Factors Associated With Differences in the Initial Location of Structural Progression in Normal-Tension Glaucoma.

PRCIS: Different clinical factors are associated with the location of the first structural progression in glaucoma. PURPOSE: The aim was to investigate the underlying clinical parameters affecting the location of the initial structural progression of glaucoma in patients with normal-tension glaucoma (NTG). METHODS: This retrospective study included 228 eyes of 228 patients with NTG. In total, 130 eyes of 130 patients demonstrated structural progression (as determined by event-based guided progression analysis using Cirrus HD-optical coherence tomography) in the peripapillary retinal nerve fiber layer (ppRNFL) or macular ganglion cell inner plexiform layer (mGCIPL). Depending on where the progression occurred first, it was defined as either ppRNFL first progression or mGCIPL first progression. Clinical parameters associated with each first progression were identified using logistic regression. RESULTS: In total, 50 eyes showed ppRNFL first progression and 64 eyes showed mGCIPL first progression. ppRNFL first progression was significantly associated with female sex [odds ratio (OR)=5.705, P=0.015], lack of systemic hypertension (OR=0.199, P=0.014), disc hemorrhage (OR=4.188, P=0.029), higher mean intraocular pressure (OR=1.300, P=0.03), and lower pattern SD (OR=0.784, P=0.028). In contrast, male sex (OR=0.450, P=0.043), lower central corneal thickness (OR=0.987, P=0.032), higher intraocular pressure fluctuation (OR=1.753, P=0.047), lower systolic blood pressure fluctuation (OR=0.839, P=0.002), and higher diastolic blood pressure fluctuation (OR=1.208, P=0.015) were significantly associated with mGCIPL first progression. CONCLUSIONS: Different clinical factors were associated with the initial site of structural glaucoma progression in patients with NTG depending on its peripapillary or macular location, and these findings suggest possible differences in underlying mechanisms of glaucoma damage.

Effect of red ginseng on visual function and vision-related quality of life in patients with glaucoma.

BACKGROUND: Red ginseng has been found to improve ocular perfusion and dry eye syndrome in glaucomatous eyes; however, its effects on visual function and vision-related quality of life have not been investigated. This study sought to evaluate the effects of red ginseng on visual function and vision-related quality of life in glaucoma patients using contrast sensitivity and a questionnaire. METHODS: Participants were randomly assigned to two groups in this prospective, randomized, double-blind study: in one group, red ginseng was taken first, followed by a placebo, and in the other, placebo was taken first, followed by red ginseng. We measured and compared changes in contrast sensitivity and vision-related quality of life between the two groups. Contrast sensitivity was measured using OPTEC® 6500P, and vision-related quality of life was evaluated using the 25-item National Eye Institute Visual Function Questionnaire. One-way and two-way repeated measure analyses of variance were used for the comparison. Relationships between respective changes in dry eye syndrome and contrast sensitivity were also analyzed. RESULTS: Daytime contrast sensitivity and ocular pain improved after the administration of red ginseng. Nighttime contrast sensitivity was improved in early or moderate glaucoma. Improved contrast sensitivity was not associated with improvement in dry eye syndrome. CONCLUSION: Red ginseng could improve contrast sensitivity and ocular pain in patients with glaucoma. The mechanism underlying improvement in contrast sensitivity appears to be associated with enhanced retinal perfusion or retinal ganglion cell function, but not dry eye syndrome.

Effect of image quality fluctuations on the repeatability of thickness measurements in swept-source optical coherence tomography.

This study investigated the effect of image quality fluctuations on the repeatability of thickness measurements of the peripapillary retinal nerve fibre (PP-RNFL) and ganglion cell-inner plexiform (GC-IPL) layers using swept-source optical coherence tomography (SS-OCT). Three consecutive OCT scans each were performed on 56 healthy subject. Finally, 168 SS-OCT results were analysed. Based on the tertile values of the mean absolute difference of image quality score, all subjects were divided into the following three groups-low-(LIQD), moderate-(MIQD), and high-(HIQD) image quality score difference groups. A linear mixed model and intraclass correlation coefficients (ICCs) were used for analyses. Despite high ICC values (> 0.9), several sectors showed significant differences in the ICC values in intergroup comparisons. For LIQD-HIQD and MIQD-HIQD, most PP-RNFL sectors showed significant differences. For GC-IPL sectors, the LIQD-HIQD comparison showed significant differences in the temporosuperior (p = 0.012), inferior (p < .001), and temporoinferior (p = 0.042) sectors. Significant differences existed in the average GC-IPL (p = 0.009), nasoinferior (p = 0.035), and inferior GC-IPL sectors (p < .001) for MIQD-HIQD comparison. With higher image quality fluctuations, the repeatability of SS-OCT decreased in several sectors, which are considered clinically relevant in evaluating glaucoma status. Therefore, maintaining high-quality image status is essential to enhance the reliability of SS-OCT.

