Purpose: To evaluate clinical trials in the literature that focus on suprachoroidal drug delivery for the treatment of noninfectious uveitis and other posterior segment diseases. Methods: A synthesis of the literature was performed. Results: In 2021, suprachoroidal space triamcinolone acetonide, a corticosteroid delivery system used for the treatment of uveitic macular edema (ME), was approved by the US Food and Drug Administration. The drug-delivery system targets the suprachoroidal space using a microneedle-based device and has a favorable pharmacokinetic profile. Suprachoroidally administered investigational therapies have also been assessed in clinical trials for other posterior segment diseases, including diabetic ME, retinal vein occlusion, age-related macular degeneration, and choroidal melanoma. Conclusions: The safety and efficacy of suprachoroidal corticosteroid injections to treat uveitic ME have been shown in recent phase III clinical trials. Multiple programs are also investigating this modality of drug delivery for use in many other retinal and choroidal pathologies.

UNASSIGNED: Vitamin D deficiency has been associated with higher rates of autoimmune disease, including noninfectious uveitis. This PRISMA-compliant review and meta-analysis aimed to analyze the correlation between noninfectious uveitis and vitamin D levels.
UNASSIGNED: We searched PubMed, Embase, Cochrane, and Web of Science databases for studies, published in English, assessing vitamin D levels in patients diagnosed with noninfectious uveitis. The outcomes of interest were vitamin D deficiency, vitamin D mean level, vitamin D supplementation, and smoking rates. A subgroup analysis of inactive uveitis and active uveitis was performed. The heterogeneity was assessed with Cochrane Q-test and I2 statistics; p > 0.10 and I2 > 50% were considered significant for heterogeneity. Statistical analysis was conducted using Review Manager 5.3.
UNASSIGNED: 9 studies were included in the meta-analysis comprising a total of 10 711 patients, of whom 1,368 were diagnosed with noninfectious uveitis. Patients with noninfectious uveitis had worse results regarding vitamin D deficiency when compared with the control group (OR 0.58; CI 95% 0.44 to 0.77; p = 0.0002; I2 = 61%). Patients with inactive uveitis had better results towards vitamin D deficiency when compared with active uveitis (OR 5.00; CI 95% 2.84 to 8.81; p < 0.001; I2 = 0%).
UNASSIGNED: Our research supports the increasing evidence that associates vitamin D deficiency with noninfectious uveitis and its activity. Further investigation into the efficacy of vitamin D screening and supplementation in reducing the recurrence of uveitis is necessary.

暂无摘要。

UNASSIGNED: Janus kinase (JAK) inhibitors have recently been used to treat patients with biologic refractory noninfectious uveitis (NIU). This narrative review updates the current evidence relevant for their application in patients with refractory NIU.
UNASSIGNED: A literature search was performed for articles published until October 2023 in the PubMed, Scopus, and CENTRAL databases using the key terms \"noninfectious uveitis\" and \"Janus kinase inhibitor\" or \"JAK inhibitor\" without any exclusion criteria. Published articles were selected based on their clinical focus, relevance for ocular disease, time since publication and study design reflecting their scientific soundness with a critical appraisal of drug safety aspects.
UNASSIGNED: Janus kinases are transmembrane signaling proteins. Their inhibition has shown therapeutic potential experimentally and in patients with multiple immune-mediated diseases, including NIU. JAK inhibitors differ from biological agents in that they inhibit not one specific but multiple cytokines. These agents can be ingested orally and seem superior to adalimumab for most indications. While there is no doubt regarding their efficacy in treating immune-mediated inflammatory diseases, reports regarding their safety are increasing, and the findings are generally confusing and contradictory. Since substantiated information about their specific safety profiles in patients with inflammatory eye disease is lacking, their position in the therapeutic algorithm for uveitis has yet to be determined.
UNASSIGNED: In the absence of evidence from controlled clinical trials, JAK inhibitor therapy is still rendered experimental and currently considered only for sight-threatening uveitis. JAK inhibitors may be considered for specific NIU entities for which there is insufficient response or secondary loss of response to conventional or biologic disease-modifying drugs.

