Akira Negi

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

PURPOSEnWe 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.nnnMETHODSnWe 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.nnnRESULTSnThese 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.nnnCONCLUSIONSnThe 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.)

Assessment of IcareONE rebound tonometer for self‐measuring intraocular pressure

Purpose:u2002 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

PURPOSEnTo 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.nnnMETHODSnThree 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.nnnRESULTSnIOP 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.nnnCONCLUSIONSnAQP9 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.

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=8.8u2005μm, p<0.0001) and 3D OCT (difference=8.1u2005μm, 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.

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).

Spectral-domain optical coherence tomography detects optic atrophy due to optic tract syndrome.

BackgroundUnilateral injury of the optic tract leads to asymmetrical optic atrophy in both eyes derived from the crossing of the nerve fibers at the chiasm. This report demonstrates unique imaging appearances of optic atrophy due to this uncommon condition detected by spectral-domain optical coherence tomography (SD-OCT).MethodsCirrus and RTVue measurements were performed in four cases of optic tract syndrome. Circumpapillary retinal nerve fiber layer (cpRNFL) thickness was obtained from both instruments and ganglion cell complex (GCC) integrity was obtained from RTVue. The presumable reduction rates of quadrant cpRNFL thickness were calculated from the published normative database and compared between eyes with temporal hemianopia and those with nasal hemianopia.ResultsBoth devices showed significant reduction of cpRNFL thickness, but did not have statistical difference in the reduction rates at temporal or nasal quadrant cpRNFL between contralateral and ipsilateral eyes to the lesion. Color-coded maps helped to visualize the unique pattern of cpRNFL and GCC thinning.ConclusionsSD-OCT can be used as a diagnostic tool for the optic tract syndrome.

Postural changes in intraocular pressure are associated with asymmetrical retinal nerve fiber thinning in treated patients with primary open-angle glaucoma

BackgroundTo determine if asymmetrical postural change-induced elevations in intraocular pressure (IOP) in eyes of patients with primary open-angle glaucoma (POAG) were associated with asymmetries in functional and structural damage.MethodsEnrolled were 132 eyes of 66 patients with POAG (male/female = 22/44, age = 55.2u2009±u200913.4 years). IOP was first measured in a seated position and then in a supine position at 10-minute intervals over a 60-minute period using a TonoPen XL. The Humphrey visual field 30-2 program and a fast retinal nerve fiber layer (RNFL) thickness acquisition protocol of Stratus optical coherence tomography (OCT) were performed. Mean deviation (MD) and average total RNFL thickness were compared between eyes with the greater magnitude of postural change-induced IOP elevation (ΔIOP) and those with the smaller magnitude of ΔIOP.ResultsThe MDs of the eyes with larger ΔIOP (6.21u2009±u20093.18xa0mmHg) and smaller ΔIOP (3.02u2009±u20090.37xa0mmHg) were −12.31u2009±u20097.63xa0dB and −9.67u2009±u20096.80xa0dB respectively (pu2009=u20090.0176). The average total RNFL thickness was 64.33u2009±u200917.83 μm in the former and 68.56u2009±u200915.10 μm in the latter (pu2009=u20090.049). The MDs and RNFL thickness were not significantly different between the eyes that had higher and lower IOP values measured in the seated position.ConclusionsIn patients with asymmetrical POAG, the magnitude of IOP elevation induced by postural changes may be related to differences in the severity of both functional and structural damage between the eyes.

Optimal conditions for multifocal VEP recording for normal Japanese population established by receiver operating characteristic analysis

The purpose of this study was to establish optimal conditions for recording multifocal visual evoked potentials (mVEPs) in Japanese individuals, whose skull frame presumably differs from Caucasians. The scalp point that was extended from the calcarine fissure was identified using magnetic resonance imaging scans of 200 subjects. MVEPs were recorded from 56 individuals using three single channels and combinations of vertical and horizontal channels. Five electrodes were placed at the inion, 4xa0cm above the inion, 2.5xa0cm below the inion, 4xa0cm to the left or 4xa0cm to the right of the inion. The signal-to-noise ratio (SNR) was obtained by measuring the root-mean-square (RMS) amplitude of a signal window (45–150xa0ms) from each of 60-local responses that was divided by the average of the 60 RMS amplitudes of the noise window (325–430xa0ms). Receiver operating characteristic (ROC) analyses were performed based on the proportion of mVEP responses that exceeded a specific SNR criterion, calculated for both the signal window and the noise window. The position of the calcarine fissure relative to the inion was significantly lower than the value reported for Caucasians. The ROC analyses disclosed that bi-channel combinations (one vertical and one horizontal) had significantly better performance to discriminate signal from noise in 60-local mVEP responses compared to any single channel and performed similarly to the tri-channel combination. Two sets of perpendicular channels should be simultaneously used in recording mVEP responses from Japanese people, among whom skull frame characteristics differ from those observed in Caucasians.

