Are cytokine gene polymorphisms associated with outcome in patients with idiopathic intermediate uveitis in the United Kingdom?

BACKGROUND/AIM: Competing levels of cytokines, either locally within the eye or systemically, may influence the eventual outcome of ocular inflammation. Polymorphism in the promoter part of the genes controlling cytokine production may result in either higher or lower production of the relevant cytokine to a given stimulus. The authors hypothesised that such polymorphisms may relate to visual outcome in patients with idiopathic intermediate uveitis. METHODS: DNA was obtained from 125 patients with idiopathic intermediate uveitis and analysed for the interleukin 10 IL-10-1082G/Alpha and IL-10-819C/T, and interferon gamma IFNgamma 874T/A gene polymorphisms. Associations with disease were calculated by both allelic frequency and haplotype analysis, and associations between ocular disease outcomes and the presence of polymorphisms were identified. A bad outcome was defined as loss of vision <6/12 Snellen in both eyes at 5 years from presentation when the eyes were quiet. RESULTS: An initial screen showed that the 874T allele of the IFNgamma gene was more prevalent in patients than controls (chi2= 7.9; p = 0.004 OR 1.7; 95% CI 1.2 to 2.6 (Pc = 0.02), whereas the IL-10-1082/-819 AT haplotype of the interleukin 10 (IL-10) gene was not. Analysis of disease outcome showed an association between IL-10-1082 AA homozygosity and bad outcome (chi2= 13; p = 0.0003). Moreover, the two cytokine polymorphisms taken together showed that up to 75% of patients with a poor visual outcome had the combined IFNgamma 874TA or TT genotype together with the IL-10-1082AA genotype (chi2= 13.2 p = 0.0008 OR 6.4; 95% CI 1.85 to 23.6 Pc = 0.1). CONCLUSION: These results show that disease outcome in intermediate uveitis may be partly determined by a complex interplay between cytokine genes and these results may have implications for future treatment with biological agents that target these cytokines.     

Results of interferon-alfa therapy in patients with Behçet uveitis

Purpose

To report on the results of interferon-α 2a (IFNα) treatment in patients with Behçet uveitis unresponsive to conventional immunosuppressive therapy.

Methods

We retrospectively analyzed the medical records of 44 patients who had been treated with IFNα between September 2001 and May 2005. The initial dose of IFNα was 6 MU/day in 37 patients (84.1%) and 3 MU/day in 7 patients (15.9%), and was gradually tapered after ocular inflammation was suppressed. Immunosuppressive agents were discontinued. Oral corticosteroids were discontinued or maintained at a dosage of less than 10 mg prednisone equivalent per day. Main outcome measures were recurrence of posterior or panuveitis attacks and changes in visual acuity.

Results

Sixteen patients (36.4%) remained relapse free during treatment, whereas 28 (63.6%) patients had recurrent uveitis attacks. Four of these were considered treatment failures and were switched to other treatments. In the remaining 40 patients, the mean duration of treatment was 12.4±10.8 months (range 3–45 months). In 9 of 40 patients (22.5%) treatment could be discontinued 22.2±13.4 months after therapy, and 8 (20%) of these patients had sustained remission for up to 24 months. Three patients (7.5%) were switched to other therapies because of side effects. The frequency of uveitis attacks per 6 months was reduced from 1.6±1.2 to 0.8±0.9 in 26 patients who had a minimum follow-up of 6 months before and after IFNα therapy (p<0.05). There was a significant improvement in visual acuity and this was preserved throughout follow-up in 38 (95%) of 40 patients.

Conclusions

A partial or complete response was obtained with IFNα therapy in 91% of Turkish patients with Behçet uveitis refractory to conventional immunosuppressive treatment. Our results suggest that there may be differences in therapeutic efficacy and side-effect profile of IFNα in different patient populations. Comparative studies are needed to investigate this hypothesis.     

Diagnostics in childhood uveitis: what tests for which uveitis?

BACKGROUND: Intraocular inflammation in children differs considerably from that found in adults. Therefore the diagnostic work-up has to be adapted to the age and specific diseases. MATERIALS AND METHODS: The published literature was reviewed for results of clinical trials and consensus meetings. In addition, the authors have incorporated their own experience. RESULTS: Recommendations for a systematic and complete diagnostic work-up are given using tables where possible. CONCLUSIONS: A close cooperation between ophthalmologists and paediatricians is very important.     

Psoriatic uveitis: a distinct clinical entity?

