Abnormal brain function in photophobic patients with dry eye disease: An fMRI study.

BACKGROUND AND OBJECTIVES: Photophobia, a frequent and disabling symptom observed in various neurological conditions and eye diseases, is thought to involve maladaptive brain functioning. We assessed this hypothesis, using functional magnetic resonance imaging (fMRI) in photophobic patients with minimal-to-severe dry eye disease (DED), as compared to healthy controls. METHODS: This prospective, monocentric, comparative, cohort study included eleven photophobic DED patients compared to eight controls. Photophobic patients had a complete evaluation of DED to exclude any other cause of photophobia. All participants were scanned with fMRI under intermittent light stimulation with a LED lamp (27s. ON, 27 s. OFF), and cerebral activations were studied with univariate contrasts between the ON and OFF conditions, and with functional connectivity methods. RESULTS: Firstly, stimulation activated the occipital cortex more strongly in patients than in controls. Moreover, stimulation deactivated the superior temporal cortex in patients less than in controls. Secondly, functional connectivity analysis showed that light stimulation induced lesser decoupling between the occipital cortex and the salience and visual networks in patients than in controls. DISCUSSION: The current data shows that DED patients with photophobia have maladaptive brain anomalies. There is hyperactivity in the cortical visual system, associated with abnormal functional interactions, both within the visual cortex, and between visual areas and salience control mechanisms. Such anomalies show similarities with other conditions such as tinnitus, hyperacusis, and neuropathic pain. Those findings support novel neurally oriented methods for the care of patients with photophobia.

Management of ocular involvement in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: french national audit of practices, literature review, and consensus agreement.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) can lead to severe ophthalmologic sequelae. The main risk factor is the severity of the initial ocular involvement. There are no recommendations for ocular management during acute phase.We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. We sent a questionnaire on ocular management practices in SJS/ TEN during acute phase to ophthalmologists and dermatologists. The survey focused on ophthalmologist opinion, pseudomembrane removal, topical ocular treatment (i.e. corticosteroids, antibiotics, antiseptics, artificial tear eye drops, vitamin A ointment application), amniotic membrane transplantation, symblepharon ring use, and systemic corticosteroid therapy for ophthalmologic indication. Nine of 11 centers responded. All requested prompt ophthalmologist consultation. The majority performed pseudomembrane removal, used artificial tears, and vitamin A ointment (8/9, 90%). Combined antibiotic-corticosteroid or corticosteroid eye drops were used in 6 centers (67%), antibiotics alone and antiseptics in 3 centers (33%). Symblepharon ring was used in 5 centers (55%) if necessary. Amniotic membrane transplantation was never performed systematically and only according to the clinical course. Systemic corticosteroid therapy was occasionally used (3/9, 33%) and discussed on a case-by-case basis.The literature about ocular management practice in SJS/ TEN during acute phase is relatively poor. The role of specific treatments such as local or systemic corticosteroid therapy is not consensual. The use of preservatives, often present in eye drops and deleterious to the ocular surface, is to be restricted. Early amniotic membrane transplantation seems to be promising.

[Evaluation of the nurse triage at the ophtalmology emergency department of Pierre-Paul-Riquet Hospital]. / Évaluation du questionnaire de tri infirmier aux urgences ophtalmologiques de l'hôpital Pierre-Paul-Riquet au CHU de Toulouse.

INTRODUCTION: The steady increase in the number of visits to the various emergency services combined with the decrease in medical demographics, make it necessary to optimize triage of patients to improve their care. The purpose of this study was to evaluate the pertinence of our triage questionnaire in the classification of ophthalmologic emergencies by severity. METHODS: We used a monocentric cross-sectional study. From September 5 through September 25 2017, 858 patients who had all been seen in the ophthalmology emergency department of Pierre Paul Riquet Hospital of Toulouse university medical center and had responded to the triage nurse questionnaire were included. According to the symptoms presented or not by the patient, a color code was attributed (GREEN, ORANGE or RED) in order of increasing level of emergency. For each patient, we compared the severity of the final diagnosis by Base Score with the level of emergency established by our questionnaire. RESULTS: There were 118 "GREEN" patients, 606 "ORANGE" patients and 134 "RED." We were able to analyze 822 patients. 21.65% of patients were correctly classified, 73.36% were overestimated (of which 87.06% by one level and 12.94% by two levels of severity), and 4.99% were underestimated (of which 90.24% by one level and 9.76% by two levels). CONCLUSION: Our current triage questionnaire is not sufficiently discriminating for effective triage of ophthalmologic emergencies. It often overestimates minor emergencies, causing a delay in treating other emergencies. We propose a new questionnaire modified according to the results obtained during our study.