Loss of Aquaporin 9 Expression Adversely Affects the Survival of Retinal Ganglion Cells

Aquaporin 9 (AQP9), an aquaglyceroporin belonging to the AQP water channel family, is permeable not only to water but also to noncharged solutes such as lactate. In neurons, lactate presumably acts as an energy substrate and as a source of NADH (the reduced form of nicotinamide adenine dinucleotide), a scavenger of reactive oxygen species (ROS). We previously reported that retinal ganglion cells (RGCs) express AQP9 and that elevated intraocular pressure reduces AQP9 expression and increases death of neurons in the retinal ganglion cell layer of rodents. In the present study, we investigated the association of AQP9 expression with serum deprivation-induced death of RGC-5 cells and with death of neurons in the rat retinal ganglion cell layer after optic nerve transection (ONT). The effect of AQP9 RNA interference on serum deprivation-induced apoptosis, ROS accumulation, and the NAD(+)/NADH ratio in RGC-5 cells was examined. Both serum deprivation and ONT significantly reduced AQP9 protein expression in RGCs and increased the rate of RGC death. Retinal AQP9 gene expression also declined after ONT. Down-regulation of AQP9 significantly increased apoptosis, ROS accumulation, and the NAD(+)/NADH ratio in the RGC-5 cells. These findings suggest that AQP9 loss adversely affects survival of RGCs, at least partly because of decreased transport of lactate as a substrate for energy and/or ROS scavenger.

Diabetes induces expression of aquaporin-0 in the retinal nerve fibers of spontaneously diabetic Torii rats

Diabetes redistributes the expression of glial aquaporin (AQP) water channels in the retina. However, it is not known whether diabetes also affects retinal AQP-0 expression. This study examined the effects of the development of diabetes on the expression of retinal AQP-0 in spontaneously diabetic Torii (SDT) rats. Malexa0SDT rats at 10 and 40 weeks of age and age-matched male Sprague-Dawley (SD) rats were used. Thexa0localization of AQP-0 was assessed immunohistochemically using sagittal cryosections of the rats retinas and optic nerves. Fold changes in AQP-0 gene expression relative to controls were assessed by real-time RT-PCR. All SDT rats spontaneously developed diabetes by 40 weeks of age (the mean hemoglobin (Hb) A1c levels were 2.8±0.2% and 11.2±1.0% at 10 and 40 weeks, respectively). SD rats did not develop diabetes (the HbA1c levels were 2.7±0.2% and 2.6±0.3% at 10 and 40 weeks, respectively). In the retinas of SD rats and in those of SDT rats at 10 weeks of age, immunoreactivity for AQP-0 was confined predominantly to the inner nuclear layer and to the border between the inner plexiform layer and the ganglion cell layer (GCL), where AQP-0 colocalized with protein kinase C-α. AQP-0 immunoreactivity was also observed in the GCL to a lesser degree, which colocalized with the neuronal nuclei. In the 40-week-old SDT rat retinas, additional AQP-0 immunoreactivity was observed in the GCL and colocalized with neurofilaments, indicating expression of AQP-0 in ganglion cell axons. However, the axonal AQP-0 immunoreactivity was restricted to the retinal nerve fibers, whereas the optic nerve axons were devoid of AQP-0. Retinal blood vessels did not express AQP-0. AQP-0 gene expression was 3.4-fold higher in SDT rat retinas than in SD rat retinas at 40 weeks of age. AQP-0 was predominantly expressed in the bipolar cells of the non-diabetic rat retinas, whereas it was also expressed in the retinal nerve fibers of diabetic rat retinas. The disrupted water transport between astrocytes and retinal nerve fibers may be associated with the known accelerated apoptosis of retinal ganglion cells induced by diabetes.