Search

Purpose: To assess the combined estimate of retinal ganglion cell (RGC) count developed by Medeiros et al. as a tool for diagnosis of glaucoma in Japanese patients., Study Design: Cross-sectional study., Methods: Thirty-one eyes of 19 healthy controls and 106 eyes of 70 glaucoma patients underwent standard automated perimetry (SAP) and three types of spectral domain optical coherence tomography (SD-OCT) imaging using the Cirrus, RTVue, and 3D-OCT instruments. RGC counts derived from SAP and SD-OCT data were estimated using the Harwerth model (SAPrgc and OCTrgc, respectively), from which the combined RGC count estimates (CRGC) were calculated using the formula developed by Medeiros et al. Receiver operating characteristic curve (ROC) analyses were conducted for mean deviation (MD), retinal nerve fiber layer thickness (RNFLT), and CRGC., Results: The mean OCTrgc derived from the Cirrus, RTVue, and 3D-OCT instruments were 1150, 1245, and 1316 (× 1000 cells), respectively, for the control group and 463, 519, and 516 (× 1000 cells), respectively, for the patient group. SAPrgc of the controls' group was 1526 and the patients' group, 731 (× 1000 cells), and were consistently greater than OCTrgc in both groups (a generalized estimating equation model, p < 0.001). Partial area under the curve (pAUC) of MD was 0.178, and that of RNFLT and CRGC for the three OCT instruments were 0.185, 0.18, 0.189 and 0.196, 0.196, 0.197, respectively. CRGC had larger pAUC than MD, whereas there was no or marginal difference in pAUC between CRGC and cpRNFLT, irrespective of OCT device used or glaucoma severity., Conclusion: CRGC proved well suited to discriminate glaucoma patients from controls. However, its clinical utility did not seem to overwhelm isolated structural measures in the tested Japanese patients.

Background/aims: Chiasmal compression affects the crossed nerve fibres originating from the nasal hemiretina, as opposed to the uncrossed fibres from the temporal hemiretina. The objectives were to evaluate circumpapillary retinal nerve fibre layer (cpRNFL) thickness by spectral-domain optical coherence tomography in eyes with band atrophy (BA) accompanying temporal hemianopia due to chiasmal damage and to estimate the distribution pattern of cpRNFL from the nasal hemiretina., Methods: This cross-sectional study included 53 eyes with optic neuropathy due to chiasmal lesions and 72 normal eyes. Visual field sensitivity (VFS) was evaluated by standard automated perimetry. Eyes with abnormalities in the nasal visual hemifield were excluded. The structure-function relationships (cpRNFL thickness and VFS in the temporal hemifield) were evaluated in eyes with BA. The base levels composed of only non-neuronal elements and cpRNFL from the temporal hemiretina were estimated in the average and 12 sector-cpRNFL thicknesses using regression analysis., Results: The base level in the average cpRNFL thickness was 71.2 µm in eyes with BA, which corresponded to 70% of average thickness of normal controls. However, the estimated base level of 12 sector-cpRNFL thicknesses represented the unique distribution pattern, in which base level-thickness localised at the 1 o'clock and 5 o'clock sectors was extensively reduced, with an even distribution of base levels at other sectors., Conclusions: The RNFL originating from the nasal hemiretina is estimated to enter into the optic disc predominantly at the 1 o'clock and 5 o'clock angles., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To compare the relationship between visual field sensitivity (VFS) and macular parameters measured using three spectral-domain optical coherence tomography (SD-OCT) instruments and to determine a base level (=floor effect) for macular parameters., Methods: We imaged 127 glaucomatous eyes (1 eye per subject) using three different OCT instruments, i.e., the Cirrus, RTVue and 3D OCT devices; 76 normal eyes were evaluated as controls using the same instruments. The thicknesses of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer+inner plexiform layer (GCL/IPL), and mRNFL+GCL/IPL (GCC) were analyzed. The VFS of the area analyzed by OCT was expressed in decibels and the 1/Lambert scale. For each parameter, the structure-function relationship and the base level were evaluated by regression analysis. The strength of the correlations between the instruments was compared by the bootstrapping method., Results: All of the macular parameters evaluated exhibited statistically significant correlations with VFS. The average GCC measured by all three SD-OCT instruments and the average mRNFL thickness measured by the Cirrus and 3D OCT instruments had similar correlations with VFS. The average GCL/IPL thickness measured by the Cirrus OCT instrument was better correlated with VFS that was measured by the 3D OCT instrument (p = 0.031). The base level GCC thickness measured by all three instruments was approximately 65% of that of normal eyes. The base level mRNFL thickness measured with the Cirrus and OCT instruments was 52 and 48%, respectively, of that of normal eyes. The base level GCL/IPL thickness measured with the Cirrus and 3D instruments was 71 and 75%, respectively, of that of normal eyes., Conclusions: The three SD-OCT instruments evaluated showed similar structure-function relationships in terms of GCC and mRNFL measurements. The base levels of the macular parameters determined by the three instruments differed, due, at least partly, to the scanning area defined by each instrument.

