METHODS: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis.
RESULTS: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups.
CONCLUSION: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.
METHODS: In this cross-sectional study, 30 severe glaucoma patients, 30 mild glaucoma patients and 30 age-matched controls were recruited. All subjects underwent standard automated perimetry, RNFL analysis and 3 T MRI examinations. Glaucoma patients were classified according to the Hodapp-Anderson-Parish classification. Pearson's correlation coefficient was used to correlate ON volume with RNFL, and receiver operating curve (ROC) analysis was performed to determine the sensitivity and specificity of ON volume in detecting glaucoma severity.
RESULTS: Optic nerve volume was significantly lower in both the left and right eyes of the severe glaucoma group (168.70 ± 46.28 mm(3); 167.40 ± 45.36 mm(3)) than in the mild glaucoma group (264.03 ± 78.53 mm(3); 264.76 ± 78.88 mm(3)) and the control group (297.80 ± 71.45 mm(3); 296.56 ± 71.02 mm(3)). Moderate correlation was observed between: RNFL thickness and ON volume (r = 0.51, p <0.001), and in mean deviation of visual field and optic nerve volume (r = 0.60, p
PURPOSE: The purpose of this study was to investigate the clinical characteristics, including 24-hour ocular perfusion pressure and risk of progression in patients with baseline central VF defect, as compared with those with peripheral VF defect in NTG.
DESIGN: This was a prospective, longitudinal study.
METHODS: A total of 65 NTG patients who completed 5 years of follow-up were included in this study. All the enrolled patients underwent baseline 24-hour intraocular pressure and blood pressure monitoring via 2-hourly measurements in their habitual position and had ≥5 reliable VF tests during the 5-year follow-up. Patients were assigned to two groups on the basis of VF defect locations at baseline, the central 10 degrees, and the peripheral 10- to 24-degree area. Modified Anderson criteria were used to assess global VF progression over 5 years. Kaplan-Meier analyses were used to compare the elapsed time of confirmed VF progression in the two groups. Hazard ratios for the association between clinical risk factors and VF progression were obtained by using Cox proportional hazards models.
RESULTS: There were no significant differences between the patients with baseline central and peripheral VF defects in terms of demography, clinical, ocular and systemic hemodynamic factors. Eyes with baseline defects involving the central fields progressed faster (difference: βcentral=-0.78 dB/y, 95% confidence interval=-0.22 to -1.33, P=0.007) and have 3.56 times higher hazard of progressing (95% confidence interval=1.17-10.82, P=0.025) than those with only peripheral defects.
CONCLUSION: NTG patients with baseline central VF involvement are at increased risk of progression compared with those with peripheral VF defect.
METHODOLOGY: We performed a cross-sectional cohort study on healthy subjects and patients with glaucoma. The AngioVue Enhanced Microvascular Imaging System was used to capture the optic nerve head and macula images during one visit. En face segment images of the macular and optic disc were studied in layers. Microvascular density of the optic nerve head and macula were quantified by the number of pixels measured by a novel in-house developed software. Areas under the receiver operating characteristic curves (AUROC) were used to determine the accuracy of differentiating between glaucoma and healthy subjects.
RESULTS: A total of 24 (32 eyes) glaucoma subjects (57.5±9.5-y old) and 29 (58 eyes) age-matched controls (51.17±13.5-y old) were recruited. Optic disc and macula scans were performed showing a greater mean vessel density (VD) in healthy compared with glaucoma subjects. The control group had higher VD than the glaucoma group at the en face segmented layers of the optic disc (optic nerve head: 0.209±0.05 vs. 0.110±0.048, P<0.001; vitreoretinal interface: 0.086±0.045 vs. 0.052±0.034, P=0.001; radial peripapillary capillary: 0.146±0.040 vs. 0.053±0.036, P<0.001; and choroid: 0.228±0.074 vs. 0.165±0.062, P<0.001). Similarly, the VD at the macula was also greater in controls than glaucoma patients (superficial retina capillary plexus: 0.115±0.016 vs. 0.088±0.027, P<0.001; deep retina capillary plexus: 0.233±0.027 vs. 0.136±0.073, P<0.001; outer retinal capillary plexus: 0.190±0.057 vs. 0.136±0.105, P=0.036; and choriocapillaris: 0.225±0.053 vs. 0.153±0.068, P<0.001. The AUROC was highest for optic disc radial peripapillary capillary (0.96), followed by nerve head (0.92) and optic disc choroid (0.76). At the macula, the AUROC was highest for deep retina (0.86), followed by choroid (0.84), superficial retina (0.81), and outer retina (0.72).
