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Among the new biological therapies for atopic diseases, dupilumab is a fully human monoclonal antibody directed against IL-4Rα, the common chain of interleukin-4 and interleukin-13 receptors. Dupilumab showed clinical improvements in patients with atopic dermatitis, asthma, and chronic rhinosinusitis and is currently under development for other indications. While dupilumab is considered to be well tolerated, a number of recent publications have reported various adverse events. This review aims to summarize the current knowledge about these adverse events, which may help clinicians to improve the follow-up of patients on dupilumab. Injection-site reactions are the most common reported adverse event. However, dupilumab has also been shown to cause ophthalmic complications (e.g., dry eyes, conjunctivitis, blepharitis, keratitis, and ocular pruritus), head and neck dermatitis, onset of psoriatic lesions, progression of cutaneous T-cell lymphoma exacerbation, alopecia areata, hypereosinophilia, and arthritis. Most are managed during dupilumab treatment continuation, but some (e.g., severe conjunctivitis) may result in a discontinuation of treatment. Their molecular origin is unclear and requires further investigations. Among other hypothesis, it has been suggested that T helper (Th)2-mediated pathway inhibition may worsen Th1/Th17-dependent immune responses. An ophthalmological examination for the presence of potential predictive indicators of ophthalmic adverse events is recommended before initiation of dupilumab therapy.

Resume La dermatite atopique (DA), est une dermatose prurigineuse inflammatoire, frequente et chronique. Elle touche aussi bien les enfants que les adultes. Son etiologie est multifactorielle et implique des interactions complexes entre une predisposition genetique, une dysregulation du systeme immunitaire, une alteration de la barriere cutanee et l’environnement. Les interleukines (IL)-4 et 13 jouent un role cle. Le dupilumab, anticorps monoclonal dirige contre la sous-unite alpha commune aux recepteurs de l’IL-4 et de l’IL-13, est la premiere biomolecule approuvee pour le traitement de la DA moderee a severe. Il s’est revele tres efficace aussi bien dans les premiers essais cliniques de phases II et III que dans la vraie vie, avec une bonne tolerance generale. Cependant, une frequence assez elevee d’evenements indesirables oculaires (de 10 a 40 %), de type conjonctivite et syndrome sec, a ete rapportee. Leur prise en charge peut dans certains cas echouer et leur gravite imposer l’arret du traitement. De plus et de facon surprenante, ces complications oculaires n’ont pas ete decrites chez les patients traites par dupilumab pour d’autres pathologies telles que l’asthme. La comprehension des mecanismes moleculaires responsables est importante pour identifier les patients a risque et adapter leur prise en charge preventive et curative a la fois dermatologique et ophtalmologique.

PURPOSE: To evaluate the efficacy and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen. METHODS: This was a prospective, non-comparative, pilot cohort study conducted at the National Reference Center for Keratoconus (Toulouse, France) on patients with progressive keratoconus. Transepithelial, pulsed, accelerated CXL was performed in an oxygen-rich atmosphere. Oxygen goggles were applied to the eyes to maintain a high level of oxygen during treatment. The main efficacy outcome was the mean change from baseline in maximum keratometry (Kmax) and the secondary outcomes were the mean changes in flat keratometry (K1), steep keratometry (K2), mean keratometry (Km), corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), and demarcation line depth. The safety outcomes were the incidence of adverse events, the mean change in pachymetry, and endothelial cell count. RESULTS: Thirty-four eyes of 34 patients were included. At 12 months postoperatively, the Kmax decreased by 1.56 ± 1.71 diopters (D) ( P < .0001) and CDVA improved by 0.093 ± 0.193 logMAR ( P < .02). The K2 and Km decreased by 0.51 ± 1.03 D ( P < .02) and 0.40 ± 0.78 D ( P < .01), respectively. There was no change in K1 and UDVA. The most frequent adverse event was corneal haze (64.78%). There were neither cases of infectious keratitis or loss of more than two lines in CDVA nor changes in pachymetry or endothelial cell count. CONCLUSIONS: Transepithelial CXL performed in an oxygen-rich atmosphere results in improved Kmax and CDVA with good safety. These promising findings suggest that this procedure could be safe and capable of halting the progression of keratoconus. [ J Refract Surg . 2021;37(1):42–48.]

