METHODS. DNA was quantitated using primary cultures of bovine retinal endothelial cells that were... more METHODS. DNA was quantitated using primary cultures of bovine retinal endothelial cells that were incubated with different doses of 17 b-estradiol (E2), VEGF, or both. The changes in expression level of VEGF and VEGF receptor-2 (VEGFR2) were measured using northern blot analysis after treatment with E2. The presence of estrogen receptors in the endothelial cells was studied by immunohistochemistry and western blot analysis.
Citation: Makiyama Y, Kikuchi T, Otani A, et al. Clinical and immunological characterization of p... more Citation: Makiyama Y, Kikuchi T, Otani A, et al. Clinical and immunological characterization of paraneoplastic retinopathy. Invest Ophthalmol Vis Sci. 2013;54:5424–5431. DOI: 10.1167/iovs.13-11868 PURPOSE. To report the clinical and immunological characterization of paraneoplastic retinopathy (PR) and to investigate the association between spectral-domain optical coherence tomography (SDOCT) findings and the targets of autoantibodies in PR.
To determine steep increase of corneal irregularity induced by advancement of pterygium. A total ... more To determine steep increase of corneal irregularity induced by advancement of pterygium. A total of 456 eyes from 456 consecutive patients with primary pterygia were examined for corneal topography and advancement of pterygium with respect to the corneal diameter. Corneal irregularity induced by the pterygium advancement was evaluated by Fourier harmonic analyses of the topographic data that were modified for a series of analysis diameters from 1Â mm to 6Â mm. Incidences of steep increases in the asymmetry or higher-order irregularity components (inflection points) were determined by using segmented regression analysis for each analysis diameter. The pterygium advancement ranged from 2% to 57%, with a mean of 22.0%. Both components showed steep increases from the inflection points. The inflection points in the higher-order irregularity component altered with the analysis diameter (14.0%-30.6%), while there was no alternation in the asymmetry components (35.5%-36.8%). For the former co...
We retrospectively studied 255 eyes of 190 diabetic patients who underwent cataract extraction wi... more We retrospectively studied 255 eyes of 190 diabetic patients who underwent cataract extraction with posterior chamber intraocular lens (IOL) implantation. One hundred forty-six eyes (57.3%) achieved the best visual acuity of 20/30 or better and 221 eyes (86.7%) achieved the acuity of 20/100 or better. Among 161 eyes that were followed up over 6 months, 26 eyes (16%) showed a progression of the retinopathy. Eight eyes developed proliferative retinopathy from non-proliferative retinopathy. The level of glycosylated hemoglobin of the progression group at the time of surgery was significantly higher than that of the non-progression group (8.0 +/- 2.4% vs 6.8 +/- 1.6%, p < 0.05). Sixty-five patients received IOL implantation in one eye. Of these patients, 10 eyes (15%) showed progression of the retinopathy. Seventy percent of the fellow eyes also showed the progression, where as 95% of the non-progression group did not show progression in the fellow eyes. The results suggested that the progression of diabetic retinopathy after IOL implantation was correlated with diabetic control at the time of surgery. Additionally, patients who developed the progression of the retinopathy in pseudophakic eyes frequently showed the progression in the fellow unoperated eyes.
The current study was designed to investigate the role of circulating bone marrow (BM)-derived st... more The current study was designed to investigate the role of circulating bone marrow (BM)-derived stem cells in the pathogenesis of polypoidal choroidal vasculopathy (PCV), a distinct type of neovascular age-related macular degeneration (AMD). Thirty one clinically documented PCV patients were enrolled. Circulating BM-derived stem cells were collected from the patients' peripheral blood and cultured. Colony forming capacity (Hill assay) and migration activity (Boyden chamber system) were examined and analyzed. Colony forming units (CFU-Hill) were significantly fewer in bilateral PCV patients than in unilateral PCV patients. CFU-Hill was impaired in patients with larger (> 5000 microm) PCV lesions compared with patients with smaller PCV lesions. Migration activity of BM-derived stem cells was also reduced significantly in the bilateral PCV patients than in the unilateral PCV patients. Similar to CNV associated with AMD, impaired functional activity of circulating BM-derived stem ...
