Abstract
Purpose :
Anti-VEGF (Vascular Endothelial Cell Growth Factor) drugs are the standard care for treatment of patients with diabetic macular edema (DME). Despite the success of anti-VEGF therapy roughly 30% of patients with DME do not respond properly to this type of therapeutic approach. Thus, there is a pressing need to understand whether and which retinal factors influence the effectiveness of anti-VEGF drugs, the aim of this project.
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 (p=0.0200), decreased CMT (central macular thickness, p=0.0480), and improved VA (visual acuity, p=0.0190). Interestingly, data analysis showed that the drug either had an immediate effect on vision parameters within 4 weeks after the first injection or none at all. Several pro-inflammatory mediators seemed to influence ranibizumab’s effectiveness in improving CMT. For example, baseline levels of interferon-γ correlated significantly with reduction in CMT (r=0.6490, p=0.0423). Other pro-inflammatory mediators such as the soluble receptors of IL-1 (interleukin-1) IL-1R1 (r=0.5985), IL-1R2 (r=0.6672), or Rantes (r=0.5640) had similar influence on ranibizumab’s effectiveness on lowering CMT.
Conclusions :
Ranibizumab’s effectiveness can be determined within the first four weeks of therapy. Its effectiveness is greatly influenced by baseline levels of specific pro-inflammatory mediators. Fully identifying those pro-inflammatory mediators and their critical baseline levels will help to predict outcome of anti-VEGF therapies early in the treatment of diabetic macular edema.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.