Matthias D. Becker

Uveitis Subtypes in a German Interdisciplinary Uveitis Center—Analysis of 1916 Patients

Objective Studies on the epidemiology of uveitis are rare and cohorts are small. We analyzed the frequencies of classified forms of uveitis in all patients at our center. Methods We studied 1916 consecutive patients with inflammatory eye disease. Data were analyzed regarding associated systemic disease, infection, ocular syndromes, anatomic localization, age, and sex. Results In 59.1% of patients, a classified form of uveitis was observed: associated systemic diseases in 43.7%, the most frequent ones sarcoidosis (17.4%) and ankylosing spondylitis (16.8%); ocular syndromes in 34.3%, the most frequent HLA-B27-positive anterior uveitis (AU; 35.1%) and Fuchs uveitis syndrome (FUS; 34.3%); and infections in 22.4%, the most frequent herpetic infections (46.1%) and toxoplasmosis (31.5%). We found AU in 45.4% of patients (15.4% HLA-B27-positive AU and 11.3% FUS), intermediate uveitis in 22.9% (unclassified 53.7% and multiple sclerosis 10.3%), and posterior uveitis in 13.5% (24.7% toxoplasmosis). Panuveitis was diagnosed in 6.2% of cases (Behçet’s disease 12.6%; sarcoidosis 10.9%). The remaining 12.0% of cases showed extrauveal manifestations (scleritis, episcleritis, keratitis, optic neuritis, myositis, and orbital inflammation). Conclusion We describe the largest cohort to date of consecutive patients from a specialized uveitis center. The high frequency of classified disease, nearly 60% in our clinic, shows the usefulness of an interdisciplinary approach, oriented on anatomic presentation.

Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor

Abstract · Background: Ocular diseases caused by neovascularization are among the leading causes of blindness. No specific pharmacological treatment is available. Among potential drugs, thalidomide deserves special interest since a wide body of clinical experience exists. However, its antiangiogenic effect is controversial. We therefore investigated the effect of thalidomide on corneal angiogenesis induced by vascular endothelial growth factor (VEGF), which has a special role among angiogenic growth factors. · Methods: Corneal neovascularization was induced in NZW rabbits by an intrastromal pellet loaded with 500 or 750 ng VEGF. Animals received two daily feedings of 200 mg/kg thalidomide. · Results: Significant inhibition of corneal angiogenesis (P<0.0001) was caused by the teratogenic dose of thalidomide after the 5th day of treatment and persisted for more than 16 days. No obvious side effects were recorded. · Conclusions: Thalidomide has a significant antiangiogenic effect against VEGF-induced neovasclar growth. Together with earlier findings this observation indicates that the drug inhibits two angiogenic pathways which are mediated through integrin adhesion molecules.

Interferon as a treatment for uveitis associated with multiple sclerosis

Aim: In addition to optic neuritis (ON), multiple sclerosis (MS) may also involve the eye with a typically bilateral intermediate uveitis. The aim of this pilot study was to evaluate the efficacy of type I interferons (IFN) for the treatment of MS associated uveitis. Methods: In this non-randomised, retrospective observational case series 13 patients (eight female, five male) with proved MS and associated uveitis from five uveitis centres who were treated with interferon β1a were included. Visual acuity (VA), cell count in the aqueous humour and vitreous, as well as the presence of cystoid macula oedema (CMO) were observed. Results: All except one patient had a bilateral form of intermediate uveitis (total of 24 eyes). Seven patients had documented CMO before IFN treatment (n = 13 eyes). Median duration of treatment was 24.6 months (range 7.9–78.7). VA improved in 17 eyes (comparing VA before therapy and at last follow up); while 10 eyes (36%) improved ⩾3 Snellen lines. Aqueous cell count improved by 1.2 (SD 1.1) grades in all eyes. Vitreous cell count improved by 1.7 (1.4) in all eyes. Only two patients still had minimal CMO on last follow up angiographically. CMO resolved after or during IFN treatment in nine eyes. Conclusions: IFN has been shown to have beneficial effects in patients with MS and/or ON. As shown in the models of experimental allergic encephalomyelitis (EAE) and uveitis, the neurological and ophthalmological manifestations seem to share similar pathogenic mechanisms. Treatment of MS associated uveitis with IFN appears to have beneficial effects on VA, intraocular inflammation activity, and the presence of CMO.

