Akiyasu Kanamori

Comparative Assessment for the Ability of Cirrus, RTVue, and 3D-OCT to Diagnose Glaucoma

PURPOSE We compared the ability of circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macular parameters obtained by three spectral-domain optical coherence tomography (SD-OCT) instruments to detect glaucoma. METHODS We enrolled 87 normal eyes and 145 glaucomatous eyes (75 early glaucomatous eyes (EGs), mean deviation > -6 dB). Each participant was imaged using Cirrus, RTVue, and 3D-OCT to evaluate the average and quadrant cpRNFL thicknesses. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer plus inner plexiform layer (GCL/IPL), and mRNFL + GCL/IPL (ganglion cell complex [GCC]) thicknesses were analyzed. The areas under the receiver operating characteristic curves (AUCs) were compared among the instruments. RESULTS These instruments revealed similar AUCs for the average cpRNFL and GCC thicknesses in EGs, and total all-stage glaucomatous eyes (TGs). RTVue showed better performance in the nasal cpRNFL thickness than Cirrus and 3D-OCT, and better performance in the temporal cpRNFL thickness than 3D-OCT in TGs. RTVue had a higher AUC for the superior GCC thickness compared to Cirrus and 3D-OCT in EGs, and TGs. Cirrus had higher AUCs for GCL/IPL parameters in TGs, and lower AUCs for the mRNFL parameters in EGs and TGs compared to 3D-OCT. CONCLUSIONS The average cpRNFL and GCC thicknesses measured using these OCT instruments exhibited similar abilities in the diagnosis of glaucoma, and RTVue exhibited better diagnostic abilities than Cirrus and 3D-OCT for nasal cpRNFL, and superior GCC thicknesses. The diagnostic performance of Cirrus and 3D-OCT was different for GCL/IPL and mRNFL parameters. (http://www.umin.ac.jp/ctr number, UMIN000006900.)

Akt is activated via insulin/IGF-1 receptor in rat retina with episcleral vein cauterization

The Akt serine/threonine kinase mediates pro-survival signalings in retina and was reported to be activated in a response to some retinal and optic nerve injuries. Human and experimental glaucoma induce apoptosis of retinal ganglion cells (RGCs). The purpose of this study is to test whether episcleral vein cauterization (EVC) to chronically elevate intraocular pressures (IOPs) in rats increase apoptosis of RGCs and affect activation of Akt and its upstream insulin-like growth factor (IGF)-1 receptor/Insulin receptor. Three episcleral veins in left eyes of Sprague-Dawley rats were cauterized to elevate IOPs. Up to 6 months, IOPs were monitored and the retina was dissected at several time points. The numbers of terminal dUTP nick end labeling (TUNEL)-positive cells and those of RGCs labeled with fluorogold were counted in flat-mounted retina. Immunohistochemistry and immunoblotting were performed to identify cells expressing phosphorylated Akt and to quantify the phospho- to total ratios of Akt and IGF-1 receptor/insulin receptor. EVC significantly elevated IOPs up to 2 months, increased TUNEL-positive cells in an IOP-dependent fashion, and reduced 34.5% of RGCs at 6 months (P<0.001) compared with contralateral retinas. Phosphorylated Akt was specifically expressed in RGCs until 1 month after cauterization. Akt (P=0.036) and IGF-1 receptor/Insulin receptor (P=0.003) were transiently phosphorylated at 3 days. Intrinsic activation of the IGF-1 receptor/Insulin receptor to Akt pathway may occur in RGCs in retina with EVC.

Assessment of IcareONE rebound tonometer for self‐measuring intraocular pressure

Purpose:  To evaluate the precision of the IcareONE rebound tonometer, which was developed for self‐measuring intraocular pressure (IOP) and to compare IcareONE measurement with Goldmann applanation tonometry (GAT).

Reduced Expression of Aquaporin-9 in Rat Optic Nerve Head and Retina following Elevated Intraocular Pressure

