Hae-Young Lopilly Park

Enhanced Depth Imaging Detects Lamina Cribrosa Thickness Differences in Normal Tension Glaucoma and Primary Open-Angle Glaucoma

OBJECTIVE To confirm the advantages of the enhanced depth imaging (EDI) mode over the standard mode of the Heidelberg Spectralis spectral domain optical coherence tomography (SD-OCT) for imaging of the lamina cribrosa, and to compare laminar thicknesses of various glaucoma types with or without disc hemorrhage in a similar state of visual field loss. DESIGN Cross-sectional, case-control design. PARTICIPANTS We included 137 glaucoma patients and 49 healthy controls. METHODS Optic nerve head B-scans were obtained by both the standard and EDI modes of the Spectralis OCT. Laminar thickness was measured at the center of mid-superior, central, and mid-inferior horizontal B-scans. Laminar thickness in patients with normal tension glaucoma (NTG) was compared with that in patients with primary open-angle glaucoma (POAG). To verify the reproducibility of EDI imaging, intraclass correlation coefficients and test-retest variability were calculated from selected B-scans. MAIN OUTCOME MEASURES Laminar thickness and mean deviation values on standard automatic perimetry. RESULTS The EDI OCT imaging showed significantly better intraobserver, interobserver, intravisit, and intervisit reproducibility than those by standard imaging. Laminar thickness in mid-superior, central, and mid-inferior regions was thinner in the POAG and NTG groups than in the normal control group (P<0.001). The mid-superior, central, and mid-inferior regions of the lamina were also significantly thinner in patients with NTG and disc hemorrhage than in those with NTG but no disc hemorrhage. CONCLUSIONS The EDI mode of the Heidelberg Spectralis SD-OCT detected differences in the lamina cribrosa by glaucoma type. The lamina cribrosa was thinner in NTG eyes and in NTG eyes with disc hemorrhage. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Optic Disc Torsion Direction Predicts the Location of Glaucomatous Damage in Normal-Tension Glaucoma Patients with Myopia

OBJECTIVE To characterize optic disc tilt and torsion in normal-tension glaucoma (NTG) patients with myopia and to evaluate the relationship between optic disc tilt and torsion with the location of visual field (VF) defect. DESIGN Retrospective, case-control design. PARTICIPANTS Two hundred twenty-five NTG patients. METHODS Patients were divided into a myopic NTG group (spherical equivalent more than -2.00 diopters [D] or axial length more than 24.0 mm; n = 166) and nonmyopic NTG group (spherical equivalent less than -0.50 D or axial length less than 24.0 mm; n = 59). Disc tilt, which was identified by the tilt ratio, disc torsion, and area of peripapillary atrophy (PPA), was measured from disc photographs. Patients were divided further into superior and inferior defect groups according to the location of the VF defect in the pattern deviation map. Logistic regression analysis was used to determine the relationship between ocular factors, including tilt ratio, torsion degree, and the VF defect location. MAIN OUTCOME MEASURES Tilt ratio, torsion degree, PPA area, and location of VF defect. RESULTS Among 225 NTG eyes, 166 (73.8%) were myopic eyes. The myopic NTG group was significantly younger (42.85 years) than the nonmyopic NTG group (60.73 years). Disc tilt (45.8%) and torsion (75.9%) were significantly more prevalent in the myopic NTG group than in the nonmyopic NTG group. Although just short of statistical significance (P = 0.057), PPA area was larger in the myopic NTG group. The VF defect location was significantly different between the 2 groups, with superior defects more prevalent in the myopic NTG group (69.9%; P<0.001). Torsion degree was significantly different in the superior defect group (18.45°) compared with the inferior defect group (-3.81°; P = 0.001). Torsion degree was the only factor related to VF defect location in both univariate (P = 0.001) and multivariate (P = 0.014) logistic regression analyses. CONCLUSIONS Korean NTG patients had a high prevalence of myopia and young age. Optic disc tilt and torsion were highly prevalent in Korean NTG patients with myopia. The direction of the optic disc torsion may predict the location of damage.

