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Future target molecules in antiglaucoma therapy: tgf-Beta may have a role to play

Agarwal R, Agarwal P

Ophthalmic Res, 2010;43(1):1-10.
PMID: 19829006 DOI: 10.1159/000246571

Glaucoma, a leading cause of irreversible blindness, is often associated with increased resistance to aqueous outflow in trabecular tissue. Increased outflow resistance has been attributed to increased extracellular matrix (ECM) deposition in trabecular tissue. A critical balance between the synthesis and breakdown of the components of extracellular tissue is important in keeping the intraocular pressure within the normal range. Multiple mechanisms have been shown to affect ECM turnover in trabecular tissue. In this review, we examine the related literature to understand the role of TGF-beta in ECM turnover, in the development and progression of glaucoma, and in possible therapeutic strategies that can be devised by targeting the TGF-beta signaling pathways.

Matched MeSH terms: Intraocular Pressure/drug effects
Fulltext Persistence and treatment patterns of fixed combination drugs for glaucoma: a retrospective claims database study in Japan

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: Intraocular Pressure/drug effects*
Difference in glaucoma progression between the first and second eye after consecutive bilateral glaucoma surgery in patients with bilateral uveitic glaucoma

Din NM, Talat L, Isa H, Tomkins-Netzer O, Barton K, Lightman S

Graefes Arch Clin Exp Ophthalmol, 2016 Dec;254(12):2439-2448.
PMID: 27495303

PURPOSE: To determine whether the second eyes (SE) of patients with bilateral uveitic glaucoma undergoing filtration surgery have more glaucomatous progression in terms of visual acuity, visual field (VF) and optic nerve changes compared to the first eyes (FE).
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.

Matched MeSH terms: Intraocular Pressure/physiology*
Role of adenosine receptors in resveratrol-induced intraocular pressure lowering in rats with steroid-induced ocular hypertension

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: Intraocular Pressure/drug effects*
Three dimensional neuro-retinal rim thickness and retinal nerve fiber layer thickness using high-definition optical coherence tomography for open-angle glaucoma

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

Matched MeSH terms: Intraocular Pressure*
Fulltext Clinical presentation, severity and progression of primary angle closure in malays

Liza-Sharmini AT, Sharina YN, Dolaboladi AJ, Zaid NA, Azhany Y, Zunaina E

Med J Malaysia, 2014 Feb;69(1):21-6.
PMID: 24814624 MyJurnal

INTRODUCTION: There is limited knowledge on primary angle closure (PAC) in Malays. Understanding the clinical presentation and progression of PAC in Malays is important for prevention of blindness in Southeast Asia.

MATERIAL AND METHODS: A retrospective record review study was conducted on Malay patients seen in the eye clinic of two tertiary hospitals in Kelantan, Malaysia. Based on the available data, Malay patients re-diagnosed as primary angle closure suspect (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG) based on the International Society Geographical Epidemiological classification. Clinical data was collected from initial presentation including the presence of acute primary angle closure until at least 5 years follow up. Progression was defined based on gonioscopic changes, vertical cup to disc ratio (VCDR), intraocular pressure (IOP) and Humphrey visual field (HVF) analysis. Progression and severity of PACG was defined based Hodapp-Parrish-Anderson classification on reliable HVF central 24-2 or 30-2 analysis.

RESULTS: A total of 100 patients (200 eyes) with at least 5 years follow up were included. 94 eyes (47%) presented with APAC. During initial presentation, 135 eyes (67.5%) were diagnosed with glaucomatous changes with 91 eyes already blind. After 5 years of follow up, 155 eyes (77.5%) progressed. There was 4 times risk of progression in eyes with PAC (p=0.071) and 16 times risk of progression in PACG (p=0.001). Absence of laser peripheral iridotomy was associated with 10 times the risk of progression.

CONCLUSION: Angle closure is common in Malays. Majority presented with optic neuropathy at the initial presentation and progressed further. Preventive measures including promoting public awareness among Malay population is important to prevent blindness.

