Association Between Ellipsoid Zone Area and Fixation Stability in Macular Telangiectasia Type 2

To determine whether ellipsoid zone (EZ) area loss, a biomarker of photoreceptor degeneration, is associated with fixation stability in macular telangiectasia type 2 (MacTel).

This retrospective analysis included 212 adults from two Phase 3 trials of revakinagene taroretcel-lwey for MacTel. EZ area loss was quantified with optical coherence tomography. Fixation stability (P1 index) was measured by microperimetry. Linear and logistic regressions evaluated associations between EZ area loss and P1 over 24 months. A median split stratified the population to evaluate whether baseline EZ area loss influenced the therapeutic effect of the implant versus sham. A receiver operating characteristic analysis identified a structural threshold for unstable fixation.

EZ area loss was significantly associated with reduced fixation stability at baseline (P = 0.002) and month 24 (P = 0.01). Each 1-mm² increase in EZ area loss doubled the odds of poor fixation stability (defined as a P1 <80%) (odds ratio, 2.07; P = 0.047). P1 change did not significantly differ between the treatment and sham groups. In exploratory analyses, stratification by median baseline EZ area loss, despite a nonsignificant treatment-by-baseline interaction (P = 0.17), revealed a greater decline in fixation stability in sham-treated eyes (mean, -3.8%) versus the implant group (+0.6%). The receiver operating characteristic analysis identified an EZ area loss threshold of 1.075 mm² for unstable fixation.

Greater EZ area loss is associated with poorer fixation stability in MacTel. An EZ area loss threshold of ∼1 mm² may serve as an exploratory marker of fixation instability risk, though this threshold requires independent validation.