Neuromyelitis optica (NMO) is an autoimmune inflammatory, neurodestructive disease primarily targeting the optic nerve and spinal cord. An autoantibody against water channel protein aquaporin-4 (AQP4), which is expressed at endofeet of astrocytes has been implicated in the pathogenesis of NMO. We evaluated the impact of sera of seropositive patients with NMO spectrum disorders (NMOSDs) on the rodent optic nerve and retina. Serum was obtained either from patients with seropositive NMOSD (AQP4+), seronegative patient with idiopathic optic neuritis (AQP4-), and healthy volunteers (control). Anti-AQP4 antibody in a serum was measured by a previously established cell-based assay. The patients' sera were applied on the optic nerve after de-sheathed. Immunohistochemistry showed that at 7 days after the treatment, the area of the optic nerve exposed to the AQP4+ sera lost expression of both AQP4 and glial fibrillary acidic protein. Also, Human-IgG immunoreactivity and marked invasion of inflammation cells were observed in the optic nerve treated with AQP4+ serum. Immnoreactivity of neurofilament was reduced at 14 days after the treatment, not 7 days. Real-time polymerase chain reaction revealed the reduced gene expression of neurofilament in retina from the eye that was exposed to the AQP4+ sera at 14 days. Retrograde fluorogold-labeling on the retinal flatmount disclosed the significantly reduced number of retinal ganglion cells when the AQP4+ sera were applied. The present model has demonstrated that the sera from patients with seropositive NMOSDs led to the regional astrocytic degeneration and inflammatory cell invasion in the optic nerve, resulting in the ultimate loss of RGCs and their axons at areas beyond the injury site., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the effects of ocular rotation on parapapillary retinal nerve fiber layer (RNFL) thickness measured by spectral-domain optical coherence tomography (SD-OCT)., Patients and Methods: Eighty-eight normal and 205 glaucomatous eyes were studied. RNFL thickness was measured by 3D OCT. Ocular rotation angle was measured from a fundus image obtained by a non-mydriatic fundus camera equipped with 3D OCT. The average, hemi-superior, and hemi-inferior RNFL thicknesses as well as those in the 4 quadrants and the 16-segmented superotemporal (ST-1) and inferotemporal (IT-4) sectors were compared both before and after correcting for ocular rotation. Receiver operating characteristic curves and the areas under the curve (AUC) for the RNFL thicknesses were calculated on the basis of the data from glaucomatous and control eyes. The relationships between RNFL thickness and retinal sensitivity in the corresponding visual field were analyzed using a Humphrey field analyzer., Results: Correction for ocular rotation did not affect the AUCs of the hemi-superior and hemi-inferior RNFL thicknesses. RNFL thicknesses in all of the quadrants and in ST-1 and IT-4 were significantly changed by correcting for ocular rotation. The correlations between all RNFL sectors and retinal sensitivity were not changed by correcting for the ocular rotation angle., Conclusions: Ocular rotation compensation affected RNFL thickness measurement with 3D OCT. However, the effect was clinically negligible in the diagnosis of glaucoma.

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.

