[Holoclar®, an autologous stem cells graft for sight recovery after ocular burns]. / Comment je traite. Les brûlures oculaires par Holoclar®, une greffe autologue de cellules souches pour rendre la vue.

Ocular chemical or physical burns currently represent 12 % of domestic accidents in Europe. They can lead to numerous ophthalmologic sequelae ranging from simple superficial keratitis to conjunctival ischemia and the destruction of limbal corneal stem cells. This results in damages to the cornea which can progress to neovascularization and corneal invasion by conjunctival tissue. Long term consequences affect ocular function (sometimes blindness, stromal degradation, infections, or even ocular perforation). Until now, few treatments were available to restore corneal transparency after a trauma. Patients affected by post-traumatic limbal stem cell deficiency unfortunately had little prospect. Regenerative cell therapy, of which Holoclar® is a part, could revolutionize the future of these patients.

Les brûlures oculaires chimiques ou physiques représentent actuellement 12 % des accidents domestiques en Europe. Ces accidents peuvent entrainer de nombreuses séquelles au niveau ophtalmologique allant de la simple kératite superficielle jusqu'à l'ischémie conjonctivale et la destruction des cellules souches limbiques cornéennes. En résultent des atteintes de la cornée pouvant évoluer vers une néovascularisation et une invasion de tissu conjonctival parfois cécitante, une dégradation stromale, des infections, voire même une perforation oculaire avec perte de la fonction oculaire. Jusqu'à présent, peu de traitements étaient disponibles pour rétablir une transparence cornéenne à distance du traumatisme, et les patients avec une déficience post-traumatique en cellules souches limbiques n'avaient malheureusement que peu de perspective. La thérapie cellulaire régénérative, dont fait partie Holoclar®, pourrait révolutionner l'avenir de ces patients.

[Peripheral ulcerative keratitis]. / Les kératites à ulcères périphériques.

Peripheral ulcerative keratitis (PUK) is a disorder of the juxtalimbal cornea characterised by a crescent-shape destructive inflammation of corneal stroma. PUK can be associated with various ocular and systemic infectious and non infectious diseases. Different systemic autoimmune vasculitis that can prove potentially fatal may present as PUK. Potentially serious ocular complications of PUK exist. A careful clinical evaluation helps in timely diagnosis and prevention of complications.

Les kératites à ulcères périphériques (PUK) sont des maladies inflammatoires destructives du stroma cornéen juxta-limbique. Celles-ci peuvent être associées à de nombreuses pathologies systémiques ou oculaires, infectieuses ou non. Plusieurs vascularites auto-immunes connues, pouvant être éventuellement fatales, peuvent présenter un mode d'entrée clinique sous la forme d'une PUK. Il existe de nombreuses complications oculaires graves. Une évaluation clinique minutieuse aide à poser un diagnostic précoce et à prévenir certaines complications. Peripheral ulcerative keratitis.

[Ophthalmologic signs in a KBG syndrome, a rare genetic disease]. / Manifestations ophtalmologiques dans un syndrome KBG, une maladie génétique rare.

KBG syndrome, named after the initials of the first 3 families reported, is a rare genetic syndrome caused by a deletion or a mutation of ANKRD11 (ankyrin repeat domain-containing protein 11) gene. Its prevalence is probably underestimated because of a variable expressivity; moreover, most of its clinical characteristics are not specific. There is no consensus about its diagnostic criteria. Ophthalmologic manifestations have sometimes been described among more frequent clinical signs. Early detection is critical and multidisciplinary care is requested in order to ensure the patient's independence. We report the case of a 16 years old boy diagnosed with a KBG syndrome after more than one year of genetic research, motivated by a short stature, high refractive errors and bilateral corneal clouding.

Le syndrome KBG, nommé selon les initiales des 3 premières familles identifiées, est un syndrome génétique rare lié à une délétion ou à une mutation du gène ANKRD11 (ankyrin repeat domain-containing protein 11). Sa prévalence est probablement sous-estimée en raison d'une expressivité variable et du fait que la plupart de ses caractéristiques cliniques ne sont pas spécifiques. Il n'existe pas de consensus quant à ses critères diagnostiques. Une atteinte ophtalmologique a parfois été décrite parmi d'autres manifestations plus fréquentes. Un diagnostic précoce est crucial et la prise en charge multidisciplinaire afin de garantir l'autonomie future du patient. Nous décrivons ici le cas d'un adolescent de 16 ans chez qui un diagnostic de syndrome KBG a été posé après plus d'un an de recherche génétique, motivée par une petite taille, une amétropie importante et des opacités cornéennes bilatérales.

