Ying-Cheng Shen

Intracameral Voriconazole Injection in the Treatment of Fungal Endophthalmitis Resulting From Keratitis

PURPOSE To report the therapeutic efficacy of intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. DESIGN Retrospective, single-institution, consecutive case series. METHODS Microbiologic and medical records were reviewed for patients with positive intraocular culture results or proven pathologic features for fungal organisms and clinically diagnosed fungal endophthalmitis resulting from keratitis. Ten eyes were treated with an intracameral injection of 100 microg voriconazole. Clinical characteristics, treatment, and causative organisms were analyzed. RESULTS Fusarium and Aspergillus were the most common causative organisms. Voriconazole was injected intracamerally from 1 to 8 times. Of the 7 patients who received 5 or more repeat injections, 6 were caused by Fusarium and 1 by Acremonium. In the remaining 3 patients who were administered 4 or fewer voriconazole injections, the causative organisms were Aspergillus and Alternaria. CONCLUSIONS Intracameral voriconazole injection may be an effective treatment for fungal endophthalmitis contiguously spreading from keratitis.

Paper-based ELISA to rapidly detect Escherichia coli.

Escherichia coli is a generic indicator of fecal contamination, and certain serotypes cause food- and water-borne illness such as O157:H7. In the clinic, detection of bacteriuria, which is often due to E. coli, is critical before certain surgical procedures or in cases of nosocomial infection to prevent further adverse events such as postoperative infection or sepsis. In low- and middle-income countries, where insufficient equipment and facilities preclude modern methods of detection, a simple, low-cost diagnostic device to detect E. coli in water and in the clinic will have significant impact. We have developed a simple paper-based colorimetric platform to detect E. coli contamination in 5h. On this platform, the mean color intensity for samples with 10(5)cells/mL is 0.118±0.002 (n=4), and 0.0145±0.003 (P<0.01⁎⁎) for uncontaminated samples. This technique is less time-consuming, easier to perform, and less expensive than conventional methods. Thus, paper-based ELISA is an innovative point-of-care diagnostic tool to rapidly detect E. coli, and possibly other pathogens when customized as appropriate, especially in areas that lack advanced clinical equipment.

Pharmacokinetics of Intracameral Voriconazole Injection

ABSTRACT Elimination of voriconazole after intracameral injection exhibited an exponential decay with a half-life of 22 min. Voriconazole levels in the vitreous humor were below the detectable limit. The aqueous concentrations achieved with a 25-μg dose during the first 2 h were greater than the previously reported MICs of organisms most involved in fungal endophthalmitis. A rapid decline in intracameral concentration suggests that frequent supplementation of intracameral voriconazole may be required in clinical settings.

Diffuse lamellar keratitis induced by toxic chemicals after laser in situ keratomileusis.

PURPOSE: To assess whether toxic chemicals produced during autoclaving sterilization were 1 of the main causes of diffuse lamellar keratitis (DLK) and to analyze the clinical outcomes of patients developing DLK after laser in situ keratomileusis (LASIK) treated with intensive topical corticosteroids. SETTING: Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China. METHODS: A total of 14 eyes of 7 patients received technically smooth LASIK and developed DLK, including 6 severe and 8 mild DLK cases. In all eyes the same microkeratome was used; it was contaminated with toxic chemical materials produced accidentally by coautoclaving instruments and a foam piece. RESULTS: Six eyes of 3 patients developed severe DLK on the same day, and 8 eyes of 4 patients developed mild DLK during the next LASIK surgery. After intensive topical corticosteroid treatment, lamellar infiltrates disappeared in 3 days in mild DLK eyes and 2 weeks in severe DLK eyes. No eye was treated with flap lifting and interface irrigation. For grade 4 DLK, the corneal opacity and flap folds disappeared in 4 weeks. There were no instances of permanent corneal scarring or loss of best spectacle‐corrected visual acuity. CONCLUSIONS: Toxic chemicals produced during instrument autoclaving sterilization are a possible cause of DLK. Immediate diagnosis and treatment with intensive corticosteroid drops are critical and can resolve severe DLK.

Supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis.

Purpose: To evaluate the efficacy of supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis (SLK). Methods: Forty eyes of 20 patients were diagnosed with SLK. All eyes with long-standing severe ocular irritation unresponsive to topical steroid and artificial tears were treated with supratarsal triamcinolone injection in addition to ongoing treatment of dry eye. Objective tarsal conjunctiva inflammation, bulbar conjunctiva, cornea staining, and subjective symptom gradings were performed before and after 2 weeks of therapy. All patients underwent laboratory evaluations of underlying systemic abnormalities. Results: All 40 eyes responded well to treatment and had long-term (average, 7.8 months) improvement of irritation and dry sensation and improvement of inflammation and staining of conjunctiva and cornea. Fourteen patients (70%) had associated autoimmune diseases. There were no irreversible complications related to this therapy. Conclusions: Supratarsal triamcinolone injection effectively and rapidly resolved symptoms and signs associated with SLK. It is helpful as primary or adjunctive therapy for SLK.