BACKGROUND Dupilumab is approved for use in moderate-to-severe atopic dermatitis (AD) and as an add-on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD. OBJECTIVES The objectives of this study were to describe the incidence and nature of dupilumab-induced OAEs and to assess the potential predisposing factors. PATIENTS AND METHODS We conducted a prospective, single-centre, real-life study in adult AD patients treated with dupilumab, who were systematically examined by an ophthalmologist before and during treatment. RESULTS Forty-six patients were included prospectively with a median age of 41.1 years and a median initial SCOring Atopic Dermatitis of 46.0 (IQR: 34.5-55.5). OAEs concerned 34.8% of patients and were mostly of mild to moderate severity. Two patients had to discontinue treatment due to OAE. The majority of patients developed or aggravated dry eye disease, with superficial punctate keratitis (SPK). Six patients developed conjunctivitis. Dupilumab-induced OAEs were associated with the following pre-existing parameters: dry eye disease with SPK (Odds ratio (OR); 6.3 [95% confidence interval (CI): 1.3-31.6]), eyelid eczema (OR: 8.7 [95%CI: 1.8-40.6]), history of food allergy (OR 3.8 (95% CI: 1.002-14,070) and IgE serum level> 1000 kU/L (OR:10.6 [CI 95%: 1.2-91.3]). CONCLUSION Atopic dermatitis patients with eyelid eczema or dry eye disease symptoms may be referred to an ophthalmologist before starting dupilumab to consider initiating preventive eye hydration measures. Further multicentric and translational studies are warranted to better explain OAEs pathophysiology.

Purpose To describe the surgical technique and report the outcomes of 2 patients treated with femtosecond laser-assisted ipsilateral rotational lamellar autokeratoplasty in central corneal scars. Methods The corneal scar depth was mapped using preoperative optical coherence tomography. An eccentric lamellar lenticule was cut with a femtosecond laser and rotated to decenter corneal opacity and free the pupil area in 2 patients with nonprogressive central corneal scars. The surgical plan was set after simulating lenticule rotation with a digital corneal image and computer software. Results In both cases, the corneal scar was decentered inferiorly, out of the pupillary area, with increased postoperative visual acuity but visual outcome limitations secondary to corneal irregularities and residual deep opacity. Conclusions Femtosecond laser-assisted ipsilateral rotational lamellar autokeratoplasty is effective for shifting central corneal opacities and can be considered in appropriate cases.

OBJECTIVES To evaluate the success rate, efficacy, and safety of the ICD 16.5 mini-scleral gas permeable (GP) contact lens. METHODS This prospective study included referred consecutive patients with irregular corneas and severe ocular surface disease (OSD) in treatment failure. All patients were fitted with the ICD 16.5 mini-scleral GP lens. Even though we had some limited experience with scleral lenses, it was our first experience with the ICD 16.5 mini-scleral GP lens. Efficacy was assessed by comparing best-corrected visual acuity (BCVA) with the mini-scleral lens to baseline BCVA. A subjective visual functioning questionnaire (comfort score, visual quality score, handling rating, and wearing time) was administered in a face-to-face structured interview. RESULTS Thirty-nine eyes of 23 patients with a mean age of 43±16 years were included. Fitting indications were keratoconus (46%), post-penetrating keratoplasty (21%), other irregular astigmatism (15%), and severe OSD (18%). Twenty-five eyes (64%) were successfully fitted with an 18-month follow-up. The mini-scleral GP lens BCVA was 0.16 logarithm of the minimum angle of resolution (logMAR; 20/25) versus a baseline BCVA of 0.44 logMAR (20/63; P

Purpose To compare the outcomes of transepithelial photorefractive intrastromal corneal crosslinking (CXL) and photorefractive keratectomy (PRK) in eyes with low myopia. Setting Purpan Hospital, Toulouse, France. Design Prospective case series. Methods Myopic patients with a manifest refraction spherical equivalent (MRSE) of −1.00 to −2.50 diopters (D) and a cylindrical component of plano to −0.75 D were included. The dominant eye had PRK (PRK eyes). The nondominant eye had transepithelial photorefractive intrastromal CXL with riboflavin (ParaCel Part 1 and 2), 30 mW/cm2 pulsed ultraviolet-A irradiation centered on the pupil (Mosaic System) for 16 minutes and 40 seconds, and a supplemental oxygen delivery mask (CXL eyes). The primary outcome measure was the change in the MRSE. Other outcome measures were the uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean keratometry, and endothelial cell count (ECC) over a 6-month follow-up. Adverse events were assessed. Results Nineteen patients were included. By 6 months, the mean MRSE had decreased by 0.72 D ± 0.42 (SD) in CXL eyes and by 1.35 ± 0.46 D in PRK eyes (P Conclusions Photorefractive keratectomy provided better visual and refractive outcomes than transepithelial photorefractive intrastromal CXL. Transepithelial photorefractive intrastromal CXL, however, showed the potential refractive effect of CXL but with a limited magnitude of myopic correction.

