Viera Kalinina Ayuso

Relapse Rate of Uveitis Post-Methotrexate Treatment in Juvenile Idiopathic Arthritis

PURPOSE To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). DESIGN Retrospective case series. METHODS Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. RESULTS Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a decrease of hazard for new relapse of 93%. CONCLUSIONS A high number of patients with inactive uveitis relapse quickly after the withdrawal of MTX. Our results suggest that a longer period of inactivity prior to withdrawal and a longer treatment period with MTX reduce the chance of relapse after withdrawal.

Male gender and poor visual outcome in uveitis associated with juvenile idiopathic arthritis.

PURPOSE To analyze visual outcome in uveitis associated with juvenile idiopathic arthritis (JIA) according to age of onset of uveitis, gender, and initial manifestation of JIA. DESIGN Retrospective nonrandomized interventional case series. METHODS Visual outcome of 117 affected eyes (65 patients) with JIA-associated uveitis was noted at onset of uveitis and after 1, 3, and 5 years. Visual outcome was analyzed according to gender, age of onset of JIA-associated uveitis (<7 years and >7 years), and initial manifestation of JIA (as uveitis or as arthritis). Linear and logistic regression with generalized estimating equation (GEE) was performed. RESULTS Median age of onset of uveitis was 4.2 years (range 1.5-16). Female-to-male ratio was 3:1. In 15 children (23%) uveitis was diagnosed before arthritis. Visual acuity of boys was significantly worse at 1 and 3 years of follow-up (both P <or= .03) but not at 5 years of follow-up (P = .45). Until 3 years after the diagnosis of uveitis, children with atypical initial manifestation of JIA (uveitis before arthritis) had significantly worse visual acuity compared with children in whom uveitis debuted after arthritis (all P <or= .05). No difference in vision between younger-onset (<7 years) and older-onset (>7 years) groups was noted. Blindness was independently associated with male gender (odds ratio [OR] = 6.61; 95% CI: 1.02-42.98; P = .048). CONCLUSIONS Male gender was an independent risk factor for poor visual prognosis in JIA-associated uveitis. Children in whom uveitis is being diagnosed before arthritis have significantly worse vision until 3 years after uveitis onset.

Male Gender as a Risk Factor for Complications in Uveitis Associated With Juvenile Idiopathic Arthritis

PURPOSE To analyze the role of baseline factors in long-term development of ocular complications in uveitis associated with juvenile idiopathic arthritis (JIA). DESIGN Retrospective nonrandomized interventional case series. METHODS Data of 117 affected eyes (65 patients) with JIA-associated uveitis with a minimum follow-up of 1 year were obtained. Development of complications was analyzed univariately and multivariately in relation to gender, age of onset of uveitis (<7 years or >7 years), and initial manifestation of JIA (as uveitis or as arthritis). RESULTS Female-to-male ratio was 3:1 and follow-up for uveitis ranged from 1.1 to 27.5 years (median 7.6 years). Time interval between arthritis and uveitis was shorter in boys (median 0.3 year) than in girls (median 1.0 year) (P < .01). At 5 years of follow-up boys suffered more frequently from cystoid macular edema (CME) (50% vs 4%; P < .01) and papillitis (31% vs 2%; P < .01), and needed more cataract surgery (59% vs 32%; P = .02). At 5 years of follow-up children with initial uveitis had more posterior synechiae, band keratopathy, and CME (all P <or= .02), but less glaucoma (P = .03). In multivariate analysis male gender appeared to be independently associated with cataract surgery (adjusted hazard ratio [HR] = 4.33; P < .01), CME (HR = 4.59; P = .01), and papillitis (HR = 4.10; P = .01). Development of posterior synechiae was independently associated with initial uveitis (HR = 3.21; P < .01). CONCLUSIONS Male gender and uveitis as initial manifestation of JIA were independently associated with a complicated course of JIA-associated uveitis. Age of onset of JIA-associated uveitis does not seem to have independent prognostic value for the course of this ocular disorder.