Comparison of Voriconazole Concentration in the Aqueous Humor and Vitreous between Non-Scraped and Scraped Corneal Epithelium Groups after Topical 1% Voriconazole Application

Purpose: To investigate the penetration of topical 1% voriconazole through the cornea into the aqueous humor in New Zealand white rabbits and to determine the effect of mechanical scraping of the corneal epithelium. Materials and Methods: The right eyes of 29 New Zealand white rabbits were maintained with the epithelium intact, and the left eyes underwent mechanical epithelium debridement of the central 7.5 mm of the cornea. A loading dose consisted of a drop of 1% voriconazole applied every 5 min for the initial half hour and followed by a maintenance dose consisting of a drop every 20 min, which was applied for about 2 hr. Then, the first sample was obtained 5 min after the first seven doses (loading dose) were given, and then four more samples were taken 5 min after four more subsequent drops (maintenance dose). The samples were analyzed by high performance liquid chromatography. Results: The mean aqueous concentration of voriconazole was 33.44 ± 5.77 μg/mL 5 min after the loading dose in the non-scraped group and 57.67 ± 6.77 μg/mL in the scraped group, respectively. The mean aqueous concentration of voriconazole was maintained in a range from 19.97 to 23.70 μg/mL 5 min after the maintenance doses in the non-scraped group and from 44.44 to 49.02 μg/ mL in the scraped group. The mean vitreous concentration of voriconazole ranged from 0.38 to 0.49 μg/mL in the non-scraped group and ranged from 0.72 to 0.94 μg/mL in the scraped group. These levels were statistically significant (P < 0.05) between the scraped and non-scraped groups. Conclusions: Topically administered voriconazole achieved minimum inhibitory concentrations in the aqueous for all the organisms most commonly involved in fungal endophthalmitis and achieved minimum inhibitory concentrations in the vitreous for some pathogenic fungi. The concentrations of voriconazole were higher in the scraped group than in the non-scraped group.

Pharmacokinetics and Safety of Intravitreal Caspofungin

ABSTRACT Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 μg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 μg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 μg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

Normal Tension Glaucoma is not Associated With the Interleukin -1?? (???889) Genetic Polymorphism

BackgroundFactors other than intraocular pressure are likely to play a role in the pathogenesis of glaucomatous optic neuropathy, particularly in individuals with normal tension glaucoma (NTG). Recent laboratory evidence has shown that there are potential similarities between Alzheimer disease and NTG in cellular apoptosis leading to neurodegeneration. IL-1α (−889) T allele polymorphism has been found to increase the risk of developing Alzheimer disease. The aim of this study was to test in a Chinese cohort the hypothesis that IL-1α (−889) polymorphism is associated with NTG. MethodsOne hundred sixty-two unrelated patients with NTG were recruited and compared with 167 controls in a Chinese population. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique. Patients and controls were genotyped for the C/T polymorphism at position −889 of the IL-1α gene promoter region. ResultsThere was no significant difference in the frequency of IL-1α (−889) alleles or genotypes in the NTG population compared with that in the control group. ConclusionsWe conclude that C/T polymorphism at position −889 of the IL-1α gene promoter region does not increase the risk of developing NTG. However, further studies on NTG are necessary to investigate the genetic basis and factors involved in the development of the neurodegenerative process.

Progressive herpetic linear endotheliitis.

Purpose: To report the clinical course of a rare case of bilateral herpetic linear endotheliitis. Methods: A 70-year-old man presented with bilateral circumferential bullous edema with stromal edema progressing centrally in the left cornea and bilateral sensorineural hearing impairment simultaneously. Serum immunoglobulin G (IgG) and IgM antibodies against herpes simplex virus type 1 (HSV1) were tested for, and aqueous humor from both eyes was examined separately using polymerase chain reaction for the presence of HSV1 DNA. Results: Serum antibody titers against HSV1 were positive. In the polymerase chain reaction, the aqueous humor showed HSV1 DNA in both eyes. Forty milligrams of prednisolone was given per day and 200 mg of oral acyclovir was given 4 times daily, but corneal edema progressed. After penetrating keratoplasty surgery in the left eye, recurrent herpetic endotheliitis also seemed to occur. Conclusions: HSV-1 may cause bilateral corneal linear endotheliitis and hearing impairment simultaneously. Linear endotheliitis should be regarded as a manifestation of HSV1 corneal infection. There is a poor prognosis, and severe corneal edema can result if aggressive treatment is not used.

Pterygium is related to a decrease in corneal endothelial cell density.

Purpose: The aim of this study was to investigate the relationship between pterygium and a decrease in the corneal endothelial cell density (ECD) in patients with unilateral primary pterygium. Methods: In this retrospective cross-sectional study, 90 consecutive patients with unilateral primary pterygium were enrolled from January 2010 to June 2012. Corneal ECD was measured in both eyes, and the fellow eyes were considered as controls. The relationship between the percentage of pterygium to cornea and a decrease in the ECD was analyzed. An increase in astigmatism in eyes with pterygium was evaluated for association with decreased ECD using the Pearson correlation test. Results: The percentage of pterygium to cornea ranged from 3.5% to 65.2%, with a median of 12.35%. The difference in the corneal ECD between eyes with pterygium and control eyes ranged from +9.6% to −37.7%, with a median of −9.75%. The results of the Pearson correlation statistical test showed a strong logarithmic correlation between a decrease in the corneal ECD and the percentage of pterygium to cornea (R = 0.688, P < 0.001). An increase in astigmatism was correlated with a decrease in the ECD in eyes with pterygium. Conclusions: Pterygium is related to a decrease in corneal ECD. Surgical intervention should be considered in patients with extensive pterygium involvement in the cornea or a significant increase in astigmatism.