Randomized, Double-Masked, Controlled Translational Investigation Of Bevacizumab For Retinal Detachment Due To Proliferative Diabetic Retinopathy

Abstract

Purpose: : The exact mechanisms underlying the pathogenesis of retinal detachment (RD) in proliferative diabetic retinopathy (PDR) are unclear. Connective tissue growth factor (CTGF) is a mediator of intraocular fibrosis and increased in eyes with active PDR. The purpose of this study was to assess the effect of VEGF inhibition on CTGF and VEGF in patients with diabetic RD.

Methods: : 20 eyes of 19 patients were randomized prospectively to receive intravitreal bevacizumab or sham injection 3-7 days prior to vitrectomy by a single surgeon for RD due to PDR. Patients with dense vitreous hemorrhage were excluded. Patient and surgeon were masked to treatment. RDs were graded as traction RD (TRD; mild, moderate, severe) or combined traction-rhegmatogenous RD (TRD/RRD). Fundus photos and SD-OCT were obtained at time of injection and on the day of surgery. Aqueous samples prior to injection and at time of surgery were collected. Vitreous samples and fibrovascular membranes were also collected. ELISA for VEGF and CTGF were performed on aqueous and vitreous samples. Statistical analysis of growth factor levels was done.

Results: : 5 eyes had moderate TRD, 8 had severe TRD, and 7 had combined TRD/RRD. 5 eyes had decreased vascularization of membranes from pre-injection to time of surgery (all in treatment arm) and only 1 of these had severe intra-operative bleeding.Median vitreous levels of VEGF were lower in the bevacizumab group than the control group (p-value=0.03). Median vitreous levels of CTGF (pg/mL) were 980 in the bevacizumab group and 1235 in the control group (p-value=0.38). CTGF levels in the aqueous were strongly correlated to those in the vitreous of controls (Spearman correlation coefficient 0.95, p-value<0.001). Correlation between VEGF and CTGF levels in the vitreous of the bevacizumab group was significant (p-value=0.01) and not observed in the control group. Clinical correlation to these laboratory findings is currently underway.

Conclusions: : Intravitreal bevacizumab administered within 3-7 days of surgery in patients with RD due to PDR effectively reduces vitreous levels of VEGF that produces a clinically observable alteration in fibrovascular membranes. Aqueous CTGF is a useful surrogate marker for vitreous CTGF in these eyes. There is a positive correlation between CTGF and VEGF levels in eyes treated with VEGF inhibition.

Clinical Trial: : http://www.clinicaltrials.gov USC-HS-09-00068

Keywords: diabetic retinopathy • retinal detachment • growth factors/growth factor receptors