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1.  Comparison of Clinical Characteristics and Progression Rates of Bilaterally and Unilaterally Progressing Glaucoma 
To compare the clinical characteristics of unilaterally progressing glaucoma (UPG) and simultaneously bilaterally progressing glaucoma (BPG) in medically treated cases.
Primary open angle glaucoma patients were classified as having UPG or BPG according to an assessment of optic disc and retinal nerve fiber layer photographs and visual field analysis. Risk factors including the presence of systemic diseases (hypertension, diabetes, cerebrovascular accident, migraine, and dyslipidema) were compared between the UPG and BPG groups. Baseline characteristics and pre- and post-treatment intraocular pressure (IOP) were compared between the progressing eye (PE) and the non-progressing eye (NPE) within the same patient in the UPG group and between the faster progressing eye and the slower progressing eye in the BPG group.
Among 343 patients (average follow-up period of 4.2 years), 43 were categorized into the UPG group and 31 into the BPG group. The prevalence of all analyzed systemic diseases did not differ between the two groups. PEs in the UPG group had more severe pathology in terms of baseline visual field parameters than NPEs (mean deviation -6.9 ± 5.7 vs. -2.9 ± 3.9 dB, respectively; p < 0.001). However, baseline IOP, mean follow-up IOP, and other clinical characteristics were not significantly different between the PE and the NPE in the UPG group. The progression rate was significantly higher in the faster progressing eye in patients with BPG than in the PE for patients with UPG (-3.43 ± 3.27 vs. -0.70 ± 1.26 dB/yr, respectively; p = 0.014).
There were no significant differences in the prevalence of systemic diseases between the UPG and BPG groups. Simultaneously bilaterally progressing patients showed much faster progression rates than those with a unilaterally progressing eye.
PMCID: PMC4309867  PMID: 25646059
Bilateral; Disease progression; Glaucoma; Unilateral; Visual fields
2.  Augmentation of Filtering Blebs with Viscoelastics in Trabeculectomy 
To evaluate the clinical outcome of viscoelastics (VE, sodium hyaluronate)-augmented trabeculectomy (VAT, 66 eyes) and conventional trabeculectomy (CT, 57 eyes) for glaucomatous eyes.
In the VAT group, half of the anterior chamber space was filled with VE via the paracentesis site at the end of CT and a balanced salt solution was injected into the anterior chamber. This procedure induced migration of VE from the anterior chamber into the bleb space; thus the bleb was elevated with underlying VE. Follow-up examinations were performed until 1 year after surgery. Success was defined as the attainment of an intraocular pressure (IOP) greater than 5 mmHg and less than 22 mmHg. If IOP was in the range of success without antiglaucoma medication, it was regarded as a complete success.
The mean postoperative IOP was significantly lower in the VAT group at postoperative 1 day, 1 week, and 1 month. The complete success rate was significantly higher in the VAT group (89%) than in the CT group (75%), though the qualified success rate was not different between the two groups. The number of IOP-lowering medications at postoperative 1 year was significantly higher in the CT group (1.30 ± 1.08 vs. 0.73 ± 0.98, p = 0.003). Among postoperative procedures, laser suture lysis was required less frequently in the VAT group (p < 0.001).
Placing VE within the bleb at the end of surgery may result in better IOP control and less need for IOP-lowering medication without any additional materials, cost, or time.
PMCID: PMC4179116  PMID: 25276081
Anti-fibrotic agent; Glaucoma; Hyaluronic acid; Trabeculectomy; Viscoelastics
3.  Assessment of Macular Ganglion Cell Loss Patterns in Neurologic Lesions That Mimic Glaucoma 
To evaluate patterns of macular retinal ganglion cell (RGC) loss measured by spectral domain optical coherence tomography in patients with neurologic lesions mimicking glaucoma.
We evaluated four patients with neurological lesions who showed characteristic patterns of RGC loss, as determined by ganglion cell thickness (GCT) mapping.
