Displaying publications 1 - 20 of 33 in total

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  1. Zhao D, Kim MH, Pastor-Barriuso R, Chang Y, Ryu S, Zhang Y, et al.
    Invest Ophthalmol Vis Sci, 2014 Oct;55(10):6244-50.
    PMID: 25183763 DOI: 10.1167/iovs.14-14151
    To examine the longitudinal association between age and intraocular pressure (IOP) in a large sample of Korean men and women.
    Matched MeSH terms: Glaucoma, Open-Angle/diagnosis; Glaucoma, Open-Angle/epidemiology; Glaucoma, Open-Angle/physiopathology*
  2. Yip VCH, Wong HT, Yong VKY, Lim BA, Hee OK, Cheng J, et al.
    J Glaucoma, 2019 01;28(1):80-87.
    PMID: 30461553 DOI: 10.1097/IJG.0000000000001125
    AIM: To study the microvascular density of the macular and optic nerve head in healthy and glaucoma subjects using optical coherence tomography angiography.

    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.

    Matched MeSH terms: Glaucoma, Open-Angle/physiopathology*
  3. Teoh SL, Allan D, Dutton GN, Foulds WS
    Br J Ophthalmol, 1990 Apr;74(4):215-9.
    PMID: 2186795
    The visual acuity, the difference in sensitivity of the two eyes to light (brightness ratio), and contrast sensitivity were assessed in 28 patients with chronic open angle glaucoma and compared with those of 41 normal controls of similar ages and visual acuity. The results obtained were related to the results of Tübingen visual field analysis in patients with glaucoma. Twenty-four of the 28 glaucoma patients (86%) had a significant disparity in brightness ratio between the two eyes. This was found to match the frequency of visual field loss. Moreover, there was a significant relationship between the interocular differences in brightness sense and the difference in the degree of visual field loss between the two eyes. Of the glaucoma patients 39% had sum contrast sensitivities outside the normal range for age-matched normal controls. No significant correlation was found between the interocular difference in brightness sense and the visual acuity or the interocular difference in sum contrast sensitivity. It is concluded that, in the presence of a normal visual acuity, the brightness ratio test warrants evaluation as a potential screening test for chronic open angle glaucoma.
    Matched MeSH terms: Glaucoma, Open-Angle/physiopathology*
  4. Tan HK, Ahmad Tajuddin LS, Lee MY, Ismail S, Wan-Hitam WH
    PMID: 26065503 DOI: 10.1097/APO.0000000000000058
    PURPOSE: To determine the mean central corneal thickness (CCT) and the relationship between the CCT and visual field progression in primary angle closure (PAC) and primary angle closure glaucoma (PACG).

    DESIGN: A combined cross-sectional and prospective study on PAC and PACG.

    METHODS: A total of 35 eyes were included in the study for each group of normal control, PAC, and PACG patients from eye clinics in Kota Bharu, state of Kelantan, Malaysia, from January 2007 to November 2009. The PAC and PACG patients were divided into thin and thick CCT groups. They were followed up for 12 to 18 months for visual field progression assessment with their mean Advanced Glaucoma Intervention Study (AGIS) score.

    RESULTS: The CCT was 516.8 ± 26.0 µm for PAC and 509.7 ± 27.4 µm for PACG. Both were significantly thinner compared with the control group with CCT of 540 ± 27.8 µm (P < 0.001). There was a statistically significant increase in the mean AGIS score after 12.9 ± 1.7 months of follow-up in the thin CCT group for PACG (P = 0.002). However, no significant increase in the mean AGIS score was found for the thick CCT group in PACG and for both thin and thick CCT in PAC.

    CONCLUSIONS: The PAC and PACG had statistically significant thinner CCT compared with the controls. Thin CCT was associated with visual field progression based on the mean AGIS score in PACG.

    Matched MeSH terms: Glaucoma, Open-Angle/diagnosis*; Glaucoma, Open-Angle/physiopathology
  5. Tajunisah I, Reddy SC, Fathilah J
    Graefes Arch Clin Exp Ophthalmol, 2007 Dec;245(12):1851-7.
    PMID: 17901971
    BACKGROUND: A case-controlled prospective study was conducted to evaluate the diurnal variation of intraocular pressure (IOP); the mean, the amplitude of variation and the peak and trough times of pressure readings in the suspected open-angle glaucoma patients as compared with a control group. We also looked at the outcome of these suspects after diurnal variation of IOP measurements.

