Norikazu Hagimura

Evaluation of central serous chorioretinopathy with optical coherence tomography

PURPOSEnTo evaluate central serous chorioretinopathy with optical coherence tomography during the acute phase and after resolution of the acute phase.nnnMETHODSnIn a prospective study, 23 consecutive eyes of 23 patients (19 men, four women; mean age +/- SD, 46.0+/-8.1 years; range, 29 to 60 years) with central serous chorioretinopathy were examined with optical coherence tomography during the acute phase and after resolution of the retinal detachment. After the initial examination, the patients were reexamined for 3 to 6 months (mean, 4.7+/-1.1 months). Cross-sectional retinal images through the center of the fovea were obtained from all eyes by optical coherence tomography. The retinal thickness at the center of the fovea was measured. The difference between the retinal thickness during the acute phase and after resolution of the retinal detachment was statistically analyzed using the Wilcoxon test. We also examined a grayish-white lesion that corresponded to the leakage point in fluorescein angiography in four eyes.nnnRESULTSnIn the acute phase, neurosensory retina was thickened within the area of serous retinal detachment in all 23 eyes. The detached retina was thicker than the reattached retina after resolution of the retinal detachment in all eyes. The retinal thickness at the center of the fovea during the acute phase (range, 157 to 236 microm; mean +/- SD, 196.9+/-22.6 microm) was significantly thickened compared with that after resolution (range, 105 to 152 microm; mean +/- SD, 124.8+/-10.7 microm; P<.0001, Wilcoxon test). In the acute phase, areas of low reflectivity localized within the detached retina were observed in 18 of the 23 eyes. In the area of the grayish-white lesion, optical coherence tomography showed a moderately reflective mass bridging the detached neurosensory retina and retinal pigment epithelium in the four eyes; the outer layer of the detached retina was more highly reflective in these eyes. The retinal pigment epithelium was focally detached beneath the subretinal reflective mass in three of the four eyes.nnnCONCLUSIONSnIn all eyes studied, neurosensory retina was thickened within the area of serous retinal detachment in the acute phase of central serous chorioretinopathy. The grayish-white lesion seems to be a fibrinous exudate that accumulates in the subretinal space and infiltrates into the outer retina.

Blockage of Ca 2+ -permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells

Glioblastoma multiforme is the most undifferentiated type of brain tumor, and its prognosis is extremely poor. Glioblastoma cells exhibit highly migratory and invasive behavior, which makes surgical intervention unsuccessful. Here, we showed that glioblastoma cells express Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors assembled from the GluR1 and/or GluR4 subunits, and that their conversion to Ca2+-impermeable receptors by adenovirus-mediated transfer of the GluR2 cDNA inhibited cell locomotion and induced apoptosis. In contrast, overexpression of Ca2+-permeable AMPA receptors facilitated migration and proliferation of the tumor cells. These findings indicate that Ca2+-permeable AMPA receptors have crucial roles in growth of glioblastoma. Blockage of these Ca2+-permeable receptors may be a useful therapeutic strategy for the prevention of glioblastoma invasion.

Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy.

BACKGROUNDnTo clarify the role of choroidal vascular abnormalities in central serous chorioretinopathy (CSC) in active stage, remission, and recurrence.nnnMETHODSnIndocyanine green angiography and fluorescein angiography were performed in 105 eyes (104 patients) with active CSC. Forty-six patients were followed up for 6 to 48 months (mean +/- standard deviation, 22.5 +/- 8.9 months) with repeated angiography (mean +/- standard deviation, 3.5 +/- 1.5 times). Indocyanine green angiography and fluorescein angiography also were performed during remission in all 46 eyes with CSC and during recurrent CSC in 6 eyes. Unaffected fellow eyes underwent angiographic examinations in all patients.nnnRESULTSnIn active CSC, indocyanine green angiography showed a choroidal filling delay (71%), venous dilation (61%), and focal choroidal hyperfluorescence (96%) surrounding leakage from the retinal pigment epithelium. Focal choroidal hyperfluorescence was present in unaffected areas of affected eyes (55%). The choroidal venous dilation (36%) and choroidal hyperfluorescence (62%) were noted even in unaffected fellow eyes. These choroidal abnormalities persisted during remission after leakage ceased throughout the follow-up period. In the six patients with recurrent CSC, new leakage developed in the areas of persistent choroidal hyperfluorescence. Central serous chorioretinopathy developed in the unaffected fellow eye in one of these six patients.nnnCONCLUSIONnChoroidal vascular abnormalities persist in both eyes even after leakage from the retinal pigment epithelium ceases. Central serous chorioretinopathy may recur in areas of choroidal vascular abnormalities.