Case 1 was a 30-year-old man who had been treated with glaucoma medication. A left homonymous vertical pattern of RGC loss was observed in his GCT map and a past brain magnetic resonance imaging (MRI) revealed a hemorrhagic lesion around the right optic radiation. Case 2 was a 72-year-old man with a pituitary adenoma who had a binasal vertical pattern of RGC loss that corresponded with bitemporal hemianopsia. Case 3 was a 77-year-old man treated for suspected glaucoma. His GCT map showed a right inferior quadratic pattern of loss, indicating a right superior homonymous quadranopsia in his visual field (VF). His brain MRI revealed a left posterior cerebral artery territory infarct. Case 4 was a 38-year-old woman with an unreliable VF who was referred for suspected glaucoma. Her GCT map revealed a left homonymous vertical pattern of RGC loss, which may have been related to a previous head trauma.
Evaluation of the patterns of macular RGC loss may be helpful in the differential diagnosis of RGC-related diseases, including glaucoma and neurologic lesions. When a patient's VF is unavailable, this method may be an effective tool for diagnosing and monitoring transneuronal retrograde degeneration-related structural changes.
PMCID: PMC4120352  PMID: 25120340
Ganglion cell thickness map; Neurologic region; Optical coherence tomography; Visual fields
4.  Relationship between the Lamina Cribrosa, Outer Retina, and Choroidal Thickness as Assessed Using Spectral Domain Optical Coherence Tomography 
To evaluate the characteristics and relationship between peripapillary choroidal thickness (pCT), lamina cribrosa thickness (LCT), and peripapillary outer retinal layer thickness (pORT) as determined using spectral domain optical coherence tomography (SD-OCT) enhanced depth imaging (EDI).
In total, 255 participants were included (87 healthy subjects, 87 glaucoma suspects (GS), and 81 glaucoma cases). The pORT, defined as the thickness between the posterior outer plexiform layer and the retinal pigment epithelium (RPE) interface, and the pCT, between the outer margin of the RPE and the choroidal-scleral interface, were manually measured using EDI scanning of the circumpapillary retinal nerve fiber layer (RNFL). LCT was determined by EDI scanning of the optic nerve head (ONH). Baseline characteristics, including axial length (AXL) and the SD-OCT measurements of the participants, were compared among the three groups. The correlation between putative factors and pCT was determined using univariate and multivariate linear regression analyses.
In all three groups, both pORT and pCT were thinnest in the inferior area among the four quadrants. In the healthy group, the mean peripapillary RNFL, pORT, and LCT were significantly greater in comparison with those of the GS and glaucoma groups (p < 0.001, p < 0.038, and p < 0.001, respectively). The pCT demonstrated no significant differences among the three groups (p = 0.083). Only age and AXL were associated with pCT by multivariate analysis.
The pCT is substantially thinner in the inferior area of the ONH. In addition, the pCT demonstrates the strongest correlation with age and AXL, but was not associated with glaucoma or LCT.
PMCID: PMC4038729  PMID: 24882957
Choroidal thickness; Glaucoma; Lamina cribrosa thickness; Optical coherence tomography; Outer retinal thickness
5.  Comparison between Glaucomatous and Non-glaucomatous Eyes with Unilateral Retinal Vein Occlusion in the Fellow Eye 
To evaluate and compare the clinical and angiographic characteristics of retinal vein occlusion (RVO) in glaucomatous and non-glaucomatous eyes with unilateral RVO in the fellow eye.
Twenty-one glaucomatous eyes (GL group) and 25 age-matched non-glaucomatous eyes (non-GL group) with unilateral RVO in the fellow eye were included in this study. Fluorescein angiographic images were assessed in both groups by 3 retina specialists in order to determine the RVO occlusion site. The occlusion site was divided into 2 types: arteriovenous (AV)-crossing and non-AV-crossing (optic cup or optic nerve sited). The clinical characteristics and prevalence of AV-crossing and non-AV-crossing RVO were compared between the 2 groups.
The mean baseline intraocular pressures of the RVO eye and the fellow eye did not differ between the 2 groups (RVO eye: 14.3 ± 2.5 mmHg [non-GL group], 15.5 ± 3.9 mmHg [GL group], p = 0.217; fellow eye: 14.4 ± 2.5 mmHg [non-GL group], 15.7 ± 3.7 mmHg [GL group], p = 0.148). The prevalence of systemic disease did not differ between the 2 groups (e.g., diabetes mellitus and hypertension, p = 0.802 and 0.873, respectively). AV-crossing RVO was significantly more frequent in the non-GL group (19 eyes; 76%) than in the GL group (4 eyes, 19%, p < 0.001).
