Decline in Ocular Toxoplasmosis over 40 Years at a Tertiary Referral Practice in the United States.

PURPOSE: To identify whether there has been a decline in ocular toxoplasmosis at a tertiary uveitis practice. METHODS: Retrospective review of new patients at the University of Illinois Uveitis Service from 1973 to 2012. RESULTS: There were 6820 patients with adequate records for inclusion; 323 (4.7%) were diagnosed with ocular toxoplasmosis. There was a 78.0% decline in prevalence of ocular toxoplasmosis from 2008 to 2012 compared with 1973 to 1977. Compared with the aggregate uveitis population, toxoplasmosis patients were more likely to be Hispanic (p<0.0001) and less likely to be African American (p<0.0001). Ocular toxoplasmosis in Hispanics commonly occurred in foreign-born patients (85.3%). CONCLUSIONS: The diagnosis of ocular toxoplasmosis at our clinic declined, with Hispanics accounting for an increasing proportion of cases. These trends are consistent with the decreasing toxoplasmosis seropositivity in the United States, but may also reflect decreased referrals due to improved management of ocular toxoplasmosis in primary clinics.

Viral retinitis following intraocular or periocular corticosteroid administration: a case series and comprehensive review of the literature.

PURPOSE: To describe viral retinitis following intravitreal and periocular corticosteroid administration. METHODS: Retrospective case series and comprehensive literature review. RESULTS: We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25-13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). CONCLUSIONS: Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy.

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.

Bilateral simultaneous-onset nongranulomatous acute anterior uveitis: clinical presentation and etiology.

OBJECTIVE To describe the etiology and outcome of patients with simultaneous-onset nongranulomatous bilateral acute anterior uveitis. METHODS The medical records of patients who presented to a single tertiary care center with simultaneous-onset nongranulomatous bilateral acute anterior uveitis between January 1990 and May 2010 were retrospectively reviewed; the clinical presentation, results of diagnostic testing, and outcome data are described. RESULTS A total of 4288 new patients with uveitis were evaluated by the Uveitis Service at the University of Illinois at Chicago Eye and Ear Infirmary between January 1990 and May 2010. Of these new patients, 44 (1%) presented with simultaneous-onset nongranulomatous bilateral acute anterior uveitis. The most common etiologies were postinfectious or drug-induced uveitis (23 of 44 patients [52%]) and idiopathic uveitis (15 patients [34%]). Tubulointerstitial nephritis and uveitis syndrome, HLA-B27-associated uveitis, inflammatory bowel disease, and Kawasaki disease each made up fewer than 5% of diagnoses. Overall, this group of patients was younger than the entire cohort of new patients with uveitis who were evaluated during the same time period (P = .002). For 14 of the 15 patients with at least a year of follow-up (93%), the disease duration was limited (<3 months). Of these 14 patients, 7 (50%) developed recurrent disease, with an average time to first recurrence of 20 months (range, 7.5-40 months) after resolution of the initial inflammatory episode. CONCLUSIONS Simultaneous-onset nongranulomatous bilateral acute anterior uveitis is a rare clinical entity that is more common in younger patients and is most frequently associated with recent infection and/or systemic antibiotic use. Tubulointerstitial nephritis and uveitis syndrome should also be considered as a diagnosis. Diagnostic evaluation should include serum antistreptolysin-O titers, HLA-B27 antigen, and urine ß2 microglobulin levels because these may reveal systemic disease that requires therapy.

Immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease.

PURPOSE: To evaluate the prevalence of immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease. DESIGN: Matched case-control study. METHODS: Patients with a diagnosis of idiopathic ocular inflammation and family history of inflammatory bowel disease who did not have inflammatory bowel disease themselves were identified and matched to control patients with idiopathic ocular inflammation. Serum was evaluated for immunologic markers using Prometheus IBD Serology 7. Genomic DNA was analyzed for single nucleotide polymorphisms (SNP) of the NOD2 gene associated with Crohn disease. RESULTS: Fifteen patients with idiopathic ocular inflammation and family history of inflammatory bowel disease were matched to 15 control patients based on age, sex, and race. Eight of 15 patients (53%) with a family history of inflammatory bowel disease had elevated p-ANCA antibody levels compared to 3 of 15 controls (20%) (1-sided P = .04) with a matched analysis odds ratio of 6.0 (1-sided P = .06). Four of 15 patients (27%) with family history of inflammatory bowel disease tested positive for immunologic markers predicting ulcerative colitis, while no control patients tested positive (1-sided P = .06). Carrier rates of NOD2 SNPs did not differ significantly between the test and control groups. CONCLUSIONS: One-quarter of patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease had immunologic markers predicting bowel disease, and one-half had elevated p-ANCA levels. Prometheus IBD Serology 7 may be useful in the evaluation of selected patients with unexplained uveitis.

Behçet uveitis in the American midwest.

