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Purpose To investigate whether progressive macular ganglion cell–inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thinning are predictive for detecting visual field (VF) progression in eyes with high myopia. Design Cohort study. Methods A total of 104 primary open-angle glaucoma (POAG) eyes with high myopia and 104 age- and VF severity-matched POAG eyes without high myopia (mean follow-up, 5.4 years) were included. High myopia was defined as a spherical equivalent 26.5 mm. Progressive GCIPL, RNFL, and VF deterioration were determined by Guided Progression Analysis (GPA) in optical coherence tomography and standard automated perimetry. The risk of VF progression was evaluated using Cox proportional hazard models. Results Highly myopic eyes with progressive GCIPL thinning had a significantly higher risk of developing VF progression after adjusting for the baseline intraocular pressure (HR 4.00; P = .001) or peak intraocular pressure (HR 3.11; P = .011) in the multivariable Cox proportional hazard model, whereas highly myopic eyes with progressive RNFL thinning were not significantly associated with VF progression. In eyes without high myopia, both progressive GCIPL (HR 4.67 or 3.62; P = .008 or .037, respectively) and RNFL (HR 6.60 or 3.97; P = .001 or .016, respectively) thinning were associated with a significantly higher risk of developing VF progression after adjusting for the baseline or peak intraocular pressure. Conclusions Monitoring macular GCIPL thickness was effective for predicting glaucoma progression regardless of the presence of high myopia

PURPOSE To compare lamina cribrosa curvature (LCC) in pseudoexfoliation glaucoma (PXG) and primary open-angle glaucoma (POAG) and to elucidate the factors associated with LCC in both groups. DESIGN Retrospective, cross-sectional study. METHOD Forty eyes with PXG and visual field mean deviation-matched 40 eyes with POAG were included. Spectral domain optical coherence tomography enhanced depth imaging was used to acquire LC images. The LCC index (LCCI) was calculated as LCC depth/LCC width × 100. Calculated LCCI values were compared between the PXG and POAG groups. Logistic regression analysis was performed to investigate the factors related to the presence of PXG. Factors associated with LCCI were determined by uni- and multivariable linear regression analyses in both groups. RESULT Visual field mean deviation (-11.7 ± 9.7 dB vs -1.0 ± 8.5 dB, P = .731) and retinal nerve fiber thickness (647.4 ± 22.7 μm vs 68.3 ± 19.9 μm, P = .857) did not differ between the 2 groups. However, the mean (8.8 ± 2.9 in PXG, 6.6 ± 1.9 in POAG) and sectoral LCCIs assessed at 0, 30, 60, 90, and 120° were significantly greater in the PXG than in the POAG group (all, P < .05), but not at 150° (P = .113). Logistic regression analysis revealed that higher average LCCI (odds ratio [OR] = 1.509 [95% confidence interval 1.180-2.047], P = .003) and older age (OR = 1.074 [95% confidence interval 1.017-1.147], P = .019) were associated with the presence of PXG. IOP was associated with mean LCCI only in the POAG group (β = 0.150 [95% confidence interval 0.018-0.281], P = .027) while none of the factors showed association with LCCI in PXG. CONCLUSION PXG eyes had more steeply curved LC than POAG eyes with a similar level of glaucoma severity. The clinical implication(s) of steeper LCC in PXG should be investigated in a forthcoming study.

Purpose To explore the clinical characteristics and profiles of newly diagnosed glaucoma subtypes in urban Korea. Methods All newly diagnosed glaucoma patients enrolled in the participating ophthalmology outpatient clinics were included. A review of medical history including family history of glaucoma was conducted. The patients underwent complete ophthalmologic examinations including visual field test. The diagnosis of glaucoma was based on the International Society of Geographical and Epidemiological Ophthalmology criteria developed by glaucoma specialists. Results A total of 198,671 patients visited the participating ophthalmology outpatient clinics during the study period (from January 1, 2001 to June 30, 2016), of which 5,530 (2.8%) were diagnosed with glaucoma. The mean age of the newly diagnosed glaucoma patients was 52.0 ± 17.3 years (range, 6 to 89) and 2,830 patients were male (51.2%). The mean untreated intraocular pressure and vertical cup-to-disc ratio of the optic nerve head of newly diagnosed glaucoma eyes were 22.1 ± 10.6 mmHg and 0.66 ± 0.22, respectively. The most frequently observed subtypes of glaucoma were: normal tension glaucoma (33.0%) primary open-angle glaucoma (28.4%), ocular hypertension (11.1%), chronic angle-closure glaucoma (6.8%), neovascular glaucoma (5.2%), glaucoma associated with inflammation (3.8%), acute angle-closure glaucoma (3.3%), and glaucoma associated with aphakia or pseudophakia (2.2%). Conclusions Normal tension glaucoma was the most frequently observed glaucoma subtype in urban ophthalmology outpatient clinics in Korea.

PRECIS Substantial proportion of primary angle closure glaucoma (PACG) eyes showed glaucomatous worsening after successful lens extraction and intraocular pressure (IOP) control, which may suggest that an earlier intervention may be required to prevent PACG. PURPOSE The purpose of this study was to investigate the longitudinal clinical course of the primary angle closure (PAC) disease spectrum, including PAC, primary angle closure suspect (PACS), and PACG patients, who underwent lens extraction. METHODS This retrospective observational study included 77 eyes from patients with PACS, PAC, and PACG who underwent lens extraction and were followed up for >2 years after surgery. The mean, peak, and fluctuation of IOP were analyzed before and after lens extraction among groups. Visual field (VF) mean deviation was compared immediately after lens extraction and the final follow-up. Postoperative glaucoma progression determined by 3 criteria (optic disc/retinal nerve fiber layer photographs, optical coherent tomography, and VF) was compared among the 3 groups. RESULTS Seventeen PACS, 24 PAC, and 36 PACG eyes were included. The mean and peak IOP, and IOP fluctuation IOP were significantly reduced postoperatively in all groups. Postoperative VF mean deviation was significantly aggravated only in the PACG group (from -7.26 to -8.82 dB, P

Primary angle-closure (PAC) eyes with no vitreous zonule (VZ) appear to have a narrower angle despite similar lens vault and iris configuration than eyes with visible VZ.To assess the clinical significance of the VZ in PAC.Medical records of 91 eyes of 91 participants with PAC or PAC glaucoma were retrospectively reviewed. Anterior segment parameters were measured using anterior segment optical coherence tomography; presence of the VZ was assessed with ultrasound biomicroscopy. Parameters were compared between eyes with vitreous zonule group (VZG) and no vitreous zonule group (NVZG). Factors associated with VZ presence were determined using logistic regression analysis.The NVZG was more likely to have PAC glaucoma than PAC (51.4% vs. 25.0%; P=0.010) and use more glaucoma medications (0.77 vs. 0.36; P=0.004) than the VZG. The NVZG had a smaller anterior chamber area than the VZG (13.6 mm vs. 15.1 mm; P=0.020) but there were no significant between-group differences in anterior chamber depth (1.97 vs. 2.08 mm; P=0.119) and lens vault (1.21 vs. 1.13 mm; P=0.337). NVZG had a smaller scleral spur angle (11.5 vs. 17.4 degrees; P0.001), angle opening distance at 500 μm (AOD500, 105 vs. 168 μm; P0.001), and trabecular-ciliary process angle (75.7 vs. 81.9 degrees; P=0.029) than VZG. Older age [odds ratio (confidence interval), 1.087 (1.014-1.164); P=0.018], less AOD500 (0.984 (0.975-0.993); P0.001), and less trabecular-ciliary process angle (0.938 (0.901-0.977); P=0.002) were independently associated with an absence of VZ.PAC eyes with no VZ had a narrower angle and required more glaucoma medications than eyes with a VZ.

PRéCIS:: This observed patient-specific features and treatment-driven conditions that were significantly associated with the impairment of health-related quality of life (HRQOL) among glaucoma patients. The results suggest that more systematic strategies should be implemented to improve an HRQOL.To determine factors contributing to an HRQOL and assess total, direct and indirect, effects that may exist between the determinants using path analysis.Data were derived from previous Korea glaucoma outcomes research. A total of 847 glaucoma outpatients with ≤2 years of eye-drop use were included in the present study. Including factors and their hypothetical pathways to an HRQOL were based on the literature review and consultation with specialists. Age, sex, comorbidities, and education levels were included as underlying conditions and treatment patterns were defined by the number of daily instillations of prescribed eye-drops. Treatment satisfaction and adherence were estimated using a Treatment Satisfaction Questionnaire for Medication, which assessed side-effects, effectiveness, convenience, global satisfaction, and pill count. An HRQOL was assessed by EQ-5D and EQ-visual analogue scale (EQ-VAS).In EQ-5D analysis, male individuals showed total effects (β=0.102, P=0.0026), including both direct (β=0.076, P=0.0095) and indirect effects (β=0.0253, P=0.0020), which were mediated by treatment satisfaction in the side effects and global satisfaction categories. Higher education (β=0.197, P=0.0020) and satisfaction in the side effect (β=0.095, P=0.0076) and global satisfaction (β=0.075, P=0.0414) categories were found to have direct effects on EQ-5D. For EQ-VAS, higher education levels had significant total effects (β=0.153, P=0.0020) accounting for direct effects (β=0.131, P=0.0030) and indirect effects (β=0.0223, P=0.0531) through global satisfaction. In addition, male individuals had indirect effects (β=0.274, P=0.0165), which was indirectly mediated by satisfaction in the global satisfaction category. Comorbidity (β=-0.096, P=0.0090) and satisfaction in the effectiveness (β=0.094, P=0.0302), convenience (β=0.076, P=0.0390), and global satisfaction (β =0.144, P=0.0020) categories showed indirect effect on EQ-VAS.Higher education and better treatment satisfaction had positive effects on HRQOL both in direct and indirect ways whereas comorbidities indirectly showed negative associations with HRQOL.

