The Joint Pathology Center/Vision Center of Excellence Approach to Analyzing Intra-Ocular "Foreign Bodies".

BACKGROUND: The Military Health System recognizes the importance of analyzing "foreign bodies" removed from US service members through several policy documents. This activity focuses on detecting potentially toxic metals. Intra-ocular "foreign bodies" (IOFBs) represent a small, clinically important subset. The development of ocular metallosis with iron and copper fragments is a specific local reaction to IOFBs. The results of the compositional analysis of removed IOFBs can influence clinical management decisions aimed at optimizing the preservation of sight. METHOD: The Joint Pathology Center (JPC) and Vision Center of Excellence (VCE) have established a pathway for the analysis of IOFBs removed from Department of Defense and Veterans Health Administration patients. The analysis of IOFBs uses analytical methods to provide information about the fragments' surface elemental and molecular composition. RESULTS: Metallic specimens analyzed included iron and copper-containing fragments. Non-metallic IOFBs analyzed include glass, plastic (polyurethane), and nitro-cellulose fragments. CONCLUSION: The JPC/VCE approach to analyzing IOFBs promotes uniform handling and shipping of specimens to minimize contamination. The analytical approach allows for the characterization of IOFBs with a wide variety of compositions. The results support clinical management decisions aimed at optimal treatment for the preservation of patients' visual acuity.

A case of recalcitrant pediatric Vogt-Koyanagi-Harada disease successfully controlled with adalimumab.

Vogt-Koyanagi-Harada (VKH) disease is uncommon in the pediatric population and can have an aggressive course with serious visual sequelae. A 12-year-old Han Chinese American female, who presented with mild headaches and panuveitis with diffuse serous retinal detachments, was diagnosed with VKH. Despite treatment with a combination of high-dose systemic corticosteroids, intravitreal triamcinolone injection, and mycophenolate mofetil, ocular inflammation was inadequately controlled. Addition of adalimumab allowed for inflammation remission, improvement of vision, and tapering of systemic corticosteroids. Escalation of immunosuppression until remission appears to be critical in this population. Further research is needed to understand the complex pathophysiology of VKH and investigation for similar efficacy of other anti-tumor necrosis factor-alpha agents will need to be performed.

Fundus image diagnostic agreement in uveitis utilizing free and open source software.

OBJECTIVE: To assess the adequacy of image agreement regarding uveitis based on color fundus and fluorescein angiography images alone, and to use free and open source applications to conduct an image agreement study. DESIGN: Cross-sectional agreement study. PARTICIPANTS: Baseline fundus and fluorescein images of patients with panuveitis, posterior, or intermediate uveitis enrolled in the Multi-center Uveitis Steroid Treatment (MUST) trial. METHODS: Three fellowship-trained specialists in uveitis independently reviewed patient images using ClearCanvas™ and responded using Epi Info™. The diagnoses of the 3 reviewers were compared with the MUST clinician as a gold standard. A rank transformation adjusted for the possible variation in number of responses per patient. Chance-corrected interobserver agreement among the 3 reviewers was estimated with the ι coefficient. Confidence interval (CI) and SE were bootstrapped. RESULTS: Agreement between the diagnoses of the respondents and the baseline MUST clinician's diagnosis was poor across all diagnostic categories, ι = 0.09 (95% CI, 0.07-0.11). The agreement among respondents alone also was poor, ι = 0.11 ± 0.02 (95% CI, 0.08-0.13). The specialists requested more patient historical and clinical information to make a diagnosis on all patients. CONCLUSIONS: The role in distinguishing the multiple conditions in uveitis appears to be limited when based on fundus imaging alone. Future studies should investigate different categories of clinical data to supplement image data. Freely available applications have excellent utility in ophthalmic imaging agreement studies.

Optical coherence tomography evaluation in the Multicenter Uveitis Steroid Treatment (MUST) trial.

PURPOSE: To describe the evaluation of optical coherence tomography (OCT) scans in the Muliticenter Uveitis Steroid Treatment (MUST) trial and report baseline OCT features of enrolled participants. METHODS: Time-domain OCTs acquired by certified photographers using a standardized scan protocol were evaluated at a reading center. Accuracy of retinal thickness data was confirmed with quality evaluation, and caliper measurement of centerpoint thickness (CPT) was performed when retinal thickness data were unreliable. Morphological evaluation included cysts, subretinal fluid, epiretinal membranes (ERMs), and vitreomacular traction. RESULTS: Of the 453 OCTs evaluated, automated retinal thickness was accurate in 69.5% of scans, caliper measurement was performed in 26%, and 4% were ungradable. Intraclass correlation was.98 for reproducibility of caliper measurement. Macular edema (centerpoint thickness ≥ 240 µm) was present in 36%. Cysts were present in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement ranged from 78 to 82% for morphological features. CONCLUSION: Retinal thickness data can be retrieved in a majority of OCT scans in clinical trial submissions for uveitis studies. Small cysts and ERMs involving the center are common in intermediate and posterior/panuveitis requiring systemic corticosteroid therapy.

