Neurotrophic keratitis: inflammatory pathogenesis and novel therapies.

PURPOSE OF REVIEW: Neurotrophic keratitis is a rare degenerative disease characterized by decrease or absence of corneal sensation. Neurotrophic keratitis varies from mild forms with mild epitheliopathy to severe manifestations such as corneal ulceration, melting and perforation that can lead to irreversible visual loss. The cause of neurotrophic keratitis comprises a long list of diseases, medications, congenital or genetic conditions as well as trauma. The mechanism of neurotrophic keratitis is complex and multifactorial and its understanding is crucial to better address the treatment strategies. We aimed to review neurotrophic keratitis pathology, mechanisms and management. RECENT FINDINGS: Corneal nerves are critical for the homeostasis of a healthy ocular surface. The lack of nerve-derived neuromediators and corneal-released neuropeptides, neuro-trophins and neurotrophic factors in neurotrophic keratitis leads to a decrease in trophic supply to corneal cells in addition to a decrease in afferent signaling to the brain. This results in pathological tear secretion, decreased blinking rate, corneal healing along with ocular surface and corneal inflammation. Lately, nerve growth factor in special gained emphasis as a treatment strategy targeting the disease mechanism rather than its manifestations. Other therapies, including surgical interventions, are in the pipeline of neurotrophic keratitis management. However, there are still no proper therapeutic guidelines and neurotrophic keratitis treatment remains challenging. SUMMARY: Neurotrophic keratitis may have a devastating outcome and treatment is still challenging. Understanding the disease pathology may assist in the development of new treatment strategies. Prompt disease recognition and immediate intervention are key factors to promote corneal healing and avoid further deterioration.

Dual inhibition of complement component 5 and leukotriene B4 by topical rVA576 in atopic keratoconjunctivis: TRACKER phase 1 clinical trial results.

PURPOSE: To evaluate the safety and preliminary efficacy of topical rVA576, a dual inhibitor of complement component 5 (C5) and leukotriene B4 (LTB4), in patients with recalcitrant atopic keratoconjunctivitis (AKC) in the open label phase 1 TRACKER clinical trial. METHODS: Three patients diagnosed with moderate or severe AKC who had been on maximal topical treatment (antihistamines and ciclosporin) for at least three months prior to entry, and showed persistent symptoms and signs of inflammation, were recruited into the trial. Patients received rVA576 eye drops twice a day for 8 weeks. Patients were seen at baseline and weeks 1, 2, 4, 6 and 8. Safety data was recorded and a composite sum score of symptoms and signs was obtained. This score comprised symptoms such as itching, mucous discharge and photophobia, and conjunctival and corneal signs such as hyperemia, tarsal papillae, punctate keratitis and corneal neovascularization, all rated individually from 0 to 3 for a maximum score of 33. RESULTS: Two of the three patients completed the initial open label phase of the trial. The third patient was unable to attend appointments and terminated the study early at day 14. Topical rVA576 was well tolerated with no serious adverse events reported. There was an average improvement in overall clinical score of 53%, composed of an improvement in symptoms of 65% [63.64-66.67%] and signs of 40% [40-40.12%] by day 56. CONCLUSIONS: In this open label phase 1 TRACKER trial, rVA576 eye drops were well tolerated and showed a response across signs and symptoms of active inflammation. This study is exploratory but supports topical rVA576 safety and shows promising efficacy for recalcitrant AKC. A phase 2 randomised control trial is currently underway.

Management and Systemic Implications of Diabetic Neovascular Glaucoma.