Optical coherence tomography of the neurosensory retina in rhegmatogenous retinal detachment

PURPOSEnTo clarify the pathologic changes of the detached neurosensory retina in rhegmatogenous retinal detachment.nnnMETHODSnRetinal images were prospectively examined by optical coherence tomography in 25 eyes of 25 consecutive patients with rhegmatogenous retinal detachment. We excluded the patients whose retinal detachment did not involve the central fovea or patients with poor fixation during optical coherence tomography (OCT) examination. Optical coherence tomography was scanned through the center of the fovea. The patients ranged in age from 15 to 77 years (mean, 45 years; SD, 20 years). The period from onset of subjective symptoms of retinal detachment to OCT ranged from 2 to 60 days (mean, 16 days; SD, 18 days). Optical coherence tomography findings, best-corrected visual acuity, and the height of the retinal detachment at the central fovea were statistically analyzed using ANCOVA (analysis of covariance) and the Mann-Whitney U test.nnnRESULTSnIn 25 eyes of 25 patients, OCT of the detached neurosensory retina at and adjacent to the center of the fovea demonstrated normal retinal structure (10 eyes, 40%), intraretinal separation (7 eyes, 28%), and an undulated separated outer retina (8 eyes, 32%). Three statistically significant factors affected best-corrected visual acuity: intraretinal separation (P = .001), intraretinal separation with undulated outer retina (P = .001), and height of retinal detachment at the central fovea (P<.001). Best-corrected visual acuity was significantly worse in the 15 eyes with intraretinal separation with or without an undulated outer retina than in the 10 eyes with retinal thickening but no intraretinal separation (P = .036). The eight eyes with undulated separated outer retina showed significantly higher retinal detachment at the central fovea than the seven eyes with intraretinal separation but no undulated outer retina (P = .009) and the 10 eyes without intraretinal separation (P = .016). The duration from onset of subjective symptoms to OCT was not related to the occurrence of intraretinal separation of the detached retina.nnnCONCLUSIONSnIntraretinal separation of the detached retina occurred frequently and shortly after retinal detachment in rhegmatogenous retinal detachment and was one of the factors associated with poor vision in rhegmatogenous retinal detachment. Best-corrected visual acuity significantly decreased in the highly detached retina.

The Role of the Premacular Liquefied Pocket and Premacular Vitreous Cortex in Idiopathic Macular Hole Development

PURPOSEnTo clarify the role of the vitreous in idiopathic macular hole formation.nnnMETHODSnWe prospectively evaluated the vitreous before and during vitreous surgery in 64 consecutive eyes of 62 patients (stage 1B, four eyes; stage 2, ten eyes; stage 3, 43 eyes; stage 4, four eyes) with macular holes; another three eyes underwent a second vitrectomy. After core vitrectomy, the premacular vitreous cortex was examined by applying gentle suction. The detached posterior hyaloid face was observed under endoilluminiation.nnnRESULTSnWe observed in all eyes a liquefied lacuna anterior to the posterior fundus before and during vitreous surgery. The premacular vitreous cortex was extremely thin and elastic upon gentle suction. A premacular ring, the diameter two to four times that of the Weiss ring, was observed in 48 of 57 eyes (84%) with stages 1B, 2, and 3 macular hole. In most cases, the vitreous cortex within the premacular ring either was absent or had a break, resulting in a premacular round defect. The vitreous cortex peripheral to the premacular ring, which was thick and less deformed, never showed a break. In eyes that had undergone a second vitrectomy, we noted residual cortex or an epiretinal membrane around the macular hole.nnnCONCLUSIONSnThe premacular vitreous cortex is extremely thin and elastic. It is sharply demarcated by a ring from the thick peripheral vitreous cortex. Tangential traction, which causes macular holes, appears to originate exclusively in the premacular vitreous cortex that forms the posterior wall of the premacular liquefied pocket.

