Vascular endothelial growth factor inhibitor is an emerging therapeutic modality for various ocular diseases with neovascularization (NV). However, for corneal NV, controversy remains regarding whether bevacizumab or ranibizumab is superior. A 32-year-old female diagnosed with herpetic keratoconjunctivitis with refractory corneal NV despite two previous subconjunctival and intrastromal bevacizumab injections, received two subconjunctival and intrastromal ranibizumab injections. Six months postoperatively, there was significant regression of the neovascular area and vessel caliber. Here, the authors report a case of improvement in corneal NV with subconjunctival and intrastromal ranibizumab injections, which was previously refractory to bevacizumab injection. The findings may suggest a new prospect in treating corneal NV.
Adult ; Angiogenesis Inhibitors/administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Conjunctiva/blood supply ; Corneal Neovascularization/*drug therapy ; Corneal Stroma/blood supply ; Female ; Humans ; Injections, Intraocular/methods ; Keratitis, Herpetic/*drug therapy ; Visual Acuity/drug effects

PURPOSE: To compare the short term effects of bevacizumab and ranibizumab injections on the regression of corneal neovascularization (NV). METHODS: Sixteen eyes of 16 patients with corneal NV were randomly assigned for an injection with 2.5 mg of bevacizumab (group 1, n = 8) or 1 mg of ranibizumab (group 2, n = 8) through subconjunctival and intrastromal routes. The patients were prospectively followed-up for one month after the injections. Corneal NV areas, as shown on corneal slit-lamp photographs stored in JPEG format, were calculated using Image J software before the injection, one week after the injection, and one month after the injection. The corneal NV areas were compared before and after the injections. RESULTS: Seven women and nine men, with an average age of 51 years, presented with corneal NV secondary to herpetic keratitis (7 cases), graft rejection (6), chemical burn (1), pemphigoid (1), and recurrent ulcer (1). In group I, the preoperative corneal NV area (8.75 +/- 4.33%) was significantly decreased to 5.62 +/- 3.86% one week after the injection and to 6.35 +/- 3.02% one month after the injection (p = 0.012, 0.012, respectively). The corneal NV area in group 2 also exhibited a significant change, from 7.37 +/- 4.33% to 6.72 +/- 4.16% one week after the injection (p = 0.012). However, no significant change was observed one month after the injection. The mean decrease in corneal NV area one month after injection in group 1 (28.4 +/- 9.01%) was significantly higher than in group 2 (4.51 +/- 11.64%, p = 0.001). CONCLUSIONS: Bevacizumab injection resulted in a more effective and stable regression of corneal NV compared to the ranibizumab injection. The potency and dose of these two drugs for the regression of corneal NV require further investigation.
Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*therapeutic use ; Antibodies, Monoclonal, Humanized/*therapeutic use ; Corneal Neovascularization/*drug therapy ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy of epigallocatechin gallate (EGCG) in treatment of corneal alkali burn injury in mice.

METHODSCorneal alkali burn injury was induced by sodium hydroxide method in C57BL/6J mice. The mice with cornea burns were treated intraperitoneally with EGCG solution or phosphate buffer solution (PBS) respectively. The healing of corneal epithelium, the formation of corneal neovascularization (CNV) and the inflammation reaction were assessed by slit -lamp microscopy and histological examination. Expression of vascular endothelial growth factor (VEGF) mRNA and protein in cornea was evaluated by real -time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Myeloperoxidase (MPO) assay was used to quantitatively evaluate the polymorphonuclear neutrophils (PMNs) infiltration in the corneas.

RESULTSThe healing rate of corneal epithelium in EGCG group was significantly higher than that of PBS group at d1, d3 and d7 after treatment (d1: 41.0%±13.0% vs 23.8%±7.6%; d3: 76.6%±7.5% vs 61.2%±6.8%; d7: 87.8%±8.5% vs 74.0%±9.1%; all P <0.05). The CNV scores and the number of CNV in the corneal sections of EGCG group were significantly lower than those of PBS group at d3, d7 and d14 after treatment (CNV score: d3: 1.1±0.5 vs 6.6±1.0; d7: 1.3±0. 3 vs 8.1±1.0; d14: 0.9±0.2 vs 9.2±1.1; CNV number: d3: 1.68±0.61 vs 2.92±0.95; d7: 4.80±1.36 vs 7.92±1.28; d14: 3.64±0.71 vs 5.88±0.76; all P<0.05) . The expression of VEGF protein at d3 (0.19±0.05 vs 0.45±0.08) and d7 (0.42±0.07 vs 0.84±0.09), the expression of VEGF mRNA at d1, d3 and d7 in EGCG group were significantly lower than those in PBS group (all P <0.05). Compared to PBS group, the inflammatory index at d3 (3.2±0.4 vs 3.7±0.5) and d7 (2.3±0.5 vs 4.0±0.0), the number of PMNs in the corneal sections and the MPO values at d3, d7 and d14 in EGCG group were significantly decreased (PMNs: d3: 34.5±15.7 vs 90.0±28.8; d7: 17.1±11.4 vs 54.9±25.9; d14: 12. 8±4.6 vs 39.0±17.9; all P <0.05).

CONCLUSIONIn the murine corneal alkali burn model, intraperitoneal injection of EGCG solution can promote the healing of corneal epithelium, inhibit the formation of CNV and reduce the inflammatory cell infiltration in the corneas.