Resume Objet Identifier les cas d’obliterations veineuses retiniennes (OVR) bien perfusees revelees par un blanc periveinulaire (BPV) isole et decrire les circonstances diagnostiques et l’evolution a court terme. Materiel et methodes Serie monocentrique, observationnelle, retrospective de cas recueillis entre janvier 2013 et janvier 2015. Parmi les 151 cas d’occlusions veineuses retiniennes suivis dans le service, nous avons recherche la presence de BPV isole ayant amene au diagnostic d’occlusion veineuse retinienne. Resultats Nous avons identifie huit patients pour lesquels un diagnostic de BPV isole avait revele une OVR non ischemique (3,9 %) : 5 presentaient une occlusion de veine centrale de retine, trois une occlusion d’hemi-veine centrale et aucun une occlusion de branche. L’acuite visuelle initiale etait conservee dans cinq cas sur huit. Dans tous les cas, le BPV apparaissait isole, sans hemorragie retinienne initiale. Les cliches monochromatiques bleus visualisaient tous les BPV. Il existait sur les examens tomographiques en coherence optique (OCT) une hyper-reflectivite segmentaire et focale des couches internes retiniennes, particulierement de la nucleaire interne. A un mois du diagnostic, il etait note une atrophie des couches retiniennes initialement interessees par l’hyperreflectivite initiale. Trois cas sur huit ont ete malencontreusement initialement diagnostiques comme une obliteration de l’artere centrale de la retine (OAR). Conclusion La complication principale du BPV est l’atrophie localisee des couches internes retiniennes a l’origine de scotomes paracentraux. Le diagnostic differentiel avec une OAR, parfois difficile initialement, repose sur les caracteristiques angiographiques et tomographiques en coherence optique et leur evolution.

Resume Introduction Le decollement de retine (DR) est une pathologie potentiellement cecitante. La rapidite de prise en charge est un facteur pronostique majeur. Nous avons etudie le delai de prise en charge chirurgicale des decollements de retine et analyse les facteurs pouvant l’influencer. Methode Enquete transversale, multicentrique, realisee sur 6 mois. Critere principal : delai separant diagnostic et chirurgie. Critere secondaire : delai separant premiers signes et chirurgie. Facteurs etudies : les caracteristiques sociodemographiques et cliniques, la distance domicile/centre chirurgical et presence d’un week-end. Resultats Nous avons inclus 159 patients. Le delai moyen diagnostic-chirurgie etait de 4,4 jours ± 12,3 (2,7 ± 4,3 pour les DR Conclusion Le delai de prise en charge des DR est relativement court dans la region Midi-Pyrenees, meme si nous avons pu constater un retard diagnostique relativement frequent, notamment chez les DR Macula-OFF, peut-etre en raison de la meconnaissance des symptomes par le patient et des difficultes d’acces aux consultations specialisees. Aucune relation n’a ete mise en evidence entre ce delai et la distance separant le domicile du patient du lieu de prise en charge.

