Long-term, drug-free remission of sympathetic ophthalmia with high-dose, short-term chlorambucil therapy.

OBJECTIVE: To evaluate the safety and effectiveness of short-term, high-dose chlorambucil therapy in achieving long-term, drug-free remission in the treatment of sympathetic ophthalmia (SO). DESIGN: Retrospective case series. PARTICIPANTS: Sixteen patients with SO treated with high-dose, short-term chlorambucil therapy between 1970 and 2010. METHODS: Descriptive and bivariate analyses were used to characterize disease and outcomes. MAIN OUTCOME MEASURES: Months of disease-free remission, prevalence rate of relapse, and prevalence of serious treatment-related adverse events. RESULTS: Sixteen patients with SO treated with short-term, high-dose chlorambucil were identified. Patients were treated with chlorambucil for a median of 14.0 weeks (mean, 14.5 weeks; range, 12.0-19.0 weeks). Median follow-up was 98.5 months (mean, 139.1 months; range, 48-441 months) from initiation of chlorambucil therapy. Control of inflammation was achieved in 100% of patients. Thirteen patients (81.3%) maintained vision of 20/40 or better in the sympathizing eye. Four patients (25%) relapsed after a median of 83 months (mean, 131 months) after cessation of systemic therapy. Seventy-five percent of relapses were controlled with topical therapy only. Conjunctival Kaposi's sarcoma developed in 1 patient. No patient demonstrated systemic malignancy. CONCLUSIONS: Short-term, high-dose chlorambucil therapy provides sustained periods of drug-free remission. With median follow-up of more than 8 years (mean, 11.6 years; range, 4-37 years), there was a low rate of recurrence and minimal long-term serious health consequences or adverse events. Because SO may be a lifelong condition and because chlorambucil therapy may offer long-term, drug-free remission, this treatment may be worth considering early in the decision-making process for severe sight-threatening disease.

Mycobacterial ocular inflammation: delay in diagnosis and other factors impacting morbidity.

IMPORTANCE: The reported outcomes of ocular mycobacterial infection are commonly unfavorable. This study is among the first to elucidate factors associated with poor outcomes, as well as highlight the continued controversies in therapy, particularly the role of oral corticosteroids. OBJECTIVE: To describe presentations and outcomes of mycobacterial ocular disease in the Midwestern United States. DESIGN Retrospective case series. SETTING: A university-based uveitis clinic. PARTICIPANTS: Twenty-six eyes of 17 patients with mycobacterial ocular inflammatory disease seen at University of Illinois at Chicago from 1995 to 2010. MAIN OUTCOME MEASURES: Bivariate and regression analyses were performed to assess factors associated with delay in referral, relapse, and irreversible visual acuity loss (≤ 20/200). RESULTS: Of 17 patients, 13 had isolated ocular disease, 1 had miliary tuberculosis (TB), 2 had TB lymphadenopathy, and 1 had active pulmonary TB. Fourteen had Mycobacterium tuberculosis and 3 had nontuberculous mycobacterial infection. Chest imaging was consistent with granulomatous disease in 46.7%. Average delay from ocular disease onset to uveitis service referral was 755.3 days. Posterior uveitis and non-Hispanic white race were associated with increased delay. A relapsing course was observed in posterior uveitis (odds ratio [OR], 20.0; 95% CI, 1.39-287; P = .03) and those treated with systemic steroids for eye disease (OR, 10.1; 95% CI,1.60-64.0; P = .01). Disease control was achieved in 81%, although 38.5% had profound visual loss, associated with age older than 50 years and delay in diagnosis. Patients diagnosed after 500 days from initial ocular symptoms were more likely to lose vision (OR, 20.0; 95% CI, 1.41-282; P = .03). CONCLUSIONS: Ocular mycobacterial infection occurs in nonendemic areas and cannot be ruled out with negative chest imaging. Tuberculosis and atypical mycobacterial infection should be in the differential diagnosis of ocular inflammation, regardless of patient ethnicity. Significant delays exist in instituting antimicrobial treatment, associated with increased morbidity. Early referral is necessary for patients not responding appropriately to anti-inflammatory therapy.

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.

Vogt-Koyanagi-Harada syndrome in a 6-year-old Hispanic boy.

