Multicenter prospective observational study of dupilumab-induced ocular events in atopic dermatitis patients.

BACKGROUND: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. OBJECTIVE: To examine the incidence, characteristics and risk factors of dupilumab-induced ocular adverse events. METHODS: A prospective, multicenter, and real-life study in adult AD patients treated with dupilumab. RESULTS: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab-induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938-30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635-21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158-13.90]; p = 0.031) were independent factors associated with dupilumab-induced blepharoconjunctivitis. LIMITATIONS: Our follow-up period was 16 weeks and some late-onset time effects may still occur. CONCLUSION: This study showed that most dupilumab-induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study.

Performance and Safety of a Sodium Hyaluronate Tear Substitute with Polyethylene Glycol in Dry Eye Disease: A Multicenter, Investigator-Masked, Randomized, Noninferiority Trial.

Purpose: To compare the performance and safety of 2 tear substitutes containing sodium hyaluronate (SH); one containing 0.15% SH and polyethylene glycol (PEG) 8000, and the other containing 0.18% SH. Methods: In this multicenter, randomized, investigator-masked, noninferiority trial, 83 patients with moderate or severe dry eye disease underwent a 2-week washout, and were then randomly assigned (1:1) to receive SH plus PEG tear substitute (n = 45) or comparator SH tear substitute (n = 38) 3-6 times daily for 3 months. The primary performance endpoint was the change from baseline in the ocular surface fluorescein staining (OSFS) score on day 28 in the per-protocol (PP) population, according to the 15-point Oxford Scheme, with a noninferiority margin of 2. Results: Both groups improved significantly in terms of signs and symptoms. Among the 78 patients without major protocol deviations (the PP population), the OSFS score decreased by 2.9 ± 2.0 on day 28 from 5.4 ± 1.3 at baseline in the SH plus PEG group and by 2.3 ± 2.2 from 5.2 ± 1.4 in the comparator group (95% confidence interval of the difference: -1.2 to 0.3), demonstrating noninferiority. On day 90, the improvement in OSFS scores was significantly greater in the SH plus PEG group (P = 0.0002). The safety profiles were satisfactory in both groups. Conclusion: SH plus PEG tear substitute was noninferior to SH tear substitute in the studied population and may provide additional benefits in the long term. ClinicalTrials.gov ID: NCT02975102.

[Restatment. Allergic-looking conjunctivitis in children]. / Conjonctivites d'allure allergique de l'enfant.

ALLERGIC-LOOKING CONJUNCTIVITIS IN CHILDREN Eye allergies are constantly on the rise in Europe and around the world. It is a common pediatric pathology in general medicine consultation. It is important to know the different clinical forms of the disease so as not to ignore the serious forms and to be able to refer them to the ophthalmologist.

CONJONCTIVITE D'ALLURE ALLERGIQUE CHEZ L'ENFANT Les allergies oculaires sont en constante progression, tant en Europe que dans le monde. Il s'agit d'une pathologie pédiatrique fréquente en consultation de médecine générale, dont il faut connaître les différentes présentations cliniques, afin de ne pas méconnaître les formes graves et de pouvoir les adresser à l'ophtalmologiste.

[Vernal keratoconjunctivitis]. / Kératoconjonctivite vernale.

Vernal keratoconjunctivitis. Chronic inflammatory disease of children and young adults, vernal keratoconjunctivitis is a rare pathology. This allergic ocular pathology should know because it may alter the visual prognosis. Its management is mostly multidisciplinary, associating the ophthalmologist and the allergologist.

Kératoconjonctivité vernale. Maladie inflammatoire chronique de l'enfant et du jeune adulte, la kératoconjonctivite vernale est une pathologie rare. Cette affection oculaire de type allergique doit être connue car elle peut altérer le pronostic visuel. Sa prise en charge thérapeutique est délicate avec un risque iatrogène important. Sa prise en charge est le plus souvent multidisciplinaire, associant l'ophtalmologiste et l'allergologue.

Eyelid fat grafting: Indications, operative technique and complications; a systematic review.