PURPOSE To explore spatial and temporal characteristics of glaucomatous visual field (VF) progression through multi-way decomposition of data. METHODS Six serial VF exams with intervals of 6.0 ± 1.0 months in 121 pre-perimetric glaucoma eyes and 80 perimetric glaucoma eyes were arranged into a three-dimensional cube. The data were decomposed using parallel factor analysis. RESULTS Three tri-linear components (i.e., spatial scores, temporal loadings, and subject-specific loadings) were identified. Component 1 clearly showed differences between superior and inferior hemispheres, linear trends over time, and wide variability in perimetric glaucoma. Findings were compatible with well-known characteristics of glaucomatous VF defects. Component 2 showed nasal and central areas in contrast with superior, inferior, and temporal peripheral locations, whereas component 3 showed a contrast between nasal and temporal hemispheres. Both components 2 and 3 failed to show clear temporal trends. CONCLUSIONS Identification of spatio-temporal patterns shows new possibilities for a multi-way decomposition methodology for earlier diagnosis and prediction of glaucomatous VF progression.

Purpose The purpose of this study was to investigate the association between dyslipidemia treatment and open-angle glaucoma (OAG). Patients and methods We included 16,939 participants aged ≥40 years from the Korea National Health and Nutrition Examination Survey (2008 to 2012) and classified them into 2 groups based on current dyslipidemia treatment. The prevalence of OAG was determined using the modified International Society of Geographical and Epidemiological Ophthalmology criteria. The association between dyslipidemia treatment and OAG was evaluated using logistic mixed-effects model and propensity-score-weighted odds ratios. Results Analyses using the 2 abovementioned models revealed that dyslipidemia treatment was not associated with OAG (odds ratio, 1.08; 95% confidence interval, 0.75-1.56; P=0.838 and 1.03; 0.71-1.48; P=0.882, respectively), presence of optic disc hemorrhage (0.64; 0.15-2.73; P=0.648 and 1.10; 0.39-3.11; P=0.855), high vertical cup-to-disc ratio or asymmetry (1.02; 0.81-1.28; P=0.736 and 0.95; 0.75-1.20; P=0.650), presence of retinal nerve fiber layer defects (0.97; 0.67-1.42; P=0.857 and 1.03; 0.75-1.42; P=0.857), and presence of visual field defects (0.93; 0.55-1.54; P=0.931 and 0.97; 0.81-1.52; P=0.528). Total cholesterol and high-density lipoprotein cholesterol were also not associated with OAG. However, higher serum triglyceride levels were associated with OAG in the treated patients (1.31; 1.02-1.68; P=0.027) but not in the untreated patients (1.03; 0.93-1.14; P=0.079). Conclusions In the Korean population, dyslipidemia treatment was not significantly associated with open-angle glaucoma. However, hypertriglyceridemia was associated with OAG in treated patients.

PRECIS The prevalence of choroidal microvascular dropout (CMvD) was significantly higher in primary open-angle glaucoma (POAG) than primary angle-closure glaucoma (PACG) or pseudoexfoliation glaucoma (PXG) in the early stage. However, in the advanced stage, it did not differ among the 3 groups. PURPOSE The purpose of this study was to compare the prevalence of peripapillary CMvD in POAG, PACG, and PXG. MATERIALS AND METHODS The presence of peripapillary CMvD was identified using optical coherence tomography angiography (AngioVue/RTVue-XR) imaging of the choroid in 186 eyes from 186 subjects [age and visual field (VF) mean deviation (MD) matched; 62 POAG, 62 PACG, and 62 PXG eyes]. Prevalence of CMvD was compared among glaucoma types in early and moderate to advanced disease, as divided by VF MD (-6 dB). The association between glaucoma type and presence of CMvD was evaluated using logistic regression analysis. RESULTS Prevalence of CMvD was significantly different between glaucoma types in early-stage disease (PACG 7.5%, PXG 25%, and POAG 46.3%, P

Precis Pseudoexfoliation glaucoma eyes had a similar level of peripapillary and superficial macular vessel densities compared with primary open-angle glaucoma eyes matched for age and glaucoma severity when assessed by optical coherence tomography angiography (OCT-A). Purpose To compare vessel density (VD) measured by OCT-A between primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) in the peripapillary and macular areas. Materials and methods The circumpapillary (cpVD), parafoveal (pfVD), and perifoveal vessel densities (perifVD) were obtained using OCT-A (AngioVue/RTVue-XR) in 98 eyes from 98 subjects [age, visual acuity, visual field (VF) mean deviation (MD) matched 49 POAG and 49 PXG eyes]. Global and 8 sectoral VDs in the peripapillary capillary layer were compared. In the macula, the superficial and deep layers of the pfVD and perifVD were analyzed globally and in 4 quadrants. Univariate and multivariate linear regression models were built using cpVD, pfVD, and perifVD as dependent variables and covariates [age, intraocular pressure (IOP), axial length, signal strength index (SSI), and retinal nerve fiber layer (RNFL) thickness] were considered independent variables. Results In the peripapillary region, none of the VDs differed between groups both before and after adjustment. When we adjusted superficial and deep layer macular VDs for age, IOP, SSI, axial length, and RNFL thickness, all of which could affect measurements, the 2 groups did not differ in any sector. The cpVD in POAG eyes significantly correlated with VF MD and RNFL thickness, whereas IOP, VF MD, and RNFL thickness affected cpVD in PXG. The macular VD in the deep layer was associated with only SSI in both groups. Conclusions Age-matched and glaucoma severity-matched PXG and POAG did not significantly differ in cpVD or in most of the superficial macular VD parameters.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging–derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection. MATERIALS AND METHODS: This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging–derived pharmacokinetic parameters (volume transfer constant [K(trans)], volume of extravascular extracellular space [v(e)](,) and blood plasma volume [v(p)]) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival. RESULTS: Baseline median K(trans), baseline first quartile K(trans), and posttreatment median K(trans) were significant independent variables, as determined by univariate analysis (P

Purpose To assess long-term changes in the anterior segment (AS) of eyes with different angle closure mechanisms. Design Retrospective cohort study. Methods In total, 133 eyes (from 75 participants) with angle closure were enrolled. All eyes received laser iridotomy (LI) during the follow-up period. Serial anterior segment optical coherence tomography (AS-OCT) imaging was performed during a mean follow-up of 4 years. Participants were categorized into four groups according to angle closure mechanisms, based on baseline AS-OCT images: pupillary block (PB), plateau iris configuration (PIC), thick peripheral iris roll (TPIR), and exaggerated lens vault (ELV). Linear mixed-effect models were applied to evaluate the longitudinal changes in AS-OCT parameters (anterior chamber depth [ACD], lens vault [LV], and angle opening distance [AOD]). Results Forty-six (35%) eyes were classified as PB, 30 (23%) as PIC, 34 (26%) as TPIR, and 23 (17%) as ELV. The follow-up period was 41−54 months. At baseline, ACD was shallowest in ELV, followed by PB, TPIR, and PIC, in order. The PIC group showed significantly wider AOD than the other groups at baseline. ACD decreased and LV increased over time in all groups, especially in the PIC group. After LI, the angle widened in the PB and TPIR groups, but not in the PIC and ELV groups. Conclusions AS parameters changed differently in the four groups. The effects of LI on AOD also differed among groups. Identification of the angle closure mechanism may help predict progressive changes in AS parameters in eyes with angle closure.

