Carsten Heinz

Intravitreal bevacizumab (avastin) as a treatment for refractory macular edema in patients with uveitis: a pilot study.

Purpose: Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) which has been successfully used for the treatment of age-related macular degeneration with choroidal neovascularization. As VEGF is involved in the pathomechanisms of inflammation and endothelial dysfunction the authors used bevacizumab as a last resort treatment in patients with persistent uveitic cystoid macular edema (CME). Patients and Methods: Persistent uveitic CME was defined by optical coherence tomography (OCT) measurements >250 &mgr;m despite previous treatments. The authors reviewed patients with persistent CME who subsequently had been treated with intravitreous bevacizumab 1.25 or 2.5 mg. Improvement was judged by visual acuity (VA) gain ≥2 lines and thickness reduction in OCT. Results: Eleven eyes of 10 patients were injected since February 2006. Median follow-up was 70 days. Reduction in central retinal thickness could be seen as early as 2 weeks with a mean foveal thickness reduction of 127.2 &mgr;m at 4 weeks. Concurrent improvement in VA was seen in 4 of 10 patients, and was unchanged in the others. Four patients received two injections and five patients received three injections. Except for progression of cataract in one eye no ocular or systemic adverse events were recorded. Conclusions: Intravitreal bevacizumab seems to be an effective and safe treatment in the management of refractory inflammatory CME. The effect is transient, and reinjections may be necessary, although the time until reinjection is needed differs individually.

Is tocilizumab an effective option for treatment of refractory uveitis associated with juvenile idiopathic arthritis

To the Editor: Anti-interleukin 6 receptor (anti-IL-6R) antibodies have been effective in experimental models of autoimmune arthritis, encephalomyelitis, and also uveitis1,2. Tocilizumab (TCZ; RoActemra®, Hoffmann-La Roche, Basel, Switzerland), a fully humanized anti-IL-6R antibody, has been approved for the treatment of rheumatoid arthritis. Efficacy has also been shown for systemic-onset juvenile idiopathic arthritis (JIA)3 and vasculitis4. To date, however, no reports have appeared concerning its efficacy in JIA-associated uveitis. In about one-third of JIA patients with uveitis, eye inflammation runs a severe course and vision-threatening complications develop, and immunosuppressive treatment is required5. Because some patients do not respond properly to the widely used disease-modifying antirheumatic drugs (DMARD), including tumor necrosis factor-α (TNF-α) inhibitors, there is a significant need … Address correspondence to Dr. A. Heiligenhaus, Department of Ophthalmology and Ophtha Lab, St. Franziskus Hospital, Hohenzollernring 74, 48145 Munster, Germany. E-mail: arnd.heiligenhaus{at}uveitis-zentrum.de

Review for Disease of the Year: Epidemiology of Juvenile Idiopathic Arthritis and its Associated Uveitis: The Probable Risk Factors

Abstract Juvenile idiopathic arthritis (JIA) is the most common systemic disease associated with uveitis in childhood. The frequency of JIA-associated uveitis (JIAU) varies geographically, and between ethnicities. Uveitis risk is high in JIA associated with oligoarthritis, young age at arthritis onset and ANA positivity. Gender alters risk for the incidence of JIA and the severity of JIAU. Familial cases support the possible role of genetic influences in the pathogenesis. Arthritis typically precedes the uveitis, but uveitis may occur up to seven years following the arthritis onset. Although complications still occur, the frequency of bilateral blindness has dropped, probably by both improved screening of high-risk patients with JIA, and the increased use of early immunosuppression. However, there is still continuing persistence of JIAU into adulthood. For improvement of epidemiological knowledge of this complicated disease, large, well-defined, long-term population-based registries are needed with the application of universally agreed case definitions and outcome measures.

Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis

AimsJuvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children.MethodsMulticentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs.ResultsInactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by ⩾50% (n=19) or topical steroids reduced to ⩽2 drops/eye/day (n=40) in selected patients. Pre-existing cystoid macular oedema did not resolve under CsA treatment in any of the patients. In nine patients (11%), CsA was discontinued because of systemic hypertension (n=1), elevated creatinine levels (n=3), or other adverse effects (n=5).ConclusionsThese observations suggest that CsA has limited value as a second-line immunosuppressive drug for the treatment of JIA-associated CAU. The efficacy was better as the combination therapy in patients not responding to other immunosuppressives (eg, MTX) than the systemic monotherapy.

Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis

Aim To investigate the therapeutic value of azathioprine as monotherapy or combined with other immunosuppressive drugs for uveitis in patients with juvenile idiopathic arthritis (JIA). Methods A retrospective multicentre study including 41 children with JIA (28 (68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis. Azathioprine was used to treat uveitis that was active in patients receiving topical or systemic corticosteroids, methotrexate or other immunosuppressive drugs. The primary end point was assessment of uveitis inactivity. Secondary end points comprised dose sparing of topical steroids and systemic corticosteroids, and immunosuppression. Results At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as combination therapy. During the entire azathioprine treatment period (mean 26 months), inactivity was obtained in 16/26 patients (61.5%) with monotherapy and in 10/15 (66.7%) when combined with other immunosuppressives (p=1.0). With azathioprine, dosages of systemic immunosuppression and steroids could be reduced by ≥50% (n=12) or topical steroids reduced to ≤2 drops/eye/day in six patients. In three patients (7.3%), azathioprine was discontinued because of nausea and stomach pain. Conclusions Azathioprine may be reconsidered in the stepladder approach for the treatment of JIA-associated uveitis. The addition of azathioprine may also be beneficial for patients not responding properly to methotrexate.

