Cytokine-Based Diagnostic Accuracy for Postoperative Endophthalmitis: Implications for Bacterial–Fungal Differentiation

This is the authors' abstract. We don't add key points for this paper.

Background Vitreous cytokines have been proposed as diagnostic biomarkers for acute post-cataract endophthalmitis, but their diagnostic accuracy has not been quantified. We reanalyzed a previously described cohort to determine the diagnostic accuracy of vitreous cytokines for distinguishing infectious endophthalmitis from non-infectious controls and for predicting culture positivity, and explored optical coherence tomography (OCT) central macular thickness as an additional biomarker correlate. Methods Individual-level vitreous concentrations of 25 cytokines, chemokines and growth factors — originally measured by multiplex immunoassay in 18 patients with acute infectious endophthalmitis after cataract extraction and 39 non-infectious vitrectomy controls — were reanalyzed. ROC analysis estimated the area under the curve (AUC), optimal Youden cut-off, sensitivity and specificity for each cytokine. Leave-one-out cross-validation (LOOCV) assessed a combined biomarker panel. Multivariable regression evaluated TNF-α versus initial visual acuity (logMAR), adjusting for age and diabetes. In patients with interpretable OCT imaging, central macular thickness was compared between affected and fellow eyes (Wilcoxon signed-rank test) and correlated with vitreous cytokines (Spearman). Results IL-6, G-CSF, IL-8, IL-1ra and TNF-α showed excellent discrimination between endophthalmitis and controls (AUC 0.97–1.00). A combined IL-6 + G-CSF panel achieved LOOCV AUC = 0.999, with no gain over IL-6 (AUC = 1.000). Within endophthalmitis cases, IL-8 predicted positive culture with moderate accuracy (AUC = 0.753; cut-off 1264 pg/mL; sensitivity 81.8%, specificity 71.4%), outperforming TNF-α (AUC = 0.675) and IL-17 (AUC = 0.597). TNF-α correlated with initial visual acuity (r = 0.51, p = 0.032), attenuated after adjusting for age and diabetes (p = 0.117). Central macular thickness was greater in affected than fellow eyes (323.5 vs 246.1 µm, p = 0.004), but no cytokine correlated with affected-eye thickness or the affected–fellow difference (maximum r = 0.41, p ≥ 0.12). Conclusions Vitreous IL-6, G-CSF and IL-8 show potential as rapid diagnostic biomarkers for bacterial post-cataract endophthalmitis, and IL-8 shows moderate value in predicting culture positivity. Together with published data on fungal endophthalmitis, these findings support a hypothesis-generating role for cytokine profiling in etiological triage, pending prospective, multicenter validation. Affected eyes showed greater central macular thickness than fellow eyes, a structural correlate not explained by the cytokine panel measured here.