Non-AV-crossing RVO, i.e., optic cup- or optic nerve-sited RVO, is more frequently associated with glaucomatous changes in the fellow eye. Therefore, this type of RVO should be monitored more carefully for indications of glaucoma in the fellow eye.
PMCID: PMC3849308  PMID: 24311930
Glaucoma; Retinal vein occlusion
6.  Clinical Characteristics of Glaucomatous Subjects Treated with Refractive Corneal Ablation Surgery 
To evaluate the clinical characteristics of newly diagnosed glaucomatous subjects who had a history of refractive corneal ablation surgery (RCAS).
Sixty-eight glaucomatous subjects who had a history of RCAS and 68 age- and visual field (VF) mean deviation-matched glaucomatous subjects with no history of RCAS were included. Intraocular pressure (IOP), central corneal thickness (CCT), VF, and retinal nerve fiber layer thickness determined by optical coherence tomography were assessed. Parameters were compared between patients with and without a history of RCAS. Between-eye comparisons in the same participant (more advanced vs. less-advanced eye, in terms of glaucoma severity) were performed in the RCAS group.
With similar levels of glaucoma severity, those with a history of RCAS showed significantly lower baseline IOP and a thinner CCT than the eyes of individuals without a RCAS history (13.6 vs. 18.7 mmHg, 490.5 vs. 551.7 µm, all p < 0.001). However, the extent of IOP reduction after anti-glaucoma medication did not significantly differ between the two groups (17% vs. 24.3%, p = 0.144). In the between-eye comparisons of individual participants in the RCAS group, the more advanced eyes were more myopic than the less-advanced eyes (-1.84 vs. -0.58 diopter, p = 0.003).
Eyes with a history of RCAS showed a similar level of IOP reduction as eyes without such a history after anti-glaucoma medication. Our finding that the more advanced eyes were more myopic than the less-advanced eyes in the same participant may suggest an association between glaucoma severity and myopic regression.
PMCID: PMC3596612  PMID: 23542822
Glaucoma; Intraocular pressure; Myopia; Myopic regression; Refractive surgical procedures
7.  Increased Intraocular Pressure after Extensive Conjunctival Removal: A Case Report 
A 50-year-old woman, who had undergone extensive removal of conjunctiva on the right eye for cosmetic purposes at a local clinic 8 months prior to presentation, was referred for uncontrolled intraocular pressure (IOP) elevation (up to 38 mmHg) despite maximal medical treatment. The superior and inferior conjunctival and episcleral vessels were severely engorged and the nasal and temporal bulbar conjunctival areas were covered with an avascular epithelium. Gonioscopic examination revealed an open angle with Schlemm's canal filled with blood to 360 degrees in the right eye. Brain and orbital magnetic resonance imaging and angiography results were normal. With the maximum tolerable anti-glaucoma medications, the IOP gradually decreased to 25 mmHg over 4 months of treatment. Extensive removal of conjunctiva and Tenon's capsule, leaving bare sclera, may lead to an elevation of the episcleral venous pressure because intrascleral and episcleral veins may no longer drain properly due to a lack of connection to Tenon's capsule and the conjunctival vasculature. This rare case suggests one possible mechanism of secondary glaucoma following ocular surgery.
PMCID: PMC3596620  PMID: 23543764
Episcleral venous pressure; Glaucoma; Intraocular pressure
8.  Clinical Outcomes after Combined Ahmed Glaucoma Valve Implantation and Penetrating Keratoplasty or Pars Plana Vitrectomy 
To evaluate whether a combination of penetrating keratoplasty (PKP) or pars plana vitrectomy (PPV) and Ahmed glaucoma valve (AGV) implantation affords a level of success similar to that of AGV implantation alone.
