Martin Roesel

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.

Elevated laser flare values correlate with complicated course of anterior uveitis in patients with juvenile idiopathic arthritis.

Purpose:  To evaluate the prognostic value of anterior chamber (AC) laser flare (LF) in uveitis associated with juvenile idiopathic arthritis (JIA).

Comparison between intravitreal and orbital floor triamcinolone acetonide after phacoemulsification in patients with endogenous uveitis.

PURPOSE To compare the effect of intravitreal and orbital floor triamcinolone acetonide (TA) on macular edema, visual outcome, and course of postoperative inflammation after cataract surgery in uveitis patients. DESIGN Prospective, randomized clinical trial. METHODS Monocenter study (40 patients) with chronic endogenous uveitis who underwent phacoemulsification with intraocular lens implantation with either 4 mg intravitreal TA (n = 20) or 40 mg orbital floor TA (n = 20). The primary outcome was influence on cystoid macular edema (CME). Secondary outcome measures were best-corrected visual acuity (BCVA), anterior chamber cell grade, laser flare photometry, giant cell deposition, posterior capsule opacification (PCO), and intraocular pressure. RESULTS Mean central foveal thickness decreased in the intravitreal TA group and increased in the orbital floor TA group (P < .001 at one and three months). CME improved in 50% of patients after intravitreal TA, whereas it was unchanged after orbital floor TA (difference between the groups at three months, P = .049). Mean BCVA (logarithm of the minimal angle of resolution) improved postoperatively (P < .001) from 0.76 and 0.74 to 0.22 and 0.23 in the intravitreal TA and orbital floor TA group, respectively. Anterior chamber cell count at one month was lower in the intravitreal TA than in the orbital floor TA group (P = .02). Laser flare photometry values and giant cell numbers were slightly higher after orbital floor TA than after intravitreal TA. The groups did not differ with respect to PCO rate and ocular hypertension. CONCLUSIONS The CME improvement and anti-inflammatory effect after intravitreal TA was better than after orbital floor TA injection in cataract surgery in uveitis patients.

Intravitreal and Orbital Floor Triamcinolone Acetonide Injections in Noninfectious Uveitis: A Comparative Study

Purpose: To compare the effect of orbital floor (OFTA) or intravitreal (IVTA) administration of triamcinolone acetonide on visual acuity and chronic cystoid macular edema (CME) in patients with uveitis. Methods: Retrospective study of patients suffering from chronic noninfectious uveitis in whom CME (n = 97) did not respond to systemic corticosteroids and/or immunosuppression combined with acetazolamide. Patients received a single injection of either IVTA (n = 48, group 1) or OFTA (n = 49, group 2). Best-corrected visual acuity, macular edema (fluorescein angiography), uveitis activity, ocular hypertension, and cataract formation were analyzed over the course of 1 year. Results: Improvement in visual acuity (≥2 lines, LogMAR) was noted in 50% (IVTA) and 34% (OFTA) after 3 months (p = 0.23), and in 18% (IVTA) and 20% (OFTA) after 12 months. CME improved in 100% (IVTA) and 76% (OFTA) of the eyes within the first month postoperatively (p = 0.36). Macular edema was reduced in 100% (group 1) and 20% (group 2) after 3 months (p < 0.01). At 1 year, cataract progression was noted in 68% (IVTA) and 27% (OFTA) (p < 0.01). Increased intraocular pressure (>21 mm Hg) was detected in 21% (IVTA) and 0% (OFTA) at 4 weeks (p < 0.01) after injection. Conclusion: Uveitic CME and visual acuity not responding to systemic immunosuppression and acetazolamide may improve after an IVTA and OFTA injection. The effect is mostly transient. While the IVTA injections were more effective for improving CME, ocular hypertension and cataracts developed more often.

Comparison of retinal thickness and fundus-related microperimetry with visual acuity in uveitic macular oedema

Purpose:  Macular oedema is a common complication and vision‐limiting factor in uveitis. The aim of this study was to compare retinal thickness as measured by optical coherence tomography and photoreceptor function as measured by fundus‐related microperimetry with respect to their correlation with visual acuity.

Elevated intraocular pressure in uveitis associated with juvenile idiopathic arthritis-associated uveitis, often detected after achieving inactivity

In patients with juvenile idiopathic arthritis (JIA)-associated anterior uveitis, secondary open angle glaucoma and ocular hypertension frequently develop during the clinical course of disease.1 Appropriate topical antiglaucomatous treatment should be started immediately after diagnosis in order to prevent the occurrence of irreversible optic neuropathy. The main underlying causes of elevated intraocular pressure (IOP) include congestion of the trabecular meshwork due to cells and debris and morphological changes in the outflow pathway.2 As screening for glaucoma in these patients can be challenging due to their young age, it is helpful to know when elevated IOP first occurred with respect to disease activity. We retrospectively analysed the time of occurrence of elevated IOP in 30 JIA patients during the course of uveitis. Groups were defined as (1) during inactivity of inflammation (≤0.5 anterior chamber cells according to the Standardization of Uveitis Nomenclature classification),3 (2) during acute inflammation or (3) after intraocular surgery. IOP was measured by Goldmann applanation tonometry. The first instance of elevated IOP was documented if IOP was ≥24 mm Hg at two consecutive measurements. All …

