CYSTOID MACULAR EDEMA IN BIRDSHOT RETINOCHOROÏDITIS: Long-Term Treatment Study in 142 Patients.

PURPOSE: To assess the long-term efficacy and safety of treatments for cystoid macular edema in birdshot retinochoroïditis. METHODS: Observational retrospective study of 142 HLA-A29-positive patients with cystoid macular edema; the main outcome was the optical coherence tomography intraretinal cysts resolution. RESULTS: During the mean follow-up of 75 months (12-178), 61.3% of patients were successfully treated using 1 to 3 treatment steps, while the others needed more steps. At 6 months, there were no significant effects on ME for anti-TNF (tumor necrosis factor) and IVIg (immunoglobulin) in contrast to antimetabolites (OR 1.98), systemic GCS (glucocorticosteroids), CsA (cyclosporine A) and tocilizumab (odds ratio closed to 2.7), intraocular injected GCS (odds ratio of 4.2), and interferon (odds ratio of 4.4). The percentages of therapeutic success trend to decrease from the initial three treatment steps to the subsequent treatment steps, for systemic GCS (84% to 70%), for anti-TNF (42% to 33%), and for CsA (71% to 33%); the success percentages did not decrease for injected GCS (83% to 89%). Macular edema recurrence occurred with the highest percentage for injected GCS (86.8%, P = 0.01) and the lowest for tocilizumab (10.5%, P = 0.001). Interferons-α and tocilizumab were associated with the lowest prednisone daily doses. CONCLUSION: The classical uveitic cystoid macular edema therapeutic algorithm could be adapted to birdshot retinochoroïditis.

Prediction of effectiveness of universal rotavirus vaccination in Southwestern Vietnam based on a dynamic mathematical model.

Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01-1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age.

Ciclosporin A in bilateral auto-immune chronic posterior uveitis associated with macular oedema: a Long-term Observational Safety and Efficacy Study.

OBJECTIVE: A non-interventional, longitudinal, retrospective follow-up study to assess CsA-induced nephrotoxicity (IN) and its reversibility after withdrawal in patients exhibiting a bilateral chronic posterior uveitis (CPU) associated with cystoid macular oedema (CMO) in at least one eye. Data from medical records between 1986 and 2013. METHODS: Primary outcome was the renal tolerance during and after CsA treatment assessed by plasma creatinine concentration and glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology (CKD-Epi) formula. Secondary outcomes were CsA through concentration, occurrence of cancers and ophthalmologic efficacy assessed by three parameters including CMO, vitreous inflammation, and best-corrected visual acuity BVCA changes. RESULTS: One hundred forty-three patients were followed for renal tolerance. Underlying diseases were Birdshot retinochoroiditis (n = 67), Behçet disease (n = 9), probable sarcoidosis (n = 23), sympathetic ophthalmia (n = 3), idiopathic (n = 41). After CsA discontinuation in 115 patients (mean treatment duration of 5.9 ± 3.8 years) mean plasma creatinine concentration was 82.2 ± 14.2 µmol/L versus 82.1 ± 14.1 µmol/L at baseline, mean GFR was 79.4 ± 13.9 mL/min versus 82.5 ± 14.3 mL/min at baseline, with no significant difference (respectively p = 0.91 and p = 0.09). Blood pressure did not significantly change during follow-up. CMO was completely resorbed in at least one eye, in 70.8% patients (n = 72) at 6 months, in 71.4% patients (n = 49) at 10 years and in 54.2% patients (n = 24) at 20 years. BCVA did not statistically change over time. CONCLUSION: Early and long-term monitoring of renal tolerance and dual adjustment of CsA doses in inflammatory stages of CPU were associated with reversible CsA IN. CsA could be effective in the treatment of CMO in CPU patients.

Neuro-ophthalmological manifestations of Behçet's disease.