Imaging the Posterior Segment of the Eye using Swept-Source Optical Coherence Tomography in Myopic Glaucoma Eyes: Comparison With Enhanced-Depth Imaging

PURPOSE To compare the detection rates of identifying the posterior border of the sclera and lamina cribrosa and measurement reproducibility of scleral and laminar thicknesses using the enhanced depth imaging (EDI) of Heidelberg Spectralis optical coherence tomography (OCT) and swept-source OCT. DESIGN Cross-sectional design. METHODS Both EDI-OCT and swept-source OCT images were obtained in 32 myopic glaucoma patients. Subfoveal choroidal, subfoveal scleral, and central laminar thicknesses were measured from obtained B-scan images. Each measurement was performed at 3 locations by 2 masked observers. The detection rates and measurement reproducibility were evaluated from selected B-scans. RESULTS The posterior border of the sclera was visible in 10 eyes (31%) using EDI-OCT. This was improved to be visible in 17 eyes (53%) using swept-source OCT. According to the McNemar χ(2) test, the detection rate of the posterior border of the sclera was significantly different between EDI-OCT and swept-source OCT (P = 0.008). The detection rate of the posterior border of the lamina cribrosa was similar for the 2 devices. In highly myopic eyes, the detection rate of the posterior border of the sclera and lamina cribrosa was not statistically different between EDI-OCT and swept-source OCT. Intersystem ICCs was 0.769 (95% CI, 0.714-0.893) for subfoveal scleral thickness and 0.900 (95% CI, 0.887-0.917) for laminar thickness. The mean subfoveal scleral thickness was 464.32 ± 213.24 μm using EDI-OCT and 650.26 ± 222.30 μm using swept-source OCT. There was statistical difference in the measured subfoveal scleral thickness by the 2 devices (P = 0.018). CONCLUSIONS Compared with EDI-OCT, swept-source OCT had an advantage in imaging the posterior sclera. Imaging the lamina cribrosa was similar when using both devices.

Diagnostic Capability of Lamina Cribrosa Thickness by Enhanced Depth Imaging and Factors Affecting Thickness in Patients with Glaucoma

OBJECTIVE To determine the diagnostic ability of laminar thickness obtained using enhanced depth imaging (EDI) of the Heidelberg Spectralis optical coherence tomography (OCT) system (Heidelberg Engineering, Heidelberg, Germany) and the factors related to laminar thickness in patients with glaucoma. DESIGN Evaluation of a diagnostic test. PARTICIPANTS A total of 144 patients with glaucoma (68 with primary open-angle glaucoma [POAG], 76 with normal-tension glaucoma [NTG]), and 65 healthy controls. METHODS All patients underwent retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) scanning with the Spectralis OCT system. Mean laminar thickness was defined at the center of the mid-superior, central, and mid-inferior horizontal B-scans of the ONH, and the mean of 3 laminar thickness measurements was used for the diagnostic test. Receiver operating characteristic (ROC) curves were obtained for average and quadrant RNFL thickness and mean laminar thickness. Areas under the ROC curve (AUCs), 95% confidence intervals (CIs), and sensitivities at a fixed specificity (90%) were calculated. Factors related to mean laminar thickness were analyzed by univariate and multivariate regression analyses in patients with glaucoma. MAIN OUTCOME MEASURES Comparison of diagnostic ability using AUCs. RESULTS Mean laminar thickness had the largest AUCs among all patients with glaucoma (AUC, 0.980; 95% CI, 0.966-0.993) and patients with NTG (AUC, 0.989; 95% CI, 0.980-0.994). The AUC of the mean laminar thickness of patients with NTG was significantly different from the AUC of the inferior RNFL thickness (AUC, 0.947; 95% CI, 0.929-0.965; P = 0.047), which had the largest AUC among the RNFL thickness parameters. The AUCs for discrimination between early glaucomatous eyes and normal eyes showed significant differences between the NTG group (AUC, 0.981; 95% CI, 0.968-0.992) and all patients with glaucoma (AUC, 0.941; 95% CI, 0.931-0.952; P = 0.007). The factor significantly associated with laminar thickness in both univariate and multivariate regression was NTG diagnosis (P = 0.001). CONCLUSIONS The diagnostic ability of laminar thickness was comparable to that of peripapillary RNFL thickness in patients with glaucoma overall and better than peripapillary RNFL thickness in patients with early NTG.

