Tokuhiko Miki

Indocyanine Green Angiographic Aspects Of Multiple Evanescent White Dot Syndrome

Purpose The authors investigated the indocyanine green angiography findings of multiple evanescent white dot syndrome (MEWDS). Methods Four patients with MEWDS underwent examination by indocyanine green angiography, conventional ophthalmoscopy, and fluorescein angiography. Results Fundus examination showed multiple white dots in the retinal pigment epithelium of the unilateral eye of each patient. Fluorescein angiography demonstrated early hyperfluorescence corresponding to the white dots. In the early phase, indocyanine green angiography showed no abnormal signs in the large choroidal vessels, but in the late phase, hypofluorescent lesions appeared, corresponding to the white dots. The hypofluorescent dots were clustered in the posterior pole and sporadic in the peripheral region, appearing to radiate away from the optic disc or fovea. The hypofluorescent dots disappeared at the recovery stage. Conclusions Previous fluorescein angiographic and electrophysiologic studies have demonstrated the involvement of the retinal pigment epithelium (RPE) and photoreceptors in MEWDS. The current findings on indocyanine green angiography suggest that MEWDS affects the choriocapillaris or precapillary arterioles as well as the RPE and photoreceptors, and that the lesions spread to the midperipheral region, centering on the optic disc or fovea.

The YXXQ motif in gp 130 is crucial for STAT3 phosphorylation at Ser727 through an H7-sensitive kinase pathway

The signal transducer and activator of transcription (STAT) 3 is essential for mediating signals from the receptors for a variety of cytokines and growth factors, including IL-6 and EGF, and from cytoplasmic tyrosine kinases. Upon stimulation, STAT3 is phosphorylated at Ser727 and Tyr705. However, the role of phosphorylation at Ser727, and the kinase pathways responsible for this phosphorylation in IL-6 signaling remain obscure. Here we show that IL-6 activates at least two distinct STAT3 serine kinase pathways and that an H7-sensitive pathway is dominant over a PD98059-sensitive one in HepG2 cells stimulated with a low concentration of IL-6. The analysis, using a series of chimeric receptors containing the extracellular domain of the G-CSF receptor, the truncated form of gp 130, and additional short peptides at the gp 130 carboxy-terminus, showed that the YXXQ motif of gp 130 was sufficient for the H7-sensitive STAT3 Ser727 phosphorylation. This YXXQ-mediated pathway does not involve Erk, p38, JNK, or PKCδ, and requires a site in the region from 533 to 711 of STAT3 for phosphorylation in vivo. Moreover, we show that Ser727 is required for full transcriptional activity of STAT3 for two different response elements. Thus, the YXXQ motif regulates STAT3 activities in two ways in response to even a low concentration of IL-6: it recruits STAT3 to the receptor for tyrosine phosphorylation, and activates an unidentified H7-sensitive pathway leading to the serine phosphorylation of STAT3.

Frequency of choroidal abnormalities in neurofibromatosis type 1

BACKGROUND Choroidal neurofibromatosis is thought to be a rare form of neurofibromatosis that involves the eyes. The development of infrared light examination with a scanning laser ophthalmoscope (SLO) and indocyanine-green fundus angiography has allowed examination of the choroid. We studied choroidal abnormalities in patients with neurofibromatosis 1 and compared their frequency with that of other ocular abnormalities. METHODS We examined 33 eyes of 17 consecutive patients diagnosed with neurofibromatosis 1 by conventional ophthalmoscopy and by non-invasive infrared monochromatic light with confocal SLO. 76 eyes of 39 age-matched controls were examined similarly by confocal SLO. 21 digital fluorescein and indocyanine-green angiographies were obtained from 11 adult patients, and 77 angiograms were obtained from age-matched controls. FINDINGS Infrared monochromatic light examination by confocal SLO showed bright multiple patchy regions at and around the entire posterior pole of all 33 eyes examined. All bright patchy regions seen in adult patients corresponded to hypofluorescent areas on their indocyanine-green angiograms. However, no abnormalities were noted in any patient at corresponding areas under conventional ophthalmoscopic examination or fluorescein angiography. In SLO and indocyanine-green studies, controls and control angiograms showed no choroidal abnormalities. Iris nodules were noted in 25 eyes (76%) of 14 patients (82%) and eyelid neurofibroma in five patients (29%). INTERPRETATION The bright patchy regions noted under infrared fundus examination and the corresponding hypofluorescent areas seen on indocyanine-green angiograms are probably of choroidal origin. The high frequency (100%) of these abnormalities suggests that the choroid is one of the structures most commonly affected by neurofibromatosis 1.

