Characteristics of patients losing vision after 2 years of monthly dosing in the phase III ranibizumab clinical trials.

PURPOSE: To investigate the cause of visual acuity (VA) loss in patients with neovascular age-related macular degeneration (AMD) receiving monthly ranibizumab injections in the pivotal ranibizumab phase III trials. DESIGN: Retrospective analysis. PARTICIPANTS: The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trials. METHODS: Demographics and lesion characteristics at baseline and month 24 were compared in patients with ≥15 letters VA loss and patients with ≥15 letters VA gain from baseline to month 24. Additional evaluations of fundus photographs from these patients were performed to assess features of non-exudative AMD, such as geographic atrophy (GA) and retinal pigment epithelium (RPE) abnormalities. MAIN OUTCOME MEASURES: Differences in lesion characteristics between patients who lost versus gained ≥15 letters of VA from baseline to month 24. RESULTS: At month 24, 9% of ranibizumab-treated patients from MARINA and 10% of ranibizumab-treated patients from ANCHOR had lost ≥15 letters VA; 30% of ranibizumab-treated patients from MARINA and 38% of ranibizumab-treated patients from ANCHOR had gained ≥15 letters VA. Baseline characteristics associated with VA loss at month 24 included older age, better VA, and larger lesions. At month 24, an increased area of RPE abnormality was associated with VA loss in both the MARINA (P = 0.0008) and ANCHOR (P = 0.0046) trials. Increased total lesion area at month 24 was associated with VA loss in both trials. In MARINA, the increase in total lesion area was attributable to an increase in the angiographic designation of atrophic scar among VA losers (P = 0.0043), but in ANCHOR it was attributable to an increased area of choroidal neovascularization (CNV) (P = 0.039) but not an increased area of leakage (P = 0.17). Increased areas of GA, fibrosis, and hemorrhage were not associated with VA loss. CONCLUSIONS: Vision loss after 2 years of monthly ranibizumab therapy was associated with lesion characteristics commonly associated with suppressed CNV, such as pigmentary abnormalities, atrophic scar, and the absence of leakage. Future VA improvements in patients receiving ranibizumab therapy may require preservation of photoreceptor and RPE function rather than strategies that target CNV.

Evaluation of optical coherence tomography findings in age-related macular degeneration: a reproducibility study of two independent reading centres.

BACKGROUND/AIMS: To determine the reproducibility among readers of two independent certified centres, the Vienna Reading Center (VRC) and the University of Wisconsin-Madison Reading Center (UW-FPRC) for optical coherence tomography (OCT) images in age-related macular degeneration (AMD). METHODS: Fast macular thickness scans and 6 mm cross hair scans were obtained from 100 eyes with all subtypes of AMD using Stratus OCT. Consensus readings were performed by two certified OCT readers of each reading center using their grading protocol. Common variables of both grading protocols, such as presence of cystoid spaces, subretinal fluid, vitreomacular traction and retinal pigment epithelial detachment, were compared using κ statistics. In addition, the intraclass correlation coefficient (ICC) was calculated for centre point thickness (CPT) of values re-measured manually in the presence of alignment errors. RESULTS: The reproducibility was dependent on the variable measured with a κ value of 0.81 for the presence of cystoid spaces, 0.78 for the presence of subretinal fluid and 0.795 for the presence of vitreomacular traction. The lowest reproducibility was found for the presence of retinal pigment epithelial detachment with a κ value of 0.51. The CPT was re-measured in 29 out of 100 scans at both sites with an ICC of the re-measured thicknesses of 0.92. CONCLUSION: OCT scan data are crucial in monitoring treatment efficacy in AMD clinical trials. For comparison of results obtained by different reading centers, the inter-reading center reproducibility is essential. Although the reproducibility is generally high, the reliability depends on the selected morphological parameters.

Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study system for evaluation of stereoscopic color fundus photographs and fluorescein angiograms: SCORE Study Report 9.

OBJECTIVE: To describe the procedures and reproducibility for grading stereoscopic color fundus photographs and fluorescein angiograms of participants in the SCORE Study. METHODS: Standardized stereoscopic fundus photographs and fluorescein angiograms taken at 84 clinical centers were evaluated by graders at a central reading center. Type of retinal vein occlusion (RVO), area of retinal thickening, and area of retinal hemorrhage are evaluated from fundus photographs; area of fluorescein leakage and area of capillary nonperfusion are measured on fluorescein angiography. Temporal reproducibility consisted of annual regrading of a randomly selected dedicated subset of fundus photographs (60 subjects) and fluorescein angiograms (40 subjects) for 3 successive years. Contemporaneous reproducibility involved monthly regrading of a 5% random selection of recently evaluated fundus photographs (n = 73). RESULTS: The intergrader agreement for RVO type and presence of retinal thickening was greater than 90% in the 3 annual regrades. The intraclass correlation (ICC) for area of retinal thickening in the 3 years ranged from 0.39 to 0.64 and for area of retinal hemorrhage, 0.87 to 0.96. The ICC for area of fluorescein leakage ranged from 0.66 to 0.75 and for capillary nonperfusion, 0.94 to 0.97. The contemporaneous reproducibility results were similar to those of temporal reproducibility for all variables except area of retinal thickening (ICC, 0.84). CONCLUSIONS: The fundus photography and fluorescein angiography grading procedures for the SCORE Study are reproducible and can be used for multicenter longitudinal studies of RVO. A systematic temporal drift occurred in evaluating area of retinal thickening.