Idiopathic Chronic Anterior Uveitis Research Articles

Clinical Course and Outcome in Pediatric Idiopathic Chronic Anterior Uveitis

To examine the clinical course and outcome in children with idiopathic chronic anterior uveitis (iCAU), and to compare the results with those of age-matched children with juvenile idiopathic arthritis-associated uveitis (JIA-U). Retrospective cohort study. Data regarding ocular complications, visual acuity, and systemic treatment were retrospectively collected for 2 patient groups that were matched regarding age and year of uveitis diagnosis. Outcome was evaluated using survival analysis. The iCAU and JIA-U groups included 48 patients with 83 affected eyes and 48 patients with 73 affected eyes, respectively. Multivariate analyses showed that iCAU was associated with a higher prevalence of posterior synechiae (adjusted hazard rate [aHR]=3.63; P < .001) and cataract surgery (aHR=2.90; P=.006). Baseline visual acuity was worse in the iCAU group compared to the JIA-U group (20/25 vs 20/20, respectively; P < .001), but improved in the iCAU group after 5 years (20/20 vs 20/20, respectively; P=.052). At the 5-year follow-up, the younger children with iCAU (≤8 years of age at diagnosis) had a higher prevalence of posterior synechiae (aHR=2.56; P=.007), secondary glaucoma (aHR=16.0; P=.020), and cataract surgery (aHR=4.79; P=.004) compared to older children with iCAU (≥9 years at diagnosis). Vision-threatening ocular complications are more common in children with iCAU compared to children with JIA-U, particularly in cases in which the onset of uveitis occurred at ≤8 years of age. However, the long-term vision of these children can be improved with adequate treatment.

Next-Generation HLA Sequence Analysis Uncovers Shared Risk Alleles Between Clinically Distinct Forms of Childhood Uveitis.

PurposeClassical alleles of the human leukocyte antigen (HLA) complex have been linked to specific entities of pediatric noninfectious uveitis, yet genetic predisposition encoded by the HLA super-locus across the patient population remains understudied.MethodsWe performed next-generation full-length sequencing of HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1 in 280 cases. Dense genotype data from 499 Dutch controls from Genome of the Netherlands were imputed using an HLA-specific reference panel (n = 5225 samples from European ancestry). Cases and controls were compared using logistic regression models adjusting for sex.ResultsIn total, 179 common and rare alleles were detected. Considering all cases and controls, HLA-DQB1*04:02 and HLA-DRB1*08:01 were identified as the principal HLA association, which was mainly driven by 92 cases with juvenile idiopathic arthritis-associated uveitis (JIA-U). The HLA-DQB1*04:02-HLA-DRB1*08:01 haplotype was also the primary association for the phenotypically similar idiopathic chronic anterior uveitis without arthritis (CAU). Also, HLA-DQB1*05:03 was an independent risk allele for CAU, but not in JIA-U. Analysis of 185 cases with other forms of uveitis revealed HLA-wide associations (P < 2.79 × 10−4) for HLA-DRB1*01:02, HLA-DRB1*04:03, and HLA-DQB1*05:03, which could be primarily attributed to cases with panuveitis. Finally, amino acid substitution modeling revealed that aspartic acid at position 57 that distinguishes the risk allele HLA-DQB1*05:03 (for CAU and panuveitis) from nonrisk alleles, significantly increased the binding capacity of naturally presented ligands to HLA-DQ.ConclusionsThese results uncovered novel shared HLA associations among clinically distinct phenotypes of pediatric uveitis and highlight genetic predisposition affecting the antigen presentation pathway.