Purpose The purpose of this study was to investigate the relationship between refractive error and ocular biometry and its implication in the pathogenesis of primary angle closure (PAC). Methods We have retrospectively recruited 119 PAC eyes and 388 non-PAC eyes with an axial length (AL) of ≤25.0 mm and a spherical equivalent (SE) of ≥−6.0 diopters (D). Stepwise multiple regression was performed for keratometry value (K), AL, anterior chamber depth (ACD), and SE. Results PAC eyes were more likely to be in women and have a higher IOP and shorter AL than non-PAC eyes. In a multiple regression analysis, SE was not associated with PAC. The associations between AL and SE or AL and ACD were not different in PAC eyes compared with non-PAC eyes. However, the cornea was flatter in PAC eyes (β = −0.448, P < 0.001), and a flatter cornea was associated with more hyperopic refraction (β = −0.454, P < 0.001) and shallower ACD (β = 0.073, P < 0.001) in PAC eyes. ACD was not associated with SE in non-PAC eyes, but shallower ACD was associated with greater myopic refraction in PAC eyes (β = 1.117, P = 0.006). Conclusions PAC eyes seem to have flatter cornea compared with non-PAC eyes. A shallower ACD seems to be associated with greater myopic refraction in PAC eyes, but not in non-PAC eyes.

To examine the performance of Guided Progression Analysis (GPA; Carl Zeiss Meditec, Dublin, CA) in spectral-domain optical coherence tomography (OCT) in detecting progressive thinning of ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) in glaucoma.Longitudinal, observational study.A total of 196 eyes of 123 primary open-angle glaucoma patients (mean follow-up, 5.0 years).Macular GCIPL and peripapillary RNFL thicknesses were measured by Cirrus HD-OCT (Zeiss, Dublin, CA), and progressive GCIPL and RNFL thinning were assessed by GPA. The reference standard of glaucoma progression was determined by visual field (VF) progression. Glaucomatous eyes were classified into mild (117 eyes) or moderate to advanced (79 eyes) groups based on VF defects. Ganglion cell-inner plexiform layer and RNFL thinning rates were compared between progressors and nonprogressors. Visual field survival estimates in eyes with and without progressive GCIPL and RNFL thinning were evaluated by Kaplan-Meier survival analysis and compared with the log-rank test.Progressive GCIPL and RNFL thinning assessed by OCT GPA.Seventy-six eyes (38.8%) and 43 eyes (21.9%) demonstrated progressive GCIPL and RNFL thinning, respectively, and 48 eyes (24.5%) were classified as progressors by reference standard. The rate of change in the average GCIPL thickness was significantly higher in progressors (-1.05±0.98 μm/year for mild glaucoma and -0.66±0.30 μm/year for moderate to advanced glaucoma) than in nonprogressors (-0.47±0.54 μm/year for mild glaucoma and -0.31±0.50 μm/year for moderate to advanced glaucoma), regardless of glaucoma severity (P0.05). Eyes with progressive GCIPL thinning had lower VF survival estimates than eyes without, regardless of glaucoma severity. However, the rate of change in the average RNFL thickness did not differ significantly in moderate to advanced glaucoma (P = 0.765; -0.26±0.55 μm/year for progressors and -0.33±0.92 μm/year for nonprogressors), and VF survival estimates did not differ significantly between eyes with and without progressive RNFL thinning in moderate to advanced glaucoma (P = 0.781).Ganglion cell-inner plexiform layer GPA provides a new approach for evaluating glaucoma progression. It may be more useful for detecting progression in the advanced stages of glaucoma than RNFL GPA.

We investigated the spontaneous recovery of non-operated traumatic brachial plexus injury (BPI). A total of 25 cases of non-operated traumatic BPI were analysed by retrospective review of medical records; in all cases, consecutive electrodiagnostic studies (ES) were conducted from 1 to 4 months and 18 to 24 months post-trauma. Injury severity was assessed using a modified version of Dumitru and Wilbourn’s scale (DWS) based on ES. Spontaneous recovery of brachial plexus components per subject was analysed using Wilcoxon’s signed-rank test. A two-tailed Fisher’s exact or Pearson’s Chi-square test was used to examine the associations between initial injury severity (DWS grade 2 vs. 3, complete vs. incomplete), accompanying injury type (open vs. closed), main lesion location (supraclavicular vs. infraclavicular lesion), and spontaneous recovery. The most common cause of BPI was traffic accident (TA) (15 cases, 60%), and the most common type of TA-induced BPI was a motorcycle TA (5 cases), accounting for 20% of all injuries. The second most common type of injury was an occupational injury (6 cases, 24%). Thirty-eight (69%) of 55 injured brachial components in 25 cases had DWS grade 3 and 17 brachial components (31%) had grade 2. The DWS grade of brachial plexus components per subject significantly differed between the first and follow-up ES (p = 0.000). However, initial injury severity, accompanying injury type, and main lesion location were not statistically associated with spontaneous recovery (p > 0.05). Spontaneous recovery may be possible even in severe traumatic BPI. Multiple factors should be considered when predicting the clinical course of traumatic BPI.

PURPOSE OF THE STUDY The purpose of the study was to evaluate vision-related quality of life in Korean glaucoma patients and to explore the associated factors. METHODS A total of 907 glaucoma patients were recruited from the prospectively designed LIGHT (Life quality of the glaucoma patient who underwent treatment) study organized by the Korean Glaucoma Society. Basic questionnaire that included items related to socioeconomic status, comorbidity, and lifestyle, and the validated Korean version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were collected. The Rasch score, a logit-based interval scale estimate to summarizing the NEI VFQ-25 responses, was calculated. The univariate and multivariable regression models were used to evaluate associations between the Rasch score and variables. RESULTS The mean patient age was 58.1±14.1 years, visual field mean deviation (VF MD) of the better and worse eyes was -4.92±6.14 and -9.77±8.31 dB, binocular-integrated VF (IVF) MD was -3.55±5.31 dB, respectively. The lower NEI VFQ-25 Rasch score showed a significant association with the presence of other ocular diseases (P=0.020), a high school level of education or less [vs. university (P=0.006), vs. graduate school or higher (P=0.019)], an anxious personality [vs. a moderate personality (P

Purpose To investigate the use of ganglion cell inner plexiform layer (GC-IPL) thickness, as measured by spectral domain optical coherence tomography, to detect central visual field (VF) progression. Methods This study included 384 eyes from 384 patients (219 preperimetric and 165 perimetric glaucomatous eyes; average follow-up, 4.3 years). Photographic assessment of retinal nerve fiber layer (RNFL) and serial VF analysis were performed to detect glaucoma progression in the central (within 10°) area. Study inclusion required at least five serial spectral domain optical coherence tomography exams at different visits. The long-term test-retest variability of average GC-IPL thicknesses was calculated in 110 stable preperimetric glaucomatous eyes. The sensitivity and specificity of GC-IPL measurements for the detection of central VF progression were calculated in an event-based analysis using the calculated variability as a cut-off and were compared with those of central RNFL photographic assessment. Results The intersession test-retest variability, defined as the 95% confidence interval, was 1.76 µm for average GC-IPL thickness. The sensitivity and specificity of the average GC-IPL thickness for detecting central VF progression were 60.7% and 78.9%, respectively. Among six sectors, the inferonasal GC-IPL sector showed the highest sensitivity (53.6%). The sensitivity of the ≥1 sector GC-IPL to detect central VF progression was significantly higher than that of central RNFL photographic progression (p = 0.013). Other GC-IPL parameters showed comparable sensitivity and specificity to detect central VF progression compared with RNFL photographic progression. Conclusions Serial GC-IPL measurements show comparable performance in the detection of central glaucomatous VF progression to RNFL photographic assessment.

Purpose To evaluate the effect of age on global and sectoral vascular parameters of the peripapillary area and macula in healthy eyes by using optical coherence tomography angiography (OCT-A). Methods This retrospective cross-sectional study included 239 eyes of 172 healthy subjects. Subjects were scanned using the high-definition disc angio scan (4.5 × 4.5 mm), retina angio scan (6 × 6 mm), and optic nerve head/ganglion cell complex (GCC) modes of OCT-A. Global and sectoral circumpapillary vessel density (VD), parafoveal VD, retinal nerve fiber layer (RNFL), and GCC thickness parameters were modeled in terms of age by using linear mixed-effect models incorporating covariates. Normalized slopes were calculated by dividing the absolute slopes by the mean value of the OCT-A parameters. Results All global and sectoral circumpapillary VDs decreased significantly with increasing age, except for those in the temporal superior sector. The steepest slopes in the circumpapillary region were observed in nasal superior (-0.098%/y) and nasal inferior (-0.096%/y) sectors. The global, temporal, and superior macular VDs also decreased with increasing age, while the foveal, nasal, and inferior parameters did not. The temporal quadrant showed the steepest slope among the macular parameters (-0.068%/y). The RNFL and GCC thickness results showed similar trends. Conclusions Age substantially affected VD in most of the peripapillary and macular areas; however, the papillomacular bundle area did not show significant age-related vascular changes. These age-related global and sectoral differences in circumpapillary and macular VDs should be considered when assessing pathologic VD changes over time.

