Abstract
Purpose :
Ranibizumab is a well-established treatment for diabetic patients with macular edema. However, very little is known about the effect of ranibizumab on regulation of VEGF (vascular endothelial cell growth factor) family members by pro- and anti-inflammatory signaling pathways, which was the aim of this study.
Methods :
Diabetic patients (n=10) aged 18 years with central diabetic macular edema, BCVA >24 and <78, and central macular thickness (CMT) greater than 250 mm were enrolled in this study (ML39638). Following a full eye exam, imaging, and an aqueous tab, patients received ranibizumab (0.3mg/0.05mL) injections at day one and weeks four and eight. At week 12, a full eye exam, imaging, and a second aqueous tab was obtained prior to the last injection of ranibizumab. Pre- and post-treatment aqueous humor samples were then analyzed using Milliplex MAP magnetic bead assays.
Results :
As expected, ranibizumab lowered levels of VEGF-A, decreased CMT (central macular thickness), and improved VA (visual acuity). Ranibizumab – induced changes in levels of VEGF-A and VEGF-C strongly correlated with changes in soluble receptors, sgp130 and sIL-6R, which are associated with IL-6 signaling. In contrast, changes in VEGF-D correlated with sIL-1R1 and sIL-1R2, soluble receptors participating in IL-1 signaling. Changes in CMT and VA did not correlate with changes in levels of VEGF family members. However, following ranibizumab treatment for 3 months, post-treatment values of CMT correlated with post-treatment levels of VEGF-C. Post-treatment VA values correlated with a wide variety of potential biomarkers linked to inflammation.
Conclusions :
Ranibizumab treatment affected production of individual VEGF family members and altered specific pro-inflammatory signaling pathways that are seemingly linked to these differing VEGFs. Thus, new drug development focusing on targeting specific VEGF family members or, alternatively, the pro-inflammatory pathways connected to these family members could improve treatment of patients with diabetic macular edema and/or allow for a more personalized treatment approach.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.