    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.

    Matched MeSH terms: Glaucoma, Open-Angle/diagnosis; Glaucoma, Open-Angle/physiopathology*
  6. Sumasri K, Raju P, Aung T, Tin A, Wong TY
    Am J Ophthalmol, 2008 Apr;145(4):766-7; author reply 767.
    PMID: 18358854 DOI: 10.1016/j.ajo.2007.12.028
    Matched MeSH terms: Glaucoma, Open-Angle/diagnosis; Glaucoma, Open-Angle/ethnology*
  7. Subramaniam S, Jeoung JW, Lee WJ, Kim YK, Park KH
    Jpn. J. Ophthalmol., 2018 Nov;62(6):634-642.
    PMID: 30229404 DOI: 10.1007/s10384-018-0620-7
    PURPOSE: To compare the diagnostic capability of three-dimensional (3D) neuro-retinal rim thickness (NRR) with existing optic nerve head and retinal nerve fiber layer (RNFL) scan parameters using high-definition optical coherence tomography (HD-OCT).

    DESIGN: Retrospective study.

    METHODS: Based on the mean deviation (MD) of the Humphrey Field Analyzer (HFA), the 152 subjects were categorized into mild (MD > - 6 dB, 100), moderate (MD - 6 to - 12 dB, 26), and severe (MD glaucoma. The HD-OCT values of NRR, RNFL and ganglion cell inner plexiform layer (GCIPL) thicknesses, along with those of other parameters (rim area, disc area) were obtained, and the average NRR thickness was calculated.

    RESULTS: For all of the HD-OCT parameters, RNFL thickness showed a higher area under the ROC (AUROC) curve (range: 0.937-1.000) than did NRR thickness (range: 0.827-1.000). There were significant RNFL, NRR, and GCIPL AUROC curve differences among the mild, moderate and severe glaucoma groups. RNFL thickness for mild glaucoma showed a significantly larger area than did NRR thickness [area difference: 0.110 (± 0.025); p value glaucoma.

    CONCLUSION: RNFL thickness remains significantly better than 3D NRR thickness in terms of glaucoma-diagnostic capability in HD-OCT.

    Matched MeSH terms: Glaucoma, Open-Angle/diagnosis*; Glaucoma, Open-Angle/physiopathology
  8. Singh M, Kaur B
    Int Ophthalmol, 1992 May;16(3):163-6.
    PMID: 1452420
    Postural behaviour of intraocular pressure (IOP) was studied in 29 glaucomatous eyes before and after argon laser trabeculoplasty (ALT) and compared with that of 60 normal eyes. Although argon laser trabeculoplasty was successful in lowering the IOP below 21 mm Hg, it produced little effect on the postural behaviour of the IOP. No significant change was observed in the amplitude of postural rise of IOP in ALT treated eyes.
    Matched MeSH terms: Glaucoma, Open-Angle/physiopathology*; Glaucoma, Open-Angle/surgery
  9. Singh M, Kaur B
    Int Ophthalmol, 1987 Jun;10(3):161-5.
    PMID: 3596909
    Twenty two Asian eyes suffering from open angle glaucoma were treated by argon laser trabeculoplasty and were followed for an average of eleven months. 77.27% of eyes were controlled with ALT alone. The pressure lowering effect of argon laser trabeculoplasty in this series was found to be consistent. Argon laser trabeculoplasty may become the preferred method of treating open angle glaucoma in the Asian population.
    Matched MeSH terms: Glaucoma, Open-Angle/surgery*
  10. Sidek S, Ramli N, Rahmat K, Ramli NM, Abdulrahman F, Kuo TL
    Eur Radiol, 2016 Dec;26(12):4404-4412.
    PMID: 26943134
    OBJECTIVE: To compare the metabolite concentration of optic radiation in glaucoma patients with that of healthy subjects using Proton Magnetic Resonance Spectroscopy (1H-MRS).

    METHODS: 1H-MRS utilising the Single-Voxel Spectroscopy (SVS) technique was performed using a 3.0Tesla MRI on 45 optic radiations (15 from healthy subjects, 15 from mild glaucoma patients, and 15 from severe glaucoma patients). A standardised Volume of Interest (VOI) of 20 × 20 × 20 mm was placed in the region of optic radiation. Mild and severe glaucoma patients were categorised based on the Hodapp-Parrish-Anderson (HPA) classification. Mean and multiple group comparisons for metabolite concentration and metabolite concentration ratio between glaucoma grades and healthy subjects were obtained using one-way ANOVA.

