Study on the effects of different anti-VEGF drugs on fibrovascular membranes of proliferative diabetic retinopathy

Abstract

Purpose: To investigate the effects of different anti-VEGF drugs on fibrovascular membranes (FVM) in proliferative diabetic retinopathy (PDR). In addition, in vitro model was used to simulate the intraocular fibroblasts barrier to explore the penetration of different anti-VEGF drugs.

Methods: 24 eyes from 24 PDR patients with FVM were recruited for this prospective observational study. The patients were randomized to receive one of three anti-VEGF drugs (Ranibizumab, Conbercept, or Aflibercept). Then neovascular structures were assessed by optical coherence tomography angiography (OCTA) before intravitreal injection (pre-IVT) and 1, 2, and 3 days after intravitreal injection (post-IVT). The changes in vessels area (VSA), vessels percentage area (VPA), junction density (JD), and average lacunarity (AL) were analyzed by using the image processing software Angiotool. In vitro penetrating model with fibroblasts barrier was used to compare the effects of the three drugs on human retinal vascular endothelial cells (HRVECs) over 3 days by Cell proliferation measurement. Moreover, the drug concentrations in the penetrating model were detected by liquid chromatography-mass spectrometry (LC-MS).

Results: The VSA, VPA, and JD all decreased, while the AL increased in Ranibizumab group(n = 8), Conbercept group (n = 8), and Aflibercept group (n = 8) within 3 days (P<0.05). Meanwhile, under the condition of the same amount of substance, the inhibition effect of Ranibizumab on HRVEC was the strongest in the penetrating model evaluated by CCK8 absorbance experiments of HRVECs (F_CCK8=6.493, P_CCK8= 0.0051), and the number of transmembrane molecules in the Ranibizumab group was also the largest within 3 days (F = 8.209, P = 0.0006) among the three groups.

Conclusion: Angiotool is feasible to reconstruct the neovascular structure on the FVM in OCTA images. The three different anti-VEGF drugs can significantly reduce the vascular area and density on the proliferating membranes, and there is no significant difference in the anti-neovascularization among the three drugs clinically. However, small molecule drug is more penetrating and move faster across membranes in vitro cell model.

Clinical trial registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2300067476).

Keywords: Anti-VEGF; Fibrovascular membrane (FVM); Optical coherence tomography angiography (OCTA); Penetration; Proliferative diabetic retinopathy (PDR).