INTRODUCTION: Many recent studies concerning autologous fat grafting in the eyelids have been published, mostly consisting of case reports and retrospective case series. However, no study on the overall complication or satisfaction rate associated with the various grafting techniques exists. We performed a comprehensive literature review to determine the outcomes and complications of eyelid fat grafting, as well as patient satisfaction. METHODS: A systematic review of the literature using the PRISMA criteria was conducted. This protocol was registered at the Prospective Register of Systematic Reviews at the National Institute for Health Research. RESULTS: Sixteen studies, representing 1,159 patients and published between June 2004 and December 2014, were included. Satisfactory results, judged by clinical examination, were observed in all studies. Few postoperative complications were reported. CONCLUSIONS: We demonstrated that the procedures were easy to perform, and achieved satisfactory and sustainable results with few complications in both reconstructive and cosmetic surgery. However, a wide disparity exists in the various fat harvesting, fat purification, and reinjection techniques. Further studies are required to assess the long-term outcomes. Our conclusions should be accepted cautiously due to the small number of articles and the lack of evidence in published studies.

Trends and topics in eye disease research in PubMed from 2010 to 2014.

BACKGROUND: The purpose of this study is to provide a report on scientific production during the period 2010-2014 in order to identify the major topics as well as the predominant actors (journals, countries, continents) involved in the field of eye disease. METHODS: A PubMed search was carried out to extract articles related to eye diseases during the period 2010-2014. Data were downloaded and processed through developed PHP scripts for further analysis. RESULTS: A total of 62,123 articles were retrieved. A total of 3,368 different journals were found, and 19 journals were identified as "core journals" according to Braford's law. English was by far the predominant language. A total of 853,182 MeSH terms were found, representing an average of 13.73 (SD = 4.98) MeSH terms per article. Among these 853,182 MeSH terms, 14,689 different MeSH terms were identified. Vision Disorders, Glaucoma, Diabetic Retinopathy, Macular Degeneration, and Cataract were the most frequent five MeSH terms related to eye diseases. The analysis of the total number of publications showed that Europe and Asia were the most productive continents, and the USA and China the most productive countries. Interestingly, using the mean Five-Year Impact Factor, the two most productive continents were North America and Oceania. After adjustment for population, the overall ranking positions changed in favor of smaller countries (i.e. Iceland, Switzerland, Denmark, and New Zealand), while after adjustment for Gross Domestic Product (GDP), the overall ranking positions changed in favor of some developing countries (Malawi, Guatemala, Singapore). CONCLUSIONS: Due to the large number of articles included and the numerous parameters analyzed, this study provides a wide view of scientific productivity related to eye diseases during the period 2010-2014 and allows us to better understand this field.

Potential of FTIR spectroscopy for analysis of tears for diagnosis purposes.

It has been widely reported that the tear film, which is crucially important as a protective barrier of the eye, undergoes biochemical changes as a result of a wide range of ocular pathology. This tends to suggest the possibility of early detection of ocular diseases on the basis of biochemical analysis of tears. However, studies of tears by conventional methods of biomolecular and biochemical analysis are often limited by methodological difficulties. Moreover, such analysis could not be applied in the clinic, where structural and morphological analyses by, mainly, slit-lamp biomicroscopy remains the recommended method. In this study, we assessed, for the first time, the potential of FTIR spectroscopy combined with advanced chemometric processing of spectral data for analysis of raw tears for diagnosis purposes. We first optimized sampling and spectral acquisition (tears collection method, tear sample volume, and preservation of the samples) for accurate spectral measurement. On the basis of the results, we focused our study on the possibility of discriminating tears from normal individuals from those of patients with different ocular pathologies, and showed that the most discriminating spectral range is that corresponding to variations of CH2 and CH3 of lipid aliphatic chains. We also report more subtle discrimination of tears from patients with keratoconus and those from patients with non-specific inflammatory ocular diseases, on the basis of variations in spectral ranges attributed notably to lipid and carbohydrate vibrations. Finally, we also succeeded in distinguishing tears from patients with early-stage and late-stage keratoconus on the basis of spectral features attributed to protein structure. Therefore, this study strongly suggests that FTIR spectral analysis of tears could be developed as a valuable and cost-saving tool for biochemical-based detection of ocular diseases, potentially before the appearance of the first morphological signs of diseases. Combined with supervised modelling methods and with use of a spectral data base acquired for representative patients, such a spectral approach could be a useful addition to current methods of clinical analysis for improvement of patient care.

