[Optical coherence tomography analysis of the optic nerve head and macula of the fellow eye in acute unilateral nonarteritic anterior ischemic optic neuropathy]. / Analyse en tomographie à cohérence optique du nerf optique et de la macula des yeux controlatéraux de neuropathie optique ischémique antérieure aiguë.

INTRODUCTION: The objective of the study was to compare the thickness of the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) of the fellow eyes of patients with acute nonarteritic anterior ischemic optic neuropathy (NAAION) to those of control subjects. METHODS: This study included 46 patients with NAAION matched for age, sex and refraction data (spherical equivalent and/or axial length) to 46 control subjects. The anatomical parameters assessed using the Cirrus SD-OCT were the mean RNFL thickness, in the 4 quadrants (inferior, nasal, temporal, superior) and according to the 12 hourly meridians, GCC mean and in 6 quadrants centered on the fovea (infero-nasal, supero-nasal, infero-temporal, supero-temporal, superior and inferior) and parameters of the optic disc (Cup ratio - Vertical and Average Disc, Rim Area, Disc Area, Cup Volume). RESULTS: Compared to the control group, the eyes contralateral to those affected by NAAION showed a greater value of the area of the neuro-retinal rim (rim area), and a smaller vertical cup/disc (C/D) ratio, mean C/D, and cup volume than the control group. There was no significant difference between the two groups for peripapillary RNFL thickness and GCC parameters. CONCLUSION: The absence of damage to the RNFL or GCC of the unaffected fellow eyes of patients with NAAION does not explain the perimetric damage. The eyes contralateral to those affected by NAAION are characterized by an overall size of the optic disc identical to those of the control subjects, but a smaller cup, a recognized risk factor for NAAION.

[Management of ocular toxoplasmosis in France: Results of a modified Delphi study]. / Prise en charge de la toxoplasmose oculaire en France : résultats d'une étude Delphi modifiée.

OBJECTIVE: To evaluate diagnostic and therapeutic practices and then establish a consensus on the management of ocular toxoplasmosis in France through a Delphi study. MATERIALS AND METHODS: Twenty-three French experts in ocular toxoplasmosis were invited to respond to a modified Delphi study conducted online, in the form of two questionnaires, in an attempt to establish a consensus on the diagnosis and management of this pathology. The threshold for identical responses to reach consensus was set at 70 %. RESULTS: The responses of 19 experts out of the 23 selected were obtained on the first questionnaire and 16 experts on the second. The main elements agreed upon by the experts were to treat patients with a decrease in visual acuity or an infectious focus within the posterior pole, to treat peripheral lesions only in the presence of significant inflammation, the prescription of first-line treatment with pyrimethamine-azithromycin, the use of corticosteroid therapy after a period of 24 to 48hours, the prophylaxis of frequent recurrences (more than 2 episodes per year) with trimethoprim-sulfamethoxazole as well as the implementation of prophylactic treatment of recurrences in immunocompromised patients. On the other hand, no consensus emerged with regard to the examinations to be carried out for the etiological diagnosis (anterior chamber paracentesis, fluorescein angiography, serology, etc.), second-line treatment (in the case of failure of first-line treatment), or treatment of peripheral foci. CONCLUSION: This study lays the foundations for possible randomized scientific studies to be conducted to clarify the management of ocular toxoplasmosis, on the one hand to confirm consensual clinical practices and on the other hand to guide practices for which no formal consensus has been demonstrated.

[Retinal vascular network: Changes with aging and systemic vascular disease (cardiac and cerebral)]. / Caractéristiques vasculaires rétiniennes : modifications lors du vieillissement et en pathologie vasculaire systémique (cardiaque et cérébrale).