Resume Introduction La chirurgie de la cataracte est une candidate ideale a une prise en charge ambulatoire. En 2013, au CHU de Toulouse, le taux de chirurgie ambulatoire concernant la phacoemulsification etait de 75,8 %. Cette etude a ete menee afin d’identifier les obstacles qui limitent le developpement de la pratique ambulatoire de la chirurgie de la cataracte dans notre etablissement. Materiel et methodes Pour cette etude retrospective, tous les sejours incluant un acte de phacoemulsification (code CCAM : BFGA004) realise au CHU de Toulouse en hospitalisation traditionnelle en 2013 ont ete inclus. Nous avons exclu les sejours pour lesquels les dossiers medicaux, infirmiers et anesthesiques, ainsi que les fiches correspondantes de programmation operatoire, etaient incomplets. Les sejours ont ete classes selon le motif d’hospitalisation et selon le type de chirurgie, cataracte geste principal ou cataracte geste combine. Resultats Notre etude a porte sur 298 sejours avec un âge moyen des patients de 66,8 ± 16,8 ans et un sex-ratio homme/femme de 0,76. L’indication d’hospitalisation traditionnelle relevait de motifs sociaux, chirurgicaux et anesthesiques dans les proportions respectives suivantes : 41, 34 et 8 % des cas. Les echecs de la prise en charge en ambulatoire representaient 7 % des cas. L’isolement social representait 89 % des motifs sociaux. Lors d’une chirurgie combinee, le motif etait chirurgical dans 89 % des cas. Conclusion Le developpement de la chirurgie ambulatoire implique tous les acteurs de la filiere. En particulier, la prise en compte du facteur social est un element essentiel impliquant une prise en charge adaptee. Au niveau chirurgical, le changement des pratiques pour developper la chirurgie ambulatoire de la cataracte doit cibler en priorite les chirurgies combinees.

Background: In preclinical studies, eltrombopag has been associated to an increased incidence of cataract in mice and rats. No increased risk has been observed in randomized controlled trials in immune thrombocytopenia (ITP) patients. During the eltrombopag extension study EXTEND, 28/302 patients developed or worsened cataract, i.e. 9.3% of the patients over a median duration of exposure of 2.4 years. Of note, 79% of these 28 patients had at least another risk factor of cataract. Real-life studies assessing the risk of cataract in ITP adult patients exposed to eltrombopag are lacking. Aim: To assess the risk of cataract with eltrombopag in a nationwide cohort of primary ITP adults. Methods: The population was the cohort of all incident primary ITP adult patients (≥18 years) in France from June 2010 (date of eltrombopag marketing in France) to June 2017. This cohort was identified within the national health insurance database using a validated algorithm combining drug exposures and international classification of diseases, version 10 (ICD-10) diagnosis codes (FAITH cohort; NCT03429660). A nested case-control study was conducted within the cohort. Cases were patients who had a surgery for cataract after ITP onset, identified using appropriate codes. Up to five controls for each case were matched on age and sex. Index date was the date of cataract surgery for cases, and the date of cataract surgery of the corresponding case for controls. Two analyses were conducted: one considering the exposure to eltrombopag as ever vs. never exposed; another considering the cumulative exposure to eltrombopag, categorized by never exposed, a 1-365 Defined Daily Dose (DDD) exposure, and a ≥365 DDD exposure. Covariables were the presence of diabetes mellitus, cumulative exposure to corticosteroids considered in prednisone equivalence dosage (by quartiles), and the presence of ophthalmological risk factors of cataract (including previous ophthalmological surgery, glaucoma and other anterior chamber risk factors). Conditional logistic regression models were used to compute adjusted odds ratios (aOR) and their 95% confidence intervals (CI). Results: The cohort included 8,502 incident primary ITP adults. During the follow-up (31,590 patient-years in total; mean follow-up: 44.4 months), 1,097 patients were exposed to eltrombopag, including 310 with a cumulative exposure ≥365 DDDs. Overall, 573 patients had a surgery of cataract; incidence: 1.90/100 person-years (95% CI: 1.75-2.06). Fifty-seven cases occurred in patients ever exposed to eltrombopag; incidence: 1.50/100 person-years (95%CI: 1.15-1.94) in this subgroup. The nested case-control study included the 573 cases and 2699 controls. Median age was 75 years and 50% were women; the median duration of disease was 24.8 months in cases and 24.2 months in controls; 57 (9.9%) cases and 314 (11.6%) controls were exposed to eltrombopag before the index date; 14 (2.4%) and 68 (2.5%) patients had cumulative exposure to eltrombopag ≥365 DDDs, respectively. Cases were more frequently exposed to corticosteroids (83.4% vs. 75.7%), with a higher cumulative exposure to corticosteroids (median: 2800 vs. 2188 mg prednisone equivalent). Diabetes mellitus was present in 25.7% of cases vs. 25.1% of controls while ophthalmological risk factors were present in 5.4% and 2.8%, respectively. In the ever/never exposed analysis, the aOR for eltrombopag was 0.79 (95% CI: 0.58-1.07). In the cumulative exposure analysis, the aOR was 0.76 (95% CI: 0.54-1.08) in the 1-365 DDD group as compared with the never exposed group, and 0.88 (95% CI: 0.49-1.59) in the ≥365 DDD group as compared with the never exposed group. Conclusions: This nationwide pharmacoepidemiological study did not identify an increased risk of cataract in primary ITP adult patients exposed to eltrombopag. Disclosures Moulis: Novartis pharma: Research Funding, Speakers Bureau; Amgen pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding.

