Maiko Naka

Regional Relationship Between Retinal Nerve Fiber Layer Thickness and Corresponding Visual Field Sensitivity in Glaucomatous Eyes

OBJECTIVE To establish the structure-function relationship between peripapillary retinal nerve fiber layer (RNFL) thickness and visual field (VF) test points in standard automated perimetry. METHODS We included 213 eyes with open-angle glaucoma and VF loss in this cross-sectional study. Correlations between individual VF sensitivity at 52 test points and peripapillary RNFL thickness divided into 16 sectors were calculated. The RNFL thickness was measured by Stratus optical coherence tomography. A new VF cluster map corresponding to RNFL sectors was generated by grouping the VF test points with the highest relation to each RNFL sector. RESULTS The VF sensitivity at each test point was significantly correlated with the sectoral RNFL thickness. The highest coefficient of determination (R(2)) for a superotemporal RNFL sector and VF sensitivity at an inferotemporal test point (9 degrees temporal and 15 degrees inferior from the center) in standard automated perimetry was 0.500 (P < .001). Clustered VF test points most highly related to the RNFL sectors were asymmetrically located between the upper and lower hemifields. A newly developed map revealed significant structure-function relationships. CONCLUSIONS We describe an association between VF sensitivity at test points and sectoral RNFL thickness. Nine clustered VF test points corresponding to 9 RNFL regions were demonstrated from the structure-function relationships.

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.

Latanoprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo

We investigated whether latanoprost has a direct anti-apoptotic effect in retinal ganglion cell (RGC) line and RGCs in the rat. RGC-5 cells were induced to undergo apoptosis by serum deprivation and exogenous glutamate. The level of cell death with or without latanoprost acid was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in the level of intracellular calcium ([Ca(2+)]i) were measured with fluo-4 fluorescence. The XTT assay revealed that latanoprost acid increased RGC-5 cell viability. Latanoprost acid significantly reduced caspase-3 positive cells and suppressed [Ca(2+)]i evoked by glutamate. U0126, a mitogen-activated protein/extracellular signal-regulated kinase 1 and 2 inhibitor, partially blocked the rescue effect of latnanoprost acid (p=0.013). In vivo, rat RGCs were degenerated by optic nerve crush. After topical instillation of latanoprost for 7days, RGCs labeled with fluorogold were significantly. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells. TUNEL-positive cells were significantly decreased in eyes with topically instilled latanoprost (p=0.015). These data suggest that latanoprost has an neuroprotective ability in RGCs.

Cluster Analyses of Grid-Pattern Display in Macular Parameters Using Optical Coherence Tomography for Glaucoma Diagnosis

PURPOSE Using spectral-domain optical coherence tomography (SD-OCT), we assessed the ability of cluster analyses, based on the grid-pattern of macular parameters, to detect glaucoma. METHODS We enrolled 75 normal eyes, 64 early glaucomatous eyes (EG), and 40 preperimetric glaucomatous eyes (PPG). Each participant was imaged using 3-dimensional optical coherence tomography (3D-OCT) to examine the macular retinal nerve fiber layer (mRNFL) and the thickness of the ganglion cell layer, together with the inner plexiform layer (GCL/IPL). Diagnostic criteria based on the clustering of abnormal grids from the mRNFL and GCL/IPL measurements were applied. The sensitivity and specificity of glaucoma detection were compared between the cluster criteria (CC) and the average thickness criteria (ATC) of total and hemiretinal sectors, and the cut-off criteria were determined using receiver operating characteristic (ROC) curve analyses from our normal controls. RESULTS The specificity values of CC and ATC from mRNFL measurements were 97% and 100%, respectively. The sensitivity of CC was 94% for EG and 68% for PPG. The sensitivity of ATC was 81% for EG and 38% for PPG. The specificity values of CC and ATC from GCL/IPL measurements were 96% and 100%, respectively. The sensitivity values of CC and ATC were 92% for EG and 63% for PPG. The sensitivity of ATC was 84% for EG and 25% for PPG. When compared to ATC and ROC-based cut-off criteria, CC showed a higher diagnostic capability. CONCLUSIONS Judging abnormality based on a clustering of abnormal grids from macular OCT parameters may be a reliable approach for diagnosing early glaucoma. (http://www.umin.ac.jp/ctr/index/htm9 number, UMIN000006900.).

