N. Stuebiger

Mycophenolate mofetil in the treatment of uveitis in children

Background: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that effectively controls the intraocular inflammation in adults. Purpose: To assess the efficacy of MMF in uveitis in children and to analyse the possible side effects. Participants and methods: A retrospective analysis was carried out on 17 children (32 eyes) with intraocular inflammation treated with MMF and followed up at the University Eye Hospital Tuebingen, Tuebingen, Germany, between 2000 and 2005. All children had chronic non-infectious uveitis and received MMF for at least 6 months. All patients were given steroids or other immunosuppressive agents before initiating treatment with MMF. Results: 17 children (10 boys and 7 girls) with a mean age of 8 (range 2–13) years at the onset of uveitis were examined. The average duration of follow-up after initiation of MMF was 3 (range 2–5) years. A steroid-sparing effect was achieved in 88% of the patients. The oral prednisolone was successfully discontinued in 41% children and reduced to a daily dose of ⩽5 mg in 47% of the children. 24% of the patients remained relapse-free during the treatment, but a reduction in the relapse rate was observed in all other patients except one. Visual acuity was increased or maintained in 13 children (76%). Mild side effects (headache, rash, gastrointestinal discomfort) occurred in 7 patients (41%) and were the cause of discontinuation of MMF in 1 patient. Conclusion: The results of our study are encouraging and suggest that MMF is an effective agent also in the treatment for uveitis in children, with marked steroid-sparing potential and an acceptable side effect profile.

Interferon alfa-2a: a new treatment option for long lasting refractory cystoid macular edema in uveitis? A pilot study.

Purpose: To perform a prospective pilot study to evaluate interferon alfa-2a (IFN alfa-2a) for the treatment of refractory cystoid macular edema (CME) in endogenous uveitis. Methods: IFN alfa-2a was administered at an initial dose of 3 or 6 million IU (depending on body weight) per day subcutaneously. Afterwards IFN alfa-2a was tapered slowly over 6 months and finally discontinued. If CME relapsed IFN alfa-2a was reinstituted and tapered slowly again to evaluate the lowest maintenance dose to keep remission. Results: A total of 15 eyes of 8 patients with refractory CME due to intermediate or posterior uveitis were included. Ineffective pretreatment consisted of systemic steroids and acetazolamide (all patients) and at least one additional immunosuppressant (6 patients). Six of 8 patients (11 eyes) responded well to IFN alfa-2a and CME resolved completely during 6 months treatment. One patient was lost to follow-up after IFN alfa-2a was stopped. In 1 patient (1 eye) even 19 months after cessation of IFN alfa-2a no recurrence of CME occurred. In 4 patients (8 eyes) IFN alfa-2a had to be reinstituted because CME relapsed. All 4 patients responded again. During a mean follow-up period of 16.4 months since restart of therapy we succeeded in all 4 patients to taper IFN alfa-2a to maintenance doses between 1.5 million IU every second and every sixth day without a recurrence of CME in any of the 8 eyes. Conclusion: IFN alfa-2a can be a treatment option for patients with otherwise treatment resistant uveitic CME.

Weak transient response of chronic uveitic macular edema to intravitreal bevacizumab (Avastin)