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.

QuantiFERON TB-Gold—A New Test Strengthening Long-Suspected Tuberculous Involvement in Serpiginous-like Choroiditis

PURPOSE To obtain a diagnosis of tuberculosis in patients with a specific subset of uveitis, serpiginous-like choroiditis. This subset has been suspicious for tuberculous etiology in single case reports and old textbooks. DESIGN Retrospective evaluation of a diagnostic test in a specific uveitis cohort. METHODS QuantiFERON is an approved, antigen-specific test that utilizes synthetic peptides representing Mycobacterium tuberculosis proteins. After incubation, interferon gamma secreted by T lymphocytes in response to these antigens is measured. We used the test in 21 of 26 patients identified from our database with serpiginous-like choroiditis. Rates of QuantiFERON positivity were compared to a group of healthy hospital employees (n = 208), another group of healthy hospital workers after tuberculosis contact (n = 117), and a group of randomly tested patients with other uveitis forms (n = 45). RESULTS Eleven of 21 serpiginous-like choroiditis patients (52%) were tested positive. The rate of QuantiFERON positivity in the healthy control groups was 8.7% and 0.9%, and 13% in the other uveitis subsets. Four of the QuantiFERON-positive serpiginous-like choroiditis patients were treated with standard anti-tuberculostatic therapy; three finished the course and improved. Seven patients are either stable without therapy (n = 4) or on low-dose prednisone (n = 3). CONCLUSIONS QuantiFERON testing revealed a high number of positive patients, which indicates a tuberculous etiology in this uveitis subset. Whether bacterial activity or secondary immunologic processes are causative remains a matter of speculation.

Static fundus perimetry using the scanning laser ophthalmoscope with an automated threshold strategy

Abstract• Purpose: The purpose of this study was to develop software that allows the performance of routine static threshold perimetry using the scanning laser ophthalmoscope (SLO) and the comparison of the results with conventional computerized cupola perimetry. The original software does not allow performance of static threshold perimetry within a reasonable examination time. • Methods: Static perimetry was performed in random order on 50 healthy eyes using our SLO staircase threshold perimetry technique and the Octopus 500 (program 38). We compared the relative sensitivities for each of 25 corresponding visual field locations. • Results: Mean sensitivity in the SLO perimetry amounted to 32.7 dB (range 25–37 dB) while it was 28.7 dB in the Octopus. For all test locations the SLO showed higher dB values on average. The mean difference between both methods was 3.7±0.8 dB (range 1.4–5.8 dB) when the test locations at the blind spot were excluded (linear regression between the two methods: r=0.843, P<0.0001). The mean time interval between two stimulus presentations was 2.5 s with the SLO perimetry. • Conclusion: With the Heidelberg software, automated static threshold perimetry using the SLO is possible within reasonably short examination times. The mean time interval between two test point presentations is about one tenth of that necessary using the original Rodenstock software. There is a systematic difference between SLO and Octopus fields of about 4 dB which was not very much influenced by the stimulus locations.

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.

Management of sight-threatening uveitis : New therapeutic options

Over the past 2 decades therapy for the treatment of intraocular inflammation (uveitis) has developed into a highly differentiated approach with an increasing number of drug options. This paper primarily summarises literature from the past 5 years (2000 to May 2004), gives an update on systemic immunosuppressive therapy for non-infectious uveitis and speculates about new developments that could become relevant in the near future for the treatment of uveitis patients. The spectrum of immunosuppressive drugs has been notably expanded by tumor necrosis factor inhibitors, but with some limitations to uveitis. Behçet’s disease is an example of uveitis where a multisystem disorder can affect the eye very severely. This clinical example has been used to investigate the utility of many different types of immunosuppressive therapies and the clinical approach is extensively discussed in this review. An accompanying table summarises the proposed mode of action, standard dosage, common adverse effects, as well as estimated cost of current treatment options.

