Non-infectious Uveitis Patients Research Articles

Vision-related Quality of Life in Patients with Non-infectious Uveitis: A Cross-sectional Study

ABSTRACTPurpose: To analyze the influence of socio-demographic, comorbidity, and clinical-related variables in the vision-related quality of life (VR-QoL) of non-infectious uveitis patients.Methods: Cross-sectional study includes 156 consecutive non-infectious uveitis patients from a tertiary uveitis clinic from Madrid (Spain). The main outcome was the log-transformed composite score of the Visual Functioning Questionnaire 25. Bivariate and multivariate ordinary least-squares regression models were performed and results expressed using effect sizes with 95% confidence intervals (95% CI).Results: In the multivariate analysis, one unit increase in the logarithm of the minimum angle of resolution scale [i.e., worse best corrected visual acuity (BCVA)] was associated with a seven times worse VR-QoL (a 0.14-fold change [95% CI: 0.07–0.27]). Patients with ocular comorbidities had a 64% worse VR-QoL (a 0.61-fold change [95% CI: 0.49–0.77]).Conclusions: Lower BCVA and the presence of ocular comorbidities had a significant, independent, and deleterious effect in the VR-QoL of non-infectious uveitis patients.

Elevated CD1c+ Myeloid Dendritic Cell Proportions Associate With Clinical Activity and Predict Disease Reactivation in Noninfectious Uveitis.

PurposeTo test the association between elevated proportions of CD1c+ myeloid dendritic cells (mDCs) and disease activation/reactivation in noninfectious uveitis.MethodsNoninfectious uveitis patients (n = 89) and healthy controls (n = 111) were recruited. The proportion of CD1c+ mDCs in the total dendritic cell (DC) population of peripheral blood was measured by flow cytometry (CD1c+ mDCs gated on Lineage 1+HLADR+ DCs). Disease activity was assessed per Standardization of Uveitis Nomenclature criteria. Uveitis reactivation was ascribed to clinically quiescent patients who developed reactivation of intraocular inflammation within 6 months.ResultsThe proportions of CD1c+ mDCs were increased in noninfectious uveitis patients, especially in active disease, compared to healthy controls. This CD1c+ mDC elevation was not associated with underlying systemic diseases, anatomic locations of uveitis, medications, or demographic factors. Longitudinal data showed that the dynamics of CD1c+ mDC levels were correlated with disease activity. The average proportion of CD1c+ mDCs in active uveitis patients was 60% so we set this as the cutoff between high and low CD1c+ mDC levels. Although 74% of quiescent patients had low proportions of CD1c+ mDCs, 26% still had high proportions. Quiescent patients with high CD1c+ mDC proportions showed increased risk of disease reactivation, compared to quiescent patients with low CD1c+ mDC proportions.ConclusionsIncreased proportions of CD1c+ mDCs were associated with clinical activity, and quiescent patients with elevated CD1c+ mDCs were more likely to undergo reactivation. This suggests that CD1c+ mDC proportion may be a potential biomarker for assessing clinical activation and reactivation in noninfectious uveitis.

Association of the C2-CFB locus with non-infectious uveitis, specifically predisposed to Vogt-Koyanagi-Harada disease.

Complement component 2 (C2) and factor B (CFB) are regulators of complement system and involved in the alternative pathway, which have been identified to be associated with multiple immune-related diseases. This study aimed to investigate the association of these genes with non-infectious intermediate and posterior uveitis. A total of 260 Chinese non-infectious uveitis patients were recruited, including 97 patients with Vogt-Koyanagi-Harada disease (VKH), 70 patients with intermediate uveitis (IU) and 93 patients with Behçet's disease (BD). Two hundred and ninety-three normal control subjects were also recruited. Five SNPs across the C2/CFB region were selected and genotyped using TaqMan SNP Genotyping Assays. Association analysis was adjusted for gender and stratified by different subtypes. The CFB SNP rs1048709 was significantly associated with non-infectious uveitis [P corr = 0.01, OR 1.49 (allele model) and P corr = 0.04, OR 1.58 (dominant model), respectively], and similar association was also detected between rs1048709 and female uveitis patients (P corr = 0.01, OR 1.70 and P corr = 0.049, OR 184, respectively). Moreover, subgroup analyses showed that CFB-rs1048709 was specifically associated with VKH, where significantly higher frequencies of A allele and AA homozygosity were observed in VKH patients compared with controls (P corr = 0.025 and P corr = 0.035, respectively), whereas none of these five SNPs was associated with IU or BD. In addition, a haplotype block across CFB (GTG) was significantly predisposed to uveitis with protective effect (OR 0.66, P corr = 0.048). Our results revealed a significant association of CFB with non-infectious uveitis, particularly predisposed to VKH disease. Genetic differences for uveitis could be gender-specific.

Myeloid dendritic cells with elevated CD1c expression in non-infectious uveitis patients exhibited mature phenotype through the regulation of TNFa-p38 MAPK pathway (HUM1P.273)

Abstract Our longitudinal data has shown that the level of CD1c+ myeloid dendritic cells 1 (mDC1) from peripheral blood reflects disease activity in autoimmune non-infectious uveitis patients. However, the role of CD1c+ mDC1 is not clear in autoimmune uveitis patients. Here, we demonstrate that the mDC1 in patients with non-infectious uveitis (n=74) was increased compared to age and gender-matched healthy controls (n=96). The increased CD1c+ mDC1 exhibited high HLADR expression and less antigen uptake. CD1c+ mDC1 were further divided into two subpopulations based on the level of CD1c expression. CD1chi mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1clo mDC1 subpopulation. Importantly, the CD1chi mDC1 subpopulation was significantly increased in uveitis patients. By utilizing monocyte-derived dendritic cells (MoDCs) for in vitro studies, MoDCs with less antigen uptake and higher levels of CD1c induced more CD4+ T helper cell activation and proliferation. TNFa, increased in uveitis patient sera, reduced the antigen uptake in a dose-dependent manner and increased the phosphorylated p38 expression on MoDCs. A p38 inhibitor significantly inhibited the expression of CD1c during dendritic cell differentiation from monocytes. In conclusion, CD1c is a maturation marker of mDC1, increased in uveitis patients and correlated with disease activity. The high CD1c expression and low antigen uptake are mediated by the TNFa-activated p38 MAPK pathway.

Levels of blood CD1c+ mDC1 and CD1chi mDC1 subpopulation reflect disease activity in noninfectious uveitis.

Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1s), the subset of human blood mDCs, is not well understood in noninfectious uveitis. Fresh peripheral blood samples from human noninfectious uveitis patients (n = 32) and healthy controls (HCs) (n = 64) were stained with FITC-Lineage 1 (Lin1), PERCP-HLADR, and PE-CD1c antibodies. The levels of mDC1 were quantified by using flow cytometric analysis. Longitudinal data from patients (n = 16) were analyzed to correlate the levels of mDC1 with disease activity. Blood CD1c(+) mDC1 and its subpopulation, CD1c(hi) mDC1, were increased in uveitis patients compared with HCs. Longitudinal data demonstrated that both the CD1c(+) mDC1 and CD1c(hi) mDC1 subpopulation reflected a dynamic change in clinical uveitis activity: CD1c expression was increased in active uveitis but decreased when uveitis became inactive. Given these observations, an alteration in blood CD1c(+) mDC1 and the CD1c(hi) mDC1 subpopulation could be a potential biomarker to monitor clinical uveitis activity within patients.

Variation of choroidal thickness and vessel diameter in patients with posterior non-infectious uveitis.

