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Biomedical subjects

Takashi Tokoro

Publications and source records attributed to Takashi Tokoro.

15 recordsLinked to original sources

Detection of paravascular retinal cysts before using OCT in a highly myopic patient.

PURPOSE: We describe a case of high myopia who developed paravascular retinal rarefaction generated by vitreoretinal adhesion on retinal vessels detected using optical coherence tomography (OCT). METHODS: A 31-year-old man received a regular ophthalmologic examination for high myopia including detailed fundus examination and OCT. RESULTS: Detailed fundus examination revealed retinal rarefaction and fissure-like findings alongside the superior temporal retinal artery and vein in the right eye. OCT images revealed vitreoretinal adhesions on the retinal artery and a paravascular cystoid space in the inner retina. There was no retinal detachment. The axial length had increased by 1.50 mm over 15 years. CONCLUSION: Paravascular retinal rarefaction as well as pseudohole formation caused by vitreoretinal adhesion on retinal vessels was detected in this patient using OCT. OCT might be useful to detect early-stage retinal pathologies caused by paravascular vitreoretinal traction in highly myopic patients.

Adult↗

Pitavastatin at low dose activates endothelial nitric oxide synthase through PI3K-AKT pathway in endothelial cells.

Pitavastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that is used for suppressing cholesterol biosynthesis. Previously, we have reported that pitavastatin induces the activation of endothelial nitric oxide synthase (eNOS) and increases nitric oxide (NO) production in vascular endothelial cells (EC). However, the mechanism of eNOS activation by pitavastatin remains unknown. Here, we examined the implications of pitavastatin-induced signaling in eNOS phosphorylation in EC. We found that treatment of EC with a low dose of pitavastatin induced eNOS phosphorylation at Ser-1177, activated Akt phosphorylation at Ser-473 in a time-and dose-dependent manner, and increased NO production. These processes were suppressed by the addition of either mevalonic acid (MEV) or geranylgeranyl pyrophosphate (GGPP). In addition, northern blot analysis revealed that pitavastatin did not increase eNOS mRNA expression level in EC. These results suggest that the activation of eNOS with a low dose of pitavastatin (0.1 microM) involves phosphoinositide 3-kinase and the Akt pathway and produces NO in EC, which is dependent on post-transcriptional regulation. This pathway is critical for cellular responses that contribute to EC function.

Blotting, Northern↗

Characteristics of patients with a favorable natural course of myopic choroidal neovascularization.

OBJECTIVE: To identify the characteristics of patients with myopic choroidal neovascularization (CNV) who had a favorable visual prognosis without treatment. METHODS: We reviewed the medical records of 52 consecutive patients (57 eyes) with myopic CNV who were followed for at least 5 years after the onset of CNV. Clinical characteristics (patient age, CNV size and location, visual acuity at onset, chorioretinal atrophy development around CNV, and degree of myopia) were compared between patients whose visual acuity 5 years after CNV onset was better than 20/40 and those whose visual acuity was worse than 20/200. RESULTS: Among 57 eyes, eight eyes (14.0%; 8 patients) had a final visual acuity better than 20/40. On the other hand, 37 eyes (64.9%; 33 patients) had a final visual acuity worse than 20/200. Statistical analysis revealed that the patients with a good prognosis (final visual acuity better than 20/40) were significantly younger, had significantly smaller CNV, and significantly better initial visual acuity (Mann-Whitney U-test, p<0.05). Juxtafoveal CNV was more frequently observed in patients with a good prognosis than in those with a poor prognosis (Fisher's exact probability test, p<0.05). Only one patient (12.5%) in the good prognosis group developed a very limited area of chorioretinal atrophy around the regressed CNV, while 91.9% of the patients in the poor prognosis group developed chorioretinal atrophy. Refractive status and the axial length measurements did not differ between the two groups. CONCLUSIONS: Some young patients with myopic CNV retain favorable vision over the long term without active treatment. These information might be useful to predict the visual outcome of patients with myopic CNV.

Adult↗

Reduction of retinal blood flow in high myopia.

