Corneal Toxicity Secondary to Latex From Asclepias curassavica in a Pediatric Patient.

PURPOSE: To report a case of corneal milkweed toxicity on the corneal endothelium with epithelial damage in a pediatric patient. METHODS: We report a case of a 13-year-old boy who presented to the emergency department with complaints of left eye pain and photophobia after direct corneal exposure to milkweed latex. He was found to have a large corneal epithelial defect and diffuse stromal edema suspected to be secondary to the cardiac glycosides present in the milkweed plant. Clinical examination and course are reported. RESULTS: The patient was seen in the outpatient clinic on multiple visits. His epithelial defect had resolved within 3 days, and all corneal damage had healed within 18 days from injury. He was treated with antibiotic and steroid eye drops. CONCLUSIONS: Corneal exposure to cardiac glycosides from milkweed plants is known to damage the endothelial sodium-potassium pumps and to cause corneal edema and decreased visual acuity. All previously documented case reports of corneal milkweed toxicity are secondary to indirect exposure to the plant's latex. Here, we report the first case of corneal endothelial toxicity because of direct latex inoculation from an Asclepias plant and the first such toxicity reported in a pediatric patient.

Bilateral anterior segment dysgenesis and persistent fetal vasculature associated with terminal 10q26 deletion.

Deletion of the 26q position on chromosome 10 results in a syndrome with well-documented systemic phenotypes. There are few reports of ophthalmic manifestations in terminal 10q26 deletion. We report a 4-week-old boy with terminal 10q26 deletion who had extensive ophthalmic abnormalities, including bilateral anterior segment dysgenesis and bilateral persistent fetal vasculature, with microphthalmia, microcornea, iris corectopia, congenital cataracts, and posterior embryotoxon.

Diacerein Alone and in Combination with Infliximab Suppresses the Combined Proinflammatory Effects of IL-17A, IL-22, Oncostatin M, IL-1A, and TNF-alpha in Keratinocytes: A Potential Therapeutic Option in Psoriasis.

Psoriasis is a chronic disorder characterized by a complex interplay between keratinocytes and inflammatory mediators. In a previous study, we evaluated diacerein's ability to diminish interleukin (IL)-1's proinflammatory effects on cultured primary human keratinocytes. In this study, we evaluated diacerein's ability to diminish the inflammatory effects of a cytokine mixture (CM) consisting of IL-17A, IL-22, oncostatin M, IL-1A, and tumor necrosis factor (TNF)-alpha on cultured primary human keratinocytes. These five cytokines have been previously shown to induce an in vivo-equivalent cell culture psoriasis model. We also evaluated diacerein's anti-inflammatory effects in comparison to and in combination with infliximab, a TNF-alpha inhibitor currently used in the treatment of psoriasis. We found 81 genes that were significantly (P < 0.05) dysregulated by CM compared to medium control. All three treatment groups (diacerein alone, infliximab alone, and diacerein plus infliximab) diminished the effects of CM on these genes, with the greatest effect seen with diacerein plus infliximab. Using enzyme-linked immunosorbent assay method on cell culture supernatant, we determined the protein concentration for five genes (IL-19, IL-6, CSF3, S100A8, and NAP-2) significantly (P < 0.05) upregulated by CM at the gene level. Diacerein alone diminished the effect of CM on the protein concentration of two genes, whereas diacerein plus infliximab diminished the effect of CM on the protein concentration of all the five genes. Based on these results, we conclude that diacerein alone or in combination with infliximab may have a therapeutic role in psoriasis by downregulating key inflammatory mediators.

COMMUNITY-ASSOCIATED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS SUBRETINAL ABSCESS IN A NONBACTEREMIC PATIENT TREATED WITH INTERNAL DRAINAGE AND RETINECTOMY.

PURPOSE: To report a case of community-associated methicillin-resistant Staphylococcus aureus subretinal abscess that continued to progress, despite intravitreal and systemic antibiotic therapy. METHODS: Retrospective chart review of a 77-year-old female patient with well-controlled diabetes mellitus who developed a left eye endophthalmitis and subretinal abscess from methicillin-resistant S. aureus colonization in the absence of any systemic focus of infection. RESULTS: The abscess and endophthalmitis resolved after the second pars plana vitrectomy that included drainage of a subretinal abscess after the failure of initial pars plana vitrectomy, and intravitreal and systemic antibiotics. Retinal detachment due to proliferative vitreoretinopathy necessitated the third pars plana vitrectomy 2 weeks after the second pars plana vitrectomy. CONCLUSION: The authors present an unusual case of methicillin-resistant S. aureus subretinal abscess in a patient with methicillin-resistant S. aureus colonization with negative blood, aqueous humor culture, and vitreous culture but a positive culture from subretinal aspirate.

Recurrent Vitreous Hemorrhage from an Optic Nerve Retinal Arterial Macroaneurysm.

