New onset of uveitis during infliximab treatment: A case report.

INTRODUCTION: Anti-tumor necrosis factor α (anti-TNF α) agents are an effective treatment for a variety of inflammatory and autoimmune diseases. In ophthalmology anti-TNF α began to emerge as a possible therapy for non-infectious uveitis, paradoxically their administration may result in the onset or recurrence of inflammatory eye disease such as uveitis. We reported a case of new onset of bilateral anterior and intermediate uveitis in a patient with rheumatoid arthritis (RA) while being treated with infliximab and we performed a review of literature. OBSERVATION: A 25-year-old female with RA under infliximab, presented with bilateral blurred vision. Anterior segment examination demonstrated retrodescmetic fine precipates, 1+ cells in the anterior chamber on both eyes. The fundus examination was difficult because of the vitritis. Fluorescein angiography demonstrated mild optic disc edema, and bilateral diffuse peripheral fern leaf cappilaritis. Optical coherence tomography showed severe cystoid macular edema bilaterally. The diagnosis of bilateral anterior and intermediate uveitis caused by infliximab was retained after exclusion of infectious and autoimmune aetiologies. She was treated with corticosteroid with good visual outcome. CONCLUSION: In our case, new onset of uveitis may be considered as paradoxical effect of anti-TNF α therapy. Rheumatologists and ophthalmologists should be aware of this effect. Careful monitoring of patients under infliximab is necessary for appropriate diagnosis and early treatment.

Risk of uveitis in autoimmune diseases patients treated with hydroxychloroquine: A population-based retrospective cohort study.

OBJECTIVE: Uveitis is a common manifestation of various autoimmune diseases and can lead to severe visual impairment. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used to treat autoimmune diseases. The aim of this study was to investigate the association between HCQ use and the incidence of uveitis in patients with autoimmune diseases, as well as to identify potential risk factors for the development of uveitis in this study. METHODS: We conducted a population-based cohort study using a nationwide database to investigate the incidence of uveitis in patients with autoimmune diseases who received HCQ treatment. We selected non-HCQ comparison cohort at a 1:1 ratio by propensity score matching on age, sex, index date, urbanization, income, comorbidities, and medications. The data were analyzed using Cox proportional hazards models, and propensity score matching (PSM) was used to reduce selection bias. RESULTS: Our study included 15 822 patients with autoimmune diseases. After 1:1 PSM, there were 4555 individuals in both the HCQ group (n = 4555) and the non-HCQ group (n = 4555). The multiple Cox proportional hazard regression analysis was used for the estimation of adjusted hazard ratios on uveitis. After PSM, the adjusted hazard ratio for the HCQ group was 0.74 (95% CI = 0.58-0.95). These findings suggest that HCQ may play a protective role in reducing the risk of uveitis in patients with autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus groups. The Kaplan-Meier survival curves also showed a significantly lower incidence of uveitis in the HCQ group (log-rank = 0.0229) after PSM. CONCLUSION: HCQ use is associated with a lower incidence of uveitis in patients with autoimmune diseases. Further studies are needed to confirm this association and to investigate the underlying mechanisms.

Unilateral Acute Retinal Necrosis with Contralateral Non-necrotizing Herpetic Uveitis.

PURPOSE: The objective of this study is to report a case of unilateral acute retinal necrosis (ARN) with contralateral eye presenting as non-necrotizing herpetic uveitis. CASE REPORTS: Case 1: A 48-year-old female presented at our clinic with blurred vision in the right eye for 7 days. She was diagnosed with ARN in the left eye 2 weeks ago. Ophthalmic examination revealed reduced visual acuity in the right eye (20/33) with the presence of optic disc swelling and macular exudation without peripheral necrotic lesions. With systemic antiviral therapy, optic disc swelling of the right eye vanished gradually, and the visual acuity improved to 20/20. Loss of retinal nerve fiber layer (RNFL) and decreased retinal thickness in the corresponding area occurred during follow-up. CONCLUSION: Non-necrotizing herpetic uveitis may occur in the contralateral eye of unilateral ARN under rare conditions. Structure abnormities, including loss of RNFL and focal decreased retinal thickness, are irretrievable.

Insights into the diagnosis and management of sarcoid uveitis: A review.