CONCLUSIONS: Microvascular density of the optic disc and macula in glaucoma patients was reduced compared with healthy controls. VD of both optic disc and macula had a high diagnostic ability in differentiating healthy and glaucoma eyes.
METHODS: This retrospective study analysed data of 60 eyes from 30 patients with bilateral uveitic glaucoma who had undergone glaucoma surgery in both eyes on separate occasions. Humphrey VF progression was assessed using the Progressor software.
RESULTS: The pre-operative IOP between the FE (43.1 ± 7.7 mmHg) and SE (40 ± 8.7 mmHg) was not statistically significant (p = 0.15). IOP reduction was greater in the FE (64 %) than SE (59.7 %) post-operatively, but the mean IOP at the final visit in the FE (12.3 ± 3.9 mmHg) and SE (14.5 ± 7 mmHg) was not statistically different (p = 0.2). There was no significant change in mean logMAR readings pre and post-operatively (0.45 ± 0.6 vs 0.37 ± 0.6, p = 0.4) or between the FE and SE. The number of SE with CDR > 0.7 increased by 23 % compared to the FE. From 23 available VFs, five SE (21.7 %) progressed at a median of five locations (range 1-11 points) with a mean local slope reduction of 1.74 ± 0.45 dB/year (range -2.39 to -1.26), whereas only one FE progressed. However, there was no significant difference between mean global rate of progression between the FE (-0.9 ± 1.6 dB/year) and SE (-0.76 ± 2.1 dB/year, p = 0.17) in the Humphrey VF.
CONCLUSION: In eyes with bilateral uveitic glaucoma requiring glaucoma surgery, the SEs had more progressed points on VF and glaucomatous disc progression compared to FEs at the final visit.
METHODS: This prospective clinical study included consecutive Asian patients with dark irides and confirmed for glaucoma. Only one eye of each patient was treated. Diode laser contact transscleral cyclophotocoagulation treatment was performed with the center of the probe placed 1.5 mm behind the limbus. About 30 pulses of 810-mm laser radiation (power, 1.8 to 2.0 W; duration, 0.3 to 0.5 second) were applied around the eye. Patients were examined at fixed postoperative intervals. Intraocular pressure levels and postoperative complications were recorded. The relation between patient and disease characteristics, total laser energy delivered, and intraocular pressure effects were analyzed.
RESULTS: Thirty-three patients were studied, with a mean follow-up period of 9.4 months. An average 56% of patients showed a 30% or greater drop in intraocular pressure. About 38% of patients achieved sustained intraocular pressure lowering to below 22 mm Hg at 18 months. Complications were few and included transient hypotony and iritis.
CONCLUSIONS: In Asian patients with refractory glaucoma or painful glaucomatous eyes with poor visual acuity (defined for this study as worse than 20/200), low-energy-setting diode laser contact transscleral cyclophotocoagulation by means of the glass ball probe is relatively effective and safe.