    RESULTS: The metabolite concentration and metabolite concentration ratio between the optic radiations of glaucoma patients and healthy subjects did not demonstrate any significant difference (p > 0.05).

    CONCLUSION: Our findings show no significant alteration of metabolite concentration associated with neurodegeneration that could be measured by single-voxel 1H-MRS in optic radiation among glaucoma patients.

    KEY POINTS: • Glaucoma disease has a neurodegenerative component. • Metabolite changes have been observed in the neurodegenerative process in the brain. • Using SVS, no metabolite changes in optic radiation were attributed to glaucoma.

    Matched MeSH terms: Glaucoma, Open-Angle/pathology*
  11. Shin HC, Subrayan V, Tajunisah I
    J Cataract Refract Surg, 2010 Aug;36(8):1289-95.
    PMID: 20656150 DOI: 10.1016/j.jcrs.2010.02.024
    PURPOSE: To evaluate changes in anterior chamber depth (ACD) and intraocular pressure (IOP) after phacoemulsification in eyes with occludable angles and compare the results with those in eyes with normal open angles.
    SETTING: Eye Clinic, Ipoh General Hospital, Ipoh, Perak, Malaysia.
    METHODS: Patients with nonglaucomatous eyes with open angles or with occludable angles were recruited. Ocular biometric measurements (ACD, axial length [AL], lens thickness and position) and IOP (tonometry) were performed preoperatively and 1 day and 1, 4, 9, and 12 weeks postoperatively.
    RESULTS: The open-angle group and occludable-angle group each comprised 35 patients. The occludable-angle group had a shallower ACD, shorter AL, thicker and relatively anterior lens position, and higher IOP preoperatively; postoperatively, there was a significant increase in ACD and a significant reduction in IOP (Popen-angle group (14.52 +/- 2.65 mm Hg) (Popen-angle group. The IOP decrease in the occludable-angle group was inversely related to the preoperative IOP (P
    Matched MeSH terms: Glaucoma, Open-Angle/physiopathology
  12. Ramli NM, Sidek S, Rahman FA, Peyman M, Zahari M, Rahmat K, et al.
    Graefes Arch Clin Exp Ophthalmol, 2014 Jun;252(6):995-1000.
    PMID: 24770532 DOI: 10.1007/s00417-014-2622-6
    PURPOSE: To measure optic nerve (ON) volume using 3 T magnetic resonance imaging (MRI), to correlate ON volume with retinal nerve fiber layer (RNFL) thickness, and to determine the viability of MRI as an objective tool in distinguishing glaucoma severity.

    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 glaucoma.

    CONCLUSIONS: MRI measured optic nerve volume is a reliable method of assessing glaucomatous damage beyond the optic nerve head. A value of 236 mm(3) and below can be used to define severe glaucoma.

