Significance of monitoring vascular endothelial growth factor, monocyte chemoattractant protein-1 and Interleukin-8 in diabetic macular edema towards early identification of nonresponders to ranibizumab therapy

• DOI: 10.4103/ijo.ijo_3109_20
• Publication Date: 2021-06-02T14:42:08Z
• Authors: Tessy Xavier; Swetha Pallikara; Neha Saji; Natasha Radhakris...; Krishnakumar N Menon; Gopal S Pillai
• Keywords: Vascular Endothelial Growth Factor A; Diabetic Retinopathy; cmt; Interleukin-8; Visual Acuity; Angiogenesis Inhibitors; RE1-994; Macular Edema; anti-vegf therapy; Ophthalmology; 03 medical and health sciences; 0302 clinical medicine; bcva; Ranibizumab; Intravitreal Injections; Diabetes Mellitus; Humans; Original Article; ranibizumab; diabetic macular edema; vegf; Chemokine CCL2; Tomography, Optical Coherence

Purpose: Identification of nonresponders prior to anti-vascular endothelial growth factor (anti-VEGF) therapy would help in the judicious clinical management of diabetic macular edema (DME) patients. Thus, a systematic study was initiated to identify nonresponding DME patient population undergoing ranibizumab treatment to figure out additional inflammatory components that may contribute to their nonresponsiveness to anti-VEGF therapy.

Methods: A total of 40 patients recruited to this investigator-initiated trial received intravitreal ranibizumab monthly for 3 months. The fourth- and fifth-month injections were according to PRN protocol and the sixth-month injection was mandatory. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and VEGF in aqueous humor were measured for all the patients. Patients were grouped into responders/nonresponders on the formulated criteria and the levels of key pro-inflammatory cytokines were also measured between the two groups at baseline, 2 month and 5 months using cytometric bead array (CBA).

Results: Eleven patients were categorized (29.72%) as responders and 10 patients (27.02%) as nonresponders. Nonresponders showed poorer BCVA (P = 0.024, 0.045, and 0.048 for 4, 5, and 6 months) and higher CMT (P = 0.021, 0.0008 and <0.0001 for baseline, 1, 2, 3, 4, 5, and 6 months) compared to responders. The cytokines IL-8, MCP-1 were significantly up regulated (P = 0.0048 and 0.029 for MCP-1 and IL-8) in nonresponders.

Conclusion: Elevated MCP-1 and IL-8 levels found in the nonresponders could be used as a prognostic marker to identify these groups of patients and can help in developing alternative treatment options along with anti-VEGF therapy.