Characterization and functional correlation of multiple imaging modalities with focal choroidal excavation.

BACKGROUND: To investigate the clinical manifestations and imaging features of near-infrared autofluorescence (NIA), infrared reflectance (IR), fundus autofluorescence (FAF), indocyanine green angiography (ICGA) and fluorescein angiography (FAG) in the detection of patients with focal choroidal excavation (FCE) identified by cross-sectional spectral-domain optical coherence tomography (SD-OCT). METHODS: This retrospective cross-sectional study included 12 eyes of 10 Taiwanese patients with FCE diagnosed by SD-OCT. The areas and depths of FCE in serial cross-sectional and en-face OCT were compared in different imaging modalities. NIA, IR, FAF, ICGA and FAG images were obtained. Best corrected visual acuity, subjective distortion area in the Amsler grid and history of maculopathies were also recorded. RESULTS: In areas where the choroid started to excavate as shown in SD-OCT, hypo-autofluorescence in NIA was noted. The area of hypo-fluorescence in NIA of all the FCE lesions showed good correlation with the size. The area of FCE was associated with complications such as choroidal neovascularization and central serous chorioretinopathy (p = 0.014, d.f = 1) and the volume (NIA area × Depth measured by SD-OCT × 1/3) was associated with subjective distortion strongly (p = 0.051, Spearman's correlation = 0.600). CONCLUSION: Among all image modalities, NIA was the most sensitive tool in area measurement of FCE and peripheral lesion detection. Also, the volume of FCE was associated with subjective distortion and the area was related to complications. Recording the area and volume of FCE could play an important role in monitoring complications.

Rapid resolution of stromal keratitis with the assistance of oral voriconazole in resistant acanthamoeba keratitis.

Acanthamoeba keratitis (AK) is an unusual infectious disease of the cornea which sometimes leads to blindness. We report the experience of adding oral voriconazole in conjunction with topical antiacanthamoebic drops to treat refractory AK. A 20-year-old girl experienced a deep stromal keratitis with large epithelial defect in the left eye, suspected as AK. The initial best-corrected visual acuity (BCVA) of the eye was counting finger. She received topical chlorhexidine 0.02% and voriconazole 1% during the first 14 days but in vain. Oral voriconazole was administered and resulted in a rapid regression of the lesion. A total resolution was achieved after 2 weeks of triple combination therapy. The BCVA of the left eye finally achieved 20/20 at 6-month follow-up. Although oral voriconazole was seldom used in treating acute AK, the additional use of oral voriconazole combined with topical antiacanthamoebic drugs may help to achieve a successful treatment effect in refractory stromal AK.

Modeling pegylated liposomal doxorubicin-induced hand-foot syndrome and intestinal mucositis in zebrafish.

Pegylated liposomal doxorubicin (PLD) has been widely used to treat cancer. The adverse effects of PLD noted in clinical practice, especially hand-foot syndrome (HFS), are regarded as unique, and the management methods for them remain limited. This study was aimed at developing a feasible experimental model for translational medicine to solve this clinical issue by using skin fluorescent transgenic zebrafish. We established an optimal protocol for the administration of Lipo-Dox™, a PLD in current clinical use, to the Tg(k18:dsred) zebrafish line expressing red fluorescence in keratinocytes. We made use of bodyweight, survival rate, gross observation, flssuorescent microscopic assessment, and pathological examination of the zebrafish to assess this model. The consecutive administration protocol of PLD resulted in growth retardation of the zebrafish embryo and survival impairment, indicating establishment of a significant toxicity. We observed fin necrosis and keratinocyte dissociation phenotypes in the PLD-treated fish after consecutive administration. The skin toxicity induced by the Lipo-Dox injection was subsequently reversible, which might be compatible with a clinical course of skin recovery after discontinuation of Lipo-Dox administration. Furthermore, we found that the number of intestinal goblet cells, an important marker of intestinal inflammation, in the Lipo-Dox-injected zebrafish was markedly increased, accompanied by impaired mucosal integrity. The intestinal inflammation induced by Lipo-Dox resembled the intestinal mucositis the clinical patients suffered from after the administration of PLD. In conclusion, we established a zebrafish model for PLD-induced HFS. The intestinal mucositis simultaneously noted in the PLD-treated zebrafish validated the similarity of clinical courses after administration of PLD. This model is easily assessable, efficient, and worthy for use in developing a new therapeutic protocol for prevention or treatment of HFS as well as intestinal mucositis. Further clinical investigations to validate the correlation between human and zebrafish data are warranted.

Embryonic exposure to diclofenac disturbs actin organization and leads to myofibril misalignment.

The objective of this study was to investigate the embryotoxicity of diclofenac. Zebrafish (Danio rerio) embryos at 12 hpf were treated with different dosages of diclofenac (0-2,000 ppm) for different time courses (12-72 hr). Results showed no evident differences in survival rates or morphological changes between the mock-treated control (0 ppm) zebrafish embryos and those with 1-ppm diclofenac-exposure (12-24, 12-36 hpf). In contrast, after higher doses (5 and 10 ppm) of exposure, embryos displayed some defective phenotypes, including malformed somite boundary, a twisted body axis, and shorter body length. In addition, diclofenac-treated embryos exhibited significantly reduced frequencies of spontaneous in-chorion contractions in comparison with mock-control littermates (mock-control: 13.20 ± 2.24 vs. 5-10 ppm diclofenac: 6.66 ± 1.35-3.03 ± 1.84). Subtle changes were easily observed by staining with specific monoclonal antibodies F59 and phalloidin to detect morphological changes in muscle fibers and formation of F-actin, respectively. Our data show that diclofenac treatment disturbs actin organization and muscle fiber alignment, thus causing malformed somite phenotypes.

Inhibitory effect of red koji extracts on mushroom tyrosinase.

Red koji has been recognized as a cholesterol-lowering diet supplement because of it contains fungi metabolites, monacolins, which reduce cholesterol synthesis by inhibiting HMG-CoA reductase. In this study, water extracts of red koji were loaded onto a C(18) cartridge, and the acetonitrile eluate was collected as test fraction. Red koji water extracts and its C(18) cartridge acetonitrile eluent had total phenols concentrations of 5.57 and 1.89 mg/g of red koji and condensed tannins concentrations of 2.71 and 1.20 mg/g of red koji, respectively. Both exhibited an antioxidant activity and an inhibitory activity to mushroom tyrosinase. The higher antioxidant activity of the red koji acetonitrile eluent was due to the existence of a high percentage of condensed tannins. The results from the kinetic study for inhibition of mushroom tyrosinase by red koji extracts showed that the compounds in the extracts competitively inhibited the oxidation of tyrosine catalyzed by mushroom tyrosinase with an ID(50) of 5.57 mg/mL.