To evaluate to what extent the modification of corneal asphericity to induce spherical aberration (SA) can improve the depth of focus and to determine whether preoperative adaptive optics assessment (Voptica SL) can predict an optimal SA value for each patient.Comparative, prospective clinical trial with paired eye control.Patients ≥45 years old who are hyperopic from +1.00 to +2.50 diopters (D), with eyes suitable for LASIK surgery.Bilateral hyperopic LASIK surgery using a 200-Hz Allegretto excimer laser. The dominant eye was operated using a conventional profile. The nondominant eye was programmed with an aspheric ablation profile and -0.75 D monovision.Primary outcome was the correlation between postoperative SA and depth of focus, defined as the pseudo-accommodation value (PAV = [1/reading distance {m}] - minimum addition [D]). Main secondary outcome was the comparison of depth of focus between patients with an induced SA close to the optimal one (group 1), patients with an induced SA far from the optimal one (group 2), and patients for whom SA induction did not increase the depth of focus (control group).We included 76 patients. Between preoperative and postoperative assessment, the mean increase of distance-corrected PAV for near vision was +0.25±0.64 D (P0.001) for dominant eyes and +0.63±0.55 D (P 0.001) for nondominant eyes. As the level of negative or positive postoperative SA increased, PAV for intermediate and near vision increased. Among the 37 eyes that followed the preoperative adaptive optics assessment, the mean PAV increase at near was significantly higher (P0.05) in group 1 (0.93±0.50 D) than in group 2 (0.46±0.42 D) and than in the control group (0.35±0.32 D). The mean optimal SA value determined by the dynamic simulation procedure to optimize the depth of focus was -0.18±0.13 μm at 4.5 mm.Aspheric hyperopic LASIK can increase the depth of focus without impairing far vision, but this benefit would be maximal and reproducible if we could define and achieve an optimal SA value determined by preoperative assessment using an adaptive optics instrument.

Purpose To evaluate the efficacy and safety of the combined implantation of a monofocal intraocular lens (IOL) in the capsular bag with a diffractive multifocal IOL designed for sulcus placement (Reverso). Setting Purpan Hospital, Toulouse, and Helios Clinic, Saint-Jean-de-Luz, France. Design Prospective case series. Methods The multifocal IOL piggyback IOL was implanted in the sulcus during cataract surgery. Visual acuity, defocus curve, contrast sensitivity, IOL positioning, and patient satisfaction were assessed with 1-year follow-ups. Results Fifty-four eyes of 27 patients were included. At 1-month, monocular uncorrected distance (UDVA) and near (UNVA) visual acuities were 0.13 logarithm of the minimum angle of resolution (logMAR) ± 0.18 (SD) and 0.20 ± 0.16 logMAR, respectively. Binocular UDVA and UNVA were 0.03 ± 0.06 and 0.12 ± 0.08 logMAR, respectively. At 1 year, the mean monocular logMAR UDVA, corrected distance visual acuity, UNVA, and corrected near visual acuity were 0.10 ± 0.11, 0.02 ± 0.06, 0.18 ± 0.12, and 0.13 ± 0.08, respectively. The defocus curve and contrast sensitivity values were comparable to those obtained with other multifocal IOLs. On Scheimpflug imaging, the mean distance between the sulcus multifocal IOL and the monofocal IOL was 517 ± 141 μm. At 1 year, ultrasound biomicroscopy showed an annular fibrosis of the anterior capsule in 94.4% of the eyes. Complications included 1 posttraumatic IOL decentration and 1 slight corectopia. Eighty-nine percent of patients reported satisfaction. Conclusions The piggyback implantation of this multifocal IOL seemed to be safe and effective. It might provide similar results as a primary in-the-bag multifocal IOL, with the advantage of reversibility that might extend primary or secondary implantation.