PURPOSE To explore the progressive change and associated factors of optic disc tilt in young myopic glaucomatous eyes by analyzing long-term follow-up data. METHODS Optic disc images were obtained from spectral-domain optical coherence tomography enhanced depth imaging from at least five different visits. At each visit, the disc tilt angle (DTA), defined as the angle between the Bruch's membrane opening plane and the optic canal plane, was estimated at the central frame that passes through the optic disc. Glaucoma progression was assessed on the basis of changes noted on serial optic disc and retinal nerve fiber layer photographs or changes in the visual field (VF). A linear mixed effect model was used to assess the influence of parameters (age, sex, baseline and follow-up intraocular pressure, retinal nerve fiber layer thickness, VF mean deviation, axial length, central corneal thickness), and presence of glaucomatous progression upon DTA change. RESULTS A total of 26 eyes of 26 young myopic primary open-angle glaucoma patients (axial length >24.0 mm; mean age, 25.1 ± 4.0 years; mean follow-up, 3.3 ± 0.9 years) were included. DTA was 7.0 ± 3.4 degrees at baseline and 8.3 ± 3.8 degrees at last visit, which represents a significant difference (p < 0.001). Worse VF mean deviation (p < 0.001) and longer axial length (p = 0.006) were significantly associated with DTA increase. CONCLUSIONS Young myopic glaucomatous eyes showed progressive optic disc tilting. Progressive optic disc tilting in young myopic glaucomatous eyes may be related to either continuous axial myopic shift or glaucomatous structural change.

To investigate whether progressive macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thinning predict development of visual field (VF) defects in glaucoma suspects.Retrospective cohort study.This study included 541 eyes of 357 glaucoma suspects with a mean follow-up of 5.7 years. Progressive GCIPL and RNFL thinning were determined using Guided Progression Analysis (GPA) in optical coherence tomography (OCT). The development of VF defect was defined as the presence of three consecutive abnormal VFs. The risk of developing VF defect was evaluated using Cox proportional hazard models.A total of 74 eyes (13.7%) and 87 eyes (16.1%) showed progressive GCIPL and RNFL thinning by OCT GPA, respectively, and 40 eyes (7.4%) developed VF defects. Eyes with progressive GCIPL (hazard ratio [HR], 7.130; 95% confidence interval [CI], 3.137-16.205) and RNFL (HR, 7.525; 95% CI, 3.272-17.311) thinning showed a significantly higher risk of developing VF defects. The rate of change in the average GCIPL and RNFL thickness was significantly higher in the eyes that developed VF defects (-0.71 and -1.13 μm/y, respectively) than the eyes that did not (-0.19 and -0.27 μm/y, respectively; all P0.05). Progressive GCIPL (43.1 vs. 63.1 months, respectively; P0.001) and RNFL (50.9 vs. 66.7 months, respectively; P0.001) thinning were detected significantly earlier than the development of VF defects.Monitoring progressive change in GCIPL, as well as RNFL, effectively predicts the development of VF defects in glaucoma suspects.

PRéCIS:: Peripapillary vessel density (pVD) assessed by optical coherence tomography angiography (OCT-A) has poor global and regional correlations with lamina cribrosa depth (LCD), except for the inferotemporal area.To investigate the global and regional relationship between the pVD assessed by OCT-A and LCD assessed by enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT).A total of 38 eyes of 38 healthy subjects and 38 eyes of 38 glaucoma patients were included. Peripapillary microvasculature and lamina cribrosa were imaged by OCT-A and enhanced depth imaging SD-OCT, respectively. The pVD and LCD were measured at temporal, superotemporal, superonasal, nasal, inferonasal, and inferotemporal sectors. Global and regional correlations between pVD and LCD were evaluated in all subjects.The pVD (59.0±2.6 vs. 54.4±5.4%) and LCD (318.5±76.4 vs. 404.6±92.5 μm) were significantly different between healthy and glaucoma subjects. The average pVD assessed by OCT-A was not significantly correlated with average LCD assessed by SD-OCT (r=-0.160, P=0.167). Regional correlation between pVD and LCD was statistically significant only in the inferotemporal sector (r=-0.301 and P=0.008). In the linear regression analysis, reduced pVD was independently associated with decreased visual field mean deviation and peripapillary retinal nerve fiber layer thickness but not with increased LCD.Global and regional correlations between pVD and LCD were poor except for the inferotemporal sector. This finding suggests that peripapillary microvascular impairment may not result directly from posterior lamina cribrosa displacement.

To explore optic disc and peripapillary retinal nerve fiber layer (RNFL) features associated with glaucomatous optic disc (GOD) in young myopia. Presence of GOD, optic disc tilt, and disc torsion were determined using fundus photographs. If the measured disc tilt ratio was >1.3, the optic disc was classified as tilted. Optic disc torsion was defined as a >15° deviation in the long axis of the optic disc from the vertical meridian. The average and four quadrants RNFL thicknesses were assessed using spectral domain optical coherence tomography (SD-OCT). Logistic regression analyses were performed to identify factors associated with the presence of GOD. Nine hundred and sixty myopic subjects were recruited from four refractive surgery clinic databases. The mean age was 26.6 ± 5.7 years and spherical equivalent (SE) was −5.5 ± 2.5 diopters. Among 960 eyes, 26 (2.7%) received GOD group classification. Among 934 normal eyes, 290 (31.0%) had titled optic discs. Eighteen eyes (69.2%) in the GOD group had tilted optic discs. When compared to normal eyes, the GOD group had significantly higher tilt ratios (1.4 ± 0.2 vs. 1.2 ± 0.1, p

To investigate the prevalence of pseudoexfoliation syndrome (PXS) and factors associated with PXS in South Koreans by analyzing data from the Korean National Health and Nutrition Examination Survey (KNHANES).Using the KNHANES database of 2009-2012, 13,223 participants aged 50 years or older were included. Participants underwent standardized interviews and systemic and ocular examinations. Systemic factors analyzed included age, sex, daily length of sun exposure, presence of Raynaud phenomenon or migraine, hypertension, diabetes mellitus, body mass index, serum lipid profile, duration and frequency of smoking, and alcohol consumption. Evaluated ocular factors were refractive error, presence of cataract and glaucoma, intraocular pressure, and peripheral anterior chamber depth. Logistic regression analysis was performed to identify factors associated with the presence of PXS.PXS was found in 16 participants (0.12%). When compared with the non-PXS group, eyes with PXS showed a higher prevalence of cataract (p = 0.020). In logistic regression analysis, age (odds ratio, OR, 1.04, 95% confidence interval, CI, 0.99-1.09; p = 0.016) and the presence of cataract (OR 8.17, 95% CI 1.06-62.84; p = 0.044) were associated with the presence of PXS. Sun exposure for ≥5 hours/day was marginally associated with the presence of PXS (OR 2.76, 95% CI 0.96-7.95; p = 0.060).The prevalence of PXS per 1000 persons was 1.10 in South Koreans aged ≥50 years. Participants with PXS had a higher prevalence of cataract, were older, and were more likely to be exposed to the sun for ≥5 hours/day than participants without PXS.

To compare progression of primary open angle glaucoma (POAG) in asymmetrically myopic eyes within the same subject and evaluate whether the degree of myopia is related to glaucoma progression. POAG patients with asymmetric myopia (axial length [AXL] ≥24 mm in both eyes, and the AXL difference between the right and left eyes to be ≥0.5 mm) were included. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer (RNFL) photographs or by serial visual field (VF) data. The progression rates of VF mean deviation (dB/year) and spectral domain optical coherence tomography measured RNFL thickness (μm/year) were compared between the more myopic eye (MME) and the less myopic eye (LME) within the same subject. A total of 55 patients (mean follow up period; 4.5 ± 1.0 years) were included. The mean AXL demonstrated a significant difference between MME and LME (26.3 ± 1.7 vs. 25.6 ± 1.7 mm; p = 0.036). The mean baseline VF MD (−3.8 ± 5.4 vs. −2.6 ± 4.7 dB; p = 0.21) and average RNFL thickness (77.5 ± 10.6 vs. 79.9 ± 12.3 μm; p = 0.36) did not differ between the MME and LME. Among the 55 patients, optic disc/RNFL photographic progression was noted in the MME in 15 patients, in the LME in 19 patients, and in both eyes in seven patients. VF progression was noted in the MME in seven patients, in the LME in seven patients, and in both eyes in four patients. The VF MD progression rates were −0.25 ± 0.34 dB/year in MME and −0.26 ± 0.34 dB/year in LME cases (p = 0.91). The mean progression rate of the average RNFL thickness also did not differ between the MME and LME (−0.59 ± 0.67 vs. -0.66 ± 0.72 μm/year, p = 0.68). The degree of myopia was not associated with glaucoma progression when assessing the same patient using either the VF or optic disc/RNFL criteria in asymmetrically myopic patients.

To compare the rate of glaucoma structural and functional progression in American and Korean cohorts.Retrospective longitudinal study.Three hundred thirteen eyes from 189 glaucoma and glaucoma suspects, followed up for an average of 38 months.All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had 5 or more reliable visits.The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and disease severity, disease subtype (high- vs. normal-tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables.The Korean cohort predominantly demonstrated normal-tension glaucoma, whereas the American cohort predominantly demonstrated high-tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thicker mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean, -0.71 μm/year vs. -0.24 μm/year; P0.01). There were no detectable differences in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change.Ethnicity, baseline disease severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies.

