A Prospective,Observational Study on the Application of Ultra-Wide-Field Angiography in the Evaluation and Management of Patients with Anterior Uveitis

Purpose

Evaluation of peripheral retinal vascular changes in anterior uveitis using ultra-wide-field fluorescein angiography.

Design

A prospective, observational study of a case series of patients diagnosed with anterior uveitis.

Methods

Setting: Clinical observation at an academic medical center. Patient or Study Population: A total of 65 eyes of 33 patients corresponded with the research criteria of anterior uveitis in the opinion of specialists of Peking University First Hospital. Observation Procedures: Patients were diagnosed primarily through clinical examinations and conventional fluorescein angiography. Subsequently, ultra-wide-field fluorescein angiograms were obtained for each patient. Main Outcome Measures: The main outcome was the detection of peripheral retinal changes by ultra-wide-field fluorescein angiography, and how these changes influenced the evaluation and management of the disease.

Results

Peripheral vessel leakage was detected in 27 eyes (42%) with anterior uveitis, of which 15 eyes displayed active inflammation and 12 eyes displayed inactive inflammation. Peripheral vessel leakage was found in seven of eight eyes with cystoid macular edema. Cystoid macular edema was detected in 7 of 27 eyes (26%) with peripheral vessel leakage, whereas 1 of 38 eyes (3%) did not display peripheral vessel leakage (p<0.01). 44.4% of the patients with peripheral vessel leakage had a specific etiology. The relevant treatment strategies were modified based on the results of the ultra-wide-field fluorescein angiography. 12 patients with peripheral vessel leakage and a quiescent anterior segment were added to those receiving topical glucocorticoids, while 3 patients with serious peripheral vessel leakage and an active anterior segment received a sub-Tenon injection of triamcinolone acetonide.

Conclusions

Ultra-wide-field fluorescein angiography was very effective in detecting peripheral retinal vascular pathology in anterior uveitis. The changes found in the periphery were important in the evaluation and management of anterior uveitis.     

Release of Prostaglandins in Ocular Inflammation in the Rabbit

VARIOUS studies have suggested that prostaglandins (PGs) may be involved in the ocular response to acute inflammation. PGs are present in ocular tissues^1–4 and can reproduce many of the characteristic changes associated with ocular trauma in the rabbit^5–7, cat⁸ and monkey⁹. We therefore examined the possibility that PGs are involved in the response of the rabbit eye to an acute immunological inflammatory reaction. Eighty-four adult albino rabbits of both sexes were used in 8 groups of 6 to 12, but 11 were discarded because uveitis did not develop and 1 because of infection. Uveitis was induced by a single intravitreal injection of a sterile solution of crystallized bovine serum albumin (British Drug Houses). The left eye was anaesthetized with topical 0·4% oxybuprocaine hydrochloride and bovine serum albumin (10 mg in 0·1 ml. normal saline) was then injected slowly into the anterior part of the vitreous. On subsequent days the eyes were examined with a slit-lamp. Immediately after the injection, small amounts of protein and cells appeared in the aqueous and a slight flare was seen. This was probably due to trauma and the eyes usually appeared normal by about the fifth day. On the 9th-15th day signs of uveitis appeared, characterized by a pronounced flare (due to liberation of large quantities of protein and cells into the anterior chamber) and by marked dilatation of iris and ciliary blood vessels. Occasionally, the pupillary margin was seen to adhere to the anterior surface of the lens (posterior synechiae). The contralateral control eye was usually unaffected, but in about 20% of cases fine filaments (probably strands of fibrin) were seen in the anterior chamber when uveitis occurred in the test eye. At the height of the inflammatory response, the animals were anaesthetized with pentobarbitone (25 mg/kg i.V.). The aqueous humour (approximately 0·2 ml./eye) was then withdrawn through a 25G needle and stored immediately at ?20°C. In each group, the aqueous humour samples from the test (left) and control (right) eyes were pooled in separate containers. Biological activity was assayed on the rat fundus preparation¹⁰ in Krebs solution containing atropine, methy-sergide and mepyramine (all 2 × 10^?7 g/ml.). Unextracted samples were assayed in some experiments, whereas in others the PG-like material was first extracted (chloroform method of Unger et al.¹¹). Alkaline hydrolysis (0·2 M NaOH, 45 min, 37° C) was used to distinguish between PGE and PGF compounds and thin layer chromatography was used to separate the PGs (a II solvent system of Gréen and Samuelsson¹²; silica gel plates or impregnated paper¹³, treated with 3% w/v silver nitrate). Cuts of the chromatograms at and between the R_F values of PGE₁, PGE₂ and PGF_2α were eluted with Krebs solution containing excess (0.2 M) NaCl to remove the silver ions prior to extraction for PGs^11,13. Samples of unextracted aqueous humour from the test eyes caused contractions (preceded by a relaxation in 1 of the 5 experiments) of the rat fundus preparation. Since atropine, methysergide and mepyramine were present the spasmogen was not acetylcholine, 5-hydroxytryptamine or histamine. The control aqueous had no effect. The material was PG-like since it extracted into chloroform¹¹ when the aqueous humour was acidified and it caused contractions of the rat fundus which were reduced in parallel with PGE₂ by the selective PG antagonist SC-19220^14,15 (Fig. 1). The biological activity was completely destroyed by alkaline hydrolysis in 3 experiments, indicating E-type prostaglandin (Fig. 1) and approximately halved in another (samples from 2 batches of aqueous humour before chloroform extraction and 2 batches after extraction). PGE₂ incubated at the same time was destroyed whereas PGF_2α was unaffected.     

