Study Describes Non-linear EZ Loss Progression in Patients with MacTel

In patients with macular telangiectasia type 2 (MacTel), ellipsoid zone (EZ) loss observed on OCT correlates closely with photoreceptor dysfunction, which is why this metric was designated as the primary endpoint in Phase III studies of Encelto (revakinagene taroretcel, Neurotech Pharmaceuticals), the first FDA-approved treatment for MacTel. Encelto is an encapsulated cell-based therapy designed to deliver ciliary neurotrophic factor directly into the vitreous, aiming to preserve photoreceptors and slow disease progression.The FDA's approval of Encelto earlier this year underscores the imperative to understand disease progression and the history of EZ loss, providing clinicians with evidence-based guidance for optimal treatment timing. A study published last week in Ophthalmology aimed to enhance knowledge of the natural history of EZ loss by evaluating one of the largest cohorts of MacTel patients in Europe to date. The retrospective longitudinal study involved 606 eyes from 327 patients, with a mean age of 59.8. Patients were selected from a single-center cohort within the Natural History Observation and Registry Studies, conducted at a university hospital in Germany. EZ loss progression was measured via OCT and classified into the following distinct patterns: Pattern 0: no EZ lossPattern 1: sharply demarcated hyporeflective areas with preserved retinal architecturePattern 2: retinal layer subsidence into the EZ area with concomitant loss of architecturePattern 3: a mix of patterns 1 and 2 This large German study found that EZ loss in MacTel follows a characteristic sigmoid trajectory. Researchers also identified an inflection point in progression occurring at approximately 0.5mm² of EZ loss.These images from the study show characteristics of different ellipsoid zone (EZ) loss morphology patterns: A-C show an absence of EZ loss as Pattern 0. D-F show Pattern 1 with sharply demarcated hyporeflective space in the outer retina (arrow) shown in the enlarged OCT (E). Further MacTel characteristics include hyperautofluorescence on fundus autofluorescence (F) due to loss of macular pigment. G-I represent Pattern 2 with the OCT B-Scan showing subsidence filling the entire EZ loss area (H white arrowheads). Pigmentary changes lead to a decrease in the FAF signal (I). (J-L) show Pattern 3, the lesion visible in the OCT (J, K) exhibits both subsidence (arrowheads) and hyporeflectivity (arrow), representing a combination of Pattern 1 and 2. Photo: Raming K, et al. Ophthalmol. November 28, 2025. Click image to enlarge. Results revealed that EZ loss in MacTel follows a characteristic sigmoid (S-shaped) trajectory, with evidence highlighting an inflection point in progression occurring at approximately 0.5mm² of EZ loss. The study quantified median EZ loss progression to be 0.08mm²/year overall, with distinct rates based on lesion morphology—pattern 1 demonstrated slow progression at 0.02mm²/year, while patterns 2 and 3 exhibited faster rates at 0.08mm²/year and 0.09mm²/year, respectively. These findings highlight a significant association between the morphology of EZ loss and its progression dynamics, indicating that the presence of subsidence in retinal layers—whether full or partial—correlates with faster disease advancement. Moreover, the researchers found a link between rapid EZ loss progression and an increased risk for secondary neovascularization. They commented in their paper that, “While there is currently no data on the effect of Encelto on the occurrence of secondary neovascularization, one may hypothesize that slowing EZ loss progression may reduce its risk.”The data also demonstrated that “the modeled time from initial small EZ loss to large areas of EZ loss spans approximately 40 years.” The researchers point out that this study is the first to pinpoint the inflection point that indicates the shift from slow to rapid progression, which could be clinically significant when advising patients about treatment options and timing.Summarizing the importance of their findings, the authors note that this research “provides valuable insights into the natural history of MacTel, demonstrating a non-linear, sigmoid progression of EZ loss in a large cohort.” They reiterated that while small, hyporeflective lesions remain stable over an extended period of time, “subsidence of retinal layers internal to the EZ into the EZ loss area indicates fast progression,” which may offer fresh insights for discussing the optimal timing for initiating treatment with the Encelto implant.Click here for the journal source. Raming K, Goerdt L, Begemann E, et al. Long-term progression of ellipsoid zone loss and associated features on optical coherence tomography in macular telangiectasia type 2. Ophthalmol. November 28, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.