CLINICAL UTILITY OF BETA-D-GLUCAN TESTING FOR ENDOGENOUS FUNGAL CHORIORETINITIS OR ENDOPHTHALMITIS.

PURPOSE: To evaluate serum beta-D-glucan (BDG) as a biomarker for endogenous fungal eye infection. METHODS: Retrospective case-control study of 88 patients with a BDG test and eye examination at UPenn (2013-2018). Cases had endogenous fungal chorioretinitis or endophthalmitis diagnosed by eye examination and confirmed with positive culture; controls were without these fungal eye findings. Charts were reviewed for BDG values, blood/vitreous cultures, and eye examinations. Outcomes were BDG sensitivity, specificity, positive predictive value, and negative predictive value for fungal chorioretinitis or endophthalmitis, using prespecified BDG cut-off points of ≥80, ≥250, and ≥500 pg/mL as test positive. RESULTS: Cases included six chorioretinitis and four endophthalmitis patients. Controls included 78 patients without chorioretinitis or endophthalmitis. Defining BDG ≥80 pg/mL as test positive, the BDG sensitivity (95% confidence interval) was 66.7% (22.3%-95.7%) for chorioretinitis and 100% (39.8%-100%) for endophthalmitis. The specificity was 74.4% (63.2%-83.6%) when BDG values ≥80 pg/mL were test positive, and 85.9% (76.2%-92.7%) when values ≥250 pg/mL were test positive. For a 1% endophthalmitis prevalence and BDG cut-off value of ≥80 pg/mL, the positive predictive value was 3.8% (2.4%-5.2%) and negative predictive value was 100% (99.1%-100%). CONCLUSION: For endogenous fungal endophthalmitis, BDG's sensitivity and specificity seem good and the negative predictive value is high; a larger ophthalmic study is indicated.

Case of cryptococcal choroiditis in adult with T-cell leukemia/lymphoma.

A rare case of 70-year-old woman with adult T-cell leukemia/lymphoma who developed multifocal choroiditis from a dissemination of Cryptococcus neoformans is reported. Ophthalmologic examination revealed multiple yellowish choroidal lesions in the posterior pole of both eyes. Sequential optical coherence tomographic images disclosed the involvement of the choroid and the consecutive changes in its architecture during the course of treatment. The recognition of these ocular manifestations may be important for the rapid diagnosis of C. nerformans-disseminated diseases. Rapid diagnosis and prompt therapy with intravitreal injection as well as systemic fosfluconazole and liposomal amphotericin B led to clinical improvement of intraocular cryptococcosis.

Serum IgE Levels: An Effective Diagnostic Tool for Evaluation and Monitoring of Orbital Fungal Granuloma.

OBJECTIVE: To determine the changes in IgE levels in diagnosis and postoperative monitoring of orbital fungal granuloma. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from July 2012 to June 2013. METHODOLOGY: Cases with clinically high index of suspicion for orbital fungal granuloma and 50 healthy volunteers were inducted as control subjects. Patients with recurrent cases of orbital fungal granuloma, previous orbital surgery, and those with very low clinical suspicion of fungal granuloma were excluded. Total serum IgE level (IU/ml), eosinophil counts and skin prick test were performed in all subjects. Independent t-test was used for comparison of healthy volunteers and patients with biopsy proven orbital fungal granuloma. Repeated measures ANOVA was used for comparing the preoperative and postoperative total serum IgE level of patients with biopsy proven fungal granuloma. RESULTS: The mean total serum IgE level for the healthy volunteers was 208.82 ±41.43 IU/ml. The mean pre-operative IgE value of histologically confirmed cases of fungal granuloma was 1613.72 ±282.83 IU/ml. The total serum IgE level gradually declined after surgery and anti-fungal treatment. The mean serum IgE level 3, 6 and 9 months postoperatively were 1039.48 ±308.40, 568.77 ±162.01 and 224.92 ±51.55 IU/ml respectively. These tests showed that the drop in IgE level in cases of fungal granuloma with treatment was statistically significant (p < 0.001). CONCLUSION: Total serum IgE level can be used as a reliable diagnostic and postoperative monitoring tool in orbital fungal granuloma.

Interleukin 17 expression in peripheral blood neutrophils from fungal keratitis patients and healthy cohorts in southern India.

Interleukin 17A (IL-17) production by peripheral blood neutrophils was examined in patients with fungal keratitis and in uninfected individuals in southern India, which has high levels of airborne Aspergillus and Fusarium conidia. Il17a gene expression and intracellular IL-17 were detected in all groups, although levels were significantly elevated in neutrophils from patients with keratitis. There were no significant differences in plasma IL-17 and IL-23 between patients with keratitis and uninfected individuals; however, combined data from all groups showed a correlation between the percentage IL-17 producing neutrophils and plasma IL-23, and between plasma IL-17 and IL-6 and IL-23.