Corroles are tetrapyrrolic macrocycles that have come under increased attention because of their unique capabilities for oxidation catalysis, reduction catalysis, and biomedical applications. Corrole-metal complexes (metallocorroles) can decompose certain reactive oxygen species (ROS), similar to metalloporphyrins. We investigated whether Fe-, Mn-, and Ga-corroles have neuroprotective effects on neurons and correlated this with superoxide scavenging activity in vitro and in vivo. Apoptosis was induced in retinal ganglion cell-5 neuronal precursor cells by serum deprivation. Cell death was measured with sodium 3'-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene-sulfonic acid hydrate and calcein-AM/propidium iodide assays. Fe- and Mn-corroles, but not the non-redox-active Ga-corrole used as control, reduced RGC-5 cell death after serum deprivation. Serum deprivation caused increased levels of intracellular superoxide, detected by an increase in the fluorescence intensity of 2-hydroxyethidium, and this was blocked by Fe- and Mn-corroles, but not Ga-corrole. In vivo real-time confocal imaging of retinas after optic nerve transection assessed the superoxide production within individual rat retinal ganglion cells. Fe- and Mn-corroles, but not Ga-corrole, scavenged neuronal superoxide in vivo. Given that the neuroprotective activity of metallocorroles correlated with superoxide scavenging activity, Fe- and Mn-corroles could be candidate drugs for delaying neuronal death after axonal injury in optic neuropathies, such as glaucoma.

Purpose: To compare the morphologic alterations between upper and lower sectors of the optic nerve head (ONH) in eyes with primary open-angle glaucoma (POAG) that have hemifield visual field defects and to evaluate the correlation between this sectoral ONH damage and visual field sensitivity loss within the corresponding clustered test points of standard automated perimetry., Methods: Visual field testing with Humphrey Field Analyzer and imaging with Heidelberg Retina Tomograph (HRT) were performed in 87 eyes from 87 Japanese patients with POAG and 150 eyes from 150 normal subjects. Global and segmental HRT topographic parameters were compared among POAG patients with superior hemifield defects, those with inferior hemifield defects, and controls. The correlation between the sectoral HRT measurements and the sum of total deviation values in the corresponding clustered visual field test points was analyzed in the 2 POAG groups., Results: The HRT measurements in both POAG groups were significantly different from those of controls, not only in the sectors corresponding to abnormal hemifield, but also in the sectors corresponding to the normal visual hemifield. There was a linear correlation between the sectoral HRT parameters and clustered visual field sensitivities in the affected hemifield areas., Conclusions: The present study indirectly supports the notion that the relationship between structural and functional damage of glaucomatous optic neuropathy is not linear when evaluated with the currently available techniques and instruments.

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.

Open-angle glaucoma (OAG) is an optic neuropathy characterized by progressive retinal ganglion cell (RGC) death and optic disk excavation. Evidence is accumulating that RGC apoptosis is the fundamental pathology of OAG. Among several risk factors for development and progression of OAG, inclusion of comorbid diabetes has been controversial. Some large population-based prevalence and incidence studies found a positive association between diabetes and OAG, whereas others did not. This inconsistency is derived from selection-, recall-, or survival-bias or misclassification due to low incidence of the two diseases. On the other hand, recent basic studies have shown that diabetes not only affects vascular tissues but also compromises neuronal and glial functions and metabolism in the retina, which ultimately gives rise to apoptotic death of retinal neurons including RGCs. The impaired metabolism of neurons and glia by diabetes may render RGCs susceptible to additional stresses related to OAG such as elevated intraocular pressure. In fact, our latest data demonstrate that retinas taken from rats with streptozotocin-induced diabetes, which underwent cauterization of three episcleral veins to become a chronic glaucoma model, had significantly more apoptotic cells than those from rats with diabetes alone or with chronic glaucoma alone. In this regard, diabetes is a 'risk factor' for glaucomatous optic neuropathy. Additionally, prospective studies are needed to determine if OAG patients with diabetes have a more aggressive course than those without diabetes., (Copyright (c) 2005 S. Karger AG, Basel.)