Purpose Matrix metalloproteinases (MMPs) are involved in extracellular matrix (ECM) maintenance and remodeling. The present study aimed to determine whether transforming growth factor (TGF)-β2 regulates MMP-2 and MMP-9 levels and activities in astrocytes derived from the optic nerve head (ONH) and the role of statins in such modulation. Methods Primary astrocytes cultured from the lamina cribrosa of human donor ONHs were incubated with three types of statins (5 µg/mL) for 1 hour followed by recombinant TGF-β2 (5 ng/mL) for various periods to test their effects. Levels and activities of MMP-2 and MMP-9 in astrocytes in vitro were determined by western blotting and zymography, respectively. Levels of phosphorylated myosin phosphatase target subunit 1 (MYPT1) in astrocyte lysates were determined by western blotting, and those of phosphorylated myosin light chain (MLC) were determined by western blotting and immunocytochemistry. Results MMP-2 and MMP-9 levels were upregulated by TGF-β2 in human ONH astrocytes. Prior incubation with simvastatin, lovastatin, and atorvastatin inhibited TGF-β2-mediated MMP-2 and MMP-9 expression and activities. Prior incubation with statins downregulated the TGF-β2-induced phosphorylation of MYPT1 and MLC, which are downstream substrates of RhoA and ROCKs. Conclusions Statins inhibited the TGF-β2-mediated regulation of MMP-2 and MMP-9 by inhibiting the RhoA/ROCK signaling pathway. Considering the role of MMP in ECM remodeling, the present findings support the notion that statins positively impact ECM remodeling within the ONH.

PURPOSE To identify factors influencing vision-related quality of life (VRQOL) according to glaucoma severity. METHODS A total of 901 patients with varying stages of glaucoma were recruited from the prospectively designed LIGHT (Life Quality of Glaucoma Patients Who Underwent Treatment) study organized by the Korean Glaucoma Society. Participants completed a basic questionnaire collecting socioeconomic status and clinical information, in addition to the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Subjects were classified by mean deviation (MD) of integrated binocular visual field (IVF) into mild, moderate and severe damage groups. Factors were evaluated for their influence on VRQOL according to glaucoma severity using univariate and multivariable regression models between Rasch-analysed NEI VFQ-25 subscale scores and different variables. RESULTS The mild, moderate and severe groups contained 720, 111 and 70 patients, respectively; the mean IVF MD in each group was -1.4, -8.5 and -17.9 dB. Significant differences were observed among the three groups with respect to age, IVF MD, visual acuity (VA), education level, income level, number of glaucoma medications prescribed and follow-up period. The most influential factor associated with VRQOL according to glaucoma severity was VA. The VA of the better eye was much more influential on VRQOL than the VA of the worse eye in the moderate and severe defect groups, and the impact of VA on VRQOL was more prominent in advanced glaucoma. CONCLUSIONS Visual acuity is the most influential factor on VRQOL in patients with glaucoma. Preservation of VA should be strongly prioritized to maintain good VRQOL.

Purpose To assess influence of the location of visual field (VF) loss on vision-related quality of life (VRQOL) in patients with glaucoma. Methods We included 826 patients with primary open-angle glaucoma (POAG) enrolled in the prospectively designed Life Quality of Glaucoma Patients Who Underwent Treatment (LIGHT) study organized by the Korean Glaucoma Society. We divided the integrated binocular visual field (IVF) into four regions and evaluated the associations between Rasch-analysed 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and location of the IVF using univariate and hierarchical multivariable linear regression. Results Mean deviation (MD) of the IVF at superior centre showed the lowest value among the four regions. Multivariable linear regression analysis revealed significant correlation of the composite score and all subscales of the NEI VFQ-25 except ocular pain and near activities at each of four IVF regions. Mean deviation at superior centre showed significant correlation with composite score (R2 = 0.181), near activities (R2 = 0.175), and social functioning (R2 = 0.166); MD at superior periphery showed highest correlation with role difficulties (R2 = 0.137); MD at inferior centre showed highest correlation with driving (R2 = 0.145); and MD at inferior periphery showed significant correlation with distance activities (R2 = 0.214) and dependency (R2 = 0.119). Conclusion Four different regions of the IVF had a similarly important impact on subscales of the NEI VFQ-25 in glaucoma patients. Preservation of the superior field should be considered as much as that of the inferior field for maintaining a good VRQOL in patients with glaucoma.

PURPOSE To investigate glaucoma progression and its relationship with corrected and uncorrected intraocular pressure (IOP) in patients with a history of refractive corneal surgery (RCS). METHODS Totally, 56 eyes of 56 primary open-angle glaucoma patients who had a history of RCS were included. Mean keratometry and central corneal thickness were measured at the time of glaucoma diagnosis. Three IOP measurements, i.e., uncorrected IOP (UCIOP) and corrected IOP calculated by applying the Kohlhaas (CKIOP) and Ehlers (CEIOP) formulas, were used. Participants were categorized into two groups (low-teen [

Purpose To investigate the spatial characteristics and patterns of progressive macular ganglion cell–inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). Design Longitudinal, retrospective, observational study. Participants Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2–8.1 years) were included. Methods Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. Main Outcome Measures Spatial characteristics and patterns of progressive GCIPL thinning. Results Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°–339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. Conclusions The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression.

To compare the rates of retinal nerve fibre layer (RNFL) thinning in subgroups of patients with glaucoma based on spherical equivalent (SE).In this retrospective study, patients were classified into three subgroups, namely, non-myopic glaucoma (NMG,0 dioptres (D)), mild-to-moderate glaucoma (MMG, 0 to -6 D) and highly myopic glaucoma (HMG,-6 D), according to their SE. Linear mixed effects models were used to evaluate the rate of change of RNFL thickness determined by spectral domain optical coherence tomography, adjusting for potentially confounding factors.Among 231 glaucomatous eyes from 231 patients (mean followed up 4.5 years), 105 (45.5%) were classified as NMG, 100 (43.2%) as MMG and 26 (11.3%) as HMG. Baseline visual field mean deviation did not differ among the three subgroups (-4.15 vs -5.44 dB vs -4.38 dB, p=0.185). Thinning rate of average RNFL did not differ among the three subgroups (-0.58, -0.52 and -0.54 μm/year, p=0.931). However, RNFL thinning rate at temporal quadrant (-0.85 vs -0.23 μm/year, p=0.046) and eight o'clock sector was greater in the HMG than in the NMG subgroups (-1.72 vs -0.35 μm/year, p=0.003), while that of one o'clock sector was greater in the NMG than in the HMG subgroups (-0.93 vs 0.45 μm/year, p=0.009).Overall rate of RNFL thinning was not different among the glaucoma subgroups based on refractive error. However, sectoral RNFL thinning showed significant difference.

To compare the lamina cribrosa (LC) depth of the optic nerve head in normal and glaucomatous eyes over a wide range of axial length (AXL).A total of 402 eyes, including 210 normal and 192 glaucomatous eyes, were imaged by spectral domain optical coherence tomography. Normal and glaucomatous eyes were each divided into three subgroups according to the level of AXL; long (26 mm), mid-level (23-26 mm), and short (23 mm). Visual field mean deviation (VF MD), LC thickness, and LC depth were compared between normal and glaucomatous eyes in each of the AXL subgroups. These parameters were also compared between normal and glaucomatous eyes in the three AXL subgroups. Factors associated with LC depth in each AXL subgroup were evaluated by univariate and multivariate regression analyses.A comparison of the three AXL subgroups in normal eyes showed that the LC was thinnest in the long AXL subgroup (short; 189.7 ± 24.1 μm, mid-level; 179.9 ± 34.3 μm, long; 149.2 ± 36.2 μm, p 0.001), but LC depth did not differ significantly in the three subgroups (short; 527.1 ± 144.4 μm, mid-level; 578.2 ± 163.5 μm, long; 594.4 ± 187.5 μm, p = 0.144). In glaucomatous eyes, glaucoma severity assessed by VF MD did not differ significantly among the three AXL subgroups (short; -6.99 ± 8.50 dB, mid-level; -6.40 ± 7.64 dB, long; -4.61 ± 5.22 dB, p = 0.168). However, LC depth was greater in the long than in the short AXL subgroup (679.5 ± 192.7 μm and 555.9 ± 134.1 μm, respectively, p = 0.004), although neither subgroup differed significantly in LC depth from the mid-level AXL subgroup (611.8 ± 162.3 μm, p = 0.385, p = 0.090). LC thickness was significantly different between normal and glaucomatous eyes (p 0.001). LC depth was not different between normal and glaucomatous eyes in both short and mid-level AXL subgroups (p = 0.297, 0.222), but differed in the long AXL subgroup (p = 0.022). The presence of glaucoma was associated with greater LC depth only in the long AXL subgroup (p = 0.012).LC depth may vary according to the level of AXL in glaucomatous eyes with a similar level of glaucoma severity, with the greatest LC depth found in eyes with long AXL. Those findings suggest that glaucomatous optic disc cupping would manifest differently according to the level of AXL.

