, 0.9–64.4%) was Type 2. Type 1 was more prevalent than Type 0 and 2 (analysis of variance, P = 0.000). Debris was present at the margin of the defect in 24.3% (149 of 612) of all assessed junctional zones; 20.0% (14 of 70) of Type 0 junctions, 28.7% (120 of 418) of Type 1, and 12.1% (15 of 124) of Type 2. Debris was more common in Type 1 than Type 2 junctions (P < 0.001). Retinal pigment epithelial irregularity was present at the margin of the defect in 34.8% (213 of 612) of all assessed junctional zones; 52.9% (37 of 70) of Type 0 junctions, 38.0% (159 of 418) of Type 1, and 13.7% (17 of 124) of Type 2. Retinal pigment epithelial irregularity was present more often at Type 0 and Type 1 than at Type 2 junctions (P < 0.001 for both).
The size of the optical coherence tomography–visible RPE and photoreceptor defect in GA lesions differ significantly. There were significant areas where the photoreceptor outer segments were preserved despite the absence of visible RPE cells, and also areas of photoreceptor outer segment loss despite apparent RPE preservation. These findings have implications for development of therapeutic strategies, particularly cell-replacement approaches.
In this study, the authors classify and quantify analysis of geographic atrophy junctional zone using spectral domain optical coherence tomography. There were significant areas where the photoreceptors survived despite the absence of visible retinal pigment epithelial cells, and also areas of photoreceptor loss despite apparent retinal pigment epithelial preservation.
*Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California;
†Department of Ophthalmology, People's Hospital of Peking University, Beijing, China; and
‡Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California.
Reprint requests: Srinivas Sadda, MD, Doheny Eye Institute, DVRC 211, 1355 San Pablo Street, Los Angeles, CA 90033; e-mail: firstname.lastname@example.org
S. Sadda is a consultant for and receives research support from Optos and Carl Zeiss Meditec, serves as a consultant for CenterVue, and has access to research instruments provided by Heidelberg Engineering, Topcon Medical Systems, Optos, Carl Zeiss Meditec, Nidek, and CenterVue. The remaining authors have no conflict of interest to disclose.