Purpose: To evaluate the relationship between visual field and retinal nerve fiber layer (RNFL) thickness measured by optical coherent tomography (OCT) and to assess the diagnostic ability of OCT to distinguish between early glaucomatous or glaucoma-suspect eyes from normal eyes., Design: Retrospective, non-randomized, cross-sectional study., Methods: A total of 160 eyes of 120 normal Japanese adults, 23 eyes of 16 patients with ocular hypertension, 38 eyes of 35 glaucoma-suspect patients, and 237 glaucomatous eyes of 140 glaucoma patients were enrolled in the study. The glaucoma group included 89 early glaucomatous eyes. Thickness of the RNFL around the optic disk was determined with three 3.4-mm diameter circle OCT scans. Average and segmental RNFL thickness values were compared among all groups. The correlation between mean deviation and RNFL thickness in glaucomatous eyes was also analyzed. Receiver operating characteristic (ROC) curve area was calculated to discriminate normal eyes from early glaucomatous or glaucoma-suspect eyes., Results: A significant relationship existed between the mean deviation and RNFL thickness in all parameters excluding the 3-o'clock area. The average RNFL thickness had the strongest correlation in all parameters (r = -0.729, P <.001). Retinal nerve fiber layer thickness at the 7-o'clock inferotemporal segment had the widest areas under the ROC curves in all parameters for early glaucomatous eyes (0.873)., Conclusions: Measurement of RNFL thickness by OCT is useful in detecting early RNFL damage. Furthermore, OCT measurements of RNFL thickness may provide clinically relevant information in monitoring glaucomatous changes.

Background: To assess the agreement and diagnostic performance between retinal nerve fiber layer (RNFL) thickness measurements obtained using the Cirrus (Carl Zeiss Meditec) and RTVue (Optovue Inc.) devices for detection of band atrophy (BA) in patients with permanent temporal hemianopia. Methods: In this retrospective study, 26 eyes with BA and 64 control eyes were enrolled. The Cirrus optic disc cube protocol and the RTVue optic nerve head map protocol were used. The Cirrus measurements were extracted and regrouped to be topographically matched with the RTVue measurements. Concordance correlation and 95 % limits of agreement were assessed. Areas under the receiver operating characteristic curves (AUC) and the Spearman's correlation coefficient between average Humphrey total deviation in the temporal hemifield and average RNFL thickness were calculated. Results: RTVue measured consistently thicker values than Cirrus in controls, whereas in eyes with BA, nasal segment measurements from the RTVue were thinner than those obtained using the Cirrus. Each quadrant showed moderate to close agreement in controls, whereas in eyes with BA, the nasal and temporal quadrants exhibited poor agreement. The RTVue measurements demonstrated significantly higher AUCs for nasal segments just above (0.95) and below (0.96) the horizontal meridian than Cirrus measurements (0.80 and 0.66, respectively) and a significant correlation with visual field loss (r = 0.46, P = 0.02 for RTVue vs. r = 0.26, P = 0.22 for Cirrus). Conclusions: The RTVue RNFL thickness measurements in nasal sectors showed better diagnostic performance in detecting BA and higher correlations with temporal hemianopia than the Cirrus measurements. [ABSTRACT FROM AUTHOR]

Purpose: To preliminarily test whether aquaporin (AQP)-9 is expressed in the primate and human optic nerve and whether glaucoma reduces its expression. Methods: The expression of AQP-4 and AQP-9 was immunohistochemically studied in the optic nerves of monkey eyes (an angle-laser-induced ocular hypertensive (OH) eye and a control fellow eye) and of human donor eyes (one control eye and one glaucomatous eye). Results: AQP-9 was immunoreactive throughout the entire region of the optic nerve in the monkey and human control eyes and was co-labeled with glial fibrillary acidic protein. In both the monkey OH and human glaucomatous optic nerves, the level of AQP-9 immunoreactivity was substantially reduced. AQP-4 was immunoreactive only in the retrobulbar region in both the monkey and human control optic nerves, whereas neither OH nor glaucoma affected the AQP-4 expression pattern. Conclusions: As has been shown in rats, the optic nerve head in monkeys and humans expresses AQP-9 but not AQP-4. Elevated intraocular pressure or glaucoma reduces AQP-9 expression in the optic nerve. The decrease in the astrocytic expression of AQP-9 in the optic nerve could be implicated in the development of glaucomatous optic neuropathy. [ABSTRACT FROM AUTHOR]

Abstract: 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 ([Ca2+]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 [Ca2+]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. [Copyright &y& Elsevier]