Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Refractive accuracy and visual outcomes after combined descemet membrane endothelial keratoplasty and cataract surgery: A French multicentric study.

PURPOSE: Descemet membrane endothelial keratoplasty (DMEK) combined with cataract extraction and intraocular lens insertion (new triple procedure) limits postoperative refractive errors. The objective of this study was to assess refractive accuracy after DMEK combined with cataract extraction and intraocular lens implantation. SETTING: Four university hospitals (Rouen, Paris, Reims, Grenoble). DESIGN: This retrospective multicenter study included patients with symptomatic corneal endothelial decompensation and cataract. METHODS: The primary outcome was the difference between the target spherical equivalent and postoperative refraction at months 2 and 6. Secondary outcomes were visual acuity, keratometry, pachymetry and endothelial cell density. RESULTS: A total of 130 eyes of 111 patients (mean age 66.2 years) were included (94% with Fuchs' endothelial dystrophy). For a mean refractive target set at -0.50 (±0.57) D, the mean (95% CI) refractive error was hyperopia of +0.49 (0.314; 0.664) D at 2 months and +0.46 (0.299; 0.619) D at 6 months. Best corrected distance visual acuity was improved in all patients: from 0.49 (±0.3) logMAR to 0.14 (±0.14) logMAR at 2 months and 0.05 (±0.1) logMAR at 6 months. Mean corneal thickness decreased from 621.6 (±37.6) µm to 515.2 (±42.6) µm at 2 months and 539.0 (±39.0) µm at 6 months. CONCLUSIONS: Good refractive accuracy was obtained after the new triple procedure with DMEK. Hyperopic shift is common after triple procedures, and its persistence should be evaluated in future studies in order to anticipate a change in its value to optimize intraocular lens power calculation.

[Efficacy of intense pulsed light therapy in the treatment of Meibomian gland dysfunction-related severe dry eye]. / Efficacité de la lumière pulsée dans le traitement des sécheresses oculaires sévères par dysfonctionnement meibomien.

INTRODUCTION: Dry eye syndrome caused by Meibomian gland dysfunction (MGD) is a common disease in the general population and impairs quality of life. Intense Pulsed Light (IPL) has mainly been used in dermatology for the treatment of skin disorders, and more recently for MGD-related dry eye. The objective of our study is to evaluate the efficacy and tolerability of IPL with the E-Eye® device (E-Swin, Houdan, France) in severe MGD-related dry eye patients. MATERIALS AND METHODS: This non-comparative study included 20 patients with MGD-related dry eye with a Break-Up Time (BUT)<10seconds, dry eye symptoms >30mm on a Visual Analog Scale (VAS), and failure of lid hygiene and artificial tears. Treatment consisted of 3 sessions of IPL on D0, D15, and D45 (5 flashes of 13J/cm2 per eye). The following parameters were assessed at each visit and at D75 : symptoms graded with a VAS and the Standard Patient Assessment of Eye Dryness questionnaire (SPEED), BUT, corneal fluorescein staining, Meibomian gland expression score, meibography, tear film lipid layer thickness by interferometry and the ocular scattering index by double-pass aberrometry (OQAS). Statistical analysis was performed on the eye most affected at baseline. RESULTS: We included 40 eyes of 20 patients, 15 female and 5 male, mean age 47±15 years (24 to 74 years). The symptoms rated by VAS were severe, averaging 69±25mm. After treatment, there was a statistically significant decrease in symptoms, with a 14mm VAS decrease (55±29mm at D75 versus 69mm at D0, P=0.048) and SPEED score of 3.4 (19.0±6mm versus 22.4±4.6, P=0.03). The number of expressible Meibomian gland ducts increased significantly (from 5.9 to 8.1, P=0.04), lid redness decreased (from 1.4 to 0.6, P=NS) and BUT improved (from 4.2 to 5.9, P=NS). Other parameters remained unchanged. Three patients (15%) complained of transient ocular burning after each treatment. CONCLUSION: IPL appears to be effective in improving signs and symptoms in patients with severe MGD-related dry eye, with a good safety profile. Its exact mechanism of action remains to be elucidated.