Elevated immunoreactive-adrenomedullin levels in the aqueous humor of patients with uveitis and vitreoretinal disorders

To clarify possible involvement of adrenomedullin in the pathophysiology of inflammation of eyes, we measured immunoreactive-adrenomedullin concentrations in the aqueous humor and plasma obtained from 14 control subjects and 56 patients with uveitis or vitreoretinal disorders. Immunoreactive-adrenomedullin levels in the aqueous humor were significantly elevated in patients with active uveitis, proliferative vitreoretinopathy and proliferative diabetic retinopathy, as compared with control subjects. The plasma immunoreactive-adrenomedullin levels were not significantly correlated with the aqueous humor levels. These findings suggest that adrenomedullin produced locally in the eyes is involved in the pathophysiology of uveitis and some proliferative vitreoretinal disorders.     

Local production of Ia-inducing activity in experimental immunogenic uveitis

The production of soluble lymphokine products of T lymphocytes was studied in the aqueous of rabbits with uveitis induced by intravitreal injection of 2.0 mg of ovalbumin. Aqueous from uveitic eyes demonstrated Ia-inducing activity at a dilution of 1:50 which diluted out at 1:250. The control aqueous and sera from normal or uveitic animals were negative. While production of interleukin 2(IL-2) in uveitic eyes could not be demonstrated in vitro, control rabbit concanavalin A-induced supernatants of nylon-wool-purified T cells contained both Ia-inducing and IL-2 activity. These data demonstrate antigen-driven production of a lymphokine activity in the aqueous of the uveitic eye. Local production of lymphokine may be a potent mechanism for amplification of the inflammatory process in uveitis.     

Chemokine gene polymorphisms in idiopathic anterior uveitis

OBJECTIVES: The aim of this study was to determine whether there are any associations between single nucleotide polymorphisms of the chemokine genes IL-8, MCP-1, their corresponding receptors CXCR1 and CCR2 and disease outcome in patients with acute idiopathic anterior uveitis. METHODS: 60 Caucasian patients with idiopathic acute recurrent anterior uveitis together with 120 healthy Caucasian control subjects were tested for the presence of 16 bi-allelic polymorphisms and HLA-B27 using polymerase chain reaction in association with sequence-specific primers with mismatches at the 3' end. The genetic data was then compared between patients and controls, and within the patient group itself for association with clinical disease outcome. RESULTS: As expected, the frequency of HLA-B27 was significantly higher in the patient group than the control group (63.33% versus 15.83%; Pearson's P<0.0001, Fisher's P<0.0001). In addition, the frequency of the T allele of MCP-1 63555 was found to be significantly higher in the control group when compared to the patient group (P=0.0160). CONCLUSION: This study describes an association between acute anterior uveitis and MCP-1 63555 polymorphisms where the T allele may be a protective marker against the disease.     

The chemical composition and the osmotic pressure of the aqueous humor and plasma of the rabbit

Measurements were made of the osmotic pressure of plasma, and of aqueous humor taken from the anterior chamber of the right and left eyes and from the posterior chamber of unanesthetized rabbits. Aqueous humor from the anterior chamber was found to be hypertonic to the plasma by approximately 3 mM/liter equivalent of sodium chloride. The aqueous humor from the anterior and posterior chambers of the right and left eyes was isotonic. The concentration of chloride in the anterior and posterior chambers was the same. The concentration of all the major components of the aqueous humor and plasma has been determined by chemical analysis on fluid samples obtained from unanesthetized rabbits at approximately the same time. The calculated osmotic pressure of the total of these substances in terms of sodium chloride equivalent agrees to within better than 1 per cent of the total osmotic pressure as measured experimentally. The distribution of some individual anions and cations of the aqueous humor and plasma was determined. This distribution is widely different from that which would obtain at a state of equilibrium. The positive and negative charges carried by the ions in the aqueous humor were approximately equal. Sources of error in the experiments are discussed.     

Selenium and zinc in patients with acute and chronic uveitis

Patients with chronic inflammation often show decreased serum levels of trace elements. This study aimed to investigate serum levels of selenium and zinc in patients with uveitis. Twenty-four patients (13 female, 11 male) with a mean age of 40.6±15.5 yr were included in this study. According to their underlying disease, they were divided into acute (n=13) or chronic (n=11) uveitis. Selenium and zinc determination was performed by atomic absorption spectroscopy in EDTA blood samples. Patients with acute or first-time uveitis showed selenium and zinc concentrations within the normal range. In contrast to this, patients with chronic recurrent uveitis tend to result in decreased selenium and zinc levels. Especially selenium showed a remarkable reduction in serum concentration below the normal range. Furthermore, there was a tendency to decreased trace element concentrations with increasing age. A sex dependency could not been found. Especially patients with chronic, recurring uveitis show remarkable decreased selenium concentration in the EDTA-blood. Further studies should investigate possible positive effects of therapeutic selenium and zinc supplementation in patients with chronic, recurrent uveitis.     

Effect of Intravitreal Methotrexate and Rituximab on Interleukin-10 Levels in Aqueous Humor of Treated Eyes with Vitreoretinal Lymphoma

Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.     

Ocular immune privilege and the impact of intraocular inflammation

Immune privilege, a characteristic of the internal compartments of the eye, is a physiologic mechanism that is designed to provide the eye with protection against pathogens while protecting the delicate visual axis from the sight-destroying potential of immunogenic inflammation. It is assumed that the presence of intraocular inflammation is incompatible with the existence of immune privilege. The validity of this assumption has been tested in four animal models of intraocular inflammation-systemic and local endotoxin-induced uveitis (EIU), mycobacterial adjuvant-induced uveitis (MAIU), and experimental autoimmune uveitis (EAU). Immune privilege was assessed in inflamed eyes by growth of intracamerally injected allogeneic tumor cells, by the capacity to support immune deviation following intracameral injection of antigen (ovalbumin, OVA), by assaying protein, leukocyte, and selected cytokine content of aqueous humor (AqH), and by capacity of inflamed AqH to suppress T cell activation in vitro. The results indicate that, irrespective of the type of inflammation, tumor cells formed progressively growing tumors in inflamed eyes. Moreover, OVA injected into the anterior chamber of eyes inflamed by MAIU and EAU failed to induce immune deviation. AqH from inflamed eyes reflected breakdown of the blood:ocular barrier as well as transient loss of its immunosuppressive properties. Immunosuppressive microenvironments routinely reemerged in inflamed eyes, and the immunosuppressive agent present under these circumstances in AqH was active TGF beta2. It is concluded that immune privilege is surprisingly resistant to abolition by intraocular inflammation, and that maintenance of immune privilege in the face of ongoing inflammation depends upon the emergence of progressive and partially different immunosuppressive mechanisms.     

Transplantation immunology of the anterior chamber of the eye. I. An intra-ocular graft-vs-host reaction (immunogenic anterior uveitis).

