Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Glaucoma: HELP
Articles from Ireland
Based on 62 articles published since 2008
||||

These are the 62 published articles about Glaucoma that originated from Ireland during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Aging and ocular tissue stiffness in glaucoma. 2018

Liu, Baiyun / McNally, Sara / Kilpatrick, Jason I / Jarvis, Suzanne P / O'Brien, Colm J. ·School of Physics, Conway Institute, University College Dublin, Dublin, Ireland; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. · Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. · Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. · Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. Electronic address: cobrien@mater.ie. ·Surv Ophthalmol · Pubmed #28666629.

ABSTRACT: Glaucoma is a progressive and chronic neurodegenerative disorder characterized by damage to the inner layers of the retina and deformation of the optic nerve head. The degeneration of retinal ganglion cells and their axons results in an irreversible loss of vision and is correlated with increasing age. Extracellular matrix changes related to natural aging generate a stiffer extracellular environment throughout the body. Altered age-associated ocular tissue stiffening plays a major role in a significant number of ophthalmic pathologies. In glaucoma, both the trabecular meshwork and the optic nerve head undergo extensive extracellular matrix remodeling, characterized by fibrotic changes associated with cellular and molecular events (including myofibroblast activation) that drive further tissue fibrosis and stiffening. Here, we review the literature concerning the role of age-related ocular stiffening in the trabecular meshwork, lamina cribrosa, sclera, cornea, retina, and Bruch membrane/choroid and discuss their potential role in glaucoma progression. Because both trabecular meshwork and lamina cribrosa cells are mechanosensitive, we then describe molecular mechanisms underlying tissue stiffening and cell mechanotransduction and how these cellular activities can drive further fibrotic changes within ocular tissues. An improved understanding of the interplay between age-related tissue stiffening and biological responses in the trabecular meshwork and optic nerve head could potentially lead to novel therapeutic strategies for glaucoma treatment.

2 Review Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway. 2017

O'Callaghan, Jeffrey / Cassidy, Paul S / Humphries, Pete. ·a Ocular Genetics Unit, Smurfit Institute of Genetics , University of Dublin, Trinity College , Dublin , Ireland. ·Expert Opin Ther Targets · Pubmed #28952395.

ABSTRACT: INTRODUCTION: Ocular hypertension in open-angle glaucoma is caused by a reduced rate of removal of aqueous humour (AH) from the eye, with the majority of AH draining from the anterior chamber through the conventional outflow pathway, comprising the trabecular meshwork (TM) and Schlemm's Canal. Resistance to outflow is generated, in part, by the extracellular matrix (ECM) of the outflow tissues. Current pressure-lowering topical medications largely suppress AH production, or enhance its clearance through the unconventional pathway. However, therapies targeting the ECM of the conventional pathway in order to decrease intraocular pressure have become a recent focus of attention. Areas covered: We discuss the role of ECM of the TM in outflow homeostasis and its relevance as a target for glaucoma therapy, including progress in development of topical eye formulations, together with gene therapy approaches based on inducible, virally-mediated expression of matrix metalloproteinases to enhance aqueous outflow. Expert opinion: There remains a need for improved glaucoma medications that more specifically act upon sites causative to glaucoma pathogenesis. Emerging strategies targeting the ECM of the conventional outflow pathway, or associated components of the cytoskeleton of TM cells, involving new pharmacological formulations or genetically-based therapies, are promising avenues of future glaucoma treatment.

3 Review Mitochondrial dysfunction in ocular disease: Focus on glaucoma. 2017

Kamel, Khalid / Farrell, Michael / O'Brien, Colm. ·Institute of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. · Neuropathology, Beaumont Hospital, Dublin, Ireland. · Institute of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. Electronic address: cobrien@mater.ie. ·Mitochondrion · Pubmed #28499981.

ABSTRACT: Mitochondrial dysfunction commonly presents with ocular findings as a part of a systemic disorder. These ophthalmic manifestations can be the first sign of a mitochondrial abnormality, which highlights the key role of a comprehensive ophthalmic assessment. On the other hand, a number of visually disabling genetic and acquired eye diseases with no curative treatment show abnormal mitochondrial function. Recent advances in mitochondrial research have improved our understanding of previously unexplained ocular disorders utilising better diagnostic approaches. Further studies on mitochondrial dysfunction and novel modalities of treatment will help to improve outcomes of these conditions. In this review article we discuss the clinical picture of common mitochondrial-related eye diseases, diagnostic approaches and possible treatment options including a very recent interesting report about gene therapy, with a particular focus on glaucoma.