Study site: Eye clinic, Hospital Universiti Sains Malaysia and Hospital
Raja Perempuan Zainab II

Matched MeSH terms: Intraocular Pressure
Fulltext Assessment of the optic nerve head parameters using Heidelberg retinal tomography III in preterm children

Alshaarawi S, Shatriah I, Zunaina E, Wan Hitam WH

PLoS One, 2014;9(2):e88056.
PMID: 24551076 DOI: 10.1371/journal.pone.0088056

Variations in optic nerve head morphology and abnormal retinal vascular pattern have been described in preterm children using digital image analysis of fundus photograph, optical coherence tomograph and serial funduscopy. We aimed to compare the optic nerve head parameters in preterm and term Malay children using Heidelberg Retinal Tomograph III.

Matched MeSH terms: Intraocular Pressure
Irreversible blindness following intravenous streptokinase

Peyman M, Subrayan V

JAMA Ophthalmol, 2013 Oct;131(10):1368-9.
PMID: 23929315 DOI: 10.1001/jamaophthalmol.2013.4489
Matched MeSH terms: Intraocular Pressure
Colloid cyst of third ventricle mimicking normal tension glaucoma

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: Intraocular Pressure
Prevalence of pseudoexfoliation in Malay population in Singapore

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: Intraocular Pressure
Argon laser trabeculoplasty in Asian eyes

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: Intraocular Pressure
Evaluation of Optic Nerve Head Parameters, Retinal Nerve Fiber Layer Thickness, and Ocular Perfusion Pressure in Migraine Patients

Michael NDB, Hussein A, Abd Halim S, Ab Hamid SA

Cureus, 2019 May 04;11(5):e4599.
PMID: 31309023 DOI: 10.7759/cureus.4599

Background Neurovascular changes occur during the migraine is believed to cause alteration in cerebral and retinal circulation that possible result in damage to the brain and even retina or optic nerve. Retinal nerve fiber layer (RNFL) thickness measurement can be used as an index to assess ganglion cell and retinal nerve fiber damages. The aim of this study was to evaluate the optic nerve head (ONH) parameters, RNFL thickness, and ocular perfusion pressure (OPP) in migraine patients. Methods This was a cross-sectional study, conducted in Hospital Universiti Sains Malaysia, Kelantan from July 2016 to November 2018, involving patients with a confirmed diagnosis of migraine and controls. Ninety-four eyes of 47 migraine patients and 94 eyes of 47 healthy subjects were included in this study. Blood pressure and intraocular pressure were measured and OPP was calculated. ONH parameters and RNFL thickness were measured using optical coherence tomography (OCT) after pupillary dilatation. Statistical analysis was done using Statistical Package for the Social Science (SPSS Inc Version 24). Results With respect to all means values of ONH parameters, there was no statistically significant difference between migraine patients and controls. For RNFL, there were significant reductions in average and superior RNFL thickness on both eyes with adjustment of age and gender (P-value: right eye (RE) average = 0.027; RE superior = 0.034; left eye (LE) average = 0.037; LE superior = 0.031). In view of OPP, there was no significant difference between migraine patients and controls (P-value = 0.172). Weak correlations were found between the ONH parameters and RNFL thickness with OPP, respectively, in migraine patients. Conclusion This study showed no difference in ONH parameters between migraine patients and healthy subjects. There was significant thinning in average and superior RNFL for migraine patients. No difference found in OPP between both groups. ONH parameters and RNFL thickness had a weak correlation with OPP in migraine patients.

Matched MeSH terms: Intraocular Pressure
Ab-Externo Implantation of XEN Gel Stent for Refractory Steroid-Induced Glaucoma After Lamellar Keratoplasty

