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  1. Sharmini AT, Yin NY, Lee SS, Jackson AL, Stewart WC
    J Ocul Pharmacol Ther, 2009 Feb;25(1):71-5.
    PMID: 19232007 DOI: 10.1089/jop.2008.0061
    The aim of this study was to evaluate risk factors for progression in chronic angle-closure glaucoma (CACG) patients.
    Matched MeSH terms: Ocular Hypertension/diagnosis; Ocular Hypertension/etiology; Ocular Hypertension/physiopathology*
  2. Agarwal P, Agarwal R
    Expert Opin Ther Targets, 2018 07;22(7):629-638.
    PMID: 29883239 DOI: 10.1080/14728222.2018.1486822
    INTRODUCTION: Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.
    Matched MeSH terms: Ocular Hypertension/drug therapy; Ocular Hypertension/pathology
  3. 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: Ocular Hypertension/diagnosis; Ocular Hypertension/physiopathology
  4. Ashworth J, Flaherty M, Pitz S, Ramlee A
    Acta Ophthalmol, 2015 Mar;93(2):e111-7.
    PMID: 25688487 DOI: 10.1111/aos.12607
    Purpose: The mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders, characterized by the accumulation of glycosaminoglycans within multiple organ systems including the eye. This study aimed to determine the prevalence of glaucoma in patients with MPS, as well as the characteristics, diagnosis and management of patients with MPS and glaucoma.
    Methods: A multicentre retrospective case-note review was carried out by ophthalmologists from four tertiary referral centres to identify patients with MPS who had been treated for glaucoma. Clinical ophthalmological data were collected using standardized data collection forms.
    Results: Fourteen patients were identified (27 eyes) of 294 patients with MPS. The prevalence of glaucoma ranged from 2.1% to 12.5%. The median age at diagnosis of glaucoma was 8 years. Diagnostic evaluation of glaucoma was incomplete in many patients: intraocular pressure was documented in all eyes, but optic disc appearance was only assessed in 67%, central corneal thickness in 26%, visual fields in 19% and iridocorneal angle in 15%.
    Conclusions: Patients with MPS need regular assessment for possible glaucoma including during childhood. Multiple factors contribute to the challenges of assessment, diagnosis and monitoring of glaucoma in these patients.
    Keywords: Hunter; Hurler; Hurler-Scheie; Maroteaux-Lamy; Morquio; Scheie; glaucoma; mucopolysaccharidosis; prevalence.
    Matched MeSH terms: Ocular Hypertension/diagnosis*; Ocular Hypertension/epidemiology; Ocular Hypertension/therapy
  5. 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: Ocular Hypertension/diagnosis; Ocular Hypertension/epidemiology; Ocular Hypertension/physiopathology*
  6. Khaw KW, Jalaludin MY, Suhaimi H, Harun F, Subrayan V
    J AAPOS, 2010 Aug;14(4):356-7.
    PMID: 20637667 DOI: 10.1016/j.jaapos.2010.04.009
    Ocular hypertension caused by endogenous Cushing syndrome from an ectopic adrenocorticotropic hormone-producing tumor is rare. We report an 11-year-old boy who presented with intraocular pressures (IOPs) of 50 mm Hg in both eyes. Surgical resection of the tumor was performed with subsequent normalization of serum cortisol and IOP levels.
    Matched MeSH terms: Ocular Hypertension/diagnosis; Ocular Hypertension/etiology*; Ocular Hypertension/physiopathology
  7. Razali N, Agarwal R, Agarwal P, Kumar S, Tripathy M, Vasudevan S, et al.
    Clin Exp Ophthalmol, 2015 Jan-Feb;43(1):54-66.
    PMID: 24995479 DOI: 10.1111/ceo.12375