METHODS: A cross-sectional study was conducted involving 150 Malay PACG patients between April 2014 and August 2016. Ocular examination was performed including Humphrey visual field (HVF) 24-2 analysis assessment. On the basis of the 2 consecutive reliable HVFs, the severity of glaucoma was scored according to modified Advanced Glaucoma Intervention Study (AGIS) by 2 masked investigators and classified as mild, moderate, and severe. Those with retinal diseases, neurological diseases, memory problem, and myopia ≥4 diopters were excluded. Their smoking status and details were obtained by validated questionnaire from Singapore Malay Eye Study (SiMES). The duration of smoking, number of cigarettes per day, and pack/year was also documented. Multiple linear regression analysis was conducted.
RESULTS: There was a significant association between education level and severity of PACG (P=0.001). However, there was no significant association between cigarette smoking and severity of glaucoma (P=0.080). On the basis of multivariate analysis, a linear association was identified between cigarette smoked per day (adjusted b=0.73; 95% CI: 0.54, 1.45; P<0.001) and body mass index (adjusted b=0.32; 95% CI: 0.07, 1.35; P=0.032) with AGIS score.
CONCLUSIONS: There was no significant association between cigarette smoking and severity of PACG. Cigarette smoked per day among the smokers was associated with severity of PACG. However, because of the detrimental effect of smoking, cessation of smoking should be advocated to PACG patients.
METHODS: Diurnal variation of intraocular pressure was measured in 202 eyes of suspected open-angle glaucoma patients and 100 control eyes, at 4-hourly intervals for 24 hours (phasing). Based on the phasing results, optic disc changes and visual field defects, the patients were diagnosed as primary open angle glaucoma (POAG), normal tension glaucoma (NTG), ocular hypertension (OHT), or physiologic cup (PC), or still remained as glaucoma suspects due to inconclusive diagnosis. The last group (glaucoma suspects) was then followed up 6-monthly for their eventual outcome.
RESULTS: The highest percentage of suspected glaucoma patients had peak (maximum) readings in the mid-morning (10-11 A.M.) and trough (minimum) readings after midnight (2-3 A.M.); the highest percentage of control group had peak readings in the late evening (6-7 P.M.) and trough readings after midnight (2-3 A.M.). The mean amplitude of variance was 6 mm Hg in suspected glaucoma group and 4 mm Hg in the control group. After 'phasing', 18.8% of the suspected glaucoma patients were diagnosed as POAG, 16.8% as NTG, 5% as OHT, and 28.7% as physiologic cup; 30.9% remained as glaucoma suspects. After 4 years follow-up, 70% of the glaucoma suspects still remained as glaucoma suspects, 6.7% developed NTG and another 6.7% POAG; 16.6% were normal.
CONCLUSIONS: Serial measurement of IOP ( phasing) in a 24-hour period is still needed, in order not to miss the peak and the trough IOP readings in suspected open-angle glaucoma patients, which helps in better management of glaucoma. Among 30.9% of patients who remained as glaucoma suspects after the initial phasing, 13.4% developed NTG/POAG over a period of 4 years.
METHODS: This is a cross-sectional study involving 27 patients with symptoms of OSAS seen at a tertiary institutional center and 25 normal controls performed between June 2015 and June 2016. All patients and controls underwent a polysomnography (PSG) test and were diagnosed with OSAS based on the apnea-hypopnea index (AHI). Patients are those with OSAS symptoms and had AHI > 5, whereas controls are staffs from the ophthalmology clinic without clinical criteria for OSAS and had PSG result of AHI
METHODS: We measured psychophysical contrast thresholds in one eye of 16 control subjects and 19 patients aged 67.8 ± 5.65 and 71.9 ± 7.15, respectively, (mean ± SD). Patients ranged in disease severity from suspects to severe glaucoma. We used the 17-region FDT-perimeter C20-threshold program and a custom 9-region test (R9) with similar visual field coverage. The R9 stimuli scaled their spatial frequencies with eccentricity and were modulated at lower temporal frequencies than C20 and thus did not display a clear spatial frequency-doubling (FD) appearance. Based on the overlapping areas of the stimuli, we transformed the C20 results to 9 measures for direct comparison with R9. We also compared mfVEP-based and psychophysical contrast thresholds in 26 younger (26.6 ± 7.3 y, mean ± SD) and 20 older normal control subjects (66.5 ± 7.3 y) control subjects using the R9 stimuli.
