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Biomedical subjects

S Yoneya

Publications and source records attributed to S Yoneya.

At least 19 recordsLinked to original sources

Fish oil (polyunsaturated fatty acid) prevents ischemic-induced injury in the mammalian retina.

The long-chain polyunsaturated omega-3 fatty acid docosahexaenoic (22:6n-3) acid (DHA) accumulates in rod outer segment disks and synaptic terminals. It has been thought to play an important role in disordering disk membranes and in providing an adequate environment for conformational rhodopsin changes and in modifying the activity of retinal enzymes. The decrease of DHA content in the retina has been shown to affect visual function in monkey. In rat retina, prolonged light exposure has produced reduction of DHA content in rod outer segments. The authors found that when DHA was administered before ischemia, it diminished pressure-induced retinal damage. The recovery of electroretinographic amplitudes in DHA-pretreated eyes was significantly greater than those in the control eyes after 4 hr of reperfusion. The histopathologic study of control eyes showed cell swelling and cell nuclei pyknosis in the inner nuclear layer after 4 hr of reperfusion and in TUNEL-positive cells in the inner and outer nuclear layers after 24-72 hr of reperfusion. The DHA pre-treated eyes had fewer pyknotic nuclei and vacuolated spaces in the inner nuclear layer and no TUNEL-positive cells for up to 72 hr of reperfusion. The precise role of the polyunsaturated n-3 fatty acid has not been identified in the retina and other tissues. Our findings showed that DHA probably prevented sensory retina from ischemic-reperfusion cell damage not only by inhibiting the formation of hydroxyl radicals, but also by reducing the non-NMDA responses or the inflammatory responses.

Animals↗

Quantitative Analysis of Indocyanine Green Angiographic Image in Central Serous Chorioretinopathy.

Purpose: To disclose the possible involvement of choroidal vascular change in developement of central serous chorioretinopathy (CSC).Methods: Indocyanine green (ICG) angiography was performed in 31 eyes with acute CSC, and 21 eyes from normal subjects. The maximum diameter of the choroidal veins and intensity of background fluorescence in the posterior fundus with ICG video images were measured for further analysis using IMAGEnet((R)) (Topcon). Then the results from CSC affected eyes, their fellow eyes, and normal eyes were compared. Aging factors were taken into consideration when we analyzed the data.Result: The maximum diameters of the choroidal veins were larger in both affected and fellow eyes than in the normal eyes (P <.001), and had a positive correlation with aging particularly in fellow eyes (r = 36). Both in the affected and fellow eyes, the background fluorescein intensity in the posterior pole of the late phase images was lower than in the normal eyes (P <.001), and was correlated with aging (r = 0.28, r = 0.43).Conclusion: This quantitative study showed that choroidal venous dilatation and the residual background fluorescence in the posterior fundus might be positive findings reflecting the pathogenesis of CSC.

Journal Article↗

Aging changes of the choroidal dye filling pattern in indocyanine green angiography of normal subjects.

PURPOSE: To study the aging changes in the choroid of healthy volunteers with indocyanine green (ICG) angiography. METHODS: Video ICG angiography with adjunctive computer-assisted image analysis was performed on 35 eyes of 30 healthy volunteers (age range, 21-81 years; mean +/- standard deviation, 50.5 +/- 16.2 years) to observe the aging changes of the choroid. RESULTS: In patients in the second and third decades of life, the subfoveal choroidal arterioles fluoresced initially with subsequent rapid filling of the feeding arterioles and choriocapillaris. The watershed zone was clearly observed. In patients older than age 50, the choroidal vasculature filled more slowly. Eventually, the margin of the watershed zone became blurred. The quantitative analysis showed that the number of choroidal arterioles and the fluorescent intensity in the macular region were reduced with age (P < 0.005). In the early venous phase, hypofluorescent patches seen in all ages increased in size and number and remained with aging. The mean fluorescence intensity was not correlated statistically with age. CONCLUSIONS: The features of normal aging patterns of the choroid that we investigated are essential to the interpretation of ICG angiography and may help in understanding the physiologic and pathologic conditions of the choroidal circulations and the choroid and retina themselves.

Adult↗

Retreatment effect of NPe6 photodynamic therapy on the normal primate macula.