Analysis of Macular and Peripapillary Choroidal Thickness in Glaucoma Patients by Enhanced Depth Imaging Optical Coherence Tomography

Background:To compare the macular and peripapillary choroidal thickness between normal and glaucoma eyes and find out factors related to choroidal thickness using enhanced depth imaging (EDI) of Heidelberg Spectralis SD-OCT. Study Design:Cross-sectional transverse study. Methods:A total of 108 glaucoma patients and 48 healthy controls were included in the analysis. Choroidal thickness was measured from 6 mm length radial B-scans at the macular and the optic nerve head by EDI OCT. Choroidal thickness was compared between normal controls, normal tension glaucoma (NTG) patients, and primary open-angle glaucoma (POAG) patients. Factors related to choroidal thickness were analyzed by regression analysis. Results:There were no differences in average, temporal, nasal, superior, and inferior macular choroidal thickness between normal, NTG, and POAG eyes. The peripapillary thickness did not differ between normal and POAG eyes; however, average, temporal, nasal, superior, and inferior peripapillary choroidal thickness were significantly thinner in NTG eyes. Axial length (&bgr;=−11.36, P<0.001) was the most significant factor associated with peripapillary choroidal thickness, followed by age (&bgr;=−5.10, P<0.001). Glaucoma type (&bgr;=−11.28, P<0.001) were also significantly associated with peripapillary choroidal thickness. Conclusions:Peripapillary choroidal thickness was significantly reduced in NTG eyes based on EDI OCT measurements in vivo.

Transneuronal Retrograde Degeneration of the Retinal Ganglion Cells in Patients with Cerebral Infarction

PURPOSE The objective of this study was to determine whether transneuronal retrograde degeneration (TRD) of the retinal ganglion cells (RGCs) could be detected by optical coherence tomography (OCT) in humans with lesions other than of the occipital lobe or visual cortex. In addition, whether laterality and severity of retinal nerve fiber layer (RNFL) damage correlated with 3 other variables was determined: laterality of hemispheric damage, arterial territory of infarct, and age of infarct. DESIGN Cross-sectional, case-control design. PARTICIPANTS Forty-six patients with cerebral ischemic infarction diagnosed based on brain magnetic resonance imaging and 46 normal controls were enrolled. METHODS All subjects underwent a complete ophthalmic examination including OCT. Cerebral infarction was categorized by arterial territory: anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA). Eyes on the same side of the infarction were referred to as ipsilateral eyes, and eyes on the opposite side of the infarction were referred as contralateral eyes. MAIN OUTCOME MEASURES Retinal nerve fiber layer thickness. RESULTS Average, superior, temporal, inferior, and nasal RNFL thicknesses were different significantly between patients with cerebral infarction and normal controls. The RNFL thicknesses were reduced significantly at the superior, inferior, and nasal quadrants in the contralateral eyes and at the superior, inferior, and temporal quadrants in the ipsilateral eyes. The RNFL thickness reduction was greater in patients with PCA infarction, followed by MCA and ACA infarction, respectively. Factors related to the average RNFL thickness were time after stroke onset and infarction territory based on both univariate (P = 0.027 and P = 0.046, respectively) and multivariate (P = 0.036 and P = 0.047, respectively) analysis. CONCLUSIONS Retinal nerve fiber layer thickness was reduced in patients with cerebral infarction, providing evidence for TRD of the RGCs. Transneuronal retrograde degeneration was more pronounced in the nasal nerve fiber layer of the contralateral side and in the temporal nerve fiber layer of the ipsilateral side of cerebral damage. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Neuronal cell death in the inner retina and the influence of vascular endothelial growth factor inhibition in a diabetic rat model.

To inhibit vascular changes in diabetic retinopathy, inhibiting vascular endothelial growth factor (VEGF) has become a mainstay of the treatment of diabetic retinopathy. However, its effects on neuronal cells remain to be elucidated. We aimed to evaluate the effect of VEGF inhibition on neuronal cells in a streptozotocin-induced diabetic rat retina. VEGF inhibition was performed by intravitreal VEGF-A antibody injection. After anti-VEGF treatment, apoptosis in retinal ganglion cells (RGCs) increased, and novel apoptosis in amacrine and bipolar cells of the inner nuclear layer was observed by TUNEL staining. Phosphorylated Akt expression was significantly higher in RGCs but was decreased in neuronal cells of the inner nuclear layer after anti-VEGF treatment by Western blot analysis and immunohistochemical staining. These results demonstrate that VEGF inhibition significantly increased RGC apoptosis and neuronal cell apoptosis in the inner nuclear layer of a diabetic retina, which seems to consist primarily of amacrine and bipolar cells. The phosphorylated Akt pathway, which plays a neuroprotective role via VEGF, was significantly affected by VEGF inhibition in the inner nuclear layer, suggesting that neurotrophic factor deprivation is the main mechanism for neuronal cell death after inhibiting VEGF. The results of this study show that inhibiting VEGF may have detrimental effects on the apoptosis of neuronal cells in the inner layers of the diabetic retina.

Optic disc tilt direction determines the location of initial glaucomatous damage.

