Subconjunctival bevacizumab for corneal neovascularization

Abstract

ABSTRACT.Purpose: This work aimed to study and evaluate the effect of subconjunctival bevacizumab injection in patients with corneal neovascularization (CNV) resulting from different ocular surface disorders. Methods: Ten eyes with CNV caused by different ocular surface disorders were studied. All eyes had both major and minor vessel CNV caused by factors such as healed corneal ulcers, long-standing chronic inflammatory diseases and corneal ischaemia (caused by contact lenses). All eyes received a single subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphological changes in the major and minor vessels were evaluated using slit-lamp biomicroscopy and corneal photography. Results: Conspicuous recession of the minor vessels of CNV was observed in all eyes at 2 weeks post-injection. The extent of CNV of the major vessels was significantly decreased at 2 weeks post-injection. The level of CNV continued to decrease noticeably for 3 months and then stabilized for the remainder of the 6-month follow-up period. Parameters used for evaluation included the total area of CNV, which amounted to 14.0 ± 5.4% of the corneal surface pre-injection, compared with 9.4 ± 3.9% post-injection (p < 0.01), reflecting a mean decrease in CNV of 33 ± 8%, and the extent of neovascularization, which decreased from 4.3 ± 1.5 clock hours pre-injection to 2.4 ± 1.1 clock hours post-injection (p < 0.01). During the 6-month follow-up, none of the 10 eyes showed any complication that could be related to subconjunctival bevacizumab injection. Conclusions: Bevacizumab can be used safely and effectively for CNV resulting from different ocular surface disorders. It represents an effective treatment for minor vessel neovascularization caused by long-standing chronic inflammation (e.g. trachoma) or long-standing corneal ischaemia (e.g. contact lenses), as well as for major vessel neovascularization resulting from different causes. Bevacizumab was well tolerated over the 6-month follow-up period.

Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model

“…Suppression of corneal neovasularization by 57-75 % with dexamethasone has been reported previously in rodent models (Hoffart et al, 2010;Hos et al, 2011;Nakao et al, 2012Nakao et al, , 2007. Anti-VEGFA treatments, however, have had a comparatively poorer efficacy in both animal and clinical studies (Bahar et al, 2008;Hoffart et al, 2010;Farid and Zaki, 2010), with some studies noting only borderline reduction in neovascular area (Oh et al, 2009) while others report greater reduction in invasion area relative to controls (Bock et al, 2007;DratvimanStorobinsjy et al, 2009;Manzano et al, 2007). In this study, a reduction of 14% in invasion area relative to sham-treated controls did not reach significance.…”

Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model

“…Steroids have long been used to promote the regression of undesirable neovessels and are well known for their anti-inflammatory and antiangiogenic effect [15][16][17]. More recently, bevacizumab, a monoclonal VEGF-A antibody approved for the treatment of metastatic colorectal cancer, has been widely used off-label to successfully induce regression in eye-related angiogenesis in cases of choroidal, retinal and corneal neovascularization in patients [18][19][20][21][22][23][24].…”

“…In both clinical and experimental studies, corneal capillary regression is commonly evaluated by degree of vascular invasion at the tissue level, using photography of visible blood vessels, fluorescein angiography, or by immunostaining of vascular endothelium at fixed time points [17,[21][22][23][24][25][26][27][28][29][30][31][32]. Little, however, is known about the morphologic characteristics of regressing capillaries at the cellular level following therapy.…”

Bevacizumab and corneal pathology

“…Zaki i suradnici u svojoj studiji na 10 pacijenata prikazali su da se subkonjunktivalna primjena 2,5 mg/0,1 ml bevacizumaba dobro podnosi i dovodi do smanjenja ukupne površine neovaskularizacija s 14 % površine rožnice na 9,4 % već 15 dana nakon 1 injekcije, s postepenom regresijom NV do 3 mjeseca nakon injekcije i stabilnim stanjem tijekom 6 mjeseci 14 . Daljnje studije sugeriraju da se djelotvornost bevacizumaba povećava pri višim dozama (5,0 mg/0,2 ml) 15 .…”