The purpose of this study was to evaluate the antifibrotic effects of pirfenidone (PFD) on primary cultured human Tenon’s fibroblasts (HTFs) from primary open-angle glaucoma (POAG) eyes, compared to mitomicin C (MMC) and 5-fluorouracil (5-FU). Samples of human Tenon’s capsule were obtained during respective surgeries from three groups of patients: patients with cataract (CAT group), patients with POAG who underwent glaucoma filtration surgery (GFS) (POAG1 group), and patients with POAG who underwent GFS due to failed bleb of previous GFS (POAG2 group). Cell toxicity, cell migration, and the expression level of α-smooth muscle actin (α-SMA) protein were evaluated in primary cultured HTFs from the three patient groups after treatment (PFD, MMC, or 5-FU). Overall, cell viability after PFD treatment was higher compared to MMC treatment (82.3 ± 5.1 % vs 56.7 ± 3.8 %; p = 0.001) and comparable to 5-FU treatment (82.3 ± 5.1 % vs 85.7 ± 10.7 %, p = 0.214) at the same concentration (0.4 mg/ml). Both 0.3 mg/ml PFD and 0.1 mg/ml MMC inhibited cell migration compared to control (without treatment) cells (p = 0.014 and 0.005, respectively), while 0.2 mg/ml 5-FU showed the highest degree of cell migration among the three agents in the POAG1 group (PFD vs MMC vs 5-FU; 29.5 ± 2.1 % vs 34.5 ± 0.7 % vs 76.0 ± 8.5 %, PFD vs MMC; p = 1.000, PFD vs 5-FU; p = 0.008, MMC vs 5-FU; p = 0.011). PFD (0.1 or 0.3 mg/ml) and MMC (0.05 and 0.1 mg/ml) treatment significantly reduced the protein expression level of α-SMA in the POAG 1 group (all p

Purpose Normal-tension glaucoma (NTG) is a heterogenous disease, and there is still controversy about subclassifications of this disorder. On the basis of spectral-domain optical coherence tomography (SD-OCT), we subdivided NTG with hierarchical cluster analysis using optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thicknesses. Patients and methods A total of 200 eyes of 200 NTG patients between March 2011 and June 2012 underwent SD-OCT scans to measure ONH parameters and RNFL thicknesses. We classified NTG into homogenous subgroups based on these variables using a hierarchical cluster analysis, and compared clusters to evaluate diverse NTG characteristics. Results Three clusters were found after hierarchical cluster analysis. Cluster 1 (62 eyes) had the thickest RNFL and widest rim area, and showed early glaucoma features. Cluster 2 (60 eyes) was characterized by the largest cup/disc ratio and cup volume, and showed advanced glaucomatous damage. Cluster 3 (78 eyes) had small disc areas in SD-OCT and were comprised of patients with significantly younger age, longer axial length, and greater myopia than the other 2 groups. Conclusions A hierarchical cluster analysis of SD-OCT scans divided NTG patients into 3 groups based upon ONH parameters and RNFL thicknesses. It is anticipated that the small disc area group comprised of younger and more myopic patients may show unique features unlike the other 2 groups.

To investigate the baseline anterior segment (AS) parameters determined by AS optical coherence tomography (AS OCT) in the prediction of long-term outcome of laser peripheral iridotomy (LPI) in primary angle closure suspect (PACS) eyes Methods: Participants were imaged at pre-LPI and at 2 weeks and 3 years post-LPI using AS OCT. Based on these images, anterior chamber depth (ACD), iris curvature (IC), anterior chamber width (ACW), iris thickness at 750 µm from the scleral spur (IT750), lens vault (LV), and iris area (IA) were estimated using the Image J software (version 1.46). Proportional change (%) in angle opening distance at 750 µm from the scleral spur (AOD750) was used as an outcome measure for LPI. Univariate and multivariate regression analyses were performed to evaluate baseline AS parameters associated with changes in AOD750.A total of 39 PACS eyes were included. At 2 weeks post-LPI, thinner IT750 (p = 0.006) and less AOD750 (p 0.001) at baseline were related to a greater AOD750 change. When assessed at 3 years post-LPI, thinner IT750 (p = 0.039) and less AOD750 (p = 0.003) at baseline were associated with a greater AOD750 change.Thin peripheral iris and less AOD750 at baseline were associated with greater changes in longitudinal assessment after LPI. PACS eyes with thick peripheral iris at baseline showed less AOD750 change at both early and late follow up after LPI; therefore, such eyes should be followed with caution despite successful LPI.

PURPOSE To identify the preoperative biometric factors, including subfoveal choroidal thickness (CT), associated with refractive outcome after cataract surgery in eyes with primary angle closure (PAC). METHODS This study included 50 eyes of 50 PAC patients who underwent uneventful cataract surgery. Preoperatively, anterior segment parameters including anterior chamber depth (ACD) and lens vault were determined by anterior segment optical coherence tomography. Subfoveal CT was measured by spectral domain optical coherence tomography enhanced depth imaging before and at one month after surgery. Mean refractive error (MRE) was calculated as the difference in spherical equivalent between actual postoperative refraction determined one month postoperatively and that predicted using each of three IOL calculation formulas (SRK/II, SRK/T, and Haigis). Regression analyses were performed to investigate potential associations between MRE and putative factors. RESULTS Mean ACD was 1.9 ± 0.4 mm, and preoperative subfoveal CT was 250.8 ± 56.9 μm. The SRK/T (MRE, 0.199 ± 0.567 diopters [D]) and Haigis (MRE, 0.190 ± 0.727 D) formulas showed slight hyperopic shift, while the SRK/II formula demonstrated a myopic shift (MRE, -0.077 ± 0.623 D) compared with that expected after cataract surgery. Mean absolute refractive error was not significantly different between formulas. Higher preoperative lens vault and shallower ACD were associated with a hyperopic shift in all formulas, but not in a statistically significant manner. Thicker preoperative subfoveal choroid was associated with a myopic shift after cataract surgery in all formulas (SRK/II: β = -0.511, p < 0.001; SRK/T: β = -0.652, p < 0.001; Haigis: β = -0.671, p < 0.001). Greater postoperative reduction of subfoveal CT was associated with a myopic shift after cataract surgery in all formulas (SRK/II: β = -0.511, p < 0.001; SRK/T: β = -0.652, p < 0.001; Haigis: β = -0.671, p < 0.001). CONCLUSIONS Our results indicate that preoperative subfoveal CT and the difference between pre- and postoperative subfoveal CT are significant factors for predicting refractive error after cataract surgery in PAC patients. These findings should be considered when performing cataract surgery to optimize visual outcomes.

PURPOSE To investigate risk factors associated with glaucomatous progression in pseudoexfoliation glaucoma (PXG) patients. PATIENTS AND METHODS A retrospective observational study with a total of 48 PXG patients and age, sex, and visual field (VF) test mean deviation-matched 48 primary open-angle glaucoma (POAG) patients recruited from 3 university-based hospitals. Glaucomatous progression was defined by 2 criteria, either optic disc/retinal nerve fiber layer photographic assessment or serial VF data. Univariate and multivariate Cox proportional hazard models were used to detect associations between risk factors and progression in each subgroup and shared frailty model were used in total participants. RESULTS In total participants, PXG diagnosis [hazard ratio (HR), 7.245; P=0.050], a higher baseline intraocular pressure (IOP) (HR, 1.221; P=0.025) and a greater number of glaucoma medications (HR, 3.537; P=0.016) were significant factors for glaucoma progression. In the PXG group, a higher baseline IOP (HR, 1.131; P

PURPOSE To evaluate outcomes and factors associated with surgical failure in patients who underwent combined phacoemulsification and Ahmed glaucoma valve (AGV) implantation. METHODS This retrospective and longitudinal study enrolled 40 eyes (38 patients) that underwent combined phacoemulsification and AGV implantation. Visual acuity, intraocular pressure (IOP), and number of antiglaucoma medications were evaluated preoperatively and postoperatively. Complete success was defined as a last follow-up IOP of 6 to 21 mmHg without medication, qualified success as an IOP of 6 to 21 mmHg with medication, and failure as an IOP of >21 or

AimTo evaluate the progressive change in peripapillary atrophy (PPA) according to its shape and to explore the relationship between PPA progression and glaucoma worsening in myopic eyes.MethodsA total of 159 eyes of 159 patients with myopic (axial length (AXL) >24 mm) glaucoma (mean follow-up 4.4 years, 35 eyes with minimal PPA, 40 concentric-type PPA eyes (>270° around the optic disc) and 84 eccentric-type PPA eyes (ResultsPatients with concentric PPA were older than patients with eccentric PPA (54.1±11.7 vs 44.1±11.7 years; PConclusionsRelationship between glaucoma worsening and PPA progression was strongest in myopic glaucomatous eyes with eccentric type PPA.