PURPOSE To explore differences in optic disc tilt and torsion between normal control and glaucoma subjects, and to determine whether the direction of optic disc tilt is consistent with the initial location of glaucomatous visual field (VF) defect. METHODS Glaucoma patients with isolated superior or inferior hemifield loss (n = 136) and normal controls (n = 99) were analyzed. Disc ovality index and torsion degree were measured on retinal photographs. Imaging of optic disc was obtained using Heidelberg retinal tomography (HRT) III and Cirrus spectral-domain optical coherence tomography (OCT). The degree of temporal disc tilt was assessed using horizontal topographic images and vertical (upward or downward) disc tilt using vertical topographic images, respectively. RESULTS In all subjects, disc ovality was significantly associated with HRT- and OCT-measured temporal disc tilt and axial length (AL) (all P < 0.001), whereas disc torsion degree was associated with HRT- and OCT-measured vertical disc tilt and AL (all P < 0.05). Association of AL with disc ovality and torsion became more evident as the mean deviation increased. When data on glaucoma patients with superior and inferior hemifield defects were compared, the vertical disc tilt (HRT- and OCT-assessed, P < 0.001 and 0.030, respectively) and the torsion degree (P = 0.002) differed significantly. Upon multivariate logistic regression analysis, the HRT-measured vertical disc tilt was an independent factor determining initial location of the VF defect (P = 0.012). CONCLUSIONS Measurement of vertical disc tilt may give valuable information about the superior versus inferior regional susceptibilities of glaucoma.

Glial cell response and iNOS expression in the optic nerve head and retina of the rat following acute high IOP ischemia–reperfusion

Acute high IOP ischemia-reperfusion induces the loss of retinal ganglion cells, supporting the hypothesis that the condition of ischemia-reperfusion contributes to the induction and progression of glaucoma. This study investigated morphological changes, glial cell response, and expression of inducible nitric oxide synthase (iNOS) in the optic nerve head and retina of the rat following acute high IOP ischemia-reperfusion. A 60-min ischemic period was administered to the rat eye by raising the IOP, followed by a reperfusion period lasting 2, 5, or 7 days. Histological examination showed that acute high IOP ischemia-reperfusion injury produced optic nerve head and retina damage. In immunohistochemical staining, GFAP and OX-45 were limited to the ganglion cell layer (GCL) or inner nuclear layer (INL) of the control retina and increased to nearly all layers of the retina after acute high IOP ischemia-reperfusion. GFAP and OX-42 were detected at the control optic nerve heads and increased after acute high IOP ischemia-reperfusion. After acute high IOP ischemia-reperfusion, expression of iNOS increased, mostly at the GCL and INL of the retina and at the optic nerve head. Western blot analysis showed that expression of iNOS increased significantly, compared with the control, in the retina and optic nerve head after acute high IOP ischemia-reperfusion. Activation of glial cells and the up-regulation of iNOS may contribute to the damage of the retina and optic nerve head of the rat following acute high IOP ischemia-reperfusion.

Stem cell-based delivery of brain-derived neurotrophic factor gene in the rat retina

As an alternative to a viral vector, the application of stem cells to transfer specific genes is under investigation in various organs. Using this strategy may provide more effective method to supply neurotrophic factor to the neurodegenerative diseases caused by neurotrophic factor deprivation. This study investigated the possibility and efficacy of stem cell-based delivery of the brain-derived neurotrophic factor (BDNF) gene to rat retina. Rat BDNF cDNA was transduced into rat bone marrow mesenchymal stem cells (rMSCs) using a retroviral vector. Its incorporation into the experimental rat retina and the expression of BDNF after intravitreal injection or subretinal injection were detected by real-time PCR, western blot analysis, and immunohistochemical staining. For the incorporated rMSCs, retinal-specific marker staining was performed to investigate the changes in morphology and the characteristics of the stem cells. Transduction of the rMSCs by retrovirus was effective, and the transduced rMSCs expressed high levels of the BDNF gene and protein. The subretinal injection of rMSCs produced rMSC migration and incorporation into the rat retina (about 15.7% incorporation rate), and retinal BDNF mRNA and protein expression was increased at 4 weeks after transplantation. When subretinal injection of rMSCs was applied to axotomized rat retina, it significantly increased the expression of BDNF until 4 weeks after transplantation. Some of the transplanted rMSCs exhibited morphological changes, but the retinal-specific marker stain was not sufficient to indicate whether neuronal differentiation had occurred. Using mesenchymal stem cells to deliver the BDNF gene to the retina may provide new treatment for glaucoma.