PURPOSE: To describe the clinical characteristics of uveitis occurring in patients with psoriasis and to compare them with patients with idiopathic anterior uveitis and HLA-B27-associated anterior uveitis. DESIGN: Case-control study. METHODS: The charts of 36 patients with a diagnosis of uveitis and psoriasis visiting the Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary between January 2000 and December 2001 were reviewed. Clinical characteristics, therapy, and outcomes of uveitis were compared with 30 randomly selected patients with either idiopathic anterior uveitis or with HLA-B27-associated anterior uveitis. RESULTS: The mean age at presentation for uveitis was significantly higher in patients with psoriasis compared with nonpsoriatic groups (44.6 years in HLA-B27-psoriatic patients vs 35.9 years in HLA-B27- nonpsoriatic patients, P = .034; 52.7 years in HLA-B27+ psoriatic vs 35.7 years in HLA-B27+ nonpsoriatic patients, P = .001). Uveitis in patients with psoriasis also tended to be bilateral (62%) and prolonged (11.2 weeks). HLA-B27+ patients with psoriasis required supplemental therapy with oral nonsteroidal anti-inflammatory drugs (95% confidence interval [CI] 1.41 to 5.36, P = .003) for anterior uveitis more often than did the HLA-B27+ nonpsoriatic group. Patients with psoriasis and uveitis who were HLA-B27+ required oral NSAIDs (95% CI 1.51 to 9.79, P = .001) for anterior uveitis more often than did HLA-B27- psoriatic patients. CONCLUSION: Uveitis in patients with psoriasis may have distinguishing clinical features. Further epidemiologic studies are required to determine the strength of association between psoriasis without arthritis but with uveitis.     

What can physicians learn from the blogs of patients with uveitis?

AIM: To identify the sources of anxiety from patient blogs. MATERIALS AND METHODS: Blogs were identified using www.blogsearch.google.com. and the following noted: age, sex, location, type of uveitis, symptoms, and the sources of anxiety. RESULTS: 103 blogs were identified. Anterior uveitis was the most common type followed by multifocal choroiditis and sympathetic ophthalmia. Sources of anxiety include acute pain, redness, photophobia and visual loss, initial misdiagnosis and monetary expenses. CONCLUSIONS: Physicians should focus on pain relief and counsel on visual loss including its impact on career or livelihood needs. Patients seen in emergency situations need early referral.     

Urinary neopterin levels in uveitis: is it a new activity marker?

PURPOSE: Neopterin is an immunologic marker for the activation of the cell-mediated immune system and it is found to be elevated in autoimmune diseases. We aimed in this study to investigate the relationship between urinary neopterin levels and disease activity in patients with uveitis. METHODS: 31 patients with active uveitis and 13 patients with inactive uveitis were compared with 27 age and sex matched controls. Disease activity was evaluated by clinical examination and fundus florescein angiography findings. Samples were studied with High Performance Liquid Chromatography. RESULTS: Urinary neopterin levels in patients with active uveitis, inactive uveitis and control subjects were 274 +/- 98, 179 +/- 61 and 166 +/- 38 micromol/mol creatinine respectively (p < 001). The difference between active uveitis, inactive uveitis and control groups were statistically significant (p < 001). CONCLUSIONS: Urinary neopterin levels are found to be increased in patients with active uveitis. Neopterin can be used as a biochemical activity marker to support the clinical findings in patients with uveitis.     

Association of intermediate uveitis with HLA-A28: definition of a new systemic syndrome?

Background: Endogenous posterior uveitis (PU) can be associated with systemic diseases, and certain forms have strong association with HLA antigens. Much less is known regarding intermediate uveitis (IU). The purpose of this study was to determine whether IU is associated with the HLA system and whether it can be associated with systemic symptoms.Methods: In 179 consecutive patients consulting for uveitis, a detailed history was obtained and a physical examination performed. HLA typing for 71 HLAA, B, DR and DQ antigens, laboratory tests, and radiography of the chest, sinuses, and sacroiliac joints were systematically performed.Results: Thirty-two patients (18%) had IU; 51 (28.5%) had PU and constituted our internal control group. Nine of the patients with IU (28%) had the HLA-A28 antigen, compared with 8.1 % of a healthy control population and 8.6% of the patients with PU (P < 0.001). An associated disease was found in four patients with IU (12.5%) (none was HLA-A28) and in 45% of the patients with PU (P < 0.01). Some 67% of HLA-A28 patients with IU had arthralgias affecting the knee(s), compared with 17% of non-HLA-A28 patients and 18% of patients with PU (P<0.05 and P<0.01 respectively); 55% had gonalgias and hypocomplementemia compared with 9% and 2% respectively (P < 0.01 and P < 0.001).Conclusions: IU is significantly associated with HLA-A28; patients having this antigen may represent a subset of the disease characterized by an increased prevalence of arthralgias and hypocomplementemia.     