OBJECTIVE: The purpose was to study the anatomical and functional outcome following single low-dose suprachoroidal triamcinolone acetonide (LD-SCTA) (2 mg) injection in noninfectious posterior uveitis.
METHODS: Eleven patients with macular edema (ME) more than 280 μ secondary to noninfectious uveitis were included in the study. A single LD-SCTA (0.5 ml) injection was performed in the study eye with the help of a novel suprachoroidal microneedle (Pricon, Iscon Surgicals, Jodhpur, Rajasthan, India). The study parameters were noted at 4 and 12 weeks post LD-SCTA injection.
RESULTS: Ten of 11 patients had a significant decrease in central macular thickness (CMT). The mean CMT measurement at baseline was 513.6 ± 191.73 μm for the 10 patients who responded to the treatment, which reduced significantly to 265.1 ± 34.72 μm (P < 0.003) and 260.6 ± 34.72 μm (P < 0.002) at 4 and 12 weeks, respectively. The mean best-corrected visual acuity (BCVA) at baseline was 0.84 ± 0.41 logMAR unit which improved to 0.52 ± 0.33 (P < 0.001) and 0.25 ± 0.22 (P < 0.000) at weeks 4 and 12, respectively. The mean intraocular pressure at baseline recorded was 16.36 ± 2.97 mmHg, 19.45 ± 4.80 mmHg (P = 0.06) at 4 weeks, and 17.27 ± 2.53 mmHg (P = 0.35) at 12 weeks. One eye which did not respond to LD-SCTA was a case of recurrent Vogt-Koyanagi-Harada disease.
CONCLUSIONS: Single LD-SCTA injection is efficacious in reducing CMT in ME, improving BCVA, and controlling the inflammation in noninfectious posterior uveitis. LD-SCTA can be used as a first-line therapy in noninfectious uveitis over other routes of steroid administration with a favorable outcome and safety profile.

To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history.
Retrospective matched cohort and crossover case series study.
A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis.
In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively.
COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history.

UNASSIGNED: To evaluate the efficacy and safety of switching from adalimumab originator (Humira, AbbVie) to SB5, adalimumab biosimilar (Adalloce, Samsung Bioepis) in patients with noninfectious uveitis (NIU).
UNASSIGNED: Fifteen patients (29 eyes) with NIU who were switched from adalimumab originator to SB5 and followed up for 6 months or longer were retrospectively included. Data consisted of best-corrected visual acuity (BCVA, logMAR), intraocular pressure (IOP, mmHg), anterior chamber (AC) cell grade, anterior vitreous (AV) cell grade, vitreous haze grade, central macular thickness (CMT, μm), and macular volume (MV, mm3) at pre-switching, 2, 4, and 6 months post-switching.
UNASSIGNED: There were no significant differences in BCVA, AC and AV cell grades, and vitreous haze grades at 2, 4, and 6 months post- compared with pre-switching, and no significant differences in CMT and MV at 2 and 6 months post-switching. CMT and MV decreased from 260.55 ± 67.44 μm and 8.37 ± 1.14 mm3 at pre-switching to 244.14 ± 60.31 μm (p = 0.032) and 8.11 ± 1.20 mm3 (p = 0.027) at 4 months post-switching, respectively. There was no recurrence of uveitis, as defined by AC cell grade, vitreous haze, or BCVA. Four patients (27%) were switched back to adalimumab originator after a mean of 9 weeks, due to discomfort during the injection (three patients) and technical difficulty with the new injection device (one patient). No other adverse events occurred after switching to SB5.
UNASSIGNED: Switching from adalimumab originator to SB5 for NIU does not result in clinically significant differences in treatment efficacy and safety.