We report the case of a 56-year-old patient, presenting with bilateral hypertensive anterior uveitis due to Leishmania infantum, in the setting of immune deficiency related to HIV infection. The etiology of the uveitis was diagnosed following detection of L. infantum DNA on anterior chamber paracentesis. Initially, the patient received an intravitreal injection of liposomal amphotericin B, systemic antiparasitic treatment, topical steroid and ocular hypotensive treatment. Due to unfavourable disease progression in the right eye, we re-evaluated the anti-inflammatory, antiretroviral and antiparasitic medications (beginning meglumine antimoniate): the uveitis in the left eye was thus able to be controlled. We followed the efficacy of treatment with weekly quantification of Leishmania DNA in the aqueous humor. Uveitis secondary to leishmaniasis is rare and serious. Physicians must be aware of this cause of uveitis, particularly in immunodeficient patients. The quantitation of Leishmania DNA in the aqueous humor is an indispensible tool for monitoring the disease.

Myopia is the most frequent refractive disorder in the world. It has become a real Public Health problem, due to its frequency and to high myopia-related blinding complications. Myopic progression depends on genetic and environmental factors. Genetic studies have identified more than forty candidate genes that take part in pathophysiological pathways, from retinal phototransduction to axial lengthening via scleral remodelling. Environmental factors also influence scleral remodelling by way of visual perception. In the case of predominant attention to near tasks, a physiological feedback loop leads to axial growth. This phenomenon, called active emmetropization, is particularly obvious in animal models and in some human populations. To date, research has failed to identify a molecule common to all the implicated metabolic pathways which could be a target for an effective preventive treatment against myopic progression.

To evaluate visual performance and factors associated with abnormal vision in patients screened for frailty at the Geriatric Frailty Clinic (GFC) for Assessment of Frailty and Prevention of Disability at Toulouse University Hospital. Retrospective, observational cross-sectional, single-centre study. Institutional practice. Patients were screened for frailty during a single-day hospital stay between October 2011 and October 2014 (n = 1648). Collected medical records included sociodemographic data (including living environment and educational level), anthropometric data, and clinical data. The general evaluation included the patient’s functional status using the Activities of Daily Living (ADL) scale and the Instrumental Activity of Daily Living (IADL) scale, the Mini-Mental State Examination (MMSE) for cognition testing, and the Short Physical Performance Battery (SPPB) for physical performance. We also examined Body Mass Index (BMI), the Mini-Nutritional Assessment (MNA), and the Hearing Handicap Inventory for the Elderly Screening (HHIE-S) tool. The ophthalmologic evaluation included assessing visual acuity using the Snellen decimal chart for distant vision, and the Parinaud chart for near vision. Patients were divided into groups based on normal distant/near vision (NDV and NNV groups) and abnormal distant/near vision (ADV and ANV groups). Abnormal distant or near vision was defined as visual acuity inferior to 20/40 or superior to a Parinaud score of 2, in at least one eye. Associations with frailty-associated factors were evaluated in both groups. The mean age of the population was 82.6 ± 6.2 years. The gender distribution was 1,061 females (64.4%) and 587 males (35.6%). According to the Fried criteria, 619 patients (41.1%) were pre-frail and 771 (51.1%) were frail. Distant and near vision data were available for 1425 and 1426 patients, respectively. Distant vision was abnormal for 437 patients (30.7%). Near vision was abnormal for 199 patients (14%). Multiple regression analysis showed that abnormal distant vision as well as abnormal near vision were independently associated with greater age (P < 0.01), lower educational level (P < 0.05), lower performance on the MMSE (P < 0.001), and lower autonomy (P < 0.02), after controlling for age, gender, educational level, Fried criteria, and MMSE score. The high prevalence of visual disorders observed in the study population and their association with lower autonomy and cognitive impairment emphasises the need for systematic screening of visual impairments in the elderly. Frailty was not found to be independently associated with abnormal vision.