A 6-year-old Hispanic boy presented to the ophthalmology department with complaints of pain, photophobia, and blurry vision of both eyes. He was found to have bilateral granulomatous panuveitis, cataracts, and high intraocular pressures. He later developed multiple asymptomatic, ovoid, hypopigmented patches over the mid-lumbosacral back. Biopsy of lesional skin was significant for low melanocyte counts and a mild lymphocytic infiltrate. The patient was diagnosed with Vogt-Koyanagi-Harada syndrome (VKH). This article reviews the literature regarding the cutaneous presentation of VKH.

Clinical features and diagnostic evaluation of biopsy-proven ocular sarcoidosis.

OBJECTIVES: To compare the clinical characteristics of uveitic sarcoidosis in African American and non-African American patients with biopsy-proven sarcoidosis and to determine which diagnostic test results were most often suggestive of sarcoidosis in patients who were ultimately diagnosed as having the disease. METHOD: Retrospective review of consecutive patients with biopsy-proven sarcoidosis evaluated by the uveitis service between 1989 and 2009. RESULTS: A total of 63 patients with uveitic sarcoidosis were identified: 39 (62%) were African American (P <.001) and 43 (68%) were female. African American patients presented at an earlier age (P <.001) and were more likely to have granulomatous anterior segment inflammation (P <.001). The levels of serum markers angiotensin-converting enzyme and lysozyme were elevated in 40% and 42% of patients tested, respectively. The levels of at least 1 marker were elevated in 18 patients (58%). Imaging study results were reported as consistent with sarcoidosis in 25 patients (69%) who underwent chest radiography and in 19 patients (100%) who underwent computed tomography. CONCLUSIONS: In this series, African American patients were more likely to be diagnosed as having uveitic sarcoidosis and to present with uveitis if they were younger than 50 years. White patients were more likely to present when they were older than 50 years. A clinical picture that included granulomatous anterior segment inflammation was more common in African American patients. The use of serum markers (angiotensin-converting enzyme and lysozyme) positively identified more patients with biopsy-proven sarcoidosis when used in combination with appropriate chest imaging.

Cutaneous melanoma metastatic to the vitreous cavity.

PURPOSE: To report a case of cutaneous melanoma metastatic to the vitreous cavity. METHODS: Retrospective case report. A 72-year-old white man with a history of cutaneous melanoma but no known distant metastases presented with floaters and decreased vision. RESULTS: The patient was initially treated for a presumptive diagnosis of ocular toxoplasmosis. After failure to respond to treatment, he underwent diagnostic pars plana vitrectomy. Pathology of the vitreous specimen was suggestive of metastatic melanoma, and systemic workup revealed metastases to the brain. CONCLUSION: In patients with a known history of cutaneous melanoma presenting with ocular inflammation, a high index of suspicion for metastatic disease should be maintained.

Pediatric uveitis secondary to probable, presumed, and biopsy-proven sarcoidosis.

PURPOSE: To describe pediatric patients with uveitis diagnosed as having sarcoidosis. METHODS: Medical records of pediatric patients evaluated between 1987 and 2008 were reviewed to identify those with ocular inflammation in whom a diagnosis of sarcoidosis was considered. A classification system including ocular findings and results of laboratory testing was devised and used to classify likelihood of sarcoidosis. RESULTS: Four hundred sixty children younger than 17 years were evaluated. Based on the classification system designed, 13 patients (2.8%) had probable, presumed, or definite sarcoidosis. The mean age was 11.6 years (range: 5 to 16 years). Elevated angiotensin-converting enzyme was measured in 6 patients and lysozyme in 5 patients. Five of 12 patients in whom chest imaging was performed had signs of sarcoidosis. Anterior segment involvement was non-granulomatous more often than granulomatous. Seven patients had multifocal choroiditis and 4 patients had retinal periphlebitis. CONCLUSION: Ocular sarcoidosis is uncommon in children, even at a tertiary referral center. Pulmonary involvement was detected in slightly less than half of the patients who had imaging, in contrast to previous reports of almost universal lung involvement in children 8 to 15 years old. The classification system of presumed, probable, and definite sarcoidosis presented may be useful in clinical practice.

Ocular sarcoidosis misdiagnosed as primary intraocular lymphoma.