    Matched MeSH terms: Glaucoma, Open-Angle/classification; Glaucoma, Open-Angle/diagnosis*
  13. Patel DK, Ali NA, Iqbal T, Subrayan V
    Ann Ophthalmol (Skokie), 2008;40(3-4):177-9.
    PMID: 19230359
    Colloid cysts are rare intracranial tumors most commonly found in the third ventricle. We present a case of colloid cyst of the third ventricle that manifested as bilateral advance optic disc cupping, superior hemifield defects in the visual fields and normal intraocular pressure.
    Matched MeSH terms: Glaucoma, Open-Angle/diagnosis*
  14. Ong LB, Liza-Sharmini AT, Chieng LL, Cheong MT, Vengadasalam SR, Shin HC, et al.
    J Ocul Pharmacol Ther, 2005 Oct;21(5):388-94.
    PMID: 16245965
    The aim of this study was to determine the effectiveness of timolol gel-forming solution as a monotherapy and to compare the efficacy of timolol gel-forming solution morning instillation versus at night application in Asians with newly diagnosed open-angle glaucoma.
    Matched MeSH terms: Glaucoma, Open-Angle/drug therapy*
  15. Nurul Hanim Nasaruddin, Nurul Hanim Nasaruddin, Ahmad NazlimYusoff, Sharanjeet, Kaur
    MyJurnal
    The purpose of this study was to characterize, differentiate and correlate visual field and brain activation in visual cortex
    for normal, glaucoma suspect (GS) and primary open angle glaucoma (POAG) participants using Standard Automated
    Perimetry (SAP) and functional Magnetic Resonance Imaging (fMRI) respectively. The fMRI scans and SAP test were both
    carried out in Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM). Two types of black-and-white checkerboard
    pattern were displayed to the participants during the fMRI scans. The fMRI data were analyzed using WFU pickatlas
    toolbox targeting visual cortex area. The results showed that there was no significant difference in number of activated
    voxel between the three groups in visual cortex (BA 17, 18 and 19) while viewing all the given stimuli (p > 0.05). The
    pattern standard deviation (PSD) of SAP for visual field also revealed no significant differences (p > 0.05) in all groups of
    participants. However, negative correlation between PSD and fMRI activation was observed. The PSD values increased with
    a decrease in fMRI activation. With reference to visual field analysis, the results suggest that glaucomatous neuropathy of
    POAG patients has led to a gradual decrease in visual cortex activation and a gradual increase in PSD.
    Matched MeSH terms: Glaucoma, Open-Angle
  16. Mushawiahti, M., Syed Zulkifli, S.Z., Aida Zairani, M.Z., Faridah, H.
    Medicine & Health, 2011;6(2):107-113.
    MyJurnal
    Central corneal thickness plays a major role in the management of many types of glaucoma. Therefore, our aim is to determine the relationship between the severity of glaucoma measured by optical coherence tomography (OCT) and central corneal thickness (CCT) among normal tension and high tension glaucoma patients. This is an observational cross sectional study on 190 patients carried out in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Three groups of patients were identified; 60 normal tension glaucoma (NTG), 61 primary open angle glaucoma (POAG) and 69 control. Patients were identified based on the glaucomatous visual field changes and previous record of intraocular pressure before treatment. Visual acuity and intraocular pressure measurements were recorded. Specular microscope was used to measure the CCT and the severity of glaucoma was evaluated objectively based on the retinal nerve fibre layer (RNFL) thickness using optical coherence tomography. Results showed NTG patients had significantly thinner cornea, 503.07±32.27µm compared to the control group, 517.45±31.74 µm (p=0.012).
    However, there was no significant difference between the CCT of POAG and NTG groups (p=0.386).Retinal nerve fibre layer (RNFL) thickness was significantly different between the glaucoma and the control groups (p
    Matched MeSH terms: Glaucoma, Open-Angle
  17. Mudassar Imran Bukhari S, Yew KK, Thambiraja R, Sulong S, Ghulam Rasool AH, Ahmad Tajudin LS
    Ther Adv Ophthalmol, 2019 08 22;11:2515841419868100.
    PMID: 31489400 DOI: 10.1177/2515841419868100
    Purpose: To determine the role of microvascular endothelial dysfunction as risk factor for primary open angle glaucoma.

    Methods: A cross-sectional study was conducted involving 114 Malay patients with POAG seen at the eye clinic of Hospital Universiti Sains Malaysia. Patients aged between 40 and 80 years who were diagnosed with other types of glaucoma, previous glaucoma filtering surgery or other surgeries except uncomplicated cataract surgery and pterygium surgery were excluded. A total of 101 patients who were followed up for dry eyes, age-related cataracts or post cataracts extraction surgery were recruited as control subjects. Those with family history of glaucoma or glaucoma suspect were excluded. Microvascular endothelial function was assessed using laser Doppler fluximetry and the process of iontophoresis. Iontophoresis with acetylcholine (ACh) and sodium nitroprusside (SNP) was used to measure microvascular endothelium-dependent and endothelium-independent vasodilatations, respectively.

    Results: In general, POAG patients demonstrated lower ACh% and AChmax values compared with controls. There was significant difference in microvascular endothelial function [ACh%: mean, 95% confidence interval = 503.1 (378.0, 628.3), and AChmax: mean, 95% confidence interval = 36.8 (30.2, 43.5)] between primary open angle glaucoma cases (p 

    Matched MeSH terms: Glaucoma, Open-Angle
  18. Mimivati Z, Nurliza K, Marini M, Liza-Sharmini A
    Mol Vis, 2014;20:714-23.
    PMID: 24883016
    PURPOSE:
    To screen for mutations in the coding region of the myocilin (MYOC) gene in a large Malay family with juvenile-onset open angle glaucoma (JOAG).

    METHODS:
    A total of 122 family members were thoroughly examined and screened for JOAG. Venipuncture was conducted. Genomic DNA was extracted from peripheral blood leukocytes. The presence of a mutation and a polymorphism was ascertained with PCR amplification followed by the direct sequencing technique.