BackgroundChoroidal thickness (CTh) and choroidal vessel diameter (VD) in the Haler’s layer were evaluated as markers of inflammatory insult in non-infectious uveitis (NIU). Spectral-domain optical coherence tomography (Spectralis®, Heidelberg Engineering Inc.) scans were acquired from 23 normal subjects (39 eyes – group 1), 7 subjects with high myopia (14 eyes – group 2), and 19 patients with NIU (23 eyes – group 3). In groups 1 and 2, CTh and VD were measured at 3 different points of the same horizontal OCT scan passing through the fovea and a mean calculated. Mean CTh and VD were calculated in 2 other locations, 2 mm superior and inferior from the chosen foveal horizontal scan. In group 3, three measurements of CTh and VD were obtained within 1 mm of a horizontal scan passing through a retinal lesion; mean CTh and VD were then computed. A ratio (R) between the VD and the corresponding CTh was calculated.ResultsGroup 1, 2 and 3 mean age was 29.6, 29.1 and 45.9 years, respectively. Sixteen normal subjects, three myopic subjects and six NIU patients were male.. Group 1 mean CTh did not differ from group 2 (261.6±45.6 vs. 260.2±50.6 µm µm; p>0.05); mean VD was marginally higher in Group 2 (159.8±32.2 vs. 163.2±33.2 µm; p>0.05). Group 3 demonstrated thinner CTh (193.6±54.6 µm) than Groups 1 and 2 (p = 0.02 and <0.001). Group 3 mean VD (123.6±37.4 µm) was also less than that in Groups 1 and 2; the difference was statistically significant only when compared to group 2, p = 0.01. R did not differ across groups (p-values >0.05), indicating that variations in CTh and VD followed the same trend.ConclusionsThe study reports potential quantitative OCT-derived parameters that may be explored in future trials of non-infectious uveitis. Thinning of choroid and decrease of vessel diameter are observed in patients with chronic NIU compared to controls.Electronic supplementary materialThe online version of this article (doi:10.1186/s12348-014-0014-z) contains supplementary material, which is available to authorized users.

Quality of life in non-infectious uveitis patients on immunosuppressive therapy.

Purpose:To assess visual function and vision related quality of life in patients with non-infectious posterior or panuveitis treated with immunosuppressives.Materials and Methods:Forty-three patients with non-inflammatory posterior or panuveitis were enrolled in this prospective study. All subjects underwent a detailed interview, complete ophthalmic examination, quality of life assessment using National Eye Institute Visual Function Questionnaire (VFQ-25), visual function evaluation (visual acuity and visual field) at baseline and at a sixth month follow up visit.Results:The mean NEI-VFQ 25 composite score of the subjects with posterior or panuveitis was 58.0 (±24.1). There was a statistically significant improvement (P = 0.004) in the composite score following treatment from 58.0 (±24.1) to 74.3 (±22.0) with effect size of 1.03. The psychological well-being and general health subscales showed significant improvement in the mean score following immunosuppressive therapy. While considering the visual function tests, there was a three-line improvement in the visual acuity score and changeover in the visual field severity from moderate to early defect with corresponding improvement in the visual field pattern. Though most of the patients complained of side effects such as tiredness, gastrointestinal upset and weight gain, there was improvement in the general health subscale.Conclusion:The significant improvement in the general health subscale despite side-effects shows that the benefit of immunosuppressive outweighs the risks of the therapy and this may also reflect the relatively low impact of these side-effects on the quality of life. This study shows that the use of immunosuppressives improves the quality of life of the individual.

