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Inflammatory Stability Index Correlates with Retinal Nerve Fiber Layer Reduction in Glaucoma
Raluca Neacșa1,2, Daniela Manasia1,2, Cristiana Tănase3,4
1Department of Medico-Surgical Disciplines, Faculty of Medicine, "Titu Maiorescu" University of Bucharest, Bucharest, Romania.
Background:
While neuroinflammation is recognized as a driver of glaucomatous neurodegeneration, the prognostic value of inflammatory markers remains unclear. Previous studies have focused on absolute cytokine levels, potentially overlooking other factors.
Objective:
To determine whether inflammatory stability over time, quantified by a proposed Inflammatory Stability Index (ISI), associates with retinal nerve fiber layer (RNFL) reduction in POAG.
Methods:
Prospective longitudinal cohort study of 57 participants (19 controls, 38 glaucoma patients) with serum cytokine profiling (IL-1β, TNF-α, IL-6) and RNFL measurements over 24 months. We developed the ISI=Median[cytokines]/{1+IQR[cytokines]} to quantify temporal inflammatory patterns, where higher values indicate stable-high inflammation and lower values indicate volatile-low inflammation.
Results:
ISI correlated significantly with RNFL progression (r = -0.491, p = 0.002). Stable-high inflammation patients (ISI > 3.5) progressed 74% faster than volatile-low patients (ISI < 1.6). ISI showed acceptable accuracy for identifying rapid progressors (AUC = 0.76). Associations persisted after multivariable adjustment. Treatment benefit was comparable across inflammatory phenotypes.
Discussion:
In this 24-month prospective cohort of 57 participants (19 controls, 38 POAG patients), ISI correlated significantly with RNFL progression rate (r = -0.491, p = 0.002). Patients with stable-high inflammation (ISI > 3.5) showed 74% faster RNFL progression than those with volatile-low inflammation (ISI < 1.6). Moreover, ISI demonstrated acceptable discriminative accuracy for identifying rapid progressors, with an area under the ROC curve of 0.76 (95% CI: 0.56-0.96). These associations remained significant after multivariable adjustment for age, sex, and treatment status (R2 = 0.426, p < 0.001), confirming that inflammatory stability patterns may be more informative than cytokine magnitude alone for predicting glaucomatous neurodegeneration.
Conclusions:
Inflammatory stability patterns may be more important than magnitude alone in glaucoma progression. The ISI identifies high-risk phenotypes and may predict treatment response, informing personalized management and patient stratification for intensive monitoring.