For over 10 years, the description of the retinal microvascular network has benefited from the development of new imaging techniques. Automated retinal image analysis software, as well as OCT angiography (OCT-A), are able to highlight subtle, early changes in the retinal vascular network thanks to a large amount of microvascular quantitative data. The challenge of current research is to demonstrate the association between these microvascular changes, the systemic vascular aging process, and cerebrovascular and cardiovascular disease. Indeed, a pathophysiological continuum exists between retinal microvascular changes and systemic vascular diseases. In the Montrachet study, we found that a suboptimal retinal vascular network, as identified by the Singapore I Vessel Assessment (SIVA) software, was significantly associated with treated diabetes and an increased risk of cardiovascular mortality. In addition, we supplemented our research on the retinal vascular network with the use of OCT-A. In the EYE-MI study, we showed the potential role of quantitative characterization of the retinal microvascular network by OCT-A in order to assess the cardiovascular risk profile of patients with a history of myocardial infarction. A high AHA (American Heart Association) risk score was associated with low retinal vascular density independently of hemodynamic changes. Thus, a better understanding of the association between the retinal microvasculature and macrovascular disease might make its use conceivable for early identification of at-risk patients and to suggest a personalized program of preventative care. The retinal vascular network could therefore represent an indicator of systemic vascular disease as well as an interesting predictive biomarker for vascular events.

Reform of the 3rd cycle in surgery training.

The main objectives of the reform of the 3rd cycle of medical studies in France that was instituted in 2017 after eight years of preparation, are to train future specialists in a consistent and equitable fashion and to replace the previous time-based qualification by training based on the progressive acquisition of skills. This reform was an opportunity for the 13 different French surgical specialty Colleges involved to share reflections on what a surgeon actually was and to define training in surgical sub-specialties. The current reform is well adapted to these specifications and has fostered training models that are consistent with each other. This article discusses the historical construction of this reform, what will change in the training of future surgeons, as well as some points that warrant caution. The third cycle reform has also triggered a reform of the second cycle, which is expected to come into force for the 2020 academic year. Its objective will be to eliminate the guillotine effect created by the National Classifying Examinations and to allow students to better understand and test their desire and skills for a given specialty. It will be up to these same surgical Colleges to determine how to do this for the sub-specialties of the "surgery" discipline.

[Treatment of noninfectious intermediate uveitis, posterior uveitis, or panuveitis]. / Traitement des uvéites intermédiaires, postérieures et panuvéites non infectieuses.

Controlling long-term inflammation during non-infectious intermediate, posterior or panuveitis while limiting side effects remains challenging. There is no standardized pre-therapeutic evaluation providing diagnostic certainty, but some simple tests allow us to identifiy the main etiologies. The ophthalmologist identifies the type of uveitis, and the internist completes the investigations according to the ophthalmologist's findings. Fundus photographs, optical coherence tomography, and fluorescein and indocyanine green angiography should be considered during diagnosis and follow-up. Ocular complications of uveitis are numerous. They require close monitoring and specific medical and sometimes surgical management. The growing number of available drugs makes it possible to optimize the management of these conditions with varied etiologies and presentations. Currently, systemic corticosteroids remain the mainstay of therapy, and other alternatives are considered in the case of poor tolerance, steroid resistance or dependence. The choice of a systemic, periocular or intravitreal treatment depends on several factors: chronicity or recurrence of uveitis, duration, bilaterality, association with a systemic inflammatory disease, the presence of contraindications to certain treatments, and also socioeconomic constraints. It is of the utmost importance to find the best compromise allowing tight control of ocular inflammation by means of adapted systemic and/or local treatment while avoiding the main complications.

[Therapeutic strategy for the treatment of non-infectious uveitis proposed by an expert panel]. / Avis d'experts pour le traitement des uvéites non infectieuses.

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

[Uveitis: Diagnostic work-up. Recommendations from an expert committee]. / Prise en charge diagnostique des uvéites : recommandations d'un groupe d'experts.

INTRODUCTION: Diagnostic work-up of uveitis involves many uncertainties. Search for an etiology should take into account the epidemiology of uveitis and focus on the most severe diseases or those, which can be treated. This work was undertaken to establish recommendations for the diagnosis work-up of uveitis. METHODS: Recommendations were developed by a multidisciplinary panel of 15 experts, including internists, ophthalmologists and a rheumatologist and are based on a review of the literature with regard to effectiveness of investigations and the results of the ULISSE study, which is the first prospective study assessing the efficiency of a standardized strategy for the etiological diagnosis of uveitis. Children, immunocompromised patients, severe retinal vasculitis and specific ophthalmological entities are excluded from these recommendations. RESULTS: Investigations should be first guided by the history and physical examination. Serological screening for syphilis is the only test appropriate in all forms of uveitis. If no diagnosis is made after this stage, we propose investigations guided by the anatomic characteristics of uveitis. It includes HLA B27 testing (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin converting enzyme, interferon-gamma release assay and chest CT (chronic uveitis), cerebral MRI and anterior chamber tap with IL10 analysis (intermediate or posterior uveitis in patients over 40 years). Investigations ordered in the absence of orientation are almost always unhelpful. CONCLUSIONS: We propose a strategy for the etiologic diagnosis of uveitis. The recommendations should be updated regularly. The efficiency of more invasive investigations has yet to be evaluated.

