Background/ Objective: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly in developed countries. Quiescent macular neovascularization (MNV) is a relatively newly described entity in AMD. Optical coherence tomography angiography (OCTA) is the ideal non-invasive imaging method that can reveal MNV in eyes without signs of clinical activity defined as the absence of subretinal or intraretinal fluid. Quiescent MNV can remain inactive for variable periods of time. The factors that determine their awakening to active disease or the relationship with geographic atrophy are unknown.
This research proposes to evaluate choriocapillaris vascular density and choroidal vascularity index (CVI) in treatment naïve quiescent MNV using spectral domain optical coherence tomography (SDOCT) and OCTA. The primary objective is to evaluate correlations of these quantitative parameters in the possible conversion to exudative MNV or geographic atrophy over a period of 24 months. The secondary objective is to detect biomarkers that may predict conversion of quiescent disease to active forms of MNV.
Methods: Prospective study design to include patients with OCTA evidence of quiescent MNV with no signs of clinical activity and age matched healthy control subjects. Comprehensive ophthalmological examination will be carried out. SDOCT and OCTA will be performed and the size and morphology of quiescent MNV will be documented. Near infrared reflectance and fundus autofluorescence will be carried out for evaluation of the choroid and signs/progression of atrophy. Data for choriocapillaris vascular density will be obtained from OCTA incorporated software. CVI will be calculated using specific software in a method described by Sonoda et al. Statistical analysis will be based on correlations of choriocapillaris vascular density, choroidal vascularity index, and fundus autofluorescence data with changes in MNV size and activity status.
Novel research has identified a possible role of the choroid and choroidal circulation in the etiopathogenetic mechanisms behind AMD, this has been possible with the advent of enhanced depth SDOCT imaging which enables choroidal thickness/morphology evaluation. The advent of OCTA in the recent years provides further information on retinal and choroidal vascularization in numerous subtypes of AMD. Few reports have dealt with quiescent, subclinical, or non-exudative treatment naïve MNV.
Structural evaluation of thickness alone cannot inform on the component involved in choroidal changes. Furthermore, OCTA enables evaluation of the choriocapillaris but not the entire choroidal vasculature. Recently CVI and quantitative assessment of the luminal and vascular area has been employed to further investigate the choroid and its role in retinal and choroidal pathology. This method has not been previously applied in the evaluation of quiescent MNV.
The focus on establishing biomarkers that may predict the exudative conversion of quiescent MNV neovascular lesions is paramount as exudative MNV in AMD is still a leading cause of blindness and a major burden on patients and healthcare systems. Research is aimed at preventing and treating disease. There are contrasting reports on the role of lesion enlargement in the prediction of exudation. The choriocapillaris has been studied in only few reports and we are not aware of studies on CVI in quiescent MNV. Therefore, we believe that our study may contribute to identify the lesions at higher risk of exudation by showing possible quantitative and anatomic correlations between choroidal vascularity and quiescent MNV and possibly identifying biomarkers of disease progression.