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N. Rocher, F. Behar Cohen, G. Renard, J. Bourges; Modulation of the Neovascular Corneal Graft Rejection Risk Factor by Anti-VEGF (Vascular Endothelial Growth Factor) Treatment. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4962.
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Corneal neovascularisation impairs both patient’s vision and graft outcome after penetrating keratoplasty (PK). As it inhibits intraocular neovessel progression in retinal diseases, we administrated anti-Vascular Endothelial Growth Factor antibody therapy (anti-VEGF) either topically or by subconjunctival injection in a murin model of acute corneal graft rejection to assessed graft’s neovascularization (nv) inhibition during the alloimmune rejection process.
Twenty four rats underwent a PK procedure according to a standardized model of acute alloimmune graft rejection. Operated eyes were divided in four groups: Group I (n=6) had a subconjunctival injection of inactivated anti-VEGF (0.02 ml/inj/3 days, 10 µg/ml), group II (n=6) had a subconjunctival injection of anti-VEGF (0.02 ml/inj/3 days, 10 µg/ml), group III (n=6) were instilled with inactivated anti-VEGF (10µg/ml drops three time a day,) and group IV (n=6) were instilled with anti-VEGF (10µg/ml drops three time a day), from the time of procedure until sacrifice at day 21. Corneal edema (E), transparency (T) and nv were scored at D3, D9, D15, and D21. The button’s vessels were quantified combining both immunochemical lectin staining and morphometric measurements on flat-mounted corneas.
After 3 weeks, mean clinical scores (mcs) statistically differed between group I and II (mcs= 4 (T); 3 (E) and 4 (nv) versus 2,33 (T); 2,16 (E) and 2,5 (nv); p0.05) but not between group III and IV (mcs= 3,5 (T); 3 (E) and 4 (nv) versus 2,66 (T); 2,16 (E) and 3 (nv); p>0.05). . Buttons less rejected in group II compared to group I (100% versus 50%, p0.05) and in group IV compared to group III (100% versus 66,65%, p>0.05). . The mean percentages of neovascular corneal area were 58% in group I versus 36% in II (p<0,05), and 57,5% in group III versus 43% in IV (p<0,05).
Subconjunctival and topical administration of anti-VEGF antibodies can reduce corneal neovessels and slow down the PK rejection process in rats. These results need therefore to be further confirmed in human patients subjected to PK procedures.
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