Combining paracentral acute middle maculopathy and peripapillary fluid as biomarkers in anterior ischemic optic neuropathy: OCT biomarkers in anterior ischemic optic neuropathy

Purpose: To determine if paracentral acute middle maculopathy (PAMM) and peripapillary intraretinal and subretinal fluid (IRF/SRF) could help distinguish between arteritic anterior ischemic optic neuropathy (A-AION) and non-arteritic AION (NA-AION) at an early stage.

Design: Nested prospective cross-sectional diagnostic accuracy study.

Methods: This study used single-center optical coherence tomography (OCT) data from 8 patients with A-AION and 24 patients with NA-AION from two prospective cross-sectional studies with consecutive sampling (ClinicalTrials.gov: NCT05248906 and NCT05305079). The diagnosis of A-AION was based on expert interpretation of biochemical markers of inflammation, temporal artery biopsy and positron emission tomography/computed tomography. The diagnosis of NA-AION was made in cases without suspicion or clinical evidence of A-AION and with confirmed neuroophthalmological expert diagnosis. For this substudy patients were also required to have an OCT scan in relation to the diagnosis of AION. Macular OCT scans were graded by two independent, masked graders for the presence of PAMM and for IRF/SRF. The extension of IRF/SRF was assessed using an Early Treatment Diabetic Retinopathy Study (ETDRS) grid.

Results: PAMM was found in 50% of patients with A-AION and in 0% of patients with NA-AION (P = 0.0019). In the setting of AION, the sensitivity of PAMM for the diagnosis of A-AION was 50% (95%CI: 16 to 84%) while the specificity was 100% (95%CI: 86 to 100%). Conversely, peripapillary IRF/SRF with extension into the ETDRS grid was observed in 83% of patients with NA-AION but in 0% of patients with A-AION (P =0.000047). The sensitivity of central macula-involving IRF/SRF for the diagnosis of NA-AION was 83% (95%CI: 63 to 95%), while the specificity was 100% (95%CI: 63 to 100%). Combining the two biomarkers, 75% of patients with AION could be classified based on OCT alone.

Conclusion: PAMM appears to be a biomarker of A-AION while extensive peripapillary fluid appears to be a biomarker of NA-AION. Combining OCT biomarkers might allow for early classification of AION and warrants further prospective studies.