Associations among visual acuity and vision- and health-related quality of life among patients in the multicenter uveitis steroid treatment trial.

PURPOSE: To evaluate the associations between visual acuity and self-reported visual function; visual acuity and health-related quality of life (QoL) metrics; a summary measure of self-reported visual function and health-related QoL; and individual domains of self-reported visual function and health-related QoL in patients with uveitis. METHODS: Best-corrected visual acuity, vision-related functioning as assessed by the NEI VFQ-25, and health-related QoL as assessed by the SF-36 and EuroQoL EQ-5D questionnaires were obtained at enrollment in a clinical trial of uveitis treatments. Multivariate regression and Spearman correlations were used to evaluate associations between visual acuity, vision-related function, and health-related QoL. RESULTS: Among the 255 patients, median visual acuity in the better-seeing eyes was 20/25, the vision-related function score indicated impairment (median, 60), and health-related QoL scores were within the normal population range. Better visual acuity was predictive of higher visual function scores (P ≤ 0.001), a higher SF-36 physical component score, and a higher EQ-5D health utility score (P < 0.001). The vision-specific function score was predictive of all general health-related QoL (P < 0.001). The correlations between visual function score and general quality of life measures were moderate (ρ = 0.29-0.52). CONCLUSIONS: The vision-related function score correlated positively with visual acuity and moderately positively with general QoL measures. Cost-utility analyses relying on changes in generic healthy utility measures will be more likely to detect changes when there are clinically meaningful changes in vision-related function, rather than when there are only changes in visual acuity. (ClinicalTrials.gov number, NCT00132691.).

Clinical manifestations of ocular toxoplasmosis.

Clinical manifestations of ocular toxoplasmosis are reviewed. Findings of congenital and acute acquired ocular toxoplasmosis include retinal scars, white-appearing lesions in the active phase often associated with vitritis. Complications can include fibrous bands, secondary serous or rhegmatogenous retinal detachments, optic neuritis and neuropathy, cataracts, increased intraocular pressure during active infection, and choroidal neovascular membranes. Recurrences in untreated congenital toxoplasmosis occur in teenage years. Manifestations at birth are less severe, and recurrences are fewer in those who were treated promptly early in the course of their disease in utero and in the first year of life. Severe retinal involvement is common at diagnosis of symptomatic congenital toxoplasmosis in the United States and Brazil. Acute acquired infections also may be complicated by toxoplasmic retinochoroiditis, with recurrences most common close to the time of acquisition. Suppressive treatment can reduce recurrent disease.

The need for validation of large administrative databases: Veterans Health Administration ICD-9CM coding of exudative age-related macular degeneration and ranibizumab usage.

We performed a validation study by chart review of data for exudative age-related macular degeneration (eAMD) and, because of the Veterans Administration (VA) therapy policy, ranibizumab usage in the largest electronic medical record system in the USA. We reviewed 5,854 distinct patients who visited an ophthalmology clinic within VA Connecticut from January 2006-December 2008. We randomly selected 98 of 138 distinct eAMD patients and 265 of 5,588 non-eAMD patients who did not receive ranibizumab. International Classification of Diseases, Ninth Revision, Clinical Modification coding of eAMD had an excellent positive predictive value of 97.8% (95% confidence interval (CI), 93.5-99.4%). The national Decision Support System (DSS) had an excellent positive predictive value of 100% (95% CI, 79.9-100%) for ranibizumab. However, the negative predictive value of the DSS dispensed ranibizumab decreased to 67.5 (95% CI, 62.1-72.4) because of a change in the way local values were stored that led to errors. Therefore, validation of clinical information over time in large databases is necessary.

Time Domain Optical Coherence Tomography in Familial Vitreous Amyloidosis Associated Transthyretin Met30 Mutation.

Vitreous amyloidosis is characterized by progressive loss of vision from amyloid accumulation of deposits on the retina and in the vitreous. Time domain optical coherence tomography (TD-OCT) was used in a case of familial transthyretin vitreous amyloidosis Met30 mutation to image the anterior vitreous deposits, which showed high reflectivity of very different from vitreous found in unaffected individuals. TD-OCT may be a useful adjunctive test to diagnose vitreous amyloidosis when masquerade syndromes are suspected. There may be more easeful imaging in TD-OCT of vitreous abnormalities than with spectral domain OCT (SD-OCT). Further study should be performed comparing TD versus SD-OCT in families with vitreous amyloidosis and TD vitreous amyloidosis versus TD in other intermediate uveitis.