    BACKGROUND: Steroid-induced ocular hypertension is currently treated in the same way as primary open-angle glaucoma. However, the treatment is often suboptimal and is associated with adverse effects. We evaluated the oculohypotensive effects of topical trans-resveratrol in rats with steroid-induced ocular hypertension and involvement of adenosine receptors (AR) in intraocular pressure (IOP) lowering effect of trans-resveratrol.
    METHODS: The oculohypotensive effect of unilateral single-drop application of various concentrations of trans-resveratrol was first studied in oculonormotensive rats. Concentration with maximum effect was similarly studied in rats with steroid-induced ocular hypertension. Involvement of AR was studied by observing the alterations of IOP in response to trans-resveratrol after pretreating animals with AR subtype-specific antagonists. Additionally, we used computational methods, including 3D modelling, 3D structure generation and protein-ligand interaction, to determine the AR-trans-resveratrol interaction.
    RESULTS: All concentrations of trans-resveratrol produced significant IOP reduction in normotensive rat eyes. Maximum mean IOP reduction of 15.1% was achieved with trans-resveratrol 0.2%. In oculohypertensive rats, trans-resveratrol 0.2% produced peak IOP reduction of 25.2%. Pretreatment with A₁ antagonist abolished the oculohypotensive effect of trans-resveratrol. Pretreatment with A₃ and A₂A AR antagonists produced significant IOP reduction in both treated and control eyes, which was further augmented by trans-resveratrol application in treated eyes. Computational studies showed that trans-resveratrol has highest affinity for A₂B and A₁, followed by A2A and A₃ AR.
    CONCLUSION: Topically applied trans-resveratrol reduces IOP in rats with steroid-induced ocular hypertension. Trans-resveratrol-induced oculohypotension involves its agonistic activity at the A₁ AR.
    KEYWORDS: adenosine receptors; docking simulation; intraocular pressure; resveratrol; topical
    Matched MeSH terms: Ocular Hypertension/chemically induced; Ocular Hypertension/drug therapy*; Ocular Hypertension/metabolism
  8. Razali N, Agarwal R, Agarwal P, Kapitonova MY, Kannan Kutty M, Smirnov A, et al.
    Eur J Pharmacol, 2015 Feb 15;749:73-80.
    PMID: 25481859 DOI: 10.1016/j.ejphar.2014.11.029
    Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.
    Matched MeSH terms: Ocular Hypertension/chemically induced*; Ocular Hypertension/metabolism; Ocular Hypertension/pathology; Ocular Hypertension/physiopathology
  9. Razali N, Agarwal R, Agarwal P, Tripathy M, Kapitonova MY, Kutty MK, et al.
    Exp Eye Res, 2016 Feb;143:9-16.
    PMID: 26424219 DOI: 10.1016/j.exer.2015.09.014
    Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.
    Matched MeSH terms: Ocular Hypertension/chemically induced; Ocular Hypertension/drug therapy*; Ocular Hypertension/enzymology; Ocular Hypertension/pathology
  10. Shatriah I, Norazizah MA, Wan-Hitam WH, Wong AR, Yunus R, Leo SW
    Pediatr Dermatol, 2013 Jan-Feb;30(1):151-4.
    PMID: 22329437 DOI: 10.1111/j.1525-1470.2011.01618.x
    High intraocular pressure is a rare ophthalmic condition associated with infantile hemangiomas that involves the orbit, eyelid, or both. Here, we describe a patient with extensive facial and orbital infantile hemangiomas associated with high intraocular pressure in the affected eye. The prompt management of this challenging condition is essential.
    Matched MeSH terms: Ocular Hypertension/etiology*; Ocular Hypertension/physiopathology
  11. Md Din N, Tomkins-Netzer O, Talat L, Taylor SR, Isa H, Bar A, et al.
    J Glaucoma, 2016 07;25(7):598-604.
    PMID: 26900824 DOI: 10.1097/IJG.0000000000000379
    PURPOSE: To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness.

