Howard H. Tessler

Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.

PURPOSE To present revised criteria for the diagnosis of Vogt-Koyanagi-Harada disease, a chronic, bilateral, granulomatous ocular and multisystem inflammatory condition of unknown cause. METHODS Diagnostic criteria and nomenclature were subjects of discussion at the First International Workshop on Vogt-Koyanagi-Harada Disease on October 19-21, 1999, at the University of California, Los Angeles, Conference Center, Lake Arrowhead, California. A committee appointed by the workshop participants was charged with drafting revised criteria for Vogt-Koyanagi-Harada disease, based on discussions held during the conference. This article is the consensus committee report. RESULTS New criteria, taking into account the multisystem nature of Vogt-Koyanagi-Harada disease, with allowance for the different ocular findings present in the early and late stages of the disease, were formulated and agreed upon by the committee. These criteria are based on additional knowledge and experience of experts in the field and are believed to reflect disease features more fully than previously published criteria. CONCLUSIONS The revised definition of Vogt-Koyanagi-Harada disease, with expanded diagnostic criteria, will facilitate performance of studies involving homogeneous populations of patients, at various stages of disease, that address unanswered questions regarding treatment and disease mechanisms.

Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel.

PURPOSE To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders. PARTICIPANTS A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care. EVIDENCE Published clinical study results. Recommendations were rated according to the quality and strength of available evidence. PROCESS The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS Although corticosteroids represent one of the mainstays in the management of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects.

Vogt–Koyanagi–Harada Syndrome

We studied 20 patients with Vogt-Koyanagi-Harada syndrome. They represented 3.7% of referred patients with uveitis. American Indian ancestry appears to be the link to Oriental racial type. Five patients had a forme fruste retinal detachment. After extensive treatment with corticosteroids, detachments flattened within an average of two to three months. Anterior inflammation continued to persist chronically. Seven of our patients had retinal vasculitis. Pregnancy had a beneficial effect on disease activity. Those patients with diabetes mellitus and sickle cell hemoglobin did not have an adverse effect. Visual outcome was good; of 20 patients, 16 had visual ascuity of 6/21 (20/70) in at least one eye.

Epidemiology and Course of Disease in Childhood Uveitis

PURPOSE To describe the disease characteristics and visual outcome of pediatric uveitis. DESIGN Retrospective, longitudinal observation. PARTICIPANTS Five hundred twenty-seven pediatric uveitis patients from the National Eye Institute, University of Illinois, Chicago, and Oregon Health Sciences University. METHODS Retrospective chart review. MAIN OUTCOME MEASURES Demographics, uveitis disease characteristics, complications, treatments, and visual outcomes were determined at baseline and at 1-, 3-, 5-, and 10-year time points. RESULTS The patient population was 54% female; 62.4% white, 12.5% black, 2.7% Asian, 2.1% multiracial, and 14.61% Hispanic. Median age at diagnosis was 9.4 years. The leading diagnoses were idiopathic uveitis (28.8%), juvenile idiopathic arthritis-associated uveitis (20.9%), and pars planitis (17.1%). Insidious onset (58%) and persistent duration (75.3%) were most common. Anterior uveitis was predominant (44.6%). Complications were frequent, and cystoid macular edema (odds ratio [OR] 2.94; P = 0.006) and hypotony (OR, 4.54; P = 0.026) had the most significant visual impact. Ocular surgery was performed in 18.9% of patients. The prevalence of legal blindness was 9.23% at baseline, 6.52% at 1 year, 3.17% at 3 years, 15.15% at 5 years, and 7.69% at 10 years. Posterior uveitis and panuveitis had more severe vision loss. Hispanic ethnicity was associated with a higher prevalence of infectious uveitis and vision loss at baseline. CONCLUSIONS The rate and spectrum of vision threatening complications of pediatric uveitis are significant. Prospective studies using standard outcome measures and including diverse populations are needed to identify children most at risk.

Herpetic Eye Disease Study: A Controlled Trial of Oral Acyclovir for Herpes Simplex Stromal Keratitis

PURPOSE To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Topical cyclosporin A in the treatment of anterior segment inflammatory disease.

Topical cyclosporin A was used in the management of 43 patients with a variety of anterior segment inflammatory disorders that had failed corticosteroid treatment. Treatment with topical cyclosporin A ranged from 1 week to 43 months, with a mean treatment period of 13 months. Thirty-five patients (81%) with disorders including highrisk keratoplasty, atopic and vernal keratoconjunctivitis, ligneous conjunctivitis, ulcerative keratitis, and Moorens ulcer had a beneficial result, with resolution, reduction, or prevention of inflammation. Six patients (14%) with scleritis, ocular cicatricial pemphigoid, or endotheliitis showed no clinical improvement. Two patients (5%) had significant ocular discomfort, and the drug had to be discontinued in them. None of the other patients developed local side effects. Twenty-seven of these patients were followed with serial cyclosporin A blood levels and serum creatinine. None of these patients developed measurable drug blood levels or renal toxicity.

Long-term follow-up of patients treated with short-term high-dose chlorambucil for sight-threatening ocular inflammation.