PURPOSE: To compare the efficacy and safety of topography-guided corneal collagen cross-linking (TG-CXL) to conventional corneal CXL (C-CXL) in progressive keratoconus. METHODS: In this prospective, nonrandomized clinical trial, 60 eyes of 60 patients were scheduled to receive either TG-CXL (30 eyes with deepithelialization focused on the cone, riboflavin application for 10 minutes, and 30 mW/cm 2 pulsed ultraviolet-A irradiance pattern according to topography) or C-CXL (30 eyes treated in accordance with the Dresden protocol). Patients were observed for 1 year postoperatively. Maximum keratometry (Kmax), mean keratometry in the inferior part of the cornea (I index), corrected distance visual acuity (CDVA), demarcation line observed in optical coherence tomography, and nerves and cell densities analyzed by confocal microscopy were compared preoperatively and at 1 year postoperatively. Results: The difference was significant for both Kmax ( P < .01) and I index ( P < .01) between the two groups. CDVA improved significantly in the TG-CXL (0.2162 ± 0.2495 logMAR, P < .05) versus the C-CXL (0.2648 ± 0.2574 logMAR, P = .104) group. A stromal demarcation line was observed in both treatment groups, with similar depth at the top of the cone ( P = .391), but it was shallower at the surrounding area in the TG-CXL group ( P < .0001). Stromal evaluation by confocal microscopy showed less damage and faster healing in the surrounding area than on the cone area in the TG-CXL group. CONCLUSIONS: At 1 year postoperatively, TG-CXL seems to be as safe as C-CXL with stronger flattening in Kmax and I index and better improvement in CDVA. TG-CXL induces a biological gradient between the cone and the surrounding area that facilitates nerve and cell recovery. [ J Refract Surg. 2017;33(5):290–297.]

International audience; Purpose: We compared an iontophoresis riboflavin delivery technique for transepithelial corneal collagen crosslinking (I-CXL) with a conventional CXL (C-CXL).Methods: We designed three experimental sets using 152 New Zealand rabbits to study riboflavin application by iontophoresis using charged riboflavin solution (Ricrolin+) with a 1-mA current for 5 minutes. The first set was to compare riboflavin concentration measured by HPLC in corneas after iontophoresis or conventional riboflavin application. The second set was to analyze autofluorescence and stromal collagen modification immediately and 14 days after I-CXL or C-CXL, by using nonlinear two-photon microscopy (TP) and second harmonic generation (SHG). In the third set, physical modifications after I-CXL and C-CXL were evaluated by stress-strain measurements and by studying corneal resistance against collagenase digestion. Results: Based on HPLC analysis, we found that iontophoresis allowed riboflavin diffusion with 2-fold less riboflavin concentration than conventional application (936.2 ± 312.5 and 1708 ± 908.3 ng/mL, respectively, P < 0.05). Corneal TP and SHG imaging revealed that I-CXL and C-CXL resulted in a comparable increased anterior and median stromal autofluorescence and collagen packing. The stress at 10% strain showed a similar stiffness of corneas treated by I-CXL or C-CXL (631.9 ± 241.5 and 680.3 ± 216.4 kPa, respectively, P = 0.908). Moreover, we observed an increased resistance against corneal collagenase digestion after I-CXL and C-CXL (61.90% ± 5.28% and 72.21% ± 4.32% of remaining surface, respectively, P = 0.154).Conclusions: This experimental study suggests that I-CXL is a promising alternative methodology for riboflavin delivery in crosslinking treatments, preserving the epithelium.

Corneal collagen crosslinking (CXL) is usually practiced on keratoconic corneas to strengthen the corneal biomechanical structure. The conventional CXL procedure, with riboflavin and ultraviolet A (UVA), initially involves corneal de-epithelialization to allow riboflavin penetration into the stroma. Discomfort and complications are related to this corneal debridement. Thus, transepithelial CXL has emerged to substitute for the conventional method. This technique preserves the epithelium and tends to ensure the same efficiency of corneal stiffening. To allow riboflavin penetration through the epithelial barrier, several chemical modifications to riboflavin, such as addition of enhancers (EDTA, benzalkonium chloride or 20% alcohol), and osmolar modifications have been applied. The most studied transepithelial riboflavin is Ricrolin TE®, which combines two enhancers: amino alcohol and EDTA. The results of clinical studies have not demonstrated effectiveness yet. Moreover, the iontophoresis technique, a noninvasive procedure during which a low-intensity electric current is applied to enhance the penetration of riboflavin into the stroma, stands out as being as efficient as conventional application of riboflavin, based on a pre-clinical study. Another area of improvement of CXL is modification of the UVA irradiation profile or shortening of the UVA irradiation time while increasing the irradiation power. A longer follow-up and more investigations are still necessary to define the future of transepithelial CXL, but it is an exciting and rapidly evolving area.

