Li-Chen Wei

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.

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.

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.

Analysis of the Interleukin-6 (-174) Locus Polymorphism and Serum IL-6 Levels with the Severity of Normal Tension Glaucoma

Purpose: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. Recent studies of glaucoma or retinal ganglion cells (RGCs) reveal that the cytokine interleukin-6 (IL-6) is linked to the pathogenesis of glaucoma and may regulate RGC survival or death. The IL-6 (-174) G allele has also been shown to increase the IL-6 protein. We hypothesized that the IL-6 (-174) polymorphism may be a predisposing genetic factor affecting the severity of glaucoma. The aim of the present study was to evaluate the IL-6 polymorphism and serum IL-6 levels as a potential risk factor related to the severity of NTG. Methods: A total of 256 subjects with NTG in the Chinese population were enrolled. The patients were genotyped for the IL-6 (-174) C/G polymorphism. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Serum IL-6 levels were measured by ELISA. Patient age at diagnosis, cup/disc (C/D) ratio, rim area (RA), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) were analyzed. The associations between genotypes of IL-6 (-174) C/G and the clinical parameters were calculated using a logistic regression. Results: The IL-6 (-174) GC genotype in NTG patients was significantly associated with a smaller C/D ratio (p = 0.04), larger RA (p = 0.04), and thicker RNFL (p = 0.05) compared with IL-6 (-174) GG patients. The allele frequency of IL-6 (-174) C was significantly higher in the NTG patients at an early-moderate stage than at an advanced stage according to the C/D ratio (OR 0.55; 95% CI 0.31-0.99). Pattern standard deviation of VF was borderline lower in IL-6 (-174) GC patients (p = 0.06), and serum IL-6 levels were borderline higher in advanced stages than in early-moderate stages (7.66 ± 3.22 vs. 4.46 ± 3.83 pg/mL; p = 0.06). Conclusion: The IL-6 (-174) GC genotype is associated with a smaller C/D ratio, larger RA, and thicker RNFL compared with IL-6 (-174) GG in NTG patients. We found that the IL-6 (-174) G/C polymorphism and serum IL-6 levels may be associated with the severity of NTG.

Subconjuntival Fat Prolapse after Autogenous Fat Graft: A Case Report

Purpose: To report an extremely rare case of subconjunctival herniated orbital fat and grafted fat after autogenous fat graft.Method: A case report.Results: A 51 year-old non-obese female suffered from redness and several subconjunctival masses in the right eye over the upper and temporal lower subconjunctival areas. The masses were noted after autogenous fat grafting from the abdomen to the periorbital hollows. The ocular examination revealed multiple subconjunctival yellow masses and conjunctival injection. Excision of the subconjunctival fat pad was done one year after autogenous fat graft surgery. The histopathology revealed fatty tissue and lipogranuloma formation with peripheral histiocyte infiltration. The orbital fat and grafted fat herniated between the conjunctiva and the sclera, presumably due to high intra-orbital pressure after fat grafting, resulting in dehiscence of the Tenons capsule.Conclusion: We present an extremely rare case of subconjunctival fat herniation, which could be complicated after autogenous fat graft. Ophthalmologists and plastic surgeons should be aware of the possibility of this complication.

Late-Onset Interface Abscess after LASIK

Purpose: To report a rare case of interface abscess 3 years after laser in situ keratomileusis (LASIK). Method: Observational case report. We described a case of 24-year-old man who had a history of uneventful corneal flap surgery and presented with interface abscess. Results: The corneal flap was lifted and irrigated with antibiotic solution. Pathology of the abscess showed scant viable epithelial cells in cell debris. Upon microbiological investigation, the microorganism isolated was Staphylococcus epidermidis. It is postulated that epithelial injury or hypoxia could induce alterations in the metabolism, break down epithelial protection, and allow epithelial cells and normal flora bacteria to enter spaces with little resistance. Conclusion: Our case indicates that infectious interface abscess can occur several years after corneal flap surgery. Rapid recognition of the causative organism and aggressive medical and surgical management of the infection can improve the prognosis. Epithelial ingrowth may be associated with an increase of the risk of late-onset interface abscess.