PREDICTIVE VALUE OF GLYCEMIC CONTROL, ANGIOGENIC FACTORS, AND MARKERS OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH SECONDARY NEOVASCULAR GLAUCOMA FOR ASSESSING LONG-TERM OUTCOMES OF ANTI-VEGF THERAPY
DOI:
https://doi.org/10.32782/2411-9164.23.2-8Keywords:
neovascular glaucoma, VEGF, von Willebrand factor, HbA1c, aflibercept, endothelial dysfunctionAbstract
Secondary neovascular glaucoma is a severe complication of ischemic retinal diseases, frequently associated with diabetes mellitus and driven by pathological angiogenesis. The effectiveness of anti-VEGF therapy in these patients is strongly influenced by systemic metabolic and vascular factors. This study aims to identify biomarkers that can predict long-term treatment outcomes. Aim. To evaluate the predictive value of glycemic control, angiogenic factors (VEGF), and endothelial dysfunction markers (von Willebrand factor) for long-term outcomes of anti-VEGF therapy in patients with secondary neovascular glaucoma (NVG) associated with diabetes mellitus. Materials and Methods. A prospective cohort study (2023–2025) included 60 patients with proliferative diabetic retinopathy and NVG. Serum VEGF dynamics, vWF antigen and activity, and annual mean HbA1c were assessed in relation to treatment response to aflibercept. Blood samples were collected at baseline, one month after the third injection, and at one year. Statistical assessment included ROC analysis, correlation analysis, logistic regression, and Kaplan–Meier survival curves. Results. Higher HbA1c and vWF levels were significantly associated with reduced duration of anti-VEGF efficacy and increased need for additional injections (r = 0.60–0.68; p < 0.05). In patients with HbA1c < 7.5%, VEGF suppression was sustained for one year, whereas those with HbA1c > 8.5% demonstrated VEGF rebound and recurrent neovascularization. Baseline VEGF was a strong predictor of recurrence (AUC ROC ≈ 0.81). Patients with vWF:Ag > 160% had a 2.1-fold higher recurrence risk and significantly poorer recurrence-free survival. Conclusions. Glycemic control and endothelial dysfunction markers are important predictors of anti-VEGF treatment response in NVG. Combined assessment of HbA1c, VEGF, and vWF enhances prediction accuracy for neovascular recurrence and supports individualized treatment strategies.
References
Kang, M. H., Lee, S. H., Hong, Y. J. (2023). Recent updates on diagnosis and management of neovascular glaucoma. Surv Ophthalmol. 68(2), 245–62.
Sun, M., Chen, Y., Li, J. (2022). Clinical predictors of anti-VEGF treatment outcomes in neovascular glaucoma: a systematic review. J Glaucoma. 31(9), 678–85.
Noma, H., Yasuda, K., Shimura, M. (2020). Aqueous humor levels of VEGF in neovascular glaucoma and ischemic retinal diseases. Int J Ophthalmol. 13(4), 660–66.
Zhang, H ., et al. (2021). Plasma VEGF and progression of diabetic microvascular ischemia. Diabetes Care. 44(5), 1135–42.
Stewart, M. W. (2020). Aflibercept in ophthalmology: mechanisms and clinical applications. Clin Ophthalmol. 14, 247–59.
Moussa, K., Kunimoto, D. Y., et al. (2023). Real-world effectiveness of aflibercept in neovascular glaucoma. J Glaucoma. 32(1), 45–52.
Huang, Y., et al. (2022). Role of PlGF and VEGF in diabetic ischemic retinopathy. Invest Ophthalmol Vis Sci. 63(6), 18.
Wakabayashi, K., et al. (2021). Angiopoietin-2 and neovascular eye diseases: current evidence. Retina. 41(9), 1835–42.
Patel, R, et al. (2023). Biomarkers of ocular neovascularization: inflammation and angiogenesis. Exp Eye Res. 227, 109338.
Paneni, F., et al. (2020). Endothelial dysfunction in diabetes and vascular complications. Lancet Diabetes Endocrinol. 8(11), 934–47.
Vischer, U. M., Lenting, P. J. (2022). von Willebrand factor in vascular pathology. Thromb Haemost. 122, 1345–57.
Blann, A. D., et al. (2019). VWF as a marker of endothelial activation in diabetic microangiopathy. Atherosclerosis. 288, 176–82.
Goto, H., et al. (2021) Placental growth factor as a driver of neovascular eye disease: updated understanding. Sci Rep. 11, 23342.
Campochiaro, P. A. (2020). Mechanisms of ocular neovascularization revisited. JAMA Ophthalmol. 138(11), 1123–30.
Minaker, K. L., et al. (2021). Endothelial biomarkers and risk stratification in diabetic vascular disease. Diabetes Metab Res Rev. 37, e3442.
Takahashi, H., et al. (2019). Long-term VEGF suppression after aflibercept injection: clinical implications. Retina. 39(7), 1358–66.
Lee, J. W., et al. (2020). Systemic biomarkers influencing response to anti-VEGF therapy. Am J Ophthalmol. 217, 25–33.
Garner, A., et al. (2021). New perspectives in neovascular glaucoma pathology. Clin Exp Ophthalmol. 49(4), 350–59.
Edwards, A. O., et al. (2020). Angiopoietin axis in retinal ischemia: clinical relevance. Ophthalmology. 127(6), 781–89.
Kida, T., et al. (2022). Prognostic factors in neovascular glaucoma treatment: a contemporary analysis. Ophthalmology. 129(3), 327–35.