PURPOSE: To evaluate the safety and efficacy of repeated photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6) on normal primate fovea and choroid. METHODS: Macaca fuscata monkeys were used as experimental subjects. Mono-L-aspartyl chlorin e6 at a dose of 2 mg/kg was administered by intravenous infusion. Laser irradiation was applied within 5 minutes using a 664-nm diode laser at a power output of 5.9 mW (750 mW/cm2), spot size of 1,000 microm, and time of 10 seconds. This resulted in a fluence of 7.5 J/cm2. Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea and posterior fundus near the arcade vessels of each eye. The animals were killed and the eyes were enucleated for histologic study 2 weeks after the last treatment. RESULTS: Limited changes could be observed in the sensory retina under light microscopy. Photoreceptor cells and outer segments were not damaged, even after repeated PDT. Proliferation and duplication of the retinal pigment epithelial cells were common findings. A plaque of fibrous tissue was present, interwoven with retinal pigment epithelial cells in eyes that received repeated PDT. The retinal vessels remained patent even after three sessions of PDT. However, occlusion of the choriocapillaris and the large choroidal vessels was observed after repeated PDT treatment. CONCLUSION: Repeated PDT of healthy nonhuman primate fundi using a hydrophilic photosensitizer (NPe6) shows preservation of the neurosensory retina components and architecture with damage confined to the retinal pigment epithelium and choriocapillaris.

Animals↗

Photodynamic therapy of experimental choroidal neovascularization with a hydrophilic photosensitizer: mono-L-aspartyl chlorin e6.

PURPOSE: To demonstrate the selective localization of the hydrophilic photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in experimental choroidal neovascularization in nonhuman primate eyes. METHODS: Sixty-seven experimental choroidal neovascular lesions (CNV) were created in the fundi of Macaca monkeys using the modified Ryan's model and documented by fluorescein and indocyanine green angiography. To determine the biodistribution of NPe6 and the optimal timing of laser irradiation after dye administration, NPe6 angiography and fluorescence microscopy with NPe6 were performed. Photodynamic therapy (PDT) was performed at various dye doses (0.5-10.0 mg/kg) and laser fluences (7.5-225.0 J/cm2) on the CNV and on 10 areas of normal retina and choroid. Treatment outcomes were assessed by fluorescein and indocyanine green angiography and confirmed by light and electron microscopy. RESULTS: NPe6 fluorescence microscopy demonstrated intense fluorescence of CNV and retinal pigment epithelial cells. Choroidal vessel walls and outer retina adjacent to CNV fluoresced moderately; retinal vessel walls and microcapillaries had trace fluorescence. The fluorescence of CNV lesions on fluorescein angiography became stronger than that of retinal vessels 20-60 minutes after dye injection. Choroidal neovascular lesion closure was achieved with NPe6 PDT without significant damage to the sensory retina. Histology demonstrated necrosis of CNV endothelial cells with minimal damage to surrounding tissues. CONCLUSIONS: NPe6 PDT selectively localizes to experimental CNV in nonhuman primates, resulting in occlusion of CNV with sparing of the neurosensory retina.

Animals↗

Thickness of Retinal Nerve Fiber Layer Decreases after Vitreous Surgery for Idiopathic Macular Hole.

Purpose: The alteration of the retinal nerve fiber thickness (NFLT) before and after vitreous surgery for a macular hole in cases with or without visual field defects was investigated.Methods: The NFLT of 23 eyes with idiopathic macular hole was measured with scanning laser polarimeter up to 12 months after surgery. The NFLT was divided into superior, inferior, nasal, and temporal quadrants. The mean NFLT of each quadrant was analyzed statistically and compared to the results of visual field tests.Results: In all cases, the NFLT decreased significantly up to 3 months after surgery, but increased gradually up to 12 months. In cases with visual field loss, the thickness of the nerve fiber layer that corresponds to the visual field defect diminished strongly, in contrast with other quadrants. Even in cases without visual field loss, the NFLT decreased significantly a month after surgery, especially in the nasal and inferior quadrants.Conclusion: This study demonstrates that the thickness of retinal nerve fiber layer decreases at least one month after surgery, even in cases without visual field defect. This may suggest the existence of a subclinical complication of vitreous surgery.

Journal Article↗

Problems with and pitfalls of photodynamic therapy.