The clinical course of juvenile idiopathic arthritis-associated uveitis in childhood and puberty

Aim The long-term course of juvenile idiopathic arthritis (JIA)-associated uveitis is not known yet. This study investigates the course and activity of JIA-associated uveitis in childhood and puberty. Design Retrospective study of the clinical data of 62 JIA patients with uveitis. The main outcome measurements consisted of uveitis activity measured as mean cell grade in the anterior chamber, topical and systemic medication and ocular complications related to disease activity. All data were scored and evaluated per year of age. Results Uveitis activity took a biphasic course with a quiet phase around the age of 9 years and showed increased activity during early teenage years. The biphasic course was significantly related to age (p=0.048) but not to uveitis duration. More patients were treated with systemic immunosuppressive medication in estimated puberty years (63% in boys, 53% in girls) compared with prepuberty years (46% and 28%, respectively), although the difference was only significant in girls (p<0.001). The presence of cystoid macular oedema and papillitis was not significantly related to estimated puberty, but the development of an hypotonous eye was more frequently observed in boys in estimated puberty years (p=0.026). Conclusions JIA-associated uveitis appears to take a biphasic course with the second phase of activity during early teenage years and more treatment with systemic immunosuppressive medication occurred during estimated puberty compared with prepuberty years.

Intraocular biomarker identification in uveitis associated with juvenile idiopathic arthritis.

PURPOSE To investigate the presence of biomarkers in aqueous humor (AH) from patients with uveitis associated with juvenile idiopathic arthritis (JIA). METHODS AH (N = 73) AND SERUM (N = 105) SAMPLES FROM 116 CHILDREN WERE ANALYZED USING SURFACE ENHANCED LASER DESORPTION/IONIZATION TIME OF FLIGHT MASS SPECTROMETRY (SELDI-TOF MS). THE SAMPLES WERE DIVIDED INTO THE FOLLOWING GROUPS JIA, silent chronic anterior uveitis (AU), other uveitis entities, and noninflammatory controls. Statistical biomarker identification was performed using the SELDI-ToF Biomarker Analysis Cluster Wizard followed by multivariate statistical analysis. Biochemical identification of biomarkers was performed by polyacrylamide gel protein separation, followed by liquid chromatography tandem mass spectrometry. ELISA was performed in a number of AH samples representing all four study groups. RESULTS In the JIA group, one AH protein peak at mass/charge (m/z) 13,762 had qualitative and quantitative differences in expression compared with the other uveitis entities and the controls, but not to the group of silent chronic AU. Its quantitative expression in AH of patients with JIA and other silent chronic AU was positively associated with uveitis activity. The protein at m/z 13,762 in AH was identified as transthyretin (TTR). The TTR concentration in AH differed significantly between the study groups (P = 0.006) with considerably higher TTR concentrations in JIA and silent chronic AU samples positive for m/z 13,762 than those of the other uveitis and control groups. CONCLUSIONS TTR is a potential intraocular biomarker of JIA- associated uveitis. Its role in the pathogenesis of silent chronic AU with and without arthritis needs further investigation.

Intraocular and plasma HIV-1 RNA loads and HIV uveitis.

Objective:The objective of this study was to analyze human immunodeficiency virus (HIV) dynamics across the blood–retinal barrier and to determine whether the high levels of HIV in the eye are associated with any ocular disorders in HIV-infected patients. Design:This study included a prospective case series of 40 HIV-positive patients with uveitis. Intervention:Clinical and laboratory examinations included plasma and intraocular HIV-1 RNA loads as well as the clinical manifestations of uveitis. Results:Intraocular HIV-1 RNA was detected in 32% (13/40) of HIV-positive patients with uveitis. Intraocular HIV-1 RNA loads were associated with high HIV-1 RNA plasma loads (P < 0.001) and not being on HAART therapy (P = 0.005). In addition, detectable intraocular HIV-1 RNA levels were higher in patients with the absence of retinal lesions (P = 0.008). In three patients, the HIV load in the eye largely exceeded that of plasma. These three patients had all bilateral anterior uveitis and/or vitritis without retinal lesions and exhibited no evidence of other intraocular infectious agents causing uveitis than HIV itself. Conclusion:The eye can form a sanctuary where HIV might replicate and cause an inflammatory reaction.

Impact of ocular graft‐versus‐host disease on visual quality of life in patients after allogeneic stem cell transplantation: questionnaire study

Purpose:  To determine the influence of ocular complications on quality of life (QoL) 3 years after allogeneic stem cell transplantation (allo‐SCT).