Factors associated with macular vessel density measured by optical coherence tomography angiography in healthy and glaucomatous eyes.

PURPOSE: To investigate factors associated with macular vessel density and to analyze their effects according to glaucoma stage. STUDY DESIGN: Retrospective cross-sectional study. METHODS: A total of 72 healthy eyes and 147 open-angle glaucomatous eyes were studied. All eyes underwent optical coherence tomography and visual field examinations. Clinical variables were compared according to the glaucoma stage. Relationships between macular vessel density (mVD) and other variables were analyzed using linear regression and segmented analyses. RESULTS: Age (P = 0.010) and signal strength (P < 0.001) were associated with macular vessel density in healthy eyes. In glaucomatous eyes, age, signal strength, ganglion cell-inner plexiform layer (GCIPL) thickness, and mean deviation (MD) correlated with macular vessel density (all P ≤ 0.005). When analyzed by glaucoma stage, age correlated with macular vessel density in early (P = 0.017 and all P ≤ 0.012, respectively) and moderate (P = 0.002 and all P ≤ 0.001, respectively) glaucoma. Conversely, GCIPL thickness was associated with macular vessel density (P = 0.004). According to segmented analysis between MD and mVD, the MD value at the change point for mVD was -17.92 dB, which was much lower than that for GCIPL thickness (-5.83 dB). CONCLUSION: Signal strength was the most significant factor associated with macular vessel density in healthy and glaucomatous eyes. Other than signal strength, factors associated with macular vessel density of glaucomatous eyes vary according to the glaucoma stage. The segmented analysis suggests that mVD could be better than GCIPL thickness in predicting MD changes in moderate-to-advanced glaucoma.

Risk Factors Associated with Structural Progression in Normal-Tension Glaucoma: Intraocular Pressure, Systemic Blood Pressure, and Myopia.

Purpose: To determine risk factors associated with structural progression in medically treated normal-tension glaucoma (NTG). Methods: This retrospective cohort study included 166 NTG patients (average age, 56.5 years; average mean deviation, -4.2 dB). The structural progression endpoint was determined by optical coherence tomography; significant thickness differences in the peripapillary retinal nerve fiber layer (RNFL) or macular ganglion cell inner plexiform layer (GCIPL) that exceeded baseline test-retest variability were identified with event-based guided-progression analysis. Intraocular pressure and systemic blood pressure (BP) were measured at each visit throughout the follow-up period, and the risk for progression was evaluated with Cox regression. Myopic disc features and antihypertensives were also analyzed. Tree analysis was used to determine the cutoff values and elucidate influential risk factors. Results: Structural progression, defined as progressive peripapillary RNFL or macular GCIPL thinning, was identified in 62 eyes. Occurrence of disc hemorrhages, presence of diabetes, and lower minimum systolic BP were associated with progression (hazard ratio [HR]: 2.116, P = 0.005; HR: 1.998, P = 0.031; HR: 0.968, P = 0.005; respectively). The cutoff value derived from the tree analysis of minimum systolic BP was 108 mm Hg. The tree analysis revealed systolic and diastolic BP to be the most influential risk factors for progressive peripapillary RFNL thinning and progressive macular GCIPL thinning, respectively. Conclusions: Low BP measured during follow-up correlated with structural progression in medically treated NTG eyes, indicating that the evaluation of hypotension is required during the management of NTG patients. The tree analysis identified BP target values that may help prevent glaucoma progression.

Diagnostic ability of vessel density measured by spectral-domain optical coherence tomography angiography for glaucoma in patients with high myopia.

