Mycophenolate mofetil therapy for sarcoidosis-associated uveitis.

PURPOSE: To evaluate the control of ocular inflammation and the steroid sparing effect in patients with sarcoidosis-associated uveitis treated with mycophenolate mofetil (MMF). METHODS: Retrospective case series. All patients with a diagnosis of sarcoidosis-associated uveitis that were treated with MMF between 2005 and 2007 were identified. The dose and duration of MMF therapy and side effects were recorded. RESULTS: Seven patients (14 eyes) with sarcoidosis-associated uveitis were treated with MMF. The mean duration of treatment was 10 +/- 4.7 months and the average time to control uveitis was 6.7 weeks. The flare-up rate was 51.5 per 100 person-years follow-up. The best-corrected mean logMAR VA revealed improvement in all 14 eyes. The efficacy of MMF in keeping disease activity under control was maintained in 6 patients. CONCLUSION: These data suggest that MMF is effective in controlling sarcoidosis-related ocular inflammation, has a corticosteroid sparing effect and a manageable side-effect profile.

Acute posterior multifocal placoid pigment epitheliopathy: outcome and visual prognosis.

OBJECTIVES: To examine the clinical outcomes and the effect of treatment in patients with acute posterior multifocal placoid pigment epitheliopathy. METHODS: Cases of acute posterior multifocal placoid pigment epitheliopathy treated at the Massachusetts Eye and Ear Infirmary from 1990 to 2002 and cases from the literature were identified. Data on visual acuity, ocular symptoms, bilateral involvement, foveal involvement at presentation, and treatment regimens were recorded. RESULTS: Visual acuity was 20/25 or worse in 226 (76.6%) eyes and 20/40 or worse in 172 (58.3%) eyes at presentation. At the last follow-up visit, visual acuity was 20/25 or less in 125 (42.3%) eyes and 20/40 or less in 70 (23.7%) eyes. Topical or systemic therapy was given in nearly half of the cases (54.4%). Overall, 87 (71.9%) eyes were symptomatic at last follow-up visit. Finally, measured visual acuity was more than 20/25 in 20 (87.5%) eyes without foveal involvement at presentation and in 28 (39.2%) eyes with foveal involvement. CONCLUSIONS: Although acute posterior multifocal placoid pigment epitheliopathy shows a relatively benign prognosis, especially when compared with some of the other white dot syndromes, there are patients who experience incomplete visual recovery.

Use of systemic T-lymphocyte signal transduction inhibitors in the treatment of atopic keratoconjunctivitis.

PURPOSE: Topical immunomodulators such as tacrolimus have revolutionized the treatment of atopic dermatitis. Because T lymphocytes are integral to the pathogenesis of atopic dermatitis, systemic treatment with T-lymphocyte signal transduction inhibitors should ameliorate both the dermatologic and ocular manifestations. We describe the successful treatment of 6 patients with severe atopic keratoconjunctivitis (AKC) resistant to conventional therapies. METHODS: Retrospective observational case series. The charts of patients with AKC assessed by 1 of the authors were reviewed to identify those treated with systemic T-cell signal transduction inhibitors. Visual acuities, previous treatments, and the response to systemic signal transduction inhibitors were observed and reported in 6 patients. RESULTS: The patients had a mean duration of AKC of 21 years. Topical corticosteroids and antihistamines had failed to control signs and symptoms of the disease in all patients, and in some patients, systemic corticosteroids and topical cyclosporine were ineffective. Three patients were treated with systemic cyclosporine, and 3 were treated with systemic tacrolimus. One patient was subsequently treated with daclizumab in addition to tacrolimus. All 6 patients experienced complete remission of their AKC and an increase in visual acuity. CONCLUSIONS: Selective systemic immunosuppression of T lymphocytes with cyclosporine or tacrolimus has proved effective in the treatment of both atopic dermatitis and atopic keratoconjunctivitis. We advocate the consideration of systemic therapy in cases that are resistant to conventional treatment to resolve inflammation and preserve vision. Further studies in this area are advocated.

Methods for identifying long-term adverse effects of treatment in patients with eye diseases: the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study.

PURPOSE: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. METHODS: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented. RESULTS: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immunosuppressives is ascertained from medical records of approximately 9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over approximately 100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents. CONCLUSIONS: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases.

Herpetic retinitis.

This paper provides an appreciation of the various forms and consequences of retinal inflammation caused by human herpesviruses. Herpes simplex virus types 1 and 2, varicella zoster virus, cytomegalovirus and Epstein-Barr virus are known to cause retinitis. The prognosis of herpetic retinitis remains poor because it is associated with a high incidence of complications, both during and after the acute disease phase. On diagnosis of retinal necrosis, antiviral treatment must be started promptly to limit disease progression; following this, prophylactic maintenance therapy may be required.

Systemic immunomodulatory therapy in severe dry eye secondary to inflammation.

