Supplemental Anti Vegf A-Therapy Prevents Rebound Neovascularisation After Fine Needle Diathermy Treatment to Regress Pathological Corneal (LYMPH)Angiogenesis

Abstract

Fine needle diathermy (FND) is an effective method to destroy and regress pathologic corneal blood and lymphatic vessels. However, it is unknown whether FND itself causes a rebound corneal neovascularisation and whether that can be prevented by VEGF blockade. In female BALB/c mice, the suture-induced inflammatory corneal neovascularisation model was used to induce hem-and lymphangiogenesis. Thereafter, prevascularized mice were divided into 2 groups: the combination therapy group received FND cauterization and subsequent VEGF TrapR 1 R 2 eye drops three times per day whereas the monotherapy group was treated only with FND. Three, 7 and 14 days after the treatment, corneas were collected and stained with FITC-conjugated CD31 and LYVE-1 followed by Cy3-conjugated secondary antibody to quantify corneal blood and lymphatic vessels. Relative mRNA expression of VEGF in the cornea was quantified by using qPCR. FND cauterization as monotherapy significantly obliterated (lymph)angiogenesis at early time points; however, this treatment led to secondary corneal hem-and lymphangiogenesis associated with significant upregulation of pro(lymph)angiogenic VEGF-A, VEGF-C, VEGF-D and infiltration of macrophages. Combining FND cauterization with VEGF trapR 1 R 2 treatment prevented the undesired effect of the FND procedure alone and significantly better regressed corneal blood and lymphatic vessels at 1 week after the treatment compared to monotherapy and control group (p < 0.01).

Chemical eye injury: pathophysiology, assessment and management

“…13). Fine needle diathermy occlusion of deep vessels combined with subconjunctival injection of Avastin [99,100] and cyanoacrylate gluing of perforations are useful adjuncts in preparation for the more definitive procedures of LSCT and keratoplasty.…”

Management of corneal neovascularization: Current and emerging therapeutic approaches

“…[ 81 ] Unfortunately, corneal diathermy may induce further CoNV due to thermal damage. In a mouse suture-induced CoNV model, FND monotherapy inhibited angiogenesis at early time points, but was associated with secondary corneal angiogenesis, with elevated proangiogenic factors such as VEGF-A, VEGF-C, and VEGF-D.[ 82 ] Hence, combination therapy with anti-VEGF agents has been proposed to complement its usage. In the same study, addition of anti-VEGF agents with FND significantly regressed corneal blood and lymphatic vessels at 1 week and prevented the undesirable effect of angiogenesis observed in the monotherapy group.…”

“…In the same study, addition of anti-VEGF agents with FND significantly regressed corneal blood and lymphatic vessels at 1 week and prevented the undesirable effect of angiogenesis observed in the monotherapy group. [ 82 ] Clinically, FND combined with subconjunctival bevacizumab treatment before penetrating keratoplasty (PK) in patients with at least one quadrant of CoNV resulted in rejection-free graft survival rates of more than 90% after 1 year and 78% after 3 years. [ 83 ] A retrospective review of children who received FND with subconjunctival bevacizumab reported complete CoNV resolution in 88.9% within 1 month of treatment and an improvement in mean corrected distance visual acuity from 0.66 ± 0.31 to 0.50 ± 0.37 logMAR ( P = 0.02).…”

Inhibitory effect of anti-Scg3 on corneal neovascularization: a preliminary study

“…And we also evaluated the effect of ranibizumab (10 mg/ml) and conbercept (10 mg/ml) in the rabbit alkali burn CNV model in our initial study. We found the CNV was stimulated caused by aggravation of the inflammatory response [ 15 , 16 ]. We still need the evaluation of degree of burn and drug concentration to verify the validity of these results.…”