We report here a patient with bilateral papillomacular retinoschisis with an enlarged glaucomatou... more We report here a patient with bilateral papillomacular retinoschisis with an enlarged glaucomatous optic nerve head cup and a focal lamina cribrosa defect, the findings of our clinical investigations of this case, and the chosen treatment and outcome. This is an observational case report. Clinical examinations were performed using simultaneous confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT). The patient was treated by pars plana vitrectomy (PPV). The left eye had a macular detachment with a presumed acquired pit of the optic nerve, while the right eye did not have an obvious optic nerve pit. Enhanced depth imaging OCT showed focal lamina cribrosa defects in both eyes. PPV was performed on the left eye, which resulted in a re-attachment of the macula and improvement of the visual acuity. Our findings suggest that the pathological changes were most likely due to focal lamina cribrosa defects in both glaucomatous eyes. This type of maculopathy can be succe...
To investigate the pathogenic variants of retinal dystrophies in the Japanese population using mi... more To investigate the pathogenic variants of retinal dystrophies in the Japanese population using microarray analysis. DNA extracted from the blood samples of 84 families (87 patients) with retinal dystrophies (retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy and Bietti's crystalline retinopathy) was screened by Asper Biotech services. All the variants detected by microarray analysis were verified by direct sequencing. Mutations were detected in 2 of 36 families with autosomal dominant retinitis pigmentosa, 2 of 4 with Leber congenital amaurosis, 11 of 24 with cone-rod dystrophy, 3 of 7 with macular dystrophy and 6 of 7 with Bietti's crystalline retinopathy. Genotype screening using microarray analysis can be effectively used to determine the variants of retinal dystrophies, except retinitis pigmentosa, in the Japanese population.
To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin in treating choro... more To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin in treating choroidal neovascularization (CNV) in young Japanese patients. Ten eyes of 10 patients aged 50 years or younger with the diagnosis of CNV were retrospectively analyzed. CNV was of idiopathic origin in 8 eyes and of myopic origin in 2. Five eyes were treated with PDT. The visual, clinical, and angiographic responses and complications were investigated. Mean follow-up period was 33.2 months. The initial mean best-corrected visual acuity (BCVA) was significantly worse in the PDT treated group than in the non-PDT treated group (0.55 vs. 0.21, p = 0.029). The mean CNV size was significantly larger in the PDT treated group (1752 microm vs. 782 microm, p = 0.014). BCVA improved in 40% (2 eyes), unchanged in 40% (2 eyes), and worsened in 20% (1 eye) in both PDT-treated and non-treated groups. No significant complications were observed. PDT seems to be a good treatment strategy in achieving a stable o...
It has been reported that 17beta-estradiol (E2) may enhance the proliferation of bovine retinal v... more It has been reported that 17beta-estradiol (E2) may enhance the proliferation of bovine retinal vascular endothelial cells (BRECs) by increasing the expression of VEGFR-2 and VEGF. The hypothesis in the current study was that estrogen may contribute to fetal vascular development and the cessation of exposure to estrogen of premature infants on birth may have an inhibitory effect on retinopathy of prematurity (ROP). Because ROP is thought to develop under relative hypoxia after exposure to high-dose oxygen, this study was conducted to investigate how estrogen modulates hypoxia-induced VEGF in BRECs and mouse ROP. Gene expression of VEGF and hypoxia-inducible factor (HIF)-1alpha were studied in BRECs, with or without E2, under normoxia and hypoxia (1% O2). A binding assay was performed to determine whether estrogen interferes with HIF-1-mediated induction of VEGF. In a mouse ROP model, effects of E2 were evaluated by avascular area, subsequent extraretinal neovascularization, and reti...
To elucidate the potential role of angiopoietins and the Tie2 system in choroidal neovascularizat... more To elucidate the potential role of angiopoietins and the Tie2 system in choroidal neovascularization. Surgically excised choroidal neovascular membranes (CNVMs) were obtained at vitrectomy from five eyes with age-related macular degeneration, three eyes with idiopathic neovascular maculopathy, and two eyes had degenerative myopia and two eyes had angioid streaks. Light microscopic immunohistochemistry was performed to detect cytokines such as vascular endothelial growth factor (VEGF), Ang1, and Ang2 and cellular components such as retinal pigment epithelial (RPE) cells, macrophages, and endothelial cells. Immunofluorescent double staining using confocal microscopy was performed to identify the cell types that secrete specific cytokines. Ang1 and Ang2 were positive in all surgically excised CNVMs, regardless of the primary disease. Double staining revealed that many of the cytokeratin, CD68 and factor VIII positive cells also had Ang1 and Ang2 immunoreactivities. In contrast to Ang1,...