PURPOSE: The purpose of this study was to describe patients initially carrying a diagnosis of primary intraocular lymphoma who were ultimately diagnosed with ocular sarcoidosis. METHODS: The medical records of patients evaluated between 1995 and 2007 fitting the criteria described earlier were identified, and pertinent clinical findings allowing for the diagnosis of sarcoidosis are described. RESULTS: Nine patients between the ages of 52 and 83 were referred with a diagnosis of primary intraocular lymphoma but were ultimately diagnosed with sarcoidosis. The most common clinical signs found in these patients that are atypical for primary intraocular lymphoma but common in sarcoidosis were multifocal choroiditis (n = 7) and cystoid macular edema (n = 6). Additional findings included keratic precipitates, posterior synechiae, and Koeppe nodules. Chest computerized tomography was consistent with sarcoidosis in seven of eight tested patients, and five of these patients had normal chest x-rays. Other findings included elevated angiotensin-converting enzyme and/or lysozyme, and biopsy revealing noncaseating granulomas. CONCLUSION: Although primary intraocular lymphoma should always be in the differential diagnosis of older patients who present with signs of ocular inflammation, ophthalmologists must also consider other etiologies, including sarcoidosis. A chest computerized tomography may be helpful in the diagnosis, particularly when laboratory findings are supportive of sarcoidosis.

Treating uveitis-associated hypotony with pars plana vitrectomy and silicone oil injection.

PURPOSE: The purpose of this study was to determine the effect on intraocular pressure (IOP) and visual acuity of treating uveitis-related hypotony in patients with vitrectomy and intravitreal silicone oil injection. METHODS: Patients who underwent pars plana vitrectomy and silicone oil injection for uveitis-associated hypotony treatment were identified retrospectively. The primary outcome was maintaining an IOP of > or =5 mmHg. Visual acuity improvement was defined as an increase in > or =2 lines of acuity. RESULTS: Twelve eyes of 10 patients were identified. Median preoperative IOP was 2 mmHg (range: 0-7 mmHg). Two of 12 eyes had an IOP of > or =5 mmHg at presentation. The number of eyes with an IOP of > or =5 mmHg was 7 of 12 eyes (58%) at 1 month, 4 of 12 eyes (33%) at 3 months, 6 of 12 eyes (50%) at 6 months, and 3 of 9 eyes (33%) at 1 year. Five of 12 eyes (42%) were reinjected between 1 and 3 times with silicone oil for recurring hypotony. Median presenting Snellen visual acuity was counting fingers (range: 20/125 to light perception). Seven of 9 eyes (78%) maintained their preoperative vision at 1 year. CONCLUSION: Intraocular pressure elevated modestly in most patients in this series. However, results were often transient, and some eyes required repeated silicone oil injections. Although silicone oil is reasonable to consider for the treatment and maintenance of IOP in patients with ocular hypotony secondary to uveitis, better treatments are needed.

Juvenile xanthogranuloma masquerading as melanoma.

Juvenile xanthogranuloma (JXG) of the uvea is a rare disease that usually responds to systemic steroids or low-dose radiotherapy. We present an atypical case of bilateral JXG involving the entire uveal tract that presented with an aggressive phenotype. The patient was unresponsive to topical and systemic corticosteroids, cyclosporine, and maximal doses of radiation therapy. The disease was ultimately controlled with the alkylating agent chlorambucil.

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.

Granulomatous inflammation in juvenile idiopathic arthritis-associated uveitis.

PURPOSE: The uveitis that is associated with juvenile idiopathic arthritis (JIA) has typically been described as nongranulomatous. This study reports the prevalence of granulomatous disease in a population with JIA-associated uveitis. METHODS: We conducted a retrospective analysis of all patients with JIA-associated uveitis seen between 1973 and 2006 at a hospital-based uveitis service. Patients with uveitis were included if they were diagnosed with JIA by a specialist and experienced at least 6 weeks of arthritis starting before the age of 16 years. Granulomatous disease was defined as Busacca or angle nodules, mutton-fat keratic precipitates (KP), or hyalinized "ghost" KPs. Statistical tests were performed to seek associations between granulomatous disease and various clinical factors. RESULTS: Seventy-one patients with JIA-associated uveitis were included. Granulomatous uveitis was observed in 28% of the population, with 7% exhibiting mutton-fat KP, and 21% "ghost" KP. There was no association between the presence of granulomatous disease and age of arthritis onset, age of uveitis onset, sex, antinuclear antibody status, or whether the arthritis was pauciarticular or polyarticular. In this population, 67% of black patients had granulomatous disease compared with 25% of nonblack patients (p < 0.05), and 24% of white patients showed granulomatous disease compared with 56% of nonwhite patients (p = 0.11). CONCLUSIONS: Granulomatous disease is more common in JIA-associated uveitis than previously thought and may be more common in black patients. Although it is necessary to exclude other forms of granulomatous uveitis, such as sarcoidosis, the presence of granulomatous uveitis is not inconsistent with a diagnosis of JIA-associated uveitis.

