Comparison of intrastromal and subconctival anti-vegf treatments in suture induced corneal neovascularization in rabbit eyes

The aim of the study was to compare the efficacies of subconjunctival and intrastromal administration of anti-vascular endothelial growth factors (anti-VEGF) on corneal neovascularization (CoNV) in a rabbit model. Accordingly, we placed an 8/0 suture on the superior part of the all rabbit corneas to induce experimental CoNV model and separated rabbits into four groups (each treatment group consisted of 6 rabbits). Only one eye of the rabbits in each groups received anti-VEGF treatments, which were as follows: subconjunctival bevacizumab, subconjunctival aflibercept, intrastromal bevacizumab and intrastromal aflibercept, respectively. The untreated fellow eyes of rabbits served as the control group. One week after the anti-VEGF injection, we analysed the CoNV areas using ImageJ program, and studied VEGF-A, VEGF-B and PIGF (placental growth factor) levels in extracted corneal samples by using ELİSA test. Histopathological examination was also performed in extracted corneal samples. Regression rates from highest to lowest in the CoNV areas were as follows: 88.1% in the intrastromal aflibercept group, 82.5% in the intrastromal bevacizumab group, 69.9% in the subconjunctival bevacizumab group, 64.5% in the subconjunctival aflibercept group, and 30.3% in the control group. VEGF-A levels were lower in eyes treated with intrastromal injection compared to those treated with subconjontival injection. VEGF-B and PIGF levels were lower in eyes treated with aflibercept compared to those treated with bevacizumab. Histopathologic examination revealed excessive neutrophilic infiltration and neovascular structures in the anterior stroma in the control group, whereas corneal layers were observed to be normal in the groups treated with intrastromal anti-VEGF injections. In conclusion, intrastromal therapy regressed CoNV more effectively than subconjunctival therapy regardless of the type of anti-VEGF treatment. Aflibercept and bevacizumab had similar effects on CoNV. Both injection techniques do not cause any clinically observed side effects on the cornea and, therefore, could be applied safely.