Noninfectious Intermediate Uveitis Research Articles

Intravitreal steroid implants in the management of noninfectious intermediate and posterior uveitis.

The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis.

Filgotinib in Active Noninfectious Uveitis

Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options. To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis. The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day). Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks. The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo. Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial. Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor. ClinicalTrials.gov Identifier: NCT03207815.

Effectiveness of Triamcinolone Acetonide Injection for the Treatment of Non-infectious Intermediate and Posterior Uveitis

Effectiveness of Triamcinolone Acetonide Injection for the Treatment of Non-infectious Intermediate and Posterior Uveitis

OCT Macular Volume as a Predictor of Vascular Leakage in Uveitis.

IntroductionThis study aimed to evaluate the optical coherence tomography (OCT) macular volume as a marker for active vascular leakage in patients with intermediate and pan uveitis.MethodsIn this single-center prospective longitudinal study, patients were included under three criteria: diagnosed with noninfectious intermediate or pan uveitis; presented vascular leakage at their initial visit; and were imaged with concurrent wide-field fluorescein angiography (FA) and OCT. A scoring system was employed to measure vascular leakage. OCT volume scans were performed on the patients to produce the corresponding thickness map. The central subfield thickness (CST) and macular volume (MV) were calculated. CST is defined as the average thickness within the 1-mm fovea circle, while MV includes the 3-mm and 6-mm circles on the thickness map. Mixed-effects models were applied to analyze the correlation between each patient’s OCT and FA imaging results.ResultsA total of 72 patients (115 eyes) were included. The median follow-up time was 11 months (interquartile range 1.8–16.1 months). A total of 679 observations across all time points were analyzed. Both CST and MV were found to be positively associated with the leakage scores (p < 0.001). In the mixed-effects models, MV in the 6-mm circle presented the strongest correlation with leakage scores, which explained 57% of the variation in leakage (p < 0.001). MV in the 3-mm circle and CST explained 45.8% and 39.5%, respectively.ConclusionCST and MV in both the 6-mm and the 3-mm circles demonstrated significant correlations with angiographic inflammatory activity. Among those imaging parameters, MV in the 6-mm circle has the highest correlation. The study results suggest that this parameter can be considered a quantitative and non-invasive alternative to FA for monitoring vasculitic inflammation in uveitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00558-z.

Зв’язок температури поверхні ока з клінічною картиною у кроликів з модельованим неінфекційним переднім та середнім увеїтом

Зв’язок температури поверхні ока з клінічною картиною у кроликів з модельованим неінфекційним переднім та середнім увеїтом

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

To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Open-label, multicenter, phase 3 extension study (VISUAL III). 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). 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. 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. 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. 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.

Effectiveness of the Dexamethasone Implant in Lieu of Oral Corticosteroids in Intermediate and Posterior Uveitis Requiring Immunosuppression

ABSTRACT Purpose To evaluate dexamethasone intravitreal implant effectiveness in lieu of high-dose oral prednisone for short-term treatment of noninfectious intermediate and posterior uveitis in patients requiring immunosuppression. Methods This is a proof-of-concept, open-label, non-comparative clinical trial with 12-month follow-up. The primary outcome was uveitis control without additional prednisone at 6 and 12 months. Secondary outcomes were need for multiple implants or additional prednisone, and safety data. Results 20 patients (28 eyes) were enrolled- 16 eyes had control by 6 months; 20 by 12 months. No patients required high-dose prednisone. 6 patients enrolled on prednisone: 2 stopped; 4 tapered to 7.5 mg daily or less by 12 months. 16 eyes required multiple implants; five required cataract surgery; 12 required drops to control IOP; 2 underwent glaucoma surgery. Conclusions The dexamethasone implant was effective in lieu of high-dose prednisone although the majority required multiple implants. All patients decreased or discontinued prednisone during follow-up.

