Long-term Progression of Ellipsoid Zone Loss and Associated Features on OCT in Macular Telangiectasia Type 2.

Abstract

To characterize the detailed natural history of ellipsoid zone (EZ) loss progression in macular telangiectasia type 2 (MacTel) and to identify structural predictors of disease acceleration using demographic and OCT-based parameters. Retrospective longitudinal cohort study. Patients with MacTel registered for the Natural History Observation Registry study at the University Hospital Bonn, Bonn, Germany. The EZ loss area was assessed on en face maps deriving from ultradense OCT volume scans. The EZ loss was graded as either no EZ loss (pattern 0), a sharply demarcated hyporeflective space in the outer retina with preserved retinal architecture (pattern 1), a subsidence of outer retinal layers into the EZ loss and a loss of retinal architecture (pattern 2), or a mix of these morphologic features (pattern 3). A random forest model was trained to predict future progression rates using the explanatory variables age, baseline EZ loss area, and pattern. Hierarchical Bayesian models adjusted for onset variability were applied to find an overall slope of disease progression. Ellipsoid zone loss progression (in square millimeters per year) dependent on pattern, baseline EZ loss area, and age, adjusting for the nested data of 2 eyes of 1 patient. The study included 606 eyes from 327 patients (mean ± standard deviation age, 59.8 ± 9.6 years; median follow-up, 5.41 years [interquartile range, 4.16-8.11 years]; single visit for 210 patients). Median EZ loss progression was 0.08 mm²/year. Lesion morphologic characteristics were associated significantly with progression: pattern 1 lesions progressed slowly (0.02 mm²/year), whereas pattern 2 and pattern 3 lesions progressed more rapidly (0.08 and 0.09 mm²/year, respectively; P < 0.001). Bayesian modeling revealed a sigmoid progression trajectory with an inflection point at approximately 0.5 mm² of EZ loss and an estimated disease duration of approximately 30 to 40 years. Type of EZ loss independently predicted acceleration beyond this threshold. Ellipsoid zone loss in MacTel follows a characteristic sigmoid trajectory, with distinct morphologic types predicting progression velocity. Although pattern 1 lesions remain stable for longer periods, pattern 2 and 3 lesions show fast progression. These findings may help to guide clinical management and treatment timing, particularly in light of emerging therapies such as revakinagene taroretcel-lwey (Encelto, Neurotech Pharmaceuticals, Inc). Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.