4 Review Life under pressure: The role of ocular cribriform cells in preventing glaucoma. 2016

Paula, Jayter S / O'Brien, Colm / Stamer, W Daniel. ·Department of Ophthalmology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA. · Ophthalmology, UCD School of Medicine, Mater Hospital, Dublin, Ireland. · Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA. Electronic address: dan.stamer@duke.edu. ·Exp Eye Res · Pubmed #27567558.

ABSTRACT: Primary open-angle glaucoma is a multifactorial blinding disease often impacting the two pressure-sensitive regions of the eye: the conventional outflow pathway and the optic nerve head (ONH). The connective tissues that span these two openings in the globe are the trabecular meshwork of the conventional outflow pathway and the lamina cribrosa of the ONH. Resident cribiform cells of these two regions are responsible for actively remodeling and maintaining their connective tissues. In glaucoma, aberrant maintenance of the juxtacanalicular tissues (JCT) of the conventional outflow pathway results in ocular hypertension and pathological remodeling of the lamina cribrosa results in ONH cupping, damaging retinal ganglion cell axons. Interestingly, cells cultured from the lamina cribrosa and the JCT of the trabecular meshwork have similarities regarding gene expression, protein production, plus cellular responses to growth factors and mechanical stimuli. This review compares and contrasts the current knowledge of these two cell types, whose health is critical for protecting the eye from glaucomatous changes. In response to pressure gradients across their respective cribiform tissues, the goal is to better understand and differentiate healthy from pathological behavior of these two cell types.

5 Review The role of lamina cribrosa cells in optic nerve head fibrosis in glaucoma. 2016

Wallace, Deborah M / O'Brien, Colm J. ·UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Dept. of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. ·Exp Eye Res · Pubmed #26675406.

ABSTRACT: Glaucoma is a chronic progressive optic neuropathy. There are extracellular matrix (ECM) changes associated with optic disc cupping in the optic nerve head (ONH) and subsequent visual field defects. The primary risk factor for onset and progression of glaucoma is raised intraocular pressure (IOP). Elevated IOP causes deformation at the ONH specifically at the lamina cribrosa (LC) region where there is also deposition of ECM causing the LC to initially undergo thickening and posterior migration with eventual shearing and collapse of the LC plates leading to a thin fibrotic connective tissue structure/scar. Cells that populate the LC region of the ONH are those cells that are positive for GFAP (the astrocytes) and those negative for GFAP (the LC cells). The LC cell plays an integral role in ECM remodelling producing ECM when exposed to high level mechanical stretch, TGF- β1 and a hypoxic environment.

6 Review Drug-induced Bilateral Secondary Angle-Closure Glaucoma: A Literature Synthesis. 2016

Murphy, Rory M / Bakir, Belal / O'Brien, Colm / Wiggs, Janey L / Pasquale, Louis R. ·*School of Medicine, University College Dublin, Dublin, Ireland †Department of Ophthalmology, Massachusetts Eye and Ear Infirmary ‡Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. ·J Glaucoma · Pubmed #25943730.

ABSTRACT: PURPOSE: We performed a literature synthesis to identify the full spectrum of compounds implicated in drug-induced, bilateral secondary angle-closure glaucoma (2° ACG). METHODS: Systematic PubMed literature review identified relevant bilateral 2° ACG case reports. We evaluated these reports with both the Naranjo adverse drug reaction probability scale to assess the causality of reported drug reactions and a 2° ACG scale scoring system we developed to determine the likelihood that the event represented bilateral 2° ACG. Two independent graders performed these analyses and their scores were averaged for interpretation. The Naranjo scale ranges from -4 to +13 and the drug reaction was considered definite if the score was ≥ 9, probable if 5 to 8, possible if 1 to 4, and doubtful if ≤ 0. The 2° ACG score ranges from 0 to 7. We considered a 2° ACG score of ≥ 4 as evidence of significant likelihood that the drug reaction represented bilateral 2° ACG. RESULTS: No drug had a definite Naranjo score, but the following drug entities had probable Naranjo scores and 2° ACG scores ≥ 4: acetazolamide, "anorexiant mix," bupropion, cabergoline, "ecstasy," escitalopram, flavoxate, flucloxacillin, hydrochlorothiazide, hydrochlorothiazide/triamterene, mefenamic acid, methazolamide, oseltamivir, topiramate, topiramate/bactrim, and venlafaxine. Root chemical analysis revealed that sulfur-containing and non-sulfur-containing compounds contributed to bilateral 2° ACG. CONCLUSIONS: Several compound preparations were implicated in drug-induced bilateral 2° ACG. Treating physicians should be aware that some forms of recreational drug use, which the patient may not admit to, could contribute to this vision-threatening side effect.

