[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.

A new set of reagents and related software used for NGS based classical and non-classical HLA typing showing evidence for a greater HLA haplotype diversity.

To evaluate the HLA typing performance of a new Long-Range PCR NGS set of reagents and its dedicated software, a panel of 41 reference homozygous cell lines from the International Histocompatibility Working Group (IHWG) and a panel of 376 volunteer bone marrow donors were analyzed for classical and non-classical HLA class I and class II genes. All results, except HLA-DPB1, were obtained without any ambiguities at the 3rd field level. Based on the high resolution performance of the reagents, a number of new alleles have been described not only for classical but also for non-classical HLA class I genes, leading to a more accurate haplotype definition. Linkage disequilibrium between HLA-A and HLA-G genes has been defined at 4th field level of resolution. Moreover, for the first time, HLA-DQA2 and DQB2 polymorphisms and their linkage disequilibrium with DQB1 were described.

Soft tissue sarcoma in children, adolescents and young adults: Outcomes according to compliance with international initial care guidelines.

BACKGROUND: Outcomes for adults with soft tissue sarcoma are better when managed at referral centers. Care guidelines advise for 5 main criteria: 1-Imaging before biopsy; 2-Tumor biopsy before surgery; 3-Multidiscipinary team discussion (MTD) before biopsy; 4-Biopsy in "expert centers"; 5-Somatic molecular biology feasible. The aim is to describe and assess the prognostic impact of initial management of STS according to the type of referring centers and the number of optimal criteria. METHODS: Monocentric retrospective analysis of the management of 127 youths (0-25 years) with localized STS treated from 2006 to 2015. RESULTS: Median age at diagnosis was 9.6 years (range: 025). Overall, only 41% patients had 5/5, 28% 3-4, 31% ≤2. No adequate imaging was performed before surgery/biopsy for 18% patients, no biopsy before treatment for 29%. Patients referred by "expert centers" had higher compliance to guidelines (P = 0.025). Upfront surgery was performed in 59/127 patients. Immediate re-operation was inversely related to the number of criteria (0% when 5 criteria vs. 14% for 3-4, 46% if ≤ 2; P < 0.001). For malignant tumors, outcome was better when 5 criteria were reached: 5 year EFS 90.8% (81.4-100.0%) vs. 71.6 for (60.4-84.9%; ≤4 criteria; p = 0.033), OS 93.6% (85.5-100%) vs. 79.5% (68.9-91.8%; p = 0.11), and LRFFS 90.6% (81.0-100.0) vs. 73.1% (62.0-86.3%; p = 0.047). CONCLUSION: Less than half of the youths with STS are initially managed according to international guidelines, highlighting the need for better information about optimal management. These results plead for immediate management in reference centers to reduce initial burden of therapy.

[Visual outcomes after Descemet's membrane endothelial keratoplasty]. / Étude de la réhabilitation visuelle après kératoplastie endothéliale manuelle.

OBJECTIVES: Evaluation and monitoring at 6 months after Descemet's membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy and study of factors influencing visual rehabilitation and postoperative quality of life. METHODS: Prospective, consecutive, interventional study of 35 eyes of 32 patients with Fuchs endothelial dystrophy who underwent surgery from February 2015 to February 2016 by DMEK. Measurement at D10, M1, M3, M6 of visual acuity, graft endothelial cell density, pachymetry, and intraocular pressure, and performance at M6 of aberrometry, macular OCT and a quality of life survey (NEI-VFQ-25). Post-DMEK aberrations are compared to those from control patients selected for refractive surgery. RESULTS: Visual acuity improvement at 6 months was statistically significant (P<0.0001), as well as pachymetry decrease (P<0.0001), endothelial cell loss (P<0.0001) and intraocular pressure increase (P=0.003). We observed a statistically significant difference between post-DMEK aberrations and those of control subjects for all aberrations from 2nd to 5th order. There were no postoperative correlations between visual acuity, pachymetry, intraocular pressure, or endothelial cell loss. The global quality of life score at six months was 87, corresponding to a good quality of life. We did not find a link between the global NEI-VFQ-25 score and visual acuity or visual aberrations. Ninety percent of patients surveyed reported a postoperative general improvement in quality of life at M6. CONCLUSION: DMEK provides good visual rehabilitation and an improvement in quality of life for patients with Fuchs endothelial dystrophy. Higher order optical aberrations in these patients, although higher than in a healthy population, are negligible and have no impact on quality of vision or postoperative quality of life.

Emergency Department care of childhood epistaxis.