Sarcoidosis is a leading cause of non-infectious uveitis that commonly affects middle-aged individuals and has a female preponderance. The disease demonstrates age, sex and ethnic differences in clinical manifestations. A diagnosis of sarcoidosis is made based on a compatible clinical presentation, supporting investigations and histologic evidence of non-caseating granulomas, although biopsy is not always possible. Multimodal imaging with widefield fundus photography, optical coherence tomography and angiography can help in the diagnosis of sarcoid uveitis and in the monitoring of treatment response. Corticosteroid remains the mainstay of treatment; chronic inflammation requires steroid-sparing immunosuppression. Features on multimodal imaging such as vascular leakage may provide prognostic indicators of outcome. Female gender, prolonged and severe uveitis, and posterior involving uveitis are associated with poorer visual outcomes.

Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Steroidal nanoformulations for the treatment of uveitis: potential, promises and future perspectives.

BACKGROUND: Intraocular inflammation, commonly referred to as uveitis, is a prevalent ocular disease. The categorization of uveitis may be based on the prevailing anatomical site, which includes anterior, intermediate, and posterior uveitis. There exists a significant body of evidence indicating that T cells play a pivotal role in the pathogenesis of autoimmune uveitis. In addition to the presence of T cells, an elevation in levels of inflammatory cytokines and a reduction in regulatory cytokines were also noted. The primary pharmacological interventions for uveitis comprise of corticosteroids, methotrexate, anti-vascular endothelial growth factor (VEGF) agents, anti-tumor necrosis factor-alpha (TNF-α) antibodies, and sirolimus. These medications offer prompt alleviation for inflammation. Nevertheless, prolonged administration of corticosteroids invariably leads to unfavorable adverse reactions. The traditional topical corticosteroids exhibit certain limitations, including inadequate transcorneal permeation and low corneal retention, leading to reduced ocular bioavailability. Consequently, there is a growing inclination towards the creation of innovative steroid drug delivery systems with the aim of reducing the potential for adverse effects, while simultaneously enhancing the drug's corneal permeation and retention. CONCLUSION: This review is an attempt to compile all the research work done so far in this field and provides a brief overview of the global efforts to develop innovative nanocarrier-based systems for corticosteroids.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha treatment for patients with Behcet's uveitis: A systematic review and meta-analysis.

AIM: This study aims to evaluate the long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha (anti-TNF-α) therapy for patients with Behcet's uveitis (BU) using meta-analysis. METHODS: We searched the Web of Science and PubMed databases for eligible studies up to December 1, 2022. The quality of each identified study was assessed using the Joanna Briggs Institute's case series literature quality assessment tool. Statistical analysis was conducted using Stata 16.0 software with a random-effects model. RESULTS: Twelve studies comprising 1156 patients with BU were included in our analysis. We found that 85.0% of patients achieved ocular inflammation remission after receiving anti-TNF-α treatment, with a 95% confidence interval (CI) ranging from 78.7% to 90.5%. Additionally, 77.4% (95% CI: 57.5%-92.5%) experienced an improvement in visual acuity (VA). Moreover, the pooled dose reduction of glucocorticoids (GCs) was 11.08 mg (95% CI: -13.34 mg to -8.83 mg). Throughout the follow-up period, the cumulative retention rate of the medication was 67.3% (95% CI: 53.7%-79.6%). Serious adverse events occurred in 5.8% (95% CI: 3.1%-8.9%) of cases, with the three most common types being severe infusion or injection reactions (2.7%; 95% CI: 0.8%-5.4%), tuberculosis (1.3%; 95% CI: 0.0%-3.9%), and bacterial pneumonia (1.3%; 95% CI: 0.1%-3.4%). Subgroup analysis revealed that ocular inflammation remission rates were 89.3% (95% CI: 81.2%-95.5%) for adalimumab treatment and 83.7% (95% CI: 75.3%-90.8%) for infliximab treatment. The drug retention rate after adalimumab therapy was 70.3% (95% CI: 62.0%-78.0%) compared to 66.4% (95% CI: 48.6%-82.2%) for infliximab treatment. Furthermore, the incidence of severe infusion or injection reactions was 2.2% (95% CI: 0.1%-5.8%) following adalimumab treatment and 3.5% (95% CI: 0.7%-7.7%) following infliximab treatment. CONCLUSIONS: Anti-TNF-α therapy represents an effective treatment for BU patients with favorable safety profile and high drug retention rate and a potential advantage of adalimumab over infliximab in terms of ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.

[Diagnostic modalities of a Behçet uveitis]. / Comment j'explore une uvéite de Behçet.