OBJECTIVE: To report a case of recurrent vitreous hemorrhage from an optic nerve retinal arterial macroaneurysm (ONRAM) successfully treated with intraoperative endolaser. PATIENT AND METHODS: A 92-year-old woman on oral aspirin and warfarin anticoagulation for atrial fibrillation developed three episodes of dense vitreous hemorrhage from an ONRAM. Due to failure of the vitreous hemorrhage to clear spontaneously, a total of three pars plana vitrectomy (PPV) procedures were performed along with a 1.25-mg intravitreal bevacizumab injection after the third episode of hemorrhage. During the third PPV procedure, a 25-gauge 532-nm green diode laser endoprobe was used to deliver low-power (100 mW) and long-duration (500 ms) laser spots directly on the ONRAM to induce intraoperative shrinkage of the ONRAM. RESULTS: After the endolaser treatment, the macroaneurysm showed involution due to fibrosis without any adverse effects on retinal circulation or visual field defect. No recurrence of vitreous hemorrhage was noted after 2 years of follow-up. CONCLUSION: Oral anticoagulant use may have been responsible for the atypical clinical course in our patient. Laser photocoagulation, including intraoperative endolaser photocoagulation, may be considered in selected cases of symptomatic ONRAMs.

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions.

A major focus of cancer research for several decades has been understand the ability of tumors to induce new blood vessel formation, a process known as angiogenesis. Unfortunately, only limited success has been achieved in the clinical application of angiogenesis inhibitors. We now know that lymphangiogenesis, the growth of lymphatic vessels, likely also plays a major role in tumor progression. Thus, therapeutic strategies targeting lymphangiogenesis or both lymphangiogenesis and angiogenesis may represent promising approaches for treating cancer and other diseases. Importantly, research progress toward understanding lymphangiogenesis is significantly behind that related to angiogenesis. A PubMed search of "angiogenesis" returns nearly 80,000 articles, whereas a search of "lymphangiogenesis" returns 2,635 articles. This stark contrast can be explained by the lack of molecular markers for identifying the invisible lymphatic vasculature that persisted until less than 2 decades ago, combined with the intensity of research interest in angiogenesis during the past half century. Still, significant strides have been made in developing strategies to modulate lymphangiogenesis, largely using ocular disease models. Here we review the current knowledge of lymphangiogenesis in the context of knockout models, ocular diseases, the biology of activators and inhibitors, and the potential for therapeutic interventions targeting this process.

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications.

BACKGROUND: Angiogenesis is the process of neovascularization from pre-existing vasculature and is involved in various physiological and pathological processes. Inhibitors of angiogenesis, administered either as individual drugs or in combination with other chemotherapy, have been shown to benefit patients with various cancers. Endostatin, a 20-kDa C-terminal fragment of type XVIII collagen, is one of the most potent inhibitors of angiogenesis. SCOPE OF REVIEW: We discuss the biology behind endostatin in the context of its endogenous production, the various receptors to which it binds, and the mechanisms by which it acts. We focus on its inhibitory role in angiogenesis, lymphangiogenesis, and cancer metastasis. We also present emerging clinical applications for endostatin and its potential as a therapeutic agent in the form a short peptide. MAJOR CONCLUSIONS: The delicate balance between pro- and anti-angiogenic factors can be modulated to result in physiological wound healing or pathological tumor metastasis. Research in the last decade has emphasized an emerging clinical potential for endostatin as a biomarker and as a therapeutic short peptide. Moreover, elevated or depressed endostatin levels in diseased states may help explain the pathophysiological mechanisms of the particular disease. GENERAL SIGNIFICANCE: Endostatin was once sought after as the 'be all and end all' for cancer treatment; however, research throughout the last decade has made it apparent that endostatin's effects are complex and involve multiple mechanisms. A better understanding of newly discovered mechanisms and clinical applications still has the potential to lead to future advances in the use of endostatin in the clinic.

Sustained ocular hypertension induces dendritic degeneration of mouse retinal ganglion cells that depends on cell type and location.

PURPOSE: Glaucoma is characterized by retinal ganglion cell (RGC) death and frequently associated with elevated IOP. How RGCs degenerate before death is little understood, so we sought to investigate RGC degeneration in a mouse model of ocular hypertension. METHODS: A laser-induced mouse model of chronic ocular hypertension mimicked human high-tension glaucoma. Immunohistochemistry was used to characterize overall RGC loss and an optomotor behavioral test to measure corresponding changes in visual capacity. Changes in RGC functional properties were characterized by a large-scale multielectrode array (MEA). The transgenic Thy-1-YFP mouse line, in which a small number of RGCs are labeled with yellow fluorescent protein (YFP), permitted investigation of whether subtypes of RGCs or RGCs from particular retinal areas were differentially vulnerable to elevated IOP. RESULTS: Sustained IOP elevation in mice was achieved by laser photocoagulation. We confirmed RGC loss and decreased visual acuity in ocular hypertensive mice. Furthermore, these mice had fewer visually responsive cells with smaller receptive field sizes compared to controls. We demonstrated that RGC dendritic shrinkage started from the vertical axis of hypertensive eyes and that mono-laminated ON cells were more susceptible to IOP elevation than bi-laminated ON-OFF cells. Moreover, a subgroup of ON RGCs labeled by the SMI-32 antibody exhibited significant dendritic atrophy in the superior quadrant of the hypertensive eyes. CONCLUSIONS: RGC degeneration depends on subtype and location in hypertensive eyes. This study introduces a valuable model to investigate how the structural and functional degeneration of RGCs leads to visual impairments.