Management of orbital lymphangioma using intralesional injection of OK-432

AIM To treat orbital lymphangioma with an intralesional injection of OK-432 (group AStreptococcus pyogenes of human origin). METHOD A 14 year old boy had a right orbital cystic lymphangioma. The visual acuity in the eye was 20/28. In an initial treatment, 0.02 mg of OK-432, was injected into the tumour after aspiration of the fluid contents, but no effect was seen. The second treatment was performed with 0.04 mg of OK-432. RESULT 4 months later, the lesion had totally shrunk to fibrous tissue. The side effects were fever, a local inflammatory reaction lasting 3 days, and increased intraocular pressure, which was managed by draining the fluid contents. Visual acuity improved to 20/15, and the visual field defect and restriction of eye movement seen before treatment disappeared. No recurrence was noted 1 year after treatment. CONCLUSION An intralesional injection of OK-432 shrunk the lymphangioma without functional disturbance and scar in the facial skin. OK-432 may be useful for orbital lymphangioma, but further studies are still warranted to determine efficacy, complications, and the optimal dose for safe treatment.

Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10

To determine the optimal treatment parameters for selective occlusion of choroidal neovascularization (CNV) by photodynamic therapy (PDT) by using the photosensitizer ATX‐S10 and a diode laser (wavelength = 670 nm).

Hepatocyte growth factor stimulates proliferation and migration during wound healing of retinal pigment epithelial cells in vitro

PURPOSE A defect in retinal pigment epithelial (RPE) cells may cause dysfunction of the neural retina, so rapid recovery of differentiated RPE cells is required after RPE injury. We investigated the effect of hepatocyte growth factor (HGF) on wound healing in RPE cells. METHODS Confluent monolayers of bovine RPE cells were denuded, and the cells were allowed to recover in the presence or absence of HGF. The effect of HGF on RPE cell proliferation was evaluated by a 3-(4;5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay. In a migration assay, mitomycin C was used to inhibit proliferation, and the number of migrated cells was counted. The signaling pathways involved were examined using inhibitors of mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 (PI3) kinase and protein kinase C pathways. RESULTS At 80 ng/mL, HGF stimulated the wound closure of RPE monolayers and rendered the restituted cells more epithelioid in shape. HGF at 10 ng/mL stimulated RPE cell migration the most, whereas 80 ng/mL of HGF inhibited migration, but stimulated proliferation the most. In particular, PI3 kinase and MAPK inhibitor inhibited PRE cell migration and proliferation, respectively. CONCLUSIONS HGF stimulated wound closure in cultured RPE cells, and rendered restituted cells epithelioid in shape. HGF may become a therapeutic candidate for RPE wound healing.

Ultrasound biomicroscopic study of ciliary body changes in the post-treatment phase of Vogt-Koyanagi-Harada disease

Aims: To investigate the usefulness of ultrasound biomicroscopy for evaluating changes in the ciliary body in patients with Vogt-Koyanagi-Harada disease. Methods: Ultrasound biomicroscopy was used to evaluate 14 eyes of seven patients diagnosed with Vogt-Koyanagi-Harada disease. Cross sectional images of the ciliary body and thickness of the pars plana 3.0 mm posterior to the scleral spur were examined. Predicted thickness of the pars plana was obtained by multiple linear regression analysis of thickness in the acute phase and in the remission phase. Results: In the active phase, the cross sectional images showed a shallow anterior chamber in eight of the 14 eyes, ciliochoroidal detachment in five eyes, and a thickened ciliary body in all 14 eyes. Internal reflectivity of the ciliary stroma was low, with ciliary processes being unclear in 13 eyes. One month after steroid treatment, slit lamp examination findings were normal in 14 eyes. 10 eyes of five patients were examined by ultrasound biomicroscopy at this stage. Ciliochoroidal detachment was no longer seen in any eye. Internal reflection of the ciliary stroma became relatively homogeneous, and the ciliary processes were seen, though not clearly. However, the pars plana remained thickened. The actual thickness was greater at 1 month after steroid treatment than the predicted thickness for the remission phase. In the remission phase, the internal reflection was homogeneous and the ciliary processes were delineated clearly in all 14 eyes. Conclusion: Objective, quantitative evaluation of the ciliary body is possible with ultrasound biomicroscopy during the course of Vogt-Koyanagi-Harada disease. Ultrasound biomicroscopy is useful in determining disease activity in the anterior segment and in monitoring the clinical course, and it may improve evaluation of the efficacy of treatment.

