Kyung Rim Sung

Macular and Peripapillary Retinal Nerve Fiber Layer Measurements by Spectral Domain Optical Coherence Tomography in Normal-Tension Glaucoma

PURPOSE To evaluate and compare the glaucoma discrimination ability of macular inner retinal layer (MIRL) thickness with that of peripapillary retinal nerve fiber layer (pRNFL) thickness measured by spectral-domain optical coherence tomography (RTVue-100; Optovue Inc, Fremont, CA) in patients with normal-tension glaucoma (NTG). METHODS Sixty-five healthy subjects and 102 with NTG were enrolled. MIRL thickness provided by a ganglion cell complex (GCC) scan and two RNFL thicknesses measured by the NHM4 (RNFL1) and RNFL 3.45 (RNFL2) modes of the RTVue-100 system were analyzed. The areas under the receiver operating characteristic curves (AUCs) of MIRL and pRNFL thicknesses for discriminating patients with NTG from control subjects were determined. The AUCs were compared between patients with central visual field (VF) defects (VF; <or=10 degrees of fixation) and peripheral VF defects (>10 degrees from fixation). RESULTS The average MIRL thickness showed a strong correlation with both RNFL1 and -2 thicknesses (R(2) = 0.773, 0.774, both P < 0.0001). The AUCs for average MIRL, RNFL1, and RNFL2 thicknesses were not significantly different at 0.945, 0.973, and 0.976, respectively. However, the AUCs of the average and superior MIRL thicknesses were significantly less than that of the pRNFL thickness in eyes with moderate-to-advanced glaucoma and eyes with peripheral VF defects. CONCLUSIONS The average MIRL thickness showed a strong correlation with pRNFL thickness, because patients with NTG at an early stage showed paracentral VF defects near the fixation point. MIRL thickness showed glaucoma discrimination ability comparable to that of pRNFL thickness in patients with NTG with early VF defects. In eyes with advanced or peripheral VF defect, pRNFL measurement showed a better glaucoma diagnostic ability than did MIRL measurement.

Comparison of Retinal Nerve Fiber Layer Thickness Measured by Cirrus HD and Stratus Optical Coherence Tomography

PURPOSE To study the relationship between retinal nerve fiber layer (RNFL) thickness measured by time domain (Stratus) and spectral domain (Cirrus HD) optical coherence tomography (OCT). DESIGN Cross-sectional study. PARTICIPANTS Sixty healthy participants, 48 glaucoma suspects, and 55 subjects with glaucoma. METHODS Participants were imaged by a single trained operator using the Stratus OCT (fast RNFL scan mode) and Cirrus HD-OCT (optic disc cube mode) at the same visit. MAIN OUTCOME MEASURES The RNFL thickness as measured by the Stratus OCT (fast RNFL scan mode) and Cirrus HD-OCT (optic disc cube mode) was compared (paired t test). The relationship between RNFL thickness measurements of the 2 OCTs were evaluated using a Pearson correlation analysis. The presence of abnormal classification, as determined by using an internal normative data base in each machine was compared (chi-square test). The sensitivity and specificity of normative classification of 2 OCT measurements were calculated. RESULTS Average RNFL thickness as determined by the 2 OCT machines was correlated (r = 0.94; P<0.001), but was significantly different with the 2 machines (Stratus, 98.0 mum, standard deviation [SD] 18.0; Cirrus, 85.6 mum, SD 14.6; P<0.001). The Cirrus HD-OCT classified a significantly higher percentage of eyes as abnormal (Stratus, 12.9%; Cirrus, 23.3%; P<0.001) in average RNFL thickness. Cirrus OCT demonstrated higher sensitivity and specificity (63.6% and 100%) than Stratus OCT (40.0% and 96.7%) in normative classification of average RNFL thickness. CONCLUSIONS There were significant differences in RNFL thickness and normative classification as determined by Stratus OCT and Cirrus HD-OCT despite an excellent correlation of RNFL thickness measurement. Overall sensitivity and specificity were higher with Cirrus OCT. These findings are particularly relevant when an individual undergoes longitudinal follow-up with different OCTs.