The Central Bright Spot Sign: A Potential New MR Imaging Sign for the Early Diagnosis of Anterior Ischemic Optic Neuropathy due to Giant Cell Arteritis.

BACKGROUND AND PURPOSE: A rapid identification of the etiology of anterior ischemic optic neuropathy is crucial because it determines therapeutic management. Our aim was to assess MR imaging to study the optic nerve head in patients referred with anterior ischemic optic neuropathy, due to either giant cell arteritis or the nonarteritic form of the disease, compared with healthy subjects. MATERIALS AND METHODS: Fifteen patients with giant cell arteritis-related anterior ischemic optic neuropathy and 15 patients with nonarteritic anterior ischemic optic neuropathy from 2 medical centers were prospectively included in our study between August 2015 and May 2016. Fifteen healthy subjects and patients had undergone contrast-enhanced, flow-compensated, 3D T1-weighted MR imaging. The bright spot sign was defined as optic nerve head enhancement with a 3-grade ranking system. Two radiologists and 1 ophthalmologist independently performed blinded evaluations of MR imaging sequences with this scale. Statistical analysis included interobserver agreement. RESULTS: MR imaging scores were significantly higher in patients with giant cell arteritis-related anterior ischemic optic neuropathy than in patients with nonarteritic anterior ischemic optic neuropathy (P ≤ .05). All patients with giant cell arteritis-related anterior ischemic optic neuropathy (15/15) and 7/15 patients with nonarteritic anterior ischemic optic neuropathy presented with the bright spot sign. No healthy subjects exhibited enhancement of the anterior part of the optic nerve. There was a significant relationship between the side of the bright spot and the side of the anterior ischemic optic neuropathy (P ≤ .001). Interreader agreement was good for observers (κ = 0.815). CONCLUSIONS: Here, we provide evidence of a new MR imaging sign that identifies the acute stage of giant cell arteritis-related anterior ischemic optic neuropathy; patients without this central bright spot sign always had a nonarteritic pathophysiology and therefore did not require emergency corticosteroid therapy.

Analysis of autofluorescence pattern in birdshot chorioretinopathy.

PURPOSE: To characterize and correlate the different patterns of fundus autofluorescence (FAF) in patients with birdshot chorioretinopathy (BSCR), with functional and anatomical parameters. METHODS: Twenty-one BSCR patients were prospectively studied in 2013 and 2014. Each patient underwent visual acuity (VA) and visual field (SITA standard 30.2) testing as well as fluorescein and indocyanine green angiography, spectral-domain optical coherence tomography (SD-OCT) B scan, enhanced depth imaging (EDI), and fundus autofluorescence (FAF) imaging. The disease was classified as active, chronic, or quiescent. RESULTS: The patients' mean age was 60.3 ± 9.2 years and 60% were female. Disease duration was 5.7 ± 3.7 years. Autofluorescence imaging showed punctiform hyper-FAF spots in 23 out of the 29 eyes (79%), which was significantly associated with a greater visual field mean deviation (-7 ± 7 versus -3 ± 2 dB, p = 0.04). Hypo-FAF was defined as peripapillary (n = 25; 86.2%), macular (n = 10; 34.5%), lichenoid (n = 17; 58.6%), and/or diffuse (n = 13; 44.8%). Lichenoid hypo-FAF was significantly associated with worse VA (0.18 ± 0.24 vs. 0.05 ± 0.07 LogMAR, p = 0.04). Macular hypo-FAF was associated with a history of macular edema (62.5%; p = 0.06). Diffuse hypo-FAF was observed more frequently (p = 0.01) in chronic disease (66.7%) than in active (0%) or quiescent disease (27.3%). CONCLUSIONS: Autofluorescence analysis in BRSC patients contributes to evaluating disease activity and could be useful to guide follow-up and treatment.

