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Purpose: HLA-A29 is the main susceptibility factor for birdshot chorioretinitis (BSCR). Our study assessed the impact of the second HLA-A allele alongside HLA-A29 on BSCR severity and susceptibility, focusing on HLA-A29 homozygous patients and those with alleles from the HLA-Aw19 group., Methods: We included 120 additional cases to our previous analysis of 286 patients with BSCR, all HLA-A29 positive. Patients were categorized based on the second allele being also HLA-A29 (A29/nonA29 vs. A29/A29) or belonging to the HLA-Aw19 family, including A29, A30, A31, and A33 (A29/nonAw19 vs. A29/Aw19). HLA-A32 was analyzed separately (A29/nonA32 vs. A29/A32). The prevalence of these groups among patients with BSCR was compared with their frequencies in a sample of 151,997 French subjects. Disease severity was approximated by assessing disease onset and visual function at the last visit and was compared between patient groups., Results: When comparing the HLA-A29-positive patients with BSCR to HLA-A29-positive French subjects, we found an overrepresentation of HLA-A29 for the second HLA-A allele (χ² = 4.34; P = 0.037; odds ratio, 1.57; confidence interval, 1.01-2.44). Within the HLA-Aw19 broad antigen family, HLA-A32 was found to be under-represented (χ² = 6.15; P = 0.013; odds ratio, 0.40; confidence interval, 0.19-0.85). The nature of the second HLA-A allele did not impact disease severity., Conclusions: Homozygosity for HLA-A29 increased the risk of developing BSCR without affecting disease severity. The under-representation of HLA-A32 in patients with BSCR suggests a potential protective role.

Background: Birdshot chorioretinitis (BSCR) is a chronic bilateral posterior uveitis, which can affect central as well as peripheral vision. The aim of this study was to assess how visual acuity and visual field evolved over time in patients with BSCR., Methods: This was a prospective, observational, single-centre study based on data from the CO-BIRD cohort. Patient visits were categorised based on the time elapsed since the first symptoms, and groups of patients with different disease duration were defined. The main outcome measures were the best corrected visual acuity (BCVA), the mean deviation (MD) and the standard pattern deviation (PSD)., Results: The study included 447 Caucasian patients (181 males and 266 females), all of whom HLA-A29 carriers. From onset to 30 years of disease duration, the number of patients in each consecutive 5-year period was 237, 250, 196, 147, 78 and 32, respectively. Overall, the range of visual acuity and visual field results increased with disease duration. BCVA gradually decreased and showed a significant decline after 11-15 years after the first symptoms. Among the visual field indices, PSD significantly increased after 16-20 years, while MD showed a significant decline after 21-25 years. No major gender differences were found in visual outcomes, indicating comparable severity. The intereye correlations of MD and PSD were stronger than those of BCVA., Conclusions: BSCR resulted in a large heterogeneity of visual outcomes, which increased with time. Our data provide an overview of the visual consequences of BSCR as a function of disease duration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Birdshot chorioretinitis (BSCR) is an ocular HLA-related disease with variable clinical progression. We examine the quality of life (QOL) of BSCR individuals aged ≥80 years, providing insights into the long-term disease impact., Methods: We utilized data from the CO-BIRD cohort (ClinicalTrials.gov Identifier: NCT05153057) conducted at Hôpital Cochin in Paris, France, focusing on BSCR patients aged ≥80. The main outcome was vision-related QOL using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). We used Spearman correlation to explore the impact of better BCVA and MD on the composite score, and the Wilcoxon test to evaluate specific visual symptoms' effects., Results: The study included 35 patients with a mean age of 83.9 ± 3.7 years, 74.3% of whom received systemic immunosuppression. The mean composite score was 58 ± 30, with a median of 75 (23-79). The lowest subscores were driving capacity (38 ± 38), mental health (49 ± 33), and role difficulties (50 ± 35), while the highest were for ocular pain (70 ± 25) and social function (70 ± 38). Decimal BCVA below 0.5 and MD below -6 dB were associated with lower subscores. BCVA and MD were strongly correlated with the composite score ( R  = 0.67). Symptoms of poor color and blurry vision were significantly associated with lower composite score ( p  < 0.005)., Conclusion: Most BSCR patients over 80 in our cohort maintained sufficient vision for daily activities. The high standard deviation and wide range of VFQ-25 results reflect the heterogeneity of visual outcomes among elderly BSCR patients.

Purpose: To assess the manifestations of birdshot chorioretinitis (BSCR) in patients aged 80 and over., Design: Among patients with BSCR followed in the CO-BIRD prospective cohort (ClinicalTrials.gov Identifier: NCT05153057), we analyzed the subgroup of patients aged 80 and over., Methods: Patients were assessed in a standardized manner. Confluent atrophy was defined as hypoautofluorescent spots on fundus autofluorescence (FAF)., Results: We included 39 (8.8%) of the 442 enrolled CO-BIRD patients. The mean age was 83.8 ± 3.7 years. The mean logMAR BCVA was 0.52 ± 0.76, with 30 patients (76.9%) having 20/40 or better in at least one eye. Thirty-five (89.7%) patients were receiving no treatment. Confluent atrophy in the posterior pole, disrupted retrofoveal ellipsoid zone and choroidal neovascularization were associated with logMAR BCVA >0.3 ( p  < .0001)., Conclusion: In patients aged 80 and over we observed a striking heterogeneity of outcomes, but most retained a BCVA that allowed them to drive.