Alkalies ; Animals ; Burns, Chemical ; drug therapy ; Catechin ; analogs & derivatives ; therapeutic use ; Cornea ; drug effects ; pathology ; Corneal Neovascularization ; prevention & control ; Disease Models, Animal ; Eye Burns ; drug therapy ; Inflammation ; drug therapy ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophils ; cytology ; RNA, Messenger ; Vascular Endothelial Growth Factor A ; metabolism

The purpose of this study was to determine whether rapamycin could inhibit corneal angiogenesis induced by basic fibroblast growth factor (bFGF). Using human dermal microvascular endothelial cells (HDMECs), we examined the effect of rapamycin on cell proliferation and migration, and the expression of vascular endothelial growth factor (VEGF). The rabbit's eye was implanted intrastromally into the superior cornea with pellet containing bFGF for the control group and pellet containing bFGF and rapamycin for the rapamycin group. Biomicrographically, corneal angiogenesis was evaluated for 10 days after pellet implantation. The neovascularized cornea also was examined histologically. bFGF induced corneal neovascularization was significantly reduced by treatment with rapamycin. Using in vitro model, rapamycin strongly inhibited bFGF induced proliferation, migration, and VEGF secretion of HDMECs. We could observe that the bFGF induced corneal angiogenesis was inhibited by rapamycin in a micropocket rabbit model. The score of neovascularization was significantly decreased in the rapamycin group than in the control group at 10 days after pellet implantation. Histologically, the cornea of rapamycin group also showed much less new vessels than that of control group. Collectively, rapamycin appears to inhibit bFGF induced angiogenesis in a rabbit corneal micropocket assay and may have therapeutic potential as an antiangiogenic agent.
Vascular Endothelial Growth Factor A/biosynthesis ; Sirolimus/pharmacokinetics/*pharmacology ; Rabbits ; Humans ; Fibroblast Growth Factor 2/pharmacokinetics/pharmacology ; Female ; Endothelial Cells/cytology/drug effects/metabolism ; Drug Implants ; Dose-Response Relationship, Drug ; Corneal Neovascularization/*drug therapy/pathology ; Cells, Cultured ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Animals ; Angiogenesis Inhibitors/pharmacokinetics/*pharmacology

PURPOSE: To determine the efficacy of topical application and subconjunctival injection of bevacizumab in the treatment of corneal neovascularization. METHODS: Corneal neovascularization was induced with a silk suture of the corneal stroma in 12 rabbits (24 eyes). One week after suturing, four rabbits were treated with topical bevacizumab at 5 mg/mL (group A) and another four rabbits were treated with topical bevacizumab 10 mg/mL (group B) in the right eyes twice a day for two weeks. A subconjunctival injection of bevacizumab 1.25 mg/mL was done in the right eyes of four rabbits (group C). All of the left eyes (12 eyes) were used as controls. The area of corneal neovascularization was measured after one and two weeks, and the concentration of vascular endothelial growth factor (VEGF) in corneal tissue was measured after two weeks. RESULTS: The neovascularized area was smaller in all treated groups than in the control group (p<0.001). Upon analysis of the neovascularized area, there was no significant difference between groups A and B. However, the mean neovascularized area of group B was significantly smaller than that of group C after two weeks of treatment (p=0.043). The histologic examination revealed fewer new corneal vessels in all treated groups than the control group. The concentration of VEGF was significantly lower in all treated groups compared to the control group (p<0.01), but no difference was shown between treated groups. CONCLUSIONS: Topical and subconjunctival bevacizumab application may be useful in the treatment of corneal neovascularization and further study is necessary.
Angiogenesis Inhibitors/*administration & dosage ; Animals ; Antibodies, Monoclonal/*administration & dosage ; Cornea/metabolism/*pathology ; Corneal Neovascularization/*drug therapy/metabolism/pathology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Male ; Ophthalmic Solutions ; Rabbits ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism

PURPOSE: To evaluate factors that can influence the prevalence of amblyopia in children with anisometropia. METHODS: We retrospectively reviewed the records of 63 children 2 to 13 years of age who had anisometropic amblyopia with a difference in the refractive errors between the eyes of at least two diopters (D). The type of anisometropia (myopia, hyperopia, and astigmatism), degree of anisometropia (<2-3 D, <3-4 D, or >4 D), best corrected visual acuity (BCVA) of the amblyopic eye at the time of initial examination, BCVA differences between sound and amblyopic eyes, whether or not occlusion therapy was performed, compliance with occlusion therapy, and the patient's age when eyeglasses were first worn were investigated. RESULTS: There was an increase in the risk of amblyopia with increased magnitude of anisometropia (p=0.021). The prevalence of amblyopia was higher in the BCVA <20/40 group and in patients with BCVA differences >4 lines between sound and amblyopic eyes (p=0.008 and p=0.045, respectively). There was no statistical relationship between the prevalence of amblyopia and the type of anisometropia or the age when eyeglasses were first worn. Poor compliance with occlusion therapy was less likely to achieve successful outcome (p=0.015). CONCLUSIONS: Eyes with poor initial visual acuities of <20/40, a high magnitude of anisometropia, and a >4 line difference in the BCVA between sound and amblyopic eyes at the initial visit may require active treatment.
Angiogenesis Inhibitors/*administration & dosage ; Animals ; Antibodies, Monoclonal/*administration & dosage ; Cornea/metabolism/*pathology ; Corneal Neovascularization/*drug therapy/metabolism/pathology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Male ; Ophthalmic Solutions ; Rabbits ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism