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.

Klebsiella endophthalmitis as the herald of occult colorectal cancer.

A 67-year-old Chinese man presented with acute loss of vision and pain in the left eye with hypopyon in the anterior chamber. The patient was afebrile with no systemic symptoms at presentation. Diagnosis of endogenous endophthalmitis was made with vitreous tap yielding Klebsiella pneumoniae Pars plana vitrectomy was performed twice to clear the infection. Thorough investigations showed no septic foci. Whole body positron emission tomography CT revealed a rectal tumour and biopsy showed adenocarcinoma. He was treated with neoadjuvant chemoirradiation followed by surgery to resect the tumour. Vision in the left eye was hand movement at 12 months postoperatively. This case illustrates Klebsiella endogenous endophthalmitis might be a herald of occult colorectal cancer. Bacteria might gain access into bloodstream via mucosal defect in the tumour.

Isolates and antibiotic susceptibilities of endogenous bacterial endophthalmitis: A retrospective multicenter study in Japan.

Endogenous bacterial endophthalmitis, also called metastatic endophthalmitis, is a rare bacterial endophthalmitis derived from distant infectious foci via the bloodstream. This infection can potentially cause not only severe visual disturbance, but also loss of the eyeball or death, as most patients are immunocompromised. This retrospective Japanese multicenter study analyzed 32 eyes in 25 definitive cases. Twelve patients (48.0%) had diabetes mellitus. Typical ocular findings were vitreous haze (87.5%), cells in the anterior chambers (62.5%) and retinal infiltrates (50.0%). Elevated body temperature (64.0%), high serum C-reactive protein (96.0%) and leukocytosis (52.0%) were also frequently observed. Culture positivity rates for intraocular fluid were higher in the vitreous (62.5%) versus aqueous humor (28.6%). High positivity rates were also observed for blood (57.1%) and central venous catheters (100%). The most common pathogen was Staphylococcus aureus (10 cases), including methicillin-resistant S. aureus (4 cases). The next most common pathogen was Klebsiella pneumoniae (7 cases), which was highly associated with liver abscess. Compared to a previous 1991 national multicenter study, there has been a fourfold increase in the ratio of S. aureus. Antibiotic susceptibility tests revealed that all Gram-positives were susceptible to vancomycin and all Gram-negatives were susceptible to third-generation cephalosporins, imipenem/cilastatin, gentamycin and levofloxacin. Prognostic factors influencing poor visual outcome included poor initial visual acuity (p < 0.01), K. pneumoniae (p = 0.027) and gram-negative bacteria (p = 0.014) as the causative bacteria. Intravitreal antibiotic injection in combination with vancomycin and ceftazidime may be applicable for use as part of the standard treatment regimen for EBE.

Diagnostic performance of blood culture bottles for vitreous culture compared to conventional microbiological cultures in patients with suspected endophthalmitis.

The purpose of this investigation was to evaluate the performance of blood culture bottles in comparison to conventional microbiological culture techniques in detecting causative microorganisms of endophthalmitis and to determine their anti-infective susceptibility profiles. All consecutive cases with clinically suspected endophthalmitis in a university-based ophthalmology department between January 2009 and December 2016 were analysed in this retrospective comparative case series. Samples from 247 patients with suspected endophthalmitis underwent microbiological diagnostic work-up. All three culture methods were performed from 140 vitreous specimens. Vitreous fluid specimens were inoculated in blood culture bottles, aerobic and anaerobic broth solutions, and on solid media. Anti-infective susceptibility profiles were evaluated by semi-automated methods and/or gradient diffusion methods. Microorganisms were grown in 82 of 140 specimens for which all methods were performed (59%). Microorganisms were more frequently grown from blood culture bottles (55%) compared to broth solution (45%, p = 0.007) and solid media (33%, p < 0.0001). Considerable differences in the performance among culture media were detected for fungal pathogens. All grown fungi were detected by blood culture bottles (11 of 11, 100%). Broth solution recovered 64% and solid media 46% of grown fungi. No Gram-positive bacterium was resistant to vancomycin and all Gram-negative pathogens except for one isolate were susceptible to third-generation cephalosporins. In suspected endophthalmitis patients, blood culture bottles have a higher overall pathogen detection rate from vitreous fluid compared to conventional microbiological media, especially for fungi. The initial intravitreal antibiotic therapy with vancomycin plus third-generation cephalosporins appears to be an appropriate treatment approach for bacterial endophthalmitis.

[Characteristics of inflammatory response in patients after senile cataract surgery].

The aim of the work was to study prognostic value of some laboratory markers (anti-DNA antibodies, cell adhesive molecules, neopterin) in heriatric patients with exudative inflammation after cataract surgery. 12 in-patients with postoperative iridocyclitis and endophthalmitis were included. The assays were taken twice: after admission and before discharging. The follow-up period was 6 months. Preliminary data show that high serum levels of sVCAM, sICAM and anti-DNA antibodies, as well as very low levels of anti-DNA antibodies seems to be associated with poor outcomes in those patients (enucleation, blindness, lens extraction). Small cohort doesn't allow us to make strict conclusion about prognostic value of these laboratory markers. The study should be continued.

[Ocular toxocariasis--case report]. / TOXOCAROZA OCULARA (PREZENTARE DE CAZ).

Ocular Toxocariasis is a parasitosis caused by Toxocara catis/canis larvae localized in the eye. The most frequent clinical manifestations are the central retinal granuloma, peripheral retinal granuloma and chronic endophthalmitis. Secondary complications due to the presence of parasite in the posterior segment of the eye may have significant consequences on visual function. We present the case of a 23 years old patient, admitted for progressive decrease of the right eye BCVA during the last 6 months. After performing clinical examination and serological tests we established the diagnosis of ocular Toxocariasis. The patient presented a particular form of the disease consisting in the presence of both a central retinal granuloma and a peripheral one. We performed 23G pars plana vitrectomy and membrane peeling. VA improved as soon as the first month after surgery.

A liver abscess deprived a healthy adult of eyesight: endogenous endophthalmitis associated with a pyogenic liver abscess caused by serotype K1 Klebsiella pneumonia.

Klebsiella pneumonia usually causes urinary tract infections, pneumonia, and other infectious diseases in hospitalized and immunocompromised patients. Among the types of Klebsiella pneumonia, serotype K1 is known to be a highly virulent pathogen. We herein report the case of a healthy 63-year-old man with a pyogenic liver abscess and bilateral endogenous endophthalmitis caused by serotype K1 Klebsiella pneumonia. Although the patient received percutaneous abscess drainage and antibiotic therapy, he lost his eyesight. To improve the poor prognoses of ocular complications, providing both an earlier diagnosis and treatment is critical.

A case of endogenous endophthalmitis complicated by neutropenia following bacteremia with Streptococcus mitis resistant to beta-lactam antibiotics.

This report is focused on a case of endogenous endophthalmitis following Streptococcus mitis bacteremia that occurred during chemotherapy for acute myeloid leukemia, despite broad-spectrum beta-lactam antibiotics and vancomycin. The patient partially recovered visual acuity. In conclusion, Streptococcus mitis bacteremia complicated by febrile neutropenia may cause endogenous endophthalmitis within a very short timeframe.

Discrepancy of in-vitro data and clinical efficacy of micafungin against Candida tropicalis endophthalmitis.

We report findings for a 74-year-old woman with Candida tropicalis endophthalmitis for whom an increase in b-D-glucan level and worsening of endophthalmitis were observed after intravenous injection of micafungin, an echinocandin antifungal agent. Endogenous endophthalmitis caused by C. tropicalis developed in both eyes. On the basis of her surgical history, laboratory data,and lesions, tentative diagnosis of fungal endophthalmitis was made. She was then treated with fluconazole and itraconazole, but the b-D-glucan level did not decrease, and there was no improvement of the endophthalmitis. The fluconazole was discontinued and replaced by micafungin.Unexpectedly, the level of b-D-glucan increased and endophthalmitis did not improve. The micafungin was immediately stopped and replaced by intravenous fluconazole with amphotericin B syrup, but the itraconazole was continued. Marked resolution of the vitreous inflammation was observed in both eyes, and the serum b-D-glucan level was reduced. Because active macular infiltrates were observed in the right eye, vitrectomy was performed. The micafungin minimum inhibitory concentration against the C. tropicalis strain isolated from our patient was 0.03 lg/ml. This paradoxical effect of micafungin should be remembered, and b-D-glucan level should be frequently monitored after intravenous injection of micafungin.

Mannose-binding lectin as part of the complement pathway: characterization in non-inflamed and inflamed human eyes.

BACKGROUND: Mannose-binding lectin plays a central effector role in the lectin pathway of complement activation. Frequently occurring MBL2 polymorphisms result in mannose-binding lectin deficiency, which increases susceptibility to infection. We characterized mannose-binding lectin levels and function in non-inflamed and inflamed human eyes, and evaluated its relationship to blood mannose-binding lectin levels and function. DESIGN: Prospective, observational clinical study with controls and cases. PARTICIPANTS: Twenty-seven patients with paired blood and ocular samples (aqueous and/or vitreous) including 15 controls (non-inflamed) and 12 cases (inflamed). METHODS: Blood and ocular samples were collected from controls (n = 15) with quiet eyes during elective cataract surgery and cases with inflamed eyes including proven/suspected endophthalmitis (n = 11) and herpetic retinal vasculitis (n = 1). Mannan-binding and C4 deposition enzyme-linked quantify mannose-binding lectin levels and function. MAIN OUTCOME MEASURES: Blood and ocular mannose-binding lectin levels and function. RESULTS: Of 27 patients, 10 (37%) were mannose-binding lectin-deficient (defined as blood mannose-binding lectin levels <500 ng/mL). Blood mannose-binding lectin levels (P= 0.16) or function (P= 0.43) were not significantly different between controls and cases. As expected, there was a high correlation between blood mannose-binding lectin levels and function (r(2) = 0.74). However, there was significantly more mannose-binding lectin in inflamed eyes than non-inflamed eyes measured as level (P < 0.01) or C4 deposition function (P < 0.01). CONCLUSIONS: Our study demonstrated that mannose-binding lectin is significantly elevated in inflamed human eyes but virtually undetectable in non-inflamed control eyes, suggesting a role in sight-threatening ocular inflammation.

[Intestinal endotoxin in the pathogenesis of ocular inflammatory diseases and the antiendoxin constituent of its treatment].

Blood was studied in 119 patients with ocular inflammatory lesions: endophthalmitis (n = 10), iridocyclitis of viral (n = 47) and unknown (n = 62) genesis, by using the procedures developed by the authors to determine the integral values of the concentration of endotoxin in systemic blood flow and the activity of antiendotoxin immunity. Intestinal endotoxin aggression was found to be involved in the pathogenesis of ocular inflammatory diseases. The use of drugs and procedures, which could diminish the entry of intestinal endotoxin into the blood stream and intensify the processes of its binding and release from systemic blood circulation, substantially enhanced the efficiency of a therapeutic process.

Family history of inflammatory bowel disease in patients with idiopathic ocular inflammation.

PURPOSE: To determine the prevalence of a family history (FMH) of inflammatory bowel disease (IBD) in patients with idiopathic ocular inflammation (OI). DESIGN: Retrospective observational study. METHODS: Medical records of idiopathic OI patients seen between January 1995 and June 2005 in the University of Illinois Uveitis Clinic were screened for a FMH of IBD. FMH included first, second, and third degree relatives. RESULTS: 727 (32.8%) patients had idiopathic OI. 26 of 727 (3.6%) and 10 of 727 (1.4%) reported a FMH of ulcerative colitis (UC) and Crohn's disease, respectively. 16 (2.2%) patients with a FMH of indeterminate colitis were excluded from subsequent comparisons. The prevalence of a FMH of IBD among patients with idiopathic OI was 3- to 15-fold higher than the prevalence of UC and Crohn's in the general population (0.055% to 0.27%). Keratoiritis was more common and granulomatous disease less frequent in patients with a FMH of IBD (P = .014 and .019). Patients tested 26.3% with a FMH of IBD, and 66.7% of patients tested with IBD themselves, were HLA-B27 positive (odds ratio [OR] 5.6, 95% confidence interval [CI] 0.77 to 45.8), compared with 40.1% of patients with neither (OR 1.87, 95% CI 0.61 to 6.83). CONCLUSIONS: A FMH of IBD may be an independent risk factor for the development of OI. In contrast to the subgroup of patients with a personal history of IBD, HLA-B27 may not be an appropriate marker in the subgroup of patients with merely a FMH of IBD, emphasizing the importance of investigating other immunologic factors that may predispose patients with IBD and their relatives to OI.

[Experimental intraocular introduction of blood serum of patients with endophthalmitis]. / Vnutriglaznoe vvedenie syvorotki krovi patsientov s éndoftal'mitom v éksperimente.

Effects of blood serum from patients with endophthalmitis, who systematically received gentamicin at therapeutic dose, exerted on the retina of healthy rabbits were experimentally studied. A moderate toxic effect produced by gentamicin on the retina, when it was administered in the vitreous body of rabbits, was detected yet on day 1 of the experiment. Changes of retinal electrogenesis were aggravating and, beginning from day 7, there were noted profound changes of the functional activity in all retinal layers. According to the results, the blood serum from patients with endophthalmitis, who were systematically receiving gantamicin at therapeutic dose, does not virtually have any negative effect on the functional condition of the retina and can be used for intracavitary administration.

[Ultraviolet irradiation of blood in combined treatment of traumatic endophthalmitis]. / Ul'trafioletovoe obluchenie autokrovi v kompleksnom lechenii travmaticheskikh éndoftal'mitov.

Thirty-five patients (35 eyes) with traumatic endophthalmitis were treated. Ultraviolet exposure of autoblood was used in 16 patients, the rest 19 were treated routinely (antibiotics, etc.). Use of ultraviolet exposure of the blood in combined therapy of traumatic endophthalmitis more rapidly (12.6 vs. 22.1 days) and effectively (93.7 vs. 68.4%) arrested intraocular infection and more often preserved the objective vision (31.3 vs. 10.5%).

[Fluconazole level in aqueous humor after oral drug administration in humans]. / Fluconazolspiegel im Kammerwasser nach oraler Wirkstoffgabe beim Menschen.

For 2 years fluconazole, a triazole antimycotic, has been available for treatment of systemic mycosis. Compared to amphotericin B fewer severe side effects have been reported. So far, no data have been published as to its penetration into the human eye. In the present study, 20 cataract patients were given 200 mg fluconazole (0.5 to 8 h preoperatively. During the cataract operation 0.1 ml of the aqueous was removed as well as 10 ml serum. With the help of high-pressure liquid chromatography (HPLC), the concentration of fluconazole in each of the samples was determine. If the aqueous humor was removed at least 2h after fluconazole application, concentrations between 2.7 and 5.4 micrograms/ml were reached (mean 3.7 +/- 2.17) In these cases the concentration in the aqueous humor was 80% of the concentration found in the serum at the same time. If the sample of the aqueous humor was collected only 1 h after application, 40% of the concentration in the serum was found in the aqueous humor. These data prove that fluconazole shows an extremely good penetration through the blood-aqueous barrier. After a single dose of 200 mg, a concentration is reached in the eye that surmounts the minimal inhibiting concentration found for Candida species sensitive to fluconazole. Therefore, fluconazole seems to be a good alternative to amphotericin B for the treatment of infections caused by such fungi.

C-reactive protein serum levels in patients with ocular disease.

Hepatocyte derived C-reactive protein (CRP) is a sensitive indicator for inflammatory or infectious processes in a variety of tissues. As several other plasma proteins it is regarded as part of the acute phase response to a variety of tissue damage. CRP is commonly used in general medicine as a tool for the follow-up of especially bacterial infections. However, it has not been widely used in ophthalmology. In the present study CRP values in serum samples from 51 patients with various acute ocular diseases were determined semiquantitatively. High CRP levels were found most frequently in patients with either preseptal cellulitis (83.3%) or endophthalmitis (25.8%) whereas in the serum of patients with keratitis and uveitis, CRP exceeded 20 mg/l in only 18.7% of the cases. In a control group of 10 patients with retinal detachment the mean CRP level was 2.3 mg/l (SD +/- 0.98 mg/ml). The clinical significance and the prognostic value of CRP determinations during ocular diseases are discussed.

[Interleukin-6 and other cytokines in the aqueous humor in uveitis and endophthalmitis]. / Interleukine-6 et autres cytokines dans l'humeur aqueuse au cours d'uvéites et d'endophtalmies.

We studied aqueous humour and serum level of 4 cytokines during uveitis and endophthalmitis: Interleukin 6, Gamma interferon, tumor necrosis factor and Granulocyte-macrophage colony stimulating factor. High levels of IL-6 were found in aqueous humour during ocular inflammation and infection. This elevation of IL-6 level was more constant and more important in the endophthalmitis group (mean level 2.992 pg/ml) than in the uveitis group (mean level 1.480 pg/ml). During endophthalmitis no evident relation was found between IL-6 level and clinical course or aspect, or bacteriological results of anterior chamber tapes. In the uveitis group, no relation was found between IL-6 level and clinical aspect or aetiology.

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.

[Endogenous candida endophthalmitis in a drug dependent patient: intravenous therapy with liposome encapsulated amphotericin B]. / Endogene Candida-Endophthalmitis bei einem Drogenabhängigen: intravenöse Therapie mit liposomal verkapseltem Amphotericin B.

We report this exemplary case of a drug addict with candida endophthalmitis where we used the new form of amphotericin B, encapsulated in liposomes. We were able to reconfirm the reduced number of side effects and the minimized nephrotoxicity reported by authors of other specialties. In our patient, a reduction or elimination of the yeast was probably achieved, nevertheless, he developed a traction retinal detachment. In future cases of fungal endophthalmitis, we recommend liposomal amphotericin B in higher doses.

Penetration of imipenem into human aqueous and vitreous humor.

Twenty-five patients about to undergo cataract surgery and ten patients about to undergo vitrectomy received a 1-g intravenous dose of imipenem before surgery. Specimens of aqueous or vitreous humor were then obtained and assayed for antibiotic content with a microbiologic disk agar technique. A mean peak aqueous humor level of 2.99 micrograms/ml was found at approximately two hours after administration, and a mean vitreous level of 2.53 micrograms/ml was found from two hours to three hours 15 minutes after administration. These concentrations were well above the minimum inhibitory concentration of imipenem for 90% (MIC90) of Staphylococcus epidermidis, S. aureus, and the Enterobacteriaceae commonly involved in bacterial endophthalmitis.