PURPOSE To investigate the effect of chronically elevated intraocular pressure (IOP) on the expression of water channel aquaporins (AQPs) 1, 4, and 9 in the optic nerve and retina in rats. METHODS Three episcleral veins were cauterized to elevate IOP in the left eyes of Sprague-Dawley rats. IOPs were monitored with a rebound tonometer. At 2 and 4 weeks after surgery, eyeballs with the attached optic nerve were enucleated for cryosectioning with immunohistochemistry, or dissected retinas and desheathed optic nerves were subjected to gene expression analyses. RESULTS IOP was significantly increased after surgery up to 4 weeks (P=0.0008). In the control optic nerve, the unmyelinated portion showed only AQP9 immunoreactivity, whereas the myelinated portion expressed both AQP4 and AQP9 immunoreactivities colabeled for glial fibrillary acidic protein but not for neurofilament. In the control retina, AQP1 was expressed in the outer nuclear layer and photoreceptors, AQP4 was expressed in Müller cell endfeet, and AQP9 was expressed primarily in NeuN-positive cells in the ganglion cell layer (GCL). Elevated IOPs substantially reduced AQP9 expression in the optic nerve head (ONH) and the GCL and decreased the retinal gene expression, but not immunoreactivity, of AQP1. CONCLUSIONS AQP9 was the only water channel expressed in the unmyelinated portion of the ONH and in the GCL whose expression was reduced after IOP elevation. Given that AQP9 presumably acts as a channel for metabolites to pass from astrocytes to neurons, the reduced expression of AQP9 at these specific sites may be implicated in the pathogenesis of glaucomatous optic neuropathy.

Unoprostone isopropyl rescues retinal progenitor cells from apoptosis in vitro

Purpose. Unoprostone isopropyl is an ocular hypotensive that was originally produced as a prostaglandin F2α analogue and is eventually recognized as a synthetic docosanoid. The compound is recently suggested to have potent neuroprotective ability in the retina. The purpose of this study is to test whether and how the biologically active metabolites of unoprostone isopropyl rescue retinal neuro-glial progenitor cells from apoptosis. Methods. R28 cells were deprived of serum for 24 hr with or without varying concentrations of unoprostone metabolite M1 or M2 or vehicle in the presence or absence of specific inhibitors against several types of signal transduction proteins. Immunocytochemistry against activated caspase-3 with Hoechst nuclear staining was performed. Results. Up to 15% of R28 cells became pyknotic and activated caspase-3 immunoreactive after 24-hr serum withdrawal. M1, but not M2, significantly reduced apoptotic cells in a dose-dependent fashion with a maximal effect at 100 μM (p <. 0001). LY294002, the phosphatidylinositol 3-OH kinase (PI3K) inhibitor, and KT5823, the protein kinase G (PKG) inhibitor, reversed the antiapoptotic effect of M1. Conclusions. The unoprostone metabolite M1 protects retinal neuro-glial progenitor R28 cells from apoptosis induced by serum deprivation via the PI3K and PKG pathways.

The ability of macular parameters and circumpapillary retinal nerve fiber layer by three SD-OCT instruments to diagnose highly myopic glaucoma.

PURPOSE To compare the ability of circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macular parameters obtained by three spectral-domain optical coherence tomography (SD-OCT) instruments to detect highly myopic glaucoma. METHODS In this study, 84 glaucomatous eyes, 53 normal eyes with high myopia, and 86 normal eyes (not highly myopic) were enrolled. Each participant was imaged using Cirrus, RTVue, and 3D OCT to evaluate the average and quadrant cpRNFL thicknesses. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL/IPL), and mRNFL + GCL/IPL (GCC) thicknesses were analyzed. The areas under the receiver operating characteristic curves (AUCs) were compared between the instruments. In addition, the best parameters for the AUC were compared between the cpRNFL parameters and macular parameters in each instrument. RESULTS These analyses revealed similar AUCs for the average cpRNFL and GCC thicknesses between the instruments. RTVue displayed a significantly higher AUC in the nasal cpRNFL thickness than both Cirrus (P = 0.0004) and 3D OCT (P = 0.0006). 3D OCT showed higher AUCs than Cirrus in the mRNFL parameters. There were no significant differences between the best cpRNFL parameters and macular parameters in each instrument. CONCLUSIONS The average cpRNFL and GCC thicknesses that were measured using these OCT instruments exhibited similar abilities for diagnosing highly myopic glaucoma, and RTVue exhibited better diagnostic abilities than Cirrus and 3D OCT for nasal cpRNFL. 3D OCT had better ability than Cirrus in the mRNFL. Both cpRNFL and GCC in each instrument were comparable, and their measurements offered good ability for diagnosing glaucoma with high myopia. (http://www.umin.ac.jp/ctr/index/htm9, UMIN000006900.).

Agreement among three types of spectral-domain optical coherent tomography instruments in measuring parapapillary retinal nerve fibre layer thickness.