Although early glaucoma detection is important to prevent visual loss due to disease progression, its clinical diagnosis in highly myopic eyes is still difficult. Many studies using optical coherence tomography (OCT) angiography (OCTA) reported decreased vessel density (VD) in glaucomatous eyes compared to normal eyes. We evaluated the diagnostic ability of peripapillary VD and macular VD measured by OCTA, comparing them with conventional valuables such as peripapillary retinal nerve fibre layer (RNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness measured by OCT. We also calculated the average VD ratio (VDR) (average outer macular VD/average inner macular VD), superior VDR (superior outer macular VD/average inner macular VD), and inferior VDR (inferior outer macular VD/average inner macular VD). Totally, 169 eyes from 169 subjects were enrolled. Among OCTA measurements, the best diagnostic parameters were average VDR (AUROC: 0.852 and 0.909) and inferior VDR (AUROC: 0.820 and 0.941) in nonhighly and highly myopic eyes, respectively. Inferior VDR showed better diagnostic ability than most of the other OCT measurements including peripapillary RNFL thickness and macular GCIPL thickness in highly myopic eyes. Accordingly, OCTA measurements can be useful for diagnosing glaucoma in highly myopic eyes, especially when using calculated indices such as average VDR or inferior VDR.

Synthesis of Thienopyrimidine Derivatives as Inhibitors of STAT3.

A series of thienopyrimidine compounds (6Aa-g and 6Ba-d) were synthesized and characterized by NMR spectroscopy and mass spectrometry. These compounds (6Aa-g and 6Ba-d) potently inhibited STAT3 expression induced by IL-6 in a dose-dependent manner with IC50 values of 5.73-0.32 µM. Among the prepared thienopyrimidine derivatives, 6Aa, 6Ab, 6Ba and 6Bc significantly suppressed the phosphorylation of STAT3 and ERK1/2 stimulated by IL-6 in Hep3B cells. Furthermore, the synthesized compounds might be useful remedies for the treatment of inflammatory diseases by inhibiting the action of IL-6.

A co-drug conjugate of naringenin and lipoic acid mediates neuroprotection in a rat model of oxidative stress.

Using our in vitro and in vivo models of oxidative stress, the current study was designed to determine the neuroprotective potential of naringenin, alone or in combination with lipoic acid. In our mixed neuronal culture exposed to hypoxia and subsequent reoxygenation, naringenin was shown to provide significant neuroprotection against cell death at a concentration of 2.5 µmol/L. Lipoic acid (LA) did not produce neuroprotection at any concentration tested (0.25-100 µmol/L). In contrast, when naringenin was covalently combined with LA, producing a novel compound named "VANL-100", significant neuroprotection was observed at a concentration as low as 2×10-2  µmol/L (100-fold more potent). An ELISA for antioxidant capacity demonstrated that naringenin and VANL-100 likely resulted in neuroprotection by increasing the free radical scavenging capacity of the neuronal cells. Pretreatment of rats with the above compounds prior to middle cerebral artery occlusion (MCAO) followed by reperfusion, showed similar results. Naringenin significantly reduced infarct volume at a dose of 10 mg/kg while VANL-100 produced significant neuroprotection at a dose as low as 1×10-4  mg/kg (10 000-fold more potent). This VANL-100-induced neuroprotection persisted even when administered 1 and 3 hours into the reperfusion time course. Taken together, these results suggest that our novel compound, VANL-100 is neuroprotective, likely via a mechanism that involves increasing the antioxidant capacity of neuronal cells. Our results also show that VANL-100 is 100-10 000-fold more potent than the parent compounds, which adds to the growing evidence in support of combination therapy targeting oxidative stress in neurodegenerative diseases.

Comparison of circumferential peripheral angle closure using iridotrabecular contact index after laser iridotomy versus combined laser iridotomy and iridoplasty.

PURPOSE: To compare the quantitative changes of peripheral angle after laser iridotomy (LI) alone (group A) or combined LI and Iridoplasty (group B) using iridotrabecular contact (ITC) index by swept-source anterior segment optical coherence tomography (AS-OCT). METHODS: In this prospective comparative observational study, OCT images were obtained before and after the procedure. In each image frame, scleral spur (SS) and the ITC end point (EP) were marked and ITC index was calculated as a percentage of the angle closure from 360°. Age, gender, diagnosis and initial ITC index in Group B were matched with group A. Changes in ITC index, anterior chamber angle parameters, and intraocular pressure (IOP) were inspected. RESULTS: Thirty-three eyes (20 patients) with shallow anterior chamber were included in each group. Initial ITC index and initial IOP were not significantly different between the two groups (both p > 0.05). However, ITC index and IOP after the procedure were significantly lower in group B than those in group A (ITC index: 31.3 ± 23.2 in group A, 19.0 ± 21.3 in group B, p = 0.011, IOP: p = 0.004). All anterior chamber angle parameters in group B and all parameters in group A except nasal trabecular-iris angles (TIA) were significantly increased after the laser procedure (all p < 0.05). CONCLUSION: In patients with shallow anterior chamber, combined LI and Iridoplasty may open the peripheral angle better than LI alone. Iridoplasty may be able to additionally relieve the peripheral angle closure caused by other mechanisms than pupillary block.