PURPOSE: To investigate changes in retinal vessel diameter and blood velocity in high myopia using laser Doppler velocimetry. METHODS: Thirty-nine subjects (39 eyes) were enrolled in the study. The subjects were divided into three groups according to their refractive status; 15 eyes (15 patients) with emmetropia (within +/-3.0 diopters), 14 eyes (14 patients) with mild myopia (between -3.0 and -8.0 diopters), and 10 eyes (10 patients) with high myopia (>-8.0 diopters). Patient age was matched between groups. Blood velocity and vessel diameter of the upper or lower temporal retinal artery were measured using laser Doppler velocimetry with an eye-tracking system, and measurements were compared between groups. RESULTS: The average retinal blood flow and vessel diameter in highly myopic eyes were significantly decreased compared with emmetropic eyes or mild myopic eyes (Mann-Whitney U test, p<0.05). Also, there was significant difference regarding retinal blood flow and vessel diameter between eyes with mild myopia and the other groups. In addition, there was no significant difference in blood velocity between the three groups. CONCLUSIONS: Retinal blood flow was decreased in high myopia, mainly due to the narrowing of the retinal vessel diameter. Impaired retinal blood flow might have a role in the development of chorioretinal atrophy in high myopia.

Adult↗

The novel HMG-CoA reductase inhibitor, Pitavastatin, induces a protective action in vascular endothelial cells through the production of nitric oxide (NO).

This study sought to induce the effect of nitric oxide (NO) production in vascular endothelial cells by Pitavastatin, which is a novel HMG-CoA reductase inhibitor (statin). The growth capacity of vascular endothelial cells significantly (p < 0.01) declined when stimulated with TNF-alpha (10 ng/ml). The growth capacity of the TNF-alpha treated cells recovered, when the TNF-alpha stimulation was performed after Pitavastatin (100 nM) pretreatment. The recovery of the growth capacity of the cells was suppressed by the presence of the NO synthase inhibitor, L-NAME. Pitavastatin increased NO production by the vascular endothelial cells in a dose and time dependent manner. The NO production was suppressed by the presence of mevalonic acid and geranylgeranyl pyrophosphate. In addition, the expression of endothelial nitric oxide synthase was strongly induced by Pitavastatin, and was suppressed by mevalonic acid and geranylgeranyl pyrophosphate by Western blot analysis. Our results show that Pitavastatin induces NO production by vascular endothelial cells, and protects vascular endothelial cells from injury due to the inflammatory reaction induced by TNF-alpha.

Cell Division↗

Factors associated with the development of chorioretinal atrophy around choroidal neovascularization in pathologic myopia.

PURPOSE: To examine the influencing factors on the development of chorioretinal atrophy, which is the main cause of long-term visual decrease in myopic choroidal neovascularization (CNV), in a large series of highly myopic patients. METHODS: Sixty-five patients (81 eyes) with myopic CNV were studied retrospectively. The influence of the patient's age, refractive error, axial length, visual acuity at onset of CNV, size of CNV, and grade of myopic retinopathy on the extent of chorioretinal atrophy more than 3 years after CNV onset was investigated by means of multiple linear regression analysis. RESULTS: Seventy-seven of 81 eyes (95.1%) developed chorioretinal atrophy around myopic CNV during the follow-up period. Multiple linear regression revealed that age was the most influencing factor for the development of chorioretinal atrophy in all the subjects. When we divided the subjects into two groups according to their age, however, CNV size was the only factor to influence the development of chorioretinal atrophy in the patients younger than 40 years, whereas age was still the only influencing factor in those older than 40 years. CONCLUSIONS: The factors influencing the development of chorioretinal atrophy differ according to patient age. Local factors, such as CNV size, determine the tendency to develop chorioretinal atrophy in young patients. Systemic factors, such as patient age, play a greater part in older subjects.

Atrophy↗

Prevalence and characteristics of foveal retinal detachment without macular hole in high myopia.

PURPOSE: To report the prevalence of foveal retinal detachment without macular hole in a large number of highly myopic eyes using optical coherence tomography (OCT), and to clarify the demographic characteristics associated with foveal retinal detachment in these eyes. DESIGN: A consecutive, prospective, observational case series. METHODS: In 134 eyes of 78 consecutive patients with high myopia (refractive error of -8 diopters or more), we performed complete ophthalmic examinations and studied cross-sectional images of the macula with OCT. The patients were divided into two groups according to the presence (group 1, n = 78 eyes of 45 patients) or absence (group 2, n = 56 eyes of 33 patients) of posterior staphyloma. Slit-lamp examination with a Goldmann three-mirror lens indicated that none of the eyes had a macular hole. RESULTS: In seven of 78 eyes (9.0%) with posterior staphyloma (group 1), OCT revealed foveal retinal detachment. Two of the seven eyes had foveal retinoschisis. Optical coherence tomography revealed no retinal detachment or retinoschisis in any eye without posterior staphyloma (group 2). Visual acuity of the seven eyes with foveal retinal detachment ranged from 20/40 to 20/200. Two of the seven eyes had visual acuity 20/50 or better. No patients complained of recent, progressive visual impairment. All seven eyes with foveal retinal detachment had severe myopic fundus changes (focal chorioretinal atrophy or bare sclera). CONCLUSIONS: In highly myopic eyes with posterior staphyloma, the prevalence of foveal retinal detachment without macular hole was 9.0%. In eyes with this type of retinal detachment, visual acuity varies and foveal retinal detachment tends to be missed on routine examination. Periodic examination using OCT is recommended for highly myopic eyes with severe myopic degenerative changes and posterior staphyloma.