Behçet disease is a chronic multisystemic inflammatory condition. The ocular disease mainly manifests as a bilateral, non-granulomatous, posterior uveitis or panuveitis, associated with occlusive retinal vasculitis. Uveitis is frequent in Behçet disease, it may be severe, and visually threatening. Early diagnosis and aggressive treatment are mandatory to preserve visual function. Therefore, the goal of this review is to describe the new diagnosis tools and therapeutic guidelines allowing for a significant improvement of the visual prognosis.

La maladie de Behçet est une pathologie inflammatoire chronique multisystémique. L'atteinte oculaire se caractérise le plus souvent par une panuvéite ou uvéite postérieure bilatérale récidivante, non granulomateuse, associée à une vascularite rétinienne occlusive. L'uvéite associée à la maladie de Behçet est fréquente, sévère et potentiellement cécitante en l'absence d'un diagnostic précoce et d'un traitement adapté. L'objectif de cette revue est de décrire les outils diagnostiques et thérapeutiques ayant permis une amélioration significative du pronostic visuel.

New onset or recurrence of uveitis following COVID-19 infection.

BACKGROUND: While the 2019 novel coronavirus disease (COVID-19) pandemic has resulted in millions of cases worldwide, there is increasing recognition of a wide range of ocular manifestations associated with the virus, including uveitis. Uveitis is an inflammatory condition of the uveal tract of the eye that can lead to permanent vision loss if not treated promptly. Here we report a retrospective observational study of patients who presented with new onset or recurrent uveitis following COVID-19 infection. METHODS: This is a retrospective observational study conducted at the Beijing Tongren Hospital. We identified patients who presented with symptoms of non-infectious active uveitis with positive real-time reverse transcription polymerase chain reaction (RT-PCR) of COVID-19 within 4 weeks. All patients received ophthalmic examinations, including anterior and posterior segment imaging, to assess the extent of ocular involvement. RESULTS: The 18 patients with a total of 33 eyes included in this study presented with symptoms of active uveitis within 4 weeks of their positive COVID-19 RT-PCR test. Among them, 9 patients presented with the development of uveitis following COVID-19 infection, and 9 patients had relapsed uveitis after COVID-19 infection. Treatment with corticosteroids resulted in improvement of symptoms and resolution of inflammation in all cases. In this study, all patients did not experience any adverse drug reactions during treatment. CONCLUSION: Our observational study highlights the potential for new onset or recurrence of uveitis following COVID-19 infection. TRIAL REGISTRATION: https://www.chictr.org.cn/ ; identifier: ChiCTR2100044365, date: 03/17/2023.

Factors Associated With Intraocular Inflammation in Neovascular Age-Related Macular Degeneration Patients Treated With Brolucizumab.

Purpose: To identify factors associated with intraocular inflammation (IOI) in patients with neovascular age-related macular degeneration (nAMD) treated with brolucizumab. Methods: In this prospective observational study, we collected aqueous humor samples from 96 eyes of 96 patients receiving treatment with brolucizumab; IOI subsequently developed in 19 eyes of 19 patients. To identify cytokines upregulated in eyes with subsequent development of IOI, we compared the aqueous humor cytokine levels between the IOI and non-IOI groups. We also collected plasma from 20 patients who developed IOI and 20 age- and sex-matched controls to identify differences in plasma biomarkers and the subfraction of CD4+ cells. Using stepwise variable selection and multivariate binary regression analysis, we developed an algorithm that accurately assessed the likelihood of IOI occurrence. Results: The IOI group showed elevated aqueous humor levels of P-selectin (584 vs. 324 pg/mL, P = 0.013), TNF-α (0.89 vs. 0.60 pg/mL, P = 0.018), and IL-1α (2.0 vs. 1.4 pg/mL, P = 0.035) compared with the non-IOI group. Serum MMP-9 concentrations were higher in the IOI group than the non-IOI group (18,310 vs. 13,450 pg/mL, P = 0.029). Furthermore, the percentage of Th2 cells was significantly decreased in the IOI compared with the non-IOI group (3.1% vs. 4.2%, P = 0.013). The receiver operating characteristic curves for the optimal models showed an area under the curve ranging from 0.71 to 0.89, indicating good performance. Conclusions: The combination of elevated concentrations of multiple aqueous humor cytokines and of serum MMP-9 and a lower number of plasma Th2 cells is associated with brolucizumab-related IOI in patients with nAMD.