Dear Editor: We want to report on our experiences with bevacizumab (Avastin; Genentech, Inc., San Francisco, CA, USA) in chronic cystoid macular edema (CME), which is the most common cause of irreversible visual loss in chronic uveitis [1, 2]. Anti-VEGF treatment has been reported to be a powerful treatment modality in reducing macular edema of different origin [3, 4]. Additionally, there is a rationale that VEGF-antagonists may also have anti-inflammatory capabilities. VEGF can induce chemotaxis and migration of monocytes [5]. Other pro-inflammatory effects are the induction of Band Tlymphocytes [6, 7]. Therefore, VEGF-inhibitors have also been considered to be effective in inflammatory autoimmune disorders such as rheumatoid arthritis. Intraocular administration of triamcinolone acetonide frequently causes a harmful increase in intraocular pressure—especially in uveitis [8]. Limited efficacy of other topical agents in otherwise systemically controlled inflammation led us to think about the use of bevacizumab in chronic CME. Six patients with chronic macular edema due to uveitis were treated with an intravitreal injection of bevacizumab 1.25 mg in 0.05 ml. Extensive evaluation had previously been performed to determine the cause of the uveitis. Offlabel bevacizumab therapy was only considered if inflammatory activity was judged completely quiet for more than 6 months, steroid-induced increase in IOP was in the history, or no response was seen to other immunosuppressive agents. All patients underwent Snellen chart visual acuity testing, ophthalmoscopic examination, flare measurement (FC-2000, Kowa Co. Ltd, Tokyo, Japan) and ocular coherence tomography at baseline, 1-week and 4-week intervals. The subjects opted for the injection, signing for informed consent after being given detailed information about the limited experience and the “off-label” nature of the treatment in compliance with IRB approval. Two patients showed a marked, but temporary decrease in the height of the edema and experienced transient improvement of visual acuity at the 1-week examination. One month after the injection, none of the patients had either significant improvement in visual acuity or decrease in central retinal thickness (CRT, Table 1). Apart from the rupture of a retinal cyst, no other adverse events were observed in any patient up to 12 months after the injection. Non-parametric Fisher–Pitman test (small sample procedure) revealed no significant difference in flare (p=0.369). CRT after 4 weeks did not differ significantly from the baseline (Wilcoxon matched pairs test, p=0.599). Thus, in this group of severe, chronic uveitis-associated CME, resistant to established therapies, bevacizumab has shown only minor and transient effects, but good tolerability. The full-length antibody was well-tolerated in the vitreous, in spite of present autoimmune disorders. The disrupted boundary of an intraretinal cyst could be explained by a coincidental and spontaneous event. However, with respect to pigment epithelium tears seen after anti-VEGF treatment [9] mechanical stress has also been thought to occur in desiccating CME. Graefe’s Arch Clin Exp Ophthalmol (2007) 245:917–918 DOI 10.1007/s00417-006-0512-2

Interferon-alpha-associated presumed ocular sarcoidosis

BackgroundInterferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha.MethodsWe report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin.ResultsIn all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations.ConclusionsUveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.

Mycophenolate sodium for immunosuppressive treatment in uveitis.

Purpose: To assess the efficacy and tolerability of mycophenolate sodium (MPS) in patients with uveitis. Methods: Retrospective analysis including uveitis patients treated with MPS (Myfortic®) for at least 3 months duration. MPS was administered in a dose of 720 mg twice daily. Results: We analyzed 35 patients (65 affected eyes) with anterior (n = 5), intermediate (n = 23), posterior (n = 6), and panuveitis (n = 1). Previous treatment consisted of systemic corticosteroids in all patients and at least one immunomodulating agent in 15 patients. Mean duration of MPS therapy was calculated as 9.6 months (3–31 months). MPS was able to control intraocular inflammation without relapse in 30 patients (85.7%). Stabilization or improvement of visual acuity was achieved in 60 eyes (92.3%). Tolerability of MPS was good or moderate in 34 patients (97.1%). Conclusions: MPS was demonstrated as an effective and well-tolerated immunosuppressive drug for different forms of uveitis.

An Unusual Case of Central Serous Chorioretinopathy in a Patient with Acute Retinal Necrosis

Purpose: In acute retinal necrosis, which is caused by herpes virus, urgent treatment is essential. Design and Methods: Here we present a 47years old male patient, who developed an acute retinal necrosis in his left eye. Therapy was initiated with systemic aciclovir and corticosteroids. Results: During the course of disease our patient achieved improvement of acute retinal necrosis but he developed central serous chorioretinopathy. Conclusions: The development of central serous chorioretinopathy in our patient was most probably due to the systemic corticosteroids he received. Especially in patients with an intraocular inflammation this diagnosis may lead to severe differential diagnostic problems.