[Descemet's membrane endothelial keratoplasty (DMEK): Analysis of a variation in Descemet's endothelial graft preparation]. / Greffes endothéliales par Descemet membrane endothelial keratoplasty (DMEK) : analyse d'une variante de découpe du greffon endothélio-descemétique.

INTRODUCTION: Descemet's membrane endothelial keratoplasty (DMEK) can replace just the corneal endothelium and respect the natural corneal anatomy. Currently, the technique of endothelial graft preparation remains manual and non-standardized. PURPOSE: To report anatomic and functional results after DMEK, and compare two techniques of graft preparation. METHODS: Single-center retrospective study, including 64 eyes of 64 patients undergoing DMEK, from September 2014 to February 2016 at Clermont-Ferrand University Medical Center. The "classic" preparation was used in 44 patients (group 1) and the "variant" preparation was used in 20 patients (group 2). An analysis of functional parameters (visual acuity), anatomy (pachymetry, corneal edema, endothelial cell count) and keratometry (sphere, cylinder, mean keratometry) was performed during the first postoperative year. RESULTS: The mean follow-up was 10.0±2.5 months. The average preparation time was 12.3±8.1minutes, with 14.4±8.8 in group 1 versus 7.8±3.0 in group 2 (P<0.001). At six months, the best corrected distance visual acuity was significantly better in group 1 with an acuity of 0.28±0.28 LogMAR in group 1 and 0.37±0.30 LogMAR in group 2 (P<0.01). The best corrected near visual acuity was also better in group 1 at 6 months, with an acuity of 0.29±0.24 LogMAR (P<0.001) in group 1 and 0.37±0.28 LogMAR in group 2 (P=0.02). Improvement in visual acuity was continuous for the 2 groups. At 6 months, endothelial cell loss was greater in group 1 than in group 2, but the difference was not significant (P=0.44). Central corneal thickness was similar between the 2 groups. Finally, no change in keratometry parameters was found between preoperative data and 6 months in each group or between the two groups. CONCLUSION: DMEK led to an improvement in all parameters as well as rapid visual rehabilitation. The new variation in preparation saved a considerable amount of time without decreasing graft survival or postoperative results.

Necrotising Scleritis and Peripheral Ulcerative Keratitis Associated with Rheumatoid Arthritis Treated with Rituximab.

Background Rheumatoid arthritis is a chronic and common inflammatory autoimmune disease. This primarily involves the synovia of the joints, but can cause many extra-articular manifestations as well, including peripheral ulcerative keratitis (PUK) and necrotising scleritis. These are often a threat to vision; they significantly compromise not only the eye's structural integrity but are also important for prognosis and need urgent management. History and signs Three cases of peripheral ulcerative keratitis associated with rheumatoid arthritis were recorded in the electronic databank of the Jules Gonin Uveitis Clinic, two with necrotising scleritis and peripheral ulcerative keratitis and one with only peripheral ulcerative keratitis. They were all followed at Jules Gonin Eye Hospital (Lausanne, Switzerland), conjointly with the Department of Rheumatology at the Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland). Therapy and Outcome Good initial therapeutic response was observed in the two patients who received rituximab therapy. The patient who received only high dose corticosteroid developed massive colon perforation as well as acute renal insufficiency a few days after her ocular event. Conclusion From our limited number of patients, we found that the two patients who received the induction therapy with rituximab were stabilised from an ocular standpoint; however, rituximab had to be switched to other molecules, either due to other systemic symptoms from the disease itself or due to adverse effect of this treatment. This contributes to the increasing number of reports that rituximab can be an effective treatment for refractory ocular complications of rheumatoid arthritis (RA), at least as an induction therapy.

[Gas-permeable scleral lens for management of severe keratoconjunctivitis sicca secondary to chronic graft-versus-host disease]. / Traitement des sécheresses oculaires sévères secondaires à la maladie du greffon contre l'hôte chronique par lentilles sclérales perméables à l'oxygène.