METHODS. DNA was quantitated using primary cultures of bovine retinal endothelial cells that were... more METHODS. DNA was quantitated using primary cultures of bovine retinal endothelial cells that were incubated with different doses of 17 b-estradiol (E2), VEGF, or both. The changes in expression level of VEGF and VEGF receptor-2 (VEGFR2) were measured using northern blot analysis after treatment with E2. The presence of estrogen receptors in the endothelial cells was studied by immunohistochemistry and western blot analysis.
Citation: Makiyama Y, Kikuchi T, Otani A, et al. Clinical and immunological characterization of p... more Citation: Makiyama Y, Kikuchi T, Otani A, et al. Clinical and immunological characterization of paraneoplastic retinopathy. Invest Ophthalmol Vis Sci. 2013;54:5424–5431. DOI: 10.1167/iovs.13-11868 PURPOSE. To report the clinical and immunological characterization of paraneoplastic retinopathy (PR) and to investigate the association between spectral-domain optical coherence tomography (SDOCT) findings and the targets of autoantibodies in PR.
To determine steep increase of corneal irregularity induced by advancement of pterygium. A total ... more To determine steep increase of corneal irregularity induced by advancement of pterygium. A total of 456 eyes from 456 consecutive patients with primary pterygia were examined for corneal topography and advancement of pterygium with respect to the corneal diameter. Corneal irregularity induced by the pterygium advancement was evaluated by Fourier harmonic analyses of the topographic data that were modified for a series of analysis diameters from 1Â mm to 6Â mm. Incidences of steep increases in the asymmetry or higher-order irregularity components (inflection points) were determined by using segmented regression analysis for each analysis diameter. The pterygium advancement ranged from 2% to 57%, with a mean of 22.0%. Both components showed steep increases from the inflection points. The inflection points in the higher-order irregularity component altered with the analysis diameter (14.0%-30.6%), while there was no alternation in the asymmetry components (35.5%-36.8%). For the former co...
We retrospectively studied 255 eyes of 190 diabetic patients who underwent cataract extraction wi... more We retrospectively studied 255 eyes of 190 diabetic patients who underwent cataract extraction with posterior chamber intraocular lens (IOL) implantation. One hundred forty-six eyes (57.3%) achieved the best visual acuity of 20/30 or better and 221 eyes (86.7%) achieved the acuity of 20/100 or better. Among 161 eyes that were followed up over 6 months, 26 eyes (16%) showed a progression of the retinopathy. Eight eyes developed proliferative retinopathy from non-proliferative retinopathy. The level of glycosylated hemoglobin of the progression group at the time of surgery was significantly higher than that of the non-progression group (8.0 +/- 2.4% vs 6.8 +/- 1.6%, p < 0.05). Sixty-five patients received IOL implantation in one eye. Of these patients, 10 eyes (15%) showed progression of the retinopathy. Seventy percent of the fellow eyes also showed the progression, where as 95% of the non-progression group did not show progression in the fellow eyes. The results suggested that the progression of diabetic retinopathy after IOL implantation was correlated with diabetic control at the time of surgery. Additionally, patients who developed the progression of the retinopathy in pseudophakic eyes frequently showed the progression in the fellow unoperated eyes.
The current study was designed to investigate the role of circulating bone marrow (BM)-derived st... more The current study was designed to investigate the role of circulating bone marrow (BM)-derived stem cells in the pathogenesis of polypoidal choroidal vasculopathy (PCV), a distinct type of neovascular age-related macular degeneration (AMD). Thirty one clinically documented PCV patients were enrolled. Circulating BM-derived stem cells were collected from the patients' peripheral blood and cultured. Colony forming capacity (Hill assay) and migration activity (Boyden chamber system) were examined and analyzed. Colony forming units (CFU-Hill) were significantly fewer in bilateral PCV patients than in unilateral PCV patients. CFU-Hill was impaired in patients with larger (> 5000 microm) PCV lesions compared with patients with smaller PCV lesions. Migration activity of BM-derived stem cells was also reduced significantly in the bilateral PCV patients than in the unilateral PCV patients. Similar to CNV associated with AMD, impaired functional activity of circulating BM-derived stem ...