Correlation Of Optical Coherence Tomography With Angiography In Retinal Pigment Epithelial Detachment Associated With Age-related Macular Degeneration

Purpose: To correlate optical coherence tomography (OCT) with angiographic signs of choroidal neovascularization (CNV) in retinal pigment epithelial detachment (PED) associated with age-related macular degeneration (ARMD). Methods: Prospectively, the authors performed OCT in 35 eyes of 35 patients (30 men and 5 women with a mean age of 71.6 years [range, 56–76 years]) with ARMD. All 35 eyes had CNV in the area of PED or adjacent to it, which was shown by fluorescein or indocyanine green angiography. Cross-sectional images were obtained by the OCT scanning line through the CNV and PED. Results: In 10 (56%) of 18 eyes in which the CNV was at the margin of the PED, a small PED was adjacent to the central, dome-shaped PED. There was a notch between the central and small mounds of PED. In 13 (76%) of 17 eyes in which the CNV was within the PED, a notch was seen in the dome-shaped PED, resulting in a contour with 2 mounds. One of the 2 mounds contained a highly reflective mass immediately beneath the detached retinal pigment epithelium in 8 (62%) of the 13 eyes. Conclusion: A tomographic notch in the PED may be diagnostically important as an indication of CNV beneath the detached retinal pigment epithelium in eyes with ARMD.

Triamcinolone acetonide suppresses interleukin-1 beta-mediated increase in vascular endothelial growth factor expression in cultured rat Müller cells.

PurposeIntravitreal injection of triamcinolone acetonide (TA) is used for the treatment of diabetic macular edema and other vitreoretinal diseases. Vascular endothelial growth factor (VEGF) plays a key role in regulating vascular permeability associated with macular edema. We investigated the effect of TA on the expression of VEGF mRNA and protein induced by interleukin-1 beta (IL-1b) and hypoxia in cultured rat Müller cells.MethodsMüller cells were isolated from removed eyeballs of 40 rats. Total RNA was prepared from Müller cells stimulated by IL-1b or hypoxia, in the absence or presence of TA, and then was subjected to Northern blot analyses. The amount of VEGF protein in the culture medium was measured by enzyme-linked immunosorbent assay (ELISA). The stability of RNA was determined by actinomycinxa0D decay assay. Reporter construct, consisting of the VEGF promoter–luciferase gene, was transiently transfected into Müller cells for luciferase assays.ResultsStimulation of Müller cells by either IL-1b or hypoxia induced VEGF mRNA expression. Pretreatment of cells with TA efficiently suppressed VEGF induction by IL-1b but not by hypoxia. ELISA showed that TA significantly reduced the production of VEGF protein from IL-1b-stimulated cells. RNA decay assays and promoter analysis of the VEGF gene indicated that TA inhibited the IL-1b-mediated increase in VEGF gene expression at the transcriptional level.ConclusionsTA suppressed VEGF expression induced by IL-1b in Müller cells at the transcriptional level. Our data sustained the clinical effect of TA for diabetic macular edema and suggested an important role of TA for the suppression of the VEGF gene expression in ocular tissues.

Effects of intraocular irrigation with melphalan on rabbit retinas during vitrectomy

PurposeTo investigate the toxic effects of perfusion of intravitreal melphalan during vitrectomy on the rabbit retina.MethodsWe performed electoretinography (ERG) in 18 eyes of 18 healthy albino rabbits before and after intraocular melphalan perfusion at concentrations of 5-, 10-, and 20-μg/ml during pars plana vitrectomy. Fellow eyes that underwent vitrectomy without melphalan served as controls. The histopathologic retinal changes were observed in both eyes of two rabbits from each group.ResultsIn the 5-μg/ml perfusion group, the ERGs and histology showed no substantial changes compared with control fellow eyes during 28xa0days postoperatively. In the 10- and 20-μg/ml groups, the mean a-wave amplitude decreased to 52% and 31% respectively of the fellow eye; the mean b-wave amplitude decreased to 52% and 19% respectively. However, the peak implicit time of the a- and b-waves did not significantly differ in the 10- and 20-μg/ml groups during 28xa0days postoperatively. Histologic sections showed necrosis of the inner nuclear layer and thinning of the outer nuclear layer in the 10-μg/ml group. Loss of the outer nuclear layer and the photoreceptor layer and necrosis of the inner nuclear layer were observed in the 20-μg/ml group.ConclusionThe intravitreal 5-μg/ml melphalan perfusion during vitrectomy appears to be nontoxic to the retina. This therapeutic modality might be a potential treatment for retinoblastoma with vitreous seeding.