INTRODUCTION: Graft-versus-host disease is a major complication of allogeneic hematopoietic stem cell transplantation. Severe keratoconjunctivitis sicca is common in patients with chronic GVH disease. The goal of this study was to evaluate the safety and efficacy of a gas-permeable scleral lens in the management of severe dry eye disease associated with chronic GVH. PATIENTS AND METHODS: This is a retrospective study from June 2009 to November 2013. Patients fitted with scleral lenses for severe keratoconjunctivitis sicca associated with chronic GVH were included. The main outcomes measured were best-corrected visual acuity and quality of life (OSDI and NEI-VFQ25) composite scores before and six months after scleral lens fitting. RESULTS: Sixteen patients were included. The mean age was 52 years (19-69 years). Mean follow-up was 20 months (3-48 months). All patients reported improvement of their ocular symptoms. Best corrected visual acuity improved from 0.21 ± 0.26 to 0.1 ± 0.14 logMAR (P = 0.002), OSDI score improved from 92.1 ± 11.3 to 23.5 ± 11.2 (P = 0.002) and NEI-VFQ25 improved from 41.3 ± 7 to 83.1 ± 15.9 (P = 0.003), 6 months after scleral lens fitting. No serious adverse events, infectious, hypoxemic or allergic complications attributable to the scleral lens occurred. CONCLUSION: Gas-permeable scleral lens use appears to be safe and effective in patients with severe dry eye related to chronic GVH.

Deletion of extracellular matrix metalloproteinase inducer/CD147 induces altered cardiac extracellular matrix remodeling in aging mice.

Extracellular matrix metalloproteinase inducer (EMMPRIN), known for its ability to induce matrix metalloproteinase (MMP) expression, was proposed to play a role in the adverse cardiac extracellular matrix remodeling. After observing an age-associated increase in cardiac EMMPRIN expression in both mice and rats, the role and mechanism of action of EMMPRIN was investigated in the myocardial age-associated changes using 3, 12 and 24 month old EMMPRIN knock-out (KO) vs. wild-type (WT) mice, by cardiac echocardiography, Western blots, immunohistochemistry, ELISA and histology. Adilated cardiomyopathy characterized by a decreased ejection fraction and an enlargement of left ventricular chamber (LV) associated with LV hypertrophy, occurred in KO mice as soon as 12 month old. The increase in interstitial collagen deposition during aging in WT mice could not be detected in KO mice. This may be related to the reduced activation (48% reduction; P < 0.05) and signaling (smad2/3 nuclear translocation) of TGF-ß in the 12 month old KO mice which paralleled with a greater reduction in the TGF-ß known activating enzymes such as MT1-MMP and MMP-1 (33% and 37% reduction respectively, between 3 and 12 month old in KO mice; P < 0.05) as well as uPA. These findings demonstrate that EMMPRIN gene silencing is associated with an aberrant extracellular matrix remodeling, characterized by the absence of a detected age-associated fibrosis and consequently to dilated cardiopathy, indicating that a fine regulation of EMMPRIN is essential for the coordinated ECM remodeling during aging.

Loss of CD147 results in impaired epithelial cell differentiation and malformation of the meibomian gland.

Meibomian gland dysfunction is a leading cause of ocular surface disease. However, little is known about the regulatory processes that control the development and maintenance of this sebaceous gland. Here, we identify a novel function for CD147, a transmembrane protein that promotes tissue remodeling through induction of matrix metalloproteinases, in regulating meibocyte differentiation and activity. We found that CD147 localized along basal cells and within discrete membrane domains of differentiated meibocytes in glandular acini containing gelatinolytic activity. Induction of meibocyte differentiation in vitro promoted CD147 clustering and MMP9 secretion, whereas RNAi-mediated abrogation of CD147 impaired MMP9 secretion, concomitant with a reduction in the number of proliferative cells and cytoplasmic lipids. Meibomian glands of CD147 knockout mice had a lower number of acini in both the superior and inferior tarsal plates of the eyelids, and were characterized by loss of lipid-filled meibocytes compared with control mice. Together, our data provide evidence showing that gelatinolytic activity in meibocytes is dependent on CD147, and supports a role for CD147 in maintaining the normal development and function of the meibomian gland.

[Scleritis: when might a systemic disease be involved?]. / Sclérites: quand évoquer une pathologie systémique?

Scleritis is typically a severe painful inflammatory disorder of the eye. This process may involve the sclera but also the cornea, adjacent episclera, and underlying uvea and therefore threaten vision. Careful clinical history taking, detailed ocular examination, appropriate investigation for systemic disease, and timely intervention with the use of immunosuppressive drugs when necessary has improved the long-term outcome of patients with scleritis.