Timing of infliximab and adalimumab initiation despite methotrexate in children with chronic non-infectious anterior uveitis

Methotrexate (MTX) is standard treatment in pediatric chronic anterior uveitis (CAU). Addition of tumor necrosis factor-α inhibitors (TNFi) is often needed. We describe the timing and risk factors for TNFi usein children with CAU on MTX. In this retrospective study, we reviewed 51 records, and 46 met inclusion criteria. Primary outcome was the addition of TNFi dueto active CAU per Standardization of Uveitis Nomenclature criteria. Time to TNFi and factors associated with their addition were assessed using survival analysis models. Of 46 children treated with MTX for uveitis (36 juvenile idiopathic arthritis-associated uveitis, 10 idiopathic CAU), 72% had ocular complications. MTX was started a median of 5.0 months, and TNFi 43 months from uveitis diagnosis. Kaplan-Meier estimates suggest that cumulatively, 12% (95% CI: 4-23%) start TNFi within 6 months of MTX, 21% (12-37%) within 1 year, and 39% (24-54%) within 2 years. On Cox Proportional Hazard regression analysis, children with idiopathic CAU required TNFi earlier in their uveitis course (at 3 months (Hazard Ratio 6.06; 95% confidence interval (1.25-29.41))). Females appeared less likely to require TNFi early. Children treated in 2012 and later were more likely to receive TNFi earlier than those treated before 2012. Little is known about optimal time to initiate treatment or factors associated with the need to add TNFi in children on MTX. Children with idiopathic CAU and males required TNFi earlier in their course. Factors associated with these potential risk factors for TNFi warrant further investigation.

Association of Cytomegalovirus with Idiopathic Chronic Anterior Uveitis with Ocular Hypertension in Korean Patients

Purpose: To investigate the association between cytomegalovirus and idiopathic chronic recurrent anterior uveitis with ocular hypertension.Methods: Medical records of 9 consecutive immunocompetent Korean patients with chronic recurrent anterior uveitis and ocular hypertension were retrospectively reviewed. Nested polymerase chain reaction was performed on aqueous humor samples for the herpes family, including cytomegalovirus, varicella zoster virus, herpes simplex virus, and Epstein-Barr virus.Results: In 7 (77.8%) of 9 patients, aqueous samples were culture-positive for cytomegalovirus (n = 6), Epstein-Barr virus (n = 2), and/or varicella zoster virus (n = 2). Two patients with cytomegalovirus had corneal endotheliitis, and 2 patients with varicella zoster virus had sectoral iris atrophy.Conclusion: Cytomegalovirus is the most common cause of idiopathic chronic unilateral anterior uveitis with ocular hypertension in immunocompetent Korean patients. The authors suggest that performing polymerase chain reaction on aqueous samples is useful in diagnosing cytomegalovirus in these patients.

Retrospective analysis of children with uveitis treated with infliximab

Tumor necrosis factor-alpha (TNF-alpha) antagonists have been successfully used in refractory cases of pediatric uveitis.(1-7) We report our experience with the monoclonal anti-TNF-alpha antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy.

Increased Vascular Endothelial Growth Factor Levels in Aqueous Humor and Serum of Patients with Quiescent Uveitis

Vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are angiogenic mediators that share a significant proinflammatory activity. Both substances have been suggested to play a key role in uveitis pathogenesis. The authors analyzed VEGF and IL-8 levels in the aqueous humor and serum of patients with different types of uveitis during a quiet phase of the disease. Thirteen patients with intermediate uveitis, uveitis associated with ankylosing spondylitis, Vogt-Koyanagi-Harada disease, Fuchs uveitis syndrome, idiopathic chronic anterior uveitis, or Behcet disease, as well as 10 normal matched subjects, were included in the study. VEGF and IL-8 concentrations were measured in aqueous humor and serum by enzyme-linked immunosorbent assay. VEGF levels were significantly higher in both the aqueous humor and serum of patients with uveitis as compared with controls. IL-8 concentrations in aqueous humor were significantly higher in patients with uveitis with extraocular manifestations than in those with eye-limited disease. These findings suggest that VEGF plays a role in uveitis pathogenesis even during inactive disease and that IL-8 levels are significantly influenced by the presence of uveitis-associated extraocular changes.

