Systemic Inflammatory and Microcirculatory Determinants of Long-Term Outcomes in Neovascular Glaucoma: A Multicenter...

Neovascular glaucoma (NVG) represents one of the most severe forms of secondary glaucoma and is characterized by an aggressive clinical course, a high risk of irreversible vision loss, and substantial variability in treatment outcomes. At the same time, the roles of systemic inflammation, ocular microcirculation, and neovascularization of the iridocorneal angle (according to the Weiss D. classification, 1978) in determining the long-term prognosis remain insufficiently investigated.

To identify clinical, microcirculatory, and systemic inflammatory predictors of long-term treatment effectiveness in secondary NVG and to compare the outcomes of surgical interventions and diode transscleral cyclophotocoagulation depending on the stage of iridocorneal angle neovascularization.

A multicenter retrospective cohort study included 87 eyes with ischemic NVG secondary to proliferative diabetic retinopathy or retinal vein occlusion treated between 2018 and 2024 in Ukraine and Moldova. Patients were divided into a surgical group (n=39) and a diode transscleral cyclophotocoagulation group (n=48). Clinical parameters, systemic inflammatory indices (SII, SIRI, AISI), HbA1c, cardiovascular comorbidity, and the rheographic coefficient (RQ), a functional microcirculation marker, were analyzed. Treatment success was defined as intraocular pressure control with stabilization of visual acuity, absence of rubeosis progression, and no need for additional invasive surgery. Multivariable logistic regression and ROC analysis were performed.

Treatment effectiveness was strongly associated with the stage of iridocorneal angle neovascularization. In the early stages, both approaches showed high success rates, whereas in the advanced stages, surgical outcomes declined markedly. In multivariable analysis, surgery increased the odds of success more than fivefold (OR=5.4; p=0.003), whereas advanced angle stages reduced it nearly sixfold (OR=0.18; p=0.007). Higher systemic inflammation was associated with poorer prognosis (SII OR=0.76; p=0.009), whereas better microcirculation was associated with improved outcomes (RQ OR=1.42; p=0.023). The combined predictive model demonstrated good discrimination (AUC = 0.84; 95% CI, 0.74-0.92).

In the present study, long-term outcomes of neovascular glaucoma were shown to be determined by the complex interaction between the stage of iridocorneal angle neovascularization, systemic inflammation, and ocular microcirculation. Our findings indicated that the Weiss stage is a key morphological factor that modifies treatment effectiveness. In contrast, systemic inflammatory indices (SII, SIRI, AISI) reflect the underlying biological burden of disease and are associated with poorer prognosis. In contrast, higher values of the microcirculatory parameter (RQ) were significantly associated with more favorable treatment outcomes, likely reflecting preserved perfusion capacity and a lower degree of ischemic tissue damage. This observation is consistent with the concept of ischemia-driven progression in NVG. Importantly, integrating these parameters into a multivariable model demonstrated good discriminative performance (AUC = 0.84), supporting the value of a combined clinical-biological approach to risk stratification. Taken together, these results suggest that NVG should be considered not only a localized ocular disorder but also a systemically influenced condition in which the interplay among angiogenesis, inflammation, and microcirculatory dysfunction determines individual treatment response.

Long-term outcomes in neovascular glaucoma appear to be determined by the interaction between the stage of iridocorneal angle neovascularization, systemic inflammation, and ocular microcirculation. Surgical treatment provides the greatest benefit in early disease, whereas cyclophotocoagulation remains a stable option in advanced stages. Combined clinical-biological modeling may support personalized treatment selection in NVG.