Efficacy and safety of immunomodulatory drugs in patients with non-infectious intermediate and posterior uveitis, panuveitis and macular edema: A systematic literature review

BackgroundNon-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management. ObjectivesTo evaluate the published evidence regarding the use of IMDs in adult patients with NINA uveitis including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular edema (ME). MethodsWe performed a systematic literature review. Search strategies were designed for Medline, Embase, and Cochrane Libraries for articles up to 2019 to evaluate the efficacy and safety of the IMDs. A quality assessment was performed using the Jadad Scale. ResultsNineteen randomized clinical trials were selected from the 1,103 articles retrieved. Characteristics of patients, treatment dosages and outcome measures were heterogeneous. The outcomes most frequently analyzed were visual acuity (VA), macular thickness and vitreous haze (VH). Different IMDs were used at their usual dosages. Methotrexate (MTX), micophenolate mofetil, cyclosporine A (CsA), tacrolimus, adalimumab and sarilumab were effective in NINA uveitis. Rituximab combined with MTX was effective in PU. Interferon-β was superior to MTX, albeit with more adverse events in IU with ME. CsA was similar to cyclophosphamide (Cyc) in Behçet uveitis. Tacrolimus was safer and similar to CsA. Cyc was effective in serpiginoid choroiditis, but when combined with azathioprine in PU, but did not improve VA. Secukinumab did not prevent NINA uveitis recurrences, although intravenously it showed a higher response rate than when used subcutaneously. Daclizumab did not show any benefits in Behçet NINA uveitis. ConclusionSeveral IMDs and their combinations can be useful in treating NINA uveitis. The available studies were heterogeneous regarding patient characteristics and outcomes.

Dexamethasone Intravitreal Implant (Ozurdex) in Paediatric Patients with Non-infectious Intermediate Uveitis and Related Cystoid Macular Oedema: Evaluation of Macular Morphology and Function with Six-month Follow-up; a Deeper Role of MfERG?

ABSTRACT Purpose To evaluate the efficacy of Ozurdex implant by analyzing macular morphology and function in pediatric uveitis and related cystoid macular edema (CMO). Methods Main outcomes were visual acuity, mfERG and photopic ERG response, and central macular thickness. Mean values recorded at each time-point were compared to baseline and correlations between functional and anatomical parameters were evaluated. Results Resolution of intraocular inflammation and CMO was achieved in all eyes 1 month after implant without procedure or drug-related complications. Mean visual acuity and mfERG amplitude improved showing a statistically significant difference to baseline values for the first 4 months. Mean central macular thickness showed a statistically significant reduction for all follow-up time. Photopic ERG did not vary significantly. Statistically significant correlation was found between trends of visual acuity, central macular thickness, and mfERG responses. Conclusion Correlation found between macular morphology and function confirms the efficacy of Ozurdex in pediatric uveitis.

Морфологічний стан здорового контралатерального ока кролика з модельованим переднім і середнім неінфекційним увеїтом

Морфологічний стан здорового контралатерального ока кролика з модельованим переднім і середнім неінфекційним увеїтом

Comparison of two techniques used in routine care for the treatment of inflammatory macular oedema, subconjunctival triamcinolone injection and intravitreal dexamethasone implant: medical and economic importance of this randomized controlled trial

BackgroundWhether they are injected peri- or intraocularly, corticosteroids are still essential tools in the therapeutic arsenal for treating inflammatory macular oedema. A few years ago, however, only triamcinolone acetonide was available to ophthalmologists. While this compound was initially developed for rheumatological or dermatological use, it has been increasingly deployed in ophthalmology, despite still being off-label. In 2011, the system for delivery of dexamethasone from a biodegradable, injectable implant into the vitreous cavity obtained approval for use in inflammatory macular oedema. While the efficacy and safety of triamcinolone in macular oedema, including inflammatory oedema, have already been studied, there are currently no publications on subconjunctival triamcinolone injections, which are simple, effective and well tolerated. To date, the dexamethasone 700 μg implant has been authorized for the treatment of noninfectious intermediate and posterior uveitis, but there have been no studies to evaluate the efficacy and safety of the different peri- and intraocular strategies, including the treatment of inflammatory macular oedema.MethodsThis protocol is therefore designed to compare the efficacy and safety of peri- and intraocular corticosteroid injections in the treatment of inflammatory macular oedema. In this ongoing study, 142 patients will be included, and the oedematous eye will be randomised to treatment with either subconjunctival triamcinolone injection or an intravitreal implant containing 700 μg dexamethasone. Follow-up is planned for 6 months with monthly visits. Each visit will include visual acuity measurement, a slit lamp examination, fundoscopy, intraocular pressure measurement, laser flare measurement (if available) and spectral domain optical coherence tomography.DiscussionThe results of this trial will have a real impact on public health if it is shown that a Kenacort retard® (i.e. triamcinolone) injection costing just €2.84 and performed in the physician’s office (with no additional overhead costs) is at least as effective as the dexamethasone 700 μg implant (Ozurdex®; costing approximately €960 with the injection performed in a dedicated room), with no increased side effects.Trial registrationClinicalTrials.gov, NCT02556424. Registered on 22 September 2015.

Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis

Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. ClinicalTrials.gov Identifier: NCT01829295.

Long-Term Outcomes of Treatment with Biological Agents in Eyes with Refractory, Active, Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

To examine a large cohort of patients treated with biologic agents for active noninfectious intermediate uveitis, posterior uveitis, or panuveitis (NIPPU) and to compare their efficacy and long-term effect. Retrospective, longitudinal study. Eighty-two patients (156 eyes) with active NIPPU after failure of treatment with corticosteroids and a second-line immunosuppression drug and treated with biologic agents who were treated at Moorfields Eye Hospital between 2001 and2016. Information was gathered from the clinical notes of all patients. Time to first disease flare, rate of treatment failure, best-corrected visual acuity, and risk factors for treatment failure. Patients were followed on average for 4.7±0.4 years (724 eye-years). All patients demonstrated active uveitis at baseline, and 34 patients (41.5%) demonstrated a coexisting active systemic disease. Control of ocular inflammation was achieved in 136 eyes (87.2%). The average oral prednisolone dose at baseline was 16.4±1.7 mg/day, and by 6 months reduced to 6.5±0.7 mg/day (P < 0.0001), remaining stable for up to 5 years follow-up. Best-corrected visual acuity at baseline was 0.5±0.1 logarithm of the minimum angle of resolution (logMAR), improved to 0.4±0.1 logMAR (P= 0.008) at 3 months, and remained stable during follow-up. After baseline, 42.3% of eyes experienced flares, and the average number of flares reduced from 1.8±0.1 flares/year to 0.6±0.1 flares/year (P < 0.0001). Median time to first flare was 5.4 years (95% confidence interval [CI], 2.2-5.4 years) with a 5-year survival rate of 58.7%. Treatment failed in 37 eyes (23.7%), with a 5-year survival rate of 68.0% and an estimated time to 75% survival of 2.9 years (95% CI, 2.1-4.4 years). The risk for treatment failure was lower when treatment used adalimumab (odds ratio, 0.4; 95% CI, 0.2-0.9; P= 0.03) but was greater when systemic disease also was active at baseline (odds ratio, 3.2; 95% CI, 1.5-7.1; P= 0.004). Overall, eyes treated with biologic agents after failure of treatment with corticosteroids and a second-line immunosuppression drug experienced satisfactory disease control (87.2%), reduced use of systemic immunosuppression, stable visual acuity, and a 23.7% risk of disease relapse. After multivariate adjustment, older age, treatment with adalimumab (versus infliximab), and inactive concomitant systemic disease were associated with a lower risk of treatment failure.

Genetic profiling of ocular inflammation: further evidence for a gender-specific association of C5 with uveitis

// Ming Ming Yang 1 , Xiao Yuan Wang 1 , Ying Wei Liu 2 , Li Dong 1 , De Ju Kong 1 , Hong Yan Sun 1 , Jiao Jie Fan 1 , Xu Hui Yu 1 , and Jun Wang 3 1 Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China 2 Department of Ophthalmology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, China 3 Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China Correspondence to: Jun Wang, email: wangjun4622@163.com Keywords: complement system; C5; ocular inflammation; uveitis; molecular genetics Received: September 19, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: February 13, 2018&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: February 17, 2018 ABSTRACT Objective: Uveitis is a major cause for visual impairment, our previous studies have made significant advancements in depicting the genetic profile of complement genes in uveitis. This study aimed to further investigate whether the terminal pathway gene, Complement component 5 ( C5 ), confers susceptibility to uveitis. Methods: Six tagging SNPs in C5 were genotyped in 592 unrelated study subjects: 141 anterior uveitis patients, 158 patients with non-infectious intermediate and posterior uveitis, and 293 controls. Multiple in-depth analyses have been conducted. Results: Among the six C5 SNPs, rs17611 was significantly associated with uveitis after adjusted for gender and SNP-gender interaction ( P = 0.017). After stratification by gender, rs17611 G allele and GG homozygosity confers an increased risk for uveitis in males ( P = 0.004, OR = 1.67 and P = 0.009, OR = 2.69, respectively) but not in females. Moreover, genotype-phenotype correlation analysis revealed an association between rs17611 and disease recurrence ( P = 0.045). The haplotype GC, defined by rs17611 and rs2269066, was also found to be associated with total uveitis and specific intermediate and posterior uveitis subtype ( P = 0.0055, OR = 1.51 and P = 0.0084, OR = 1.58, respectively). Other polymorphisms were not significantly associated with either investigated uveitis entities. Conclusions: This study shows a gender-specific association of C5 -rs17611 with uveitis, indicating that C5 may have an epistatic effect with gender in the pathogenesis of uveitis. This study help us depict the disease profile and estimate the contribution of each complement activation pathway in ocular immunologic process.