Cytokine gene polymorphisms involved in chronicity and complications of anterior uveitis

The aim of this study was to identify key cytokine polymorphisms associated with disease susceptibility, clinical phenotype, and outcome in patients with chronic anterior uveitis (CAU) as compared to those with recurrent self-limiting anterior uveitis (RAU). One hundred fifty seven British Caucasian patients with anterior uveitis were identified and divided into those where the inflammatory process lasted less than 3 months (RAU = 118) and those where the inflammation persisted longer than 3 months (CAU = 39). Patients with CAU were further sub-divided into idiopathic CAU, CAU associated with systemic disease, CAU with and without complications (posterior synechiae, posterior subcapsular lens opacity, raised intraocular pressure, cystoid macular oedema, and poor response to treatment). Sixty-six healthy controls were ethnically matched. TaqMan PCR amplification was used to genotype five single nucleotide polymorphisms in cytokine genes; IL-1RN+2018, IL-6−174, IL-10−1082, TNF−238, TNF−308 and these were correlated with clinical phenotype.

Uveitis in children: population-based study in Finland.

To investigate the incidence and prevalence rates of different types of uveitis in children, and to compare them with the rates in adults. For this population-based retrospective study the medical records of all residents of the district of Turku University Hospital with a diagnosis of uveitis seen at the Eye Clinic of Turku University Hospital during the years 1980-1982 and 1988 were reviewed. A total of 1122 uveitis cases were identified, and 55 (4.9%) of them were children under 16 years. The incidence per 100 000 population per year for all uveitis cases in children was 4.3 (95% confidence interval [CI], 2.2 to 6.4), and the prevalence was 27.9 (95% CI, 17.1 to 38.6), which was significantly lower compared with the rates in adults (p=0.001 for incidence and prevalence). The vast majority of children, 50 (90.9%), had anterior uveitis (AU), and the incidence and prevalence rates of AU were significantly lower than in adults (p=0.001 for incidence and prevalence). Three (5.5%) children had posterior uveitis (PU), but there was no significant difference in the incidence and only marginally significant difference in the prevalence rate of PU in children compared with the rates in adults (p=0.33 for incidence, and p=0.07 for prevalence). Only one case (1.8%) was found with intermediate and one with panuveitis, but no new cases. The commonest diagnostic groups in children were AU associated with juvenile rheumatoid arthritis, idiopathic acute anterior uveitis, and idiopathic chronic anterior uveitis. Toxoplasmic retinochoroiditis was found in all of the PU cases with the incidence 0.3, and the prevalence 1.1, which did not differ significantly from the rates in adults (p=1.0 for incidence, and p= 0.48 for prevalence). Uveitis is rarer in children than in adults. However, in contrast to studies from tertiary referral centers, the distribution of different forms of uveitis in children in this population-based study seems to resemble the distribution in adults.

Incidence and prevalence of different uveitis entities in Finland.

We studied the case records of 1122 patients with endogenous uveitis including 418 new cases treated at the University Eye Clinic in Turku during the years 1980-1982 and 1988. The mean annual incidence and prevalence rates (per 100,000 population) of idiopathic acute anterior uveitis were 17.1 and 48.5, respectively, sarcoid anterior uveitis 0.5 and 1.5, Posner-Schlossman syndrome 0.4 and 1.9, herpes zoster uveitis 0.4 and 0.7, idiopathic chronic anterior uveitis 0.3 and 7.3, herpes simplex keratouveitis 0.3 and 0.5, juvenile rheumatoid arthritis 0.2 and 2.4, Fuchs' heterochromic iridocyclitis 0.2 and 0.5, intermediate uveitis 0.3 and 1.4, and of toxoplasmic retinochoroiditis 0.3 and 2.4. The incidence and prevalence rates of acute anterior uveitis associated with ankylosing spondylitis were 2.0 and 10.3 per 100,000 population, respectively, and this disease association occurred more often in men than in women (p < 0.001). The mean annual incidence of idiopathic acute anterior uveitis was significantly lower in the age group 0-19 years than in the other age groups (p < 0.001).