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ABSTRACT: To investigate the concordance between subjectively and objectively acquired visual fields in patients with subjectively determined hemianopsia.
Retrospective observational study.
Ten patients, six men and four women, ranging in age from 28 to 68 years, were studied. Goldmann or Humphrey perimeters were used to obtain the subjectively determined visual fields for up to 25 degrees of eccentricity, and the VERIS Scientific System (Electro-Diagnostic Imaging, San Francisco, California, USA) was used to record multifocal visual evoked potential [VEPs] (mfVEPs) to obtain the objective visual fields. Each of the 60 black-and-white segments of the checkerboard stimulus was alternated according to a binary m sequence. The first slices of the second-order kernels were extracted and analyzed.
In five cases, the visual field loci where the mfVEPs were within normal limits corresponded to the scotomatous areas obtained by conventional perimetry. In these discordant cases, the lesions (e.g., arteriovenous malformation) were located in the occipital lobe. Two of these cases had a complete recovery of the subjective visual field. The lesions of the concordant cases were located outside the occipital lobe (e.g., pituitary adenoma). In these cases, no visual field improvement was seen. The temporal crescent syndrome was ruled out in patients with posterior lesions by computed tomography (CT) or magnetic resonance imaging (MRI) findings.
In some patients with occipital lesions, the subjective and objective visual field results are discordant, and some of them will show a recovery of the visual field deficits.
American Journal of Ophthalmology 03/2007; 143(2):295-304. · 4.22 Impact Factor
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ABSTRACT: The involvement of downstream messengers of transforming growth factor (TGF)-beta in the differentiation of corneal fibroblasts into myofibroblasts was investigated. The effects of insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 upregulated by TGF-beta were examined in human corneal fibroblasts, and the possible involvement of IGF axis components in corneal wound healing was assessed in a mouse model.
Human corneal fibroblasts were incubated with TGF-beta2 or IGF-I, to investigate IGF-I, IGF-II, IGFBP-3, type I collagen, and alpha-smooth muscle actin (alpha-SMA) mRNA, as well as IGFBP-3 protein expression, during myofibroblast differentiation. DNA synthesis was evaluated with a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. IGFBP-3 mRNA expression, protein expression, and immunolocalization were investigated in mouse corneas after photorefractive keratectomy (PRK).
TGF-beta2 treatment induced expression of IGF-I and IGFBP-3 mRNA and of IGFBP-3 protein in human corneal fibroblasts. TGF-beta2 and IGF-I both stimulated expression of type I collagen. TGF-beta2 but not IGF-I potently stimulated alpha-SMA mRNA expression. IGF-I potently stimulated basal DNA synthesis, whereas IGFBP-3 inhibited it. IGF-I potently stimulated proliferation of TGF-beta2-activated myofibroblasts without reversing the activated fibrogenic phenotype, whereas IGFBP-3 suppressed IGF-I-induced proliferation of corneal fibroblasts. IGFBP-3 mRNA and protein increased in mouse corneas soon after PRK, when in vivo immunostaining of the corneas showed expression of IGFBP-3 in the deep layer of the corneal stroma.
These results suggest that during corneal wound healing, TGF-beta stimulates IGF axis components, whereas IGFBP-3 may modulate IGF-I-induced myofibroblast proliferation to suppress corneal mesenchymal overgrowth.
Investigative Ophthalmology & Visual Science 03/2006; 47(2):591-8. · 3.60 Impact Factor
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ABSTRACT: Fibrovascular tissue formation in diabetic retinopathy necessitates not only angiogenic activity but also proteolytic activity, which is at least in part attributable to the induction of membrane-type 1 matrix metalloproteinase (MT1-MMP) in retinal glial cells. However, little is known about the triggers for MT1-MMP induction in the diabetic retina. In the present study, the effect of tissue hypoxia on MT1-MMP expression in retinal glial cells was investigated.
Retinal glial cells were isolated from the rabbit retina and cultured under either normoxic (20% O(2)) or hypoxic (1% O(2)) conditions in the presence or absence of the inhibitor for vascular endothelial growth factor (VEGF) receptor signal transduction or a neutralizing antibody against VEGF. The expression level of MT1-MMP in retinal glial cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, Western blot analysis and immunocytochemistry. Expression of VEGF and VEGF receptors, VEGFR-1 and VEGFR-2, was also examined by RT-PCR.