    RESULTS:
    Thirty-two of the 122 screened family members were identified to have JOAG (11 new cases and 21 known cases). An autosomal dominant inheritance pattern with incomplete penetrance was observed. A C→A substitution at position 1440 in exon 3 that changes asparagine (AAC) to lysine (AAA) was identified in affected family members except two probands (III:5 and IV:6). Six probands were identified as having the Asn480Lys mutation but have not developed the disease yet. An intronic polymorphism IVS2 730 +35 G>A was also identified. There was a significant association between Asn480Lys (p<0.001) and IVS2 730+35G>A (p<0.001) in the affected and unaffected probands in this family.

    CONCLUSIONS:
    The Asn480Lys mutation and the IVS2 730+35 G>A polymorphism increased susceptibility to JOAG in this large Malay pedigree. Identifying the MYOC mutations and polymorphisms is important for providing presymptomatic molecular diagnosis.
    Matched MeSH terms: Glaucoma, Open-Angle/genetics*; Glaucoma, Open-Angle/epidemiology*; Glaucoma, Open-Angle/physiopathology
  19. Md Noh SM, Sheikh Abdul Kadir SH, Bannur ZM, Froemming GA, Abdul Hamid Hasani N, Mohd Nawawi H, et al.
    Exp Eye Res, 2014 Oct;127:236-42.
    PMID: 25139730 DOI: 10.1016/j.exer.2014.08.005
    Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. The effects of this humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player of post trabeculectomy scar formation, are not fully understood. This study was conducted to understand the effects of ranibizumab on extracellular matrix production by HTF. The effect of ranibizumab on HTF proliferation and cell viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions. Supernatants and cell lysates from samples were assessed for collagen type 1 alpha 1 and fibronectin mRNA and protein level using quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death under serum-free culture conditions (p 
    Matched MeSH terms: Glaucoma, Open-Angle/surgery
  20. Marcus AJ, Iezhitsa I, Agarwal R, Vassiliev P, Spasov A, Zhukovskaya O, et al.
    Eur J Pharmacol, 2019 May 05;850:75-87.
    PMID: 30716317 DOI: 10.1016/j.ejphar.2019.01.059
    Ocular hypertension is believed to be involved in the etiology of primary open-angle glaucoma. Although many pharmaceutical agents have been shown to be effective for the reduction of intraocular pressure (IOP), a significant opportunity to improve glaucoma treatments remains. Thus, the aims of the present study were: (1) to evaluate the IOP-lowering effect of four compounds RU-551, RU-555, RU-839 (pyrimido[1,2-a]benzimidazole), and RU-615 (imidazo[1,2-a]benzimidazole) on steroid-induced ocular hypertension in rats after single drop and chronic applications; and (2) to test in silico and in vitro conventional rho-associated kinase (ROCK) inhibitory activity of the selected compound. This study demonstrated that RU-551, RU-555, RU-839, and RU-615 significantly reduced IOP in Sprague Dawley rats with dexamethasone (DEXA) induced ocular hypertension after single drop administration (0.1%), however RU-615 showed the best IOP lowering effect as indicated by maximum IOP reduction of 22.32% from baseline. Repeated dose topical application of RU-615 caused sustained reduction of IOP from baseline throughout the 3 weeks of treatment with maximum IOP reduction of 30.31% on day 15. This study also showed that the steroid-induced increase in IOP is associated with increased retinal oxidative stress and significant retinal ganglion cells (RGCs) loss. Prolonged treatment with RU-615 over 3 weeks results in normalization of IOP in DEXA-treated rats with partial restoration of retinal antioxidant status (catalase, glutathione and superoxide dismutase) and subsequent protective effect against RGC loss. Thus, IOP lowering activity of RU-615 together with antioxidant properties might be the factors that contribute to prevention of further RGC loss. In vitro part of this study explored the ROCK inhibitory activity of RU-615 using dexamethasone-treated human trabecular meshwork cells as a possible mechanism of action of its IOP lowering activity. However, this study didn't show conventional ROCK inhibition by RU-615 which was later confirmed by in silico consensus prediction. Therefore, in the future studies it is important to identify the upstream target receptors for RU-615 and then delineate the involved intracellular signalling pathways which are likely to be other than ROCK inhibition.
    Matched MeSH terms: Glaucoma, Open-Angle
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