BACKGROUND: The neuro-ophthalmological manifestations of Behcet's disease (BD) are rare, and data regarding their characteristics and outcome are lacking. OBJECTIVE: To report prevalence, main characteristics and outcome of neuro-ophthalmological manifestations in BD. PATIENTS AND METHODS: This is a retrospective monocentric study of 217 patients diagnosed with neuro-Behçet's disease (NBD), of whom 29 (13.3%) patients presented with neuro-ophthalmological manifestations (55% of men and mean±SD age of 26±8 years). All patients underwent a detailed ophthalmological examination and were followed up in the internal medicine and the ophthalmology departments. RESULTS: Neuro-ophthalmological manifestations were the first presentation of BD in 45% of patients and developed later in the course of the disease in 55% of patients. They are divided into parenchymal (PM) and non-parenchymal (NPM)-related manifestations in, respectively, 13 patients (45%) and 16 patients (55%). PM included papillitis in seven patients (53.8%), retrobulbar optic neuritis in four patients (30.8%) and third cranial nerve palsy in two patients (15.4%). NPM included papilloedema related to cerebral venous thrombosis in all 16 patients, of whom 6 patients (37.5%) had sixth cranial nerve palsy. At initial examination, 93.1% of patients had visual alterations, including mainly decreased visual acuity visual field defects and/or diplopia. All patients were treated with corticosteroids and 79% of patients received immunosuppressive agents. After treatment, the visual outcome improved or stabilised in 66.7% of patients while it worsened in 33.3. The mean±SD logarithm of the minimum angle of resolution visual acuity improved from 0.4±0.3 at diagnosis to 0.2±0.3 after therapy. 10.3% and 3.4% of patients were legally blind at diagnosis and after therapy, respectively. CONCLUSION: Neuro-ophthalmological manifestations of BD represented 13% of NBD. They could be potentially severe and disabling. Prompt treatment is the key factor in improving visual outcome.

Chronic Herpetic Retinitis: Clinical Features and Long-Term Outcomes.

INTRODUCTION: Chronic uveitis treated with immunosuppressive agents may have unfavorable outcomes due to delays in diagnosis. The aim of this study was to review initial data from clinical and ocular assessments and patient outcomes following specific treatments for atypical herpes virus ocular infections. METHODS: The records of four consecutive patients with recurrent uveitis for at least five years treated in our department between 2001 and 2016 were retrospectively reviewed. They had atrophic retinal lesions resulting in an unfavorable outcome with lesion progression and vision loss under immunosuppressive treatment. Varicella zoster virus (1 case) and herpes simplex virus type 2 (3 cases) were detected in ocular samples. RESULTS: Uveitis was granulomatous and bilateral (3 cases) or unilateral (1 case). Immunosuppressive treatments worsened the clinical situation whereas antiherpetic treatments improved the control of intraocular inflammation. CONCLUSION: This description should be added to the broad repertoire of clinical polymorphisms associated with herpes virus infections. Recognizing these cases should be useful due to their sensitivity to antiherpetic treatments.

Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course?

PURPOSE: Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. METHODS: Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. RESULTS: A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (p<0.05), with a tendency toward a higher rate of chronic uveitis (p = 0.06). CONCLUSIONS: MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.

Rabbit hunter uveitis: case report of tularemia uveitis.

BACKGROUND: Literature reports on ophthalmological manifestations related to tularemia, a zoonose caused by the bacterium Francisella tularensis, largely refer to Parinaud's oculoglandular syndrome, which consists of the association of conjunctivitis with preauricular lymphadenitis. In this paper, we report a case of intraocular inflammation during tularemia infection. CASE PRESENTATION: A 52-year-old Caucasian man was diagnosed with unilateral uveitis. The uveitis was posterior, with a 2+ vitritis and a large yellowish lesion involving the macula with an overlying sub-retinal detachment, extending inferiorly, and subretinal hemorrhages. Fluorescein angiography showed a late hyperfluorescence with focal vascular leakage. Ultrasound biomicroscopy confirmed the presence of a 3.8 mm parietal granuloma with a few calcifications in the left eye. While extensive work-up eliminated any other infectious and non-infectious etiology, tularemia was diagnosed by advanced serology consisting of two-dimensional Western-immunoblotting. The patient, a hunter, recalled having killed rabbits in the days before the symptoms appeared. Uveitis was rapidly controlled following treatment with doxycycline, yet three years after initiation of the treatment, the patient still complained of loss of vision in the left eye with a central scotoma. CONCLUSIONS: Posterior uveitis may be an infrequent manifestation of tularemia infection, and therefore this infection should be considered in the differential diagnosis of intraocular inflammation in areas where F. tularensis is endemic.