OBJECTIVE: To delineate the various factors that may influence the outcome of photodynamic therapy of the retina and choroid. DESIGN: Experimental animal study. ANIMALS: Pigmented and nonpigmented rabbits; rhesus monkeys. INTERVENTION: The hydrophilic photosensitizer, mono-L-aspartyl chlorin e6, which is maximally activated at 664 nm, was studied after intravenous injection into pigmented and nonpigmented rabbits and rhesus monkeys. Laser light was supplied by a red diode laser coupled to a modified slit-lamp biomicroscope and delivered to the ocular fundus after passing through a standard fundus contact lens. Standard photodynamic parameters were used. The effects of fundus pigmentation, intraocular pressure, spot focus and defocus, region of fundus treated, equivalent fluence, and retreatment were observed in the different animal species. MAIN OUTCOME MEASURES: Slit-lamp biomicroscopy, fluorescein angiography, light and transmission electron microscopy. RESULTS: Fundus pigmentation appeared to be a factor only at the lowest fluence level tested, where only 4 of 12 lesions attempted in pigmented fundi were noted on fluorescein angiography, compared with 12 of 12 lesions in albino rabbits. At normal intraocular pressures and a given fluence, 10 of 10 lesions were fully manifested on fluorescein angiography, compared with 4 of 10 at 30 mmHg and 0 of 10 at pressures sufficient to blanch the optic nerve (>60 mmHg). For laser spots either focused or defocused, there were 6 of 6 lesions that were fully manifested on fluorescein angiography for each of the parameters. Lesions treated in the fovea resulted in larger spots on fluorescein angiography. The fluence of 5 mW for 10 seconds resulted in a larger lesion on angiography than the equivalent fluence of 10 mW for 5 seconds. Areas of retreatment in rabbits demonstrated more thinning of the neurosensory retina and loss of photoreceptor outer segments and nuclei than corresponding areas receiving one treatment. CONCLUSIONS: Photodynamic therapy results varied, depending on intraocular pressure, region of fundus treated, ocular pigmentation, and the total time of exposure to the photosensitizer. Retreatment resulted in progressive thinning of the neurosensory retina with loss of photoreceptor outer segments and nuclei in the rabbit eye.

Animals↗

[Laser photocoagulation for choroidal neovascularization developed in a patient with optic disc drusen and angioid streaks].

BACKGROUND: Optic disc drusen accompanied by angioid streaks is rarely seen in Japan. Laser photocoagulation for choroidal neovascularization (CNV) in patients with angioid streaks is controversial. CASE: A 45-year-old woman presented with bilateral papilledema. Clinical examination revealed optic disc drusen and angioid streaks. During the follow-up period, juxtapapillary CNV developed in both eyes. CNV in the right eye developed progressively towards the fovea and was eventually treated by laser, but the CNV in the left eye regressed spontaneously. CONCLUSION: These are the first precise clinical records on optic disc drusen with angioid streaks to be reported. The outcome of laser treatment for CNV in this case was favorable, because alteration of Bruch's membrane was mild, in the form of angioid streaks.

Angioid Streaks↗

[Thickness of retinal nerve fiber layer decreases after vitreous surgery for idiopathic macular hole].

PURPOSE: To investigate the alteration of the retinal nerve fiber thickness (NFLT) before and after vitreous surgery for a macular hole in cases with or without visual field defects. METHODS: The NFLT of 23 eyes with idiopathic macular hole was measured with scanning laser polarimeter upto 12 months after surgery. The NFLT was divided into superior, inferior, nasal, and temporal quadrants. The mean NFLT of each quadrant was analyzed statistically and compared to the results of visual field tests. RESULTS: In all cases, the NFLT decreased significantly upto 3 months after surgery, but increased gradually upto 12 months. In cases with visual field loss, the thickness of the nerve fiber layer that corresponds to the visual field defect diminished strongly, in contrast with other quadrants. Even in cases without visual field loss, the NFLT decreased significantly a month after surgery, especially in the nasal and inferior quadrants. CONCLUSION: This study demonstrates that the thickness of retinal nerve fiber layer decreases at least one month after surgery, even in cases without visual field defect. This fact may suggest the existence of a subclinical complication of vitreous surgery.

Female↗

[Quantitative analysis of indocyanine green angiographic image in central serous chorioretinopathy].