RESULTS: The best intraclass correlations between R9/C20 thresholds were for the central and outer regions: 0.82 ± 0.05 (mean ± SD, p ≤ 0.0001). The areas under receiver operator characteristic plots for C20 and R9 were as high as 0.99 ± 0.012 (mean ± SE). Canonical correlation analysis (CCA) showed significant correlation (r = 0.638, p = 0.029) with 1 dimension of the C20 and R9 data, suggesting that the lower and higher temporal frequency tests probed the same neural mechanism(s). Low signal quality made the contrast-threshold mfVEPs non-viable. The resulting mfVEP thresholds were limited by noise to artificially high contrasts, which unlike the psychophysical versions, were not correlated with age.
CONCLUSION: The lower temporal frequency R9 stimuli had similar diagnostic power to the FDT-C20 stimuli. CCA indicated the both stimuli drove similar neural mechanisms, possibly suggesting no advantage of FD stimuli for mfVEPs. Given that the contrast-threshold mfVEPs were non-viable, we used the present and published results to make recommendations for future mfVEP tests.
DESIGN: Prospective, longitudinal study.
METHODS: Sixty-five NTG patients who were followed up for 5 years are included in this study. All the enrolled patients underwent baseline 24-h IOP and BP monitoring via 2-hourly measurements in their habitual position and were followed up for over 5 years with reliable VF tests. Modified Anderson criteria were used to assess VF progression. Univariable and multivariable analyses using Cox's proportional hazards model were used to identify the systemic and clinical risk factors that predict progression. Kaplan-Meier survival analyses were used to compare the time elapsed to confirmed VF progression in the presence or absence of each potential risk factor.
RESULTS: At 5-year follow-up, 35.4% of the enrolled patients demonstrated visual field progression. There were statistically significant differences in the mean diastolic blood pressure (p 43.7 mmHg (log rank = 0.018).
CONCLUSION: Diastolic parameters of BP and OPP were significantly lower in the NTG patients who progressed after 5 years. Low nocturnal DOPP is an independent predictor of glaucomatous visual field progression in NTG patients.
DESIGN: A cross-sectional, non-interventional study.
METHODS: The IOP measurements by handheld Icare rebound tonometer (Finland) were first performed by a primary care physician. Then the IOP was measured using Perkins Mk3 applanation tonometer (Haag-Streit, UK) by an ophthalmologist who was masked to previous readings from the Icare rebound tonometer. The mean IOP measured by each tonometer was compared. Pearson correlation coefficient was used to explore the correlation between the IOP measurements of the 2 instruments. The level of agreement between them was assessed using the Bland and Altman method.
RESULTS: A total of 420 left eyes were examined. The mean age of subjects was 38.6 ± 18.2 years. Approximately 67% of subjects were female. The mean IOP was 16.3 ± 4.0 mm Hg using Icare and 13.4 ± 2.3 mm Hg using PAT. Pearson correlation coefficient showed a moderate positive correlation between the 2 methods (r = +0.524, P < 0.001). Linear regression analysis revealed a slope of 0.28 with R² of 0.255. The mean difference between the 2 methods was 2.90 ± 3.5 mm Hg and the sample t-test revealed a statistically significant mean difference from 0 (P < 0.001). The 95% limits of agreement between the 2 methods were between -9.73 and 3.93 mm Hg.
CONCLUSIONS: The handheld Icare rebound tonometer is a reasonably acceptable screening tool in community practices. However, Icare overestimated IOP with a mean of 2.90 mm Hg higher than the PAT. Thus, using Goldmann applanation tonometer as a confirmatory measurement tool of IOP is suggested.