Systemic inflammation in optic neuropathies: comparative insights from hematological and composite indices

To compare complete blood count (CBC)-derived inflammatory indices among patients with multiple sclerosis-associated optic neuritis (MS-ON), non-arteritic anterior ischemic optic neuropathy (NAION), idiopathic intracranial hypertension-related optic neuropathy (IIH-ON), and healthy controls, while accounting for demographic confounding.

This retrospective study included 135 participants: 36 patients with MS-ON, 29 with NAION, 34 with IIH-ON, and 36 healthy controls. Six composite inflammatory indices, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), and hemoglobin-albumin-lymphocyte-platelet (HALP) score, were calculated from routine laboratory measurements obtained at diagnosis before treatment. Log-transformed indices were compared using analysis of covariance adjusted for age and sex. False discovery rate correction was applied across the six indices. Receiver operating characteristic (ROC) analysis was performed for indices showing significant adjusted group effects.

Significant differences in age and sex distribution were observed among the groups. After adjustment for age and sex, overall group effects remained for NLR (p = 0.008) and SIRI (p = 0.033), although only NLR remained significant after false discovery rate correction (q = 0.047). Bonferroni-adjusted pairwise comparisons demonstrated higher NLR in MS-ON than in healthy controls (adjusted geometric means 2.83 vs. 1.80, p = 0.005). NLR discriminated MS-ON from controls with an area under the ROC curve (AUC) of 0.681 (95% CI, 0.554-0.807), while SIRI showed a comparable AUC of 0.661 (95% CI, 0.535-0.787). Among conventional hematological parameters, red cell distribution width remained elevated in IIH-ON, whereas serum albumin remained lower in MS-ON and IIH-ON after adjustment.

In the primary analysis, NLR was the only index that retained significance after adjustment for age, sex, and multiple testing, with higher values in MS-ON than in healthy controls. The sensitivity of several other indices to robust inference and the modest ROC performance warrant cautious interpretation and prospective validation.