A three-centre experience with adalimumab for the treatment of non-infectious uveitis

Objective The aim of this study was to assess the efficacy of adalimumab in patients with active non-infectious uveitis in three different centres. Methods In a retrospective study we identified patients from our databases who were treated with adalimumab. The composite outcome measure for efficacy included reduction of macular oedema by optic coherence tomography, visual acuity, anterior chamber cells, reduction of frequency of flares and reduction of prednisone dose during the treatment. At least one of the criteria had to be improved and none worsened to declare treatment as effective. Results 60 patients with an average age of 37.3 years (range 4–71 years) were treated with adalimumab over an average follow-up period of 87.9 weeks (range 12–222 weeks). The indication for treatment was in 41 (68.3%) patients the activity of both uveitis and systemic disease and in 19 (31.7%) patients uveitis activity only. 15 (25%) patients were treated before with etanercept and 10 (16.7%) patients with infliximab. 49 out of 60 (81.7%) patients improved, while the other 11 (18.3%) patients did not meet improvement criteria and were given additional or alternative immunosuppressive treatment. At the last follow-up, 47 (78.3%) patients were still on adalimumab treatment. 13 (21.6%) patients stopped adalimumab treatment, due to inefficacy in eight, another three patients due to side effects (liver enzyme elevation and furunculosis), one patient due to pregnancy and one patient died. Conclusions This large retrospective case series showed that adalimumab is effective in up to 80% of patients with uveitis.

Transscleral diode laser cyclophotocoagulation as primary surgical treatment for secondary glaucoma in juvenile idiopathic arthritis: high failure rate after short term follow up

Aim: To evaluate the success rates of transscleral diode cyclophotocoagulation (TD-CPC) for secondary glaucoma in patients with juvenile idiopathic arthritis (JIA) as primary surgical treatment. Methods: Retrospective chart review of 12 paediatric patients with JIA associated uveitis and secondary open angle glaucoma. Results: 21 eyes of the 12 patients had chronic anterior uveitis, 21 eyes had secondary open angle glaucoma, and 19 eyes were treated 41 times with TD-CPC. Patients underwent a mean of 2.15 treatment sessions per eye. Pretreatment intraocular pressure (IOP) was 30.2 (5.5) mm Hg before the first treatment, 30.5 (5.7) mm Hg before the second treatment, and 28.7 (6.3) mm Hg before the third treatment. Reduction of IOP 6 weeks after treatment was highest after the second and third treatments with 9.4 (8.8) and 8.7 (5.8) mm Hg, respectively and 5.2 (10.7) mm Hg after the first treatment. Qualified success (IOP ⩽21 mm Hg with glaucoma medication) was achieved at the end of follow up in six of 19 eyes (32%, follow up time 10.1 (9.3) months). Conclusion: TD-CPC as a primary surgical treatment in JIA patients, is often unsatisfactory in eyes with uveitic glaucoma.

Prevalence of uveitic secondary glaucoma and success of nonsurgical treatment in adults and children in a tertiary referral center.

Purpose: The aim of this study is to compare treatment strategies, the success of topical and systemic therapy, and the need for glaucoma surgery in children and adults with secondary uveitic glaucoma. Methods: Retrospective observational case series with 1997 consecutive new uveitis patients. Results: Overall, 176 patients (8.8%) suffered from secondary glaucoma (n = 126) or ocular hypertension (n = 50). All patients received topical therapy, and 107 (62%) patients also received systemic glaucoma therapy. Topical therapy was successful (IOP ≤ 21 mmHg) in 24% of adults and 26% of children. Surgery was required in 59% of children and in 35% of adults (p =.02). The number of surgical interventions differed per patient with 2.6 procedures in children compared to 1.6 procedures in adults (p <.001). Conclusions: Only a limited number of patients with secondary uveitic glaucoma can be sufficiently controlled with topical and systemic antiglaucomatous therapy alone. There is a significantly higher need for glaucoma operations in children.

Rituximab as a Treatment Option for Refractory Endogenous Anterior Uveitis

Background: To report on anti-CD20 antibody therapy in a patient with uveitis refractive to immunosuppression therapy. Methods: Case report with ophthalmoscopic, optical coherence tomography and fluorescein-angiographic findings. Results: A 49-year-old woman was suffering from bilateral, noninfectious chronic anterior uveitis refractive to corticosteroids and immunosuppressive drugs. Bilateral visual acuity was 20/100 due to cataract and cystoid macular edema (CME). After treatment with rituximab, vision and CME improved, and uveitis was stable until the final visit (follow-up at 12 months). Conclusion: The case report suggests that rituximab may be helpful for selected patients with chronic anterior uveitis refractive to corticosteroids and immunosuppressive medication.

Favourable outcome after cataract surgery with IOL implantation in uveitis associated with juvenile idiopathic arthritis

Purpose:  Management of uveitic cataract in patients with juvenile idiopathic arthritis (JIA) is challenging, and intraocular lens (IOL) implantation is controversial. This study investigated the outcome after minimally invasive surgery with IOL implantation.