Adolescent↗

Myopic choroidal neovascularization: a 10-year follow-up.

PURPOSE: To clarify the long-term visual outcome of choroidal neovascularization (CNV) in eyes with high myopia in Asian patients. DESIGN: We reviewed the medical records of 25 consecutive patients (27 eyes) with myopic CNV who were followed up for at least 10 years after the onset of CNV. Visual acuity was examined 10 years after CNV onset. INTERVENTION: Demographic and clinical data were obtained from the patients' medical records. MAIN OUTCOME MEASURES: Visual acuity readings during the 10 years after CNV onset. RESULTS: At the onset of CNV, 19 eyes (70.4%) had a visual acuity better than 20/200, and six eyes (22.2%) had a visual acuity better than 20/40. Three years after the onset of CNV, 15 eyes (55.5%) retained a visual acuity of better than 20/200. At 5 and 10 years after the onset, however, visual acuity dropped to 20/200 or less in 24 eyes (88.9%) and in 26 eyes (96.3%), respectively. The logarithm of the minimum angle of resolution (logMAR) visual acuity was significantly worse at 5 and 10 years after onset as compared with that at CNV onset. Chorioretinal atrophy developed around the regressed CNV in 26 eyes (96.3%) at 5 and 10 years after the onset of CNV. CONCLUSIONS: Long-term visual outcome of myopic CNV is extremely poor. The visual acuity of almost all of the patients dropped to 20/200 or less within 5 to 10 years after the onset of CNV, secondary to the development of chorioretinal atrophy around the regressed CNV. These findings indicate that active treatments should be recommended to prevent long-term visual impairment in Asian patients with myopic CNV.

Adult↗

Long-term visual prognosis of choroidal neovascularization in high myopia: a comparison between age groups.

OBJECTIVE: To analyze visual outcome in highly myopic patients of different age groups with choroidal neovascularization (CNV). DESIGN: Retrospective observational case series. PARTICIPANTS: We reviewed the medical records of 63 consecutive patients (73 eyes) with myopic CNV. The patient population was divided into two groups according to age at onset of CNV (< or =40 and >40 years old). INTERVENTION: Demographic and clinical data were obtained from the patients' medical records. MAIN OUTCOME MEASURES: Visual acuity at least 3 years after CNV diagnosis. RESULTS: Group 1 (< or =40 years old) consisted of 22 patients (26 eyes), and group 2 (>40 years old) consisted of 41 patients (47 eyes). Throughout the follow-up period, group 1 retained better visual acuity than group 2. Almost half the patients in group 1 retained a final visual acuity better than 20/40. No significant change occurred in the logarithm of the minimum angle of resolution (logMAR) in group 1 during follow-up. Group 2 had worse visual acuity at the initial evaluation than did group 1, and a statistically significant worsening of logMAR was found during the follow-up period. More than half of the patients in group 2 had a final visual acuity less than 20/200. In addition, group 2 had a larger area of CNV, and chorioretinal atrophy was more frequently seen after the regression of CNV than in group 1. CONCLUSIONS: The visual prognosis of myopic CNV is influenced by age at onset. The results of this study indicate that patient age at the time of onset of myopic CNV should be considered when determining the therapeutic course.

Adult↗

Optical coherence tomography of choroidal neovascularization in high myopia.

AIM: To investigate morphologic changes in the eye with choroidal neovascularization (CNV) in high myopia using optical coherence tomography (OCT). METHODS: Optical coherence tomography was performed in 35 patients (42 eyes) with myopic CNV. Myopic CNV was divided into active, scar, or atrophic stages based on funduscopic and fluorescein angiographic findings. The characteristics of OCT findings in each stage were identified. RESULTS: In the active stage (11 eyes), OCT clearly displayed a neovascular membrane as a highly reflective dome-like elevation above the retinal pigment epithelium (RPE). No apparent subretinal fluid accumulation around the CNV was identified. In the scar stage (12 eyes), only the surface of the CNV showed high reflectivity, which was markedly attenuated below the surface. In the atrophic stage (19 eyes), the CNV had become totally flat and chorioretinal atrophy around the regressed CNV showed high reflectivity. CONCLUSIONS: Optical coherence tomography demonstrated characteristic features at each stage of myopic CNV. Optical coherence tomography appears to be useful in evaluating the stage and activity of myopic CNV.