[Assessment of astigmatism associated with the iris-fixated ARTISAN aphakia implant: Anterior fixation versus posterior fixation, study of postoperative follow-up at one year]. / Évaluation de l'astigmatisme associé à l'implant ARTISAN Aphakia fixé à l'iris en face antérieure versus face postérieure : étude du suivi postopératoire sur un an.

PURPOSE: The goal of our retrospective, single-center study of a case series was to compare the total, corneal, and internal astigmatism, and the visual acuity at one year after combined or stand-alone surgery consisting of iris fixation of an iris-claw intraocular lens (ARTISAN aphakia) in aphakic patients, according to whether the lens was fixated to the anterior (n=21) or posterior (n=51) surface of the iris. RESULTS: We did not find a significant difference between these two types of fixation for any of the studied variables. The surgically induced astigmatism was 1.67 D at 176° in group A versus 1.19 D at 11° in group P. CONCLUSION: Although this surgery creates additional corneal astigmatism, it has not been proven that it differs depending on the type of fixation of the iris-claw. If we adhere to the notion that the posterior fixated iris-claw decreases the risk of endothelial decompensation in case the implant becomes disenclavated, then reverse iris fixation of the iris-claw makes sense.

Visual Impairment Screening at the Geriatric Frailty Clinic for Assessment of Frailty and Prevention of Disability at the Gérontopôle.

OBJECTIVES: 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. DESIGN: Retrospective, observational cross-sectional, single-centre study. SETTING: Institutional practice. PARTICIPANTS: Patients were screened for frailty during a single-day hospital stay between October 2011 and October 2014 (n = 1648). MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: 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.

[Efficacy of corneal cross-linking for the treatment of keratoconus]. / Efficacité du cross-linking du collagène cornéen pour le traitement du kératocône.

Keratoconus (KC) is a complex disease whose pathophysiology is only partially understood. The priority in management is to halt the progression of corneal deformation as soon as possible in the course of KC disease. Corneal cross-linking (CXL) is at present the only dedicated treatment for this purpose. Its biochemical mechanism of action leads to changes in the viscoelastic properties of the cornea induced by matrix bonding and renewal of keratocytes. The effect of CXL is difficult to quantify when measured in in-vivo conditions because of a lack of consistent tools adapted for clinical practice. Nevertheless, a large amount of evidence has been collected so far confirming the positive action of CXL on corneal structural reinforcement, and numerous studies have demonstrated significant efficacy in halting progression of KC with long-term follow-up. Published studies, however, are of relatively low scientific power given the great heterogeneity of the disease and the numerous associated biases in evaluation. The purpose of this paper is to summarize the consistent evidence of efficacy of CXL and to justify its role in our therapeutic armamentarium for management of progressive KC.

[High myopic patients: A survey of their history, feelings, beliefs and needs]. / Enquête sur l'histoire, le ressenti, les croyances et les besoins des patients myopes forts.

BACKGROUND AND OBJECTIVES: High myopia (HM), which affects 0.9 to 3.1% of the population, is a major cause of vision loss. The purpose of this investigation was to study and evaluate the impact of their high myopia on the daily lives of patients and to better understand their expectations in order to better meet their needs. MATERIALS AND METHODS: The survey was conducted between February 19 and March 21, 2014. To be eligible, patients had to have myopia of at least -8 diopters and be over 40 years of age, with or without myopic complications. Patients' degree of myopia was defined as the optical prescription of their worse eye. The 123 patients included were interviewed by phone using a questionnaire developed and validated by a scientific committee composed of experts and members of the patients' Association against myopic maculopathy (AMAM). The phone interview, semi-structured, lasted 20 minutes. RESULTS: On average, myopia was -11.7 diopters. Women accounted for 71% of the population, 89% of patients were under 65 years and were mostly professionals (65%). Over half of the subjects reported myopic complications; 5% of patients had choroidal neovascularization (CNV). Only 29% had been informed of the risk of CNV or maculopathy. HM was a handicap in sports for 64% of patients, in leisure activities for 51%, and in professional activities for more than a quarter (28%). Only 56% of HM patients reported living perfectly well with their condition. CONCLUSIONS: This survey is the first study on the daily life of people with HM aiming to analyze their social and emotional environment. It shows that HM has a profound impact on the daily lives of patients and may affect social life and professional activity. Most myopic patients possess incomplete or unclear information about the nature and risk of myopic complications. They expressed the desire to be better informed about their condition earlier, before the onset of complications.

