Intrastromal versus subconjunctival anti-VEGF agents for treatment of corneal neovascularization: a rabbit study

Objective To determine whether subconjunctival or intrastromal administration of anti-VEGF agents is more effective on suture-induced corneal neovascularization (CoNV) in rabbits. Methods CoNV was induced in 48 eyes of 24 New Zealand white rabbits by using an 8/0 silk suture. On the 7th day after suturing, the rabbits were divided into four treatment groups as follows: six rabbits received subconjunctival bevacizumab (group 1), six rabbits received subconjunctival aflibercept (group 2), six rabbits received intrastromal bevacizumab (group 3) and six rabbits received intrastromal aflibercept (group 4). On the 7th and 14th days after suturing, the CoNV area was calculated by standardised analysis of photographs using the Image-J program. On the 14th day after suturing, all rabbits were sacrificed and then corneal tissue was harvested for the analysis of vascular endothelial growth factor (VEGF)-A, VEGF-B and placental growth factor (PIGF) levels. Results On the 7th day after suturing, CoNV areas were 17.10 ± 2.98, 18.88 ± 3.78, 17.36 ± 4.52, 18.57 ± 4.16 and 17.31 ± 2.81 mm 2 in the groups 1–4 and control group, respectively. On the 7th day after intervention and removal of suture, CoNV areas were 4.85 ± 1.99, 6.66 ± 1.73, 2.83 ± 1.08, 2.63 ± 1.16 and 11.93 ± 2.64 mm 2 in the group 1–4 and control group, respectively. CoNV area was reduced by 88.1% and 82.5% in eyes receiving intrastromal aflibercept and bevacizumab, respectively (both p < 0.001), and by 64.5% and 69.9% in eyes receiving subconjunctival aflibercept and bevacizumab, respectively (both p = 0.001). Conclusion Intrastromal anti-VEGF therapy regressed CoNV more effectively than subconjunctival therapy regardless of the type of anti-VEGF agent.