Effects of Age on Optical Coherence Tomography Measurements of Healthy Retinal Nerve Fiber Layer, Macula, and Optic Nerve Head

PURPOSE To determine the effects of age on global and sectoral peripapillary retinal nerve fiber layer (RNFL), macular thicknesses, and optic nerve head (ONH) parameters in healthy subjects using optical coherence tomography (OCT). DESIGN Retrospective, cross-sectional observational study. PARTICIPANTS A total of 226 eyes from 124 healthy subjects were included. METHODS Healthy subjects were scanned using the Fast RNFL, Fast Macula, and Fast ONH scan patterns on a Stratus OCT (Carl Zeiss Meditec, Dublin, CA). All global and sectoral RNFL and macular parameters and global ONH parameters were modeled in terms of age using linear mixed effects models. Normalized slopes were also calculated by dividing the slopes by the mean value of the OCT parameter for interparameter comparison. MAIN OUTCOME MEASURES Slope of each OCT parameter across age. RESULTS All global and sectoral RNFL thickness parameters statistically significantly decreased with increasing age, except for the temporal quadrant and clock hours 8 to 10, which were not statistically different from a slope of zero. Highest absolute slopes were in the inferior and superior quadrant RNFL and clock hour 1 (superior nasal). Normalized slopes showed a similar rate in all sectors except for the temporal clock hours (8-10). All macular thickness parameters statistically significantly decreased with increasing age, except for the central fovea sector, which had a slight positive slope that was not statistically significant. The nasal outer sector had the greatest absolute slope. Normalized macular slope in the outer ring was similar to the normalized slopes in the RNFL. Normalized inner ring had shallower slope than the outer ring with a similar rate in all quadrants. Disc area remained nearly constant across the ages, but cup area increased and rim area decreased with age, both of which were statistically significant. CONCLUSIONS Global and regional changes caused by the effects of age on RNFL, macula, and ONH OCT measurements should be considered when assessing eyes over time. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Retinal nerve fibre layer thickness measurement reproducibility improved with spectral domain optical coherence tomography

Background/aims: To investigate retinal nerve fibre layer (RNFL) thickness measurement reproducibility using conventional time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT), and to evaluate two methods defining the optic nerve head (ONH) centring: Centred Each Time (CET) vs Centred Once (CO), in terms of RNFL thickness measurement variability on SD-OCT. Methods: Twenty-seven eyes (14 healthy subjects) had three circumpapillary scans with TD-OCT and three raster scans (three-dimensional or 3D image data) around ONH with SD-OCT. SD-OCT images were analysed in two ways: (1) CET: ONH centre was defined on each image separately and (2) CO: ONH centre was defined on one image and exported to other images after scan registration. After defining the ONH centre, a 3.4 mm diameter virtual circular OCT was resampled on SD-OCT images to mimic the conventional circumpapillary RNFL thickness measurements taken with TD-OCT. Results: CET and CO showed statistically significantly better reproducibility than TD-OCT except for 11:00 with CET. CET and CO methods showed similar reproducibility. Conclusions: SD-OCT 3D cube data generally showed better RNFL measurement reproducibility than TD-OCT. The choice of ONH centring methods did not affect RNFL measurement reproducibility.

Twenty-four hour ocular perfusion pressure fluctuation and risk of normal-tension glaucoma progression.

PURPOSE To investigate the relationship between clinical factors including 24-hour mean ocular perfusion pressure (MOPP, (2/3) x mean arterial pressure [MAP] - intraocular pressure [IOP]) and visual field (VF) progression in eyes with medically treated normal-tension glaucoma (NTG). METHODS One hundred one eyes of 101 NTG patients followed up for more than 4 years (mean follow-up, 6.2 years +/- 12.1 months) were included after retrospective chart review. Several clinical factors including demographic, systemic, ocular risk factors, and 24-hour MOPP were explored for associations with decreasing VF. Kaplan-Meier analyses were performed to compare outcomes with reference to four risk factors (age, myopia, and elevated MAP and MOPP fluctuation) for VF deterioration. Hazard ratios (HRs) for the association between potential risk factors and glaucoma progression were obtained using Cox proportional hazards models. RESULTS Overall VF progression was detected in 29 (28.7%) eyes. There were significant differences between progressors and nonprogressors in nocturnal MAP and MOPP fluctuations (both P < 0.0001), 24-hour MAP, and MOPP fluctuations (both P < 0.0001), initial mean deviation (P = 0.0034), and pattern standard deviation (PSD) score (P < 0.0001). Both elevated 24-hour MAP and MOPP fluctuations were associated with greater VF progression probabilities based on Kaplan-Meier analyses. Among all risk factors investigated, the Cox proportional hazards model indicated that VF progression was significantly associated with 24-hour MOPP fluctuation and initial PSD score. CONCLUSIONS Clinical factors other than IOP were associated with VF progression in our series of medically treated NTG eyes. Twenty-four-hour MOPP fluctuation was the most consistent prognostic factor for glaucoma progression.