PURPOSE: To report four patients with unusually severe acute keratitis sicca secondary to lacrimal tissue and ocular surface inflammation who eventually required systemic immunosuppressive therapy. METHODS: Observational case series of four patients with extremely severe acute dry eye syndrome who were profoundly disabled by pain and photophobia (to the extent of staying in dark rooms) despite aggressive conventional therapy. Clinical data including visual acuities, other treatments administered for dry eye, systemic medical conditions, Schirmer and rose bengal staining results, degree of conjunctival injection, and medications were recorded. All four patients were treated with systemic immunomodulatory therapy. RESULTS: All four patients were female with a mean age at presentation of 40 years (range 22-58 years), and all had systemic autoimmune diseases: systemic lupus erythematosus (SLE) and Sjogren's syndrome (n = 2), Sjogren's syndrome (n = 1), rheumatoid arthritis (RA) and psoriasis (n = 1). Schirmer test values at onset ranged from 0 to 2 mm. All patients had failed aggressive lubrication, topical cyclosporine, lid care, and punctual plugs. In two patients, serum tears and hyphrecation punctal occlusion were tried without success. Various systemic immunosuppressive agents were used to control inflammation of the lacrimal glands: methotrexate and cyclosporine A (patient 1), cyclosporine A (patient 2), prednisone (patient 3), and methotrexate and infliximab (patient 4). Treatment with systemic immunomodulatory agents resulted in resolution of the acute inflammatory assault on the lacrimal glands and control of signs and symptoms of keratoconjunctivitis sicca in all four patients, and visual acuities improved in all of them. Post-treatment Schirmer values ranged from 7 to 10 mm. CONCLUSION: Systemic immunosuppressive agents may be required in the treatment of recalcitrant primary and secondary Sjogren's syndrome caused by systemic autoimmune conditions. We show that systemic immunomodulatory therapy leads to significantly improved tear production and resolution of the keratoconjunctivitis in these rare but severe cases.

Chronic cicatrizing conjunctivitis in a patient with epidermolysis bullosa acquisita.

OBJECTIVE: To describe a nonconventional diagnostic technique used to diagnose a case of cicatrizing conjunctivitis associated with epidermolysis bullosa acquisita. METHODS: Direct immunofluorescence of a biopsy specimen of the patient's conjunctiva was performed using fluorescein-conjugated rabbit antihuman antibodies against IgA, IgG, and IgM; complement C3; and fibrinogen. Immunoblot assay using healthy human skin as substrate was performed to investigate for the presence of antibodies in the patient's serum. After the diagnosis of systemic autoimmune disease was established, intravenous immunoglobulin therapy was administered. RESULTS: Direct immunofluorescence of the conjunctiva revealed linear deposition of IgA and IgG, and C3 at the epithelial basement membrane zone. Immunoblot analysis demonstrated the presence of IgG antibodies in patient serum directed against a 290-kDa protein in human skin. A diagnosis of epidermolysis bullosa acquisita was established. All signs and symptoms improved dramatically 4 months after initiation of intravenous immunoglobulin therapy and remained stable during follow-up. CONCLUSIONS: Epidermolysis bullosa acquisita can manifest in the eye as chronic cicatrizing conjunctivitis indistinguishable from ocular cicatricial pemphigoid. A nonconventional diagnostic tool (immunoblot assay) might be helpful in establishing the diagnosis of an underlying systemic autoimmune disease in patients with chronic cicatrizing conjunctivitis. Intravenous immunoglobulin therapy was effective against chronic cicatrizing conjunctivitis associated with epidermolysis bullosa acquisita.

Elevated levels of interleukin 6 in the vitreous fluid of patients with pars planitis and posterior uveitis: the Massachusetts eye & ear experience and review of previous studies.

INTRODUCTION: Although the exact mechanisms that lead to uveitis are not entirely known, the role of cytokines in the pathogenesis of this disease has been shown to be important. Prior studies described the presence of an array of cytokines in the intraocular fluid of patients with uveitis. Review of these studies indicate that Interleukin-6 (IL-6) is present, and animal data suggest the important role of IL-6 in the regulation of ophthalmologic immune responses. PURPOSE: We investigated whether IL-6, TNF-alpha, IL-1 alpha, beta, IL-2 are present in the vitreous of patients with active intermediate and posterior uveitis. METHODS: Vitreous specimens were collected from 23 eyes of patients with active intermediate and posterior uveitis who underwent diagnostic or therapeutic vitrectomies. TNF-alpha, IL-1 alpha and beta, IL-2 and IL-6 were measured by enzyme-linked immunosorbent assay. Eight vitreous fluid samples from eye bank eyes were used as control. RESULTS: IL-6 was higher in the vitreous of patients with uveitis compared to control samples (p = 0.0119). No TNF-alpha, IL-2, IL1-alpha or beta was detected. The levels of IL-6 did not correlate with a specific clinical diagnosis, but patients with pars planitis and panuveitis had the highest levels (p = 0.58) CONCLUSIONS: IL-6 is elevated in the vitreous of patients with active intermediate and posterior uveitis.