Tan SY, Md Din N, Mohd Khialdin S, Wan Abdul Halim WH, Tang SF

Cureus, 2021 Feb 12;13(2):e13320.
PMID: 33738163 DOI: 10.7759/cureus.13320

The hazy corneal donor-recipient interface after corneal transplant may cause difficulties when implanting the XEN gel stent via ab-interno approach. We aim to describe XEN gel stent implantation via ab-externo approach in refractory steroid-induced glaucoma after corneal lamellar keratoplasty. Under local anaesthesia, the XEN injector needle was inserted 7 mm behind the limbus with the bevel facing up, directly beneath the conjunctiva and advanced to the marked 2.5 mm scleral entry wound. The needle then pierced the sclera until the needle tip was just visible in the anterior chamber (AC). The slider was pushed until the tip of the XEN stent was seen in the AC. The needle was slowly withdrawn while still pushing the slider to complete stent deployment. Subconjunctival Mitomycin C 0.01% (30 µg/0.3 mL) was then injected posterior to the bleb. Three eyes of three patients with steroid-induced glaucoma after lamellar keratoplasty underwent XEN gel stent implantation via ab-externo approach placed at the superotemporal quadrant. Pre-operatively, all patients had uncontrolled IOP between 30-45 mmHg despite maximum medications and selective laser trabeculoplasty. After XEN gel stent implantation, IOP ranged between 10-17 mmHg with one or two topical antiglaucoma at 12 months. Complications include hypotony maculopathy, stent migration and hyphaema, all of which were successfully managed. Corneal graft remained clear at 12 months. XEN gel stent implantation via ab-externo approach is able to achieve good intraocular pressure (IOP) control without compromising cornea graft in patients with steroid-induced glaucoma after lamellar keratoplasty at 12 months.

Matched MeSH terms: Intraocular Pressure
Fulltext Management of open angle glaucoma: focus on mechanisms of action and adverse drug reactions

Amy Suzana Abu Bakar, Norhafiza Razali, Mohammad Daniel Shafiq Hassan, Renu Agarwal

Journal of Clinical and Health Sciences, 2021;6(1):4-17.
MyJurnal

Glaucoma is an optic neuropathy characterised by optic nerve degeneration associated with
visual field defects. It remains the world’s number one cause of irreversible blindness and
patients usually present at late stage of the disease since it is generally asymptomatic until
severe. The disease is subdivided into primary and secondary with primary open-angle
glaucoma (POAG) being the most common type. At present, lowering the intraocular pressure
(IOP) remains the only proven efficient approach in delaying the onset or preventing the
progression of the disease. Medical treatment with topical antiglaucoma agents is the
treatment of choice in open angle glaucoma. The use of antiglaucoma drugs aims to reduce
IOP by enhancing aqueous humour (AH) outflow, reducing AH production, or both. The choice
to use any available treatment option should be carefully considered in an attempt to maximise
benefits and reducing the risk of developing adverse drug reactions. This review highlights the
six classes of ocular hypotensive agents currently in use for POAG treatment including
prostaglandin analogues; -adrenergic receptor blockers; -2 adrenergic receptor stimulants;
carbonic anhydrase inhibitors; muscarinic receptor stimulants; rho kinase inhibitors with
regards to their mechanism/s of action and potential adverse drug reactions, and
antiglaucoma fixed drug combinations.

Matched MeSH terms: Intraocular Pressure
Fulltext The association between body weight status, sodium intake and blood pressure with intraocular pressure among orang asli adolescents in Semenyih, Selangor

Nurulain Asri, Tasneem Shaari, Mohd Zaki Awg Isa

Journal of Optometry, Eye and Health Research, 2020;2(1):48-56.
MyJurnal

Abnormal intraocular pressure (IOP) if left untreated it can lead to glaucoma and permanent vision loss. However, the correlation between IOP and body weight status, sodium intake, and blood pressure (BP) are unclear among adolescents. This cross-sectional study aimed to determine the relationship between body weight status, sodium intake, and BP with IOP among orang Asli adolescents. A total sample of 50 adolescents of Orang Asli aged 13 to 17 participated in this study. Three days' dietary intake was recorded through 24-hour diet recall to determine the sodium intake. The questionnaire was administered to acquire socio-demographic information, and measurements Body Mass Index (BMI) and BP were done according to standard protocols, and IOP was measured using Tonopen. Data obtained involving 40% boys and 60% girls. Two boys (4%) were underweight, 13 boys (26%) and 17 (34%) girls were normal weight, 4 (8%) boys and 11 (22%) girls were overweight, 1 (2%) boy and 2 (4%) girls were obese. Sixty percent of subjects have exceeded the Lowest-Observed-Adverse-Effect-Level (LOAEL) of 2300 mg of sodium intake. Hypertension stage 1 was found higher than hypertension stage 2 in male and female subjects, with 38% of the female have stage 1 hypertension compared to only 14% in male subjects. 98% of subjects have normal IOP and only 2% of subjects have high IOP. There was a significant association between BMI and IOP (p

Matched MeSH terms: Intraocular Pressure
Fulltext Relationship between central corneal thickness and severity of open angle glaucoma using optical coherence tomography

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: Intraocular Pressure
Fulltext Dramatic response of iris and retinal neovascularisation following usage of intravitreal ranibizumab as pre-operative adjunct in vitrectomy for advanced proliferative diabetic retinopathy

Malisa, A., Mae-Lynn, C.B.