Smoking complicates the course of non-infectious uveitis

BackgroundData concerning the association of smoking and uveitis are limited. The aim of this study was to evaluate the effect of tobacco smoking on uveitis activity and complications of noninfections uveitis and the need for immunosuppressive therapy.MethodsWe conducted an observational cross-sectional study in 350 patients with noninfectious uveitis. All patients completed a questionnaire concerning smoking habits. Primary outcome measure was uveitis activity in smokers as compared to nonsmokers; secondary outcome measures were need for immunosuppression and uveitis complications.ResultsIn all 115 patients (32.9%) were smokers. Smokers had an increased risk for active uveitis (OR 1.8; 95% CI, 1.2–2.9; p = 0.007). Smokers with anterior uveitis had anterior chamber cells more often than nonsmokers (p = 0.008) and required significantly more topical steroid eyedrops (p = 0.002). Uveitis developed at a younger age in smokers than in nonsmokers (p = 0.027). The number of smokers who needed any second-line immunosuppression (p = 0.642) and the number of immunosuppressive agents required (p = 0.794) did not differ from that for nonsmokers. The number of pack-years significantly increased the risk of macular edema (p = 0.020) und cataract (p = 0.022).ConclusionsSmoking is associated with uveitis activity, leading to increased need for steroid eyedrops and increased incidence of cataract and macular edema. The results highlight the need to encourage uveitis patients to stop or at least to reduce their smoking.

Oral voclosporin: novel calcineurin inhibitor for treatment of noninfectious uveitis.

Voclosporin, a novel immunomodulatory drug inhibiting the calcineurin enzyme, was developed to prevent organ graft rejection and to treat autoimmune diseases. The chemical structure of voclosporin is similar to that of cyclosporine A, with a difference in one amino acid, leading to superior calcineurin inhibition and less variability in plasma concentration. Compared with placebo, voclosporin may significantly reduce inflammation and prevent recurrences of inflammation in patients with noninfectious uveitis. Future studies have to show if these advantages are accompanied by greater clinical efficacy and fewer side effects compared with the classic calcineurin inhibitors.

H1N1 and Uveal Effusion Syndrome

Dear Editor: The course of the new H1N1 influenza virus infection in the pediatric population is usually mild and commonly presents with fever and cough. However, in November 2009 during the H1N1 influenza pandemic, we observed a child with proven H1N1 influenza and concomitant severe visual loss due to uveal effusion syndrome. Herein, we report on an 11-year-old girl who presented 1 day after onset of a painful red left eye associated with severe visual loss. Additionally, she suffered from fever, cough, malaise, and fatigue. The flu-like symptoms began 2 days before the eye complaints. Her past medical history was otherwise uneventful. Visual acuity was counting fingers in the affected left eye and 20/20 in the right eye. The right eye examination was unremarkable and left eye showed diffuse conjunctival congestion, tenderness, and pain associated with ocular movements. Anterior chamber was quiet and was significantly shallow. On ophthalmoscopy, we found vitreous cells and swelling of the whole posterior segment, indicating choroidal and subretinal exudation. Ultrasonographic B-scan demonstrated thickening of the retinal/choroidal complex as compared to the unaffected eye. Fluorescein angiography showed early leakage at the entire posterior pole and circumscribed hypofluorescence, indicating subretinal detachment (Fig 1; available at http://aaojournal.org). Optical coherence tomography demonstrated massive retinal thickening in the macular area. Refraction was altered from preexisting slight hyperopia to –6.5 diopters myopia. We diagnosed uveal effusion syndrome with myopic shift in the left eye. Treatment was instituted immediately, consisting of oral prednisolone (2 mg per kg body weight initially), doxycycline 200 mg daily, and scopolamine eyedrops twice daily. The diagnostic work-up included a complete blood count with differential, creatinine, liver enzymes, angiotensin-converting enzyme, antinuclear antibody, antineutrophil cytoplasmic antibody, Lyme titers and Western blot, fluorescent treponemal antibody absorption, polymerase chain reaction (PCR) for H1N1 RNA, and chest X-ray. The PCR for H1N1 RNA was positive, whereas all other work-up was unremarkable. At the follow-up examination 9 days later, the girl no longer had fever, and the cough had largely cleared up. The affected left eye had no conjunctival injection and was not tender on palpation anymore. Visual acuity had improved to 12/20. Objective refraction had changed to 1.25 spherical diopters, and the anterior eye chamber was as deep as in the contralateral eye. Funduscopy did not reveal any persistent exudation or swelling at the posterior pole or outer retina/ choroid and the ultrasonographic B-scan examination did not show any pathologic findings. Optical coherence tomography still demonstrated a slight subretinal fluid accumulation and an irregular tissue architecture within the outer retinal layers (Fig 2; available at http://aaojournal.org). Doxycycline and scopolamine were withdrawn and oral prednisolone was tapered off rapidly. According to our knowledge, this is the first report on the coincidence of H1N1 influenza and uveal effusion syndrome. However, the underlying pathophysiologic mechanism remains speculative and includes direct viral invasion in the eye and intraocular bystander immune reaction and breakdown of the blood-retinal barrier. Interestingly, the first autopsy case of H1N1 influenza demonstrated that the serum concentrations of various cytokines/chemokines (interleukin [IL]-2R, IL-6, IL-8, interferon [IFN]-alpha, monocyte chemotactic protein-1) were elevated. During such a systemic immune activation period, the blood retinal barrier may break down. Yoser et al described influenza associated with retinitis and choroiditis. Adverse reactions after influenza vaccination presenting with systemic vasculitis have also been observed. However, the coincidence of systemic H1N1 infection and uveitis suggests a causative etiology. Ophthalmologists must be aware of possible concomitant ocular inflammation in patients with H1N1 influenza.