Eighteen eyes underwent simultaneous PPV and AGV, 14 eyes with PKP and AGV and 30 eyes with AGV implantation alone were evaluated. Success was defined as attainment of an intraocular pressure (IOP) >5 and <22 mmHg, with or without use of anti-glaucoma medication. Kaplan-Meier survival analysis was performed to compare cumulative survival between the combined surgery groups and the AGV implantation-alone group. Cox proportional hazard regression analysis was conducted to identify factors predictive of success in each of the three groups.
Mean (±standard deviation) preoperative IOP was 30.2 ± 10.2 mmHg in the PKP + AGV, 35.2 ± 9.8 mmHg in the PPV + AGV, and 36.2 ± 10.1 mmHg in the AGV implantation-alone group. The cumulative success rate at 18 months was 66.9%, 73.2%, and 70.8% in the three groups, respectively. Neither combined surgery group differed significantly in terms of cumulative success rate compared with the AGV implantation-alone group (p = 0.556, p = 0.487, respectively). The mean number of preoperative anti-glaucoma medications prescribed was significantly associated with success in the PKP + AGV implantation group (hazard ratio, 2.942; p = 0.024).
Either PKP or PPV performed in conjunction with AGV implantation afforded similar success rates compared to patients treated with AGV implantation alone. Therefore, in patients with refractory glaucoma who have underlying corneal or retinal pathology requiring treatment with PKP or PPV, AGV implantation can be performed simultaneously.
PMCID: PMC3506817  PMID: 23204798
Ahmed valve; Glaucoma; Intraocular pressure; Pars plana vitrectomy; Penetrating keratoplasty
9.  Asymmetry in Hemifield Macular Thickness as an Early Indicator of Glaucomatous Change 
Measurement of asymmetry in macular hemifield thickness showed better performance than average cRNFL thickness measurements in terms of diagnostic sensitivity in eyes with early stage glaucoma. This strategy may serve as a useful alternative diagnostic aid in the early detection of glaucoma.
To investigate whether asymmetry in hemifield macular thickness can serve as an early indicator of glaucomatous structural damage using spectral domain optical coherence tomography.
Five zones in the macular thickness map were defined. Each zone included reciprocal areas in the superior and inferior hemifield. Differences in average retinal thickness (DRT) between corresponding regional pairs were measured in each of the five zones in 50 healthy eyes. An abnormality was defined as the DRT value lying outside the 95% confidence intervals. An eye was considered to yield an “abnormal macular hemifield test” (MHT) if abnormality was evident in any zone. The sensitivity and specificity for glaucoma detection of MHT and average circumpapillary retinal nerve fiber layer (cRNFL) classification were determined.
A total of 114 healthy, 103 glaucoma-suspect, and 74 glaucomatous eyes were included. Overall, 5.8%, 36.9%, 88.4%, and 77.4% of the eyes of the healthy, glaucoma-suspect (GS), early glaucoma (EG), and advanced glaucoma (AG) groups yielded abnormal MHT results, respectively. In EG eyes, the sensitivity of an abnormal MHT result was significantly greater than that of abnormal average cRNFL classification (P = 0.008). In the GS and AG groups, the sensitivity did not significantly differ between an abnormal MHT result and an average cRNFL classification (P = 0.880, 0.180). Compared with sectoral cRNFL thickness measurements, MHT showed a similar level of diagnostic performance. Specificity was not different between an abnormal MHT result and an average cRNFL classification (P = 0.687).
Evaluation of asymmetry in hemifield macular thickness may serve as an assessment tool in the early diagnosis of glaucoma.
PMCID: PMC3979493  PMID: 22247461
10.  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.
PMCID: PMC3421150  PMID: 21030413
11.  Factors Associated with the Signal Strengths Obtained by Spectral Domain Optical Coherence Tomography 
The aim of this study was to investigate factors associated with the signal strengths (SS, image quality scores) of optic disc and macular images obtained using Cirrus spectral domain optical coherence tomography (OCT).
Ninety-two glaucomatous eyes were imaged using the Cirrus OCT macular and optic disc cube modes after pupil dilation. The influences of patient age, spherical equivalent, cataract presence, and cataract and glaucoma severity (visual field mean deviation), on the SS of images obtained using the two cube modes were compared between patients whose images showed high SS (SS ≥7) and low SS (SS <7).
