Chronic Noninfectious Uveitis Research Articles

Therapeutic drug monitoring guides the management of patients with chronic non-infectious uveitis treated with adalimumab: a retrospective study

AimTo assess the relevance of therapeutic drug monitoring (TDM) of adalimumab (ADA) treatment for the control of intraocular inflammation and treatment adjustment in chronic non-infectious uveitis (CNIU).MethodsRetrospective study of CNIU...

Non-infectious Chronic Uveitis in Childhood: Assessment and Treatment in the Biological Era

Non-infectious Chronic Uveitis in Childhood: Assessment and Treatment in the Biological Era

Endothelin-1 Serum Concentration in Pediatric Chronic Idiopathic Uveitis.

PurposeThe aim of our study was to determine endothelin-1 (ET-1) concentration in chronic idiopathic uveitis in children and adolescents depending on anatomical location and grade of inflammation.MethodsThe cross-sectional study was conducted among 17 patients with chronic idiopathic uveitis and 22 healthy controls. Concentration of ET-1 in serum was determined using a commercially available ELISA kit. The concentration of C reactive protein (CRP) in serum was determined by immunoturbidimetric method using CRP4 reagent kit (Roche Diagnostics GmbH, Mannheim, Germany).ResultsStatistically significant difference between ET-1 concentration in patients with chronic idiopathic uveitis and controls was found 1.33 (1.22; 1.48) vs 1.93 (1.1; 3.11), p = 0.008). No correlations were found between ET-1 concentration and age, either in chronic idiopathic uveitis patients or controls. Nine out of 17 patients presented with anterior uveitis, 5 with posterior and 3 with panuveitis. There were no differences in ET-1 concentration between anterior, posterior and panuveitis (p = 0.634), and in terms of grade of inflammation.ConclusionET-1 expression is disturbed in pediatric chronic idiopathic uveitis irrespective of the anatomical location and grade of inflammation. Lower expression of ET-1 plays a crucial role in disturbed vascular tone control and can result in permanent visual impairment in chronic non-infectious uveitis.

A Systematic Switch From Originator Infliximab to Biosimilar Infliximab in Patients With Non-Infectious Uveitis

To investigate the efficacy of biosimilar infliximab compared to that of the originator infliximab for the treatment of chronic non-infectious uveitis. Before-and-after study. All patients in the Central Norway Health Region between 2007 and 2018 were included. They were switched from originator to biosimilar infliximab therapy from 2014 to 2017. The primary outcome was quiescence of uveitis before and after the switch. All patients were seen every 1-3months. Visits were binned into 3-month long periods for each patient takingboth medications. Poisson regression analysis was used to estimate the incidence rate ratio (IRR) of quiescence between the 2 treatments. Twenty-nine patients were treated with infliximab. Twenty-three of those patients were switched from originator to biosimilar infliximab. The majority were white (87%), female (92%), and had chronic anterior uveitis (65%). For patients taking the originator and biosimilar drugs, the median treatment duration was38months (range: 8-131months) and 15months (range: 5-55months), respectively. Concomitant immunosuppressive medications and topical and oral steroids were used similarly during treatment with both originator and biosimilar infliximab. The IRR for quiescence was 0.91 (95% confidence intervals [CI]: 0.7-1.1; P= 0.38), which indicated no statistically significant differences in achieving quiescence after the switch. Also, there were no differences in the incidence rate of flare events with the switch (IRR: 1.04; 95% CI: 0.36-2.98; P= 0.95). IRR adjusted for intraocular surgery was 0.90 (95% CI: 0.7-1.1; P= 0.37). No evidence of differences in effectiveness were found in comparing biosimilar to originator infliximab in patients with chronic non-infectious uveitis.

Biologic Therapies in Sarcoidosis and Uveitis: A Review.

Sarcoidosis and uveitis are chronic inflammatory conditions with potentially debilitating effects on quality of life. Steroids form the mainstay standard therapy in both conditions. Biologic agents are considered to be appropriate alternatives for treatment in steroid-refractory sarcoidosis and uveitis due to the role of tumor necrosis factor (TNF) in mediating the inflammatory cascade seen in both conditions. We performed a thorough literature search using PubMed to compare the extent of use, efficacy, and safety profile of individual anti-TNF agents in the management of these conditions. Our review consists of two systematic reviews with meta-analysis, thirteen observational studies, and fifteen case series/reports. Infliximab had the widest range of organ-system usage in extra-pulmonary sarcoidosis but is equivalent to adalimumab in terms of efficacy. In uveitis, adalimumab was found to be the most efficacious agent for maintaining disease remission in adults and children with chronic non-infectious uveitis. Etanercept was neither used widely, nor was it efficacious in the management of either condition. In terms of safety profile, biologic agents were found to be well tolerated and have a similar safety profile. More randomized clinical trials are needed to inform evidence-based use of biologic agents in these conditions.

