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1.  Bimatoprost 0.01% in treatment-naïve patients with open-angle glaucoma or ocular hypertension: an observational study in the Korean clinical setting 
BMC Ophthalmology  2014;14:160.
This study evaluates the efficacy and tolerability (ie, occurrence and severity of hyperemia) of bimatoprost 0.01% in treatment-naïve patients with open-angle glaucoma (OAG) or ocular hypertension in the Korean clinical setting.
In this multicenter, open-label, observational study, treatment-naïve patients with OAG, including patients with normal-tension glaucoma (NTG, defined as IOP ≤21 mm Hg), or ocular hypertension received bimatoprost 0.01% once daily. Hyperemia was assessed at baseline and weeks 6 and 12, graded by a masked evaluator using a photonumeric scale (0, +0.5, +1, +2, +3), and grouped as (0 to +1) and (+2 to +3). Shifts between groupings were reported as no change, improved ([+2 to +3] to [0 to +1]), or worsened ([0 to +1] to [+2 to +3]). Other adverse events were monitored. Mean IOP changes from baseline at weeks 6 and 12 were reported. Supplemental analyses were conducted for IOPs >21 versus ≤21 mm Hg.
Of 295 treatment-naïve patients included in the intent-to-treat/safety population, 73 (24.7%) had baseline IOP >21 mm Hg (mean, 25.7 ± 5.0 mm Hg) and 222 (75.3%) had baseline IOP ≤21 mm Hg (mean, 16.3 ± 3.0 mm Hg); 96.3% had hyperemia graded none (36.3%) to mild (17.3%). At week 12, hyperemia was graded none to mild in 83.7% (n = 220). Worsening occurred in 12.3% of patients by week 6 and 12.7% by week 12. Small improvements occurred in 0.8% and 0.5% of patients at weeks 6 and 12, respectively. Hyperemia scores were generally low and the majority of patients had no change in severity during the study. Mean IOP at weeks 6 and 12 was reduced to 16.4 ± 4.0 mm Hg (-34.5%; P < 0.0001) and 16.7 ± 3.9 mm Hg (-32.0%; P < 0.001) in the baseline-IOP >21 mm Hg group versus 13.3 ± 2.6 mm Hg (-17.8%; P < 0.001) and 13.7 ± 2.8 mm Hg (-15.9%; P < 0.001) in the baseline-IOP ≤21 mm Hg group, respectively.
In treatment-naïve patients, bimatoprost 0.01% induced low shifts in worsening of hyperemia and significant reductions in IOP, regardless of baseline IOP.
Trial registration
Clinical trial registration number: NCT01594970
PMCID: PMC4289567  PMID: 25519810
Bimatoprost; Glaucoma; Hyperemia; Intraocular pressure; Prostaglandin analog; Prostamide
2.  Flammer syndrome 
The EPMA Journal  2014;5(1):11.
The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.
PMCID: PMC4113774  PMID: 25075228
Flammer syndrome; Primary vascular dysregulation; Vasospasm; Cold extremities; Systemic hypotension; Normal tension glaucoma; Tinnitus; Optic disc hemorrhages; Retinal vein occlusion; Predictive preventive personalized medicine
3.  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
4.  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
5.  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
6.  Mutation spectrum of CYP1B1 and MYOC genes in Korean patients with primary congenital glaucoma 
Molecular Vision  2011;17:2093-2101.
To elucidate the incidence of cytochrome P450 1B1 (CYP1B1) and myocillin (MYOC) mutations in Korean patients with primary congenital glaucoma (PCG).
Genomic DNA was collected from peripheral blood of 85 unrelated Korean patients who were diagnosed as having PCG by standard ophthalmological examinations and screened for mutations in the CYP1B1 and MYOC genes by using bi-directional sequencing.
Among 85 patients with PCG, 22 patients (22/85; 25.9%) had either one (n=11) or two (n=11) mutant alleles of the CYP1B1 gene. Among 11 different CYP1B1 mutations identified, a frameshift mutation (c.970_971dupAT; p.T325SfsX104) was the most frequent mutant allele (6/33; 18.2%) while p.G329S and p.V419Gfs11X were novel. In the MYOC gene, two variants of unknown significance (p.L228S and p.E240G) were identified in two PCG patients (2/85; 2.4%), respectively. No patient had mutations in both genes.
Although CYP1B1 mutations are major causes of PCG in Korea, ~70% of PCG patients have neither CYP1B1 nor MYOC mutations suggesting a high degree of genetic heterogeneity. Furthermore, the fact that 11 out of 22 patients had only one mutant allele in the CYP1B1 gene necessitates further investigation for other genetic backgrounds underlying PCG.
PMCID: PMC3156779  PMID: 21850185
7.  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
8.  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
To evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes.
Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques.
In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05).
The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP.
PMCID: PMC2629948  PMID: 18323701
GDx-ECC; GDx-VCC; Structure-function relationship; Scanning laser polarimetry
To compare quantitative polarimetric measurements in eyes with NTG and HTG using GDx-VCC. Both groups were matched by age and glaucoma stage based on the Humphrey visual field test.
We retrospectively reviewed the records of 146 patients who underwent Humphrey field analysis (HFA) and GDx-VCC. We compared outcomes of retinal nerve fiber layer (RNFL) parameters among the three groups by ANOVA and between each pair of groups using the Tukey-Kramer Post-Hoc test. We also evaluated the sensitivity and specificity of GDx-VCC in detecting glaucoma in each group.
The mean age and HFA mean deviation (MD) were 55.6±9.5 years and -0.8±1.5 dB in 47 control patients, 59.4±9.0 years and -5.77±4.38 dB in 49 NTG patients, and 59.4±11.7 years and -8.09±6.77 dB in 51 HTG patients, respectively. All thickness parameters were lower in HTG patients compared to NTG patients, but there were no significant differences in ratio parameters between age-matched early HTG and NTG patients. The sensitivity of GDx-VCC was significantly higher in both early and total HTG patients compared to the respective groups of NTG patients.
Compared to eyes with NTG, eyes with HTG showed reduced RNFL thickness and ratio parameters when patients were age and visual field matched. GDx-VCC appeared to be more sensitive in detecting RNFL damage in HTG patients.
PMCID: PMC2908813  PMID: 16768187
Normal-tension glaucoma (NTG); High-tension glaucoma (HTG); scanning laser polarimetry with variable corneal compensation (GDx-VCC)

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