First identification of the herpes simplex virus by skin-dedicated ex vivo fluorescence confocal microscopy during herpetic skin infections.

BACKGROUND: Skin-dedicated ex vivo fluorescence confocal microscopy (FCM) has so far been used to identify cutaneous tumours on freshly excised samples using acridine orange as fluorochrome. AIM: To use FCM for a new indication, namely, the identification of the herpes simplex virus (HSV) in skin lesions, using fluorescent antibodies. METHODS: Six roof samples from skin vesicles suspicious for HSV lesions were incubated with anti-HSV-1 and anti-HSV-2 antibodies coupled with fluorescein isothiocyanate, and examined under skin-dedicated ex vivo FCM. The positive controls were swabs taken from the floor of each vesicle and observed under conventional direct fluorescence assay (DFA) and by viral cultures. Roof samples from three bullae of bullous pemphigoid were the negative controls. RESULTS: Using ex vivo FCM, the samples from the lesions clinically suspicious for HSV infection were seen to be fluorescent after incubation with anti-HSV-1, and were negative after incubation with anti-HSV-2 antibodies. Conventional DFA with an optical microscope and cultures confirmed the presence of HSV-1 infection. CONCLUSIONS: By using fluorescent antibodies to identify precise structures, ex vivo FCM can be used for indications other than tumour identification. More specifically, it can be an additional diagnostic tool for HSV infection.

Efficacy and safety of intense pulsed light delivered by the C.STIM® for treatment of Meibomian gland dysfunction.

INTRODUCTION: Intense pulsed light (IPL) appears to be a promising treatment for Meibomian gland dysfunction (MGD), the most common cause of dry eye disease. C.STIM® is a new IPL device. We report the first safety and efficacy study in clinical practice. MATERIALS AND METHODS: Patients with moderate MGD treated with C.STIM® were included. Three IPL sessions were performed at D0, D15 and D45 with 4 shots per side (fluence of 8J/cm2). Clinical evaluation was performed at D0, D45 and M3 with several parameters: BUT, OSDI and Oxford scales, meibomian gland evaluation (morphology, quality and expressibility of meibum). The Lacrydiag® imaging device was used for objective evaluation of interferometry, meibography, tear meniscus height and NIBUT. The primary endpoint was the change in NIBUT between D0 and M3. Data collection was retrospective. Longitudinal analysis and a non-parametric linear mixed-effects model (R software) were used for statistical analysis. RESULTS: Thirty-five patients were included. NIBUT increased significantly between D0 and M3, with a mean difference of 2.6seconds (95% CI 2.0; 3.1, P<0.001). The other parameters studied also changed significantly, except for meibography (percentage of loss and morphology) and tear meniscus height. No adverse event was noted. CONCLUSION: C.STIM® appears safe and effective in the treatment of MGD, although a randomized controlled trial is needed to validate these results.

Poloxamines for deswelling of organ-cultured corneas.

BACKGROUND: Poloxamines are amphiphilic tetrofunctional block copolymers composed of four polyoxyethylene-polyoxypropylene arms joined to a central ethylene diamine bridge. Their safe profile allows diverse pharmaceutical and biomedical applications. AIM: To assess their use for corneal deswelling using a porcine model of organ culture (OC). METHODS: Five poloxamines (T90R4, T904, T908, T1107 and T1307) were dissolved in a standard commercial OC medium (control) to reach 350 mosm kg(-1). In vitro cytotoxicity was tested using MTT assay on human corneal epithelial and endothelial cell (EC) lines and on primary human corneal fibroblasts. Paired porcine corneas stored in OC for 3 days were assigned for 48 h to a poloxamine medium or to a standard deswelling medium containing 5% dextran T500. Corneal EC density, morphometry, mortality, stromal thickness and transparency were evaluated before and after deswelling. Post-deswelling, EC viability/mortality was determined using a fluorescent live/dead assay. RESULTS: Besides similar corneal thickness reduction and transparency improvement, T908, T1107 and T1307 decreased EC loss (5.4 ± 1.7% vs. 9.9 ± 2.6% in controls (p < 0.001)) and mortality, improved EC morphometry and reduced endothelial lesions compared to dextran. CONCLUSION: On this porcine model, poloxamines T908, T1107 and T1307 appear as good candidates to replace dextran for the deswelling. Experiments on human corneas are now necessary to confirm their efficiency and safety profile in OC.