PURPOSE: To disclose the possible involvement of choroidal vascular change in development of central serous chorioretinopathy (CSC). METHODS: Indocyanine green (ICG) angiography was performed in 31 eyes with acute CSC, and 21 eyes from normal subjects. The maximum diameter of the choroidal veins and intensity of background fluorescence in the posterior fundus with ICG video images were measured for further analysis using IMAGEnet (Topcon). Then the results from CSC affected eyes, their fellow eyes, and normal eyes were compared. Aging factors were taken into consideration when we analyzed the data. RESULT: The maximum diameters of the choroidal veins were larger in both affected and fellow eyes than in the normal eyes (p < 0.001), and had a positive correlation with aging particularly in fellow eyes (r = 0.36). Both in the affected and fellow eyes, the background fluorescein intensity in the posterior pole of the late phase images was lower than in the normal eyes (p < 0.001), and was correlated with aging (r = 0.28, r = 0.43). CONCLUSION: This quantitative study showed that choroidal venous dilatation and the residual background fluorescence in the posterior fundus might be positive findings reflecting the pathogenesis of CSC.

Adult↗

Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration.

Retinal pigment epithelial cells (RPE) and the choriocapillaris are on opposite sides of Bruch's membrane and control transport in and out of the retina. In age-related macular degeneration (AMD), they may also be responsible for deposition of material in and on Bruch's membrane and the formation or regression of choroidal neovascularization (CNV). Indocyanine green (ICG) angiography can be used to visualize the choroidal vasculature and CNV. Filling of the choriocapillaris with ICG was delayed in subjects older than 50 years of age, and areas of hypofluorescence were observed in maculas of AMD subjects, often associated with CNV. Laser Doppler flowmetry of the choriocapillaris in the macula demonstrated that choroidal blood flow and volume are reduced in subjects older than 46 years of age and further decreased in subjects with AMD. The human choriocapillaris can be histologically studied in two dimensions by incubating the tissue for alkaline phosphatase activity, flat-embedding it in transparent polymer and sectioning it. Using this technique, choriocapillaris dropout was found to be associated with deposition of material in Bruch's membrane in diabetic subjects. When RPE are removed from Bruch's membrane, the choriocapillaris degenerates; the regeneration of choriocapillaris can be blocked by Genistein, a tyrosine kinase inhibitor. Finally, RPE cells may produce substances that both stimulate the formation and regression of CNV in animal models. These studies suggest that there may be a reduction in choriocapillaris flow in AMD, and this loss of choriocapillaris can be associated with the Bruch's membrane deposits that are hallmarks of AMD. Furthermore, RPE may stimulate the formation and regression of CNV and RPE loss can result in loss of choriocapillaris.

Adult↗

Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-L-aspartyl chlorin e6).

PURPOSE: To demonstrate the efficacy of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in closing choroidal vessels at low energy levels, that tissue uptake and clearance are rapid, and that low concentrations of drug are needed to achieve clinical effects. DESIGN: Experimental animal study. ANIMALS: Pigmented rabbits and Japanese monkeys were used in this study. METHODS: Using a modified 664-nm diode laser, the fundi of pigmented rabbits and Japanese monkeys were irradiated after intravenous administration of NPe6 (2-100 mg/kg). Time from injection to irradiation varied from 5 to 15 minutes, and duration of exposure varied from 1 to 10 seconds. Power output at the corneal surface was either 3.6 or 5.9 mW. Animals were examined by indirect ophthalmoscopy and fluorescein angiography at 2 hours and 7 days after treatment. After enucleation 7 days after treatment, specimens were prepared for light and electron microscopy. MAIN OUTCOME MEASURES: Angiographic evidence of occlusion and histopathologic evidence of retinal damage. RESULTS: Both clinical and histopathologic examination demonstrated effects on the choroidal vasculature and the retinal pigment epithelium, including necrosis of endothelial cells and occlusion in choroidal vessels, particularly within the choriocapillaris, at low energy levels. Overlying neurosensory retina was minimally affected. Fluorescein angiography of lesions treated with 2 mg/kg and laser fluence of 2.3 to 7.5 J/cm2 showed a normal appearance 2 hours after treatment, which changed to early hypofluorescent and later hyperfluorescent lesions 7 days after treatment. In contrast, those animals receiving the 10-mg/kg dose and laser fluence of 0.46 to 0.75 J/cm2 showed marked hypofluorescence of choroidal lesions and occlusion of retinal vessels 7 days after treatment. CONCLUSIONS: Effective occlusion of normal choroidal vessels was achieved at 2 mg/kg using 2.3 to 7.5 J/cm2 or at 10 mg/kg using 0.46 to 0.75 J/cm2 with minimal injury to overlying neurosensory retina.