Leflunomide for the Treatment of Immune-Mediated Uveitis in a Dog.

A 5 yr old castrated male bichon frise presented with chronic bilateral uveitis that had previously been controlled with systemic steroid administration for 6 mo, resulting in weight gain, polyuria, and polydipsia. To control the uveitis without systemic side effects, oral cyclosporine was started after discontinuing oral steroid, but discontinued one month later because of severe vomiting. Leflunomide (2 mg/kg q 12 hr) was initiated, and the uveitis symptoms resolved after 2 mo. The dose was tapered according to the remission of clinical signs, with no relapse during the following 13 mo. Leflunomide therapy was then discontinued due to vomiting caused by severe gastroenteritis and pancreatitis, and topical prednisolone monotherapy was continued . At 8 mo after discontinuation of leflunomide, bilateral uveitis recurred, and leflunomide therapy was resumed. However, the patient lost vision due to the progression of clinical signs at 33 mo after commencing leflunomide, and evisceration of the glaucomatous right eye was performed at 43 mo. Histopathologic examination revealed lymphocyte and plasma cell infiltration and melanin-laden macrophages in the uveal tissue, and the patient was diagnosed with immune-mediated uveitis. This case indicated that oral leflunomide may be a viable treatment option for canine idiopathic immune-mediated uveitis.

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness-a protocol for a randomised controlled trial (ASTUTE trial).

INTRODUCTION: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care. METHODS AND ANALYSIS: The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted. ETHICS AND DISSEMINATION: The trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available. TRIAL REGISTRATION: ISRCTN31474800. Registered 14 April 2020.

Epstein-Barr Virus Uveitis Confirmed via Aqueous Humor Polymerase Chain Reaction and Metagenomics-A Case Report.

This is a case report of Epstein-Barr virus (EBV) uveitis confirmed via aqueous humor polymerase chain reaction (PCR) and metagenomics. This 72-year-old male with a history of diabetes and herpes zoster complained of redness and blurred vision in his right eye for eight months. Mild conjunctival injection, anterior chamber cells, mutton-fat keratic precipitates, and vitreous haze were noted. Fluorescein angiography revealed dye leakage from retinal vessels without retinal ischemic changes. Only the serum anti-cytomegalovirus (CMV) IgG was positive while the aqueous humor PCR for VZV (Varicella-zoster virus), HSV (Herpes simplex viruses), CMV, and EBV was initially negative. Inflammation recurred and vitreous haze worsened after discontinuing nine-month topical ganciclovir and oral prednisolone. the aqueous humor PCR was repeated due to persistent low-grade inflammation. The EBV PCR turned out to be positive. Shotgun metagenomics revealed 1459 classified sequences (1.62%) and confirmed the EBV infection. Topical ganciclovir and methylprednisolone treatment was resumed. Conjunctival injection improved while pigmented keratic precipitates lessened. Elderly patients with diabetes or under immunosuppression may be susceptible to chronic uveitis associated with subsequent EBV infection. Repeated aqueous humor PCR and shotgun metagenomics are important tools in the diagnosis of this case of chronic indolent panuveitis.

Efficacy of golimumab in patients with refractory non-infectious panuveitis.

This study investigated the efficacy of golimumab in the management of refractory non-infectious panuveitis. Nineteen patients (38 eyes; mean age, 31 years) were retrospectively reviewed between June 2016 and June 2022. All patients had bilateral eye involvement and Behçet's disease was the most common diagnosis (57.9%). Compared to the period before golimumab treatment, the rate of uveitis relapses after golimumab treatment significantly decreased from 1.73 to 0.62 events per person-years (incidence ratio 0.33, 95% confidence interval 0.19-0.57, P < 0.001). After golimumab therapy, 12 patients (63.2%) were able to reduce the number or dosage of immunosuppressive drugs, and the median dosage of systemic corticosteroids was reduced from 15.0 to 7.5 mg/d (P = 0.013) compared to baseline. The median logMAR visual acuity improved from 0.9 at baseline to 0.6 at the last visit (P = 0.006). Golimumab demonstrated efficacy against refractory non-infectious panuveitis in terms of a corticosteroid-sparing effect and reduced the rate of uveitis relapses to approximately one-third.