Choroidopathy after blunt trauma to the eye: a fluorescein and indocyanine green angiographic study.

PURPOSE To describe the uses of fluorescein angiography and indocyanine green angiography in highlighting traumatic choroidopathy. METHODS In a prospective study, 21 patients (21 eyes) who presented with traumatic retinal opacity ophthalmoscopically underwent fluorescein angiography and indocyanine green angiography. With indocyanine green angiography, the subtraction method was used for detailed examination. RESULTS In 11 of 21 eyes, fluorescein angiography showed no abnormalities. On indocyanine green angiography, delayed filling in the choroid was found locally in nine of these 11 eyes. Delayed filling of the choroidal veins was clearly visualized by the subtraction method. In six eyes, intrachoroidal indocyanine green leakage around the choroidal vessels, including vortex veins, was found. In the remaining 10 of the 21 eyes, fluorescein angiography showed fluorescein leakage or a salt-and-pepper appearance in the region of retinal opacity. On indocyanine green angiography, a triangular-shaped area of delayed filling of the choroidal arteries was observed in four eyes. Delayed filling of the choroidal veins was visualized in all 10 eyes, intrachoroidal indocyanine green leakage was found in eight, and dilation and/or narrowing of the choroidal veins and changes in choroidal vasculature were visualized in five eyes. Furthermore, in regions with fluorescein leakage, indocyanine green leakage or hypofluorescence was observed, suggesting damage to the choriocapillaris. CONCLUSION Indocyanine green angiography allows the analysis of various degrees of choroidal vascular damage. Because the choroidal circulation nourishes the outer retinal layer, traumatic choroidopathy may play a role in the prognosis for visual recovery in eyes affected by contusion retinal opacities.

Retinal sensitivity measurement over drusen using scanning laser ophthalmoscope microperimetry.

Abstract · Background: Retinal sensitivity over drusen was examined using a scanning laser ophthalmoscope to confirm a previous report of no change in sensitivity over drusen. · Methods: Microperimetry was performed using a scanning laser ophthalmoscope in 23 eyes of 19 subjects. Subject age ranged from 42 to 86 years (mean 68.5 years). Fifty-four drusen bigger than the diameter of a major retinal vein at the optic disc rim were examined, and drusen were classified as soft drusen and other large drusen. · Results: Nine eyes of eight subjects showed a decrease in retinal sensitivity over drusen. The decrease in retinal sensitivity was more than 5 dB less than the sensitivity at a peripheral non-drusen area peripheral to the measurement point. The sensitivity decrease was noted over 15 of 29 large drusen and the decrease was statistically significant (P<0.02). However, no relationship between the size of the drusen and the amount by which sensitivity decreased was found. Nevertheless, a decrease in retinal sensitivity was not seen over any of 25 soft drusen. · Conclusion: Large drusen may influence retinal sensitivity and function.

Long-term follow-up of severe central serous chorioretinopathy using indocyanine green angiography

Background: The severe types of central serous chorioretinopathy (CSC) have a chronic nature, suggesting that a pathological process persists subclinically. Indocyanine green(ICG) angiography recently revealed intrachoroidal dye leakage and its static nature in CSC. As the intrachoroidal dye leakage was suspected to be relevant to the disease process, the long-term persistence of intrachoroidal ICG leakage was examined in four patients of the severe types of CSC. Methods: ICG angiography was performed periodically over more than three years in three patients and two years in one patient. One patient had CSC with bullous retinal detachment, and the other three had chronic CSC or diffuse retinal pigment epitheliopathy. Results: Intrachoroidal ICG leakage persisted in all the patients. However, a change in location of persistent intrachoroidal leakage or disappearance of intrachoroidal leakage regardless of no progression of retinal pigment epithelial alteration was noted in one eye of two patients. Conclusions:Pathology causing intrachoroidal ICG leakage persisted subclinically for a long period. However, location and extent of the intrachoroidal leakage could change during along-term follow-up period.