Non-Infectious Chronic Uveitis in Childhood: Assessment and Treatment in the Biological Era

Report of currently available treatment strategies for childhood chronic uveitis in the biologic era. The management of non-infectious chronic uveitis in children is based on immunomodulatory treatment. In case of failure to conventional disease-modifying anti-rheumatic drugs (cDMARDs) and/or frequent flares, tumor necrosis factor alfa (TNF-α) blocking agents represent the first biologic choice. Adalimumab is the TNF-α inhibitor more frequently adopted. Two multicenter, double-blind, randomized, placebo-controlled trials stated its efficacy and safety in this clinical setting. For refractory diseases, not responsive to TNF-α inhibitors, emerging biologic therapies have been reported. Most of the current literature refers to expert opinion and remains non-standardized. However, retrospective studies and short-case series report tocilizumab, abatacept, and rituximab as promising biologic alternatives in patients with refractory, sight-threatening uveitis even in children. A window of opportunity is currently emerging for JAK inhibitors. The role of anti-TNF-α inhibitor in chronic uveitis therapy met unanimous level of agreement. Rescue therapy approach still remains controversial. Randomized controlled trials and large series with long-term follow-up are mandatory to assess efficacy, safety, and cost-effectiveness in this challenging disease.

Withdrawn: Reduced Risk of Recurrence of Noninfectious Posterior Segment Uveitis After 0.18-mg Fluocinolone Acetonide Insert: Randomized Trial

Abstract Purpose To evaluate the safety and efficacy of 0.18 mg fluocinolone acetonide intravitreal (FAi) insert in chronic non-infectious uveitis affecting the posterior segment of the eye. Design Prospective, multicenter, randomized, doubled-masked, sham-controlled, 3-year, phase 3 clinical trial. Methods Eligible patients were randomized in a 2:1 ratio to receive either FAi (0.18 mg) insert (N=87) or sham injection (N=42). Primary efficacy endpoint was the recurrence of uveitis within 6 months. Secondary endpoints were recurrence within 12 months, resolution of macular edema, change in best corrected visual acuity, intraocular pressure (IOP) and adverse events. Results Uveitis recurrence rates were significantly lower in FAi group compared to sham at 6 (18.4 vs 78.6%; p Conclusion FAi demonstrated significant benefit in extending anti-inflammatory effect and reducing the likelihood of uveitis flares through 12 months. A higher proportion of FAi eyes had elevated IOP, but IOP-lowering medication and surgeries were used in similar proportions in both groups. Additional data from this three-year study will provide further insight into the safety, efficacy, and duration of effect of this treatment.

A New Approach for Diabetic Macular Edema Treatment: review of clinical practice results with 0.19 mg fluocinolone acetonide intravitreal implant including vitrectomized eyes.

Fluocinolone acetonide is a synthetic fluorinated glucocorticoid. It has selective and potent agonist properties by binding to the cytosolic glucocorticoid receptor with high affinity; it is devoid of mineralocorticoid activity. Two extended-release (i.e. lasting up to 3 years) drug delivery systems containing fluocinolone acetonide (FAc) have been approved by the FDA for intravitreal use: Retisert ® (Bausch&Lomb, New Jersey, USA) and Iluvien ® (Alimera Sciences, Atlanta, USA). The former contains 0.59 mg of FAc, which is approved for the treatment of chronic noninfectious posterior segment uveitis. The latter contains a dose of 0.19 mg of FAc and is approved for the treatment of diabetic macular edema and here we review the results published in the clinical literature relating to its use in the treatment of diabetic macular edema (DME). The 0.19 mg FAc implant (Iluvien®) is a new approved treatment approach for DME. It is a non-biodegradable implant that continuously releases a microdose of FAc into the vitreous cavity for up to three years. It is effective in chronic DME with the added value of decreasing the treatment burden of multiple intravitreal injections. Recently, clinical practice studies are reporting its efficacy and safety profile (intra-ocular pressure rise and cataract), as well as its use in clinical setting not included in clinical trial such as vitrectomized eyes. The FAc implant has demonstrated in clinical practice results that mirror the results of the clinical trials efficacy wise. Regarding its safety profile, cataract is a common complication, however, intra-ocular pressure rises may be lower than the ones reported in trials. The implant has shown effectiveness in vitrectomized eyes. An increasing evidence of real-world studies have supported utility of the implant in DME patients. It's extended-release format for up to 3 years benefits to the patient and carer as it means fewer injections and visits to the clinic.