[What were the obstacles to the development of outpatient cataract surgery in Toulouse University Hospital in 2013?]. / Quels obstacles au développement de la chirurgie ambulatoire de la cataracte au CHU de Toulouse en 2013?

INTRODUCTION: Cataract surgery is an ideal candidate for outpatient care. In 2013, in the Toulouse University Hospital, outpatient care rate for phacoemulsification was 75.8%. We conducted this study to identify the barriers that limit the development of outpatient cataract surgery in our establishment. MATERIAL AND METHODS: A retrospective observational study was conducted. We included all patients who underwent phacoemulsification (Medical Act Code BFGA004) as a traditional inpatient in 2013. We excluded admissions for which the medical, anesthesia or nursing records, as well as scheduling sheets, were incomplete. Patients were classified according to the reason for inpatient hospitalization and the type of surgery: cataract as primary surgery or cataract as combined procedure. RESULTS: Two hundred and ninety-eight stays were included with a mean age of 66.8 ± 16.8 years, and a male/female ratio of 0.76. The indication for inpatient hospitalization was a social, surgical or anesthetic reason in the following respective proportions: 41, 34 and 8% of cases. Failure of ambulatory care represented 7% of cases. Social isolation represented 89% of social reasons. In a combined gesture, the reason was surgical in 89% of cases. CONCLUSION: Development of outpatient surgery requires the participation of all involved. Taking into account the social factors is an essential element for developing ambulatory surgery. Social isolation is a frequent situation requiring a societal response. With regard to surgical considerations, practice patterns must target outpatient combined procedures in particular.

Peptides derived from the dependence receptor ALK are proapoptotic for ALK-positive tumors.

ALK is a receptor tyrosine kinase with an oncogenic role in various types of human malignancies. Despite constitutive activation of the kinase through gene alterations, such as chromosomal translocation, gene amplification or mutation, treatments with kinase inhibitors invariably lead to the development of resistance. Aiming to develop new tools for ALK targeting, we took advantage of our previous demonstration identifying ALK as a dependence receptor, implying that in the absence of ligand the kinase-inactive ALK triggers or enhances apoptosis. Here, we synthesized peptides mimicking the proapoptotic domain of ALK and investigated their biological effects on tumor cells. We found that an ALK-derived peptide of 36 amino acids (P36) was cytotoxic for ALK-positive anaplastic large-cell lymphoma and neuroblastoma cell lines. In contrast, ALK-negative tumor cells and normal peripheral blood mononuclear cells were insensitive to P36. The cytotoxic effect was due to caspase-dependent apoptosis and required N-myristoylation of the peptide. Two P36-derived shorter peptides as well as a cyclic peptide also induced apoptosis. Surface plasmon resonance and mass spectrometry analysis of P36-interacting proteins from two responsive cell lines, Cost lymphoma and SH-SY5Y neuroblastoma, uncovered partners that could involve p53-dependent signaling and pre-mRNA splicing. Furthermore, siRNA-mediated knockdown of p53 rescued these cells from P36-induced apoptosis. Finally, we observed that a treatment combining P36 with the ALK-specific inhibitor crizotinib resulted in additive cytotoxicity. Therefore, ALK-derived peptides could represent a novel targeted therapy for ALK-positive tumors.