Safety and Efficacy of Intravitreal Dexamethasone Implant for Refractory Uveitic Macular Edema in Adults and Children

ABSTRACTPurpose: To assess safety and efficacy of intravitreal dexamethasone (DEX) implant in refractory uveitic macular edema (ME).Methods: We retrospectively analyzed medical records of patients with nonresponsive ME secondary to chronic, noninfectious intermediate or posterior uveitis, treated with intravitreal DEX implants.Results: A total of 42 eyes of 34 patients (aged 6–67 years) received 56 implants. Mean follow-up was 19.2 ± 2.2 months after DEX implant. The mean visual acuity (0.48 ± 0.06 logMAR to 0.34 ± 0.1 logMAR) and mean central retinal thickness (472.2 ± 35 to 274.7 ± 60.6 µm) improved considerably before and after DEX implant. A total of 11 eyes needed repeat implants after a prolonged time to recurrence (12.6–20.9 months). A total of 10 eyes needed no additional treatment. Oral steroids could be stopped in 40% patients. Intraocular pressure increased in seven and cataract progressed in six eyes.Conclusion: Intravitreal DEX implant is safe and effective adjunct therapy. It reduces dependence on systemic steroids, immunosuppressives and provides long-term effects.

Disease Remission in Children and Adolescents with Intermediate Uveitis: A Survival Analysis

Purpose: To report the incidence rate (IR) of remission in pediatric noninfectious intermediate uveitis (IU). Methods: Longitudinal retrospective cohort study, including 19 patients (32 eyes) between 1985 and 2014, followed-up until loss or January 2016. Remission was defined following the Standardization of Uveitis Nomenclature workshop criteria, prolonged remission as a remission spanning 12 months and until the end of follow-up, and relapse as recurrence of inflammatory activity in an eye in remission. Results: Median follow-up time was 6.3 years. IRs (95% confidence interval) for remission, relapse, and prolonged remission were 18.6 (13.1–26.5), 32.3 (20.6–50.7), and 6.7 (3.8–11.9) episodes per 100 eye-years, respectively. 48% of eyes relapsed in the first year following remission. 25 and 50% of eyes achieved prolonged remission after 5 and 10 years of follow-up, respectively. Conclusions: Inflammatory relapses may be frequent in noninfectious IU affecting children and adolescents, appearing early after remission. Also, prolonged remission seems infrequent, being achieved late during follow-up.

A systematic review and economic evaluation of adalimumab and dexamethasone for treating non-infectious intermediate uveitis, posterior uveitis or panuveitis in adults.

Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biological drugs. To evaluate the clinical effectiveness and cost-effectiveness of subcutaneous adalimumab (Humira®; AbbVie Ltd, Maidenhead, UK) and a dexamethasone intravitreal implant (Ozurdex®; Allergan Ltd, Marlow, UK) in adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis. Electronic databases and clinical trials registries including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and the World Health Organization's International Clinical Trials Registry Platform were searched to June 2016, with an update search carried out in October 2016. Review methods followed published guidelines. A Markov model was developed to assess the cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from a NHS and Personal Social Services (PSS) perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken. Of the 134 full-text articles screened, three studies (four articles) were included in the clinical effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with limited standard care also provided in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer in the adalimumab group than in the placebo group, with a hazard ratio of 0.50 [95% confidence interval (CI) 0.36 to 0.70; p < 0.001] in the VISUAL I trial and 0.57 (95% CI 0.39 to 0.84; p = 0.004) in the VISUAL II trial. The adalimumab group showed a significantly greater improvement than the placebo group in the 25-item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial (mean difference 4.20; p = 0.010) but not the VISUAL II trial (mean difference 2.12; p = 0.16). Some systemic adverse effects occurred more frequently with adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single 0.7-mg dexamethasone implant against a sham procedure, with limited standard care also provided in both arms. Dexamethasone provided significant benefits over the sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous haze score of zero (p < 0.014), the mean best corrected visual acuity improvement (p ≤ 0.002) and the percentage of patients with a ≥ 5-point improvement in VFQ-25 score (p < 0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than with the sham procedure. The incremental cost-effectiveness ratio (ICER) for one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis compared with limited current practice, as per the HURON trial, was estimated to be £19,509 per quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis compared with limited current practice, as per the VISUAL trials, was estimated to be £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggested that the rate of blindness has the biggest impact on the model results. The interventions may be more cost-effective in populations in which there is a greater risk of blindness. The clinical trials did not fully reflect clinical practice. Thirteen additional studies of clinically relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain because of the limited evidence base. Two RCTs of systemic adalimumab and one RCT of a unilateral, single dexamethasone implant showed significant benefits over placebo or a sham procedure. The ICERs for adalimumab were estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was estimated to fall below standard thresholds. However, there is substantial uncertainty around the model assumptions. In future work, primary research should compare dexamethasone and adalimumab with current treatments over the long term and in important subgroups and consider how short-term improvements relate to long-term effects on vision. This study is registered as PROSPERO CRD42016041799. The National Institute for Health Research Health Technology Assessment programme.

Enteric-coated mycophenolate sodium in the treatment of non-infectious intermediate uveitis: results of a prospective, controlled, randomised, open-label, early terminated multicentre trial

Background/aimsTo evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (EC-MPS) in combination with low-dose corticosteroids compared with a monotherapy with low-dose corticosteroids in subjects with non-infectious intermediate uveitis...

Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis

To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Randomized, controlled, multicenter clinical trial. STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4mg/kg TCZ and group 2 received IV infusions of 8mg/kg TCZ. Infusions were given every 4weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6. A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was-83.88 ± 136.1μm at month 6 (-131.5 ± 41.56μm in Group 1 and-38.92 ± 13.7μm in Group 2). Mean change in VA was+8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated. Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

The Efficacy of a Posterior sub-Tenon’s Capsule Triamcinolone Injection in Patients with Non-infectious Intermediate Uveitis and Posterior Uveitis

Abstract To investigate the efficacy of a posterior sub-Tenon’s capsule triamcinolone injection for treating eyes with non-infectious posterior and intermediate uveitis. A total of 31 eyes from 20 patients with non-infectious posterior uveitis and 18 eyes from 10 patients with non-infectious intermediate uveitis that inadequately responded to treatment with systemic corticosteroids and second-line immunosuppressive agents were enrolled in the study. All patients received a posterior sub-Tenon’s injection of 20 mg/ml triamcinolone. The parameters we examined included the following: best corrected visual acuity, central foveal thickness, fluorescein angiography score and intraocular pressure. The mean best corrected visual acuity was significantly improved from the control visit, 0.15±0.30 logMAR (Snellen equivalent 0.7), compared to the baseline measurements, 0.60±0.30 logMAR (Snellen equivalent 0.25; P&lt;0.05). The mean central foveal thickness (CFT) and the mean score for fluorescein angiography (FA) were significantly decreased from the baseline (CFT: 320±34 μm; FA mean score: 5.9±1.9) compared to the twelve-week control visit (CFT: 235±30 μm; FA mean score: 1.2±1.1; P&lt;0.001). Five eyes had intraocular pressure spikes that required a topical anti-glaucomatous treatment. A posterior sub-Tenon’s injection of triamcinolone can significantly improve visual acuity and decrease macular oedema in patients with non-infectious posterior and intermediate uveitis. Complications were minimal, and there were no eyes that required surgical treatment for elevated intraocular pressure. The results suggest that the posterior sub-Tenon’s injection of triamcinolone is an important form of therapy for non-infectious posterior and intermediate uveitis.