RT-PCR and real-time PCR analyses showed a 2.3-fold induction of MT1-MMP expression in retinal glial cells under hypoxic conditions. VEGF, especially its isoform VEGF(165), and VEGFR-2 were also upregulated in retinal glial cells by hypoxia, and hypoxia-induced MT1-MMP expression was inhibited in the presence of the VEGFR-2 inhibitor SU1498 or the anti-VEGF antibody.
Hypoxia can induce MT1-MMP expression in retinal glial cells, and the hypoxia-induced expression of MT1-MMP is mediated by VEGF in an autocrine fashion.
Investigative Ophthalmology & Visual Science 11/2005; 46(10):3817-24. · 3.60 Impact Factor
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ABSTRACT: To compare vitreous concentrations of triamcinolone acetonide (TA) achieved by prior therapeutic intravitreal and subtenon injections.
Interventional case series.
Vitreous samples were collected from patients who required vitreous surgery, six having received a subtenon injection of TA and another six, an intravitreal injection. Vitreous concentrations of TA were measured by high-performance liquid chromatography.
Vitreous concentrations of TA after intravitreal injection were 1.22 +/- 0.24 mug/ml, significantly higher than those after subtenon injection (<0.001 mug/ml, P = .003). Vitreous concentrations of TA after subtenon injection and TA-assisted vitrectomy performed in a few patients to visualize the transparent vitreous gel were 0.20 +/- 0.11 mug/ml, an intermediate amount between these two groups.
Much higher vitreous concentrations of TA after intravitreal injection than subtenon injection may accelerate therapeutic effect when intravitreal injections are given to reduce macular edema. Subtenon injections of TA may act via the sclera as opposed to the vitreous.
American Journal of Ophthalmology 01/2005; 138(6):1046-8. · 4.22 Impact Factor
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Retina 01/2005; 24(6):962-4. · 2.81 Impact Factor
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Retina 01/2005; 24(6):970-2. · 2.81 Impact Factor
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ABSTRACT: To report breakage of a 25-gauge vitreous cutter during vitreous surgery.
Interventional case report.
A 60-year-old woman was referred for management of an epiretinal membrane at the macula. Visual acuity was 20/100 in the affected left eye. Vitreous surgery using a 25-gauge vitrectomy system was carried out with a combination of conventional cataract surgery.
The vitreous cutter was lodged within the sclerotomy cannula after peripheral vitrectomy and was pulled together with the cannula. The cannula was reinserted by trocar, but as the floating peeled epiretinal membrane was dissected with the vitreous cutter, the tip of the cutter was broken and was aspirated with the membrane. Stereoscopic microscopy and scanning electron microscopy demonstrated that the edge that had broken at the cutter port was smooth.
Although 25-gauge instruments remain useful, care should be taken against rare surgical complications related to their fragility.
American Journal of Ophthalmology 12/2004; 138(5):867-9. · 4.22 Impact Factor
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ABSTRACT: We describe a novel ultrastructural finding observed in an epiretinal membrane excised from a patient with von Hippel-Lindau disease.
This interventional case report presents a 45-year-old woman who noted decreased vision in her right eye and was referred for treatment of a macular hole secondary to von Hippel-Lindau disease. Blindness had occurred previously in the left eye because of exudative retinal detachment. Funduscopic examination revealed a macular hole associated with a delicate epiretinal membrane, multiple retinal angiomas, and multiple old laser scars. Vitrectomy was performed in her right eye. The epiretinal membrane was peeled off and processed for light and electron microscopy.
Postoperatively the macular hole was successfully closed, and vision recovered to 20/20 from 20/40. In the excised epiretinal membrane, flattened glial cells and extracellular matrix containing fibrous elements formed a multilayered pattern. Ultrastructurally, the fibrous elements appeared as wormlike, wavy tangles of filaments (WWTF) with an orientation parallel to the surface of the epiretinal membrane. Just above the WWTF, flattened glial cells frequently extended thin cytoplasmic processes with pinocytotic vesicles.
The ultrastructure suggested that retinal glial cells had induced a remodeling of the collagenous stroma in the posterior vitreous cortex, resulting in tangential macular traction.
Albrecht von Graæes Archiv für Ophthalmologie 11/2004; 242(10):881-6. · 2.17 Impact Factor
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ABSTRACT: It is important to exclude germ line mutation in cases of unilateral retinoblastoma(RB) to estimate hereditary or possible secondary cancer. We investigated whether genetic diagnosis is feasible in a health check screening program.
Five patients with RB had surgery for enucleation in Keio University Hospital. Tumor cells from enucleated eyes and lymphocytes representing systemic cells were collected and analyzed genetically by fluorescence in situ hybridization(FISH) and restriction fragment length polymorphism (RFLP).