[Multimodal imaging in the diagnosis of acute macular neuroretinopathy]. / Intérêt de l'imagerie multimodale dans le diagnostic de neurorétinopathie maculaire aiguë

INTRODUCTION: Acute macular neuroretinopathy is a retinal disease, usually presenting with a "normal fundus". Thus, this condition can be mistaken for optic neuropathy. Herein we present five clinical cases of patients affected with acute macular neuroretinopathy; one of them is a retrospective diagnosis while the others were diagnosed on initial examination. In the five cases, multimodal imaging with infrared photography and OCT helped to establish the diagnosis. MATERIAL AND METHODS: Retrospective study of five clinical cases. Initial and final best visual acuities as well as infrared and OCT imaging were collected for all patients. RESULTS: All patients initially reported a visual disturbance associated with a more or less severe decrease in visual acuity. Infrared imaging showed a dark, perifoveolar appearance of the lesions. In all cases, OCT images showed thickening and hyperreflectivity of the outer plexiform layer, extending towards the outer retinal layers. CONCLUSION: Acute macular neuroretinopathy is a clinical entity that has been long-described, which now benefits widely from new imaging technologies, allowing an earlier and more accurate diagnosis, but calling into question the actual name of this condition. The exact pathophysiology of the condition remains nonetheless incompletely elucidated.

[Recurrent bilateral anterior uveitis due to Leishmania infantum in a patient with immune deficiency related to HIV infection: a case report and literature review]. / Uvéite antérieure bilatérale récidivante à Leishmania infantum chez un patient présentant un déficit immunitaire lié à une infection à VIH : à propos d'un cas et revue de la littérature.

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.

[Pathophysiology of myopia: nature versus nurture]. / Physiopathologie de la myopie, entre hérédité et environnement.

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.

[Keratoconus]. / Kératocône.

Keratoconus is a slowly progressive, non-inflammatory disorder of the eye characterized by thinning and protrusion of the cornea. Typically diagnosed in the patient's adolescent years, keratoconus may lead to substantial distortion of vision primarily from irregular astigmatism and myopia, and secondarily from corneal scarring. The classic histopathologic features include breaks in Bowman's layer and thinning of the corneal stroma. The etiology of keratoconus remains unclear. Form fruste keratoconus shows little progression, and has become known due to videotopographic analysis; it is very important to rule out in refractive surgery candidates. Treatment begins first and foremost with contact lenses, progressing to surgery as contact lens intolerance develops, with the goal of stabilization, including: cross-linking, intrastromal corneal ring segments and corneal transplantation.

[Surgical management of a recurrent iris stromal cyst]. / Prise en charge chirurgicale d'un kyste du stroma irien récidivant.

INTRODUCTION: Cysts of the iris stroma may be congenital or acquired. They are rare tumors of the anterior segment. We describe the case of a 51-year-old patient presenting with a recurrent iris stromal cyst. OBSERVATION: The patient presented emergently for sudden recurrence of an iris stromal cyst with decreased visual acuity. He had already undergone needle aspiration and argon laser photocoagulation of the cyst 1 year previously. A Ultrasound BioMicroscopy (UBM) examination was performed to rule out any malignant tumor of the iris or ciliary body. Surgical treatment consisted of complete removal of the external layer of the cyst with Implantable Contact Lens (ICL) forceps after marsurpialization with scissors. The postoperative course was uneventful. CONCLUSION: Cysts of the iris stroma are rare benign tumors that pose problems due to their extension into the anterior chamber and recurrence.

Pediatric cataract, myopic astigmatism, familial exudative vitreoretinopathy and primary open-angle glaucoma co-segregating in a family.

PURPOSE: To describe an Australian pedigree of European descent with a variable autosomal dominant phenotype of: pediatric cortical cataract (CC), asymmetric myopia with astigmatism, familial exudative vitreoretinopathy (FEVR), and primary open-angle glaucoma (POAG). METHODS: Probands with CC, FEVR, and POAG were enrolled in three independent genetic eye studies in Tasmania. Genealogy confirmed these individuals were closely related and subsequent examination revealed 11 other family members with some or all of the associated disorders. RESULTS: Twelve individuals had CC thought to be of childhood onset, with one child demonstrating progressive lenticular opacification. One individual had severe retinal detachment while five others had dragged retinal vessels. Seven individuals had POAG. Seven individuals had myopia in at least one eye ≤-3 Diopters. DNA testing excluded mutations in myocilin, trabecular meshwork inducible glucocorticoid response (MYOC) and tetraspanin 12 (TSPAN12). Haplotype analysis excluded frizzled family receptor 4 (FZD4) and low density lipoprotein receptor-related protein 5 (LRP5), but only partly excluded EVR3. Multipoint linkage analysis revealed multiple chromosomal single-nucleotide polymorphisms (SNPs) of interest, but no statistically significant focal localization. CONCLUSIONS: This unusual clustering of ophthalmic diseases suggests a possible single genetic cause for an apparently new cataract syndrome. This family's clinical ocular features may reflect the interplay between retinal disease with lenticular changes and axial length in the development of myopia and glaucoma.