Immunologic markers as potential predictors of systemic autoimmune disease in patients with idiopathic scleritis.

PURPOSE: To determine the clinical value of serological testing in patients with idiopathic scleritis. DESIGN: Retrospective case series. METHODS: Medical records of patients with scleritis seen at an institutional referral center over an 11-year period were reviewed. RESULTS: Of 119 patients with scleritis seen at the University of Illinois Uveitis Clinic, 91 (76.5%) patients had no known etiology at initial presentation. Seventy of the 91 patients were tested for rheumatoid factor (RF), 19 (27.1%) of whom had a positive result. Ten (52.6%) of these RF positive patients were subsequently diagnosed with rheumatoid arthritis (RA) during a mean follow-up of 10.6 months (range, zero to 72 months), whereas only one of 51 (2.0%) RF negative patients developed RA, producing an odds ratio for developing RA in RF positive patients of 55.6 (95% confidence interval (CI) 7.8 to 369.8, P=.00001). Of the 70 patients who were tested for anti-neutrophil cytoplasmic antibody (ANCA), seven (10.0%) tested positive. Three (42.9%) of the ANCA positive patients subsequently developed Wegener granulomatosis (WG), whereas only two of 63 ANCA negative patients (3.2%) developed WG during a mean follow-up of 8.4 months (range, zero to 72 months). The odds ratio for developing WG in patients with idiopathic scleritis and a positive ANCA screen compared with a negative ANCA was 22.9 (95% CI 3.4 to 154.2, P=.006). CONCLUSIONS: The likelihood of patients with idiopathic scleritis developing RA and WG was increased if they had a positive RF or ANCA, supporting the role of immunologic marker testing in patients who present without systemic disease.

Mycobacterium haemophilum: a rare cause of endophthalmitis.

Nontuberculous mycobacterial (NTM) infections are becoming an increasingly important complication in ophthalmology, particularly among immunocompromised patients. We report a case of NTM in a 66-year-old male immunosuppressed after cardiac transplantation. Chronic granulomatous iridocyclitis progressed to purulent endophthalmitis despite intraocular and systemic antimicrobial therapy. Direct immunoflourescent staining of the vitrectomy specimen revealed acid-fast bacilli. Biopsies of nodular skin lesions revealed non-caseating granulomas with acid-fast bacilli. Cultures of skin and eye biopsies yielded Mycobacterium haemophilum. Despite aggressive combination antimicrobial therapy, the eye was eventually enucleated. Resolution of systemic infection occurred with the addition of granulocyte macrophage-colony stimulating factor. This is the first reported case of M. haemophilum endophthalmitis.

Epidemiologic relationship between fuchs heterochromic iridocyclitis and the United States rubella vaccination program.

PURPOSE: To investigate an epidemiologic association between Fuchs heterochromic iridocyclitis (FHI) and the rubella vaccination program in the United States. DESIGN: Observational case series. METHODS: The percentages of patients with FHI, idiopathic chronic iridocyclitis, and idiopathic chronic granulomatous iridocyclitis at the University of Illinois were compared over time. Analysis of country of origin (United States vs foreign-born) was also performed. Findings were correlated with implementation of the rubella vaccination program in the United States in 1969. RESULTS: A total of 3,856 patients were seen between 1985 and 2005. Percentages of patients with FHI and idiopathic chronic granulomatous iridocyclitis born between 1919 and 1958 were similar (FHI 3.51% to 5.19%; idiopathic chronic granulomatous iridocyclitis 3.51% to 4.72%), with more variability in the idiopathic chronic iridocyclitis group (6.63% to 11.32%). A 64.8% reduction in FHI subjects was seen for those born the following decade (1959 to 1968). An additional 39.7% drop in FHI occurred in patients born between 1969 and 1978. Only one patient with FHI was born during the decade 1979 to 1988. The trend over time for FHI differed significantly from idiopathic chronic iridocyclitis (P = .0007) and idiopathic chronic granulomatous iridocyclitis (P = .0002), with no difference between the controls (P = .5437). The percentage of foreign-born patients with FHI increased after the institution of the rubella vaccination program (42% to 55%) compared with those born in previous decades (24% to 25%). This was not observed in the controls. CONCLUSION: FHI is less common in patients born since the introduction of the US rubella vaccination program, with a corresponding increase in percentage of foreign-born cases. This epidemiologic study supports a relationship between the rubella virus and FHI.