Infliximab Versus Adalimumab in the Treatment of Refractory Inflammatory Uveitis: A Multicenter Study From the French Uveitis Network.

OBJECTIVE: To analyze the factors associated with response to anti-tumor necrosis factor (anti-TNF) treatment and compare the efficacy and safety of infliximab (IFX) and adalimumab (ADA) in patients with refractory noninfectious uveitis. METHODS: This was a multicenter observational study of 160 patients (39% men and 61% women; median age 31 years [interquartile range 21-42]) with uveitis that had been refractory to other therapies, who were treated with anti-TNF (IFX 5 mg/kg at weeks 0, 2, 6, and then every 5-6 weeks [n = 98] or ADA 40 mg every 2 weeks [n = 62]). Factors associated with complete response were assessed by multivariate analysis. Efficacy and safety of IFX versus ADA were compared using a propensity score approach with baseline characteristics taken into account. Subdistribution hazard ratios (SHRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The main etiologies of uveitis included Behçet's disease (BD) (36%), juvenile idiopathic arthritis (22%), spondyloarthropathy (10%), and sarcoidosis (6%). The overall response rate at 6 and 12 months was 87% (26% with complete response) and 93% (28% with complete response), respectively. The median time to complete response was 2 months. In multivariate analysis, BD and occurrence of >5 uveitis flares before anti-TNF initiation were associated with complete response to anti-TNF (SHR 2.52 [95% CI 1.35-4.71], P = 0.004 and SHR 1.97 [95% CI 1.02-3.84], P = 0.045, respectively). Side effects were reported in 28% of patients, including serious adverse events in 13%. IFX and ADA did not differ significantly in terms of occurrence of complete response (SHR 0.65 [95% CI 0.25-1.71], P = 0.39), serious side effects (SHR 0.22 [95% CI 0.04-1.25], P = 0.089), or event-free survival (SHR 0.55 [95% CI 0.28-1.08], P = 0.083). CONCLUSION: Anti-TNF treatment is highly effective in refractory inflammatory uveitis. BD is associated with increased odds of response. IFX and ADA appear to be equivalent in terms of efficacy.

Visual Acuity in Birdshot Retinochoroidopathy Evaluation.

PURPOSE: To determine the statistical correlation between visual acuity (VA) and various quantitative parameters relevant to birdshot retinochoroidopathy (BRC) evaluation. DESIGN: Hospital-based retrospective observational study. METHODS: setting: Institutional. STUDY POPULATION: Consecutive HLA29+ BRC patients were included between May and August 2013 at a single tertiary center (Pitié-Salpétrière Hospital, Paris). OBSERVATION PROCEDURES: Demographic data and quantitative parameters relevant to BRC at baseline were collected: VA, degree of anterior and posterior inflammatory reaction, foveal thickness measured by optical coherence tomography (OCT), Arden ratio, and electrooculography (EOG) light peak. MAIN OUTCOME MEASURES: Correlation between VA and the other parameters of the ipsilateral and fellow eye was performed using Spearman rank correlation coefficients. RESULTS: Fifty-five patients were included. Mean VA was 6/9.5 in the right eye (OD) and 6/12 in the left eye (OS). Mean foveal thickness was 240 µm OD (range: 112-606) and 251 µm OS (range: 85-662). Mean Arden ratio was 159% OD and 160% OS. EOG light peak was 714 mV OD (range: 316-1379) and 746 mV OS (range: 272-1652). VA of a given eye was moderately correlated with VA of the contralateral eye (r = 0.4). On the contrary, all other parameters showed a strong correlation between both eyes (all r > 0.7, P < .01). Overall, none of the studied parameters was correlated with its VA (all r < 0.5). CONCLUSION: In BRC, visual acuity alone does not seem to fully reflect the disease severity in terms of clinical or ancillary quantitative findings at baseline.

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

Tocilizumab in severe and refractory non-infectious uveitis.