[Vascular factors in glaucoma]. / Facteurs vasculaires du glaucome.

The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation.

Correlation between clinical data and antibiotic resistance in coagulase-negative Staphylococcus species isolated from 68 patients with acute post-cataract endophthalmitis.

Coagulase-negative staphylococci (CNS) cause the majority of post-cataract endophthalmitis, which can lead to anatomical and/or functional loss of the eye. This study reports the antibiotic susceptibilities of CNS isolates associated with acute post-cataract endophthalmitis cases and correlates antibiotic resistance with severity and outcome of infection in these patients. Clinical data (initial ocular examination, final prognosis, antibiotic treatment) and the antibiotic susceptibilities of the isolated CNS strains were obtained from 68 patients with post-surgical endophthalmitis recruited during a 7-year period by the FRench Institutional ENDophthalmitis Study (FRIENDS) group. The CNS strains displayed 100% susceptibility to vancomycin, 70% to fluoroquinolones, 83% to fosfomycin, 46% to imipenem and 18% to piperacillin. The most effective antibiotic combinations were fosfomycin plus a fluoroquinolone and imipenem plus a fluoroquinolone, which were considered adequate in 80% and 58% of patients, respectively. Methicillin resistance was significantly associated with older age (p 0.001), diabetes mellitus (p 0.004), absence of fundus visibility (p 0.06), and poor visual prognosis (p 0.03). Resistance to fluoroquinolones was significantly associated with absence of fundus visibility (p 0.05) and diabetes mellitus (p 0.02). This large prospective study demonstrates that methicillin resistance and, to a lesser extent, fluoroquinolone resistance in CNS strains causing postoperative endophthalmitis are both prevalent in France and associated with a poorer visual prognosis. These results emphasize the need for an effective surveillance of this antibiotic resistance and the development of new diagnostic tools for rapid detection for early optimization of antibiotic therapy in endophthalmitis patients.

Intravitreal dexamethasone implant versus anti-VEGF injection for treatment-naïve patients with retinal vein occlusion and macular edema: a 12-month follow-up study.

PURPOSE: The objective of his study was to compare the visual and anatomical outcomes in treatment-naïve patients with macular edema secondary to retinal vein occlusion after intravitreal injections of dexamethasone implants (DEX) and anti-VEGF. METHODS: One hundred two patients (64 in the anti-VEGF group, 38 in the DEX group) without previous treatment were included in this multi-center retrospective study and evaluated at baseline and 1, 3, 6, and 12 months after the onset of treatment. Patients were defined as "good responders" if central macular thickness (CMT) was less than or equal to 250 µm in TD-OCT or 300 µm in SD-OCT after the injections. RESULTS: At month 3 (n = 102), BCVA had increased significantly, by 0.1 ± 0.3 logMAR in the anti-VEGF group (p = 0.04) and 0.4 ± 0.4 logMAR in the DEX group (p < 0.001); the difference between the two groups was statistically significant (p = 0.007). CMT decreased significantly, by 138 ± 201 µm (-19 %, p < 0.001) in the anti-VEGF group and 163 ± 243 µm (-21 %, p < 0.001) in the DEX group. After 3 months, five patients (13 %) in the DEX group and 20 (31 %) in the anti-VEGF group (p < 0.001) changed treatment. Among the 77 patients who did not switch from their initial treatment, no significant functional or anatomical difference between the two groups was observed at months 6 and 12. Elevation of intraocular pressure > 21 mmHg was more frequent in the DEX group (21 %) than in the anti-VEGF group (3 %, p = 0.008). CONCLUSIONS: Visual acuity recovery was better in the DEX group than in the anti-VEGF group at month 3, but with no difference in CMT. In patients who did not change treatment, the long-term anatomical and visual outcome was similar between the DEX and anti-VEGF groups.

[Managing antithrombotic therapy in vitreoretinal surgery]. / Comment gérer les antithrombotiques en chirurgie vitréorétinienne ?