Purpose: To assess the effect of corticosteroids (CS) on choroidal neovascularization (CNV) occurrence and recurrence of activity over 2 years in patients with punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC)., Methods: Retrospective longitudinal study. Previous use of CS was analyzed between group without CNV and group with CNV occurrence and recurrence., Results: Thirty-six patients were included. Patients with CNV were less likely to have received CS in the 6 months following PIC or MFC diagnosis (17% versus 65%, p-value = 0.01). Patients with CNV who had a recurrence of neovascular activity were less likely to have received a previous CS therapy (20% versus 78%; odds ratio = 0.08, p-value = 0.005)., Conclusions: This study suggests that patients with PIC and MFC should be treated by CS to prevent CNV development and decrease CNV recurrences.

Purpose: The healthcare system emits greenhouse gas emissions and produces waste that in turn threatens the health of populations. The objective of our study was to measure the ecological threat related to intravitreal injections., Methods: Emissions were separated into scope 2 corresponding to Heating, Ventilation and Air Conditioning (HVAC) of the building, and scope 3 corresponding to travels (patients and staff), and life cycle assessment (LCA) of medical devices (MD) and pharmaceutics. Greenhouse gas (GHG) emissions and waste for a single injection were first measured through a waste audit, and secondly anticipated theoretically with a calculator., Results: The average GHG emissions and waste measured were 277kgCO2eq/IVI and 0.5kg/IVI, respectively. Pharmaceuticals were responsible for 97% of total emissions. Emissions unrelated to pharmaceuticals counted for 8.4kgCO2eq/IVI. GHG emissions and waste estimated with the calculator were 276kgCO2eq/IVI and 0.5kg/IVI, respectively, showing that the calculator was accurate., Conclusion: Our study provides a puzzle piece to carbon footprint and waste assessment in the field of ophthalmology. It may help provide concrete data for future green vs. vision discussions., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: We assessed whether the immediate pressure adjustments provided by a phacoemulsification handpiece with a built-in pressure sensor (Active Sentry, AS) could decrease the amount of energy delivered in the eye during cataract surgery., Methods and Analysis: The Study of Active Sentry in Cataract Surgery was a multicentre prospective clinical trial. The Centurion system (Alcon Labs) was used and we compared phacoemulsifications performed with the AS handpiece with procedures using a sensor placed in the phacoemulsifier (non-AS). The primary outcome measure was the cumulative dissipated energy (CDE) used during the procedures. The secondary outcome measures were the total, longitudinal and torsional ultrasound (US) times, the duration of the surgery and the amount of fluid used during the surgeries., Results: The study analysed 1432 (800 AS and 632 non-AS) procedures. The mean patient age was 72.4±10.0 years. The median CDE was respectively 6.3 (IQR 3.5-9.9) and 6.7 (IQR 4.5-11.5) with and without AS (p=0.0001). The median US time was, respectively, 48.0 s (IQR 34.0-68.0) and 55.0 s (IQR 38.0-80.0) with and without AS (p<0.0001). Torsional and longitudinal US times were reduced with AS. The median duration of the procedure was, respectively, 9.0 min (IQR 7.0-12.0) and 10.0 min (IQR 7.0-13.0) (p=0.0002) with and without AS. The median balanced salt solution volume used was 52.0 cm 3 (IQR 41.0-72.0) and 57.0 cm 3 (IQR 42.0-81.0) with and without AS (p=0.0018)., Conclusion: The phacoemulsifications performed with a pressure sensor built in the handpiece delivered less energy in the eye and were shorter., Trial Registration Number: NCT04732351., Competing Interests: Competing interests: AB, DM, FL and PR are consultants for Alcon., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Nd:YAG (neodymium:yttrium-aluminum-garnet) capsulotomy (Nd:YAG-caps) is the gold standard for the treatment of PCO (Posterior Capsule Opacification). There is a lack of real-world data about Nd:YAG-caps use., Purpose: This study's objectives were to estimate Nd:YAG-caps incidence in France, to describe the patient characteristics, and to analyze the time between surgeries and capsulotomies., Setting: The study was based on data extracted from the EGB database, a 1/97th sample representative of the French population., Design: observational, retrospective, cohort study using national claims data., Methods: French adult patients who underwent Nd:YAG-caps between 2014 and 2017 were selected. Main outcomes were the number of patients and procedures performed and the risk factors associated with early Nd:YAG-caps., Results: During the study period, Nd:YAG-caps were performed in 8,425 patients accounting for 10,774 procedures. The extrapolation to the French population led to estimate that 253.10 3 patients had Nd:YAG-caps, representing 312.10 3 procedures in 2017. The mean age at Nd:YAG-caps was 75.1 (± 10.2) years. About 36% of patients presented at least one ocular comorbidity. Nd:YAG-caps was performed within 2 years after surgery in 33.0% of patients and within one year in 9.8% of patients. Patients with Nd:YAG-caps within the first year (OR CI95 0.721 [0.673-0.772]) or in the first two years (OR CI95 0.721 [0.673-0.772]) were younger than patients with later Nd:YAG-caps and had a more frequent history of treated ocular diseases (OR 1.516 and 1.178, respectively)., Conclusions: This study brought new real-world and large-scale data regarding Nd:YAG-caps use and gave an updated insight into the patients' characteristics., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a systemic hyperinflammatory state described in children recently infected with SARS-CoV-2. Ophthalmologically, non-purulent conjunctival injection is the most common symptom, but cases of uveitis have been described. Here, we present a case of bilateral granulomatous anterior uveitis in a 10-year-old boy, 12 days after diagnosis of PIMS-TS. Symptoms resolved after a week of topical treatment and there was no relapse after six months. We carried out a focus review on uveitis in children with PIMS-TS and found eight studies. All in all, 21 children were reported with a median age of 11.5 years. Most of them had bilateral anterior inflammation, without synechiae nor hypertonia, which lasted five to seven days and responded well to the use of corticoids. This symptom is a potential predictor of a more severe disease and this link should be further explored.

Background/aims: To identify characteristics that can distinguish AAION from NAAION in emergency practice., Methods: This is a multicentre retrospective case-control study. Ninety-four patients with AAION were compared to ninety-four consecutive patients with NAAION. We compared the clinical, biological, and ophthalmological characteristics at baseline of patients with AAION and those with NAAION., Results: Patients with AAION were older and more likely to have arterial hypertension. Cephalic symptoms and acute-phase reactants were more frequent in AAION. Profound vision loss and bilateral involvement were more frequent in AAION at baseline. Central retinal and cilioretinal artery occlusions was only observed in AAION, and delayed choroidal perfusion was more frequently observed in AAION than in NAAION. Using logistic regression, an age >70 years (OR = 3.4, IC95% = 0.8-16.1, p = 0.105), absence of splinter haemorrhage (OR = 4.9, IC95% = 1.4-20.5, p = 0.019), delayed choroidal perfusion (OR = 7.2, IC95% = 2.0-28.0, p = 0.003), CRP > 7 mg/L (OR = 43.6, IC95% = 11.6-229.1, p < 0.001) and platelets >400 × G/L (OR = 27.5, IC95% = 4.6-270.9, p = 0.001) were independently associated with a diagnosis of AAION. An easy-to-use score based on these variables accurately distinguished AAION from NAAION with a sensitivity of 93.3% and specificity of 92.4%., Conclusion: In patients presenting with AION, a set of ophthalmological and laboratory criteria can efficiently discriminate patients with AAION and NAAION and can identify which patients would benefit from high-dose glucocorticoids. External validation of our results is required., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To estimate the incidence and assess the risk factors associated with 3 adverse events (AEs) after neodymium:yttrium-aluminum-garnet posterior capsulotomy (Nd:YAG-caps): ocular hypertension (OHT), macular edema (ME), and retinal detachment (RD)., Design: Observational cohort study using a nationwide claims database., Participants: Adults who underwent Nd:YAG-caps between 2014 and 2017, with no ocular disease history in the year before., Methods: Patients who underwent Nd:YAG-caps were identified using data from the French national representative sample and followed up for 12 months postprocedure. The time to AE was assessed using the Kaplan-Meier method. Factors associated with AE were assessed using Cox models., Main Outcome Measures: Neodymium:YAG-caps epidemiology, patients' characteristics, proportion of patients with AE, and hazard ratios (HRs) associated with variables identified as factors associated with AEs., Results: During the study period, 6210 patients received Nd:YAG-caps (7958 procedures). The mean age (± standard deviation) at Nd:YAG-caps was 75.0 (± 10.3) years. The 3-month and 12-month overall AE rates (≥ 1 AE of interest) were 8.6% and 13.3%, respectively. Among patients with ≥ 1 AE of interest, 68.4% of AEs occurred within 3 months post-Nd:YAG-caps. Three-month rates were ≈5% for OHT and ME. Retinal detachment remained ≤ 0.5% over follow-up. Cox models showed that patients with Nd:YAG-caps performed within 1 year after cataract surgery had a higher risk of AEs than those with later Nd:YAG-caps (hazard ratio [HR], 1.314 [1.034-1.669], P = 0.0256), notably ME (HR, 1.500 [1.087-2.070], P = 0.0137). Diabetic patients were more at risk of OHT (HR, 1.233 [1.005-1.513], P = 0.0448) and ME (HR, 1.810 [1.446-2.266], P < 0.0001) than nondiabetic patients. Patients with Nd:YAG-caps performed between 1 and 2 years after cataract surgery were more at risk of OHT than patients with later Nd:YAG-caps (HR, 1.429 [1.185-1.723], P = 0.0002)., Conclusions: According to a national claims database, OHT and ME were the most frequent AEs of interest post-Nd:YAG-caps, mainly observed within 3 months postprocedure, highlighting the need for a close follow-up during this period or a delayed capsulotomy. Diabetes and an early Nd:YAG-caps after cataract surgery were among the main drivers for AE occurrence., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report a case of Hodgkin lymphoma (HL) associated retinopathy., Method: Single-case, retrospective review of ophthalmological and systemic manifestations., Results: A bilateral panuveitis in a 17-year-old Caucasian woman led to the diagnosis of HL. The ocular findings were characterized by anterior uveitis, vitritis, white chorioretinal lesions, papillitis and vasculitis. The diagnosis of nodular sclerosis stage IIA HL was confirmed by a cervical ganglion biopsy. Other causes of uveitis were excluded. The remission of HL was obtained by chemotherapy and the ocular lesions became quiescent, with pigmented chorioretinal scars, predominating along retinal vessels. Recurring visual symptoms one year later led to the diagnosis of the relapse of the HL. The remission of the HL was again obtained by a second line of chemotherapy while ocular symptoms subsided., Conclusions: Hodgkin lymphoma may be added to the list of diseases that can occasionally be revealed by ocular paraneoplastic syndromes.

Introduction: To evaluate real-life efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in posterior segment inflammation due to non-infectious uveitis (treatment-naïve or not) in French clinics., Methods: In this prospective, multicenter, observational, non-comparative, post-reimbursement study, consecutive patients with posterior segment inflammation due to non-infectious uveitis were enrolled and evaluated at baseline (day 0). Those who received DEX on day 0 were re-evaluated at months 2, 6, and 18. Retreatment with DEX and/or alternative therapies was allowed during follow-up., Primary Outcome: patients (%) with at least a 15-letter gain in best corrected visual acuity (BCVA) at 2 months. Secondary outcomes included patients (%) with at least 15-letter BCVA gains at 6 and 18 months; mean BCVA change from baseline at 2, 6, and 18 months; and patients (%) retreated, mean central retinal thickness (CRT), and adverse events (AEs) at all post-baseline visits., Results: Ninety-seven of 245 enrolled patients with posterior segment inflammation due to non-infectious uveitis (80% previously treated) and disease duration of 5 years (average) received DEX on day 0 and were included in efficacy analyses. At month 2 (n = 91), 20.5% of patients (95% CI 12.0-28.9) gained at least 15 letters from a baseline mean of 60.9 letters; the mean gain was 6.2 letters (95% CI 3.5-8.9). At month 6, 50.0% (n = 38/76) of patients did not receive alternative treatment or DEX retreatment, mostly because inflammation had sufficiently subsided (n = 27/38, 71.1%). Although early study termination prevented efficacy analysis at 18 months (n = 12), CRT reductions persisted throughout follow-up. From baseline to month 18, 21/245 (8.6%) patients had DEX-related AEs; 17/245 (6.9%) had ocular hypertension (most common AE)., Conclusion: LOUVRE 2 confirms DEX efficacy on visual acuity and CRT in predominantly DEX-pretreated patients with relatively old/stabilized uveitis. DEX tolerability was consistent with known/published data, confirming treatment benefits in posterior segment inflammation due to non-infectious uveitis., Gov Identifier: NCT02951975., (© 2022. The Author(s).)

Birdshot chorioretinopathy (BSCR) is a bilateral chronic inflammation of the eye with no extraocular manifestations. BSCR affects middle-aged individuals from European descent and is strongly associated with the human leucocyte antigen (HLA)-A29 allele. The immune mechanisms involved are not fully understood, but recent advances have shown the role of Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) in disease pathogenesis. Multimodal imaging, including fluorescein angiography, indocyanine angiography, fundus autofluorescence, and optical coherence tomography, are useful in confirming the diagnosis and monitoring disease activity. Visual field testing is also important to assess the disease progression. To date, there is no consensus for optimal treatment regimen and duration. Local and systemic corticosteroids can be used for short periods, but immunosuppressive or biological therapies are usually needed for the long-term management of the disease. Here, we will review publications focused on birdshot chorioretinopathy to give an update on the pathophysiology, the multimodal imaging, and the treatment of the disease.

Purpose: To report a case of multiple pre-retinal and intra-retinal lesions in the context of probable sarcoidosis., Observations: A 31-year-old black woman presented with a bilateral panuveitis and multiple pre-retinal and retinal nodules. The workup showed enlarged mediastinal lymph nodes as well as meningitis with an increased cerebrospinal fluid angiotensin-converting enzyme (ACE) [0.36 UI/L (1.44 × normal)] leading to the diagnosis of probable sarcoidosis. The nodules were hyper-reflective, with posterior shadowing on OCT imaging, and appeared as multiple hypoautofluorescent spots: their characteristics were suggestive of intra and preretinal granulomas. The intraretinal nodules were located in the ganglion cell layer. The posterior segment manifestations were limited to the retina while the choroid appeared uninvolved including on indocyanine green angiograms. The lesions disappeared after corticosteroid treatment., Conclusions and Importance: Retinal and pre-retinal nodules have rarely been reported as the sole posterior manifestations of ocular sarcoidosis without choroidal involvement., Competing Interests: The following authors have no financial disclosures: GSS, CG, ACD, DM, APB., (© 2022 The Authors.)

Purpose: To assess the carbon footprint of cataract surgery in a French university hospital., Setting: Operating room of Cochin University Hospital, Paris, France., Design: Single-center component analysis., Methods: One day of surgery was used as a reference. Greenhouse gases (GHG) related to patient and staff transportation were calculated based on the distance travelled and the means of transportation used. The annual consumption of energy (heating and electricity) of our building was converted in kg equivalent of carbon dioxide (CO 2 eq), and the principle of proportionality was used to calculate what was used for a single cataract procedure. GHG emissions related to the life cycle assessment (LCA) of the equipment used and the sterilization process were calculated., Results: The LCA of disposable items accounted for 59.49kg (73.32%) of CO 2 eq for each procedure. A single procedure generated 2.83±0.10kg of waste. The average CO 2 eq produced by the transportation of the patients to and from our center, adjusted for one procedure, was 7.26±6.90kg (8.95%) of CO 2 eq. The CO 2 eq produced by the sterilization of the phacoemulsifier handpiece was 2.12kg (2.61%). The energy consumption of the building and staff transportation accounted for the remaining CO 2 eq emissions, 0.76kg (0.93%) and 0.08kg (0.10%) respectively. Altogether, the carbon footprint of one cataract procedure in our center was 81.13kg CO 2 eq - the equivalent of an average car driving 800km., Conclusion: Our data provide a basis to quantify cataract surgery as a source of GHG and suggests that reductions in emissions can be achieved., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background/objectives: To assess the ratio of scarred/active areas of fundus lesions in patients with presumed ocular toxoplasmosis., Subjects/methods: Retrospective monocentric study of patients with presumed ocular toxoplasmosis seen between May 2004 and February 2018. Patients with a positive anti-Toxoplasma serology presenting characteristic fundus lesions. Cases with images of both baseline active and scarred lesions of the fundus were included. The borders of each active or scarred lesion were delineated on colour photographs by two independent observers and the area of the lesions was calculated using Digimizer 4.2.2 (MedCalc Software, Ostend, Belgium). The interobserver variability of the measures was recorded and their means were used for further calculations. To study the ratio of the area of scarred retinochoroiditis over the area of the baseline active lesion (R)., Results: A total of 171 cases (83 males, 88 females) with a mean age of 31.6 ± 13.8 years were included. The average areas of active and scarred retinochoroiditis were, respectively, 1.32 ± 1.59 and 1.79 ± 2.36 optic disc area. The average ratio between scarred and active areas of retinochoroiditis was 1.36 [range 0.54-2.18]. The administration of a systemic treatment [R = 1.25, p = 0.003], the absence of a pre-existing scar [R = 1.05, p < 0.001] and a peripapillary location of the lesion [R = 0.85, p < 0.001] were each significantly associated with smaller scarred/active area ratios., Conclusions: We assessed in a standardized manner the ratio of scarred/active areas of toxoplasmic lesions and showed that the area of scarred lesions was on average slightly larger than the area of active retinochoroiditis., (© 2020. The Author(s).)

Purpose: To assess the perception of patients undergoing cataract surgery under topical anesthesia in an open-space operating hall., Methods: The study was set in the department of ophthalmology, Cochin Paris Descartes University Hospital, in a newly built open-space operating hall dedicated to ophthalmic surgery. It was a prospective study of consecutive patients undergoing cataract surgery by 11 surgeons. Our population study comprised 250 patients operated in an open-space operating hall with 3 surgical areas. Only first-eye standard cataract surgeries performed under topical anesthesia were included. Responses to a face-to-face questionnaire administered by a single interviewer to patients before their discharge on the day of their surgery were analyzed., Results: Fifty-two patients (21%) knew beforehand that their procedure would take place in an open-space operating hall, 118 (47%) realized that they were in such an environment on the occasion of their surgery and 80 (32%) did not notice. Conversations and noises unrelated to their own surgeries were overheard respectively by 15 (6%) and 37 (15%) patients. Of the 250 patients, 237 (95%) did not report any discomfort associated with the fact that their procedure had been performed in an open-space operating hall., Conclusions: Cataract surgery performed in an open-space setting did not seem to affect the patients' comfort during the procedure., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Purpose: We report the case of a 19-year-old patient who presented with an ocular hypotony due to a transscleral filtration through an isolated congenital chorioretinal coloboma in his right eye., Observations: The initial examination showed a decimal best corrected visual acuity (BCVA) decreased to 0.7 and a marked hypotony. A localized infero-nasal chemosis and a conjunctival hyperemia were observed. The fundus examination showed chorioretinal folds and an edematous disc. In the infero-nasal retinal periphery, a chorioretinal coloboma was seen with a full-thickness scleral defect. Ultrasound biomicroscopy showed the area of the coloboma through which the percolation of fluid occurred., Conclusions and Importance: A favorable outcome was observed within 6 weeks and BCVA improved to 1.0 three months later. The intraocular pressure (IOP) increased to 11 mmHg, but the bleb-like filtration could still be seen together with some persistent chorioretinal folds. Ultrasound Biomicroscopy (UBM) imaging was helpful to understand the mechanism of this uncommon complication of a coloboma., Competing Interests: The following authors have no financial disclosures: B.S.; Q.D; P.D.; V.S; A.B., (© 2020 The Authors. Published by Elsevier Inc.)

The progressive deterioration of the visual function in patients on waiting lists for cataract surgery has a negative impact on their quality of life, especially in the elderly population. Patient waiting times for cataract surgeries in many healthcare settings have increased recently due to the prolonged stop or slowdown of elective cataract surgery as a result of coronavirus disease 19 (COVID-19). The aim of this review is to highlight the impact of such a "de-prioritization" of cataract surgery and to summarize some critical issues and useful hints on how to reorganize cataract pathways, with a special focus on perioperative diagnostic tools during the recovery phase and beyond. The experiences of a group of surgeons originating from nine different countries, named the European COVID-19 Cataract Group (EUROCOVCAT), have been combined with the literature and recommendations from scientific ophthalmic societies and healthcare institutions. Key considerations for elective cataract surgery should include the reduction of the number of unnecessary visits and examinations, adoption of precautionary measures, and implementation of telemedicine instruments. New strategies should be adopted to provide an adequate level of assistance and to guarantee safety conditions. Flexibility will be the watchword and regular updates would be necessary following scientific insights and the development of the pandemic.

Sarcoidosis is a systemic granulomatosis characterized by the formation of epithelioid and giant cell granulomas without caseous necrosis. To make the diagnosis, it is necessary to prove systemic granulomatosis involving at least two organs; but in practice, a combination of clinical, paraclinical and histologic findings is used. It affects predominantly women with a bimodal age distribution: 25-29years and 65-69years. The most commonly affected organs are the mediastinal lymphatic system, lungs, skin and eyes. Ophthalmological involvement is present in 20 to 50% of cases. The typical ocular presentation is that of granulomatous uveitis associated with venous retinal vasculitis and lesions of peripheral multifocal choroiditis. This ophthalmological presentation, although very evocative, is not always associated with systemic disease. The diagnosis of ocular sarcoidosis is then presumed in the absence of histological evidence. Algorithms combining ophthalmological and systemic signs have been proposed in cases of isolated uveitis. They make it possible to establish the diagnosis of ocular sarcoidosis with various levels of probability. The absence of significant granulomas on a systemic level during primary ocular involvement remains the main hypothesis to explain these diagnostic difficulties. Treatment is well described, as the uveitis of sarcoidosis is most often steroid responsive. In the case of corticosteroid-dependent uveitis, the first-line immunosuppressant remains methotrexate. The use of anti-tumor necrosis factor-alpha is an interesting alternative in patients whose ocular sarcoidosis is refractory to conventional immunosuppressants., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis., Methods: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF)., Results: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years)., Conclusions: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

Sarcoidosis is a systemic granulomatosis characterized by the formation of epithelioid and giant cell granulomas without caseous necrosis. To make the diagnosis, it is necessary to prove systemic granulomatosis involving at least two organs; but in practice, a combination of clinical, paraclinical and histologic findings is used. It affects predominantly women with a bimodal age distribution: 25-29 years and 65-69 years. The most commonly affected organs are the mediastinal lymphatic system, lungs, skin and eyes. Ophthalmological involvement is present in 20 to 50% of cases. The typical ocular presentation is that of granulomatous uveitis associated with venous retinal vasculitis and lesions of peripheral multifocal choroiditis. This ophthalmological presentation, although very evocative, is not always associated with systemic disease. The diagnosis of ocular sarcoidosis is then presumed in the absence of histological evidence. Algorithms combining ophthalmological and systemic signs have been proposed in cases of isolated uveitis. They make it possible to establish the diagnosis of ocular sarcoidosis with various levels of probability. The absence of significant granulomas on a systemic level during primary ocular involvement remains the main hypothesis to explain these diagnostic difficulties. Treatment is well described, as the uveitis of sarcoidosis is most often steroid responsive. In the case of corticosteroid-dependent uveitis, the first-line immunosuppressant remains methotrexate. The use of anti-tumor necrosis factor alpha is an interesting alternative in patients whose ocular sarcoidosis is refractory to conventional immunosuppressants., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The early diagnosis of cancer is of crucial importance and a key prognostic factor. Cancer-associated retinopathy (CAR) can be symptomatic prior to other manifestations directly related to malignant tumors. The aim of this study was to show that, in selected cases, ophthalmic findings are consistent enough with the diagnosis of CAR to trigger investigations aimed at detecting a previously unknown malignancy., Methods: This was a monocentric retrospective case series performed in a tertiary referral center. Patients with a diagnosis of CAR were included. Diagnosis was based on the clinical presentation, the visual field and electroretinogram alterations. The clinical presentation, visual field testing and electroretinographic results were analyzed as well as the malignancies identified following the diagnosis of CAR. Follow-up data was collected., Results: Four patients (two men, two women, median age 65.5 years) were included. All patients presented with posterior segment inflammation at initial presentation as well as advanced visual field loss and an extinguished electroretinogram. The best corrected decimal visual acuity was 0.8 or better in both eyes of three patients and decreased to 0.3 OD and O.2 OS in one patient due to a bilateral macular edema. No patient had a previously known history of cancer. Once the diagnosis of CAR was made, investigations aimed at identifying a malignant tumors subsequently led to the diagnosis of two cases of small cell lung tumors, of one prostate carcinoma and of a uterine sarcoma. The treatment of CAR included plasmapheresis, systemic corticosteroids, azathioprine, cyclosporine and periocular or intraocular corticosteroid injections. In all cases the intraocular inflammation resolved, but pigment mottling, diffuse retinal atrophy, optic disc pallor and arterial narrowing were among manifestations observed during the follow-up of the patients., Conclusion: In selected patients, findings suggestive of CAR can be useful for the early detection of a cancer.

Purpose: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis., Design: Phase 3, open-label, multicenter clinical trial extension (VISUAL III)., Participants: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF., Methods: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78., Main Outcome Measures: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff., Results: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials., Conclusions: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: A. Brézin déclare être consultant pour le laboratoire AbbVie.

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics., Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents., Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence., Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed., Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) is a rare inflammatory eye disease that affects the Retinal Pigment Epithelium and outer retina. The purpose of this study was to describe its presentations, as well as its prognosis in a series of untreated patients., Methods: Records of patients seen in the department of Ophthalmology at Cochin University Hospital, Paris, between April 2002 and June 2015 were retrospectively studied. Patients were included if they presented with the typical findings of APMPPE characterized by whitish or yellowish bilateral placoid lesions, a typical pattern of early hypofluorescence and late hyperfluorescence on fluorescein angiography. Only untreated patients who had been followed for at least 1 month were included., Results: Out of 22 patients' records with a diagnosis of APMPPE, 10 patients (9 women, 1 man), with a mean age of 24.5 ± 4.2 years, fulfilled the study criteria with a diagnosis of typical untreated APMPPE. Prodromal symptoms were reported in 7/10 patients. Macular lesions were observed in 18/20 eyes. Sub-retinal fluid was seen at presentation in 3 eyes. Initial mean BCVA was 0.56 ± 0.81 LogMAR [- 0.10 to 2.30]. In 9 out of 10 cases, the time interval between manifestations in the first affected eye and the fellow eye was less than 3 days. After 1 month, BCVA had improved to 0.05 ± 0.089 LogMAR [0-0.3], with a decimal BCVA ≥0.8 in 17/20 eyes., Conclusions: In these 10 cases of untreated APMPPE, a favorable outcome was observed.

Purpose: This study aimed at reporting lymphocytic meningitis in patients diagnosed with sympathetic ophthalmia (SO)., Methods: In this single-center retrospective observational case series, we reviewed cases diagnosed with SO. We analyzed the patients' inciting injuries, the characteristics of uveitis and the cerebrospinal fluid (CSF) analyses., Results: Nine patients were diagnosed with SO and CSF analyses were available in all cases. Four cases had lymphocytic pleocytosis, 3 of which showed marked CSF inflammation with more than 300 lymphocytes/mm 3 . The inciting event in these 3 patients was a globe perforation injury, whereas 4 patients without meningitis had SO following a surgical intervention., Conclusions: In this case series of patients with SO, lymphocytic meningitis was a common finding. The prevalence of meningitis in patients with SO and its value for the diagnosis of the disease needs to be further studied.

Wagner disease is a rare nonsyndromic autosomal-dominant vitreoretinopathy, associated with splice mutations specifically targeting VCAN exon 8. We report the extensive genetic analysis of two Wagner probands, previously found negative for disease-associated splice mutations. Next-generation sequencing (NGS), quantitative real-time PCR, and long-range PCR identified two deletions (3.4 and 10.5 kb) removing at least one exon-intron boundary of exon 8, and both correlating with an imbalance of VCAN mRNA isoforms. We showed that the 10.5-kb deletion occurred de novo, causing somatic mosaicism in the proband's mother who had an unusually mild asymmetrical phenotype. Therefore, exon 8 deletions are novel VCAN genetic defects responsible for Wagner disease, and VCAN mosaic mutations may be involved in the pathogenesis of Wagner disease with attenuated phenotype. NGS is then an effective screening tool for genetic diagnosis of Wagner disease, improving the chance of identifying all disease-causative variants as well as mosaic mutations in VCAN., (© 2016 WILEY PERIODICALS, INC.)

Purpose of Review: The ocular manifestations in autoimmune polyendocrinopathy syndrome type 1 (APS1) are frequent and have a poor prognosis. The phenotype of these APS1-associated ocular features have been recently characterized in molecularly confirmed patients with APS1., Recent Findings: Keratopathy and retinopathy can be severe manifestations of APS1. Heterogeneous corneal involvement can be observed, ranging from minimal superficial punctate staining to severe stromal scarring with deep corneal neovascularization. This phenotypic heterogeneity, observed even in patients with identical AIRE mutations, is suggestive of a poor genotype-phenotype correlation. Similarly, in patients with retinopathy, peripheral pigmentary changes are noted in all cases, yet with heterogeneous severity, ranging from isolated patchy atrophy of the retinal pigment epithelium to a retinitis pigmentosa-like fundus. Macular atrophy with vision loss is found in most cases. The severity of ophthalmic findings is uncorrelated to that of systemic manifestations. An autoimmune origin with specific autoantibodies directed against corneal and/or retinal autoantigens is the main mechanism believed to be responsible for the ocular manifestations of APS1., Summary: Progressive keratopathy and/or retinopathy can lead to severe visual loss and pain in patients with APS1. Although no treatment has shown efficacy regarding the APS1-associated ocular manifestations, ophthalmologic examinations are recommended in these patients.

Background: Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids., Methods: We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≥18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838., Findings: Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39-0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group)., Interpretation: Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis., Funding: AbbVie., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis., Methods: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported., Results: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years)., Conclusions: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

Hydroxychloroquine (HCQ) and chloroquine have been used for more than 50 years to treat systemic lupus erythematosus (SLE) and other rheumatic diseases. In general, these drugs are well tolerated and rarely need to be discontinued because of an adverse systemic reaction. However, both medications can be irreversibly toxic to the retina. A new study indicates that toxicity is not as rare as once believed, but depends critically on daily dosage and duration of use, as well as other risk factors. With attention to dosage and other factors, and with proper screening for early signs of toxicity, HCQ can be prescribed with relative safety even over long periods of time.

Purpose: To evaluate the spectrum of morphologic abnormalities in patients with Wagner syndrome by spectral-domain optical coherence tomography (SD OCT)., Design: Retrospective comparative case study., Methods: Institutional study of patients entered into the French Vitreoretinopathy Study Group database. Twelve eyes of 9 patients from 3 unrelated families with genetically confirmed Wagner syndrome and 28 eyes from 15 age- and sex-matched healthy family controls were scanned by SD OCT. Morphology and layer thickness of the total retina, inner retinal layers, outer retinal layers, and photoreceptor layer at different degrees of eccentricity from the fovea were compared between the 2 groups., Results: A thick multilayered membrane adherent to the perifovea but completely detached from the fovea, thus forming a bridge over the foveal pit, was observed in 84% of eyes from patients with Wagner syndrome. At the equatorial area, SD OCT imaging allowed visualization of the architecture of an avascular vitreous veil with localized retinal traction. Most retinal layers were significantly thinner in patients with Wagner syndrome compared to the control group, except at the foveal center where abnormal persistence of 1 or more inner retinal layers could be observed., Conclusion: SD OCT provides better structural insight into the range of retinal defects at the vitreoretinal interface and fovea, which is not only useful for improving diagnosis and management, but also for understanding the pathogenesis of Wagner syndrome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To report the spectrum of phenotypes in patients with autoimmune polyendocrinopathy syndrome type 1 (APS1)-related keratopathy., Methods: In this retrospective observational case series, 6 patients followed for APS1 were included. Data collected included family history, age at presentation, and systemic and ophthalmic manifestations. The 14 coding exons of the autoimmune regulator (AIRE) gene were sequenced., Results: The age at the onset of keratopathy ranged from 4 to 20 years. The ocular symptoms varied from mild photophobia to severe pain, and visual acuity was from light perception to 20/20 Snellen equivalent. Heterogeneous corneal involvement was observed, ranging from minimal superficial punctate staining to severe stromal scarring with deep corneal neovascularization. The severity of ophthalmic findings was uncorrelated to that of systemic manifestations. The genetic analyses identified 2 novel mutations (c.173C>A in exon 2 and c.892G>T in exon 8) and 4 known mutations (c.62C>T in exon 1, c.415C>T in exon 3, c.1096-1G>A in intron 9, and c.1193delC in exon 10) in the AIRE gene. In patients with identical AIRE mutations, including within a sib-pair, heterogeneous phenotypes were observed., Conclusions: Keratopathy can be an early and severe manifestation of APS1, which contributes to the global prognosis of the disease. Its mechanisms remain to be elucidated.

Purpose. To weigh ocular emergency events according to their severity. Methods. A group of ophthalmologists and researchers rated the severity of 86 common ocular emergencies using a Delphi consensus method. The ratings were attributed on a 7-point scale throughout a first-round survey. Then, the experts were provided with the median and quartiles of the ratings of each item to reevaluate the severity levels being aware of the group's first-round responses. The final severity rating for each item corresponded to the median rating provided by the last Delphi round. Results. We invited 398 experts, and 80 (20%) of them, from 18 different countries, agreed to participate. A consensus was reached in the second round, completed by 24 experts (43%). The severity ranged from subconjunctival hemorrhages (median = 1, Q1 = 0; Q3 = 1) to penetrating eye injuries collapsing the eyeball with intraocular foreign body or panophthalmitis with infection following surgery (median = 5, Q1 = 5; Q3 = 6). The ratings did not differ according to the practice of the experts. Conclusion. These ratings could be used to assess the severity of ocular emergency events, to serve in composite algorithms for emergency triage and standardizing research in ocular emergencies.

Importance: This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma., Objective: To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy., Design, Setting, and Patients: In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital., Main Outcomes and Measures: Patients' demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced., Results: Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients., Conclusions and Relevance: This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients' survival were greater than the risk to their vision.

Purpose: Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune disease characterized by inaugural uveomeningitidis and hearing loss and at late stages a depigmentation in eyes and skin. Melanocytes are the cells common to the four affected tissues, namely eye, brain, inner ear, and skin. Melanocytes are therefore considered as the source of self-antigens. The melanocytic proteins tyrosinase-related protein-1 (TRP1), TRP2, tyrosinase, and gp100 have been proposed as the proteins targeted by autoreactive T cells from VKH patients bearing human leukocyte antigen (HLA)-DRB1*04:05, the HLA allele classically associated with VKH disease. The objective of this work was to determine the antigens recognized by a large number of potentially autoreactive CD4 T lymphocytes obtained from the cerebrospinal fluid of one VKH patient who did not express HLA-DRB1*04:05., Methods: T cells were isolated from the cerebrospinal fluid of a newly diagnosed HLA-DRB1*14:01,*15:03;-DPB1*01:01,*04:02 patient in the acute phase of the VKH disease and cloned by limiting dilution. Each of the 107 T cell clones, of which 90% were CD4(+), was tested for its ability to secrete cytokines upon contact with autologous antigen-presenting cells loaded with either of the melanocytic proteins TRP1, TRP2, tyrosinase, gp100, Melan-A and KU-MEL-1. The sensitivity of our recombinant bacteria-based approach was validated with a CD4 T cell clone with known antigen specificity. The ability of each of the 107 clones to secrete cytokines upon nonspecific stimulation was verified., Results: None of the 107 T cell clones was able to secrete tumor necrosis factor-α, interferon-γ, interleukin (IL)-5, or IL-17 upon contact with autologous B cells loaded with any of the six common melanocytic proteins. Nine clones secreted high-level IL-17 upon stimulation with beads coated with antibodies., Conclusions: The self-antigens that triggered the VKH disease in this patient probably derive from proteins other than the six melanocytic proteins mentioned above. Further study of antigens that are recognized by potential autoreactive T cells from VKH patients is likely to benefit from testing a broader set of melanocytic proteins.