Multimodal Imaging of Subretinal Fibrosis in Neovascular AMD

Research questions/hypotheses: Age-related macular degeneration (AMD) is the main cause of legal blindness among elderly patients in industrialized countries. The main reason for severe and irreversible visual impairment among these patients is subretinal fibrosis (SF). Large-scale interventional trials (e.g. CATT) have shown that half of all eyes affected by choroidal neovascularization (CNV) develop clinically visible fibrotic scarring over two years despite optimal treatment, causing irreversible retinal damage and functional loss. Thus, prevention of fibrosis in AMD is currently the focus of researchers worldwide. Clearly defined end points for interventional trials, however, are lacking because detection and quantification of SF is challenging. Clinical staging of SF is subjective and current gold standard imaging modalities such as color fundus photography (CFP), fluorescein angiography (FA) and optical coherence tomography (OCT), even in concert, do not allow a distinct and early delineation of SF. Novel imaging modalities such as polarization-sensitive OCT (PS-OCT), OCT angiography (OCTA) and adaptive optics (AO)-OCT are promising means to objectively detect SF and provide detailed insights into the biology of the microvascular and neurosensory compartments. Our group recently demonstrated that PS-OCT offers automated identification and quantification of SF in AMD based on tissue-specific contrast. Aim of the proposed research project is to detect and characterize the angiofibrotic switch, i.e. the transition from active and reversible neovascularization to irreversible fibrosis, in neovascular AMD under anti-VEGF treatment. We hypothesize to detect the initiating events of fibrotic conversion including even subclinical stages of fibrosis by non-invasive PS-OCT and identify the association with fibrovascular and retinal changes by OCTA and AO-OCT, respectively.

Scientific/scholarly innovation/originality of the project: The combination of PS-OCT, OCTA and AO-OCTA to non-invasively detect pathognomonic features of fibrovascular conversion is a novel and unprecedented approach towards objective visualization and quantification of disease pathomechanisms. Outcomes of this study may provide clearly defined morphological endpoints for future interventional trials.

Methods: Eighty eyes of 80 patients with chronic nAMD will be included and examined cross-sectionally to evaluate the accuracy of PS-OCT to detect and quantify fibrosis in comparison to gold standard imaging. In addition, OCTA and AO-OCT will be performed to analyze the relationship between fibrous, vascular and retinal structures. Furthermore, forty eyes of 40 participants with treatment-naïve nAMD will be included in a prospective study and followed for one year under treatment. PS-OCT, AO-OCT and OCTA imaging will be performed according to a standardized protocol at predefined visits. Gold standard imaging will be performed for validation.