Relationship between Visual Field Sensitivity and Macular Ganglion Cell Complex Thickness as Measured by Spectral-Domain Optical Coherence Tomography

PURPOSE To evaluate the strength and pattern of the relationship between visual field (VF) mean sensitivity (MS), assessed by standard automated perimetry (SAP), and macular ganglion cell complex thickness (GCCT), measured with spectral-domain optical coherence tomography (SD-OCT). METHODS Ninety-seven glaucoma patients were enrolled. GCCT, determined by ganglion cell complex (GCC) scanning, and two peripapillary retinal nerve fiber layer thickness (pRNFLT) measurements, using the NHM4 (RNFL1) and RNFL 3.45 (RNFL2) modes, were recorded. MS was recorded on the decibel (dB) and 1/L scales. The relationship between function (MS) and structure (GCC, pRNFLT) was sought. RESULTS The association of MS (in decibels) with GCC global (r = 0.445) and sectoral (superior, r = 0.528; inferior, r = 0.370) thicknesses was not significantly different from that of MS to global (RNFL1, r = 0.505; RNFL2, r = 0.498) and sectoral (RNFL 1 superior, r = 0.559; inferior, r = 0.440; RNFL 2 superior, r = 0.535; inferior, r = 0.443) pRNFLT, on linear regression analysis. The relationship pattern was curvilinear on the dB scale against GCCT and RNFLT. Logarithmic regression of MS (using both the dB and 1/L scales) against GCCT and RNFLT was better than linear regression in describing the pattern of association. CONCLUSIONS GCCT, determined by SD-OCT, showed correlation to MS of a strength similar to that demonstrated between MS and pRNFLT.

Progression Detection Capability of Macular Thickness in Advanced Glaucomatous Eyes

PURPOSE To evaluate the progression rate of macular and circumpapillary retinal nerve fiber layer (RNFL) thickness in advanced glaucomatous eyes using spectral domain optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA). DESIGN Longitudinal, observational study. PARTICIPANTS A total of 98 eyes of 98 patients with advanced glaucoma (visual field [VF] mean deviation [MD] <-10 dB) with a mean follow-up time of 2.2 years. METHODS Three glaucoma experts independently reviewed optic disc and RNFL photographs and classified patients into 3 groups: progressed, stable, and undetermined (criterion 1). Patients in the undetermined group could not be evaluated because of advanced optic disc cupping. The eyes were also classified into 2 groups, progressed and stable, by serial VF data (criterion 2). MAIN OUTCOME MEASURES Progression rates as determined by linear regression analysis against patient age using serial macular and RNFL thickness parameters were compared among different groups. RESULTS By criterion 1, 25 eyes (25.5%) were classified as stable, 13 eyes (13.3%) were classified as progressed, and 60 eyes (61.2%) were classified as undetermined. By criterion 2, 86 eyes (87.8%) were classified as stable, and 12 eyes (12.2%) were classified as progressed. By criterion 1, the mean progression rate of average macular thickness was significantly higher in the progressed group than in the stable and undetermined groups (-4.74±4.40, -0.53±1.44, and -2.72±4.75 μm/year, respectively; P = 0.01). The undetermined group showed a higher progression rate than the stable group (P = 0.045). However, the progression rate of average RNFL thickness did not differ significantly among the 3 groups (-1.19±2.62, -0.33±1.29, and -1.21±2.75 μm/year, respectively; P = 0.34). By criterion 2, the mean progression rate of average RNFL thickness did not differ significantly between the stable and progressed groups (-0.90±2.42 and -2.08±2.85 μm/year; P = 0.459). However, the progression rate as revealed by average macular thickness was significantly different between the 2 groups (-2.22±4.33 and -5.12±2.40 μm/year, respectively; P = 0.039). CONCLUSIONS Exploration of changes over time in macular thickness may improve detection of progression in patients with advanced glaucoma.