A 48 Week Study to Evaluate the Efficacy and Safety of Two (2) EYS606 Treatment Regimens in Subjects With Active Chronic Non-infectious Uveitis (CNIU)

A 48 Week Study to Evaluate the Efficacy and Safety of Two (2) EYS606 Treatment Regimens in Subjects With Active Chronic Non-infectious Uveitis (CNIU)

Preliminary evaluation of YUTIQ™ (fluocinolone acetonide intravitreal implant 0.18mg) in posterior uveitis.

Uveitis is a major cause of ocular morbidity, potentially leading to significant visual impairment. The recent adoption of alternative drug delivery options has led to the development of new sustained-delivery corticosteroid systems, able to manage successfully chronic noninfectious posterior uveitis. The treatment goal is to target the site of inflammation with low dose of corticosteroids, delivered over an extended period of time, to minimize the cumulative damage resulting from repeated recurrences, reducing both injections frequency and ocular side effects. This article will review the pharmacology and preliminary clinical data of the 0.18mg fluocinolone acetonide intravitreal implant (YUTIQ™), to show its efficacy and safety in the treatment of noninfectious posterior uveitis.

Indicators of Post-Operative Intraocular Pressure Elevation after Naïve Fluocinolone Acetonide Surgical Implantation

ABSTRACT Purpose To determine factors conferring an increased risk of developing ocular hypertension secondary to the fluocinolone acetonide (FA) sustained-release surgical implant (Retisert). Design Retrospective, observational case series. Methods Patients with a history of chronic noninfectious posterior uveitis undergoing naïve surgical FA implantation from 2007 to 2018 at the University of Colorado were studied. Patient demographics and multiple clinical measures were noted one year before and after FA implantation. Results Twenty-nine eyes of 21 patients were studied. The median age experiencing an IOP rise vs median age experiencing no IOP rise post-FA implantation was 27.0 and 54.0 years old, respectively (p = .01). A pre-FA implant risk factor of needing future glaucoma surgery after FA implantation is prior to maximum IOP (p = .02). Conclusions A risk factor of elevated post-FA implantation IOP includes younger age. A potential risk factor for glaucoma surgery after FA implantation was higher maximum IOP before FA implantation.

Chronic and recurrent non-infectious paediatric-onset uveitis: a French cohort

ObjectiveTo evaluate the demographics, aetiologies, complications, treatments and visual prognoses of chronic and recurrent non-infectious paediatric-onset uveitis in France.MethodsDescriptive, retrospective and bicentric study in patients whose disease started before 17...

Chirurgie de la cataracte uvéitique non infectieuse de l’enfant : bilan des pratiques actuelles en France

To evaluate the medical-surgical management of cataract surgery in children with chronic uveitis in various French pediatric ophthalmology centers. Two-part study: first, a descriptive observational segment on the evaluation of French practices. A questionnaire was sent to the various pediatric ophthalmologists in France. A second retrospective chart review, including children with non-infectious chronic uveitis who had cataract surgery in the pediatric ophthalmology department of Bordeaux University Hospital from 2008 to 2017. Twenty-one ophthalmologists responded to the questionnaire. Only 23.8% systematically initiated immunosuppressive drugs (aside from corticosteroids) before surgery. A total of 88.2% prescribed oral corticosteroid treatment preoperatively. Eleven surgeons administered intravenous corticosteroid boluses during the surgery, and primary lens implantation is the most common method used in 95.2%. A total of 76.2% initiated oral steroid therapy after surgery. Postoperatively, all surgeons started local therapy with high-dose corticosteroids. At one year, 100% achieved improvement of visual acuity greater than or equal to 2 lines. On our service, 10 eyes (7 children) underwent cataract surgery. Seven were treated with systemic immunosuppressive drugs (aside from corticosteroids) and 80% of cases received oral corticosteroid therapy a few days before surgery. An intravenous corticosteroid bolus was administered preoperatively in 8 cases, and primary lens implantation was performed in 100% of cases. Postoperatively, 5 children received oral corticosteroid treatment. All were treated with local high dose steroids. At one year, the mean best-corrected visual acuity was 0.18 LogMar (0-0.7, SD: 0.25). When performed with an aggressive anti-inflammatory protocol, cataract surgery leads to a good visual outcome in selected children with chronic uveitis.