Diagnostic Value of Ganglion Cell-Inner Plexiform Layer Thickness in Glaucoma With Superior or Inferior Visual Hemifield Defects.

PURPOSE: To determine the diagnostic value of the ganglion cell-inner plexiform layer (GCIPL) thickness in glaucomatous eyes with superior or inferior visual hemifield defects. PATIENTS AND METHODS: Eighty-five patients with glaucoma (42 isolated superior hemifield defects and 43 isolated inferior hemifield defects) and 46 normal subjects were enrolled. All patients underwent Cirrus high-definition optical coherence tomography and standard automated perimetry. The area under the receiver operating characteristic curve (AUC) was calculated to determine the diagnostic ability of the GCIPL and peripapillary retinal nerve fiber layer (pRNFL). RESULTS: In the superior hemifield defect glaucoma group, the best parameters for discriminating normal eyes from glaucomatous eyes were the inferotemporal GCIPL thickness (0.942), inferior quadrant RNFL thickness (0.974), and 7 o'clock sector RNFL thickness (0.999). For diagnosing inferior hemifield defect glaucoma, the AUCs of all GCIPL parameters (0.331 to 0.702) were significantly lower than that of the superior quadrant RNFL thickness (0.866, P<0.05). CONCLUSIONS: The diagnostic ability of GCIPL parameters was similar to that of the pRNFL parameters in superior hemifield defect glaucoma. However, the diagnostic performance of the GCIPL parameters was significantly inferior to those of the pRNFL parameters in eyes with inferior hemifield defect glaucoma.

Spinal cord stimulation for neuropathic pain following idiopathic transverse myelitis: A case report.

We present a patient with intractable neuropathic pain because of idiopathic transverse myelitis unresponsive to medical treatment. After a successful trial of spinal cord stimulation, a permanent stimulator was implanted. Improvement was noted in visual analogue scale, medication usage and daily function. Spinal cord stimulation may offer a therapeutic option for patients with neuropathic pain resulting from transverse myelitis and should be considered when other treatments are failed.

Fenofibrate prevents obesity and hypertriglyceridemia in low-density lipoprotein receptor-null mice.

Our previous study demonstrated that fenofibrate improves both lipid metabolism and obesity, in part through hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) activation, in female ovariectomized, but not in sham-operated, low-density lipoprotein receptor-null (LDLR-null) mice. The aim of this study was to determine whether fenofibrate prevents obesity and hypertriglyceridemia in male LDLR-null mice. Mice fed a high-fat diet for 8 weeks exhibited increases in body and white adipose tissue (WAT) weights and developed severe hypertriglyceridemia compared with mice fed a low-fat control diet. However, these effects were effectively prevented by fenofibrate. Mice given a fenofibrate-supplemented high-fat diet showed significantly reduced body weight, WAT weight, and serum triglycerides versus high-fat diet-fed animals. Triton WR1339 study showed that fenofibrate-induced reduction in circulating triglycerides was due to the decreased secretion of triglycerides from the liver. Moreover, the administration of fenofibrate not only resulted in liver hypertrophy and reduction in hepatic lipid accumulation, but also regulated the transcriptional expression of PPARalpha target genes, such as hepatic acyl-coenzyme A (CoA) oxidase and apolipoprotein C-III (apoC-III). Therefore, our results suggest that alterations in hepatic PPARalpha action by fenofibrate seem to suppress diet-induced obesity and severe hypertriglyceridemia caused by LDLR deficiency in male mice.

Effect of a new beta-sitosterol analogue on plasma lipid concentrations in rats.

N-Substituted succinamic acid beta-sitosteryl ester derivatives were prepared and evaluated. Compounds 1 and 2 were prepared in 76-92% yields by the reaction of beta-sitosterol and succinic anhydride, followed by the activation of the resulting acid compound 1 by thionyl chloride or methyl chloroformate, and finally by amination with appropriate amines. Compound 2a (DANA87) was also easily obtained in one step by the direct addition of beta-sitosterol to dicyclohexylcarbodiimide (DCC) in 80% yield. Administration of the dietary compound DANA87 resulted in significant decreases in total plasma cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations compared with controls in a rat model. High-density lipoprotein cholesterol and plasma triglyceride levels were not affected. These findings indicate that DANA87 functions as TC and LDL cholesterol-reducing agent.