Clinical Outcomes of Cyclosporine Treatment for Noninfectious Uveitis

PurposeTo assess the clinical outcomes of cyclosporine treatment for noninfectious uveitis.MethodsA retrospective review of medical records was completed for 182 noninfectious uveitis patients who were treated with cyclosporine between January 2001 and August 2010. Data was obtained relevant to demographic characteristics, anatomic classification, and laterality of uveitis, associated systemic disorder, dosage of cyclosporine and prednisolone, usage of other immunosuppressive drugs, visual acuity (VA), control of uveitic activity, and adverse effects during the cyclosporine use.ResultsUveitic activity was controlled to a level of minimal inflammation in 89.0% and completely in 78.6% of patients by the median duration of 49 and 98 days, respectively. Prednisolone-sparing (dose ≤10 mg) control of inflammation equal to or less than the minimal activity was achieved in 75.3% of patients. VA was aggravated more than 0.2 logarithm of the minimum angle of resolution in 17.3% of eyes in spite of cyclosporine treatment for the mean follow-up of 698.4 days. Dose reduction and cessation of cyclosporine was required only in 3.3% and 9.3%, respectively, due to the intolerable toxicity, although 44.0% of patients experienced mild to moderate adverse effects.ConclusionsCyclosporine combined with corticosteroids or other immunosuppressive drugs as needed is an effective treatment for noninfectious uveitis, thus minimizing the adverse effects of corticosteroids and other toxic drugs. However, careful monitoring for the toxicity of cyclosporine is needed, because a small group of patients cannot tolerate its toxicity.

Interplay between innate and adaptive immunity in the development of non-infectious uveitis.

In vertebrates, the innate and adaptive immune systems have evolved seamlessly to protect the host by rapidly responding to danger signals, eliminating pathogens and creating immunological memory as well as immunological tolerance to self. The innate immune system harnesses receptors that recognize conserved pathogen patterns and alongside the more specific recognition systems and memory of adaptive immunity, their interplay is evidenced by respective roles during generation and regulation of immune responses. The hallmark of adaptive immunity which requires engagement of innate immunity is an ability to discriminate between self and non-self (and eventually between pathogen and symbiont) as well as peripheral control mechanisms maintaining immunological health and appropriate responses. Loss of control mechanisms and/or regulation of either the adaptive or the innate immune system lead to autoimmunity and autoinflammation respectively. Although autoimmune pathways have been largely studied to date in the context of development of non-infectious intraocular inflammation, the recruitment and activation of innate immunity is required for full expression of the varied phenotypes of non-infectious uveitis. Since autoimmunity and autoinflammation implicate different molecular pathways, even though some convergence occurs, increasing our understanding of their respective roles in the development of uveitis will highlight treatment targets and influence our understanding of immune mechanisms operative in other retinal diseases. Herein, we extrapolate from the basic mechanisms of activation and control of innate and adaptive immunity to how autoinflammatory and autoimmune pathways contribute to disease development in non-infectious uveitis patients.

Aqueous Humour Levels of Asymmetric Dimethylarginine (ADMA) are Correlated with Pigment Epithelium-derived Factor (PEDF) in Patients with Uveitis

The association between the aqueous humour levels of asymmetric dimethylarginine (ADMA) and pigment epithelium-derived factor (PEDF) was evaluated. Aqueous humour levels of ADMA and PEDF were measured by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively, in 31 uveitis samples and nine cataract control samples. Aqueous humour ADMA and PEDF levels were significantly higher in infectious and non-infectious uveitis patients than in controls (0.67+/-0.04 nmol/ml and 0.55+/-0.03 nmol/ml versus 0.43+/-0.04 nmol/ml for ADMA; 8.22+/-1.45 microg/ml and 5.22+/-0.95 microg/ml versus 1.32+/-0.22 microg/ml for PEDF). A significant positive correlation between ADMA and PEDF levels in aqueous humour was found in control and uveitis patients. These results demonstrated that the aqueous humour level of ADMA is correlated with PEDF in humans and suggest that both ADMA and PEDF in aqueous humour may be elevated in response to inflammation in uveitis.

Aqueous humor levels of asymmetric dimethylarginine (ADMA) are positively associated with monocyte chemoattractant protein-1 (MCP-1) in patients with uveitis

Background/aims:The aim of the study was to evaluate whether aqueous humor levels of asymmetric dimethylarginine (ADMA) are associated with monocyte chemoattractant protein-1 (MCP-1).Methods:Aqueous humor levels of ADMA and MCP-1 were...