Treatment of chronic non-infectious uveitis and scleritis.

Ocular inflammations such as uveitis and scleritis can lead to significant visual impairment if not treated properly. To limit potentially sight-threatening complications, good control of the inflammation in the acute phase is necessary. Corticosteroids have been the mainstay of ocular therapies for many years, but high doses of corticosteroids, which are required to maintain quiescence in severe uveitis, can be associated with many systemic and ocular complications. In order to limit steroid side-effects, classic immunosuppressant and immunobiologic agents have been widely used as steroid-sparing agents. In this review, we summarise the immunosuppressive drug therapy utilised in the treatment of ocular inflammatory diseases.

Visual and Clinical Outcome of Macular Edema Complicating Pediatric Noninfectious Uveitis

To investigate the clinical course and visual outcome of macular edema (ME) in pediatric patients with chronic noninfectious uveitis. Retrospective case series. The databases of the uveitis clinics of 4 tertiary medical centers in Israel and the UK were searched for all children treated for uveitic ME in the years 2005-2015. Data were collected from the medical records as follows: demographics, diagnosis, visual acuity, clinical and imaging findings, and treatment given specifically for ME. Findings at baseline and at 3, 6, 12, and 24months were evaluated. The cohort included 25 children (33 eyes) of mean age 8.5 ± 3.4 years. The most common diagnosis was intermediate uveitis, in 14 children (7 idiopathic, 7 pars planitis). Uveitis was active at ME diagnosis in 28 eyes (84.8%). Median duration of follow-up was 48months. Median time to resolution of ME was 6months, with complete resolution in 25 eyes (75.8%) by 24months. Baseline visual acuity was ≥20/40 in 8eyes (24.2%), increased to 57.6% at 3months (P < .0001), and remained stable thereafter. Treatment regimens included corticosteroids (systemically and/or locally), immunosuppression, and biologic therapies. No correlation was found between outcome and either structural characteristics of ME or specific treatment strategy. The prognosis of pediatric uveitic ME is favorable despite its chronic course. Larger randomized controlled trials are needed to define differences among treatment regimens.

Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Chronic Noninfectious Uveitis Affecting the Posterior Segment: Twelve-Month Results

To assess the safety and efficacy of an intravitreal fluocinolone acetonide (FA) insert to manage inflammation associated with chronic noninfectious posterior uveitis. Multicenter, randomized, prospective, doubled-masked, sham-controlled, 3-year phase 3 clinical trial. One hundred twenty-nine participants with recurrent noninfectious posterior uveitis were assigned randomly to FA insert (n= 87) or sham injection (n= 42). The more severely affected eye in participants with bilateral disease was designated as the study eye. The insert (FA, 0.18 mg) was injected into the vitreous cavity; sham injection mimicked the insert delivery procedure. Ophthalmic examinations, OCT, and ocular tolerability and discomfort assessments were conducted; study visits were on days 7 and 28 and months 2, 3, 6, 9, and 12. Uveitis recurrence was treated as needed. The 6-month recurrence rate was the primary outcome measure. The 6-month (28% and 91%) and 12-month (38% and 98%) uveitis recurrence rates were significantly lower (P < 0.001) with FA insert vs. sham, respectively. Fewer recurrences per study eye (mean, 0.7 vs. 2.5), lower incidence of 15-letter or more decrease in best-corrected visual acuity (14% vs. 31%), and reduced systemic (19% vs. 40%) and local (7% vs. 62%) uveitis adjunctive treatments were observed with FA insert vs. sham, respectively. The FA insert group showed higher rates of cataract. Intraocular pressure-lowering treatment use was similar between groups. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. Chronic noninfectious posterior uveitis was managed successfully in this study population; FA insert eyes experienced fewer uveitis recurrence episodes, required fewer adjunctive treatments, and demonstrated less visual acuity loss compared with sham eyes. The FA insert treatment group showed higher rates of cataract; delivery by injection was not associated with an increase in ocular adverse events or any other safety measures not typically associated with local steroid use, suggesting the procedure is appropriate for an officesetting.

