Adalimumab (ADA) in Pediatric Non-infectious Uveitis: An Observational Study.

OBJECTIVES:  Pediatric uveitis is a rare but sight-threatening condition. Prompt and adequate treatment is crucial to preserve vision and avoid long-term complications. In cases that are resistant to corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), anti-tumor necrosis (anti-TNF) biologic agents are usually added. In this study, we report our experience with adalimumab (ADA) anti-TNF use in this group of patients. METHODS:  This is a retrospective observational study conducted in a tertiary pediatric uveitis clinic, in Manchester Royal Eye Hospital. All patients were pediatric patients (aged 2-18 years old) under follow-up during the period of six months. The patients' data were analyzed according to the diagnosis, age of onset of uveitis, systemic medications used before and concomitantly with ADA, duration of uveitis before starting ADA, its effect, and time to notice the therapeutic effect in controlling inflammation. Finally, cases were reviewed for the development of anti-drug antibodies. RESULTS:  Forty-two patients were included in the study. Idiopathic uveitis was diagnosed in 47.6% of patients and 40.5% of patients were associated with juvenile idiopathic arthritis (JIA). Most (97.6%) of patients were using topical steroids before starting ADA and 95.2% continued using steroids after established ADA use, but systemic steroid use was reduced from 33.3% to 14.3%. The most common non-biologic DMARD used before ADA was methotrexate (MTX) (90.5%). One-third of the patients started ADA between 6 and 12 months after the diagnosis of uveitis, while this percentage dropped to 9.5% the year after diagnosis. Seventy-eight percent of patients acquired complete clinical control of inflammation on ADA use. Almost 78.6% of patients showed a full response in less than six months. In eight patients who were not controlled or were transiently controlled on ADA, three patients had positive anti-drug antibodies. In one patient, antidrug antibodies were identified after 12 years of ADA use, and in another, after 4 years. CONCLUSION:  Adalimumab is an effective, well-tolerated drug in children with uveitis refractory to non-biologic DMARD therapy. DMARDs were usually used alongside ADA in this cohort and few patients had confirmed ADA antibodies.

Update on the systemic management of noninfectious uveitis in children and adolescents.

Noninfectious uveitis (NIU) in children and adolescents is a rare but treatable cause of visual impairment in children. Treatments for pediatric NIU and their side effects, along with the risks of vision loss and the need for long-term disease monitoring, pose significant challenges for young patients and their families. Treatment includes local and systemic approaches and this review will focus on systemic therapies that encompass corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and biological disease-modifying antirheumatic drugs (bDMARD). Treatment is generally planned in a stepwise approach. Methotrexate is well-established as the preferential csDMARD in pediatric NIU. Adalimumab, an antitumor necrosis factor (TNF) agent, is the only bDMARD formally approved for pediatric NIU and has a good safety and efficacy profile. Biosimilars are gaining increasing visibility in the treatment of pediatric NIU. Other bDMARD with some evidence in literature for the treatment of pediatric NIU include infliximab, tocilizumab, abatacept, rituximab and, more recently, Janus kinase inhibitors. Important aspects of managing children on these systemic therapies include vaccination issues, risk of infection, and psychological distress. Also, strategies need to address regarding primary nonresponse/secondary loss of response to anti-TNF treatment, biological switching, and monitoring regimens for these drugs. Optimal management of pediatric uveitis involves a multidisciplinary team, including specialist pediatric uveitis and rheumatology nurses, pediatric rheumatologists, psychological support, orthoptic and optometry support, and play specialists.

Prognostic factors of cataract surgery in patients with uveitis.

PURPOSE: To evaluate the long-term visual outcomes of patients with uveitis undergoing cataract surgery and to identify possible factors influencing the visual prognosis and the development of postoperative complications. METHODS: Retrospective study of all patients with uveitis who underwent cataract surgery between January 2015 and February 2020 in our tertiary referral center. RESULTS: A total of 78 eyes from 78 patients were included in the study. The best-corrected visual acuity (BCVA) improved in 86% of patients, and a BCVA of 0.5 or better was achieved in 57 (73%) patients. A significant correlation was shown between the preoperative and postoperative BCVA (Spearman r = 0.521, p < 0.01). Final BCVA differed between diverse anatomical uveitis entities (p = 0.047), and anterior uveitis demonstrated the best outcomes. Chronic uveitis resulted in a worse final BCVA than acute recurrent uveitis (p = 0.001). The presence of CME any time before the surgery and intermediate uveitis were associated with worse visual prognosis, while systemic therapy for uveitis before surgery and iris manipulation during surgery were not related to visual outcomes. Postoperative development of cystoid macular edema (CME) was closely associated with preexisting CME (p < 0.001) and intermediate uveitis (p = 0.01). CONCLUSIONS: Visual results of cataract surgery in patients with uveitis were beneficial, but limited visual outcomes were more frequently observed in patients with chronic uveitis and intermediate uveitis with a history of CME. In consequence, prevention, or adequate treatment of CME, especially in patients with intermediate uveitis, might result in better visual results of their cataract surgery.

Intravitreal Fluocinolone 0.19mg Implant in the Management of Chronic Non-Infectious Uveitis: 12-Month Outcomes from a Single Tertiary Centre.