OBJECTIVES: To report the safety and efficacy of tocilizumab in patients with severe and refractory non-infectious uveitis. METHODS: Eight consecutive unselected patients with severe and refractory non-infectious uveitis [Birdshot chorioretinopathy (n=1), Behçet's disease (n=1) and idiopathic bilateral panuveitis (n=6)] treated with tocilizumab (8mg/kg every 4 weeks intravenously) were included. The primary outcome was the response to treatment, defined by decrease of inflammatory ocular signs. RESULTS: Four (50%) patients were of female gender and the median (IQR) age was 41 (31-47) years. The median number of previous immunosupressants was of 5.5 (4-6.7). Seven patients had been previously treated with anti-TNF-α [infliximab (n=5) and adalimumab (n=2)]. The immunosupressive drugs used in association with tocilizumab were azathioprine (n=2), mycophenolate mofetil (n=2) and methotrexate (n=2). After a median follow-up of 8 months (6-25), 6/8 (75%) improved under tocilizumab and 2 (25%) were non-responders. The visual acuity improved in five patients. The median dose of prednisolone decreased from 16mg/day (10.6-20.5) to 10 mg/day (10-13.7), at baseline and at the end of follow-up, respectively. Tolerance of tocilizumab was satisfactory and side effects included bronchitis (n=1) and grade 1 leukopenia (n=1) and thrombocytopenia (n=1). CONCLUSIONS: Tocilizumab seems to be a safe and promising therapy in severe and refractory non-infectious uveitis.

Management of idiopathic retinal vasoproliferative tumors by slit-lamp laser or endolaser photocoagulation.

PURPOSE: To report the efficacy of laser photocoagulation in treating idiopathic (primary) retinal vasoproliferative tumors. DESIGN: Retrospective noncomparative interventional case series. PATIENTS AND METHOD: Thirty eyes of 30 patients (22 women and 8 men) with retinal vasoproliferative tumors. Main outcome measures were best-corrected visual acuity (BCVA), presence of retinal hard exudates, retinal detachment (RD), cystoid macular edema (CME), and epiretinal membrane (ERM). Laser photocoagulation was performed at the slit lamp or during pars plana vitrectomy for telangiectasia visible at the retinal vasoproliferative tumors surface. RESULTS: Fifteen eyes were treated with slit-lamp laser. Mean follow-up was 36.5 months (range 7 months to 11 years). Mean BCVA increased from 20/40 to 20/32 at the end of the follow-up. Hard exudates and CME regressed completely in 15 of 15 and 5 of 6 eyes, respectively. Fifteen eyes underwent vitrectomy owing to the presence of ERM (10 eyes), large exudative RD (4 eyes), or vitreous hemorrhage (1 eye). Mean follow-up was 24 months (9 months to 3.5 years). Mean BCVA increased from 20/125 to 20/40 at the end of the follow-up. No vision loss occurred. The retina reattached in all cases. Hard exudates regressed completely in 14 of 15 eyes and decreased significantly in 1. Postoperative complications were rhegmatogenous RD in 2 eyes, successfully reattached after additional surgery. CONCLUSION: Selective laser photocoagulation of retinal telangiectasia at the retinal vasoproliferative tumors' surface induced the regression of retinal exudation. Slit-lamp laser photocoagulation was sufficient in half of the cases. In more severe conditions, direct endolaser photocoagulation of the telangiectasia was required.

Measure of herpesvirus-specific ocular antibody production in patients with uveitis.