Journal of Surgical Academia, 2011;1(1):61-64.
MyJurnal

A 37-year-old Malay woman presented with progressive deterioration in vision and was diagnosed with advanced proliferative diabetic retinopathy with neovascular glaucoma. Intravitreal ranibizumab injection (an anti-vascular endothelial growth factor) was administered prior to vitrectomy. Slit lamp assessment 2 days post-injection revealed significant regression of both iris and retinal neovascularisation. This resulted in adequate reduction of intra-ocular pressure prior to surgery. In addition, the regression of retinal vessels reduced the risk of intra-operative haemorrhage, thus aiding the surgical excision of the fibrovascular membranes. Periodic post-operative assessment in the first 3 weeks showed minimal inflammation and no recurrence of vitreous haemorrhage. This case illustrates that intravitreal ranibizumab has a role as an adjunct therapy prior to diabetic vitrectomy to significantly reduce the risk of intra-ocular haemorrhage.

Matched MeSH terms: Intraocular Pressure
Fulltext Retinitis punctata albescens presenting with tunnel vision: diagnostic dilemmas

Norhayaty S., Nurul Dalila M.S., Tai, Evelyn L.M., Liza Sharmini A.T., Zunaina E., Azhany Y.

Journal of Biomedical and Clinical Sciences, 2017;2(1):20-22.
MyJurnal

Tunnel vision is a classic sign among patients with advanced glaucoma. However, other conditions such as retinitis pigmentosa, optic neuritis and rod-cone dystrophy may be characterized by similar visual field defects. A 52-year-old lady with a family history of glaucoma presented with bilateral gradual loss of peripheral vision for two years. She claimed to have poor night vision about 20 years prior to this presentation. Her visual acuity was 6/7.5 in both eyes. The anterior chamber depth was moderate bilaterally, with Schaffer grading on gonioscopy of grade I to II. The intraocular pressure was 14 mmHg in both eyes. The optic discs appeared normal. Fundus examination showed scattered hypopigmented changes sparing the fovea. Humphrey visual field test revealed bilateral constricted visual fields. She was diagnosed with retinitis punctata albescens (RPA) based on her symptom of poor night vision, supported by the diffuse hypopigmented changes in her fundi. The management of this condition involves careful counselling regarding the genetic nature of the disease and its progressive course. We discuss this case to illustrate the importance of a thorough history taking and careful fundus examination in the workup of patients presenting with tunnel vision.

Matched MeSH terms: Intraocular Pressure
Intraocular pressure-lowering effects of imidazo[1,2-a]- and pyrimido[1,2-a]benzimidazole compounds in rats with dexamethasone-induced ocular hypertension

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: Intraocular Pressure
Fulltext Aqueous humor TGF-β2 levels in patients with open-angle glaucoma: A meta-analysis

Agarwal P, Daher AM, Agarwal R

Mol Vis, 2015;21:612-20.
PMID: 26019480

Elevated intraocular pressure (IOP) in glaucomatous eyes is often due to increased resistance to aqueous outflow. Previous studies have shown that increased extracellular material deposition in outflow pathways leads to increased resistance to aqueous outflow, and transforming growth factor (TGF)-β seems to play a role in the deposition of extracellular material. TGF-β2 is the predominant isoform in ocular tissue. Hence, comparison of the aqueous humor TGF-β2 level between patients with open-angle glaucoma (OAG) and controls would provide direct evidence for the role of TGF-β2 in the etiology of OAG. Hence, we performed this meta-analysis to develop an accurate estimate of the changes in aqueous humor TGF-β2 levels among OAG patients.

Matched MeSH terms: Intraocular Pressure

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