Detection of Histoplasma capsulatum DNA in peripheral blood from a patient with ocular histoplasmosis syndrome.

Ocular histoplasmosis syndrome (OHS) is a significant cause of vision loss in young and middle-aged adults. We report here a case of an immunocompetent 37-year-old man who presented fever, malaise, headache, and anterior cervical lymphadenopathy for one week, after which he started to experience a sudden loss in visual acuity of his right eye. Fluorescent angiography and an optical coherent tomography demonstrated the presence of a type II choroidal neo-vascular membrane in the right eye, suggesting a diagnosis of OHS. A peripheral blood sample was tested by nested PCR to detect Histoplasma capsulatum using a set of primers known to amplify a DNA sequence coding for a specific 100-kDa protein of this fungus (Hc100-PCR). The blood sample was Hc100-PCR-positive and sequence analysis showed an identity of 97% with the reference sequence. The patient received intravitreal bevacizumab injection and itraconazol therapy, leading to an improvement in media vision acuity. In this case, the molecular test provided evidence linking the ocular lesions with an earlier infection by H. capsulatum and demonstrated that the Hc100-nested PCR assay is a valuable tool in the diagnosis of histoplasmosis.

Elevated serum beta-D-glucan level and depressed neutrophil phagocytosis in a heatstroke patient.

Endotoxemia has been reported as a mechanism for the fatal sequela after heatstroke. Subsequent disseminated fungal infection in a heatstroke patient has been also described. Beta-D-glucan, a constituent of the fungal cell wall, is an early diagnostic measure for fungal infection. In a heatstroke case, we examined for the first time levels of serum beta-d-glucan and endotoxin. A 34-year-old man with a body temperature of 43.5 degrees C was admitted in a state of shock. Prior to the development of disseminated intravascular coagulopathy (DIC), a remarkable elevation of serum beta-D-glucan level to 116 pg/mL (normal level<6.0 pg/mL) was revealed on the first day of admission. However, serum endotoxin was not detected when using a method that excluded beta-D-glucan contamination from endotoxin measurement (normal level<1.0 pg/mL). This change of beta-D-glucan level was accompanied by a depressed neutrophil function, especially in phagocytosis of 34% (normal range 70-90%) but not in bacterocidal function (81% versus a normal range of 70-100%). After intensive care including continuous hemodiafiltration, the patient regained consciousness but remained ataxic due to cerebellar infarction, which might have resulted from DIC, and subsequent bilateral fungal oculitis were revealed 45 days after admission. This case report demonstrates the elevation of serum beta-D-glucan but normal endotoxin levels after heatstroke, which may prompt further study to re-examine the serum levels of endotoxin in such catastrophic insults.

The syndrome of presumed ocular histoplasmosis in Mexico: a preliminary study.

A study to screen for the syndrome of presumed ocular histoplasmosis (SPOH) among native populations from three Mexican states was performed. Two of these states, Guerrero and Querétaro, were selected as histoplasmosis is endemic there, whereas Tlaxcala was considered a control, due to the absence of reported cases. A total of 253 individuals were submitted to ocular fundus examination to obtain evidence of SPOH. A high percentage of positive reactors to histoplasmin skin test (ST) was observed in Guerrero (83%) and Querétaro (53%), whereas in Tlaxcala positive ST were almost absent (2.04%). Only five individuals had retinal lesions, although these lesions were not characteristic of the syndrome. Stimulation of these individual's cells showed different patterns in the histoplasmin-induced lymphocyte transformation response, and two out of five individuals with retinal lesions presented a stimulated response, as well as three controls without lesions. Histocompatibility antigens (HLA) were determined in a sample of each population and no particular allele, including HLA-B7, was found to be related to SPOH as reported in the USA; however, HLA-B22 was found in three individuals who developed pulmonary histoplasmosis. Results do not provide clinical evidence or data on specific HLA risk factors, for the presence of SPOH in the population studied.

Increased D-arabinitol/creatinine ratio in sera of patients with Behçet's disease during an active phase.

The ratios of D-arabinitol (a major metabolite of Candida species) to creatinine were examined in 46 sera of 40 patients with ocular inflammatory disease and in 50 age-matched normal controls (25 men and 25 women). The mean ratio in patients with endogenous Candida endophthalmitis was higher than in the normal controls. Seven samples taken from patients with Behçet's disease during an active phase showed higher values than in the controls. Fourteen patients with Behçet's disease in remission showed D-arabinitol/creatinine values within normal range. In four patients with sarcoidosis, in two patients with Vogt-Koyanagi-Harada disease, and in 16 patients with bilateral uveitis of an unknown cause, the ratios were within normal range. It is possible that D-arabinitol, or a metabolite of Candida species, may be related in part to the active phase of Behçet's disease.