Differential effects of dexamethasone and indomethacin on Tenon's capsule fibroblasts: Implications for glaucoma surgery.

Dysregulated wound healing and subsequent fibrosis represents the most common cause of failure in glaucoma filtration surgery. Primary means to prevent this outcome are the anti-metabolite surgical adjuvants, however, topical corticosteroids are commonly used postoperatively to permit further control of wound healing and development of the filtration bleb. Unfortunately, they carry important side effects such as raised intraocular pressure, cataract and increased infection risk. Non-steroidal anti-inflammatory drugs (NSAIDs) show promising results in clinical trials as an alternative wound modulatory drug. NSAIDs exhibit non-inferiority to steroids in terms of post-operative intraocular pressure control and secondary IOP lowering interventions, however there is little known about the differing effects these drugs exert on human Tenon's capsule fibroblast (HTCF) mediated wound healing. The purpose of this study was to assess the individual effects of dexamethasone and indomethacin on the extracellular matrix modifying actions of HTCFs in vitro. To this end, HTCFs were cultured in 3D collagen matrices as well as in 2D monolayers and exposed to clinically relevant concentrations of dexamethasone or indomethacin for up to seven days. HTCF-mediated wound healing functions were assayed through collagen matrix contraction, extracellular matrix morphology, estimation of HCTF proliferation and differentiation into myofibroblasts within the collagen matrices, as well as western blot. Both drugs significantly reduced HTCF-mediated collagen contraction relative to control however there was a significant trend towards greater inhibition with indomethacin exposure compared to dexamethasone. Indomethacin exposure significantly reduced HTCF-mediated collagen remodelling activity compared vehicle control, whereas dexamethasone was unable to reduce remodelling activity at any of the studied exposures. Both drugs reduced myofibroblast differentiation, however indomethacin alone demonstrated an inhibitory effect on final cell number relative to control whereas dexamethasone had no significant effect at any studied exposure. These findings demonstrate that both steroidal and NSAID treatment can mitigate HTCF-mediated collagen contraction and αSMA expression. However, NSAIDs may function to better impede HTCF proliferation and remodelling activity. Taken in the context of previous glaucoma surgical trials, NSAIDs appear to be a viable alternative to steroids for post-operative wound modulation.

Working under Pressure: Scleroderma Presenting with Bilateral Exudative Retinal Detachment in the Context of Scleroderma Renal Crisis: A Case Report.

This is an observational case report to detail a novel case of scleroderma renal crisis presenting as bilateral exudative retinal detachments in a patient with newly diagnosed systemic sclerosis. An otherwise healthy 58-year-old female presented primarily with vision complaints and was found to have malignant hypertension (230/120 mm Hg) and bilateral exudative retinal detachment on dilated fundus examination and macular OCT scan. Further history revealed sclerodactyly, mild dysphagia, and dyspnea. She was diagnosed with diffuse systemic sclerosis and Sjogren's syndrome complicated by an episode of scleroderma renal crisis based on initial medical workup. She was admitted to intensive care for management of refractory hypertension with IV antihypertensive therapy. Three months after treatment, her visual symptoms and ocular findings resolved. The presence of exudative retinal detachment among other signs of hypertensive retinopathy warrants thorough systemic screening for underlying causes of malignant hypertension, including systemic sclerosis. Treatment of the underlying disease with urgent antihypertensive therapy resolved the exudative retinal detachments and restored vision in the case of a scleroderma renal crisis.

Orbital Edema Secondary to a Sphenoidal Mass as the Presenting Symptom of High-Risk Precursor B-Cell Acute Lymphoblastic Leukemia.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, known to present with ocular manifestations in rare cases. Case Presentation: We describe the case of a 9-year-old previously healthy male who developed a 2-day history of periocular swelling and was found on MRI to have a large sphenoidal mass. Further work up showed involvement of the spinal cord, iliac crests, and kidneys. His initial blood work showed no hematological abnormalities. A bone marrow biopsy taken from the iliac crest demonstrated >90% B lymphoblasts and flow cytometry was positive for CD19. Overall, his investigations were consistent with a diagnosis of precursor B-cell ALL (pre B-ALL). His neuro-ophthalmic exam showed right-sided subtle periocular edema, decreased palpebral fissure height, and proptosis. Posterior exam showed mild nasal elevation of the right optic disc without vessel obscuration and mild tortuosity of the peripheral vessels. He otherwise had no overt signs of afferent or efferent dysfunction despite the proximity of the mass to his optic nerve and globe. Conclusion: This case demonstrates that high-risk pre B-ALL, a childhood cancer not commonly associated with orbital manifestations, can present with orbital edema and normal leukocyte count in an otherwise healthy child.

The Pro-Fibrotic Behavior of Human Tenon's Capsule Fibroblasts in Medically Treated Glaucoma Patients.

PURPOSE: The aim of this study was to compare human Tenon's capsule fibroblasts (HTCFs) obtained from patients who received medical therapy for glaucoma (glaucomatous patients) and patients not treated for glaucoma (non-glaucomatous patients) in terms of wound healing and fibrosis. PATIENTS AND METHODS: Bioartificial tissues (BATs) were generated using primary HTCF-populated collagen lattices. Pro-fibrotic gene expression within HTCFs was compared between glaucomatous patients and non-glaucomatous patients after BAT culture. The BATs were also assessed regarding fibroblast-myofibroblast transition, collagen remodeling and collagen contraction using alpha-smooth muscle actin immunohistochemistry, picrosirius red staining and collagen contraction assays, respectively. RESULTS: Pro-fibrotic gene expression in BAT-cultured HTCFs derived from glaucomatous patients was significantly increased compared to non-glaucomatous patients. BATs imbued with HTCFs collected from glaucomatous patients exhibited a greater proportion of myofibroblasts as well as increased collagen contraction/remodeling compared to HTCFs isolated from non-glaucomatous patients. CONCLUSION: HTCFs from glaucomatous and non-glaucomatous patients differ in the expression of genes involved in fibrosis, proportion of fibroblasts undergoing transdifferentiation into myofibroblasts, contractile properties and collagen remodeling. These results suggest that for any number of reasons, at a cellular level, patients who received medical therapy for glaucoma have eyes primed for fibrosis.