Given the growing number of patients on antithrombotic therapy we are increasingly confronted with the management of this therapy before, during and after vitreoretinal surgery. In the absence of a consensus, the decision to withdraw antithrombotic therapy is based on the cardiovascular thromboembolism risk versus the theoretical risk of bleeding if the antithrombotic treatment is continued. As suggested by the literature, antiplatelet therapy (acetylsalicylic acid or clopidogrel) may be safely continued for vitreoretinal surgery, including retinal detachment repair. However, the risk/benefit ratio for patients being treated with two antiplatelet therapies is unknown. It appears that an International Normalized Ratio (INR) less than 3 for patients treated with anticoagulant therapy does not increase the perioperative risk of ocular bleeding. This risk has not been evaluated in patients treated by new antithrombotic therapies (prasugrel, ticagrelor as antiplatelet medication, or dabigatran, rivaroxaban, apixaban as anticoagulant therapy), and there is a need to study it further.

[Proliferative vitreoretinopathy: prophylactic treatment]. / Prolifération vitréo-rétinienne: traitement préventif.

Proliferative vitreoretinopathy (PVR) is a complex process. It causes contractile fibrocellular membranes that may prevent retinal reattachment. PVR therefore remains one of the most severe complications of rhegmatogenous retinal detachment (RD), with an incidence of 5-11%, and is among the most frequent causes of surgical failure (50-75%). Its severity derives from the complexity of the surgery required to treat patients and from its uncertain anatomic and functional prognosis. The first step in preventing PVR is to identify patients at risk by means of clinical and/or biological factors such as the characteristics of retinal tears (large size, number) and detachment (preexisting PVR, extent), and the use of cryotherapy. Surgeons must therefore adapt their surgical approach to the risk of PVR. The study of animal models and the natural history of the condition in humans demonstrate the importance of early antiproliferative treatment in the early stage of the disease. Combining 5-fluoro-uracil and heparin in the vitrectomy infusion lowers the rate of postoperative PVR onset in patients with PVR risk factors. The evaluation of new molecules and new dosages will lead to a decisive step in the fight against PVR.

[Proliferative vitreoretinopathy: pathophysiology and clinical diagnosis]. / Prolifération vitréo-rétinienne : physiopathologie et diagnostic clinique.

Proliferative vitreoretinopathy (PVR) remains one of the most common causes of failed retinal detachment (RD) surgery. Many histological and clinical studies have highlighted the chain of events leading to PVR: cellular migration into the vitreous cavity, cellular differentiation, myofibroblast proliferation and activation, synthesis of extracellular matrix proteins, then contraction of preretinal tissues. The development of PVR can be explained schematically by cellular exposure to growth factors and cytokines (particularly retinal pigment epithelial cells and glial cells), in the context of break-down of the blood-retinal barrier (inflammation, choroidal detachment, iatrogenic effect of cryotherapy and surgery) and of cellular contact with the vitreous. Although the pathophysiology of PVR is now better understood, its severity remains an issue. A systematic search for preoperative PVR risk factors allows the most suitable therapeutic option to be chosen.

[Proliferative vitreoretinopathy: curative treatment]. / Prolifération vitréo-rétinienne : traitement curatif.

Proliferative vitreoretinopathy (PVR), which causes contractile fibrocellular membranes that may prevent retinal reattachment, remains one of the most severe complications of rhegmatogenous retinal detachment (RD), with an incidence of 5-11%, and one of the most frequent causes of surgical failure (50-75%). Its severity is due to the complexity of the surgery required to treat patients, and to its uncertain anatomic and functional prognosis. Curative treatment of PVR includes vitrectomy, sometimes associated with phacoemulsification or scleral buckling; systematic peeling of epiretinal membranes, occasionally retinectomy; and systematic retinopexy by endolaser photocoagulation. The current preferred internal tamponade is silicone oil. Silicone oils of various densities are undergoing comparative studies.

[Ocular syphilis]. / Atteinte oculaire de la syphilis.