Animals↗

[Vitreoretinal tomography and foveolar traction in macular hole development and macular pseudohole].

OBJECT: To clarify the morphologic features and foveolar traction in macular hole development and macular pseudohole. METHODS: The vitreoretinal tomography of idiopathic macular holes and macular pseudoholes was observed with optical coherence tomography (OCT). RESULTS: In stage 1 and 2, foveolar intraretinal splitting was evident. The posterior hyaloid membrane was detected in 7 of 10 eyes with stage 1 and 2 holes. Dome-shaped vitreoretinal separation was seen in 6 of 7 eyes in which the posterior hyaloid membranes were detected. A complete posterior vitreous detachment was seen around a stage 3 hole. In the macular pseudohole with preretinal membrane, there was anterior and central displacement of the inner retina in the perifoveal region, resulting in a U-shaped deformation of the macular lesion. In contrast, the structure of the central fovea was virtually intact. CONCLUSIONS: On the basis of the OCT findings, the intraretinal splitting and the cyst formation are important features in the development of a macular hole. The dome-shaped vitreoretinal separation in the early stages of macular holes suggests that the posterior hyaloid membrane may not be taut but slack, and would not cause a tractional force continuously even in early-stage macular holes.

Aged↗

The improved image of indocyanine green angiography in young healthy volunteers.

PURPOSE: The authors performed indocyanine green (ICG) angiography in healthy volunteers using a high resolution ICG video system to obtain baseline images for subsequent studies. METHODS: Ten eyes of 10 healthy, young volunteers were studied. Before ICG angiography, all eyes were examined ophthalmoscopically and biomicroscopically and found to be intact. Indocyanine green (50 mg) dissolved in 2 mL of distilled water was injected through the antecubital vein. Video ICG angiogram was recorded until 30 minutes after the dye injection. RESULTS: Although the choroidal dye filling varied among subjects, it always began in the macular area. In the 10 volunteers, initial dye filling had two patterns: flush (n = 2) and reticular (n = 8). Patchy dye-filling delay in the posterior fundus was a common finding (n = 9). Vertical filling delay running between the medial and nasal cilial arteries was observed in nine eyes. The choroidal circulation filled completely before the retinal circulation did. At 30 minutes after dye injection, interstitial tissue staining of the choroid and vascular silhouette resulting from dye washout was observed in all eyes. CONCLUSIONS: Arterioles and capillaries of the choroid were well delineated by ICG angiography, resulting in better understanding of the physiologic and pathologic conditions of the choroidal circulations and the chorioretina itself.

Adult↗

[Aging of macular function as seen in multifocal electroretinograms].

Multifocal electroretinograms were recorded from 32 eyes of 32 young and aged healthy volunteers to investigate the change in electrophysiological functions with age in the central, nasal, temporal, superior, and inferior retina. The amplitude and latency of the first negative and positive waves were analyzed statistically in correlation with age. In all regions, amplitudes of focal responses tended to diminish with age. There was significant inverse correlation between amplitude and age in the central retina at 2 and 8 degrees, but no significant correlation was found in the other regions. These facts suggest that the macular retina tends to show functional deterioration with age when compared with other retinal areas.

Adolescent↗

[Correlation of pathological features of surgically excised choroidal neovascular membranes with age-related macular degeneration and indocyanine green videoangiographic findings].

We surgically excised subfoveal neovascular membranes from eight patients with age-related macular degeneration. The correlation of the histopathological features of choroidal neovascularization and preoperative indocyanine green (ICG) videoangiographic findings were studied. Neovascular membranes which demonstrated hyperfluorescence at an early phase of ICG videoangiography had many vascular channels and a large lumen without enclosure of retinal pigment epithelium (RPE). Fibrovascular tissues contained small vessels with fibrotic stroma that showed hyperfluorescence only at a late phase of ICG videoangiography. In contrast, the membrane which showed hypofluorescence of ICG videoangiography was composed of paucivascular fibrotic tissue covered extensively with RPE. Moreover, newly formed vessels with proliferative endothelium could be observed in the neovascular membranes that showed weak fluorescence or hypofluorescence. These results could provide a morphological basis for the interpretation of ICG videoangiographic features of choroidal neovascularization. It also may be useful in planning the treatment for subfoveal neovascular membranes.

Aged↗