Immunoprofiling of Nonarteritic Anterior Ischemic Optic Neuropathy

Abstract

Purpose : Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in those older than 50. There is no blood diagnostic test or effective treatment for NAION, and the etiology for progression of vision loss in some patients remains unclear. We investigated the suitability of blood inflammatory proteins as biomarkers and potential therapeutic targets of NAION.

Methods : We conducted a prospective case-control study including 18 patients with NAION (n=5 acute, n=13 chronic) and 9 age-matched controls. NAION was confirmed by clinical exam and optical coherence tomography. Subjects underwent peripheral blood collection; plasma was isolated within 2h and analyzed using a 76-plex array of cytokines, chemokines and growth factors.

Results : In acute NAION, there was increased peripapillary retinal thickness on optical coherence tomography consistent with optic disc edema. Plasma profiling revealed significant changes of the levels of 20 inflammatory proteins in NAION. Analysis of these 20 proteins using principal component analysis (PCA), hierarchical clustering and Spearman correlation generally segregated controls and NAION. In acute NAION, Eotaxin-3, MCP-2, TPO and TRAIL were the top biomarker candidates. In chronic NAION, out of 10 top-ranked molecules, IL-1a and CXCL10 emerged as the strongest therapeutic targets. Statistical analysis of the 20 top-ranked molecules in NAION revealed that there was only 15% overlap in acute and chronic NAION. Longitudinal data from one patient demonstrated an evolving inflammatory pattern from acute to chronic NAION matching that of the PCA.

Conclusions : Profiling of 76 immune molecules in plasma of NAION patients revealed significant inflammation in acute NAION. Surprisingly, there was even more inflammation in chronic NAION, which may be related to neurodegeneration. Of the 20 significantly changed molecules, there was little overlap between the acute and chronic NAION groups, so a larger study to better delineate immune changes over time in the same NAION patients can help elucidate potential therapeutic targets for treatment of patients with visual deterioration.

This is a 2021 ARVO Annual Meeting abstract.