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Previously known as the "great imitator", this disease can have numerous and complex manifestations. The ophthalmologist should suspect the diagnosis in patients with uveitis or optic neuropathy and high-risk sexual behavior and/or another sexually transmitted disease (such as HIV) or those presenting with posterior placoid chorioretinitis or necrotising retinitis. Ocular involvement in acquired syphilis is rare, tending to occur during the secondary and tertiary stages of the disease. Syphilis may affect all the structures of the eye, but uveitis (accounting for 1-5% of the uveitis in a tertiary referral center) is the most common ocular finding. Granulomatous or non-granulomatous iridocyclitis (71%), panuveitis, posterior uveitis (8%) and keratouveitis (8%) are often described. In the secondary stage, the meninges and the central nervous system can be affected, sometimes with no symptoms, which justifies performing lumbar puncture in patients with uveitis and/or optic neuropathy. The diagnosis of ocular syphilis requires screening with a non-treponemal serology and confirmation with a treponemal-specific test. Parenterally administered penicillin G is considered first-line therapy for all stages of ocular syphilis. Systemic corticosteroids are an appropriate adjunct treatment for posterior uveitis, scleritis and optic neuritis if ocular inflammation is severe. Prolonged follow-up is necessary because of the possibility of relapse of the disease. With proper diagnosis and prompt antibiotic treatment, the majority of cases of ocular syphilis can be cured.

FRIENDS Group: clinical and microbiological characteristics of post-filtering surgery endophthalmitis.

PURPOSE: To study the clinical and microbiological characteristics as well as the prognostic factors for post-filtering surgery endophthalmitis. METHODS: Twenty-three eyes were included in the study in four tertiary centres between 2004 and 2010. The clinical and microbiological data were collected prospectively (minimum follow-up, 6 months). Microbiological diagnosis was based on conventional cultures and panbacterial PCR (16SrDNA amplification and sequencing). RESULTS: The onset of endophthalmitis was early (<6 weeks) in 22 % of the cases and delayed in 78 %. Elevated intraocular pressure and hypopyon were more frequent in delayed than in early presentations (p = 0.04). By combining the results of culture and panbacterial PCR, a bacterial species could be identified in 73.9 % of the cases, including 56.5 % of commensal species of the digestive tract such as Moraxella spp., oropharyngeal streptococci and Enterococcus faecalis. Good final visual acuity (VA ≥ 20/40) was correlated with initial VA greater than light perception (p = 0.05). Poor final VA (≤20/400) was correlated with a higher virulence of the infecting bacterial species (p = 0.006), and was noted in all patients with early-onset endophthalmitis. CONCLUSION: Acute early- or delayed-onset post-filtering surgery endophthalmitis is frequently caused by bacteria of the digestive tract (e.g., Streptococcus and Enterococcus spp.). The combination of conventional cultures and panbacterial PCR allowed us to identify the causative microorganism in three-quarters of the cases, i.e., 21 % more cases than through culture alone. Despite adequate antibiotic and surgical treatment, the anatomical and visual prognosis remains poor.

Auto-antibodies to vascular endothelial cadherin in humans: association with autoimmune diseases.

To identify patients with autoimmune diseases who are at high risk of developing vascular cell dysfunction, early biomarkers must be identified. This study was designed to detect and characterize circulating autoantibodies to VE-cadherin (AAVEs) in patients with early-stage autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) was developed to capture autoantibodies, using a recombinant human VE-cadherin fragment covering the extracellular domains as a target antigen. AAVEs specificity for the target antigen was confirmed by western blotting. Basal AAVEs levels were determined for healthy donors (n=75). Sera from patients (n=100) with various autoimmune diseases, including rheumatoid arthritis (n=23), systemic lupus erythematosus (SLE, n=31), systemic sclerosis (n=30), and Behçet's disease (BD, n=16) were also tested. Levels of AAVEs were significantly higher in rheumatoid arthritis (P<0.0001), SLE (P<0.05), and BD (P<0.05) populations than in healthy subjects. Purified immunoglobulin G (IgG) from a BD patient with exceptionally high AAVEs levels recognized the EC1-4 fragment in western blots. Further characterization of the epitopes recognized by AAVEs showed that BD patients had antibodies specific for the EC3 and EC4 domains, whereas SLE patients preferentially recognized the EC1 fragment. This suggests that distinct epitopes of human VE-cadherin might be recognized in different immune diseases. Purified IgG from BD patients was found to induce endothelial cell retraction, redistribution of VE-cadherin, and cause the formation of numerous intercellular gaps. Altogether, these data demonstrate a potential pathogenic effect of AAVEs isolated from patients with dysimmune disease. This is the first description of AAVEs in humans. Because regions EC1 and EC3-4 have been shown to be involved in homophilic VE-cadherin interactions, AAVEs produced in the course of dysimmune diseases might be specific biomarkers for endothelial injury, which is part of the early pathogenicity of these diseases.