Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). DESIGN: Prospective cohort study within a randomized clinical trial. PARTICIPANTS: The 1185 CATT participants. METHODS: Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks. MAIN OUTCOME MEASURES: Presence of SHRM, as well as location and size, and associations with VA, scar, and GA. RESULTS: Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 µm, 120 µm, and 122 µm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05). CONCLUSIONS: In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.

Reading Center Characterization of Central Retinal Vein Occlusion Using Optical Coherence Tomography During the COPERNICUS Trial.

PURPOSE: To determine the impact of segmentation error correction and precision of standardized grading of time domain optical coherence tomography (OCT) scans obtained during an interventional study for macular edema secondary to central retinal vein occlusion (CRVO). METHODS: A reading center team of two readers and a senior reader evaluated 1199 OCT scans. Manual segmentation error correction (SEC) was performed. The frequency of SEC, resulting change in central retinal thickness after SEC, and reproducibility of SEC were quantified. Optical coherence tomography characteristics associated with the need for SECs were determined. Reading center teams graded all scans, and the reproducibility of this evaluation for scan quality at the fovea and cystoid macular edema was determined on 97 scans. RESULTS: Segmentation errors were observed in 360 (30.0%) scans, of which 312 were interpretable. On these 312 scans, the mean machine-generated central subfield thickness (CST) was 507.4 ± 208.5 µm compared to 583.0 ± 266.2 µm after SEC. Segmentation error correction resulted in a mean absolute CST correction of 81.3 ± 162.0 µm from baseline uncorrected CST. Segmentation error correction was highly reproducible (intraclass correlation coefficient [ICC] = 0.99-1.00). Epiretinal membrane (odds ratio [OR] = 2.3, P < 0.0001), subretinal fluid (OR = 2.1, P = 0.0005), and increasing CST (OR = 1.6 per 100-µm increase, P < 0.001) were associated with need for SEC. Reading center teams reproducibly graded scan quality at the fovea (87% agreement, kappa = 0.64, 95% confidence interval [CI] 0.45-0.82) and cystoid macular edema (92% agreement, kappa = 0.84, 95% CI 0.74-0.94). CONCLUSIONS: Optical coherence tomography images obtained during an interventional CRVO treatment trial can be reproducibly graded. Segmentation errors can cause clinically meaningful deviation in central retinal thickness measurements; however, these errors can be corrected reproducibly in a reading center setting. TRANSLATIONAL RELEVANCE: Segmentation errors are common on these images, can cause clinically meaningful errors in central retinal thickness measurement, and can be corrected reproducibly in a reading center setting.

Optical coherence tomography reader agreement in neovascular age-related macular degeneration.

PURPOSE: To determine the interreader and intrareader agreement at the Optical Coherence Tomography (OCT) Reading Center at Duke for images produced for an interventional neovascular age-related macular degeneration (AMD) clinical trial. DESIGN: Retrospective, observational case series. METHODS: OCT was performed using the Stratus OCT Fast Macular Thickness Map (Carl Zeiss Meditec, Dublin, California, USA) scan mode and a 7-mm line scan centered on the fovea. Experienced OCT readers, certified to grade scans according to a standardized protocol, independently determined whether a scan was gradable. If gradable, each of the scans was graded for multiple morphologic characteristics. In addition, retinal thickness, subretinal fluid thickness, and choroidal neovascularization (CNV) thickness at the fovea were measured for each gradable scan. Interreader agreement was determined among three reader pairs. Readers regraded a subset of scans and intrareader agreement was determined. RESULTS: The interreader agreement was high for scan gradability and scan grades among three reader pairs, ranging from 84% to 100% and from 84% to 96%, respectively. Similarly, the intrareader agreement for scan gradability and scan grade, including comparison of adjudicated scan grades with readjudicated scan grades, was high and ranged from 91% to 100% and from 79% to 98%, respectively, except for scan grades of retinal pigment epithelium atrophy, when CNV was present. Highly reproducible results also were found for quantitative thickness measurements. CONCLUSIONS: Well-trained OCT readers can grade independently, with a high level of interreader and intrareader agreement, multiple morphologic parameters of OCT scans obtained from eyes with neovascular AMD. Reproducible Stratus OCT scan data will be valuable to monitor treatment efficacy in interventional clinical trials of neovascular AMD.