One out of three unilateral RB cases could be diagnosed as non-hereditary by the finding of no copies of the RB gene in the tumor cells using the FISH method and no signal in the RFLP method. A decrease of signal in tumor cells to less than 50% in the RFLP method was observed in another case of unilateral RB that seemed to be non-hereditary, but the case ultimately could not be diagnosed as non-hereditary because polycopies were found in the FISH method. No abnormality in tumor cells could be found in another unilateral case or in systemic cells of two bilateral cases.
A combination of FISH and RFLP methods can be used to diagnose some cases of RB as non-hereditary.
Nippon Ganka Gakkai zasshi 09/2004; 108(8):482-8.
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ABSTRACT: To determine the cDNA sequences and analyze the expression of porcine optineurin and myocilin in trabecular meshwork cells (TMCs) and astrocytes from the optic nerve head under normal and experimental conditions.
Both porcine optineurin and myocilin were cloned to determine the cDNA sequences. Porcine TMCs and astrocytes were isolated and treated with dexamethasone (500 nM) for 2 weeks, incubated under hypoxic conditions (7% O(2)) for 72 hours, or exposed to 33 mm Hg hydrostatic pressure for 72 hours. A 10% mechanical stretch for 24 hours was also performed on TMCs. The expression level of the optineurin and myocilin transcripts was analyzed by real-time quantitative PCR.
The sequences of porcine optineurin and myocilin cDNA were determined, and the expression of both genes was confirmed in both TMCs and astrocytes. Amino acid sequences of porcine optineurin and myocilin were homologous to those of humans by 84% and 82%, respectively, and shared protein motifs and modification sites. The expression of myocilin mRNA by TMCs and astrocytes was increased by 8.0- and 5.5-fold, respectively, after exposure to dexamethasone. In contrast, the expression of optineurin was suppressed to 68% in TMCs and 48% in astrocytes after exposure to dexamethasone. A significant reduction of myocilin expression was observed after 72 hours of incubation under hypoxic conditions in both types of cells, whereas optineurin was not affected. Hydrostatic pressure for 72 hours and mechanical stretching for 24 hours had minimal affects on gene expression of both optineurin and myocilin.
The high homology of porcine optineurin and myocilin to the comparable human genes indicates that pigs can be used to study changes in gene expression in hypertensive eyes. The alterations in expression of myocilin but not of optineurin under stress suggest that different mechanisms in the phenotype of glaucoma associated with the two genes are involved in development of glaucoma.
Investigative Ophthalmology & Visual Science 09/2004; 45(8):2652-9. · 3.60 Impact Factor
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ABSTRACT: To present the clinical features of two brothers with molecularly confirmed X-linked juvenile retinoschisis (xlRS) but with non-characteristic electrophysiological findings.
Comprehensive ophthalmological examinations were performed. The electroretinograms (ERGs) were recorded under ISCEV standards, and ERGs elicited by long-duration stimuli were also evaluated. Standard genetic analysis of peripheral blood leukocytes was performed.
Molecular testing revealed a novel 473-bp deletion including exon 4 in the XLRS1 gene in both siblings. This resulted in a frameshift mutation and a premature termination at codon 78. The scotopic and photopic ERGs were reduced, but the "negative-type" ERG, characteristic of xlRS, was not observed. Flicker ERGs were also highly reduced. Long-duration stimuli elicited ERGs with a complete loss of the b-wave and a preservation of the off-response, i.e., negative-type ERG. The phenotype/genotype relationship was not determined.
The consistency of the ERGs elicited by long-duration stimuli in xlRS patients suggests that this type of stimuli provides responses that are a better indicator for the progression or stage of the disease.
Albrecht von Graæes Archiv für Ophthalmologie 08/2004; 242(7):561-5. · 2.17 Impact Factor
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ABSTRACT: To describe a patient with subfoveal choroidal neovascularization (CNV) associated with combined hamartoma of the retina and retinal pigment epithelium (CHRRPE), treated successfully by submacular surgery.
Interventional case report.
A 12-year-old girl was referred to our clinic for evaluation. Visual acuity was 20/30 in the affected left eye. Ophthalmoscopy disclosed juxtapapillary CHRRPE and subfoveal pigmented CNV. Vitreous surgery was carried out because of visual deterioration to 20/60.
The posterior vitreous was strongly attached to glial tissue at the superior margin of the optic disk in the CHRRPE region. The CNV, which was not connected with the CHRRPE, was carefully removed, resulting in visual improvement to 20/20 5 months after surgery. Histologically, the excised membrane showed fibroblast-rich cellular component and a type 2 configuration.