PURPOSE: Behçet disease is most common in Asia, the Middle East, and North Africa (Silk Road). The authors compare clinical presentation and course of Behçet uveitis in patients of Silk Road and non-Silk Road descent. METHODS: Retrospective review of patients evaluated at the University of Illinois January 1983-July 2010. RESULTS: Of 6134 new uveitis patients, 36 with available medical records met diagnostic criteria for Behçet disease. Ten (28%) were of Silk Road origin. Retinal vasculitis was the most common ocular manifestation, followed by panuveitis and retinitis. Ocular and systemic manifestations were similar between groups. Seventy-eight percent were treated with systemic immunosuppression, which reduced inflammatory attack rate. CONCLUSIONS: Behçet disease is uncommon in the midwestern United States. Three-quarters of patients in this series were not of Silk Road descent. Physicians should consider the diagnosis of Behçet disease in any patient with retinal vasculitis or uveitis regardless of ethnicity.

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.

Chronic anterior uveitis in common variable immunodeficiency.

PURPOSE: To describe patients with uveitis and common variable immunodeficiency (CVID). DESIGN: Retrospective observational case series. METHODS: Retrospective review of patients with uveitis and CVID, specifically focusing on clinical presentation and treatment. RESULTS: Three patients with CVID and uveitis were identified. All patients had chronic anterior uveitis. Two required systemic immunosuppression to control uveitis, with one of these patients relapsing after discontinuation of immunoglobulin therapy. One improved on topical steroid therapy; however, follow-up on this patient did not extend beyond 4 months. CONCLUSIONS: CVID can be associated with chronic anterior uveitis. Patients presenting with uveitis should be questioned about frequent infections and autoimmune disorders as part of the uveitis evaluation.

Posterior syphilitic uveitis: clinical characteristics, co-infection with HIV, response to treatment.

PURPOSE: To describe the characteristics and clinical course of patients with active posterior syphilitic uveitis evaluated between 1991 and 2009. METHODS: Retrospective chart review. RESULTS: Thirteen patients with active posterior syphilitic uveitis were identified at a single institution. All were men, and all with available data were men having sex with men (MSM). Ten of 12 (83%) with available data were HIV positive. Four (31%) had a history of syphilis. Clinical findings included infiltrative retinitis, necrotizing retinitis and optic neuritis. Two of 8 patients tested (25%) had a positive Venereal Disease Research Laboratory test in the cerebrospinal fluid. Treatments included intravenous penicillin, intramuscular penicillin and intramuscular ceftriaxone. All treated cases improved and, in some cases, inflammatory lesions completely resolved without scarring. CONCLUSIONS: In this series, syphilitic posterior uveitis presented only in men, and all with available data were MSM. The majority were concomitantly infected with HIV. Clinical presentations varied and all patients demonstrated either significant improvement or complete resolution of inflammation.

Presentation and outcome of patients with punctate inner choroidopathy at a tertiary referral center.

PURPOSE: To describe the clinical course of patients with punctate inner choroidopathy seen at the University of Illinois, with emphasis on development of choroidal neovascularization (CNV). METHODS: Patients with a diagnosis of punctate inner choroidopathy were identified retrospectively. The diagnosis was made clinically based on findings of multiple, small "punched-out" lesions in the posterior pole without intraocular inflammation. Medical records were evaluated for evidence of CNV. RESULTS: Twelve patients with a diagnosis of punctate inner choroidopathy were identified. Average age at presentation was 32 years (range, 24-52 years). Eleven were women, and 11 were white. Eleven patients had available refractive data: 10 were myopic. Eight had CNV at initial presentation, and 1 later developed CNV. Eight had follow-up averaging 4 years (range, 1.4-9.6 years). Of these, five had CNV at initial presentation, and five developed new CNV. Four had multiple CNV membranes. All 6 patients with follow-up of ≥ 3 years had visual acuity at 3 years postpresentation of >20/40 in at least 1 eye. Four had visual acuity >20/40 bilaterally. CONCLUSION: Of punctate inner choroidopathy patients in this series, 75% had CNV, and more than 30% developed multiple neovascular membranes. With treatment, all patients with follow-up of ≥ 3 years had >20/40 vision in at least 1 eye.

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.

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.

Etiologies of chronic anterior uveitis at a tertiary referral center over 35 years.

PURPOSE: To describe the epidemiology of chronic anterior uveitis (CAU) at a tertiary center over 35 years. METHODS: Data regarding etiology of CAU was collected from medical records of patients evaluated between 1973-2007. Relative frequencies of each diagnosis of CAU were calculated. Linear regression analyses were performed on the common types of CAU. RESULTS: 5970 patients were evaluated between 1973-2007; 31% carried a diagnosis of CAU. Idiopathic disease was diagnosed in 54% of patients (39 to 72% annually), ocular sarcoidosis in 14% of patients (2 to 20% annually), Fuchs heterochromic iridocyclitis (FHI) in 12% of patients (4 to 22% annually), and juvenile idiopathic arthritis (JIA) in 6% of patients (2 to 13% annually). The frequency of diagnosis of idiopathic CAU decreased over time, with no significant change for sarcoidosis, FHI or JIA. An increase in frequency of diagnosis was observed for HLA-B27-related disease and uveitis related to multiple sclerosis and inflammatory bowel disease. CONCLUSIONS: The relative frequency of idiopathic disease has decreased over the past 35 years at our center. This may be related to an increase in the diagnosis of CAU associated with HLA-B27 positivity, inflammatory bowel disease (including family history) and multiple sclerosis. Despite the advances over the last 35 years, idiopathic disease still comprises at least 39% of our patients with CAU each year.

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.

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.