    PATIENTS AND METHODS: Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP.

    RESULTS: IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 μm) compared with NU eyes (142.1±32.0 μm, P=0.043).

    CONCLUSIONS: Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

    Study site: Moorfields Eye Hospital, London
    Matched MeSH terms: Ocular Hypertension/chemically induced; Ocular Hypertension/physiopathology
  12. Renu Agarwal, SK Gupta, Sushma Srivastava, Rohit Saxena
    MyJurnal
    Introduction: Ocimum basilicum (OB), a herb known for its antihypertensive,
    anticholinesterase and antioxidant properties was investigated for possible intraocular
    pressure (IOP) lowering effects in rabbits with ocular hypertension (OHT). Methods: The
    IOP lowering effect of a single drop of OB extract (OBE) was evaluated in oculonormotensive
    rabbits using three concentrations (0.25, 0.5 and 1% w/v). The concentration showing
    maximum IOP reduction was further evaluated in rabbits with water-loading and steroidinduced OHT. Results: IOP lowering effect of OBE 0.5% in oculonormotensive rabbit eyes
    was significantly greater compared to OBE 0.25% (p0.05) to
    OBE 1%. Therefore, 0.5% concentration was selected for further evaluation. Pretreatment
    with OBE (0.5%) caused significantly lower increase in IOP after water loading amounting to
    23.39% above baseline as compared to 54.00% in control eye, 15 minutes post water
    loading. At 60 minutes, post water loading, mean IOP rise was 95.12% and 63.58% in
    control and test eyes, respectively. Significant difference between the mean IOP of two eyes
    persisted during the 2nd hr. In rabbits with steroid induced OHT, OBE 0.5% produced a
    mean IOP reduction of 24.73% at the end of first hr and the mean peak IOP reduction of
    31.63% was observed at the end of 2 hr. A significant difference between the IOP of test and
    control eyes persisted from 1 to 6 hr. Conclusions: Ocimum basilicum seed extract showed
    significant IOP lowering effect in rabbits with water loading and steroid induced OHT,
    however, its utility as an effective antiglaucoma medication needs further investigations.
    Matched MeSH terms: Ocular Hypertension
  13. 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: Ocular Hypertension
  14. Abdullah SN, Sanderson GF, Husni MA, Maddess T
    PMID: 32034583 DOI: 10.1007/s10633-020-09750-7
    PURPOSE: To compare two forms of perimetry that use large contrast-modulated grating stimuli in terms of: their relative diagnostic power, their independent diagnostic information about glaucoma and their utility for mfVEPs. We evaluated a contrast-threshold mfVEP in normal controls using the same stimuli as one of the tests.

    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.

    Matched MeSH terms: Ocular Hypertension/physiopathology
  15. Razali N, Agarwal R, Agarwal P, Froemming GRA, Tripathy M, Ismail NM
    Eur J Pharmacol, 2018 Nov 05;838:1-10.
    PMID: 30171854 DOI: 10.1016/j.ejphar.2018.08.035
    Trans-resveratrol was earlier shown to lower intraocular pressure (IOP) in rats; however, its mechanisms of action remain unclear. It has been shown to modulate adenosine receptor (AR) and TGF-β2 signaling, both of which play a role in regulating IOP. Hence, we investigated effects of trans-resveratrol on AR and TGF-β2 signaling. Steroid-induced ocular hypertensive (SIOH) rats were pretreated with A1AR, phospholipase C (PLC) and ERK1/2 inhibitors and were subsequently treated with single drop of trans-resveratrol. Metalloproteinases (MMP)-2 and -9 were measured in aqueous humor (AH). In another set of experiments, effect of trans-resveratrol on AH level of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) was determined after single and multiple drop administration in SIOH rats. Effect of trans-resveratrol on ARs expression, PLC and pERK1/2 activation and MMPs, tPA and uPA secretion was determined using human trabecular meshwork cells (HTMC). Further, effect of trans-resveratrol on TGF-β2 receptors, SMAD signaling molecules and uPA and tPA expression by HTMC was determined in the presence and absence of TGF-β2. Pretreatment with A1AR, PLC and ERK1/2 inhibitors antagonized the IOP lowering effect of trans-resveratrol and caused significant reduction in the AH level of MMP-2 in SIOH rats. Trans-resveratrol increased A1AR and A2AAR expression, cellular PLC, pERK1/2 levels and MMP-2, tPA and uPA secretion by HTMC. Additionally, it produced TGFβRI downregulation and SMAD 7 upregulation. In conclusion, IOP lowering effect of trans-resveratrol involves upregulation of A1AR expression, PLC and ERK1/2 activation and increased MMP-2 secretion. It downregulates TGFβRI and upregulates SMAD7 hence, inhibits TGF-β2 signaling.
    Matched MeSH terms: Ocular Hypertension/chemically induced; Ocular Hypertension/drug therapy*
  16. Din NM, Taylor SR, Isa H, Tomkins-Netzer O, Bar A, Talat L, et al.
    JAMA Ophthalmol, 2014 Jul;132(7):859-65.
    PMID: 24789528 DOI: 10.1001/jamaophthalmol.2014.404
    IMPORTANCE: Uveitic glaucoma is among the most common causes of irreversible visual loss in uveitis. However, glaucoma detection can be obscured by inflammatory changes.

