Microvascular Volume Loss Exceeds Nerve Fiber Layer but Not Neuroretinal Rim Tissue Loss During Progression of Nonhuman Primate Experimental Glaucoma

Purpose: The purpose of this study was to test whether loss of functional microvascular (MV) or large vessel (LV) volume exceeds loss of retinal nerve fiber layer (RNFL) and optic nerve head (ONH) rim tissue volume in a nonhuman primate (NHP) model of experimental glaucoma (EG). Methods: Rhesus macaques (N = 28) were imaged by optical coherence tomography (OCT) and OCT angiography (OCTA) during baseline and after induction of unilateral EG. ONH and RNFL tissue volume were compared to MV and LV vascular volume (the same voxels weighted by their OCTA signal). Linear regression was used to compare rates of change between EG and fellow control eyes for each parameter after normalization to their pre-EG baseline average values, and mixed-effects models were used to compare baseline average values to those at the onset of significant change of ONH minimum rim width, RNFL thickness, and the final time point. Results: ONH rim volume, the LV proportion of rim volume, and RNFL volume significantly declined in EG eyes compared to control eyes (P < 0.0001). The MV proportion of non-vascular rim tissue remained constant (P = 0.053), but the MV proportion of non-vascular RNFL significantly declined in EG eyes only (P < 0.0001). Cross-sectional analysis demonstrated significant reductions in MV proportion of the RNFL but not the ONH rim at the onset of structural change in EG eyes. Conclusions: Progressive loss of functional microvasculature (adequately perfused capillaries) within the RNFL, occurring early and in excess of the neuroglial tissue it supplies, supports future investigation of therapeutic strategies that target vascular function.