PURPOSE To determine the effectiveness of short-term high-dose chlorambucil in the treatment of sight-threatening uveitis and to ascertain the incidence of severe side effects, particularly late malignancy. DESIGN Retrospective, noncomparative interventional case series. PARTICIPANTS Fifty-three patients treated at the University of Illinois at Chicago Eye and Ear Infirmary and the private office of one of the authors for severe sight-threatening uveitis. METHODS Treatment with short-term high-dose chlorambucil (2-9 months of therapy). MAIN OUTCOME MEASURE Visual acuity and degree of inflammation were assessed at every visit. The development of systemic side effects, including malignancy, was assessed using a detailed questionnaire. RESULTS Total cumulative dose of chlorambucil ranged from 392 to 5200 mg with an average of 1429 mg. The maximum daily dose ranged from 10 to 30 mg with an average of 20 mg. Average duration of treatment was 16 weeks with a range of 7 to 40 weeks. Seventy-seven percent of patients treated were in remission with an average follow-up of 4 years (range: 6 months to 24 years). Forty-seven percent had at least two lines of improvement in Snellen visual acuity after treatment, with an average gain of 3.5 lines. Adverse effects include secondary amenorrhea, nonophthalmic herpes zoster, testicular atrophy, and erectile dysfunction. None of the patients had developed a malignancy as of their last follow-up. CONCLUSION Short-term high-dose chlorambucil therapy may be a reasonable option in patients with intractable sight-threatening uveitis.

Adalimumab therapy for refractory uveitis: results of a multicentre, open-label, prospective trial

Objective Tumour necrosis factor (TNF) blockers have been demonstrated to be effective in the treatment of systemic and ocular inflammatory diseases. We conducted a prospective, multicentre, open-label Phase II clinical trial to assess the effectiveness and safety of adalimumab, a fully human anti-TNF monoclonal antibody, in treating refractory uveitis. Methods Subjects with non-infectious uveitis refractory to corticosteroids and at least one other immunosuppressive medication were enrolled. Treatment outcome was ascertained by a composite endpoint comprised of visual acuity, intraocular inflammation, ability to taper immunosuppressives, and posterior segment imaging. Clinical response was defined by improvement in at least one parameter, worsening in none, and well controlled intraocular inflammation. Week 10 responders were permitted to continue receiving adalimumab for the study duration of 50 weeks. Results Twenty-one of 31 patients (68%) were characterised as clinical responders at 10 weeks, of whom 12 patients (39%) exhibited durable response after 50 weeks. The most common reason for study termination was primary or secondary inefficacy. No patients experienced treatment-limiting toxicity clearly related to study therapy. Conclusions Adalimumab was safe and effective in 68% of refractory uveitis patients 10 weeks after study enrolment, and maintained in 39% after 1 year. Ongoing study is required to determine the place of adalimumab and other TNF blockers in the treatment of uveitis.

Successful treatment of serpiginous choroiditis with alkylating agents

OBJECTIVE To describe the management and long-term outcomes of patients with serpiginous choroiditis treated with alkylating agents. DESIGN Retrospective, noncomparative case series. PARTICIPANTS Nine patients with active, vision-threatening serpiginous choroiditis who had progressive inflammation while on steroids and/or immunosuppressive agents other than alkylating agents treated at three tertiary care uveitis referral centers. METHODS Patients received systemic immunosuppression with an alkylating agent, either chlorambucil or cyclophosphamide. Prednisone also was given initially and was tapered and discontinued. MAIN OUTCOME MEASURES Visual acuity, clinical disease activity, duration of treatment, duration of drug-free disease remission, and side effects of alkylating agent therapy. RESULTS No patients had recurrences while on therapy. No further visual loss was encountered after starting the therapy. Six of the patients regained vision. All but two patients achieved prolonged drug-free remissions, ranging in duration between 15 and 96 months (median, 78 months). Side effects included transient bone marrow suppression, nausea, and fatigue. Secondary malignancy was encountered in one patient, whose carcinoma of the urinary bladder was treated successfully. CONCLUSIONS Adequate immunosuppression with alkylating agents may favorably alter the long-term prognosis of patients with serpiginous choroiditis.

Multifocal choroiditis in patients with familial juvenile systemic granulomatosis

PURPOSE To document clinical features of uveitis in patients with familial juvenile systemic granulomatosis. DESIGN Retrospective chart review. METHODS Ophthalmologic examination, medical history, and clinical course in 16 patients from eight families examined at six academic medical centers. RESULTS Of the 16 patients, 15 had evidence of panuveitis with multifocal choroiditis. One patient had only an anterior uveitis. Ischemic optic neuropathy, presumably due to a small vessel vasculopathy, and retinal vasculopathy each occurred in one patient. Ocular complications were common, including cataracts in 11, glaucoma in six, band keratopathy in six, cystoid macular edema in six, and optic disk edema in six. All 16 patients had polyarthritis, and at least nine had skin rash. Often patients were misdiagnosed initially as having either juvenile rheumatoid arthritis or sarcoidosis. CONCLUSIONS Familial juvenile systemic granulomatosis is an uncommon genetic disease characterized by polyarthritis and uveitis. Panuveitis and multifocal choroiditis often may be present. Patients with a diagnosis of juvenile rheumatoid arthritis but having a family history of the disease and multifocal choroiditis should be suspected of having familial juvenile systemic granulomatosis.