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.

These experiments show the ability of these new techniques for determining tear volume and estimating tear osmolarity in mice. By mimicking the findings of human dry eye disease, these findings validate the relevance of the mouse model for studying the pathogenesis of human keratoconjunctivitis sicca.

ObjectiveTo report the incidence of endophthalmitis, in addition to its clinical and microbiological aspects, after intravitreal injection of vascular-targeting agents.MethodsA retrospective review of a consecutive series of 10,142 intravitreal injections of vascular targeting agents (bevacizumab, ranibizumab, triamcinolone acetonide, and preservative-free triamcinolone acetonide) between June 1, 2007 and January 31, 2010, performed by a single service (TGM) at the Bascom Palmer Eye Institute.ResultsOne case of clinically-suspected endophthalmitis was identified out of a total of 10,142 injections (0.009%), presenting within three days of injection of bevacizumab. The case was culture-positive for Staphylococcus epidermidis. Final visual acuity was 20/40 after pars plana vitrectomy surgery.ConclusionsIn this series, the incidence of culture-positive endophthalmitis after intravitreal injection of vascular agents in an outpatient setting was very low. We believe that following a standardized injection protocol, adherence to sterile techniques and proper patient follow-up are determining factors for low incidence rates.

Another aspect of NVG prevention is represented by treating the patients with central/hemi-CRVOs in whom ocular neovascularization already has appeared but IOP still remains within normal limits (eg, the preglaucomatous stage of NVG 2 ). In such cases we administer IVB injections, topical steroids, and cycloplegics; unless the neovascularization subsides with these treatments, we promptly apply panretinal photocoagulation that may prevent or delay any developing of the intractable sightthreatening NVG.In conclusion, we believe that at a dose of 2.5 mg injected promptly before occurrence of neovascularization and IOP elevation, IVB offers a real benefit and promise for the prevention of NVG in patients with acute central/hemi-CRVOs. Early diagnosis and treatment with bevacizumab are required in order to maintain a good visual status and a satisfactory IOP control. Conflict of interestThe authors declare no conflict of interest. Author contributionsBoth authors (DC and MC) were involved in design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript.

Age-related macular degeneration (AMD) is a progressive disease of photoreceptors and retinal pigment epithelium (RPE). Geographic atrophy (GA) is initiated by dysfunction and loss of RPE cells followed by photoreceptor loss. Thus, replacing lost and sick RPE with healthy cells may restore vision in GA. Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) are two main sources for this replacement. There are currently two major approaches to RPE stem cell integration with the human retina. The first employs bolus injections of RPE cell suspension under the retina and the second relies on prefabricated RPE stem cell sheets implanted in the subretinal space. Due to immune considerations, current hESC-RPE trials use immunosuppressant medications for a limited period up to, during, and after implantation. RPE stem cell grafts show great promise in restoring vision in patients with geographic atrophy due to AMD, as limited clinical trials in humans have already shown positive results, and more results are forthcoming.