OBJECTIVES: To study the efficacy and safety of different treatments for diabetic neovascular glaucoma (NVG). We additionally attempt to determine if the presence of NVG could be a predictor of cardiovascular disease or death. METHOD: This is a retrospective, observational cohort study including patients diagnosed with diabetic NVG from 2006 to 2016 at the Hospital Clínico Universitario de Valladolid (Spain). Extracted data included clinical characteristics of the patients, glycated haemoglobin levels, and ocular treatment. Visual acuity (VA), intraocular pressure (IOP), cardiovascular events, and deaths were registered. RESULTS: 30 eyes from 23 patients were followed for a mean of 4.48 years (SD = 2.82 years). The IOP-lowering intervention groups were: Ahmed implant (11 eyes), laser cyclo-photocoagulation (CPC; 6 eyes), both (4 eyes), or none (9 eyes). IOP success was achieved in 100% of the eyes with Ahmed and/or laser CPC and in 44.4% of the eyes with no IOP-lowering procedure (p= 0.002). Most eyes with Ahmed implant (with or without CPC) maintained or improved their VA (100 and 63.6%, respectively). 33.3% of the eyes with laser CPC and 25% of those with no IOP-lowering intervention maintained or improved their VA (p = 0.028). Hypotony was the only adverse effect (after laser CPC). No statistically significant difference could be established between low VA (finger count or worse), poor IOP control, or bad metabolic control and mortality or cardiovascular event (p > 0.05), however, the four patients who died had poor VA at the time of NVG diagnosis. CONCLUSIONS: Ahmed implant surgery is a safe and effective treatment option for diabetic NVG. Medical treatment alone is not the best option for most cases. Advanced NVG could be an indicator of higher mortality risk in diabetic patients.

Black and white box: Take good gross pathology photographs.

Macroscopic study of surgical samples sent to the histopathology lab provides the first diagnostic approach. Obtaining quality photographs of these pieces facilitates proper case documentation for publication, sharing, teaching and research.This device has been originally designed for enucleated eyes but it could be used for a wide diversity of human or animal samples including thyroids, pituitary glands, prostates… It can be coupled to any smartphone camera.The Black and White Box is an affordable and easy option for taking gross pathology photographs of high quality. In this work we provide full instructions on how to make it.

Glue and glide: a novel technique for pterygium conjunctival autograft.

Conjunctival autograft adhesion with fibrin glue has gained rapid popularity in pterygium excision surgery and is now the technique of choice in many centers worldwide. It has enabled a suture-free technique, reducing surgical time and postoperative pain. However, the adhesive's components form a fibrin clot 10 seconds after mixing, and in this time, the surgeon must complete glue application, grabbing of the instruments and adequate placement of the conjunctival patch. This easy and new technique explains how separate application of glue components on the receiving site and cornea with subsequent sliding of graft results in even mixing of the components on site. It enables the surgeon to spend all 10 seconds in adjusting the position of the conjunctival autograft, resulting in an easier and more precise surgery.

Pattern of Local Recurrence After I-125 Episcleral Brachytherapy for Uveal Melanoma in a Spanish Referral Ocular Oncology Unit.

PURPOSE: To describe the time, frequency, and clinical characteristics of treatment failure after I-125 brachytherapy in patients with uveal melanoma treated and followed in a Spanish referral ocular oncology unit. DESIGN: Prospective, consecutive, interventional case series. METHODS: Patients diagnosed with uveal melanoma from 1995 to 2016 and treated with episcleral brachytherapy were included. Demographic data collection, ophthalmic evaluation, ultrasound scan, and systemic studies were performed at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Recurrence was defined as presence of tumor growth after treatment. Baseline analysis was performed by descriptive methods and survival by Kaplan-Meier curves. RESULTS: From 732 patients diagnosed with uveal melanoma, 311 were treated with brachytherapy. In the follow-up (mean 79 months, standard deviation = 55), 16 local tumor recurrences (5.1%) were detected. All relapsing patients had choroidal tumors and 15 presented with visual symptoms. All patients were treated with I-125 brachytherapy, and 2 received associated transpupillary thermotherapy. All the eyes were enucleated after recurrence. Kaplan-Meier analysis showed a mean time of recurrence of 3.7 years (standard deviation = 2.94 years, ranging from 1 to 12 years). Three patients had metastasis in the follow-up. Kaplan-Meier analysis showed worse survival for patients with recurrence. CONCLUSION: Local treatment failure was a relatively infrequent event after I-125 brachytherapy in our series. Recurrences appear not only early but also late in the follow-up. They do not have a distinctive clinical pattern and are associated with poorer survival.