Scalability and severity of keratoconus in children.

PURPOSE: To assess the severity of keratoconus at diagnosis and its scalability over a period of 2 years in children compared to adults. DESIGN: A retrospective monocentric study was conducted in the National Reference Center for Keratoconus, Bordeaux (France), between October 1997 and November 2010. METHODS: In total, 216 patients were studied, comprising 49 patients (22.7%) aged ≤ 15 and 167 patients (77.3%) aged ≥ 27 years at diagnosis, who were seen within 2 years of diagnosis. Severity at diagnosis was assessed using Krumeich's classification, and the scalability criteria of the US Food and Drug Administration (2010) were used. Student t tests and χ(2) tests were performed to compare the 2 groups. RESULTS: Keratoconus in children was significantly more severe at diagnosis, with 27.8% being stage 4 vs 7.8% of adults (P < .0001). In addition, ophthalmoscopic signs were more frequent in children (42.9% vs 29.5%, P = .05), while mean values of maximum, average, and minimum keratometry as well as simulated keratometric astigmatism were higher (P < .0001, P = .0002, P = .0005, and P = .001, respectively). After diagnosis, keratoconus did not evolve more frequently in children. However, in the case of progression, keratoconus evolved faster in children, with significant differences in the spherical equivalent and maximum and minimum keratometry (P = .03, P = .02, P = .04, respectively). CONCLUSION: At diagnosis, keratoconus is often more advanced in children than in adults, with faster disease progression. Early detection and close monitoring are therefore crucial in young patients.

Outcomes of deep anterior lamellar keratoplasty for keratoconus: learning curve and advantages of the big bubble technique.

PURPOSE: To evaluate retrospectively the outcomes of a case series of deep anterior lamellar keratoplasties by air dissection (DALK-AD) using the big bubble (BB) technique, in the surgical treatment of keratoconus (KC). METHODS: Forty-four consecutive keratoplasties of 42 patients for KC were performed at the French National Reference Center for KC from January 2008 to June 2010 by the same surgeon with the aim of systematically performing DALK-AD with the BB technique. The outcomes of the DALK-AD not converted to penetrating keratoplasty were analyzed, and a learning curve was established to successfully achieve the DALK-AD using the BB technique. RESULTS: Thirty-two DALK-AD procedures were successfully performed among 44 consecutively operated keratoplasties, with 12 being converted to penetrating keratoplasty during the surgical procedure. At 12 months, the mean best-corrected logarithm of the minimum angle of resolution visual acuity was 0.88 ± 0.14 with 93.3% seeing best-corrected visual acuity ≥ 20/30 and 100% seeing best-corrected visual acuity ≥ 20/40. The mean gain of visual acuity in logarithm of the minimum angle of resolution lines at 6 and 12 months was 6.12 ± 3.97 (P < 0.0001) and 6.94 ± 4.18 (P < 0.005), respectively. The rate for intraoperative and postoperative complications was 31.8% and 4.5%, respectively. CONCLUSION: Despite a learning period needed to successfully perform deep lamellar anterior keratoplasty with the BB technique, this approach is safe and provides very good visual outcomes when adequate baring of Descemet membrane is achieved. The learning curve showed that complications related to this technique decrease significantly after the first 10 cases.

Ophthalmological features associated with COL4A1 mutations.

OBJECTIVE: To investigate the wide variability of ocular manifestations associated with mutations in the COL4A1 gene that encodes collagen IValpha1. METHODS: We clinically evaluated 7 patients from 2 unrelated families in whom ocular features segregated with COL4A1 mutations that were identified by direct sequencing. RESULTS: The G2159A transition (c.2159G>A) that leads to the missense mutation p.Gly720Asp was identified in family A. An ocular phenotype of variable severity was observed in all affected relatives. The missense mutation c.2263G>A, p.Gly755Arg was identified in family B. One patient from family B also displayed notable ocular features. CONCLUSIONS: The COL4A1 mutations may be associated with various ophthalmologic developmental anomalies of anterior segment dysgenesis type, which are reminiscent of Axenfeld-Rieger anomalies (ARA). Cerebrovascular disorders should be added to the list of signs potentially associated with ARA. CLINICAL RELEVANCE: These data suggest that cerebral magnetic resonance imaging may be recommended in the clinical treatment of patients with apparently isolated ARA, even when neurological symptoms or signs are lacking.