The signal strength was significantly higher in images obtained using the macular cube compared to the optic disc cube mode (7.8 ± 1.3 vs. 6.9 ± 1.1, respectively; p = 0.001). Age and visual acuity of patients differed significantly between the high- and low-SS groups when data acquired using the optic disc (p = 0.027 and 0.012, respectively) and macular cube modes (p = 0.046 and 0.014, respectively) were analyzed. When the optic disc cube mode was employed, the extent of cataracts was significantly related to SS, whereas when the macular cube mode was used, none of the factors analyzed was significantly associated with SS.
Age, visual acuity, and the extent of cataracts were significantly associated with images of higher SS when the Cirrus OCT optic disc cube mode was employed.
PMCID: PMC3364427  PMID: 22670072
Glaucoma; Macular cube mode; Optic disc cube mode; Optical coherence tomography; Signal strength
12.  Glaucoma Progression Detection by Retinal Nerve Fiber Layer Measurement Using Scanning Laser Polarimetry: Event and Trend Analysis 
To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma.
Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA, linear regression analysis of the visual field index). SLP progression was defined as a reduction of RNFL exceeding the predetermined repeatability coefficient in three consecutive exams, as compared to the baseline measure (EA). The slope of RNFL thickness change over time was determined by linear regression analysis (TA).
Twenty-two eyes (14.5%) progressed according to the VF EA, 16 (10.5%) by VF TA, 37 (24.3%) by SLP EA and 19 (12.5%) by SLP TA. Agreement between VF and SLP progression was poor in both EA and TA (VF EA vs. SLP EA, k = 0.110; VF TA vs. SLP TA, k = 0.129). The mean (±standard deviation) progression rate of RNFL thickness as measured by SLP TA did not significantly differ between VF EA progressors and non-progressors (-0.224 ± 0.148 µm/yr vs. -0.218 ± 0.151 µm/yr, p = 0.874). SLP TA and EA showed similar levels of sensitivity when VF progression was considered as the reference standard.
RNFL thickness as measurement by SLP was shown to be capable of detecting glaucoma progression. Both EA and TA of SLP showed poor agreement with VF outcomes in detecting glaucoma progression.
PMCID: PMC3364428  PMID: 22670073
Event analysis; Glaucoma; Progression; Scanning laser polarimetry; Trend analysis
13.  Characterization of Peripapillary Atrophy Using Spectral Domain Optical Coherence Tomography 
To characterize the features of peripapillary atrophy (PPA), as imaged by spectral-domain optical coherence tomography (SD-OCT).
SD-OCT imaging of the optic disc was performed on healthy eyes, eyes suspected of having glaucoma, and eyes diagnosed with glaucoma. From the peripheral β-zone, the retinal nerve fiber layer (RNFL), the junction of the inner and outer segments (IS/OS) of the photoreceptor layer, and the Bruch's membrane/retinal pigment epithelium complex layer (BRL) were visualized.
Nineteen consecutive eyes of 10 subjects were imaged. The RNFL was observed in the PPA β-zone of all eyes, and no eye showed an IS/OS complex in the β-zone. The BRL was absent in the β-zone of two eyes. The BRL was incomplete or showed posterior bowing in the β-zone of five eyes.
The common findings in the PPA β-zone were that the RNFL was present, but the photoreceptor layer was absent. Presence of the BRL was variable in the β-zone areas.
PMCID: PMC2992563  PMID: 21165234
Bruch's membrane; Glaucoma; Peripapillary atrophy; Retinal nerve fiber layer; Spectral-domain optical coherence tomography
14.  Macula assessment using optical coherence tomography for glaucoma diagnosis 
The British journal of ophthalmology  2012;96(12):1452-1455.
