Altered corneal epithelial barrier function is the cause for ocular irritation and visual morbidity in dry eye disease. Increased matrix metalloproteinase (MMP)-9 activity has been observed in the tear fluid of dry eye patients. To determine the pathogenic role of MMP-9 in the corneal epithelial disease of dry eye, the effects of experimentally induced dry eye on corneal epithelial morphology and barrier function were compared in MMP-9 knockout mice and their wild-type littermates. Dry eye was created through cholinergic blockade and exposure to a desiccating environment. The tear fluid MMP-9 concentration increased in response to dryness in wild-type mice. Corneal epithelial permeability to three different-sized molecules increased in dry eye wild-type mice, but not in MMP-9 knockout mice. Topical administration of active MMP-9 to dry eye MMP-9 knockout mice significantly increased corneal epithelial permeability. Compared to MMP-9 knockout mice, wild-type mice showed greater desquamation of differentiated apical corneal epithelial cells that expressed the tight junction protein occludin in response to dryness. This was accompanied by an increase in lower sized (50 kd) occludin in the corneal epithelia of wild-type mice. These findings could be replicated in cultured human corneal epithelial cells that were treated with active MMP-9. These studies indicate that increased MMP-9 activity on the ocular surface in response to dryness disrupts corneal epithelial barrier function. This appears to be because Corneal epithelial disease, termed keratitis sicca, is a severe and sight-threatening complication of dry eye. 1 A key clinical feature of keratitis sicca is disruption of corneal epithelial barrier function. [2][3][4] This results in eye irritation, corneal surface irregularity, blurred and fluctuating vision, and increased risk for corneal ulceration. 4 -8 Ocular surface inflammation has been implicated in the pathogenesis of keratitis sicca. Elevated levels of proinflammatory cytokines, such as interleukin (IL)-1, have been detected in the tear fluid of patients with this condition. 9 -11 Furthermore, the concentration and activity of matrix metalloproteinase (MMP)-9 in the tear fluid was found to be significantly increased in these eyes, with the highest concentrations observed in eyes with the severe corneal epithelial disease or sterile corneal ulcers. 10 -12 We hypothesize that MMP-9 plays an important role in the disruption of corneal epithelial barrier function in dry eye. We previously reported an experimental murine model of dry eye that disrupts corneal epithelial barrier function similar to human dry eye disease. 13 The purpose of this study was to compare the effects of experimentally induced dry eye (EIDE) on corneal epithelial morphology and barrier function in MMP-9 knockout mice and their wild-type (WT) littermates. Materials and Methods MiceThis research protocol was approved by the Baylor College of Medicine Center for Comparative Medicine and it conformed to the standards in the Association...

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Aims To compare the outcomes of neovascular glaucoma (NVG) treated with and without intravitreal bevacizumab in a large case comparison study. Methods The study is a retrospective, comparative, case series of 163 eyes of 151 patients with NVG, including 99 treated without and 64 treated with intravitreal bevacizumab. Medical and surgical treatments for NVG were assessed. The main outcome measures were visual acuity (VA) and intraocular pressure (IOP).Results At the time of NVG diagnosis, the median VA was count fingers (CF) in the non-bevacizumab group and 2/300 in the bevacizumab group. IOP (mean ± SD) was 43.1 ± 13.0 mm Hg in the non-bevacizumab group and 40.8 ± 11.5 mm Hg in the bevacizumab group. IOP (mean ± SD) decreased to 18.3 ± 13.8 mm Hg in the nonbevacizumab group and 15.3 ± 8.0 mm Hg in the bevacizumab group, and the median VA was CF in both treatment groups at a mean follow-up of 12 months. Panretinal photocoagulation (PRP) substantially reduced the need for glaucoma surgery (Po0.001) in bevacizumab treated NVG eyes. Conclusions Although bevacizumab delayed the need for glaucoma surgery, PRP was the most important factor that reduced the need for surgery. Vision and IOP in eyes with NVG treated with bevacizumab showed no long-term differences when compared with eyes that were not treated with bevacizumab. Thus, intravitreal bevacizumab serves as an effective temporizing treatment, but is not a replacement for close monitoring and definitive treatment of NVG. PRP remains the treatment modality that affects the course of NVG in terms of decreasing the need for surgery to control IOP.