Submacular surgery can be effective for the treatment of secondary CNV associated with CHRRPE.
American Journal of Ophthalmology 08/2004; 138(1):155-6. · 4.22 Impact Factor
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ABSTRACT: We describe 2 cases of calcification of hydrogel intraocular lenses (IOLs) evaluated by optical coherence tomography. Dense or slight surface opacities of hydrogel IOLs were detected initially by slitlamp biomicroscopy in a 55-year-old woman and a 77-year-old woman. The opacities resulted in complaints of hazy vision after uneventful phacoemulsification and IOL implantation. Optical coherence tomography was used to further assess the opacities and showed calcification by high reflectivity on the anterior and posterior IOL surfaces in the first patient and on the anterior surface in the second patient. No abnormal reflectivity was seen on the surface of a hydrophobic acrylic IOL in the second patient's fellow eye. Optical coherence tomography may be useful to detect calcification of a hydrogel IOL.
Journal of Cataract [?] Refractive Surgery 08/2004; 30(7):1590-2. · 2.26 Impact Factor
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Retina 07/2004; 24(3):481-2. · 2.81 Impact Factor
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ABSTRACT: Ciliary neurotrophic factor (CNTF) has been known to inhibit the differentiation of presumptive rod photoreceptor cells; however, the underlying mechanisms have remained to be elucidated. We demonstrated that STAT3 activation, but not SHP2 activation, is responsible for the CNTF/gp130 signaling that inhibits expression of Rhodopsin and its upstream activator, crx, in the retinal explants derived from P0 mice (P0 retinal explants), utilizing STAT3-deficient retina and electroporation of dominant-negative form of STAT3 (STAT3F). We also demonstrated that STAT3 activation in presumptive rod photoreceptor cells at E18.5 is rapidly downregulated at P0, when Rhodopsin expression starts during retinal development. Persistent STAT3 activation in the P0 retinal explants prevented Rhodopsin expression and rapid upregulation of crx expression. STAT3-deficient retinas did not exhibit precocious rod photoreceptor cell differentiation as a whole, although they occasionally exhibited precocious upregulation of crx mRNA. Thus, we conclude that downregulation of STAT3 activation is required, but insufficient, for rod photoreceptor cell differentiation in the postnatal retina.
Molecular and Cellular Neuroscience 07/2004; 26(2):258-70. · 3.66 Impact Factor
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ABSTRACT: In humans with albinism, a large percentage of the ganglion cell axons from the temporal retina decussate abnormally in the chiasm and synapse in the contralateral LGN. The aim of this study was to determine whether the misrouting of the optic fibers can be detected by magnetoencephalography (MEG). Visually evoked magnetic fields (VEFs) were recorded from three patients with albinism. After monocular stimulation, the isofield contour maps of the VEFs showed a single current dipole pattern over the contralateral hemisphere in patients with albinism. These results clearly illustrated the reduced uncrossed retinofugal pathway of patients with albinism.
Vision Research 06/2004; 44(10):1033-8. · 2.41 Impact Factor
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ABSTRACT: To quantify the degree of heteroplasmy of a mitochondrial DNA (mtDNA) mutation in Leber's hereditary optic neuropathy (LHON) a biplex Invader assay was applied.
To determine the optimum condition for the Invader assay, mtDNAs were assayed in various amounts of total DNA in 1-4-h incubations at 63 degrees C. To evaluate the suitability of the Invader assay to detect the three mutations, G3460A, G11778A, and T14484C, 10 ng of DNAs from 224 patients with bilateral optic atrophy was assayed. To quantify mtDNA heteroplasmy, a standard curve of known mixture ratios of mutation against calculation by the Invader assay was constructed. Seventy-two of the 224 patients had one of the three mutations, which corresponded with the mutation detected earlier by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. The percentages of mutant mtDNAs were calculated by the Invader assay in five heteroplasmic families, including 30 individuals with the G11778A mutation. The results were compared with those calculated earlier by labeled polymerase chain reaction followed by single-strand conformation polymorphism (PCR-SSCP) analysis.
In 1-8 ng of DNA, the fluorescence intensity increased near linearly during a 4-h assay. With more than 16 ng of DNA, the intensities were saturated even at the 2-h assay. A linear relationship was observed between the results obtained from separate mixtures and from the Invader assay analysis. Because two fluorescent intensities are not always the same, one of the two intensities was modified to adjust to that of the other. Complete concordance was observed between PCR-RFLP analysis and Invader assay genotyping for the 224 patients. Results of percentage of heteroplasmy in five LHON families obtained by the Invader assay were consistent with those by the PCR-SSCP analysis.