AIM: To present efficacy and safety of 0.19 mg fluocinolone acetonide insert (FAi) to treat chronic noninfectious uveitis (NIU) in a single referral center. METHODS: A retrospective observational clinical study of 11 eyes with NIU complicated by chronic cystoid macular edema (CMO). RESULTS: The main indication for treatment was chronic CMO in all 11 eyes. The mean central retinal thickness (CRT) at baseline was 435 µm ± 176, improving to 296 µm ± 67 at 12 months. Raised intraocular pressure (IOP) was the commonest adverse event. An IOP >21 mmHg was observed in three eyes, and >30 mmHg in one eye, managed with topical therapy. The mean best corrected visual acuity (BCVA) was stable at 12 months. There were no observed recurrences of uveitis. Two eyes received adjunctive treatment for worsening CRT. CONCLUSIONS: Our results suggest FAi is an effective maintenance treatment for NIU with favorable functional and anatomical outcomes.

Paracentral Acute Middle Maculopathy in A Young Girl Treated with Interferon-Beta for Nasopharyngeal Carcinoma.

PURPOSE: To describe a case of interferon-beta retinopathy associated with paracentral acute middle maculopathy. CASE REPORT: A 15-year-old girl with Epstein-Barr virus-positive advanced nasopharyngeal carcinoma WAS REFERRED with reduced visual acuity. Multimodal imaging findings, including optical coherence tomography angiography, at presentation and evolution following cessation of interferon therapy are presented. CONCLUSION: The presentation of paracentral acute middle maculopathy in this patient supports the presumed ischaemic pathogenesis in interferon retinopathy. The imaging findings provide evidence of deep capillary plexus involvement in interferon retinopathy with evolution to permanent structural damage within the inner nuclear layer.

Evaluating the Safety, Efficacy and Patient Acceptability of Intravitreal Fluocinolone Acetonide (0.2mcg/Day) Implant in the Treatment of Non-Infectious Uveitis Affecting the Posterior Segment.

Long-acting, slow-release injectable fluocinolone intravitreal implants have been approved for the treatment of non-infectious uveitis affecting the posterior segment. We summarise the development of intravitreal fluocinolone implants and discuss the technology including pharmacokinetics. We conducted a systematic review of evidence for the efficacy, safety and patient acceptability of fluocinolone 0.18 mg and 0.19 mg injectable implants. We summarise evidence from the pivotal phase 3 studies that lead to the approval of these implants and evaluate real-world including disease-specific evidence. Safety including injection-related events and long-term adverse events is presented.

Clinical Features of Acute Anterior Uveitis with Complicated Course in a Slovenian Patient Population.

PURPOSE: To report on patients who needed hospitalization due to acute anterior uveitis (AAU) and within this group to compare clinical features and outcomes of treatment of HLA-B27+ and HLA-B27- AAU in the population of Slovenian patients. METHODS: Retrospective study of hospitalized patients with AAU in the last 39 months at the Eye Hospital in Ljubljana. The data of AAU patients were retroactively studied and compared on the basis of HLA-B27 antigen presence: visual acuity upon admission, visual outcome, the presence of hypopyon, fibrinous reaction, posterior iris synechiae, and complications, such as elevated intraocular pressure, cataract, and cystoid macular edema (CME). We compared the investigations in the diagnostic process, the associated systemic disease, and the treatment administered. Statistical analyses included Student's t-test Fisher's exact test, and the Kolmogorov-Smirnov test. A p value of <0.05 was considered statistically significant. RESULTS: A total of 37 hospitalized patients with AAU were included. HLA-B27 antigen was detected in 73% of patients. In the HLA-B27+ group, women were more commonly affected, while the males were more affected in the HLA-B27- group. The occurrence of fibrin was significantly more common in HLA-B27+ patients, as well as hypopyon and posterior synechiae; only fibrin reached the statistical significance (p < 0.05). The incidence of cataracts, ocular hypertension, and glaucoma did not differ significantly between the two groups. HLA-B27+ AAU was more often associated with systemic diseases, and patients in this group were more frequently treated with systemic immunomodulatory drugs, however, no difference reached the statistical significance. We did not notice any major differences in the final visual acuity in the comparing groups. CONCLUSION: Almost ¾ of AAU patients that required hospitalization were HLA-B27+. In this group, disease was more severe, more frequently associated with ocular complications and systemic disease, but final visual acuity was the same in both groups. HLA-B27 typing has no prognostic value in our group of complicated AAU patients, but it eases the decision about necessary diagnostics and treatment.

MiRNA as biomarker for uveitis - A systematic review of the literature.

AIM: A systematic review of miRNA profiling studies in uveitis. METHODS: Literature search strategy - Pubmed central central database, using miRNA/microRNA and intraocular inflammation/uveitis as keywords. RESULTS: We found twenty publications regarding the experimental and clinical use of miRNA in uveitis, published between 2011 and 2018. CONCLUSION: The publications regarding the role of miRNA in uveitis are very scarce, but provide some valuable information about the potential new mechanisms in uveitis. Some of the identified miRNAs in different uveitis entities could serve as a biomarker of intraocular inflammation. Possible candidate miRNAs could be let-7e, miRNA-1, miR-9-3, miR-20a-5p, miR-23a, mir-29a-3p, miR-140-5p, miR-143, miR-146a and miR-146a-5p, miR-155, miR-182 and miR-182-5p, miR-196a2, miR-205, miR-223-3p, miR-301a. MiR-146a, miR-146a-5p, miR-155, miR-182, miR-223-3p, have been found to be possibly associated with uveitis disease in both, human and animal species.