Interferon-alpha as an effective treatment for noninfectious posterior uveitis and panuveitis

PURPOSE: Several studies have shown the capacity of interferon-alpha (IFN-alpha) to control ocular Beh?et disease. The authors aimed to determine whether IFN-alpha was effective in treating patients with severe, refractory sight-threatening intraocular inflammation (uveitis) from a wider range of causes, including Beh?et disease. DESIGN: Prospective, interventional case series. METHODS: Twelve patients with sight-threatening uveitis that failed to respond to one or more immunosuppressive regimens were enrolled to this study. Recombinant human IFN-alpha-2b was administered subcutaneously daily, and the dose was adjusted according to the clinical response. Main outcome measures were visual acuity, clinical activity of uveitis (including binocular indirect ophthalmoscopy [BIO] score and presence or absence of macular edema), and adverse effects of the treatment. RESULTS: The mean observation period was 11 months (range, one to 29 months). A positive clinical response was observed in 83% of patients. Median visual acuity improved from 0.54 to 0.2 (logarithm of the minimum angle of resolution units; P < .001) and median BIO score decreased from 1.0 to 0.5 (P < .05) within one month of treatment. Macular edema, if present, resolved in all patients within days of treatment. The main adverse events were tiredness, lymphopenia, flu-like symptoms, and transient increase of liver enzymes. Weight loss occurred in four patients. Four patients experienced depression, one of them attempting suicide. Three patients experienced typical features of IFN-alpha-associated retinopathy, which resolved on reducing the dose. CONCLUSIONS: IFN-alpha seems to have significant potential in treatment of severe, sight-threatening refractory uveitis from a variety of causes. A range of adverse events, including IFN-alpha-associated retinopathy, may occur and could limit the use of this immunomodulatory drug.     

Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis

Background We evaluated the outcomes of patients with different forms of chronic uveitis treated with mycophenolate mofetil (MMF) as an immunomodulatory and steroid-sparing agent. The multi-system side effects that arise after long-term treatment with corticosteroids and other immunosuppressants prompted us to use MMF. MMF is a selective inhibitor of inosine monophosphate dehydrogenase, thus blocking purine synthesis via the de novo pathway preferentially used by T and B lymphocytes.Methods Between 1998 and 2003, 106 patients were treated for uveitis (anterior n=26, intermediate n=51, posterior n=23, panuveitis n=6) with MMF at a dose of 1g twice daily. Treatment duration was at least 6 months (n=10), in most cases greater than 12 months (n=77) and in 25 cases between 24 months and 41 months, when the present retrospective evaluation was undertaken. Patient charts were analysed according to a standardized evaluation protocol.Results In 95 patients MMF was combined with prednisolone at a dosage of 2.5–10 mg per day. In 8 patients MMF was used as a monotherapy, and in 3 cases one further systemic immunosuppressant was required. The number of recurrences during MMF treatment was none or one in 92 patients, two in 6 cases and three or more in 8 patients. In none of the patients had MMF been stopped at the time of data analysis. The most frequently observed side effects were gastrointestinal upset (15%), followed by headache (9.3%), fatigue (5.7%), eczema (5%), and hair loss (3.5%). Other side effects were sporadic. Most of these phenomena were transitory. Forty-two patients experienced no side effects at all. In 4 patients MMF was judged ineffective due to failure to reduce the number of recurrences of severe inflammation compared with the previous therapeutic regime, or indeed occurrence of persistent macular oedema.Conclusions Our results show that MMF is an effective immunosuppressant in patients with uveitis. We provide evidence that MMF controls the disease in the majority of patients with an acceptable profile of side effects.     

Lens-induced uveitis: an update

Graefe's Archive for Clinical and Experimental Ophthalmology - Ocular inflammation resulting from a lens pathology is rare in the absence of a cataract or lens trauma because of the lens’...     

Tuberculous uveitis after treatment with etanercept

Background Etanercept is a tumor necrosis factor (TNF) inhibitor that has been licensed in the United States for the treatment of adult and juvenile rheumatoid arthritis as well as psoriatic arthritis. Reactivation of tuberculosis is a complication of its use. We report the first case of tuberculous uveitis due to etanercept. Methods We performed a clinical chart review. Case A 58-year-old Caucasian woman was referred to our hospital for chronic unilateral granulomatous panuveitis of the right eye (RE). She was on etanercept and methotrexate for rheumatoid arthritis. Since the patient was immunosuppressed with etanercept and since the uveitis was granulomatous we considered tuberculosis as a possible etiology. An aqueous humor tap was performed and sent for polymerase chain reaction analyses of Herpes simplex, Herpes zoster, and Mycobacterium tuberculosis (MT). This last test was positive. Another aqueous humor sample was taken and sent for microscopic examination of sputum for acid-fast bacilli and culture, both of which were positive for MT. A diagnosis of tuberculous uveitis was established; the patient was treated with rifampin, isoniazid pyrazinamide, and ethambutol and etanercept was stopped. Four months later there were no cells in the anterior chamber and the vitreous was clear. Discussion To our knowledge this is the first reported case of tuberculous uveitis following treatment with etanercept. This etiology has to be considered in patients taking this drug who present with intraocular inflammation. The authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review our data upon request.     

Cyclosporin treatment in uveitis

With Cyclosporin, a recently developed immunosuppressant drug, the authors treated eight patients with noninfectious chronic uveitis: intermediate uveitis (4), Behcet's disease (2), chorioiditis (1), and anterior uveitis (1). Therapy had to be discontinued in six patients who responded poorly or manifested severe side effects. In four cases the Cyclosporin concentration in the aqueous humor was determined. In spite of a concentration of about 900 ng/ml there was a deterioration in two cases with intermediate uveitis and Behcet's disease. Only one of the eight patients with intermediate uveitis responded well without any recurrence.     

