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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.
Romanian Journal of Ophthalmology
|May 18, 2026
Summary
Inflammatory stability, measured by the Inflammatory Stability Index (ISI), is a better predictor of glaucoma progression than absolute cytokine levels. High inflammatory stability indicates faster retinal nerve fiber layer loss in patients with primary open-angle glaucoma (POAG).
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Neuroinflammation is a known factor in glaucomatous neurodegeneration.
- The prognostic significance of inflammatory markers in glaucoma remains uncertain.
- Previous research focused on absolute cytokine levels, potentially missing crucial temporal dynamics.
Purpose of the Study:
- To investigate the association between inflammatory stability over time and retinal nerve fiber layer (RNFL) reduction in primary open-angle glaucoma (POAG).
- To introduce and validate the Inflammatory Stability Index (ISI) as a measure of temporal inflammatory patterns.
Main Methods:
- A prospective longitudinal cohort study involving 57 participants (19 controls, 38 POAG patients) over 24 months.
- Serum cytokine profiling (IL-1β, TNF-α, IL-6) and RNFL measurements were collected.
- The Inflammatory Stability Index (ISI) was developed using the formula: ISI = Median[cytokines] / (1 + IQR[cytokines]) to quantify inflammatory stability.
Main Results:
- The ISI significantly correlated with RNFL progression rate (r = -0.491, p = 0.002).
- Patients with stable-high inflammation (ISI > 3.5) exhibited 74% faster RNFL progression compared to those with volatile-low inflammation (ISI < 1.6).
- The ISI demonstrated acceptable accuracy in identifying rapid progressors (AUC = 0.76) and remained significant after multivariable adjustments.
Conclusions:
- Inflammatory stability patterns, as quantified by the ISI, are more informative for predicting glaucoma progression than absolute cytokine levels.
- The ISI can identify high-risk inflammatory phenotypes in POAG patients.
- This index may aid in personalized management strategies and patient stratification for closer monitoring.
Keywords:
ANOVA = Analysis of VarianceAUC = Area Under the CurveBCa = Bias-Corrected and Accelerated (bootstrap confidence interval)CI = Confidence IntervalCV = Coefficient of VariationHD-OCT = High-Definition Optical Coherence TomographyIFN-γ = Interferon gammaIL-10 = Interleukin-10IL-1β = Interleukin-1 betaIL-4 = Interleukin-4IL-6 = Interleukin-6IOP = Intraocular PressureIQR = Interquartile RangeISI = Inflammatory Stability IndexLR+ = Positive Likelihood RatioLR− = Negative Likelihood RatioMAD = Median Absolute DeviationNPV = Negative Predictive ValueOCT = Optical Coherence TomographyPGA = Prostaglandin AnalogsPOAG = Primary Open-Angle GlaucomaPPV = Positive Predictive ValueQALY = Quality-Adjusted Life YearRGCs = Retinal Ganglion CellsRNFL = Retinal Nerve Fiber LayerROC = Receiver Operating CharacteristicSD Standard = DeviationSTROBE = Strengthening the Reporting of Observational Studies in EpidemiologyTNF-α = Tumor Necrosis Factor alphabiomarkerscytokinesglaucomaneuroinflammationretinal