Backgrounds/aims To evaluate the agreement of parapapillary retinal nerve fibre layer (RNFL) thickness among three spectral-domain optical coherence tomography (OCT) instruments. Methods Two hundred and three glaucomatous eyes and 88 normal eyes were imaged by Cirrus, RTVue and 3D OCT. The average and the four quadrant RNFL thicknesses were evaluated. Agreement among RNFL measurements was evaluated using Bland–Altman analysis and linear regression analysis. The percentage of each quadrant in the average RNFL thickness value was compared among the three instruments. Results Cirrus showed significantly smaller thickness values than RTVue (difference=8.8 μm, p<0.0001) and 3D OCT (difference=8.1 μm, p<0.0001). Although RNFL measurements among the instruments were highly correlated, the Bland–Altman analysis revealed proportional biases for most of the pair-wise agreements. Additionally, 3D OCT showed strong proportional biases with RTVue and 3D OCT. RTVue had a smaller occupied proportion of nasal quadrants (30.2%) and a larger proportion of inferior quadrants (32.4%) compared with Cirrus and 3D OCT. Conclusions RNFL measurements among the instruments were well correlated but had different values for thickness. The measurement circle of RTVue might be more superior-temporally located compared with the other instruments. Differences in the measurement protocols might be affected by the disagreements. These instruments should not be used interchangeably.

Retinal Nerve Fiber Layer Thickness in Optic Tract Syndrome

BackgroundOptic tract syndrome (OTS) is characterized by incongruous homonymous hemianopia and a perpendicular pattern of bilateral optic atrophy due to the optic tract lesion. However, loss of retinal nerve fiber layer thickness (RNFLT) associated with OTS has not been quantitatively assessed.CaseA 20-year-old woman with blunt head trauma showed normal visual acuity, color vision, ocular motility, and intraocular pressure. Because of a relative afferent pupillary defect in her left eye and left-sided homonymous hemianopia, we suspected right-sided optic tract damage, although magnetic resonance imaging detected no intracranial lesion.ObservationsUsing optical coherence tomography (OCT), the RNFLT of this case was measured at 31 months after the trauma and compared with age-matched normal controls (n = 41). Nasal, temporal, superior, and inferior quadrant RNFLT was reduced by 22%, 21%, 5%, and 46% in the right eye and 76%, 64%, 25%, and 27% in the left eye, respectively. The reduction was > 3 × the standard deviation of the normal mean values in the nasal and temporal quadrants of the left eye and in the inferior quadrant of the right eye.ConclusionsOCT can determine the RNFLT reduction corresponding to the characteristic patterns of optic atrophy of OTS. Jpn J Ophthalmol 2005;49:294–296

Structure-function relationship among three types of spectral-domain optical coherent tomography instruments in measuring parapapillary retinal nerve fibre layer thickness.

Purpose: To compare the relationships of parapapillary retinal nerve fibre layer (RNFL) thickness among three spectral‐domain optical coherence tomography (SD‐OCT) instruments with visual field sensitivity (VFS).

The detection of macular analysis by SD-OCT for optic chiasmal compression neuropathy and nasotemporal overlap.

PURPOSE To assess the diagnostic performance of the macular parameters detected by spectral-domain optical coherence tomography (SD-OCT) in band atrophy (BA) eyes. METHODS Forty-nine BA eyes with permanent temporal hemianopia and 89 normal eyes were enrolled. Any patients who had nasal visual field loss were excluded. Each participant was imaged by three-dimensional (3D) OCT-2000, and 10 × 10 grids in the macula were automatically allocated. The thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL)+ (GCL+inner plexiform layer [IPL]), and GCL++ (RNFL+GCL+IPL) in both nasal and temporal hemiretina was calculated and compared between the BA and normal eyes. The areas under the receiver operating characteristic curves (AUCs) in these parameters were compared between the nasal hemiretina and the temporal hemiretina. RESULTS All the parameters in the BA eyes were significantly thinner than those in the normal eyes. The AUCs for the mRNFL, GCL+, and GCL++ thickness in the nasal hemiretina were 0.890, 0.988, and 0.981, respectively. The parameters in the nasal hemiretina showed significantly higher AUCs than those parameters in the temporal hemiretina. In the temporal hemiretina, the damaged grids in the mRNFL were located in the arcuate areas in each hemifield. CONCLUSIONS The inner macular parameters in the nasal hemiretina exhibited high diagnostic abilities to detect BA. The GCL+ was more affected than mRNFL. The characteristic pattern of mRNFL and GCL+ thinning was implicated in the anatomical architecture regarding the nasotemporal overlap of the crossed and uncrossed fibers around the fovea. (www.umin.ac.jp/ctr number, UMIN000006900.).