Purpose: To investigate the different appearances of vascular changes in macular telangiectasia type 2 (MacTel) and to describe their possible progression, the vascular patterns in different retinal layers were analyzed with optical coherence tomography angiography (OCT-A) and the findings were correlated with a spectral-domain OCT (SD-OCT) disease severity scale based on the extent of ellipsoid zone (EZ) loss.
Methods: Participants from the MacTel Study Group in Muenster and a healthy cohort were investigated with OCT-A using RTVue XR Avanti. After segmentation of the superficial capillary network, the deep capillary network, and the outer retina (OR), flow density was analyzed using Optovue software. Then, the images were exported using the software Fiji (National Institute of Mental Health, Bethesda, MD, USA) and analyzed with the automated MATLAB program (Mathworks, Version R2014b). Four parameters (total vessel length, number of vessel branches, number of vessel segments, and fractal dimension) were examined on the vascular skeletons (temporal, foveal, nasal, and total fields of the ETDRS grid). In addition, linear and area measurements of EZ loss were performed on SD-OCT volume scans. Progression characteristics and correlation between linear and area measurements were analyzed using linear mixed effects models.
Results: Twenty eyes of healthy probands (20 OCT-A and 20 SD-OCT scans) and 122 eyes of 61 MacTel patients were included. In order to classify the severity of the disease, MacTel eyes were assigned to a SD-OCT "disease severity scale" (grade 1 = no EZ loss; grade 2 = EZ loss temporal to the fovea; grade 3 = EZ loss including the fovea and the region nasal to the fovea). Flow density and total vessel length showed only limited differences between healthy eyes and different grades of MacTel, but particularly the numbers of branches and vessel segments, as well as the fractal dimension values, demonstrated significant and progressive reduction in the superficial and deep capillary networks of the temporal, nasal, and total ETDRS fields. Moreover, the outer retina showed a progressive presence of hyperreflective material in SD-OCT grades 2 and 3 eyes with associated vascular patterns in the OR on OCT-A.
Conclusions: In SD-OCT, the severity of MacTel is characterized by progressive EZ loss, which may be used as a simple clinical "disease severity scale". In addition, OCT-A enables visualization and quantification of vascular patterns with mathematical methods. The morphological progression of the disease correlated significantly with progressive vascular changes, especially in respect of the numbers of branches and vessel segments as well as fractal dimension. This suggests that the severity of neurodegenerative and neurovascular changes develops in parallel and that the analysis and quantification of the vascular changes in the superficial and deep capillary networks may become an additional parameter for future treatment trials. Moreover, the significant association between hyperreflective material progressively visible on SD-OCT in the OR, which most often contains vessels in OCT-A, and advancing SD-OCT severity grades, as well as vascular changes in OCT-A, supports the concept of retinal neovascularization in the OR in patients with advanced MacTel.
Keywords: Disease severity scale; MacTel; Macular telangiectasia type 2; OCT; OCT angiography; Vascular changes.