Purpose To compare the demographics and ocular characteristics, including anterior segment optical coherence tomography images and zonular instability, in eyes with a history of acute angle closure (AAC) attack and subsequent cataract surgery. Design Retrospective case-control study. Methods A total of 68 eyes of 56 patients with a history of AAC attack who underwent cataract surgery were enrolled. Fourteen eyes were assigned to the zonular instability (+) group and 54 were assigned to the zonular instability (−) group based on the presence of zonular instability during cataract surgery. The peak intraocular pressure, preoperative spherical equivalent (SE), axial length (AL), anterior chamber depth (ACD), and lens vault (LV) were measured and compared between 2 groups. Intereye (intraindividual) comparison was also performed. Factors associated with zonular instability were assessed. Results In the zonular instability (+) group, 9 eyes were from male and 5 from female participants. Eyes in the zonular instability (+) group showed less hyperopic SE values, longer AL, shallower ACD, and higher LV, as compared with those in the zonular instability (−) group (all P ≤ .001). Moreover, eyes in the zonular instability (+) group had less hyperopic SE, shallower ACD, and higher LV than their fellow eyes. Less hyperopic SE, longer AL, and higher LV were significantly associated with zonular instability on multivariate logistic regression analysis. Conclusions Clinicians should consider the possibility of zonular instability during cataract surgery for eyes with less hyperopic SE, longer AL, and higher LV among those with a history of AAC attack.

PURPOSE To identify factors associated with visual field (VF) progression in optical coherence tomography (OCT)-guided progression analysis (GPA) using a topographic approach. METHODS Topographic components of OCT-GPA maps (Cirrus HD-OCT; Carl Zeiss Meditec) were classified according to location (temporal, superotemporal, superonasal, nasal, inferornasal, and inferotemporal), size (small, medium, and large), shape (wedge and irregular types), and pattern of retinal nerve fiber layer (RNFL) progression (widening, deepening, and new development). All positive findings in OCT-GPA (RNFL thickness maps, profiles, and average RNFL thickness) were defined as strong RNFL progression. VF progression was determined by linear regression analysis of VF mean deviation over time. Univariate and multivariate logistic regression analyses were performed to evaluate the association of VF progression with OCT-GPA parameters. RESULTS In total, 276 primary open-angle glaucoma patients were followed up for 5.1 years. According to OCT-GPA, 89 eyes were found to have RNFL progression. Of these, VF progression was detected in 27 (30.3%) eyes. Eyes with progressed VF group showed topographically different characteristics, which were wedge-shaped (80.6%), large-sized (40.0%), and widening (69.5%) or deepening (11.1%) pattern of RNFL progression in the inferotemporal (44.4%) and superotemporal (30.6%) regions, compared with eyes with non-progressed VF group. In multivariate analysis, strong RNFL progression and widening or deepening pattern of RNFL progression were significantly associated with VF progression (P=0.012 and 0.016, respectively). CONCLUSIONS Topographic analysis in OCT-GPA maps showed different characteristics between progressed VF and nonprogressed VF groups. Glaucoma patients with widening or deepening pattern of RNFL progression should be carefully monitored for greater risk of VF progression.

Transneuronal retrograde degeneration (TRD) of retinal ganglion cells (RGCs) has been reported to induce retinal nerve fiber layer (RNFL) loss [1,2,3]. RNFL loss eventually causes neuroretinal rim thinning of the optic disc. Glaucoma is one example of an optic neuropathy, and is characterized by progressive loss of RGCs, reduction of RNFL thickness, thinning of the neuroretinal rim, and increased excavation of the optic disc. Although the underlying pathology mechanisms are completely different, the eventual loss of RGCs and the RNFL may make it difficult to differentiate between the distinct pathologies of TRD and glaucoma. Clinical clues, such as rim pallor, which is more common in TRD cases, or signs specific to glaucoma (e.g., optic disc hemorrhage), may help discriminate between these two pathologies. However, when these signs are absent, it is often difficult to make a specific diagnosis by only observing the optic disc. Optical coherence tomography (OCT) is a device used to image the posterior pole of the eye. RNFL thickness is measured by OCT and is widely used for the assessment of glaucomatous structural changes as well as for evaluation of the neuro-ophthalmologic area [4,5,6,7,8]. With improved image resolution provided by spectral domain (SD) OCT, evaluation of segmented inner retinal layer thickness, which targets RGC thickness, has become commercially available [9,10,11]. Ganglion cell thickness (GCT), which includes measurement of the ganglion cell layer and the inner plexiform layer, has showed promise for the detection of glaucoma and the detection of glaucoma progression [9,12]. More than 50% of RGCs are located in the inner area of the macula, which consists of several layers. Measurement of GCT in the macular area is being used in clinical practice as well as in research [13,14,15,16]. Nasal-sided RGC axons in the optic nerve cross at the optic chiasm and join with temporal-sided RGC axons of the contralateral eye at the post-chiasmal area; these become the optic track of the contralateral side, which radiates to the lateral geniculate body, the optic radiation, and the visual cortex. Temporal-sided RGC axons in the optic nerve become the optic track of the ipsilateral side after joining with nasal-sided RGC axons of the contralateral eye. Therefore, chiasmal and post-chiasmal lesions manifest as a visual field (VF) defect with respect to the vertical meridian, which is helpful for differentiation between brain lesions and glaucoma. Glaucomatous VF defects manifest with respect to the horizontal meridian. Considering this anatomical characteristic of axonal distribution, we hypothesized that the pattern of RGC loss in the macula may also exhibit these characteristics. Hence, we analyzed a GCT map using SD-OCT and explored the pattern of RGC loss in eyes with chiasmal and post-chiasmal lesions. To the best of our knowledge, this is the first study to investigate the pattern of RGC loss in neurologic lesions.

To evaluate whether pointwise regression analysis of serial measures of retinal sensitivity can predict future visual field (VF) loss.Medical records of 158 patients with glaucomatous eyes with at least 6 years follow-up and 10 reliable VF exams were retrospectively analyzed. The entire follow-up period was divided into two, roughly corresponding to the first (early period) and second (late period) half of follow-up. Retinal sensitivity data obtained from the Swedish interactive threshold algorithm standard or full-threshold VF tests were analyzed, and linear and first-order exponential regression analyses of retinal sensitivity against time were performed to obtain the slope of regression analysis in each VF test location. Paired t tests were used to compare the slopes of the early and late period in each regression analysis.When assessed by linear regression analysis, inferior nasal location showed highest rate of change (-0.52 dB/year) in early period. Late period showed generally faster rate of progression compared to early period. Superior arcuate and superior and inferior nasal locations showed that early and late slopes did not show significant difference (p value, 0.19 ∼ 0.49). Central and edged locations showed significant difference between the two slopes (p value 0.05). First-order exponential regression analysis showed similar result.Superior arcuate and superior and inferior nasal areas in VF had a consistent rate of change of retinal sensitivity, indicating that these locations may have the higher capability for prediction of future deterioration. These results suggest that location should be considered when predicting glaucomatous VF progression.

Purpose This study compared the glaucoma diagnostic abilities of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). In addition, the possibility of enhancing diagnostic capability by combining the two modalities was investigated. Methods A total of 131 healthy eyes and 113 glaucomatous eyes were imaged by both OCT and OCTA. In OCT, glaucoma was defined as when the color of the superior or inferior quadrant of the peripapillary retinal nerve fiber layer thickness map was yellow (borderline

Purpose To investigate whether the relationship between circumpapillary vascular density (cpVD) and visual field (VF) mean sensitivity (MS) differs between primary open-angle (POAG) and angle-closure glaucoma (PACG). Methods The cpVD and retinal nerve fiber layer thickness (RNFLT) were obtained using optical coherence tomography angiography (OCTA, AngioVue/RTVue-XR) in 146 eyes from 146 subjects (age- and VF mean deviation-matched 86 POAG and 60 PACG). Global and regional relationships (superotemporal [ST], superonasal [SN], nasoupper [NU], nasolower [NL], inferonasal [IN], inferotemoporal [IT], temporolower [TL], and temporoupper [TU] sectors) were estimated between cpVD and VF MS using multiple linear regression models controlling for the confounding variables in two disease categories. Uni- and multivariate linear regression models were built using cpVD as the dependent variable and covariates (age, intraocular pressure [IOP], axial length, signal strength index, and RNFLT) as independent variables. Results In PACG eyes, the cpVD was associated with the corresponding VF MS in five sectors (semipartial correlation coefficient [sr]: 0.144-0.567, P < 0.05): IN, IT, ST, TL, and SN, while the RNFLT showed association in four sectors (sr: 0.047-0.544, P < 0.05). In POAG eyes, the cpVD of all sectors was associated with the corresponding VF MS (sr: 0.246-0.574, P < 0.05). Greater IOP and lower RNFLT were independently associated with reduction of cpVD in the PACG group (P = 0.002, P < 0.001). In the meantime, only lower RNFLT was associated with reduction of cpVD in the POAG group (P < 0.001). Conclusions POAG and PACG eyes differed in vascular-function relationship determined by OCTA and VF MS.