BACKGROUND: The amount of specific antiviral IgG in aqueous humour (AH) provides a major contribution to the diagnosis of herpesvirus uveitis. Ocular antibody production is often evaluated by comparing levels of specific and total IgG in serum and AH. The small volume of AH is a major limit for diagnosis. OBJECTIVES: To simplify the measure of ocular antibody production, we tested the quotient of serum/AH ratios of specific and control antiviral IgG, using automated quantitative serology methods on minimal volumes of AH, in confirmed and suspected herpesvirus uveitis. STUDY DESIGN: Serum and AH samples from herpesvirus PCR-positive uveitis patients, and from PCR-negative cases who were highly suspected to have viral uveitis were retrospectively analysed for ocular production of specific antiviral IgG using 40 µl of AH, and quantitative Enzygnost ELISA-based methods. Cataract and Fuchs cyclitis cases were used as controls. RESULTS: Ocular production of specific antiviral IgG was demonstrated in 32 (51.6%) of 62 herpesvirus PCR-positive uveitis cases, in none of 42 controls, and in 21 (55.2%) of 38 PCR-negative cases clinically suspected to have herpesvirus uveitis. The test had absolute specificity, and its sensitivity depended on the virus, pathology and timing of sampling. CONCLUSION: Ocular antibody production can be measured by simple quantitative ELISA-based methods on serum and minimal volumes of AH. This specific and sensitive test, implemented in the routine virology laboratory should help the diagnosis and specific antiviral therapy management of herpesvirus uveitis.

Small vessel involvement in Takayasu's arteritis.

OBJECTIVES: To describe the small retinal and systemic vessel involvement in Takayasu's arteritis. METHODS: We described 3 patients with Takayasu's arteritis and small retinal vessel occlusion seen in our department between 2004 and 2011. We performed an extensive literature review and provided a global analysis of small retinal vessel involvement in Takayasu arteritis (i.e., total number of patients analyzed=9). RESULTS: Seven patients had small retinal artery occlusion, and two had venous involvement. Four cases were inaugural of the disease (44.4%). Takayasu's arteritis was extended (Type V) in the majority of patients presenting with small retinal vessel occlusion (5/9, 55.6%), and 8/9 reported cases (88.9%) presented with involvement of the supra-aortic branches. Immunosuppressive regimen allowed an improvement in 5/9 patients and stabilization in 1/9, but the situation worsened in 3/9 patients. The visual outcome was severe, and 3/9 patients (33.3%) experienced irreversible blindness. CONCLUSION: Occlusion of small retinal vessels is a rare and severe microcirculatory complication in Takayasu's arteritis, as well as necrotizing cutaneous vasculitis or myocarditis. Small retinal vessel involvement can be inaugural of the disease and seriously impact the visual prognosis in TA patients.

Alagille syndrome in a Vietnamese cohort: mutation analysis and assessment of facial features.

Alagille syndrome (ALGS, OMIM #118450) is an autosomal dominant disorder that affects multiple organ systems including the liver, heart, eyes, vertebrae, and face. ALGS is caused by mutations in one of two genes in the Notch Signaling Pathway, Jagged1 (JAG1) or NOTCH2. In this study, analysis of 21 Vietnamese ALGS individuals led to the identification of 19 different mutations (18 JAG1 and 1 NOTCH2), 17 of which are novel, including the third reported NOTCH2 mutation in Alagille Syndrome. The spectrum of JAG1 mutations in the Vietnamese patients is similar to that previously reported, including nine frameshift, three missense, two splice site, one nonsense, two whole gene, and one partial gene deletion. The missense mutations are all likely to be disease causing, as two are loss of cysteines (C22R and C78G) and the third creates a cryptic splice site in exon 9 (G386R). No correlation between genotype and phenotype was observed. Assessment of clinical phenotype revealed that skeletal manifestations occur with a higher frequency than in previously reported Alagille cohorts. Facial features were difficult to assess and a Vietnamese pediatric gastroenterologist was only able to identify the facial phenotype in 61% of the cohort. To assess the agreement among North American dysmorphologists at detecting the presence of ALGS facial features in the Vietnamese patients, 37 clinical dysmorphologists evaluated a photographic panel of 20 Vietnamese children with and without ALGS. The dysmorphologists were unable to identify the individuals with ALGS in the majority of cases, suggesting that evaluation of facial features should not be used in the diagnosis of ALGS in this population. This is the first report of mutations and phenotypic spectrum of ALGS in a Vietnamese population.

Minor salivary gland biopsy in diagnosing ocular sarcoidosis.