Adult↗

[The quality of life in patients with pathologic myopia].

PURPOSE: To evaluate the functional status of daily life and the quality of life of pathologic myopia patients. METHODS: A cross-sectional study was conducted using data from pathologic myopia patients(n = 211) and control subjects(n = 144). The influence of the disease on the daily life and the quality of life of patients were evaluated using a self-rating questionnaire. The questionnaire covered the full range of the status of patients' daily life and the quality of life of pathologic myopia patients, including daily tasks depending on visual acuity, social and emotional handicaps, and cognition of disease. RESULTS: The functional status of daily life and the quality of life of patients was reduced compared with control subjects. The influence of pathologic myopia on the patients' daily lives was primarily the result of three major factors: handicap, disability, and support. All three correlated with the quality of life, the degree of handicap having the strongest correlation. CONCLUSION: The functional status of daily life and the quality of life of patients was reduced; this reduction in quality of life was attributed to disability and handicap caused by pathologic myopia.

Adolescent↗

Retinal pigment epithelium atrophy secondary to dilated choroidal artery in the macula of a highly myopic patient.

BACKGROUND: Indocyanine green angiography revealed a markedly bent and tortuous choroidal artery in the macula of the left fundus in a highly myopic patient. CASE: The patient's corrected visual acuity was 1.0 in both eyes, and he had no visual symptoms. OBSERVATIONS: Ten years after the initial examination, atrophy of the retinal pigment epithelium (RPE) developed above the dilated choroidal artery. CONCLUSIONS: Optical coherence tomography demonstrated that the RPE was stretched above the markedly dilated choroidal artery. Thus, mechanical stretching of the RPE by an abnormally dilated choroidal artery might underlie the development of RPE atrophy.

Arteries↗

Fundus characteristics of high myopia in children.

PURPOSE: To evaluate the fundus characteristics of highly myopic eyes in children. METHODS: We reviewed the medical records of 46 children (1 to 8 years old; mean age, 6.8 years) (80 eyes) with high myopia (4 D or more for children younger than 5 years, 6 D or more for children aged 6-8 years) seen consecutively during a 10-year period at the high-myopia clinic in our hospital. Children of up to 8 years of age at the initial visit were included in the study. RESULTS: Fundus examination revealed posterior staphyloma in only one eye (1.3%) and mild chorioretinal atrophy around the optic disc in 13 eyes (16.3%). There were no patients with choroidal neovascularization or geographic atrophy in the posterior fundus. Myopic peripapillary crescent was observed in 26 eyes (33.8%), but the area of the crescent was relatively small (mean, 0.5 disc area). CONCLUSIONS: The results of the present study showed that myopic fundus changes are uncommon and mild in children. They suggest that aging, in addition to mechanical stretching of the eyeball, might be important for the development of myopic fundus changes.

Atrophy↗

Involvement of mechanical stretch in the gelatinolytic activity of the fibrous sclera of chicks, in vitro.

PURPOSE: To investigate the role of mechanical stretch in the regulation of matrix metalloproteinase-2 (MMP-2) in scleral fibroblasts of chick embryos. METHODS: Scleral fibroblasts derived from chick embryos were seeded onto flexible bottom culture plates, and subjected to a pulsatile stretch when the cells became subconfluent. After stretching, the cells and the conditioned medium were harvested. One portion of the conditioned medium was activated by reduction, alkylation, and 4-aminophenylmercuric acetate (APMA) treatment. The conditioned medium, with and without the treatment, was subjected to gelatin zymography and quantitative assays. Total cytoplasmic RNA was extracted from the cells, and the expression of MMP-2 and the tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA was examined by Northern blot analysis. RESULTS: The predominant gelatinolytic enzyme secreted by scleral fibroblasts was MMP-2. The mechanical stretch increased the gelatinolytic activities significantly in the conditioned medium with reduction, alkylation, and APMA treatment. Mechanical stretch also enhanced the expression of MMP-2 and TIMP-2 mRNA in scleral fibroblasts significantly. CONCLUSIONS: These results suggest that mechanical stretch may be involved in the regulation of the extracellular matrix in the fibrous sclera of chicks in vivo.

Animals↗