[Osteo-odonto-keratoprosthesis: a tooth to regain sight]. / L'ostéo-odonto-kératoprothèse : une dent pour retrouver la vue.

As the leading cause of blindness in the world, corneal diseases are second only to cataracts. However, the epidemiology of corneal disease is complex and includes a wide variety of infectious and inflammatory eye diseases (trachoma), immune sequelae (cicatricial pemphigoid on Lyell's disease) of after trauma (chemical burn). The general treatment for severe corneal disease is the corneal transplantation with penetrating keratoplasty. However, the failure of this treatment is virtually certain when the ocular surface is severely compromised. Keratoprosthesis is therefore the only viable option to restore vision in these patients. Only practiced by less than a dozen teams in the world, the osteo-odonto-keratoprosthesis (OOKP) is regularly practiced at the University Hospital of Liège, thanks to a close collaboration between the ophthalmology and maxillofacial surgery teams. Thanks to removal of a tooth and his bone support, patients suffering from bilateral dry eye following pathologies such as burns or cicatricial pemphigoid can benefit from this technique in order to recover an optimal visual acuity in a sustainable way.

En tant que cause majeure de cécité dans le monde, les maladies de la cornée se trouvent au second rang après la cataracte. L'épidémiologie des maladies cornéennes est complexe et englobe une grande variété de maladies oculaires infectieuses (trachomes) et inflammatoires, de séquelles immunitaires (pemphigoïde oculaire cicatricielle, syndrome de Lyell) ou après traumatisme (brûlure chimique). Le traitement habituel en cas de maladie cornéenne grave est la greffe cornéenne par kératoplastie transfixiante. Cependant, l'échec de cette technique est pratiquement inéluctable lorsque la surface oculaire est gravement compromise. La kératoprothèse représente alors la seule option viable pour restaurer la vue chez ces patients. Seulement pratiquée par moins d'une dizaine d'équipes dans le monde, la technique de l'ostéo-odonto-kérato-prothèse (OOKP) est pratiquée au CHU de Liège. Elle nécessite une collaboration étroite entre ophtalmologues et chirurgiens maxillo-faciaux expérimentés. Grâce au prélèvement d'une dent et de ses tissus de soutien, les patients atteints de cécité cornéenne bilatérale peuvent bénéficier de cette technique afin de récupérer une acuité visuelle optimale de manière durable.

The culture, mental health and psychosocial wellbeing of Rohingya refugees: a systematic review.

AIMS: Despite the magnitude and protracted nature of the Rohingya refugee situation, there is limited information on the culture, mental health and psychosocial wellbeing of this group. This paper, drawing on a report commissioned by the United Nations High Commissioner for Refugees (UNHCR), aims to provide a comprehensive synthesis of the literature on mental health and psychosocial wellbeing of Rohingya refugees, including an examination of associated cultural factors. The ultimate objective is to assist humanitarian actors and agencies in providing culturally relevant Mental Health and Psychosocial Support (MHPSS) for Rohingya refugees displaced to Bangladesh and other neighbouring countries. METHODS: We conducted a systematic search across multiple sources of information with reference to the contextual, social, economic, cultural, mental health and health-related factors amongst Rohingya refugees living in the Asia-Pacific and other regions. The search covered online databases of diverse disciplines (e.g. medicine, psychology, anthropology), grey literature, as well as unpublished reports from non-profit organisations and United Nations agencies published until 2018. RESULTS: The legacy of prolonged exposure to conflict and persecution compounded by protracted conditions of deprivations and displacement is likely to increase the refugees' vulnerability to wide array of mental health problems including posttraumatic stress disorder, anxiety, depression and suicidal ideation. High rates of sexual and gender-based violence, lack of privacy and safe spaces and limited access to integrated psychosocial and mental health support remain issues of concern within the emergency operation in Bangladesh. Another challenge is the limited understanding amongst the MHPSS personnel in Bangladesh and elsewhere of the language, culture and help-seeking behaviour of Rohingya refugees. While the Rohingya language has a considerable vocabulary for emotional and behavioural problems, there is limited correspondence between these Rohingya terms and western concepts of mental disorders. This hampers the provision of culturally sensitive and contextually relevant MHPSS services to these refugees. CONCLUSIONS: The knowledge about the culture, context, migration history, idioms of distress, help-seeking behaviour and traditional healing methods, obtained from diverse sources can be applied in the design and delivery of culturally appropriate interventions. Attention to past exposure to traumatic events and losses need to be paired with attention for ongoing stressors and issues related to worries about the future. It is important to design MHPSS interventions in ways that mobilise the individual and collective strengths of Rohingya refugees and build on their resilience.