Optical coherence tomography (OCT) is an interferometry-based imaging modality that generates high-resolution cross-sectional images of the retina. Circumpapillary retinal nerve fiber layer (cpRNFL) and optic nerve head assessments are the mainstay of glaucomatous structural measurements in OCT. However, because these measurements are not always available or precise, it would be useful to have another reliable indicator. The macula has been suggested as an alternative scanning location for glaucoma diagnosis. Using time-domain (TD-) OCT, macular measurements have shown to provide good glaucoma diagnostic capabilities. With the adoption of spectral-domain OCT, which allows a higher image resolution than TD-OCT, segmentation of inner macular layers becomes possible. These layers are specifically prone to glaucomatous damage and thickness measurements show a comparable performance to that of glaucomatous cpRNFL measurements. The role of macular measurements for detection of glaucoma progression is still under investigation. More sophisticated measurement and analysis tools that can amplify the advantages of macular measurements are expected. For example, improvement of image quality would allow better visualization, development of various scanning modes would optimize macular measurements, and further refining of the analytical algorithm would provide more accurate segmentation. With these achievements, macular measurement can be an important surrogate for glaucomatous structural assessment.
PMCID: PMC3718015  PMID: 23018425
15.  Retinal Nerve Fiber Layer Measurement Variability with Spectral Domain Optical Coherence Tomography 
To evaluate the effect of the scanning laser ophthalmoscope (SLO) guided re-test mode on short- and long-term measurement variability of peripapillary retinal nerve fiber layer (RNFL) thickness obtained by spectral domain-SLO optical coherence tomography (SD-SLO/OCT).
Seventy five healthy eyes were scanned 3 times per day (intra-session variability) by both the SLO guided re-test mode and the independent mode of SD-SLO/OCT. Subjects were scanned 3 times by both modes at visits within a 2-week interval (inter-session variability). For testing longitudinal variability, 3 separate exams were performed over 6 months by both modes. The coefficient of variation (CV), reproducibility coefficient (RC) and intraclass correlation coefficient of RNFL thickness were compared between the two modes.
The intra-session RC and CV ranged from 5.4 to 12.9 microns and 1.76% to 5.72% when measured by independent mode and 5.4 to 12.5 microns and 1.75% to 5.58% by re-test mode, respectively. The inter-session RC and CV ranged from 5.8 to 13.3 microns and 1.89% to 5.78% by independent mode and 5.8 to 12.7 microns and 1.90% to 5.54% by re-test mode, respectively. Intra-session and inter-session variability measurements were not significantly different between the two modes. The longitudinal RC and CV ranged from 8.5 to 19.2 microns and 2.79% to 7.08% by independent mode and 7.5 to 14.4 microns and 2.33% to 6.22% by re-test mode, respectively. Longitudinal measurement variability was significantly lower when measured by the re-test mode compared to the independent mode (average, p = 0.011).
The SLO guided re-test mode for RNFL thickness measurement in SD-SLO/OCT employing a tracking system improved long-term reproducibility by reducing variability induced by inconsistent scan circle placement.
PMCID: PMC3268166  PMID: 22323883
Optical coherence tomography; Reproducibility; Retinal nerve fiber layer; Tracking system
16.  Effects of Age on Optical Coherence Tomography Measurements of Healthy Retinal Nerve Fiber Layer, Macula and Optic Nerve Head 
Ophthalmology  2009;116(6):1119-1124.
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).
Retrospective, cross-sectional observational study.
226 eyes from 124 healthy subjects were included.
Healthy subjects were scanned using the Fast RNFL, Fast Macula, and Fast ONH scan patterns on a Stratus OCT. 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 inter-parameter comparison.
Main Outcome Measures
Slope of each OCT parameter across age.
All global and sectoral RNFL thickness parameters statistically significantly decreased with increasing age, except for the temporal quadrant and clock hours 8-10, 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 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 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.
Global and regional changes due to the effects of age on RNFL, macula and ONH OCT measurements should be considered when assessing eyes over time.
PMCID: PMC2747246  PMID: 19376593
17.  Assessing the Relationship between Central Corneal Thickness and Retinal Nerve Fiber Layer Thickness in Healthy Subjects 
American journal of ophthalmology  2008;146(4):561-566.
To determine the relationship between central corneal thickness (CCT) and retinal nerve fiber layer (RNFL) thickness obtained by scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Dublin, CA) confocal scanning laser ophthalmoscopy (HRT II; Heidelberg Engineering, Heidelberg, Germany) and optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Dublin, CA).
