Purpose The purpose of this one-year prospective study was to investigate

Purpose The purpose of this one-year prospective study was to investigate how induction/pro re nata (PRN) ranibizumab intravitreal treatment of eyes with neovascular age related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. OCT) a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography (FA) was also assessed to evaluate late retinal leakage. Results After one year mean area of TG 100572 CNV measured with ICG decreased by 5.8%. MinIP OCT mean area of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of FA leakage decreased by 6.3%. Both the area of outer retinal disruption measured with minIP OCT and the area of leakage on TG 100572 FA typically exceeded the area of CNV on NOL7 ICG at baseline and one year. Conclusion CNV treated with induction/PRN intravitreal ranibizumab for one year essentially remained static. MinIP OCT suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on ICG and minIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation. images of the retina were generated from Cirrus OCT macular cube data using proprietary software and the resulting 20 degree images of the retina were analyzed. ICG images were captured with the following parameters. After injection of 8.3 mg/1mL of ICG dye the study eye was imaged with a 30 degree angle of view on the Heidelberg HRA2 to obtain a movie of the early frames showing filling of the CNV. FA images were obtained with Topcon TRC-50EX after injection of fluorescein sodium 10% (500mg/5mL) TG 100572 with a 50 degree angle of view. To facilitate tracing the borders of the CNV the NIH-developed software ImageJ was used to create an image stack. Frames with eye blinks were removed and the remaining frames from the first minute after choroidal filling were aligned to create a composite static image. This 30 degree static composite image was then used for CNV lesion measurement. A representative 50 degree late FA image (10 minutes post-infusion) was also selected for analysis of maximal leakage extent. Two trained graders traced all lesions on the ICG (DN BT) FA (DN NJ) and MinIP images (DN NJ). The location of the choroidal neovascular membrane on the ICG image was identified collaboratively by three graders and then each grader independently outlined the full extent of the choroidal neovascular membrane using the freehand drawing tool in ImageJ. The goal was to trace the borders of the CNV tightly. If multiple foci of CNV existed the lesions were traced separately and the areas were added together. Since it was difficult to outline a feeder vessel tightly only the “fleurette” component of the CNV complex was traced. The area occupied by the membrane in pixels was then calculated by ImageJ and the measurements by the two graders were averaged. In the event of a >20% disagreement between the two graders in the area measurement (our group thought TG 100572 that less than 20% differences were difficult to detect qualitatively so we set 20% as the benchmark for this study based on our personal experience) a third grader (CM) measured the membrane and the three values were averaged for further analysis. The area of maximal late hyperfluoresence on FA was measured similarly in ImageJ while the abnormally bright and dark areas corresponding to the outer retinal tissue alterations overlying the CNV were measured on the MinIP OCT images. Data Analysis Baseline and one year lesion size in pixels visual acuity central retinal thickness (CRT) and outer segment length were compared using a signed rank test. Pixels were converted into micron measurements for all area measurements. Pixel count was correlated with total degrees in an image based on an area of 36mm2 for a 20 degree minIP OCT image 81 for a 30 degree HRA image and 177 mm2 for a 50 degree Topcon image. The conversion formulas were as follows:

Area of CNV on ICG in mm2={CNV area(pixels)/