Interferon-alpha2a and Systemic Corticosteroid in Monotherapy in Chronic Uveitis: Results of the Randomized Controlled BIRDFERON Study

Macular edema is the leading cause of vision loss in bilateral chronic noninfectious posterior uveitis, and is currently being treated using corticosteroids, immunosuppressive agents, and biotherapies. The aim of this trial was to assess and compare the efficacy and safety of corticosteroids and interferon-α (IFN-α) in adults with such conditions. Randomized controlled trial. Subjects: Adult patients with bilateral posterior autoimmune noninfectious and nontumoral uveitis complicated by macular edema in at least 1 eye. Patients received either subcutaneous IFN-α2a, systemic corticosteroids, or no treatment for 4months. The efficacy and safety were assessed for up to 4months. The main endpoint was the change of the central foveal thickness (CFT) obtained by optical coherence tomography. Forty-eight patients were included. In intention-to-treat analysis, the median CFT change showed no significant difference. However, the per-protocol analysis showed a significant difference between groups for both eyes (OD and OS), and for the worse and better eyes. Statistically significant difference was found between the control and corticosteroid groups for the OD (P= .0285), and between the control and IFN-α groups for the OD (P= .0424) and worse eye (P=.0354). Serious adverse events occurred in 2 patients in the IFN group, in 1 patient in the corticosteroid group, and in 2 patients in the control group and were completely resolved after switch. IFN-α and systemic corticosteroids, compared with no treatment, were associated with significant anatomic and visual improvement shown in the per-protocol study.

An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis.

There are no standardized treatment protocols for pediatric non-infectious uveitis. Topical corticosteroids are the typical first-line agent, although systemic corticosteroids are used in intermediate, posterior and panuveitic uveitis. Corticosteroids are not considered to be long-term therapy due to potential ocular and systemic side effects. In children with severe and/or refractory uveitis, timely management with higher dose disease-modifying antirheumatic drugs (DMARDs) and biologic agents is important. Increased doses earlier in the disease course may lead to improved disease control and better visual outcomes. In general, methotrexate is the usual first-line steroid-sparing agent and given as a subcutaneous weekly injection at >0.5 mg/kg/dose or 10-15 mg/m2 due to better bioavailability. Other DMARDs, for instance mycophenolate, azathioprine, and cyclosporine are less common treatments for pediatric uveitis. Anti-tumor necrosis factor-alpha agents, primarily infliximab and adalimumab are used as second line agents in children refractory to methotrexate, or as first-line treatment in those with severe complicated disease at presentation. Infliximab may be given at a minimum of 7.5 mg/kg/dose every 4 weeks after loading doses, up to 20 mg/kg/dose. Adalimumab may be given up to 20 or 40 mg weekly. In children who fail anti-tumor necrosis factor-alpha agents, develop anti-tumor necrosis factor-alpha antibodies, experience adverse effects, or have difficulty with tolerance, there is less data available regarding subsequent treatment. Promising results have been noted with tocilizumab infusions every 2-4 weeks, abatacept monthly infusions and rituximab.

How do fluocinolone implants compare with standard-of-care therapy in people with chronic non-infectious uveitis?

How do fluocinolone implants compare with standard-of-care therapy in people with chronic non-infectious uveitis?

Combined Ahmed Glaucoma Valve Placement, Intravitreal Fluocinolone Acetonide Implantation and Cataract Extraction for Chronic Uveitis.

To report the outcomes of combined Ahmed glaucoma valve (AGV) placement, intravitreal fluocinolone acetonide implant, and cataract extraction procedure in the treatment of chronic noninfectious uveitis. Retrospective case series of patients with chronic noninfectious uveitis who underwent AGV placement, intravitreal fluocinolone acetonide implantation, and cataract extraction in a single surgical session performed at 1 institution from January 2009 to November 2014. Outcome measures included intraocular pressure (IOP) and glaucoma medication use. Secondary outcome measures included visual acuity, systemic anti-inflammatory medications, number of uveitis flares, and complications. Fifteen eyes of 10 patients were studied, with a mean age of 40.3±15.7 and mean follow-up duration of 26 months (range, 13 to 39 mo). Before surgery, the IOP was 18.5±7.3 mm Hg and patients were using 1.5±1.5 topical glaucoma medications. At the 12-month follow-up, IOP was 12.8±3.2 mm Hg (P=0.01) and patients were using 0.5±0.8 (P=0.03) topical glaucoma medications. At 36 months of follow-up, late, nonsustained hypotony had occurred in 3 eyes (20%), and 1 eye (6%) had received a second AGV for IOP control. Before treatment, patients had 2.7±1.5 uveitis flares in the year before surgery while on an average of 2.1±0.6 systemic anti-inflammatory medications, which decreased to an average of 0.1±0.3 (P<0.01) flares the year after surgery while on an average of 0.4±1.1 (P<0.01) systemic medications. Combined AGV, intravitreal fluocinolone acetonide implant, and cataract extraction is effective in controlling IOP and reducing the number of glaucoma medications at 12 months after treatment in patients with chronic uveitis.