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis

Japanese Journal of Ophthalmology - To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. A retrospective, observational study....     

Ocular structural changes in patients with Duane retraction syndrome: Does a correlation exist?

Purpose:The purpose of this study was to investigate the structural changes (axial length, central macular thickness (CMT), subfoveal choroidal thickness, and keratometry) in subjects with unilateral Duane retraction syndrome (DRS) as compared with the normal fellow eye.Methods:In this prospective study, we included 34 subjects with unilateral DRS from January 2016 to December 2016 seen at our institute. Data was collected for axial length, keratometry using partial coherence interferometry, CMT, subfoveal choroidal thickness using the enhanced depth imaging-optical coherence tomography (EDI-OCT). All these measurements were compared between the affected and fellow eye.Results:During this period, we included 34 subjects with unilateral DRS (22 Type I, 1 Type II, and 11 Type III). The mean age (±SD) of subjects was 14 ± 8 years (range: 5–28 years). There were 15 males and 19 females. Eyes with DRS were significantly shorter (median axial length 22.4 mm, interquartile range (IQR): 21.56 - 23.17) as compared to fellow eye (median axial length 22.7 mm, IQR: 22.35-23.55), P = 0.04. Choroidal thickness, CMT, and average keratometry were similar in DRS and fellow eyes (P = 0.39, 0.06, and 0.11, respectively). A significant difference in axial length was found only between Type I and Type III DRS (P = 0.03).Conclusion:This study suggests that in subjects with DRS, the affected eye has shorter median axial length when compared with the fellow eye. Prevalence of refractive error in eye with DRS was higher compared to fellow eye. But, there was no difference in magnitude of refractive error found between eye with DRS and normal fellow eye.     

Volumetric colour Doppler imaging: a useful tool for the determination of ocular blood flow in glaucoma patients?

PURPOSE: Disturbed ocular haemodynamics are discussed to contribute to the pathogenesis of glaucoma. Up to now there is no method available allowing direct determination of blood flow, which is the most relevant dimension for studies on haemodynamics. In this study, volumetric colour Doppler imaging (vCDI) is evaluated systematically in glaucoma patients. METHODS: A Siemens Elegra ultrasound set-up with a linear 7.5 MHz probe was used for all CDI measurements. For vCDI, the cross-sectional area of a vessel and the flow velocity is determined. From both these parameters blood flow can be calculated. Ocular pulse amplitude (OPA) was assessed by the method of Langham using a pneumatic applanation tonometer. RESULTS: (1) Velocity measurements using CDI in the ophthalmic artery and central retinal artery were highly reproducible (n=20). In contrast, reproducibility of vCDI measurements was low (n=20). Reproducibility improved if five vCDI measures were averaged. (2) Results from two different CDI-operators did not differ regarding the velocity measurements, but there was a difference in vCDI measurements (n=20). (3) Results from vCDI did not correlate with measurements of OPA in 69 patients. (4) In 15 patients, vCDI failed to detect changes of ocular perfusion induced by the application of dorzolamide. CONCLUSION: vCDI is not applicable in ophthalmology at present.     

Preoperative vitreous hemorrhage associated with rhegmatogenous retinal detachment: a risk factor for postoperative proliferative vitreoretinopathy?

Background: We conducted a prospective clinical study to elucidate the role of preoperative vitreous hemorrhage in the development of postoperative proliferative vitreoretinopathy (PVR) in primary rhegmatogenous retinal detachment. Materials and methods: We prospectively evaluated 409 eyes of 390 patients affected by primary rhegmatogenous retinal detachment referred before any failed attempt to reattach the retina. Single and multiple logistic regression analysis were used to test 14 categories of variables. Results: Postoperative PVR occurred in 48 (11.7% of 409 eyes). Postoperative PVR developed in 41 (11.8%) of the 347 eyes with no preoperative vitreous hemorrhage, and 7 (11.3%) of the 62 eyes with preoperative vitreous hemorrhage (P=0.90). The results of multiple logistic regression analysis showed that only four variables were significant factors which had independently and jointly an effect on the risk of postoperative PVR: (1) 90° or greater circumferential extent of the retinal tears; (2) preoperative PVR grade B; (3) preoperative PVR grade C-D; and (4) the use of cyrotreatment as the method of retinopexy. Conclusion: With the surgical techniques currently used, mild preoperative vitreous hemorrhage is not an independent risk factor for postoperative PVR in primary rhegmatogenous retinal detachment. The role of moderate and severe vitreous hemorrhage remains to be fully evaluated in a larger series of eyes.