Medical treatment of macular edema in patients with uveitis

Purpose: To determine the efficacy of medical treatment of cystoid macular edema (CME) in patients with uveitis. Methods: Retrospective study of 40 patients (57 eyes) with uveitis and CME. Inclusion criteria were presence of CME with minimal and no macular pathology, or vascular disease which could account for CME. Patients who had undergone intraocular surgery or had visual aucity (VA) of ≥20/40 were excluded. The diagnosis of CME was based on clinical and/or angiographic findings. Three treatment groups were defined: (1) transseptal injection of steroids (n=13 eyes); (2) systemic non steroidal anti-inflammatory drugs (NSAIDs) (n=11 eyes); both 1 and 2 (n=33 eyes). Results: Overall, 79% of eyes improved 3 or more lines of Snellen VA after treatment: 51% improved 4 or more lines. The average number of lines improved was 3.8 for eyes treated with transseptal injections of steroids, 2.9 for eyes treated with NSAIDs, and 4 for eyes treated with both. For all 3 treatment groups between 60–70% of eyes improving 2 or more lines reached best VA only after a minimum of 6 months of follow up. Conclusions: CME, a vision threatening complication of uveitis, respond fairly well to medical treatment; however, the best VA is achieved after several months. The improvement in VA did not differ markedly among the three treatment groups. This revised version was published online in July 2006 with corrections to the Cover Date.     

Tropicamide (1%): an effective cycloplegic agent for myopic children.

PURPOSE. To evaluate the cycloplegic effect of 1% tropicamide in myopic children and to determine whether its efficacy is associated with age, gender, iris color, ethnicity, magnitude of the refractive error, or latent error. METHODS. Four hundred sixty-nine children enrolled in the Correction of Myopia Evaluation Trial (COMET; a multicenter, randomized, double-masked clinical trial evaluating the rate of progression of juvenile-onset myopia in children wearing progressive-addition versus single-vision lenses) were given 1 drop of proparacaine in each eye followed 1 minute later by 1 drop of 1% tropicamide and then a second drop of 1% tropicamide 4 to 6 minutes later. Five accommodative responses to 20/100 letters located at 4 m and 33 cm were obtained in each eye with an autorefractor, 20 minutes after the second drop. Residual accommodation was calculated as the difference between the mean spherical equivalent responses obtained at the two distances. An examiner graded iris color, and ethnicity was reported by the children's parents or guardians. RESULTS. The mean residual accommodation was small: 0.38 +/- 0.41 diopters (D) in the right eye and 0.30 +/- 0.41 D in the left eye. Small but statistically significant differences in residual accommodation were associated with ethnicity, but not with any of the other factors. CONCLUSIONS. Tropicamide (1%) is an effective cycloplegic agent in myopic children.     

Rifabutin-associated with bilateral uveitis in an HIV negative patient

BACKGROUND: Rifabutin-associated uveitis has often been described in patients with HIV. We present the case of a bilateral non-granulomatous uveitis in an HIV negative patient on rifabutin therapy. HISTORY AND SIGNS: A 79-year-old man presented with acute pain and decreased vision in the left eye. He had a 2-months history of Mycobacterium avium pneumonia and was treated with rifabutin, clarithromycin and ethambutol since then. At presentation, the visual acuity was hand movement. On biomicroscopy, the anterior chamber showed inflammatory sings such as hypopyon and early posterior synechiae. Ultrasound revealed no vitreal infiltration. The fellow eye was initially without any pathology. Serological testing and blood cultures were negative. THERAPY AND OUTCOME: The next day, the fellow right eye was also affected showing signs of anterior and posterior uveitis. Following intensive topical steroidal therapy, clinical findings improved within hours. Rifabutin therapy was discontinued. Later on the visual acuity of both eyes improved to 20 / 100. CONCLUSIONS: Bilateral rifabutin-associated uveitis may also occur in an HIV negative patient. A toxic reaction due to concomitant clarithromycin therapy might be causal. Well directed history, intensive topical steroids and the cessation of rifabutin therapy are helpful in the management of such rare uveitis.     

Biologics in the treatment of uveitis

PURPOSE OF REVIEW: This review summarizes the current evidence for biologic therapies in the treatment of uveitis. The review emphasizes published research in this field since 2005. RECENT FINDINGS: The anti-tumour necrosis factor-alpha infliximab and adalimumab have demonstrated significant efficacy in controlling uveitis associated with seronegative spondyloarthropathies and juvenile idiopathic arthritis; however, etanercept has failed to show a similar treatment effect in uveitis associated with these conditions. The majority of reports of biologic therapies in posterior uveitis have been uncontrolled trials, or retrospective studies, of uveitis resistant to immunosuppression. Encouragingly, successful control of such refractory intraocular inflammation has been consistently reported with infliximab and interferon alpha, particularly Behcet's disease-associated uveitis. A limited number of reports of anti-interleukin therapies, daclizumab and anakinra, have supported a role for these therapies in some types of uveitis. SUMMARY: Biologic therapies have increased the treatment options for sight-threatening uveitis. Despite experimental rationale, the lack of evidence from randomized controlled studies limits our understanding of when to commence therapy, which agent to choose and how long to continue treatment. Additionally, the high cost and potential side effects of all biologic agents have limited their current use to uveitis refractory to immunosuppression.