Lesões coriorretinianas em mães de crianças com toxoplasmose congênita no national collaborative Chicago-based, toxoplasmosis study / Chorioretinal lesions in mothers of children with congenital toxoplasmosis in the national collaborative Chicago-based, congenital toxoplasmosis study

Aims: To determine whether mothers of children with congenital toxoplasmosis have chorioretinal lesions consistent with toxoplasmosis. Methods: Prospective cohort study. Ophthalmologists in our study have examined 173 children with congenital toxoplasmosis in a hospital outpatient setting. These children were referred to us by their primary care physicians. One hundred and thirty mothers of these children had retina examinations of both eyes at least once. Main outcome measure was lesion(s) consistent with ocular toxoplasmosis. Results: Of 130 mothers examined between 1991-2005, 10 (7.7%, 95% Confidence Interval 3.8%, 13.7%) had chorioretinal lesions which likely represent resolved toxoplasmic chorioretinitis. Most of these were small peripheral chorioretinal lesions. None reactivated between 1991-2005. Conclusions: Chorioretinal lesions consistent with quiescent ocular toxoplasmosis occur in mothers of children with congenital toxoplasmosis in the United States.

Chorioretinal lesions in mothers of children with congenital toxoplasmosis in the National Collaborative Chicago-based, Congenital Toxoplasmosis Study.

AIMS: To determine whether mothers of children with congenital toxoplasmosis have chorioretinal lesions consistent with toxoplasmosis. METHODS: Prospective cohort study. Ophthalmologists in our study have examined 173 children with congenital toxoplasmosis in a hospital outpatient setting. These children were referred to us by their primary care physicians. One hundred and thirty mothers of these children had retina examinations of both eyes at least once. Main outcome measure was lesion(s) consistent with ocular toxoplasmosis. RESULTS: Of 130 mothers examined between 1991-2005, 10 (7.7%, 95% Confidence Interval 3.8%, 13.7%) had chorioretinal lesions which likely represent resolved toxoplasmic chorioretinitis. Most of these were small peripheral chorioretinal lesions. None reactivated between 1991-2005. CONCLUSIONS: Chorioretinal lesions consistent with quiescent ocular toxoplasmosis occur in mothers of children with congenital toxoplasmosis in the United States.

Cryptococcal chorioretinitis with immune reconstitution inflammatory syndrome.

Immune Reconstitution Inflammatory Syndrome (IRIS) is an inflammatory syndrome in the context of immune restoration directed at a specific infectious antigen despite resolution of infection, often associated with opportunistic infections. IRIS has been reported in 30% to 35% of HIV patients who have cryptococcosis in whom antiretroviral therapy was initiated. We would like to report a case of IRIS localized to the eye secondary to cryptococcal infection.

Whole-body 18FDG PET-CT imaging of systemic sarcoidosis: ophthalmic oncology and uveitis.

PURPOSE: To describe whole-body 18-fluorodeoxyglucose (FDG) positron emission tomography/computed radiographic tomography (PET-CT) imaging of ophthalmic patients with systemic sarcoidosis. METHODS: Four systemic sarcoidosis patients were evaluated with PET-CT for staging. Two had been treated for conjunctival melanoma and two had been referred for atypical choroidal tumors. PET-CT images were studied for presence of tumor or tissue with increased standardized uptake values, indicating increased metabolic activity. RESULTS: In all cases, PET-CT revealed focal systemic lesions with increased uptake (SUV range 1.7-5.9 kg/mL). Cases 1 and 2 had a previous diagnosis of sarcoidosis (without ocular involvement), while cases 3 and 4 were diagnosed during their work-up. PET-CT revealed the presence and distribution of systemic sarcoid granulomas. CONCLUSIONS: In this series, PET-CT staged patients with eye cancer and systemic sarcoidosis and aided in differentiating between a metastatic choroidal tumor and uveal sarcoid granuloma. PET-CT offers a method to assess the presence and distribution of systemic sarcoidosis.

Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life.

PURPOSE: To determine the incidence of new chorioretinal lesions in children with toxoplasmosis diagnosed after, and therefore not treated during, their first year. DESIGN: Prospective longitudinal cohort study. METHODS: Thirty-eight children were evaluated in Chicago between 1981 and 2005 for new chorioretinal lesions. Thirty-eight children and mothers had serum IgG antibody to Toxoplasma gondii. RESULTS: Twenty-eight of 38 children had one of the following: diagnosis with serum antibody to T. gondii indicative of chronic infection at age 24 months, central nervous system calcifications, hydrocephalus, illness compatible with congenital toxoplasmosis perinatally but not diagnosed at that time. Twenty-five returned for follow-up during 1981 to 2005. Their mean (range) age at last exam was 10.9 +/- 5.7 (range, 3.5 to 27.2) years and mean follow-up was 5.7 +/- 2.9 years. Eighteen (72%) children developed at least one new lesion. Thirteen (52%) had new central lesions, 11 (44%) had new peripheral lesions, and six (24%) had both. Thirteen (52%) had new lesions diagnosed at age > or =10 years. New lesions were found at more than one visit in four (22%), and bilateral new lesions developed in seven (39%) of 18 children who developed new lesions. Of 10 additional children with eye findings and serologic tests indicative of chronic infection, six returned for follow-up, four (67%) developing new lesions at > or =10 years of age. CONCLUSIONS: More than 70% developed new chorioretinal lesions. New lesions were commonly diagnosed after the first decade of life.