A graft-vs-host reaction (GVHR) expressed as an anterior uveitis was elicited within the anterior chambers of the eyes of F1 hybrid rats by the inoculation of suspensions of allogeneic, parental lymph node cells. This response resembled local GVHRs induced in other sites, except for the failure of refractoriness to appear following resolution of the acute phase. Because lymphoid cells within the anterior chamber have been shown to leave and make an impact on the systemic immunologic apparatus of the recipient, rather than remain isolated within the eye, it was suggested that the vascular route by which these cells disseminate is an important determinant of whether refractoriness will ensue from a local GVHR.     

Cytokine Profile in Human Eyes: Contribution of a New Cytokine Combination for Differential Diagnosis between Intraocular Lymphoma or Uveitis

Primary intraocular lymphoma (PIOL), also called primary vitreoretinal lymphomas, often masquerades as uveitis. This misdiagnosis can result in subsequent brain involvement and oculocerebral lymphoma (OCL). In this study, we sought to characterize the helper T-cell type 1 (Th1)/Th2 cytokine profile in vitreous samples from patients with PIOL, OCL, uveitis and controls with non-inflammatory disease. Vitreous and aqueous humor samples from 87 patients with PIOL (n = 30), OCL (n = 12), uveitis (n = 34), and retinal detachment (RD) without hemorrhage (n = 11) were analyzed and their concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were determined by flow cytometric bead arrays (CBA). The IL-10 levels determined by CBA were compared with those by ELISA. IL-10 concentrations measured by CBA and ELISA were highly correlated. IL-2, IL-4, and TNFα were not detected in any sample. The only cytokine detected at a significant level in samples from RD vitreous was IL-6. The IL-10/IL-6 ratio, as previously reported, was slightly higher in PIOL than in uveitis samples, but not for all patients. Cytokine profiles from PIOL and OCL samples did not differ. The combination of the IL-10/IL-6 and IL-10/IFNγ ratios was highly informative for discriminating PIOL/OCL from uveitis samples and for therapeutic follow up of PIOL. This strategy might be very helpful as an initial screening to rule out PIOL in patients thought to have uveitis.     

Clinical features of ocular toxoplasmosis in Korean patients

We report here the records of 10 consecutive Korean patients (10 eyes) with ocular toxoplasmosis which showed the typical clinical manifestations with seropositivity for Toxoplasma gondii specific IgG antibodies by micro-ELISA between 2006 and 2010. Nine patients were males and 1 was female; their age was 50.5 ± 13.8 years. The most common accompanying signs were vitritis (100%), anterior uveitis (70%), and scattered white deposit (80%). Pre-existing retinochoroidal scar was found in 1 (10%) patient. All patients received antiparasitic chemotherapy and systemic corticosteroid treatment, which resolved the presenting attack and recovered the visual acuity better than initial one in 9 patients and worse in 1. Optic atrophy, cataract, and retinal neovascularization were observed during the follow-up period and recurrence was detected in 3 eyes (30%) 6 to 20 months after the initial attack. In Korea, although rarely detected and reported, ocular toxoplasmosis needs more attention in clinical field of retinal diseases.     

Postoperative outcomes after implantation of intraocular lenses in eyes with cataract and uveitis

Despite advances in surgical technique and implant materials, cataract surgery in patients with uveitis is still a challenging procedure. We retrospectively evaluated postoperative outcomes of cataract surgery in 35 eyes of 29 patients with uveitis. Phacoemulsification with posterior chamber intraocular lens implantation was performed in all eyes. Postoperative evaluations were performed at day 2, and then at 7 days, 1, 3, and 6 months respectively. There were 16 males, and 13 females, aged 31 to 68 years. Follow-up ranged from 4 to 35 months. At final follow-up 33 eyes (94%) had an improvement in visual acuity compared with preoperative levels (p < 0,05). Giant cells were observed in the intraocular lens optic in 7 eyes (20%). Posterior capsule opacification occurred in 10 eyes (29%). Clinical cystoid macular edema was observed in 4 eyes, and 2 eyes required trabeculectomy with mitomycin C due to secondary glaucoma. Cataract surgery in patients with uveitis leads to successful visual results after correct surgical timing, and adequate anti-inflammatory therapy. There were no significant differences in the degree of inflammation after implantation of various types of intraocular lenses.     