Who first described Descemetorhexis without endothelial keratoplasty (DWEK) for the management of Fuchs' corneal endothelial dystrophy?

We present here in a historical focus on the first descriptions in the 1950's by Louis Paufique of Descemetorhexis without endothelial keratoplasty (DWEK) for the treatment of Fuchs' endothelial dystrophy. This article places the introduction of this surgical technique in the context of its time, describes its principles, and puts into perspective the place of this relevant treatment in the therapeutic arsenal of today and tomorrow.

[Corneal perforation with tyrosine kinase inhibitor chemotherapy: REGORAFENIB]. / Perforation cornéenne sous chimiothérapie inhibiteur des tyrosines kinases : REGORAFENIB.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) are active in a variety of metastatic cancers. They have a good general tolerance with mainly hepatic and dermatological side effects. Rarely, ophthalmologic side effects may occur: eyelash abnormalities, eyelids abnormalities, disorders of the ocular surface with ocular dryness or even corneal erosions that can even lead to perforation. Regorafenib is a new oral multi-targeted tyrosine kinase inhibitor that inhibits multiple protein kinases, including those involved in tumor angiogenesis, oncogenesis and tumor microenvironment. CASE DESCRIPTION: We describe, to the best of our knowledge, the first case of complicated bilateral ulcers of corneal perforation in a patient under REGORAFENIB. OBSERVATION: 20-year-old patient with metastatic chondrosarcomas of the pelvis, mandible and thorax received chemotherapy with REGORAFENIB. A few weeks after initiation of treatment, he experienced an increased dry eye syndrome associated with bilateral corneal ulcers complicated by perforation. Despite discontinuation of chemotherapy and maximal medical and surgical treatment (iterative amniotic membrane grafts and corneal transplantation), the progression was unfavorable. DISCUSSION: This is the first known case of corneal perforation under REGORAFENIB. The pathophysiology is multifactorial. On the one hand, this chemotherapy targets angiogenesis (VEGFR), oncogenesis (KIT, RET, RAF1, BRAF) and the tumor microenvironment (PDGFR, FGFR). On the other hand, other triggers are added, namely mixed dry eye syndrome, hypovitaminosis A (anorexia), the neurotrophic component, as well as the toxicity of chemotherapy via tears. CONCLUSION: First described case of corneal perforation under REGORAFENIB, non-regressive at the end of chemotherapy, and despite medical and surgical treatments. Ophthalmologic surveillance is therefore necessary for patients under chemotherapy with tyrosine kinase inhibitors, as serious ocular complications, especially corneal ones, may occur.

First identification of ITM2B interactome in the human retina.

Integral Membrane Protein 2 B (ITM2B) is a type II ubiquitous transmembrane protein which role remains unclear. ITM2B mutations have been associated with different disorders: mutations leading to longer mutant proteins have been reported in two distinct Alzheimer-like autosomal dominant disorders with early-onset progressive dementia and cerebellar ataxia. Both disorders share neurological features including severe cerebral amyloid angiopathy, non-neuritic plaques, and fibrillary tangles as in Alzheimer disease. Our group reported a missense mutation in ITM2B, in an unusual retinal dystrophy with no dementia. This finding suggests a specific role of ITM2B in the retina. As the identification of retinal-specific ITM2B partners could bring new insights into the cellular functions of ITM2B, we performed quantitative proteomics of ITM2B interactome of the human retina. Overall, 457 ITM2B partners were identified with 8 of them involved in visual transduction. In addition, bulk Gene Ontology analyses showed that many ITM2B partners are involved in several other biological functions, such as microtubule organization, protein translation and interestingly, mitochondrial homeostasis. These data represent the first report of the ITM2B interactome in the human retina and may serve as a valuable inventory of new potential ITM2B partners for future investigations of ITM2B physiological functions and dysfunctions.

[What will cataract surgery look like in the future? Alternatives in the pipeline]. / Que sera la chirurgie de la cataracte du futur ? Alternatives et voies de développement.

Phacoemulsification is the most frequently performed surgery in the world. Over the past few years, this surgery seems to have reached a plateau with no further innovative breakthroughs. In this paper, we focus on alternatives techniques, the latest innovations, and the research and development pipeline in this field.