Neovascular age-related macular degeneration (AMD) is the leading cause of blindness among elderly in the United States.1 Ranibizumab, an inhibitor of all forms of vascular endothelial growth factor (VEGF), is the first FDA-approved treatment for AMD that significantly improves vision in a quarter to a third of patients and maintains or improves vision in greater than 90% of patients. Ranibizumab decreases the vasopermeability as measured by decreased leakage and fluid on fluorescein (FA) and optical coherence tomography. However, the effect of ranibizumab on the structure and hemodynamics of the choroidal neovascularization (CNV) in AMD, as measured with high-speed indocyanine green angiography (HS-ICG), is not known. The effect or lack of effect on the physical structure of the CNV may help explain the variability of injection frequencies and visual responses among different patients. Since anti-VEGF therapy is designed to inhibit exudative CNV, it is clinically important to develop a standard reproducible method to assess HS-ICG.

In this observational study, our primary objective is to assess whether induction/pro re nata (Induction/PRN) 0.5 mg intravitreal ranibizumab-based treatment for neovascular AMD decreases the size and pattern of the CNV as measured on HS-ICG, as opposed to simply decreasing leakage and fluid as seen on FA and OCT. Although combination therapy is likely the standard treatment for AMD in the future, participants will not be allowed to receive other AMD experimental agents (e.g., immunosuppressive drugs) for either the study or fellow eye while on this study. In consultation with various reading centers, we will attempt to develop a reproducible schema for evaluation of HS-ICG by reviewing pre-treatment and post-treatment HS-ICGs. The grading system development is a secondary objective to achieve a better understanding of anatomical and functional results and an important task for future research. In this study, the first 10 cases will be used to attempt to develop a reproducible grading system. The NEI retina group will review these ICGs and attempt to identify gradable aspects of the lesions that are consistently present on the ICGs. During this time we will continue to collect additional cases for evaluation. The grading system proposed from the first 10 cases will be implemented in the next 10 cases. There will be two independent gradings for each ICG. The results of this dual grading will then be reviewed and problematic areas of grading will be identified. The grading system will be modified based on this experience and reproducibility of the modified grading system will be assessed by re-grading the images in a masked fashion. The modified grading system will be utilized in the next 10 cases. This iterative process will be continued until we have either developed a reproducible and useful grading system or completed the full participant analysis. Another important secondary objective is to examine whether an increased dose of 1 mg of intravitreal ranibizumab-based treatment (administered as 1 mg monthly or 0.5 mg bi-monthly) will decrease leakage and fluid as seen on FA and OCT and/or decrease the size and pattern of CNV on HS-ICG for participants not becoming fluid-free on the standard dose.