Anti-TNF therapies in the management of acute and chronic uveitis

Patients with anterior uveitis may be treated with topical therapy alone but patients with posterior uveitis and those with sight threatening complications of anterior uveitis usually require systemic treatment especially if the disease is bilateral. The mainstay of treatment is corticosteroids and additional immunosuppressive agents such as cyclosporin and mycophenolate are used when necessary. There remains a significant cohort of patients in whom this therapy is either not tolerated or is ineffective. The use of the anti-tumour necrosis factor (TNF) antibodies has been very successful in controlling other immune-mediated disorders such as rheumatoid arthritis and has subsequently been extended to use in other arthritidies and other disorders such as psoriasis and Crohn's disease. TNF is known to play a key role in ocular inflammation as shown by animal studies and its detection in the ocular fluids of inflamed eyes in man. In some disorders all types of anti-TNF antibodies have similar efficacy but that does not appear to be the case with uveitis where infliximab is at present looking to be more effective than etanercept. The data on the use of anti-TNF drugs in uveitis is presented together with new data on its role as a steroid sparing agent.     

Aqueous Cytokine Changes Associated with Posner-Schlossman Syndrome with and without Human Cytomegalovirus

Aim

To study the differences in aqueous cytokines in Posner-Schlossman Syndrome (PSS) patients with and without human cytomegalovirus (CMV) DNA in the aqueous humor.

Methods

This is a prospective study. Fifty-three uveitis patients with clinical signs of PSS were enrolled and aqueous humor samples were collected. Fourteen PSS patients were positive of CMV DNA in the aqueous by polymerase chain reaction (PCR) analysis. These eyes were negative of common ocular pathogens such as herpes simplex virus, varicella-zoster virus, rubella virus and toxoplasma. Twenty-five otherwise healthy cataract patients were enrolled as controls. Cytokine concentration was measured by a magnetic color-bead-based multiplex assay and analyzed using statistical and classification approaches.

Results

The average age of 53 PSS patients was 48.74±13.43 years (yrs) (mean ± standard deviation) and 66.3±15.0 yrs for the controls. The median CMV viral DNA copy number was 26000/mL aqueous (range 1400 to 85000 copies/mL) in 14 CMV positive patients as determined by quantitative PCR. PSS aqueous had significantly higher Interleukin (IL)-8 (CXCL8), monocyte chemotactic protein-1 (CCL2), macrophage inhibitory protein 1-β (CCL4), granulocyte colony-stimulating factor (GCSF) and transforming growth factor-β (TGF-β) levels than controls after adjusted by age and gender. IL-2, IL-12, tumor necrosis factor-α (TNF-α) and interferon-α (IFN-α) levels were significantly lower in PSS aqueous than controls. No difference between CMV positive PSS and CMV negative PSS aqueous was observed. Over 97% of PSS samples were distinguished from controls by elevated CXCL10 (>500 ng/mL), CXCL8 (>30 ng/mL) and CCL2 (>60 ng/mL) levels.

Conclusion

PSS eyes were characterized by elevated aqueous chemokine concentration. The presence of CMV viral DNA was not associated with significant change of the type of cytokine expression in PSS patients.     

Estrogen protects against cellular infiltration by reducing the expressions of E-selectin and IL-6 in endotoxin-induced uveitis.

Anterior uveitis associated with Behcet's disease and ankylosing spondylitis preferentially occurs in adult men, which may suggest the effects of sex hormones on acute anterior uveitis. Recently, estrogen receptors in the vascular endothelium have been reported to be involved in several pathological conditions. In the present study, we examined the gender differences in susceptibility to endotoxin-induced uveitis (EIU) and the effects of estrogen on anterior inflammation. EIU was induced in adult male, female, and ovariectomized female Lewis rats (200 g) by hind footpad injection of 200 microg of LPS. In EIU, cellular infiltration was more marked in male than in female rats, and ovariectomy increased cellular infiltration. Treatment with 10 microg of 17beta-estradiol significantly reduced the cell number in male and ovariectomized female rats with EIU. Estrogen receptor immunoreactivity was found in the nucleus of vascular endothelium and in some stromal cells of the iris-ciliary body. Semiquantitative PCR revealed that E-selectin and IL-6 gene expressions were increased in rats following LPS injection, and an overdose of tamoxifen, an estrogen receptor antagonist, reversed the effect of 17beta-estradiol on E-selectin, but not its effect on IL-6. These observations suggested that the down-modulation of these inflammatory genes by estrogen may contribute to the reduction in cellular infiltration in acute anterior uveitis.     