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.

Filtering Bleb Structure Associated with Long-Term Intraocular Pressure Control after Amniotic Membrane-Assisted Trabeculectomy

Purpose/Aim: To determine whether amniotic membrane transplantation (AMT) at trabeculectomy affects intrableb structures and which intrableb parameters are significantly correlated with the long-term intraocular pressure (IOP) control. Materials and Methods: Enrolled were 64 eyes of 56 glaucoma patients who underwent trabeculectomy without (36 eyes) or with (28 eyes) AMT. Bleb structure was evaluated by ultrasound biomicroscopy (UBM) at least one year after surgery. IOP control was defined as good when the eyes had a more than 30% decrease in the preoperative IOP and an IOP value <18 mmHg if the preoperative IOP was higher than 21 mmHg. Logistic regression analyses were conducted to identify factors significantly associated with IOP control. Results: Intervals between surgery and the timing of the UBM examinations (median; 2.5 years) and the overall frequency of good IOP control (28/36 in the eyes without AMT and 17/28 in those with AMT; chi-square test, P = 0.2276) were similar in the two groups. The eyes with AMT had a significantly lower number of type H (high reflective) or L (low reflective) blebs and a higher number of type E (encapsulated) blebs compared to those without AMT (P < 0.0001). Among independent variables, which included age, sex, glaucoma type, lens status, the number of ocular hypotensives, and previous intraocular surgeries, only type F (flattened) bleb in eyes without AMT (P = 0.0008, odds ratio [OR] = 0.0256) and no or limited intrableb fluid-filled space in eyes with AMT were significantly associated with poor IOP control (P = 0.0026, OR = 0.0111, and 0.0071, 0.0167, respectively). Conclusions: Intrableb structures after trabeculectomy alone versus AMT-assisted trabeculectomy were distinct. The bleb wall reflectivity in the former and the extent of the subconjunctival fluid-filled space in the latter were factors associated with long-term IOP control.

Comparison of mean deviation with AGIS and CIGTS scores in association with structural parameters in glaucomatous eyes.

ObjectiveTo evaluate which of the 3 clinically used visual field indices including mean deviation (MD), Advanced Glaucoma Intervention Study (AGIS) score, and Collaborative Initial Glaucoma Treatment Study (CIGTS) score are best in evaluating functional damage of glaucomatous optic neuropathy. MethodsIn 213 glaucomatous eyes, peripapillary retinal nerve fiber layer thickness (RNFLT) and optic disc configuration were measured with Stratus optical coherence tomography and Heidelberg Retina Tomograph-2, respectively. Visual field was measured with standard automated perimetry 30-2. Correlations of the structural parameters compared with the 3 VF indices using second polynomial regression were calculated. In addition, these correlations were analyzed among eyes of 3 different stages of glaucoma, as defined by MD score (early, MD≥−6 dB; moderate, −12 dB≤MD<−6 dB; advanced, MD<−12 dB). ResultsAmong structure-function relationships in all subjects, the highest correlation determination (R2) was MD with RNFLT (=0.298). CIGTS score showed better R2 than MD or AGIS score with rim area, but these values were not higher than any R2 with RNFLT. In analyses of 3 groups depending on MD, statistically significant structure-function correlations were observed only in patients with an advanced stage. ConclusionsNo clear difference was found among MD and AGIS/CIGTS scores in expressing functional damage of glaucomatous eyes. MD is suggested to be no worse than others in monitoring glaucoma in clinical setting.