Nonarteritic anterior ischemic optic neuropathy (NAION) remains one of the most frustrating conditions in ophthalmology. Diagnosis is clinical, biomarkers are lacking, and its precise pathogenesis is still incompletely understood. While systemic vascular risk factors such as hypertension, diabetes, and dyslipidemia are well recognized, there is no widely used laboratory indicator that helps stratify risk or support diagnosis in borderline cases.
A new study published in Translational Vision Science & Technology explores whether two novel lipid-derived indices – the atherogenic index of plasma (AIP) and the triglyceride–glucose (TyG) index – could serve as systemic biomarkers associated with NAION.
The China-based group of researchers conducted a retrospective case–control study including 44 patients with acute NAION and 42 age- and sex-matched controls. Importantly, patients with overt hyperlipidemia were excluded, allowing the investigators to assess subtler metabolic differences that might not be captured by conventional lipid panels.
All participants underwent comprehensive ophthalmic evaluation, including best-corrected visual acuity (BCVA), automated perimetry, and peripapillary RNFL thickness measurement, alongside fasting lipid and glucose testing. Traditional lipid parameters were largely within normal limits in both groups. Total cholesterol and LDL-C did not differ significantly. However, triglycerides were higher and HDL-C lower in the NAION group.
The more interesting signal emerged from the derived indices. Both AIP and TyG (a logarithmic index incorporating triglycerides and fasting blood glucose) were significantly elevated in patients with NAION compared with controls. Even after adjusting for fasting blood sugar, TyG remained significantly higher in this patient cohort.
While the values displayed in the study fall short of a stand-alone diagnostic test, they suggest that systemic metabolic vulnerability – even in patients without overt hyperlipidemia – may be measurable.
Interestingly, neither AIP nor TyG correlated with functional or structural severity measures, and there were no significant associations observed between these indices and BCVA, RNFL thickness, or mean deviation on visual field testing. This finding is clinically relevant – the indices may not reflect the extent of optic nerve damage once NAION has occurred, but instead represent a background metabolic milieu that predisposes patients to ischemic events.
The authors propose a plausible mechanism: elevated AIP reflects a more atherogenic lipid profile, while TyG is increasingly recognized as a surrogate marker of insulin resistance. Both of these are associated with endothelial dysfunction and impaired microvascular hemodynamics. In the context of NAION – a condition believed to involve compromised perfusion of the short posterior ciliary arteries – subtle systemic endothelial dysfunction may lower the threshold for ischemia. These indices may therefore signal chronic vascular susceptibility rather than acute injury severity.
For ophthalmologists, the key question is whether these markers add meaningful value in clinical practice. At present, AIP and TyG are not ready to change management. The study is retrospective, single-center, and relatively small. Furthermore, patients with known hyperlipidemia were excluded, which may limit generalizability. However, the findings do reinforce a broader point: NAION may be as much a systemic metabolic disease as a local optic nerve event. In patients with otherwise unexplained NAION – particularly those without obvious dyslipidemia – expanded metabolic profiling could reveal subclinical vascular risk.
Future prospective studies will be needed to determine whether these indices predict incident NAION or fellow-eye involvement. For now, this work adds to the growing evidence that lipid metabolism – even when considered “normal” by traditional standards – may play a subtler role in optic nerve ischemia than previously thought.