Imaging of the retinal nerve fibre layer with spectral domain optical coherence tomography for glaucoma diagnosis

Optical coherence tomography (OCT) techniques have been applied to develop a new generation of the technology, called spectral domain (SD) or Fourier domain (FD) OCT. The commercially available SD-OCT technology offers benefits over the conventional time domain (TD) OCT such as a scanning speed up to 200 times faster and higher axial resolution (3 to 6 μm). Overall, SD-OCT offers improved performance in terms of reproducibility. SD-OCT has a level of discriminating capability, between healthy and perimetric glaucoma eyes similar to that obtained with TD-OCT. Furthermore, the capabilities and features of SD-OCT are rapidly evolving, mainly due to three-dimensional imaging and image rendering. More sophisticated approaches for macular and optic disc assessment are expected to be employed in clinical practice. Analysis software should be further refined for interpretation of SD-OCT images in order to enhance the sensitivity and specificity of glaucoma diagnostics. Most importantly for SD-OCT is determination of its ability to diagnostic structural glaucomatous progression. Considering the recent launch time of the commercially available SD-OCT and slow progressing characteristic of glaucoma, we must wait for longitudinal SD-OCT data, with a long enough follow-up, to become available.

Detection of glaucoma progression by assessment of segmented macular thickness data obtained using spectral domain optical coherence tomography.

PURPOSE We evaluated the clinical use of segmented macular layer thickness measurement in terms of glaucoma diagnosis and the ability to detect progression, and to compare such outcomes to those by circumpapillary retinal nerve fiber layer (cRNFLT) and total macular thickness (TMT) measurements. METHODS The study included 141 glaucomatous and 61 healthy eyes. All glaucomatous eyes were subjected to at least four spectral domain optical coherence tomography (SD-OCT) examinations (mean follow-up, 2.13 years). Segmented macular layers were the macular nerve fiber layer (NFL), ganglion cell and inner plexiform layer (GCA), and outer retinal layer (ORL; from outer plexiform layer to retinal pigment epithelium). Areas under receiver operating characteristic curves (AUCs) discriminating healthy from glaucomatous eyes were determined in baseline measurements. The sensitivity and specificity of these parameters in terms of glaucoma progression detection were determined, with reference to assessment of optic disc/retinal nerve fiber layer (RNFL) photographs/visual field (VF) deterioration as standard(s). RESULTS GCA afforded the best diagnostic performance among three macular layers. The AUC of the GCA thickness (GCAT) was less than that of cRNFLT (0.869 vs. 0.953, P = 0.018), but superior to that of TMT (0.790, P = 0.05). Of the eyes, 38 showed progression during follow-up by standard METHODS The sensitivities of TMT, GCAT, and cRNFLT values in terms of detection of progression were 14%, 8%, and 5%, respectively. CONCLUSIONS Although baseline cRNFL measurement was optimal in terms of glaucoma diagnosis, the GCAT and TMT showed similar levels of sensitivity in progression detection.

Characteristics of visual field progression in medically treated normal-tension glaucoma patients with unstable ocular perfusion pressure.

PURPOSE To investigate the characteristics of visual field (VF) progression in medically treated normal-tension glaucoma (NTG) patients (Koreans) with unstable ocular perfusion pressure (OPP). METHODS One hundred one eyes of 101 NTG patients followed up for more than 4 years (mean follow-up, 6.2 years ± 12.1 months) were included. Modified Anderson criteria (MC) and linear regression analysis (LA) of VF mean deviation (MD) within the central 10° and 10° to 24° area were assessed for determining VF progression in groups with lowest (LMF) and highest (HMF) 24-hour mean OPP [MOPP = 2/3;(mean arterial pressure - IOP)] fluctuation. Kaplan-Meier analyses were used to compare the elapsed time of confirmed VF progression in the two groups. Hazard ratios (HRs) for the association between clinical risk factors including 24-hour MOPP and central VF progression were obtained by using Cox proportional hazards models. RESULTS Three of 33 eyes in the LMF progressed, whereas 12 of 34 eyes in the HMF progressed within the central 10° according to the MC; the between-group difference was significant (P = 0.010). By LA within the central 10°, two eyes from the LMF and nine from the HMF groups showed progression (P = 0.025). The HMF showed a greater cumulative probability of central VF progression than the LMF, by both LA and MC (Kaplan-Meier analysis, P = 0.003, 0.015, log-rank test). In multivariate analysis, only 24-hour MOPP fluctuation was significantly associated with central VF progression (P = 0.014). CONCLUSIONS The 24-hour MOPP fluctuation was the most consistent prognostic factor among various IOP, blood pressure, and clinical factors for central VF glaucomatous progression in our series of NTG eyes.