Angiofibrotic Response to Vascular Endothelial Growth Factor Inhibition in Diabetic Retinal Detachment

Abstract

Purpose To assess the effect of bevacizumab on connective tissue growth factor (CTGF) and VEGF in ocular fluids of patients with diabetic traction retinal detachment. To determine whether intra- and post-operative complications are decreased in eyes given adjunctive pre-operative bevacizumab. Methods Twenty eyes of 19 patients were randomized to receive intravitreal bevacizumab or sham 3–7 days prior to vitrectomy for severe proliferative diabetic retinopathy. Aqueous samples prior to injection and at time of surgery were collected. Undiluted vitreous samples were extracted. Results Five eyes had decreased vascularization of membranes from pre-injection to time of surgery (all in treatment arm). Median visual acuity was 20/400 in controls at baseline and 3 months post-op; counts fingers in the treated group at baseline and 20/100 at 3 months (p=0.30 between controls and treated at 3 months). All retinas were attached at post-operative month 3. Vitreous levels of VEGF were significantly lower in the bevacizumab group than the control group (p-value=0.03). Vitreous levels of CTGF were slightly lower in the bevacizumab group compared to controls but this was not statistically significant (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). Conclusions Intravitreal bevacizumab reduces vitreous levels of VEGF and produces a clinically observable alteration in diabetic fibrovascular membranes. Ocular fluid levels of CTGF are not significantly affected within the week following VEGF inhibition. Retinal reattachment rates and visual acuity are not significantly altered by pre-operative intravitreal bevacizumab at post-operative month 3.

Monitoring intraocular proangiogenic and profibrotic cytokines within 7 days after adjunctive anti‐vascular endothelial growth factor therapy for proliferative diabetic retinopathy

“…After anti-VEGF treatment, the balance favours CTCF and an 'angio-fibrotic switch' is flipped, with increase in intraocular fibrosis (Kuiper et al 2008). In this work, we found the vitreous CTGF level was higher in PDR patients compared with MH/ERM patients, but not increased within 7 days after IVC, which was similar to the results from Jiao et al (2019) (Sohn et al 2012). El-Sabagh et al (2011) reported that fibrotic elements (such as smooth muscle actin and collagen) were not abundant after 10 days post-IVB.…”

Apoptosis and Angiofibrosis in Diabetic Tractional Membranes After Vascular Endothelial Growth Factor Inhibition

“…In this randomized controlled study we found that fibrovascular membranes from eyes with diabetic traction detachments treated with and without preoperative intravitreal bevacizumab had histologically detectable growth factors associated with angiogenesis (VEGF) and fibrosis (CTGF). VEGF levels in the vitreous published in the first report from this study using ELISA were positively correlated at a modest level to VEGF in membranes of the same patients while CTGF levels in vitreous were negatively correlated to CTGF content in the membranes 2 . Apoptotic cells, detected by TUNEL staining, were more numerous in eyes treated with bevacizumab compared to controls.…”

Ocular findings, surgery details and outcomes in proliferative diabetic retinopathy patients with chronic kidney disease

“…Previous work showed that subretinal fluid could spontaneously resolve 2-12 months after PPV, and long-standing subretinal fluid is unrelated to visual prognosis [15][16][17]. Contrary to previous works focusing on the influence of subretinal fluid on visual recovery in PDR patients who underwent PPV, we focused on the presence of long-standing subretinal fluid, which may hold back the application of PRP and, in turn, increase the chance of postoperative NVI.…”