Interferon versus Methotrexate in Intermediate Uveitis With Macular Edema: Results of a Randomized Controlled Clinical Trial

PURPOSE To compare interferon (IFN) beta with methotrexate (MTX) in the treatment of intermediate uveitis with macular edema. DESIGN Monocentric, prospective, randomized, controlled clinical trial. METHODS SETTING Specialized uveitis center at the University of Heidelberg. PATIENT OR STUDY POPULATION: Patients with either primary intermediate uveitis or uveitis associated with multiple sclerosis. MAIN INCLUSION CRITERIA: Visual acuity of 20/30 or worse (0.2 logarithm of the minimal angle of resolution) and macular edema of more than 250 μm (central 1-mm in optical coherence tomography; Stratus). Randomization into either IFN beta 44 μg subcutaneously 3 times weekly or 20 mg MTX subcutaneously once weekly. MAIN OUTCOME MEASURES At 3 months, the primary outcome parameter of mean change in visual acuity was evaluated and efficacy was determined. Secondary parameters were macular edema by optical coherence tomography, inflammatory activity, and retinal sensitivity by microperimetry (MP-1; Nidek). In case of treatment failure, switching to the other treatment arm was possible. RESULTS Nineteen patients were included. Ten were randomized to MTX, and 9 were randomized to IFN beta. At 3 months, visual acuity improved a mean 0.31 logarithm of the minimal angle of resolution (range, -0.02 to -0.96, 15.6 letters on the Early Treatment Diabetic Retinopathy Study chart) in the IFN beta group versus a mean 0.09 logarithm of the minimal angle of resolution (range, 0.12 to -0.38, 4.7 letters) in the MTX arm (P = .0435, Mann-Whitney U test). Macular thickness decreased by a mean of 206 μm (range, -41 to -416 μm) in the IFN arm, but increased by 47 μm (range, 108 to -28 μm) in the MTX group (P < .0001). CONCLUSIONS Although the sample size is small, results of the trial support superiority of IFN beta over MTX in the treatment of macular edema in the setting of intermediate uveitis.

Incidence of presumed endophthalmitis after intravitreal injection performed in the operating room: a retrospective multicenter study.

Purpose: To evaluate the incidence of presumed endophthalmitis (EO) after intravitreal injection (IVI) of anti–vascular endothelial growth factor agents performed in the operating room. Methods: Retrospective study at 2 Swiss eye hospitals between 2004 and 2012. Hospital records were used to identify patients treated with an IVI of an anti–vascular endothelial growth factor agent between 2004 and 2012 and those treated for EO, defined as any intraocular inflammation treated with intravitreal antibiotics. All IVIs were performed using standard sterile technique in a Swiss Class 1 operating room. No patient received preinjection topical antibiotics. Postinjection topical antibiotics were used only in one hospital. Results: A total of 40,011 IVIs were performed at the 2 centers during the study period. Of the IVIs, ranibizumab was injected in 36,398 (91%), bevacizumab in 3,518 (9%), aflibercept in 89 (0.2%), and pegaptanib in 6 (<0.1%). Three cases of post-IVI presumed EO occurred, yielding a combined incidence of 0.0075% per injection (95% confidence interval: 0.0026–0.0220%) or 1 case per 13,337 IVIs. Two of the three cases of EO occurred in patients using post-IVI antibiotics. All three cases followed ranibizumab injection and were culture negative by anterior chamber tap or vitreous biopsy. Conclusion: The risk of EO after IVI performed under the sterile conditions of the operating room was very low.