Multi-center clinical trial, retrospective cross-sectional study.
One hundred and nine healthy subjects from the Advanced Imaging in Glaucoma Study were enrolled in this study. All subjects had a standard clinical examination, including visual field and good quality scans from all three imaging devices. Central corneal thickness was measured using an ultrasonic pachymeter. A linear mixed effects model was used to assess the relationship between RNFL thickness and CCT, accounting for clustering of eyes within subjects, testing site, ethnicity, family history of glaucoma, axial length intraocular pressure and visual field global indices.
For OCT and GDx, there was a slight non-statistically significant positive relationship between CCT and RNFL thickness. For HRT, there was a slight non-statistically significant negative relationship between CCT and RNFL thickness. Relationships for each device were found to differ between sites.
CCT was not statistically significantly related to RNFL thickness in healthy eyes.
PMCID: PMC2605942  PMID: 18657796
18.  Comparison of Optic Disc Margin Identified by Color Disc Photography and High-Speed Ultrahigh-Resolution Optical Coherence Tomography 
Archives of ophthalmology  2008;126(1):58-64.
To determine the correspondence between optic disc margins evaluated using disc photography (DP) and optical coherence tomography (OCT).
From May 1, 2005, through November 10, 2005, 17 healthy volunteers (17 eyes) had raster scans (180 frames, 501 samplings per frame) centered on the optic disc taken with stereo-optic DP and high-speed ultrahigh-resolution OCT (hsUHR-OCT). Two image outputs were derived from the hsUHR-OCT data set: an en face hsUHR-OCT fundus image and a set of 180 frames of cross-sectional images. Three ophthalmologists independently and in a masked, randomized fashion marked the disc margin on the DP, hsUHR-OCT fundus, and cross-sectional images using custom software. Disc size (area and horizontal and vertical diameters) and location of the geometric disc center were compared among the 3 types of images.
The hsUHR-OCT fundus image definition showed a significantly smaller disc size than the DP definition (P<.001, mixed-effects analysis). The hsUHR-OCT cross-sectional image definition showed a significantly larger disc size than the DP definition (P<.001). The geometric disc center location was similar among the 3 types of images except for the y-coordinate, which was significantly smaller in the hsUHR-OCT fundus images than in the DP images.
The optic disc margin as defined by hsUHR-OCT was significantly different than the margin defined by DP.
PMCID: PMC2743170  PMID: 18195219
19.  Structural and Functional Relationships in Glaucoma Using Standard Automated Perimetry and the Humphrey Matrix 
To evaluate and compare correlations between structural and functional loss in glaucoma as assessed by optical coherence tomography (OCT), scanning laser polarimetry (GDx VCC, as this was the model used in this study), standard automated perimetry (SAP), and the Humphrey Matrix (Matrix).
Ninety glaucomatous eyes identified with SAP and 112 eyes diagnosed using Matrix were independently classified into six subgroups, either S1/M1 (MD>-6dB), S2/M2 (-12
In the SAP subgroups, RNFL thickness values obtained by OCT in the nasal and temporal quadrants and the inferior averages of GDx VCC did not differ between the S1 and S2 subgroups (p=0.137, 0.738 and 0.149, respectively). In the Matrix subgroups, no measurement parameters differed between the M1 and M2 groups except for the overall mean and average inferior RNFL thickness given by OCT and the NFI values of GDx VCC (p=0.013, 0.016 and 0.029, respectively). When abnormal classifications were compared, all measurement parameters, without exception, were significantly different in both the SAP and the Matrix subgroups.
SAP subgroups showed a good correlation of structural and functional defects when assessed using OCT and GDx VCC. These correlations were weaker in the Matrix subgroups, especially in the early stages of glaucoma.
PMCID: PMC2739974  PMID: 19794944
Correlation; GDx VCC; Matrix; SAP; Stratus OCT
To compare high-sensitivity C-reactive protein (hsCRP) levels and lipid profiles between Korean normal tension glaucoma (NTG) patients and healthy controls.