A direct test of the diathesis-stress model for depression.

The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10-3) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci.

Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

[Updates in corneal transplantation]. / Nouvelles approches des greffes de cornée.

Corneal transplantation or keratoplasty has rapidly developed over the last 10 years. Penetrating keratoplasty, a well-known operation consisting of full thickness replacement of the cornea, has remained the dominant procedure for a long time. It allows appropriate therapy of most causes of corneal blindness. However, this technique is currently evolving toward slamellar keratoplasties which selectively treat the specific affected layers: deep anterior lamellar keratoplasty replaces the diseased corneal stromal layers; endothelial keratoplasty replace the affected endothelium. This article will present these techniques, and briefly discuss their advantages.

[How I treat...a red eye]. / Comment je traite...un oeil rouge.

Before any initiation of treatment for a red eye, an accurate differential diagnosis must absolutely be done, as considered in a previous article. Red eye can result from benign diseases, but also from serious pathologies which shouldn't be neglected, as they require a rapid ophtalmologist management. This is the case for keratitis, uveitis, acute glaucoma attack, or endophtalmitis. Treatment of red eye will just be symptomatic in benign diseases but, in contrast, will absolutely need an etiological diagnosis and therapeutic approach in more serious cases. Generally speaking, topical steroids should never be prescribed in doubt of infectious keratitis. Moreover, local anaesthetics, because of their toxicity for the cornea, should not be prescribed under any circumstances.

[How I explore ... differential diagnosis of a red eye]. / Comment j'explore ... le diagnostic différentiel d'un oeil rouge.

As a common reason for consultation, red eye can be a symptom of benign diseases, such as conjunctivitis, subconjunctival hemorrhage, dry eye syndrome,..., which can be managed by the general practitioner or internist. Conversely, more serious pathologies require a ophthalmologist management: these are keratitis, uveitis, acute glaucoma attack, or endophtalmitis. This article is intended to help practitioner to guide diagnosis when he's faced with a red eye.

[Clinical case of the month. Acute post-traumatic panophthalmitis]. / Panophtalmie post-traumatique fulgurante.

Panophtalmitis is an intra-ocular and intra-orbital rare infection, but its consequences are often horrendous, with loss of both function and anatomy of the eye. The surgical approach and the antibiotherapy should be given as soon as possible, both by intra-vitreal and intra-venous injections. We report the case of a 49-year-old man who developed a Bacillus cereus panophtalmitis. A delay in the diagnosis lead to the loss of vision and the evisceration of the sick eye. Bacillus cereus panopthalmitis should be suspected in all cases of post-traumatic endophtalmitis with a soiled metallic foreign body, in patients with important local inflammatory signs as well as systemic signs. Vitrectomy, surgical extraction of the foreign body, intra-vitreal and systemic antibiotherapies should be given as soon as possible, even before the results of the bacteriological analysis.

[Overview of a decade of advances in ophtalmology]. / Resume d'une décennie de progrès ophtalmologiques.

This review summarizes the most important advances that occurred in ophthalmology during the last decade, with a focus on corneal pathology, cataract surgery, glaucoma and retinal diseases.

[Retinal vascular occlusions: diagnosis and management]. / Les occlusions vasculaires rétiniennes: diagnostic et prise en charge.

PURPOSE: The diagnosis of retinal venous and arterial occlusions is usually easily evoked on visual symptoms and ophthalmoscopic features. However, their management (etiologic explorations and treatment) has not been formally established and remains controversial. CURRENT KNOWLEDGE AND KEY POINTS: Some retinal vascular occlusions may result of loco-regional ocular causes. They more often occur in patients with cardiovascular pathologies or risk factors, or sometimes other systemic diseases that need to be recognized for a proper treatment. Therefore, a comprehensive management of patients with retinal vascular occlusions is necessary to correct associated diseases or predisposing abnormalities that could lead to local recurrences or systemic events. CONCLUSION: Along with a review of the literature, we suggest a practical approach for the management of retinal vascular occlusions, which requires a collaboration between the ophthalmologist and other physicians: general practitioner, cardiologist, internist... as appropriate according to each case.