[Predictive factors for successful Ferrara intracorneal ring segment implantation in keratoconus]. / Facteurs prédictifs de succès des anneaux intracornéens de Ferrara dans le kératocône.

OBJECTIVE: To define predictive factors after manual implantation of intrastromal corneal ring segments (Ferrara ring) for the management of keratoconus. PATIENTS AND METHODS: Twenty-five eyes of 25 patients with keratoconus were implanted with Ferrara intracorneal ring segments using a mechanical procedure. We measured corneal ring implantation depth, best spectacle-corrected visual acuity (BSCVA), as well as refractive and keratometric outcomes. Patients were separated into two groups according to the gain of at least two lines of BSCVA ("good response") or the gain of only one line of BSCVA, no change, or the loss of lines of BSCVA ("poor response"). RESULTS: After a 6-month follow-up, 41% patients experienced a gain of at least two lines of BSCVA, 31.8% a gain of only one line, 13.6% no change, and 13.6% a loss of BSCVA. The sphere reduced from 4.39 to 2.34D (p<0.01), the cylinder from 4.19 to 2.77D (p<0.01), and the mean keratometry from 51.44 to 48.74D (p<0.02). As successful predictive factors, we found the asymmetry of keratoconus (p<0.01) in relation to the steepest meridian and patients implanted with a single ring (p<0.02). CONCLUSION: Defining preoperative successful predictive factors for Ferrara intracorneal ring segments is essential to enhance postoperative outcomes.

[Characterization of the biometric eye profile of a high myopic population: does high myopia correspond to a homogenous phenotype?]. / Caractérisation du profil biométrique oculaire d'une population myope fort: la myopie forte correspond-elle à un phénotype homogène?

PURPOSE: High myopia is a public health problem because of its high prevalence and is a major cause of blindness. The physiopathology of myopia remains unknown and mechanisms causing the disease are most probably complex, combining acquired environmental and genetic factors. The most recent data suggest that genetic determinisms of high myopia could be highly dependent on subject phenotype. The aim of this study was to analyse the ocular components of a high myopic population to verify whether high myopia corresponds to a homogeneous phenotype. PATIENTS AND METHODS: We analysed the biometric characteristics of 718 myopic eyes with a spherical equivalent of less than -5 diopters. The biometric parameters (corneal radius, axial length, and intraocular pressure) were compared controlling for sex and the degree of myopia. RESULTS: We found a difference between the phenotype of males and females. For men, axial length was the only determinant of the myopic phenotype, whereas for women, the myopic phenotype was determined by axial length and corneal radius. This difference between the phenotypes was more evident for myopia with a spherical equivalent greater than -10 diopters (moderate myopia). This difference between males and females disappeared in myopia less than -15 diopters. CONCLUSION: There are intersex differences considering the high myopia phenotype at a spherical equivalent less than -5 diopters. However, this difference disappears for extremely high myopia with a spherical equivalence of less than -15 diopters.

Matrix metalloproteinase 14 overexpression reduces corneal scarring.

Once a corneal scar develops, surgical management remains the only option for visual rehabilitation. Corneal transplantation is the definitive treatment for a corneal scar. In addition to the challenges posed by graft rejections and other postoperative complications, the lack of high-quality donor corneas can limit the benefits possible with keratoplasty. The purpose of our study was to evaluate a new therapeutic strategy for treating corneal scarring by targeting collagen deposition. We overexpressed a fibril collagenase (matrix metalloproteinase 14 (MMP14)) to prevent collagen deposition in the scar tissue. We demonstrated that a single and simple direct injection of recombinant adeno-associated virus-based vector expressing murine MMP14 can modulate gene expression of murine stromal keratocytes. This tool opens new possibilities with regard to treatment. In a mouse model of corneal full-thickness incision, we observed that MMP14 overexpression reduced corneal opacity and expression of the major genes involved in corneal scarring, especially type III collagen and α-smooth muscle actin. These results represent proof of concept that gene transfer of MMP14 can reduce scar formation, which could have therapeutic applications after corneal trauma.