Previously published studies have reported a correlation between retinal vein occlusion (RVO) and glaucoma [1-5]. In particular, the population-based Beaver Dam Eye Study found that the optic cup-to-disc ratio was a significant predictor of RVO [4]. The Blue Mountain Study reported that RVO was significantly associated with glaucoma, hypertension, stroke, and angina [5]. More recently, Kim et al. [3] showed that the thickness of the retinal nerve fiber layer (RNFL) was thinner in the fellow eyes of patients with unilateral RVO, especially in the infero- and superotemporal sectors, compared with control eyes. True glaucomatous changes cannot be easily assessed in RVO-affected eyes because the retinal hemorrhage and edema generated by this disorder affect the states of the optic disc, RNFL, and visual field (VF). In patients with unilateral RVO, the fellow eye can serve as an appropriate surrogate for determining the relationship between glaucoma and RVO [3]. Because glaucoma is mostly a bilateral disease, the observation of structural glaucomatous changes in the fellow eye of patients with unilateral RVO suggests that these 2 disease entities (glaucoma and RVO) may share a common pathogenic mechanism. Additionally, the status of the fellow eye is important in cases of unilateral RVO, because if RVO-induced irreversible damage occurs, then only the fellow eye remains functional for sight. Thus, the possibility of glaucoma developing in the fellow eye of an RVO patient is of clinical importance in patient care. Although the relationship between glaucoma and RVO is well recognized, not every patient with unilateral RVO shows glaucomatous structural changes in the fellow eye. Some (or many) eyes with unilateral RVO in the fellow eye do not demonstrate glaucomatous optic disc changes, although glaucomatous damage may be indicated in the future as this may be a cross-sectional observational effect. Therefore, we hypothesized that there might be some differences between glaucomatous and non-glaucomatous eyes with unilateral RVO in the fellow eye in terms of the baseline characteristics and RVO types. Hence, the aim of the present study was to compare the baseline characteristics of the patients and the fluorescein angiographic findings in RVO, especially in terms of the occlusion sites of RVO, between glaucomatous and non-glaucomatous eyes (with apparently healthy optic discs) that had unilateral RVO in the fellow eye.

To compare the outcomes of Cirrus spectral-domain optical coherence tomography (OCT) and optic disc/retinal nerve fiber layer (RNFL) photographic assessment in detecting glaucomatous progression.Two-hundred twenty-six eyes of 130 glaucoma patients (mean follow-up: 2.5 years) with at least 5 OCT examinations were included. Eyes were classified into one of four groups (diffuse RNFL defect; localized RNFL defect; no RNFL defect; unidentifiable RNFL status) based on baseline RNFL photographs. After performing the entire series of optic disc/RNFL photographic assessments, the eyes were classified into one of three groups: stable, progressed, and undetermined. Progression was divided into one of four categories (optic disc rim thinning; widening RNFL defect; deepening RNFL defect; new disc hemorrhage). OCT progression was determined using guided progression analysis (GPA) software.One-hundred thirty-nine eyes had diffuse RNFL defects, 34 eyes had localized RNFL defects, 42 eyes had no RNFL defects, and 11 eyes had unidentifiable RNFL at baseline. Forty-six eyes showed at least one category of progression upon expert assessment of optic disc/RNFL photographs, while OCT GPA detected progression in 35 eyes. Among the 34 eyes in which progression was observed in photographs only, 15 showed a new disc hemorrhage, 12 presented deepening of an RNFL defect, 10 showed optic disc rim change, and 6 had widening of an RNFL defect. Among the 23 eyes processed only by OCT GPA, 18 had a diffuse RNFL defect at baseline.OCT GPA was more sensitive in eyes with a diffuse RNFL defect whereas photographic assessment was better for detecting optic disc hemorrhage and deepening of an RNFL defect when evaluating structural progression.

To compare the rate of change of circumpapillary retinal nerve fiber layer (cRNFL) thickness, macular volume and thickness, and optic nerve head (ONH) parameters assessed using spectral-domain optical coherence tomography (SD-OCT) between eyes with progressing and nonprogressing glaucoma.Longitudinal, observational study.Two hundred seventy-nine eyes from 162 glaucoma patients followed for an average of 2.2 years.Eyes were classified as progressors and nonprogressors according to assessment of optic disc and RNFL photographs and visual field progression analysis. Linear mixed effects models were used to evaluate the overall rate of change of cRNFL thickness, macular volume and thickness, and ONH parameters after adjustment for age, spherical equivalent, signal strength, and baseline SD-OCT measurements.The rate of change of cRNFL thickness, macular volume, and thickness and ONH parameters.Sixty-three eyes (22.6%) from 52 subjects were identified as progressors. Average, inferior quadrant, and 6- and 7-o'clock sector cRNFL thickness decreased faster in progressors than in nonprogressors (-1.26 vs -0.94, -2.47 vs -1.75, -3.60 vs -2.52, and -2.77 vs -1.51 μm/year, respectively; all P0.05). The ONH rim area decreased faster, and average and vertical cup-to-disc ratio increased faster in progressors than in nonprogressors (-0.016 vs -0.006 mm(2)/year, and 0.004 vs 0.002 and 0.006 vs 0.004 per year, respectively; all P0.05). Macular cube volume and the thickness of temporal outer and inferior inner macular sectors decreased faster in progressors than in nonprogressors (-0.068 vs -0.048 mm(3)/year, and -2.27 vs -1.67 and -2.51 vs -1.73 μm/year, respectively; all P0.05).Serial measurement of parameters in all 3 areas (cRNFL, macula, and ONH) by SD-OCT may permit identification of progression in glaucomatous eyes.The authors have no proprietary or commercial interest in any of the materials discussed in this article.

To compare the clinical courses of patients with myopic primary open angle glaucoma (POAG) with and without optic disc shape alterations.In this longitudinal retrospective study, 146 eyes from 146 patients with myopic (axial length(AXL),24 mm) POAG were classified according to optic disc shape alterations defined by optic disc tilt and/or rotation. Glaucomatous progression was determined by either serial optic disc/retinal nerve fibre layer photographs or visual field (VF) exams. Rate of progression was calculated from serial VF mean deviation (MD) and visual field index values.Mean age, AXL and follow-up duration were 50.1±12.7 years, 26.1±1.6 mm and 4.6±1.3 years, respectively. The progression rate was faster in eyes with a non-tilted optic disc than with a tilted optic disc (-0.30(95% CI; -0.42 to -0.16) vs 0.05(-0.07 to 0.17) dB/year, -0.85(-1.20 to -0.49) vs -0.35(-0.68 to -0.03) %/year, all p0.05). Twenty eyes (21.3%) in the non-tilted group but only one eye (1.9%) in the tilted group showed VF progression in both superior and inferior hemifields. By logistic regression analysis, worse initial VF MD and less optic disc tilt were significantly associated with both superior and inferior VF progression (OR=0.909 and 0.561 (for 0.1 tilt ratio); p=0.020 and 0.018, respectively).Significant differences in glaucomatous progression were found between eyes with and without optic disc shape alterations, particularly disc tilt. More localised and stable courses of glaucoma progression were observed in eyes with tilted optic discs.

To investigate peripapillary vessel density at various spatial locations and layers in healthy and normal tension glaucoma eyes using optical coherence tomography angiography (OCTA). A commercial OCTA device (AngioPlex; Carl Zeiss Meditec) was used to image microvasculature in a 6 × 6-mm optic disc region. Vessel densities of superficial and deep retinal layers were calculated using an automatic thresholding algorithm. Vessel density maps were plotted by averaging individual angiogram images. The spatial characteristics of vessel densities were analyzed at clock-hour sectors and in five 0.7-mm-thick concentric circles from a diameter of 2.0 to 5.5 mm. Areas under the receiver operating characteristics curves (AUCs) assessed the glaucoma diagnostic ability. Vessel density maps of superficial and deep retinal layers were significantly reduced at the 7 and 11 o’clock positions in glaucomatous eyes. In superficial layer, vessel density significantly decreased as the distance from the optic disc margin increased, except in the innermost circle (2.0–2.7-mm). There were significant differences in AUCs of superficial vessel density between innermost circle and the other outer circles. In the deep layer, the innermost circle showed significantly higher vessel density than the outer circles. Vessel density at 7 o’clock showed the best diagnostic performance (AUCs, 0.898 and 0.789) both in the superficial and deep layers. The innermost circle showed eccentric feature compared to the outer circles in terms of spatial characteristics and diagnostic ability. Understanding of the spatial characteristics of peripapillary vasculature may be helpful in clinical practice and determining the optimal measurement area of vessel density.