BACKGROUND: To ascertain the sensitivity, specificity, and positive and negative predictive value of minor salivary gland biopsy in subsets of patients with uveitis consistent with ocular sarcoidosis. METHOD: Minor salivary gland biopsies performed in 230 patients with uveitis of indeterminate origin but clinically compatible with ocular sarcoidosis were reviewed. The biopsy results were analysed together with clinical features of uveitis and with the results of other relevant examinations, such as serum levels of angiotensin-I-converting enzyme and lysozyme, tuberculin skin test, chest radiography or CT scan, pulmonary function tests and bronchoalveolar lavage. RESULTS: Only seven of the 230 patients with uveitis had sarcoid granulomas on the minor salivary gland biopsy. All seven of these patients had a granulomatous uveitis and a compatible chest x-ray with sarcoidosis. The profitability of minor salivary gland biopsy can be improved by limiting the procedure to patients having granulomatous uveitis and a compatible chest x-ray. In these conditions, the positivity rate of minor salivary gland biopsy increased from 3% to 24% without loss of sensitivity. CONCLUSION: Minor salivary gland biopsy is most useful for assessing the diagnosis of sarcoid uveitis in a second-line investigation for patients with granulomatous uveitis and a radiologic pattern compatible with sarcoidosis.

Bilateral fungal endophthalmitis masquerading as multifocal chorioretinitis.

PURPOSE: Spontaneous healing of ocular Candida infection is extremely rare, and early clinical manifestations may be misleading. This report explicates how to make the appropriate diagnosis when facing atypical presentation of the disease. METHODS AND PATIENTS: Case report. RESULTS: A 36-year-old woman presented with bilateral chorioretinitis. Intravenous drug abuse was not suspected, and a diagnosis of multifocal chorioretinitis was made. Oral corticosteroid treatment was started. Three months later, all previously seen lesions had healed on the right eye but had increased on the left with development of severe endophthalmitis. Microbiologic analysis of scalp pustules yielded Candida albicans. She underwent vitrectomy, intravitreous amphotericin B injection, and systemic fluconazole treatment. The uveitis responded well to this treatment regiment, but subsequent development of macular edema and retinal detachment in the left eye limited the final visual acuity to 20/200. Visual acuity remained 20/20 on the right without any evidence of inflammation. CONCLUSION: This case demonstrates a broad range of potential outcomes after Candida endophthalmitis in the same patient, from very rare healing without antifungal treatment in one eye to severe panuveitis in the other eye. The delayed diagnosis in this case led to the inappropriate treatment with corticosteroids alone and delayed antifungal treatment. Early differentiation of Candida chorioretinitis from multifocal chorioretinitis is critical to final visual outcome.

Pre-S2 deletion mutants of hepatitis B virus could have an important role in hepatocarcinogenesis in Asian children.

Although many studies on the risk factors and their carcinogenesis in adult hepatocellular carcinoma (HCC) have been reported, they remain poorly understood in childhood HCC. A retrospective study of 42 HCC cases in Asian children was conducted. Hepatitis B virus (HBV)-DNA in HCC tissues was detected in 36 of 42 (86%) cases tested, while no hepatitis C virus (HCV)-RNA was detectable in any of HCCs. Twenty of 36 (56%) HCC cases were accompanied by cirrhosis. Surprisingly, very high prevalence of the HBV pre-S deletion mutant was recognized in 27 of 30 (90%) HCCs examined. They occurred most frequently in pre-S2 (20/27, 74%) followed by pre-S1 (5/27, 18.5%), and both pre-S1/S2 (2/27, 7.4%). Interestingly, the pre-S2 mutant consistently appeared with deletion at nt 4-57 in all of the 20 cases with the pre-S2 mutant (100%) and within this locus in the two cases with both pre-S-1/S2 mutants. Type II ground-glass hepatocytes in non-tumorous livers were seen in 15 of the 22 HCCs with the pre-S2 deletion mutant (68%). This hotspot mutation in the pre-S2 was further confirmed by complete genomic sequence of HBV in a Japanese boy who eventually developed HCC. Our result strongly suggests that HBV is a major contributor to the development of HCC in Asian children. The HBV pre-S2 deletion mutant at nt 4-57 which has a CD8 T-cell epitope could be responsible for the emergence and aggressive outcome of childhood HCC. Determination of this hotspot mutation in the pre-S2 region could be a useful index for predicting the clinical outcome of HCC development.