Longitudinal study of new eye lesions in treated congenital toxoplasmosis.

OBJECTIVE: To determine the incidence of new chorioretinal lesions in patients with congenital toxoplasmosis who were treated throughout their first year of life. DESIGN: Prospective longitudinal observation of a cohort. PARTICIPANTS: One hundred thirty-two children were studied as part of the longitudinal observation. METHODS: One hundred thirty-two children were treated during their first year of life with pyrimethamine, sulfadiazine, and leucovorin. They had eye examinations at prespecified intervals. MAIN OUTCOME MEASURES: New chorioretinal lesions on fundus examination and fundus photographs. RESULTS: The mean age (+/- standard deviation) is 10.8+/-5.1 years (range, 0.2-23). One hundred eight children have been evaluated for new chorioretinal lesions. Thirty-four (31%; 95% confidence interval, 23%-41%) of 108 children developed at least one chorioretinal lesion that was previously undetected. These occurred at varying times during their follow-up course. Fifteen children (14%) developed new central lesions, and 27 (25%) had newly detected lesions peripherally. Ten (9%) had more than one occurrence of new lesions developing, and 13 (12%) had new lesions in both eyes. Of those who developed new lesions, 14 children (41%) did so at age 10 or later. CONCLUSION: New central chorioretinal lesions are uncommon in children with congenital toxoplasmosis who are treated during their first year of life. This finding contrasts markedly with earlier reports in the literature for untreated children or those treated for only 1 month near birth, in whom new lesions were much more prevalent (>/=82%). Our observation that 14 (41%) of the 34 children with new chorioretinal lesions had occurrences when they were 10 years or older indicates that long-term follow-up into the second decade of life is important in assessing the efficacy of treating toxoplasmosis during infancy.

Cataracts in congenital toxoplasmosis.

PURPOSE: To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis. METHODS: Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed. RESULTS: In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions. CONCLUSIONS: In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.

Giant sarcoid tumor of the iris and ciliary body.

PURPOSE: To report the occurrence of a giant iridociliary sarcoid tumor. METHODS: The patient was evaluated by medical history, ophthalmoscopic examination (including photography and ultrasonography) as well as systemic, hematologic, and radiographic examinations. Tumor biopsies allowed for cytopathologic, histopathologic, and immunohistochemical analysis. RESULTS: The 39-year-old black male was found to have a right iris and ciliary body tumor. Ultrasonography revealed a 10 x 12-mm base, 5.6-mm height, low internal reflectivity, and vitreous debris. Radiographic imaging revealed mediastinal and bilateral hilar lymphadenopathy. A purified protein derivative (PPD) and a hematologic survey were negative. Pathology evaluations of the surgical specimens revealed features of non-caseating granulomata consistent with sarcoidosis. A combination of topical and systemic steroid therapy was locally curative. CONCLUSIONS: We describe a giant iridociliary sarcoid tumor in a patient with no lacrimal gland enlargement, conjunctival nodules, or skin lesions. A biopsy was required to establish the diagnosis.

Mechanical energy from intraocular instruments cause emulsification of silicone oil.

AIM: The complications of intraocular silicone oil include emulsification, which may lead to vision-threatening disorders such as keratopathy, secondary glaucoma and retinopathy. The authors study the effect of mechanical energy from surgical instruments on the emulsification of silicone oil. METHODS: Three different handpieces (phacofragmentation, phacoemulsification, high-speed vitrectomy) were placed at the interface of balanced salt solution and silicone oil (1000 and 5000 cst, 200 fluid; Dow Corning). The phacofragmentation handpiece was evaluated over different ultrasound powers and duration. Emulsification was quantified with phase-contrast microscopy and manual counting of digital photographs by a masked examiner. In addition, phacoemulsification was performed in the anterior chamber of a human ex vivo eye with full-fill silicone oil. RESULTS: Emulsification increases with higher phacofragmentation power and duration and is greater for 1000 cst silicone oil. Emulsification of silicone oil occurs with phacoemulsification and high-speed vitrectomy handpieces. CONCLUSIONS: The energy from surgical handpieces is sufficient to result in silicone oil emulsification.