Cutaneous and ocular signs of childhood rosacea.

UNLABELLED: Objectives To describe the clinical features of cutaneous and ocular manifestations of childhood rosacea, to propose diagnostic criteria, and to emphasize the possible severity of ocular complications in this age group. DESIGN: Retrospective study. SETTING: Tertiary referral center. Patients Children aged 1 to 15 years who had received a diagnosis of cutaneous and/or ocular rosacea and were seen between January 1, 1996, and December 31, 2005. RESULTS: Of 20 patients, 11 had ocular and cutaneous rosacea, 6 had isolated cutaneous involvement, and 3 had isolated ocular involvement. Dermatologic examination results were sufficient to diagnose rosacea in 12 of the patients (60%). The most common presentation was a papulopustular eruption on a telangiectatic background. In 11 patients (55%), ocular involvement preceded the skin eruption. Among the ophthalmologic manifestations, chalazions and blepharoconjunctivitis were the main presenting symptoms; keratitis was observed in 4 patients and corneal ulcers in 2. Ten patients were treated with oral metronidazole. Intermittent treatment for at least 3 months was used to avoid neurologic toxic effects and to achieve complete remission. Conclusion Although rare, childhood rosacea should be recognized because of the possible severity of ocular involvement.

Axenfeld-Rieger anomaly: a novel mutation in the forkhead box C1 (FOXC1) gene in a 4-generation family.

OBJECTIVE: To characterize DNA mutations in a pedigree of Axenfeld-Rieger anomaly (ARA) (Online Mendelian Inheritance of Man 601631), a clinically and genetically heterogeneous, autosomal dominantly inherited disorder associated with anterior chamber abnormalities and glaucoma. DESIGN: Observational case-control and DNA linkage and screening studies. PARTICIPANTS: Affected (10 cases) and unaffected (5 controls) members of a family with ARA. METHODS: Clinical characteristics of ARA were documented by history or physical examination of symptomatic individuals. With their informed consent, a blood sample was collected from each of 10 affected and 5 unaffected family members. DNA was tested for linkage to the IRID1 locus at chromosome 6p25, a known locus for ARA/Rieger syndrome. A candidate gene previously mapped at this locus, FOXC1, was screened for mutations in cases and controls. Main Outcome Measure Linkage of the ARA phenotype at the 6p25 locus and mutation detected in FOXC1. RESULTS: Direct sequencing of FOXC1 detected a new mutation, T272C, that segregated with the ARA phenotype in this family and was not detected in DNA from family members without ARA. This mutation, a T-->C transition, is predicted to result in a change of isoleucine to threonine (Ile9lThr) in a highly conserved location within the first helix of the forkhead domain. CONCLUSION: Characterization of the FOXC1 mutation in family members with ARA furthers our understanding of the molecular origin of developmental glaucoma and other anterior segment disorders.

Penetrating corneal transplant with inadvertent corneal button inversion.

PURPOSE: To report a penetrating corneal transplant in which there was inadvertent inversion of the corneal button. DESIGN: Interventional case report. METHODS: A 48-year-old man with lattice corneal dystrophy had a third penetrating keratoplasty in the right eye 3 years after the second procedure and 2 years following renal transplantation. RESULTS: Histologic examination of the corneal button from the second penetrating keratoplasty disclosed inadvertent corneal graft inversion. Survival epithelium from the donor in the anterior chamber may be explained by the ocular anterior chamber-associated immune deviation or by the patient's systemic cyclosporine A (CsA) treatment after renal transplantation. CONCLUSIONS: Histologically proven corneal button inversion is a rare cause of corneal graft failure.