The Association of Aqueous Cytokines with Long-Term Response to Intravitreal Ranibizumab In Diabetic Macular Edema

Abstract

Purpose : To identify the association of baseline aqueous humor cytokine levels with long-term response to intravitreal ranibizumab in patients with diabetic macular edema (DME).

Methods : This is a prospective longitudinal cohort study that included treatment-naïve patients with centre-involving DME and central subfield macular thickness (CST) ≥310 μm on spectral domain optical coherence tomography (OCT). All patients received monthly intravitreal ranibizumab for 3 months. Aqueous fluid specimens at baseline and at 2 months were obtained immediately prior to ranibizumab injections. Multiplex immunoassay of aqueous samples was carried out for vascular endothelial growth factor (VEGF), placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Following 3 months of follow-up, patients were longitudinally followed as per standard of care. Response to ranibizumab over the study period was assessed by OCT parameters. Patients were classified as, i) responsive if there was resolution of DME with ranibizumab, and ii) unresponsive if persistent and/or recurrent DME was present despite ongoing ranibizumab therapy.

Results : A total of 40 eyes (39 patients) with a mean age of 64.45 ± 10.47 years were followed between December 2011 and November 2017. The mean followup period was 3.76 ± 1.9 years. Twenty-eight eyes (70%) were responsive to ranibizumab, while 12 (30%) were unresponsive. The mean change from baseline in macular volume cube (mm3) at last follow-up was significantly higher for the responsive versus the unresponsive group (2.36 ± 2.01 vs 1.3 ± 1.1, p = 0.037). Aqueous VEGF concentration (pg/mL) was significantly associated with long-term treatment response and was lower in the responsive group at baseline (882.2 ± 501.7 vs 1045.9 ± 754.2, p = 0.041) and at 2 months follow-up (108.4 ± 203.3 vs 243.4 ± 534.1, p = 0.024). A greater decline in baseline aqueous concentration of ICAM-1 (pg/mL) at the 2-month follow-up showed a trend for association with long-term response to ranibizumab (489.2 ± 688.1 vs 371.6, p = 0.058).

Conclusions : Lower levels of baseline and post intravitreal ranibizumab aqueous VEGF in patients with DME are associated with favorable long-term response to treatment.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.