This cross-sectional study included 38 Korean patients with NTG and 38 age- and sex-matched healthy control subjects. We excluded the patients with cardiovascular risk factors and other systemic diseases that might affect CRP levels and lipid profiles. Each patient underwent a Humphrey visual field examination and blood sampling for hsCRP and lipid profile analyses. Subsequently, the NTG patients were classified into two groups based on their untreated intraocular pressure (IOP) level: low NTG (LNTG) with IOP≤13 mmHg (13 subjects) and high NTG (HNTG) with relatively high IOP (>13 and ≤21 mmHg, 25 subjects). The hsCRP levels and lipid profiles were compared between NTG patients and healthy controls, and between LNTG, HNTG, and healthy controls.
There were no significant differences in hsCRP and lipid profiles between either the NTG patients and healthy controls, or between the LNTG, HNTG, and controls (p>0.05) after exclusion of Korean patients with cardiovascular risk factors. There was no significant association between hsCRP and visual field indices (p>0.05).
High-sensitivity C-reactive protein-related vascular inflammatory conditions may not be directly associated with the development of NTG, regardless of the untreated IOP level.
PMCID: PMC2739962  PMID: 19794947
Atherosclerosis; C-reactive protein; Lipid profiles; Normal tension glaucoma
To compare the intraocular pressures (IOPs) measured by dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT), and to investigate the association of IOPs on eyes of varying central corneal thickness (CCT).
In this prospective study, 451 eyes of 233 subjects were enrolled. IOPs were measured by GAT and DCT. CCT was measured three times and the average was calculated. Each eye was classified into one of three groups according to CCT: low CCT (group A, CCT<520 µm, n=146); normal CCT (group B, 520 µm ≤ CT ≤ 550 µm, n=163); and high CCT (group C, CCT>550 µm, n=142). In each group, we investigated the association of CCT with IOP measurement by GAT and DCT.
The IOPs measured by GAT and DCT were significantly associated for all eyes (R=0.853, p<0.001, Pearson correlation). CCT was related with both IOP measurement by GAT and DCT with statistical significance (mixed effect model, p<0.001). However, subgroup analysis showed that CCT affected IOP measured by GAT for groups B and C, whereas it affected IOP measured by DCT only for group C.
IOP measured by DCT was not affected by CCT in eyes with low to normal CCT, whereas this measurement was affected in eyes of high CCT range. CCT may have less effect on IOP measurements using DCT than those obtained by GAT, within a specified range of CCT.
PMCID: PMC2655749  PMID: 19337476
Central corneal thickness; Dynamic contour tonometry; Goldmann applanation tonometry
To investigate the relationship between blood pressure (BP) parameters in the habitual position and glaucomatous damage at initial presentation in patients with untreated normal tension glaucoma (NTG).
Fifty-four eyes from 54 subjects diagnosed with NTG were consecutively enrolled. BP was measured with an automated ambulatory monitoring device in the habitual position during 24-hour in-hospitalization. Patients were classified into three groups: non-dippers, dippers, and over-dippers. corresponded to the degree of reduction in their nocturnal mean arterial pressure (MAP) compared with their diurnal MAP. Regression models were used to evaluate potential risk factors, including: age, pre-admission office intraocular pressure (IOP), central corneal thickness (CCT), and BP parameters. Functional outcome variables for glaucomatous damage included mean deviation (MD) and pattern standard deviation (PSD) on a Humphrey field analyzer (HFA). Anatomic outcome variables were TSNIT score (temporal, superior, nasal, inferior, and temporal) average, superior average, inferior average, and nerve fiber indicator (NFI) score on scanning laser polarimetry with variable corneal compensation (SLP-VCC; GDx-VCC).
Marked systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP fluctuation were noted in the over-dipper group (p<0.05). A linear regression analysis model revealed that nocturnal trough DBP and MAP, average nocturnal SBP, and MAP were all significantly associated with a decreased average TSNIT score and an increased NFI score.
Nocturnal BP reduction estimated in the habitual position was associated with structural damage in eyes with NTG. This finding may suggest systemic vascular etiology of NTG development associated with nocturnal BP reduction.
PMCID: PMC2655738  PMID: 19337477
Blood pressure; Habitual position; Normal tension glaucoma; 24-hour

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