We report here a patient with bilateral papillomacular retinoschisis with an enlarged glaucomatou... more We report here a patient with bilateral papillomacular retinoschisis with an enlarged glaucomatous optic nerve head cup and a focal lamina cribrosa defect, the findings of our clinical investigations of this case, and the chosen treatment and outcome. This is an observational case report. Clinical examinations were performed using simultaneous confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT). The patient was treated by pars plana vitrectomy (PPV). The left eye had a macular detachment with a presumed acquired pit of the optic nerve, while the right eye did not have an obvious optic nerve pit. Enhanced depth imaging OCT showed focal lamina cribrosa defects in both eyes. PPV was performed on the left eye, which resulted in a re-attachment of the macula and improvement of the visual acuity. Our findings suggest that the pathological changes were most likely due to focal lamina cribrosa defects in both glaucomatous eyes. This type of maculopathy can be succe...
To investigate the pathogenic variants of retinal dystrophies in the Japanese population using mi... more To investigate the pathogenic variants of retinal dystrophies in the Japanese population using microarray analysis. DNA extracted from the blood samples of 84 families (87 patients) with retinal dystrophies (retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy and Bietti's crystalline retinopathy) was screened by Asper Biotech services. All the variants detected by microarray analysis were verified by direct sequencing. Mutations were detected in 2 of 36 families with autosomal dominant retinitis pigmentosa, 2 of 4 with Leber congenital amaurosis, 11 of 24 with cone-rod dystrophy, 3 of 7 with macular dystrophy and 6 of 7 with Bietti's crystalline retinopathy. Genotype screening using microarray analysis can be effectively used to determine the variants of retinal dystrophies, except retinitis pigmentosa, in the Japanese population.
To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin in treating choro... more To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin in treating choroidal neovascularization (CNV) in young Japanese patients. Ten eyes of 10 patients aged 50 years or younger with the diagnosis of CNV were retrospectively analyzed. CNV was of idiopathic origin in 8 eyes and of myopic origin in 2. Five eyes were treated with PDT. The visual, clinical, and angiographic responses and complications were investigated. Mean follow-up period was 33.2 months. The initial mean best-corrected visual acuity (BCVA) was significantly worse in the PDT treated group than in the non-PDT treated group (0.55 vs. 0.21, p = 0.029). The mean CNV size was significantly larger in the PDT treated group (1752 microm vs. 782 microm, p = 0.014). BCVA improved in 40% (2 eyes), unchanged in 40% (2 eyes), and worsened in 20% (1 eye) in both PDT-treated and non-treated groups. No significant complications were observed. PDT seems to be a good treatment strategy in achieving a stable o...
It has been reported that 17beta-estradiol (E2) may enhance the proliferation of bovine retinal v... more It has been reported that 17beta-estradiol (E2) may enhance the proliferation of bovine retinal vascular endothelial cells (BRECs) by increasing the expression of VEGFR-2 and VEGF. The hypothesis in the current study was that estrogen may contribute to fetal vascular development and the cessation of exposure to estrogen of premature infants on birth may have an inhibitory effect on retinopathy of prematurity (ROP). Because ROP is thought to develop under relative hypoxia after exposure to high-dose oxygen, this study was conducted to investigate how estrogen modulates hypoxia-induced VEGF in BRECs and mouse ROP. Gene expression of VEGF and hypoxia-inducible factor (HIF)-1alpha were studied in BRECs, with or without E2, under normoxia and hypoxia (1% O2). A binding assay was performed to determine whether estrogen interferes with HIF-1-mediated induction of VEGF. In a mouse ROP model, effects of E2 were evaluated by avascular area, subsequent extraretinal neovascularization, and reti...
To elucidate the potential role of angiopoietins and the Tie2 system in choroidal neovascularizat... more To elucidate the potential role of angiopoietins and the Tie2 system in choroidal neovascularization. Surgically excised choroidal neovascular membranes (CNVMs) were obtained at vitrectomy from five eyes with age-related macular degeneration, three eyes with idiopathic neovascular maculopathy, and two eyes had degenerative myopia and two eyes had angioid streaks. Light microscopic immunohistochemistry was performed to detect cytokines such as vascular endothelial growth factor (VEGF), Ang1, and Ang2 and cellular components such as retinal pigment epithelial (RPE) cells, macrophages, and endothelial cells. Immunofluorescent double staining using confocal microscopy was performed to identify the cell types that secrete specific cytokines. Ang1 and Ang2 were positive in all surgically excised CNVMs, regardless of the primary disease. Double staining revealed that many of the cytokeratin, CD68 and factor VIII positive cells also had Ang1 and Ang2 immunoreactivities. In contrast to Ang1,...
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