    OBJECTIVE: To determine whether retinal nerve fiber layer (RNFL) measurement can be used to detect glaucoma in uveitic eyes with elevated intraocular pressure (IOP).

    DESIGN, SETTING, AND PARTICIPANTS: Comparative case series of RNFL measurement using optical coherence tomography performed from May 1, 2010, through October 31, 2012, at a tertiary referral center. We assigned 536 eyes with uveitis (309 patients) in the following groups: normal contralateral eyes with unilateral uveitis (n = 72), normotensive uveitis (Uv-N) (n = 143), raised IOP and normal optic disc and/or visual field (Uv-H) (n = 233), and raised IOP and glaucomatous disc and/or visual field (Uv-G) (n = 88).

    EXPOSURES: Eyes with uveitis and elevated IOP (>21 mm Hg) on at least 2 occasions.

    MAIN OUTCOMES AND MEASURES: Comparison of RNFL values between groups of eyes and correlation with clinical data; risk factors for raised IOP, glaucoma, and RNFL thinning.

    RESULTS: Mean (SD) global RNFL was thicker in Uv-N (106.4 [21.4] µm) compared with control (96.0 [9.0] µm; P ocular hypertension, is in fact occurring. Measurement of RNFL may detect signs of damage before disc or visual field changes and therefore identifies a subgroup that should receive more aggressive treatment.

    Matched MeSH terms: Ocular Hypertension/diagnosis*
  17. Kashiwagi K, Chono E, Koesters S, Yap PS
    BMC Ophthalmol, 2020 Jun 10;20(1):223.
    PMID: 32522181 DOI: 10.1186/s12886-020-01508-8
    BACKGROUND: Poor persistence with glaucoma therapy can lead to disease progression and subsequent blindness. Persistence with second-line glaucoma combination treatment in a Japanese real-world setting and whether it differed from fixed and unfixed combination drugs was investigated.

    METHODS: This was a retrospective, non-interventional, cohort study using data from a Japanese medical claims database. Patients with glaucoma aged ≥20 years with a first drug claim for glaucoma treatment between 01 July 2005 and 30 October 2014 and with data for > 6 months before and after this first prescription were included. The primary endpoint was duration of drug persistence among glaucoma patients with and without the use of fixed combination drugs in the year following initiation of second-line combination treatment.

    RESULTS: Of 1403 patients included in the analysis, 364 (25.94%) received fixed combination drugs and 1039 (74.06%) received unfixed combination drugs as second-line treatment. Baseline characteristics were generally comparable between the groups. A total of 39.01% of patients on fixed combination drugs, compared with 41.67% of patients on unfixed combination drugs, persisted on their glaucoma drugs 12 months post second-index date. Median persistence durations for the fixed combination drugs and unfixed combination drugs groups were 6 (95% confidence interval [CI]: 5-8) and 7 months (95% CI 6-9), respectively. Patients who received prostaglandin analogs (PGAs) were the most persistent with their treatment (n = 99, 12.84%). Patients diagnosed with primary open-angle glaucoma were less likely to experience treatment modification (hazard ratio [HR]: 0.800, 95% CI 0.649-0.986, P = 0.036), while those diagnosed with secondary glaucoma were more likely to experience treatment modification (HR: 1.678, 95% CI 1.231-2.288, P = 0.001) compared with glaucoma suspects.

    CONCLUSIONS: In this retrospective claims database study, the persistence rate of second-line glaucoma combination treatment was low, with no difference in persistence between glaucoma patients receiving unfixed combination drugs compared with fixed combination drugs. Patients on PGA showed greater persistence rates compared with other treatments.

    Matched MeSH terms: Ocular Hypertension/drug therapy
  18. 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: Ocular Hypertension
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