International audience; Purpose: To characterize the expression of the bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases (collectively called BTPs), which include BMP-1, mammalian tolloid (mTLD), and mammalian tolloid-like 1 (mTLL-1) and 2 (mTLL-2), as well as the associated proteins procollagen C-proteinase enhancers (PCPE-1 and -2), in corneal scarring. Methods: Using a mouse full-thickness corneal excision model, wound healing was followed for up to 28 days by transmission electron microscopy, immunohistology (BMP-1/mTLD and PCPE-1), and quantitative PCR (Q-PCR: collagen III, BMP-1/mTLD, mTLL-1, mTLL-2, PCPE-1, PCPE-2). Bone morphogenetic protein-1/mTLD and PCPE-1 were also immunolocalized in cases of human corneal scarring following injuries. Results: In the mouse model, throughout the follow-up period, there was a large increase in collagen III mRNA expression in the stroma. By transmission electron microscopy, there was marked cellular infiltration into the wound as well as disorganization of collagen fibrils, but no significant difference in fibril diameter. In control corneas, by Q-PCR, BMP-1/mTLD showed the highest expression, compared to low levels of mTLL-1 and undetectable levels of mTLL-2, in both epithelium and stroma. Following wounding, both BMP-1/mTLD and PCPE-1 mRNA and protein increased, while PCPE-2 mRNA decreased. Finally, by immunofluorescence, BMP-1/mTLD and PCPE-1 were strongly expressed in the scar region in both mouse and human corneas. Conclusions: Bone morphogenetic protein-1/mTLD and PCPE-1 are upregulated in corneal scars. Both proteins may therefore contribute to the process of corneal scarring.

Purpose Very low-density lipoprotein receptor mutant mice (Vldlr(-/-)) demonstrate retinal neovascularisation. Monoclonal antibody CL1-R2 recognizes human membrane receptor CD160, which is expressed on activated endothelial cells of neovessels but not in vessels of healthy tissues. In this study, we evaluated the therapeutic potential of CL1R2 antibody in Vldlr(-/-) mice as a model for exudative age-related macular degeneration and macular telangiectasia. Methods Thirty Vldlr(-/-) mice benefitted at postnatal day (P) 42 from retinal angiography. Mice population was then divided in three groups (ten mice per group). According to the groups, mice underwent intravitreal injection of CL1-R2 or Bevacizumab or control antibody. At P56, mice benefitted from angiography and were sacrificed. Results At P42, Vldlr(-/-) retinas presented with neovascular lesions. At P56, we observed decrease of neovascular lesions in eyes treated with CL1R2 antibody and with bevacizumab. This decrease of neovascular lesions was not observed in control mice. Conclusion CL1R2 antibody, as well as Bevacizumab, promotes the regression of pathologic retinal neovascularization in the Vldlr knockout mouse. As CL1R2 is an activator of NK cells, our result suggest that the activation of NK cells inhibits the development of Vldlr(-/-) mice retinal neovascularisation.

Cassagne Myriam. L'utilisation des éléments de technique de danse dans les compositions des gymnastes. In: Les Cahiers de l'INSEP, n°18-19, 1997. G.R.S., le sens d’une évolution. pp. 137-145.

Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. Methods and results A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband9s mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. Conclusions We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.

Phakic intraocular lenses (pIOLs) implantation concerns high ametropia. Initially developed for high myopia correction, the treatment fields were expanded to astigmatism and hyperopia corrections. Thr

Keratoconus (KC) is a vision-threatening condition characterized by thinning and deformation of the cornea. It is one of the most common indications for corneal grafting in industrialized countries. The disease prevalence is approximately 1 in 2000. Familial aggregation, together with increased familial risk, suggests important genetic influences on its pathogenesis. To date, it has been shown that several genomic regions are linked to KC rare familial forms but no genes have been identified as responsible for common KC. Aside from genetic determinants, environmental stresses such as eye rubbing or atopy have been suggested as possible causes or aggravating factors in KC. The interaction of genetics and environmental factors in diseases occurrence contributes to the development of complex and multifactorial trait, such as KC. And, despite the many attempts to reveal KC pathophysiology, the mechanisms leading to its corneal characteristics and vision impairment are still poorly understood. In this presentation, we will discuss all works that have been achieved on keratoconus pathophysiology and we will consider future directions on this topic.