Screening for juvenile idiopathic arthritis associated uveitis with laser flare photometry in the pediatric rheumatology office: a prospective observational study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) Associated Uveitis (JIA-U) remains one of the most serious complications of JIA in children. Historically, pediatric JIA is diagnosed by an Optometrist or Ophthalmologist; however, barriers to scheduling increase wait times that may delay diagnosis and treatment. The purpose of this study was to evaluate laser flare photometry (LFP) use to diagnose JIA-U in the Pediatric Rheumatology clinic for patients with JIA. METHODS: This prospective, observational study assessed pediatric patients diagnosed with JIA without a previous history of uveitis between January 2020 and September 2022. All patients underwent at least one evaluation of both eyes using a Kowa FM-600 laser flare photometer during a routine Rheumatology appointment, as well as a standard slit lamp examination (SLE) by optometry or ophthalmology during routine clinical care. Data collected at patient visits included demographics, JIA characteristics, treatment, LFP readings, and anterior chamber (AC) cell grade score utilizing the SUN grading system. Data were summarized using descriptive analyses and the uveitis false positive rate was calculated. RESULTS: The study cohort included 58 pediatric patients diagnosed with JIA. The mean age was 8.4 years (1.2-16.3 years) at diagnosis and 11.9 (4.8-16.5 years) at enrollment. The mean duration of disease at time of enrollment was 42 months (range; 0-157 months). Participants were predominantly female (n = 43, 74.1%) and white/Caucasian race (n = 37, 63.8%). The most common JIA subtypes included persistent oligoarticular JIA (n = 19, 32.8%), and RF negative polyarticular JIA (n = 12, 20.7%). There were 12 ANA positive patients (20.7%). At enrollment, 16 patients (27.6%) were not on medications, with 20 (34.5%) on methotrexate, 20 (34.5%) on adalimumab, 6 (10.3%) on tocilizumab, and 5 (8.6%) on etanercept. During the study period, no eye exams detected active uveitis based on SLE with a SUN grade over 0. However, of the 135 LFP readings, 131 (97.0%) were normal, yielding a false positive rate of 3% (95% CI: 0.8%, 7.4%). CONCLUSIONS: LFP is a non-invasive tool that can be utilized in the pediatric rheumatology clinic to evaluate for JIA-U. There is a low false positive rate of LFP when compared with standard slit lamp exam.

The use of shotgun label-free quantitative proteomic mass spectrometry to evaluate the inflammatory response in aqueous humor from horses with uveitis compared to ophthalmologically healthy horses.

OBJECTIVE: The objective of this study was to use shotgun label-free tandem mass spectrometry (LF-MS/MS) to evaluate aqueous humor (AH) from horses with uveitis (UH) compared to ophthalmologically healthy horses (HH). ANIMALS STUDIED: Twelve horses diagnosed with uveitis based on ophthalmic examination and six ophthalmologically healthy horses (postmortem) purchased for teaching purposes. PROCEDURES: All horses received a complete ophthalmic examination and physical exam. Aqueous paracentesis was performed on all horses and AH total protein concentrations were measured with nanodrop (TPn) and refractometry (TPr). AH samples were analyzed with shotgun LF-MS/MS and proteomic data were compared between groups using Wilcoxon rank-sum test. RESULTS: A total of 147 proteins were detected, 11 proteins had higher abundance in UH, and 38 proteins had lower abundance in UH. Proteins with higher abundance included apolipoprotein E, alpha-2-macroglobulin (A2M), alpha-2-HS-glycoprotein, prothrombin, fibrinogen, complement component 4 (C4), joining chain for IgA and IgM, afamin, and amine oxidase. There were positive correlations between TPn (p = .003) and TPr (p = .0001) compared to flare scores. CONCLUSION: Differential abundance of A2M, prothrombin, fibrinogen, and C4 indicate upregulation of the complement and coagulation cascade in equine uveitis. Proinflammatory cytokines and the complement cascade have potential as therapeutic targets for equine uveitis.

Hydroxychloroquine Therapy in Sarcoidosis-Associated Uveitis.