Indocyanine green angiographic features of idiopathic submacular choroidal neovascularization

PURPOSEnTo clarify the indocyanine green angiographic features of idiopathic submacular choroidal neovascularization.nnnMETHODSnWe performed fluorescein and indocyanine green angiography in 16 eyes of 16 patients (nine men, seven women; mean age +/- SD, 35.6 +/- 6.9 years; range, 24 to 48 years) with idiopathic submacular choroidal neovascularization. During the mean follow-up of 11.4 +/- 7.9 months (range, 1 to 28 months), angiography was repeated (mean, 2.6 +/- 0.5 times; range, 2 to 3 times) in 12 eyes and performed only once in four eyes.nnnRESULTSnIn the early phase of indocyanine green angiography, a network of choroidal neovascularization was observed in 11 of the 16 eyes with well-defined choroidal neovascularization seen by fluorescein angiography. Choroidal hyperfluorescent areas were noted in 10 of the 16 eyes in the late-phase angiography. Three of the 10 eyes showed focal dilatation of choroidal veins within the hyperfluorescent areas. Choroidal neovascular membrane was located within the hyperfluorescent areas in eight of the 10 eyes with choroidal hyperfluorescent areas. A dark rim surrounding choroidal neovascularization was observed in 13 of the 16 eyes at the initial examination. Indocyanine green angiography was repeated in nine of the 13 eyes and in the other three eyes without dark rim initially. During the follow-up period, the dark rim became prominent in eight of the nine eyes and developed in one eye without dark rim initially. Choroidal neovascular membrane regressed in these nine eyes. Choroidal neovascularization remained active or enlarged in three eyes in which the dark rim was stationary or invisible.nnnCONCLUSIONSnThe dark rim surrounding the choroidal neovascularization in indocyanine green angiograms appeared to reflect regression of idiopathic choroidal neovascularization. Choroidal vascular abnormalities such as hyperfluorescent areas or focal venous dilatation seem to be the background lesion predisposing to the choroidal neovascularization.

Optical coherence tomographic features of idiopathic submacular choroidal neovascularization

PURPOSEnTo clarify the morphologic features of idiopathic submacular choroidal neovascularization using optical coherence tomography.nnnMETHODSnUsing optical coherence tomography, we prospectively examined 17 consecutive eyes (17 patients; eight men, nine women; mean age +/- SD, 36.0 +/- 9.3 years) with idiopathic submacular choroidal neovascularization. During the follow-up period (mean +/- SD, 7.5 +/- 3.8 months), we repeated optical coherence tomography in 15 eyes; optical coherence tomography was performed only at the initial examination in two eyes that underwent submacular surgery.nnnRESULTSnChoroidal neovascularization was observed in the subsensory retinal space anterior to the retinal pigment epithelium as a highly or moderately reflective mass, which protruded from the retinal pigment epithelium in 13 of 17 eyes (protruding type). In four eyes, choroidal neovascularization was a highly reflective fusiform mass at the level of the retinal pigment epithelium and choriocapillaris (fusiform type). During the follow-up period, choroidal neovascularization regressed and the protruding mass became a highly reflective fusiform mass in 10 of 11 eyes with the protruding type that underwent repeated examination. In three of the 10 eyes, during 5 to 10 months from initial examination, the choroidal neovascularization was exacerbated and it again protruded into the subsensory retinal space anterior to the retinal pigment epithelium. Four eyes with the fusiform type remained the same throughout the follow-up period. The overlying retina was thickened and had low reflectivity in all 17 eyes at the initial examination. Optical coherence tomography identified subretinal fluid in only 11 of the 13 eyes with protruding type choroidal neovascularization.nnnCONCLUSIONSnOptical coherence tomography confirmed subsensory retinal location of idiopathic submacular choroidal neovascularization anterior to the retinal pigment epithelium. Protruding choroidal neovascularization transforms to fusiform tissue at the level of the retinal pigment epithelium during the process of regression. Sensory retinal edema was always associated with choroidal neovascularization.