The effect of combinations of flurbiprofen, low molecular weight heparin, and doxycycline on the inhibition of corneal neovascularization.
ABSTRACT To determine the efficacy of various combinations of flurbiprofen, low molecular weight heparin (LMWH), and doxycycline on the inhibition of corneal neovascularization in rats.
Chemical cauterization of the cornea in 32 eyes of 32 rats was performed using silver nitrate/potassium nitrate sticks. The animals were divided into 4 groups. Topical instillation of 0.015% flurbiprofen with 5 mg/mL LMWH (group 1); flurbiprofen with 10 mg/mL doxycycline (group 2); doxycycline with LMWH (group 3), and saline (group 4; control) was performed twice a day for 7 days. Slit-lamp photography was used to determine the percent areas of cornea covered by neovascularization and also by scar in each group. The means were compared to find any significant (P < 0.05) difference between groups. The animals were euthanized and the eyes enucleated for histological evaluation.
The mean of percent area of corneal neovascularization 5 in group 1 was 48.5 +/- 13.1; group 2, 6.6 +/- 5.5; group 3, 22.0 +/- 27.6 and group 4, 64.6 +/- 9. The means of percent area of neovascularization in groups 2 and 3 were significantly lower compared with control and group 1. There was no significant difference in the percent corneal neovascularization between groups 2 and 3 or between group 1 and the control group. Histological findings were consistent with slit-lamp evaluations.
Topical instillation of combinations of doxycycline with either flurbiprofen or LMWH can effectively inhibit corneal neovascularization made by chemical cauterization of the cornea in rats.
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ABSTRACT: To evaluate the inhibitory effects of regorafenib (BAY 73-4506), a multikinase inhibitor, on corneal neovascularization (NV). Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (n = 6) received 0.9% NaCl, Group 2 (n = 6) received dimethyl sulfoxide, Group 3 (n = 6) received regorafenib 1 mg/mL, Group 4 (n =6) received bevacizumab 5 mg/mL and Group 5 (n = 6) received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea's total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining. A statistically significant difference in the percent area of corneal NV was found among the groups (P <0.001). Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (P >0.005). There was a statistically significant difference among the groups in apoptotic cell density (P = 0.002). The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (P <0.05). The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2. Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats.International Journal of Ophthalmology 01/2014; 7(2):220-225. · 0.12 Impact Factor
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ABSTRACT: Corneal neovascularization (CNV) is a complication of inflammatory and hypoxic ocular pathologies or immune response to ocular infections. CNV is a manifestation of an imbalance between pro-angiogenic and anti-angiogenic signaling molecules. Despite a magnitude of evidence suggesting angiogenic signaling molecules play a pivotal role in modulating CNV, there are insufficient current pharmacologic treatment options for CNV. Thus, targeting signaling molecules appears to be one promising treatment. Multiple drugs have been used off-label and have shown success in treating CNV, most notably the anti-VEGF medications. In addition, novel drugs are being developed and studied for CNV. This article will describe various molecular mechanisms that induce angiogenesis in the cornea, in addition to potential chemotherapies for CNV that inhibit these molecular mechanisms. This review is pertinent but not all-inclusive. The authors will give examples of publications that have reported novel discoveries related to potential future anti-CNV therapies.Expert Review of Ophthalmology 01/2014; 8(2).
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ABSTRACT: Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization. Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1) or subconjunctival instillation of 1 mg/mL tigecycline (group 3) for 7 days. Control rats received topical (group 2) or subconjunctival (group 4) 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically. Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI), 44.2-55.8%) and 33.5% (95% CI, 26.6-39.2%), respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (P = 0.03 and P < 0.001, resp.). Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups. Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.Journal of ophthalmology. 01/2014; 2014:452685.