The Effect of an Ahmed Glaucoma Valve Implant on Corneal Endothelial Cell Density in Children With Glaucoma Secondary to Uveitis

PURPOSE To assess the effect of Ahmed glaucoma valve implants on corneal endothelial cell density (ECD) in children with uveitic glaucoma. DESIGN Cross-sectional study. METHODS setting: Institutional. patientpopulation: Eighty eyes from 42 patients diagnosed with uveitis before the age of 16. Twenty-eight eyes had an Ahmed glaucoma valve implant because of secondary glaucoma. Fifty-two eyes without an implant served as controls. intervention orobservationprocedure(s): Corneal ECD was examined cross-sectionally using a noncontact specular microscope. Univariate and multivariate generalized estimating equations analyses with correction for paired eyes were performed. mainoutcomemeasure(s): Correlation of ECD with the presence of an Ahmed glaucoma valve implant and with the time following implantation. RESULTS ECD was significantly lower in the Ahmed glaucoma valve group than in controls (2359 and 3088 cells/mm(2), respectively; P < .001) following an average of 3.5 years after Ahmed glaucoma valve implantation. Presence of an Ahmed glaucoma valve implant, previous intraocular surgery, age, duration of uveitis, and history of corneal touch by the implant tube were all significantly associated with decreased ECD. Following a multivariate analysis, presence of an Ahmed glaucoma valve implant (B = -340; adjusted P < .011) and older age (B = -58; adjusted P = .005) remained independently associated with decreased ECD. Within the implant group, the age-adjusted time interval following Ahmed glaucoma valve implantation was highly correlated with decreased ECD (B = -558, P < .001). CONCLUSIONS Ahmed glaucoma valve implants in children with uveitic glaucoma are independently associated with decreased ECD, and this effect is associated with the time interval following Ahmed glaucoma valve implantation.

Ocular Complications in Children Within 1 Year After Hematopoietic Stem Cell Transplantation

IMPORTANCE It is essential to have insights into the risk of ocular involvement after hematopoietic stem cell transplantation (HSCT) in the pediatric population because young and severely ill children are unaware of their ocular problems. OBJECTIVE To study the development of ocular complications in children within 1 year after HSCT. DESIGN AND SETTING This prospective study includes all consecutive patients who had undergone an HSCT at the Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, the Netherlands, in 2009 and 2010. PARTICIPANTS Forty-nine consecutive patients underwent systematic ophthalmologic evaluations before HSCT, before leaving the HSCT unit after HSCT, and 3, 6, and 12 months after HSCT. Additional examinations were performed during systemic viral reactivations. MAIN OUTCOME MEASURE Development of ocular complications, including uveitis, hemorrhagic complications, optic disc edema, and dry eye syndrome. RESULTS Thirteen patients (27%) developed an ocular complication after HSCT. These complications included DES (n = 7 [14%]), (sub)retinal hemorrhage (n = 6 [12%]), optic disc edema (n = 3 [6%]), chorioretinal lesions (n = 2 [4%]), vitritis (n = 1 [2%]), and increased intraocular pressure (n = 1 [2%]). Median time to the development of dry eye syndrome was 5 months after HSCT, whereas all other ocular complications were detected within the first 3 months after HSCT. In most cases, the symptoms were mild and self-limiting. Children with malignant disease had a higher risk of the development of ocular complications compared with children with nonmalignant disease. CONCLUSIONS AND RELEVANCE Ocular complications in pediatric HSCT patients are common, although mostly mild. The risk of viral uveitis development during systemic viral reactivations is low; however, the potential risk of vision-threatening complications in this population cannot be ruled out.

Infiltration of Plasma Cells in the Iris of Children With ANA-Positive Anterior Uveitis

PURPOSE We investigated inflammatory cell infiltrates in iris biopsies in uveitis associated with juvenile idiopathic arthritis (JIA) in comparison with other pediatric uveitis entities and noninflammatory pediatric controls. METHODS Iridectomy specimens were obtained during elective trabeculectomy from 31 eyes of 25 patients: 12 eyes with JIA-associated uveitis, 13 eyes with other uveitis entities, and 6 eyes with open angle nonuveitic juvenile glaucoma. Histopathologic and immunohistochemical analyses were performed. A semiquantitative scoring system was used with a scale ranging from 0 to 4 depending on the number of stained cells. RESULTS An inflammatory infiltrate was present in 8/12 (67%) specimens with JIA-associated uveitis. The cellular infiltrate in JIA specimens was characterized by the presence of CD138+ plasma cells and CD68+ macrophages, while the presence of CD20+, CD4+, and CD8+ cells was variable. Presence of plasma cells in the inflammatory infiltrates in anterior uveitis correlated with antinuclear autoantibody (ANA) positivity regardless of the diagnosis of JIA. CD4+ and CD8+ T cells were not always detectable in the iris biopsies of all childhood uveitis patients, although a slight predominance of CD4+ cells was noted. CONCLUSIONS Children with ANA-positive anterior uveitis often show an infiltrate of plasma cells, regardless of the diagnosis of JIA. The iris of JIA-associated uveitis patients is additionally characterized by the presence of various numbers of macrophages.