Invader assay is a simple, rapid, and reliable method of genotyping mtDNA mutations as well as quantifying heteroplasmy simultaneously under optimum conditions.
Clinical Biochemistry 05/2004; 37(4):268-76. · 2.08 Impact Factor
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ABSTRACT: Involvement of leukocytes in three major pathologic conditions in the retina, i.e., edema, ischemia, and angiogenesis, has recently been thoroughly investigated. The accumulated evidence will lead to an integrated understanding of the relationship between leukocytes and retinal disorders, which is required for clinical applications of new medical treatment.
Leukocyte roles in the retinal vascular pathology were assessed by reviewing the related literature.
Vascular endothelial growth factor(VEGF)-induced leukocyte adhesion to the retinal vessels was shown to result in blood-retinal barrier breakdown, and the leukocyte-mediated pathogenesis was also seen in a model of diabetic retinopathy. A possible mechanism by which retinal angiogenesis develops intraviteral proliferation instead of compensating the avascular retina is that VEGF-producing monocytes/macrophages infiltrate the vitreous with subsequent migration of retinal vascular endothelial cells. On the other hand, cytotoxic T lymphocyte-mediated apoptosis of endothelial cells appears to cause the suppression of pathological retinal angiogenesis and the formation of ischemic retina secondary to vascular regression.
Leukocytes are considered to regulate retinal edema, ischemia, and angiogenesis.
Nippon Ganka Gakkai zasshi 05/2004; 108(4):193-201.
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ABSTRACT: To report the efficacy of intravitreal injection of triamcinolone acetonide(TA) for cystoid macular edema remaining after vitreous surgery.
Eight eyes of 7 patients aged from 32 to 84 years old were studied. The original diseases that caused macular edema were central retinal vein occlusion in 2 eyes, branch retinal vein occlusion in one eye, Irvine-Gass syndrome in 2 eyes, and diabetic retinopathy in 3 eyes. 4 mg of TA was injected intravitreally and visual acuity and foveal thickness measured by optical coherence tomography(OCT) were evaluated in before and after the surgery.
Macular edema resolved rapidly after injection of TA in all cases and cysts were extinguished or diminished. The foveal thickness in OCT was reduced significantly from preoperative 495 +/- 116 (mean +/- standard deviation) microns to 267 +/- 117 microns after one week, and 246 +/- 81 microns after one month. The effect persisted for three months. Visual improvement of more than two Snellen lines was seen in 4 eyes. No side effects were observed except a temporary increase of intraocular pressure in one eye.
Intravitreal injection of TA is effective in a short-term for cystoid macular edema remaining after vitrectomy.
Nippon Ganka Gakkai zasshi 03/2004; 108(2):92-7.
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ABSTRACT: To evaluate long-term efficacy and safety of treatment combining topical beta-blockers and isopropyl unoprostone in primary open-angle glaucoma and normal-tension glaucoma patients.
A prospective, open-label, parallel-group clinical comparison trial was performed to evaluate efficacy and safety of treatment combining 0.5% betaxolol and 0.12% isopropyl unoprostone (B&U) or 0.5% timolol and 0.12% isopropyl unoprostone (T&U). Forty eyes of 40 patients, which were matched in the aging and the stage of glaucomatous visual field defect, were studied. Twenty patients were treated with B&U and the other twenty patients with T&U twice daily for 24 months. Goldmann intraocular pressure(IOP), Humphrey automated perimetry, blood pressure, heart rate, and peak flow were done every six months in each group.
In the B&U treatment group, mean IOP was 21.2 mmHg at baseline and 18.3 mmHg(p < 0.005) after 2 years, and in the T&U treatment group it was 21.1 mmHg at baseline and 17.9 mmHg (p < 0.001) after 2 years. The cases in which MD value decreased over 2 dB were one in the B&U treatment group and three in the T&U treatment group. The average MD value was significantly improved from -7.40 dB to -5.90 dB after 2 years with B&U treatment(p < 0.05), but there was no difference with the T&U treatment. None of the patients stopped combined therapy because of side effects, though heart rate was significantly reduced only in T&U treatment group.
Both combined treatments were effective for IOP reduction in glaucoma patients, and the data from the B&U treatment group suggested that B&U was more effective in maintaining visual field than T&U.
Nippon Ganka Gakkai zasshi 01/2004; 108(1):23-8.