OBJECTIVE: The aim of this review is to determine an efficient and safe primary strategy care for paediatric epistaxis. DATA SOURCES: We searched PubMed and Cochrane databases for studies referenced with key words 'epistaxis AND childhood'. This search yielded 32 research articles about primary care in childhood epistaxis (from 1989 to 2015). Bibliographic references found in these articles were also examined to identify pertinent literature. We compared our results to the specific management of adult epistaxis classically described in the literature. RESULTS: Epistaxis is one of the most common reasons for referral of children to a hospital ENT outpatient department. The bleeding usually originates from the anterior septum, as opposed to adults. Crusting, digital trauma, foreign bodies and nasal colonisation with Staphylococcus aureus have been suggested as specific nosebleed factors in children. Rare aetiologies as juvenile nasopharyngeal angiofibroma appear later during adolescence. There are different modes of management of mild epistaxis, which begin with clearing out blood clots and bidigital compression. An intranasal topical local anaesthetic and decongestant can be used over 6 years of age. In case of active bleeding, chemical cauterisation is preferred to anterior packing and electric cauterisation but is only feasible if the bleeding site is clearly visible. In case of non-active bleeding in children, and in those with recurrent idiopathic epistaxis, antiseptic cream is easy to apply and can avoid 'acrobatic' cauterisation liable to cause further nasal cavity trauma. CONCLUSIONS: Aetiologies and treatment vary with patient age and the existence or not of active bleeding at the time of the examination. Local treatments are usually easy to perform, but physicians have to ponder their indications depending on the possible complications in order to inform parents and to know paediatric epistaxis specificities.

[Femtosecond-assisted Ferrara intrastromal corneal ring implantation for treatment of keratoconus: Functional outcomes at one year]. / Anneaux intra-cornéens Ferrara implantés au laser femtoseconde dans le traitement du kératocône : résultats fonctionnels à 1 an.

INTRODUCTION: Intrastromal corneal rings (ICR) have been used for several years for the correction of irregular astigmatism in patients with keratoconus. OBJECTIVE: To evaluate the effectiveness of femtosecond-assisted ICR implantation for treatment of keratoconus and to define predictive factors of success. PATIENTS AND METHODS: We undertook a retrospective study of patients with keratoconus who underwent femtosecond-assisted Ferrara ICR implantation between December 2012 and May 2014 at the University Hospital of Besançon. To determinate predictive factors of success, we divided patients into 2 groups based on the gain of at least two lines of best corrected visual acuity (BCVA) at 1 year after surgery ("good responders") or the gain of only one line of BCVA, no change, or the loss of lines of BCVA ("poor responders"). For each group, we analyzed preoperative refractive and keratometric values. Moreover, to verify if preoperative visual acuity could be a predictive factor of success, four groups were created based on initial visual acuity, and postoperative BCVA was compared. RESULTS: We retrospectively studied 32 eyes of 29 patients with keratoconus who underwent femtosecond-assisted Ferrara ICR implantation between December 2012 and May 2014 at the University Hospital of Besançon. From one month to 1 year postoperatively, we observed a significant improvement in BCVA and a significant decrease in cylinder and keratometry values (P<0.05). In total, 90.6% of patients had an increase in visual acuity (VA) of at least one line within 1 year while 9.4% had a decrease or stability of their VA. The average cylinder value decreased from -4.81±2.45 diopters (D) preoperatively to -2.39±1.94 D (P<0.001) at 1 year postoperatively, and the average of the maximum keratometry from 51.14±3.89 D to 48.52±4.00 D (P<0.05). Four predictive factors of success were statistically significant: type of ectasia (type 1 or 2), stage of keratoconus (Krumeich 1 or 2), implantation of only 1 ICR and a preoperative VA less than 0.4 (decimal scale). Eighty-six percent of patients with an initial VA<0.4 (decimal scale) gained 2 lines of BCVA within 1 year and 80% 3 lines versus 52% and 41%, respectively for patients with initial VA≥0.4 (decimal scale). CONCLUSION: Femtosecond-assisted Ferrara ICR implantation for treatment of keratoconus is a reliable and reversible technique. Implantation results in greater efficiency for patients with moderately advanced asymmetric keratoconus with an initial VA<0.4 (decimal scale).

[Quality of life in patients wearing scleral lenses]. / Qualité de vie des patients équipés en verres scléraux.

OBJECTIVE: To evaluate the contribution of scleral lenses in terms of improving the quality of life in the treatment of astigmatism after penetrating keratoplasty or in keratoconus. METHODS: We conducted an observational retrospective study, evaluating quality of life (QOL) of patients who failed to adapt to RPG lenses, fitted with SPOT(®) scleral lenses between October 2007 and March 2011 in the University Hospital of Besançon Department of Ophthalmology. QOL was assessed before and after scleral lens adaptation with the French version of the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ 25). RESULTS: We included 47 patients (83 eyes) fitted with scleral lenses on one or both eyes: 56 eyes with keratoconus and 27 post-keratoplasty eyes. The average duration of wearing scleral lenses was 18±10months and the average wearing time was 14±3hours per day. The rate of participation in the survey was 86.5% (41 patients). Visual acuity in the better eye progressed from 0.68±0.46 to 0.15±0.17 logMAR at the 6th month after scleral lens adaptation (P<0.0001). The average scores on the NEI-VFQ 25 questionnaire of patients fitted with scleral lenses for at least 6 months were significantly higher than those without scleral lenses, with a global score of 80.2/100 with, versus 48.1/100 without, scleral lenses (P<0.0001). The global score increased by an average of 32.1±4.6 points (-28, 82) (P<0.0001). Statistical analysis found no significant difference in global score between patients in the keratoconus and keratoplasty groups (P>0.05). Scleral lenses showed a significant improvement in quality of life for patients who had failed or are intolerant to conventional rigid gas permeable contact lenses. In our two main optical indications, keratoconus and keratoplasty, they represent an alternative or a step prior to surgery.

MRI measurement of liver fat content predicts the metabolic syndrome.

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk.