ANCA-associated scleritis: impact of ANCA on presentation, response to therapy and outcome.

OBJECTIVES: To describe the characteristics, treatment and outcome of isolated ANCA-associated scleritis at diagnosis compared with idiopathic scleritis with negative ANCA tests. METHODS: This retrospective multicentre case-control study was performed within the French Vasculitis Study Group (FVSG) network and in three French tertiary ophthalmologic centres. Data from patients with scleritis without any systemic manifestation and with positive ANCA results were compared with those of a control group of patients with idiopathic scleritis with negative ANCA tests. RESULTS: A total of 120 patients, including 38 patients with ANCA-associated scleritis and 82 control patients, diagnosed between January 2007 and April 2022 were included. The median follow-up was 28 months (IQR 10-60). The median age at diagnosis was 48 years (IQR 33-60) and 75% were females. Scleromalacia was more frequent in ANCA-positive patients (P = 0.027) and 54% had associated ophthalmologic manifestations, without significant differences. ANCA-associated scleritis more frequently required systemic medications, including glucocorticoids (76% vs 34%; P < 0.001), and rituximab (P = 0.03) and had a lower remission rate after the first- and second-line treatment. Systemic ANCA-associated vasculitis (AAV) occurred in 30.7% of patients with PR3- or MPO-ANCA, after a median interval of 30 months (IQR 16.3-44). Increased CRP >5 mg/l at diagnosis was the only significant risk factor of progression to systemic AAV [adjusted hazard ratio 5.85 (95% CI 1.10, 31.01), P = 0.038]. CONCLUSION: Isolated ANCA-associated scleritis is mostly anterior scleritis with a higher risk of scleromalacia than ANCA-negative idiopathic scleritis and is more often difficult to treat. One-third of patients with PR3- or MPO-ANCA scleritis progressed to systemic AAV.

Incidence of Retinal Detachment, Macular Edema, and Ocular Hypertension after Neodymium:Yttrium-Aluminum-Garnet Capsulotomy: A Population-Based Nationwide Study-The French YAG 2 Study.

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.

Incidence of Nd:YAG laser capsulotomy following cataract surgery: a population-based nation-wide study - FreYAG1 study.

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 253.103 patients had Nd:YAG-caps, representing 312.103 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.

Femtosecond laser-assisted versus phacoemulsification cataract surgery (FEMCAT): a multicentre participant-masked randomised superiority and cost-effectiveness trial.

BACKGROUND: Cataract surgery is one of the most common operations in health care. Femtosecond laser-assisted cataract surgery (FLACS) enables more precise ocular incisions and lens fragmentation than does phacoemulsification cataract surgery (PCS). We hypothesised that FLACS might improve outcomes in cataract surgery compared with PCS despite having higher costs. METHODS: We did a participant-masked randomised superiority clinical trial comparing FLACS and PCS in two parallel groups (permuted block randomisation stratified on centres via a centralised web-based application, allocation ratio 1:1, block size of 2 or 4 for unilateral cases and 2 or 6 for bilateral cases). Five French University Hospitals enrolled consecutive patients aged 22 years or older who were eligible for unilateral or bilateral cataract surgery. Participants, outcome assessors, and technicians carrying out examinations were masked to the surgical treatment allocation until the last follow-up visit and a sham laser procedure was set up for participants randomly assigned to the PCS arm. The primary clinical endpoint was the success rate of surgery, defined as a composite of four outcomes at a 3-month postoperative visit: absence of severe perioperative complication, a best-corrected visual acuity (BCVA) of 0·0 LogMAR (logarithm of the minimum angle of resolution) or better, an absolute refractive error of 0·75 dioptres or less, and unchanged postoperative corneal astigmatism power (≤0·5 dioptres) and axis (≤20°). The primary economic endpoint was the incremental cost per additional patient who had treatment success at 3 months. Primary outcomes were assessed in all randomly assigned patients who met all eligibility criteria (missing data considered as failure). We used mixed logistic regression models or mixed linear regression models for statistical comparisons, adjusted on centres and whether cataract surgery was bilateral or unilateral. The study is registered with ClinicalTrials.gov, NCT01982006. FINDINGS: Of the 907 patients (1476 eyes) randomly assigned between Oct 9, 2013, and Oct 30, 2015, 870 (704 eyes in FLACS group and 685 eyes in the PCS group) were analysed. We identified no significant difference in the success rate of surgery between the FLACS and PCS groups (FLACS: 41·1% [289 eyes]; PCS: 43·6% [299 eyes]); adjusted odds ratio 0·85, 95% CI 0·64-1·12, p=0·250). The incremental cost-effectiveness ratio was €10 703 saved per additional patient who had treatment success with PCS compared with FLACS. We observed no severe adverse events during the femtosecond laser procedure, and most of the complications in the FLACS group related to the primary outcome measures occurred during the phacoemulsification phase or postoperatively. INTERPRETATION: Despite its advanced technology, femtosecond laser was not superior to phacoemulsification in cataract surgery and, with higher costs, did not provide an additional benefit over phacoemulsification for patients or health-care systems. FUNDING: French Ministry of Social Affairs and Health.

Ocular Safety Profile of BRAF and MEK Inhibitors: Data from the World Health Organization Pharmacovigilance Database.

PURPOSE: BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) significantly improved metastatic melanoma prognosis. Ocular adverse effects (OAEs) represent an uncommon but disabling toxicity of these drugs. We aimed to characterize the ocular safety profile of BRAFi or MEKi and to detect possible safety signals. METHODS: We performed a retrospective, observational, pharmacovigilance study using VigiBase, the World Health Organization global safety database. Ocular adverse effects were classified according to the eye segments and the inflammatory pattern based on the Standardization of Uveitis Nomenclature. Associations among BRAFi monotherapy, MEKi monotherapy, and BRAFi+MEKi combination therapy and OAE reporting were assessed using disproportionality analysis. Results were expressed with the reporting odds ratio (ROR) and its 95% confidence interval (CI). RESULTS: From January 2010 to October 2019, 1568 OAE cases were reported with BRAFi or MEKi. Among them, 1006 cases with sufficient data were included, corresponding to 310 (30.8%), 124 (12.3%), and 572 (56.9%) cases reported with BRAFi, MEKi, or BRAFi+MEKi combination therapy, respectively. BRAF inhibitor monotherapy was significantly associated with the reporting of iris and ciliary body abnormalities (ROR, 8.7; 95% CI, 6.0-12.5), diffuse abnormalities (ROR, 7.1; 95% CI, 5.4-9.4), anterior uveitis (ROR, 8.6; 95% CI, 6.0-12.1), and panuveitis (ROR, 7.1; 95% CI, 5.4-9.4). MEK inhibitor monotherapy was associated with the reporting of retinal and choroid abnormalities (ROR, 9.5; 95% CI, 7.4-12.2), diffuse abnormalities (ROR, 2.5; 95% CI, 1.1-6.1), and panuveitis (ROR, 2.5; 95% CI, 1.1-6.1). Combinations of BRAFi and MEKi therapies were associated with OAEs from both drugs, with a possible synergistic or additive effect for diffuse abnormalities and panuveitis. CONCLUSIONS: Our study characterizes the ocular safety profile of BRAFi and MEKi. We identify possible safety signals for several OAEs not previously reported with BRAFi and MEKi. Our data provide the rationale for a personalized management of OAE in patients with BRAFi+MEKi combination therapy according to the type of ocular reaction.

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME AND POSTERIOR OCULAR INVOLVEMENT: Case Series of 11 Patients and Literature Review.

PURPOSE: To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome. METHODS: Retrospective case series of patients presenting with catastrophic antiphospholipid syndrome and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at catastrophic antiphospholipid syndrome diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best-corrected visual acuity. RESULTS: This study included 23 patients (11 cases treated by the authors and 12 published case reports); 21 (91%) of them female. Their median age at diagnosis was 28 years (range, 16-79 years). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n = 11, 48%), or retinal vasculitis (n = 1, 4%). Final best-corrected visual acuity was not significantly worse than the best-corrected visual acuity at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months (range, 2-132 months), nearly half the patients (n = 11, 48%) had permanent vision loss including best-corrected visual acuity of <20/400 for 4 patients. CONCLUSION: Posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.

Choroidal and peripapillary changes in high myopic eyes with Stickler syndrome.

BACKGROUND: To compare different clinical and Spectral-Domain Optical Coherence Tomography (SD-OCT) features of high myopic eyes with Stickler syndrome (STL) with matched controls. METHODS: Patients with genetically confirmed STL with axial length ≥ 26 mm and controls matched for axial length were included. The following data were obtained from SD-OCT scans and fundus photography: choroidal and retinal thickness (respectively, CT and RT), peripapillary atrophy area (PAA), presence of posterior staphyloma (PS). RESULTS: Twenty-six eyes of 17 patients with STL and 25 eyes of 19 controls were evaluated. Compared with controls, patients with STL showed a greater CT subfoveally, at 1000 µm from the fovea at both nasal and temporal location, and at 2000 and 3000 µm from the fovea in nasal location (respectively, 188.7±72.8 vs 126.0±88.7 µm, 172.5±77.7 vs 119.3±80.6 µm, 190.1±71.9 vs 134.9±79.7 µm, 141.3±56.0 vs 98.1±68.5 µm, and 110.9±51.0 vs 67.6±50.7 µm, always P< 0.05). Furthermore, patients with STL showed a lower prevalence of PS (11.5% vs 68%, P< 0.001) and a lower PAA (2.2±2.1 vs 5.4±5.8 mm2, P=0.03), compared with controls. CONCLUSIONS: This study shows that high myopic patients with STL show a greater CT, a lower PAA and a lower prevalence of PS, compared with controls matched for axial length. These findings could be relevant for the development and progression of myopic maculopathy in patients with STL.

New clinical forms of hereditary apoA-I amyloidosis entail both glomerular and retinal amyloidosis.

Apolipoprotein A1 amyloidosis (ApoAI) results from specific mutations in the APOA1 gene causing abnormal accumulation of amyloid fibrils in diverse tissues. The kidney is a prominent target tissue in ApoAI amyloidosis with a remarkable selectivity for the renal medulla. Here, we investigated six French families with ApoAI Glu34Lys, p.His179Profs∗47, and a novel p.Thr185Alafs∗41 variant revealing unprecedented clinical association of a glomerular with a retinal disease. Comprehensive clinicopathological, molecular and proteomics studies of numerous affected tissues ensured the correlation between clinical manifestations, including novel unrecognized phenotypes, and apoA-I amyloid deposition. These ophthalmic manifestations stemmed from apoA-I amyloid deposition, highlighting that the retina is a previously unrecognized tissue affected by ApoAI amyloidosis. Our study provides the first molecular evidence that a significant fraction of ApoAI amyloidosis cases with no family history result from spontaneous neomutations rather than variable disease penetrance. Finally, successful hepatorenal transplantation resulted in a life- and vision-saving measure for a 32-year-old man with a hitherto unreported severe ApoAI amyloidosis caused by the very rare Glu34Lys variant. Our findings reveal new modes of occurrence and expand the clinical spectrum of ApoAI amyloidosis. The awareness of glomerular and ocular manifestations in ApoAI amyloidosis should enable earlier diagnosis and avoid misdiagnosis with other forms of renal amyloidosis. Thus, documented apoA-I amyloid deposition in the retina offers new biological information about this disease and may change organ transplantation practice to reduce retinal damage in patients with ApoAI amyloidosis.

Anterior segment optical coherence tomography imaging in peripheral ulcerative keratitis, a corneal structural description.

BACKGROUND: Anterior segment optical coherence tomography (AS OCT) is a helpful tool used to diagnose and manage many corneal conditions, but its use has not been reported in case of peripheral ulcerative keratitis (PUK). The aim of this study is to describe AS OCT findings in cases of PUK. METHODS: Retrospective observational case series of six eyes presenting with a PUK and proven systemic vasculitis. Clinical course, slit lamp photographs, and AS OCT findings were the main outcomes. RESULTS: The AS OCT findings were found to correlate with the ocular disease's level of activity. In the acute stage, an absence of corneal epithelium, a scrambled appearance of the anterior stroma and a heterogeneous stromal reflectivity were observed. During the reduction of disease level activity, an irregular hyporeflective epithelium, a smoother anterior stroma, and a homogenous hyperreflective stroma were seen. At the healed stage, a filling of the corneal defect by a hyporeflective thick epithelium, the persistence of the hyperreflective underlying stroma, and a demarcation line were observed. The mean total corneal thickness at last follow-up was significantly thicker (509 ± 147 µm) compared with the mean corneal thickness at onset (408 ± 131 µm; P = 0.03). CONCLUSIONS: AS OCT provides an assessment of structural changes occurring in PUK, useful for its diagnosis and monitoring.

Adalimumab in Patients with Active Noninfectious Uveitis.

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 .).

Acute anterior uveitis in spondyloarthritis: a monocentric study of 301 patients.

OBJECTIVES: To assess the cumulative incidence of uveitis in spondyloarthritis (SpA) and its associated factors and to evaluate the effect of DMARD treatment on uveitis in a real-life setting. METHODS: A cross-sectional monocentric observational study (COSPA) was conducted. Patients with definite SpA underwent a face-to-face interview. General data and specific data concerning uveitis were collected. Cumulative incidence of uveitis flares was estimated by Kaplan-Meier survival curves. Factors associated with uveitis were determined by Cox analysis. Treatment effectiveness was evaluated by comparing the number of uveitis flares before/after treatment using Wilcoxon test. RESULTS: In total, 301 patients were included, 186 (61.8%) were men, with mean age and disease duration of 44.8 (±13.6) and 16.8 (±11.9) years, respectively. Among them, 82 (27.2%) had at least one uveitis flare. Prevalence of uveitis at the time of SpA diagnosis was 11.5 % (±1.9%) and increased over time to reach 39.3% (±4.1%) 20 years after diagnosis. HLA B27 positivity and heel pain were independently associated with uveitis (HR [IC 95%] = 4.5 [1.3-15.2] and 1.8 [1.1-2.9], respectively). A significant reduction in the number of uveitis before/after treatment was observed in patients treated with anti TNF monoclonal antibodies (n=27), (1.83 (±4.03) vs. 0.41 (±1.22), p=0.002), whereas it was not with etanercept (n=19), (0.44 (±0.70) and 0.79 (±1.36), p=NS). CONCLUSIONS: Prevalence of uveitis in SpA seems to increase with disease duration and seems more likely to appear with HLA B27 positivity and heel pain. Anti-TNF monoclonal antibodies seemed to be more effective in the reduction of uveitis flares.

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

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.

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III.

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.

Cancer-associated retinopathy preceding the diagnosis of cancer.

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.

Untreated Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE): a case series.

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.