BACKGROUND/PURPOSE: To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis. METHODS: Retrospective study on all patients with sarcoidosis-associated uveitis who were treated with hydroxychloroquine between 2003 and 2019 in a French university hospital. RESULTS: Twenty-seven patients with sarcoidosis-associated uveitis received hydroxychloroquine. The mean duration of treatment was 20.0 ± 10.9 months. At the end of the follow-up, hydroxychloroquine success was achieved in 15 (55.6%) patients. Four of them were also on oral corticosteroids, with a prednisone dose ≤5 mg/day. Under treatment, the median prednisone dose decreased from 20.0 (interquartile range (IQR), 7-25) to 5.0 (IQR, 3-6.5) mg/day (p = .02). The incidence rate of flare decreased from 204.6 to 63.8 per 100 person-years (p = .02). Hydroxychloroquine was discontinued in 12 (44.4%) patients during follow-up, including 8 (29.6%) for ineffectiveness, and three who experienced side effects. CONCLUSION: Hydroxychloroquine appears as an interesting option in sarcoidosis-associated uveitis.Abbreviations: AZA: Azathioprine; BAL: Bronchoalveolar Lavage; BCVA: Best-Corrected Visual Acuity; ENT: Ears, Nose and Throat; HCQ: Hydroxychloroquine; IOP: Intra-Ocular Pressure; IQR: interquartile range; MHC: Major Histocompatibility Complex; MMF: Mycophenolate Mofetil; MTX: Methotrexate; PMSI: Programme de Médicalisation du Système d'Information; SAU: Sarcoidosis-Associated Uveitis; SD: Standard Deviation; SUN: Standard Uveitis Nomenclature.

A Comparative Preclinical Evaluation of a Novel Difluprednate 0.04% BID Ophthalmic Solution and Marketed 0.05% QID Ophthalmic Emulsion.

Purpose: The purpose of this study was to compare the efficacy, and ocular pharmacokinetics of a new 0.04% w/v bis in die means twice a day (BID) ophthalmic solution and marketed 0.05% w/v quater in die means four times a day (QID) ophthalmic emulsion of difluprednate in New Zealand white (NZW) rabbits. Methods: The preclinical proof of concept was established in paracentesis-induced acute inflammation, endotoxin-induced acute uveitis, and bovine serum albumin-induced chronic uveitis in NZW rabbit animal models. A comparison of clinical score, total cell count, and total protein was performed to determine efficacy. An ocular pharmacokinetic study was conducted to study the influence of the vehicle on the ocular absorption of the drug. Results: In both uveitis models, the new solution formulation and marketed emulsion formulation inhibited total clinical score, total cell count, PGE2, and total protein significantly more than the placebo and lipopolysaccharide (disease control) groups and were comparable. In an ocular pharmacokinetic study, the Cmax and AUC0-t of difluoroprednisolone 17-butyrate in humor were ∼2-fold higher after 14 days' instillation of new solution formulation (0.04% w/v, BID) compared with 14 days' instillation of marketed emulsion (0.05% w/v, QID). Conclusions: The study demonstrated that the efficacy of the solution formulation at a lower dose and reduced dosing regimen were comparable to that of the emulsion formulation. The reduction in strength and regimen may result in improved patient adherence and outcomes.

Diagnosis and Management of Non-Infectious Uveitis in Pediatric Patients.

Uveitis in children accounts for 5-10% of all cases. The causes vary considerably. Classically, uveitis is distinguished according to its infectious or inflammatory origin and whether it is part of a systemic disease or represents an isolated ocular disease. It is important to highlight the specificity of certain etiologies among children such as juvenile idiopathic arthritis. The development of visual function can potentially be hindered by amblyopia (children aged < 7 years), in addition to the usual complications (synechiae, macular edema) seen in adult patients. Moreover, the presentation of uveitis in children is often "silent" with few warning signs and few functional complaints from young children, which frequently leads to a substantial diagnostic delay. The diagnostic approach is guided by the presentation of the uveitis, which can be characterized by its location, and corresponds to the initial and main site of intraocular inflammation; its presentation, whether acute or chronic, granulomatous or not; and the response to treatment. Pediatricians have an important role to play and must be aware of the various presentations and etiologies of uveitis in children. Juvenile idiopathic arthritis is the most common etiology of pediatric non-infectious uveitis, but other causes must be recognized. Promptly initiated treatment before complications arise requires early diagnosis, recognition, and treatment. Any dependence on prolonged local corticosteroid therapy justifies discussing the introduction of a corticosteroid-sparing treatment considering the risk to develop corticoid-induced glaucoma and cataracts. Systemic corticosteroid therapy can be required for urgent control of inflammation in the case of severe uveitis. Long-lasting immunosuppressive treatment and biotherapies are most often prescribed at the same time to reinforce treatment efficacy and to prevent relapse and corticosteroid dependency. We review the different causes of uveitis, excluding infection, and the diagnostic and therapeutic management aimed at limiting the risk of irreversible sequelae.