Detection of Ocular Toxoplasma gondii Infection in Chronic Irregular Recurrent Uveitis by PCR

Toxoplasma gondii is a zoonotic parasite resulting in human infections and one of the infectious pathogens leading to uveitis and retinochoroiditis. The present study was performed to assess T. gondii infection in 20 ocular patients with chronic irregular recurrent uveitis (20 aqueous humor and 20 peripheral blood samples) using PCR. All samples were analyzed by nested PCR targeting a specific B1 gene of T. gondii. The PCR-positive rate was 25% (5/20), including 5% (1) in blood samples, 25% (5) in aqueous humor samples, and 5% (1) in both sample types. A molecular screening test for T. gondii infection in ocular patients with common clinical findings of an unclear retinal margin and an inflammatory membrane over the retina, as seen by fundus examination, may be helpful for early diagnosis and treatment.     

Uveitis- a rare disease often associated with systemic diseases and infections- a systematic review of 2619 patients

ABSTRACT: BACKGROUND: Uveitis is an autoimmune disease of the eye that refers to any of a number of intraocular inflammatory conditions. Because it is a rare disease, uveitis is often overlooked, and the possible associations between uveitis and extra-ocular disease manifestations are not well known. The aim of this study was to characterise uveitis in a large sample of patients and to evaluate the relationship between uveitis and systemic diseases. METHODS: The present study is a cross-sectional study of a cohort of patients with uveitis. Records from consecutive uveitis patients who were seen by the Uveitis Service in the Department of Ophthalmology at the Medical University of Vienna between 1995 and 2009 were selected from the clinical databases. The cases were classified according to the Standardization of Uveitis Nomenclature Study Group criteria for uveitis. RESULTS: Data were available for 2619 patients, of whom 59.9% suffered from anterior, 14.8% from intermediate, 18.3% from posterior and 7.0% from panuveitis. 37.2% of all cases showed an association between uveitis and extra-organ diseases; diseases with primarily arthritic manifestations were seen in 10.1% of all cases, non-infectious systemic diseases (i.e., Behcet's disease, sarcoidosis or multiple sclerosis) in 8.4% and infectious uveitis in 18.7%. 49.4% of subjects suffering from anterior uveitis tested positively for the HLA-B27 antigen. In posterior uveitis cases 29% were caused by ocular toxoplasmosis and 17.7% by multifocal choroiditis. CONCLUSION: Ophthalmologists, rheumatologists, infectiologists, neurologists and general practitioners should be familiar with the differential diagnosis of uveitis. A better interdisciplinary approach could help in tailoring of the work-up, earlier diagnosis of co-existing diseases and management of uveitis patients.     

TNF receptor-associated factor 5 gene confers genetic predisposition to acute anterior uveitis and pediatric uveitis

Introduction

TNF Receptor-Associated Factor 5 (TRAF5) has been shown to be associated with autoimmune disease. The current study sought to investigate the potential association of TRAF5 with acute anterior uveitis (AAU) and pediatric uveitis in Han Chinese.

Methods

Three TRAF5 SNPs were analyzed in 450 AAU patients with or without ankylosing spondylitis (AS), 458 pediatric uveitis patients, and 1,601 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP Genotyping Assay. Numerous variables were evaluated, including age, sex distribution, and clinical and laboratory observations.

Results

Two SNPs (rs6540679, rs12569232) of TRAF5 were associated with pediatric uveitis, and rs12569232 also showed a relation with the presence of microvascular leakage. No significant associations were found when patients were subdivided according to their rheumatoid factor (RF) or anti-nuclear antibody (ANA) status or whether they had juvenile idiopathic arthritis (JIA). Rs12569232 predisposed to AAU and its subgroups (with ankylosing spondylitis (AS) or HLA-B27 positive). No association was found between rs10863888 and either pediatric uveitis or AAU.

Conclusion

This study revealed that TRAF5 is involved in the development of AAU and pediatric uveitis. Further stratified analysis according to the clinical and laboratory observations suggested that rs12569232/TRAF5 may play a role in the development of retinal vasculitis.