UNASSIGNED: To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies.
UNASSIGNED: Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database.
UNASSIGNED: Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW.
UNASSIGNED: Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models.
UNASSIGNED: Hazard ratios and IRs for COVID-19 infection, hospitalization, and death.
UNASSIGNED: This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P < 0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P < 0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P = 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P = 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P = 0.04).
UNASSIGNED: Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

OBJECTIVE: To assess noninfectious uveitis (NIU) risk after coronavirus disease 2019 (COVID-19) vaccination in patients without a history of uveitis.
METHODS: A retrospective matched cohort study and self-controlled case series (SCCS) analysis using a longitudinal data asset with claims data from the OptumLabs Data Warehouse from December 11, 2020, through November 30, 2021.
METHODS: The matched cohort analysis included patients continuously enrolled for 730 days before December 11, 2020, who received a COVID-19 vaccination during the study period. This COVID-19-vaccinated group was matched to a COVID-19-unvaccinated historical cohort enrolled in 2018 and 2019. The SCCS design included individuals from the vaccinated cohort who experienced an NIU event during the study period. Enrollees with a history of uveitis were excluded.
METHODS: Hazard ratios (HRs) were calculated using Cox proportional hazards models in the matched cohort design. Incidence rate ratios (IRRs) comparing NIU incidence in exposed risk periods after vaccination and unexposed control periods within individuals were calculated using conditional Poisson regression models in the SCCS design. Models were adjusted for age, recent receipt of non-COVID-19 vaccinations, corticosteroid or immunosuppressive use, and smoking history. Subgroup analyses were conducted by vaccination type and age group.
METHODS: Rates of NIU identified with International Classification of Diseases, Tenth Revision, codes.
RESULTS: The matched cohort analysis included 4 611 378 patients, with 2 305 689 per cohort. The adjusted HR comparing NIU incidence in the COVID-19-vaccinated and unvaccinated cohort was 0.91 (95% confidence interval [CI], 0.75-1.10; P = 0.33). The SCCS analysis included 686 patients. The IRR comparing NIU risk after vaccination with risk during control intervals was 1.05 (95% CI, 0.89-1.23; P = 0.57). An increased risk was found in the subgroup aged 5 to 44 years (IRR, 1.40; 95% CI, 1.04-1.87; P = 0.024).
CONCLUSIONS: The matched cohort and SCCS analyses did not detect increased NIU risk after COVID-19 vaccination overall in individuals without history of uveitis, providing reassurance about the vaccine\'s safety. The finding of increased risk in the youngest subgroup suggests heightened immune responses in younger individuals, warranting further investigation.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

UNASSIGNED: To assess the efficacy of simvastatin 80 mg/day versus placebo in patients with noninfectious nonanterior uveitis receiving prednisolone ≥ 10 mg/day.
UNASSIGNED: Randomized, double-masked, controlled trial.
UNASSIGNED: Adult patients with noninfectious nonanterior uveitis on oral prednisolone dose of ≥ 10 mg/day.
UNASSIGNED: Patients were randomly assigned at a 1:1 ratio to receive either simvastatin 80 mg/day or placebo. A total of 32 patients were enrolled (16 in each arm), all of whom completed the primary end point, and 21 reached the 2-year visit (secondary end points).
UNASSIGNED: The primary end point was mean reduction in the daily prednisolone dose at 12 months follow-up. Secondary end points were mean reduction in prednisolone dose at 24 months, percent of patients with a reduction in second-line immunomodulatory agents, time to disease relapse, and adverse events.
UNASSIGNED: Our results show that simvastatin 80 mg/day did not have a significant corticosteroid-sparing effect at 12 months (estimate: 3.62; 95% confidence interval [CI]: -8.15 to 15.38; P = 0.54). There was no significant difference between the groups with regard to prednisolone dose or change in dose at 12 and 24 months. There was no difference between the 2 groups in percent of patients with reduction in second-line agent by 24 months. Among patients who achieved disease quiescence, the median time to first relapse was longer for those receiving simvastatin (38 weeks, 95% CI: 14-54) than placebo (14 weeks, 95% CI: 12-52), although this was not statistically significant. There was no significant difference in adverse events or serious adverse events between the 2 groups.
UNASSIGNED: Simvastatin 80 mg/day did not have an effect on the dose reduction of corticosteroids or conventional immunomodulatory drugs at 1 and 2 years. The results suggest that it may extend the time to disease relapse among those who achieve disease quiescence.
UNASSIGNED: The author(s) have no proprietary or commercial interest in any materials discussed in this article.