7 Review Thiol redox homeostasis in neurodegenerative disease. 2015

McBean, Gethin J / Aslan, Mutay / Griffiths, Helen R / Torrão, Rita C. ·UCD School of Biomolecular and Biomedical Science, University College, Dublin, Ireland. Electronic address: gethin.mcbean@ucd.ie. · Department of Medical Biochemistry, Akdeniz University School of Medicine, Antalya, Turkey. · School of Life and Health Sciences, Aston University, Birmingham, UK. ·Redox Biol · Pubmed #25974624.

ABSTRACT: This review provides an overview of the biochemistry of thiol redox couples and the significance of thiol redox homeostasis in neurodegenerative disease. The discussion is centred on cysteine/cystine redox balance, the significance of the xc(-) cystine-glutamate exchanger and the association between protein thiol redox balance and neurodegeneration, with particular reference to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. The role of thiol disulphide oxidoreductases in providing neuroprotection is also discussed.

8 Review The Function of Matricellular Proteins in the Lamina Cribrosa and Trabecular Meshwork in Glaucoma. 2015

Wallace, Deborah M / Pokrovskaya, Olya / O'Brien, Colm J. ·1 School of Medicine and Medical Science, University College Dublin , Dublin, Ireland . · 2 Department of Ophthalmology, Mater Misericordiae University Hospital , Dublin, Ireland . ·J Ocul Pharmacol Ther · Pubmed #25848892.

ABSTRACT: PURPOSE: To review the current literature regarding the role of matricellular proteins in glaucoma, specifically in the lamina cribrosa (LC) region of the optic nerve head (ONH) and the trabecular meshwork (TM). METHODS: A literature search was performed for published articles describing the expression and function of matricellular proteins such as thrombospondin (TSP), connective tissue growth factor (CTGF), secreted protein acidic and rich in cysteine (SPARC), and periostin in glaucoma. RESULTS: In glaucoma, there are characteristic extracellular matrix (ECM) changes associated with optic disc cupping in the ONH and subsequent visual field defects. Matricellular proteins are a family of nonstructural secreted glycoproteins, which enable cells to communicate with their surrounding ECM, including CTGF, also known as CCN2, TSPs, SPARC, periostin, osteonectin, and tenascin-C and -X, and other ECM proteins. Such proteins appear to play a role in fibrosis and increased ECM deposition. Importantly, most are widely expressed in tissues particularly in the TM and ONH, and deficiency of TSP1 and SPARC has been shown to lower intraocular pressure in mouse models of glaucoma through enhanced outflow facility. CONCLUSION: This article highlights the role of matricellular proteins in glaucoma pathology. The potential role of these proteins in glaucoma is emerging as some have an association with the pathophysiology of the TM and LC region and might therefore be potential targets for therapeutic intervention in glaucoma.

9 Review Metabolomics/Proteomics strategies used to identify biomarkers for exfoliation glaucoma. 2014

McNally, Sara / O'Brien, Colm J. ·*Department of Ophthalmology, Mater Misericordiae University Hospital †UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. ·J Glaucoma · Pubmed #25275907.

ABSTRACT: It is currently estimated that 60 to 70 million people worldwide are affected by open-angle glaucoma and the majority of patients who present to clinic have raised intraocular pressure, visual field loss, and cupping of the optic nerve. Although exfoliation glaucoma (XFG) correlates with age, it is the most common cause of secondary open-angle glaucoma in the world and, with elevated intraocular pressure at onset, this disease runs an aggressive clinical course. XFG differs from primary open-angle glaucoma, in that patients have a diminished response to medication, show accelerated rates of disease progression, and therefore have a higher need for surgery. Here we highlight some major findings in the literature, which relate to the search for biomarkers of XFG by metabolomics and proteomics strategies.

10 Review The role of matricellular proteins in glaucoma. 2014

Wallace, Deborah M / Murphy-Ullrich, Joanne E / Downs, J Crawford / O'Brien, Colm J. ·UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Dept. of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. Electronic address: deborahmwallace1@gmail.com. · Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Department of Ophthalmology, Center for Ocular Biomechanics and Biotransport, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Dept. of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. ·Matrix Biol · Pubmed #24727033.

ABSTRACT: Glaucoma is an optic neuropathy affecting approximately 60million people worldwide and is the second most common cause of irreversible blindness. Elevated intraocular pressure (IOP) is the main risk factor for developing glaucoma and is caused by impaired aqueous humor drainage through the trabecular meshwork (TM) and Schlemm's canal (SC). In primary open angle glaucoma (POAG), this elevation in IOP in turn leads to deformation at the optic nerve head (ONH) specifically at the lamina cribrosa (LC) region where there is also a deposition of extracellular matrix (ECM) molecules such as collagen and fibronectin. Matricellular proteins are non-structural secreted glycoproteins that help cells communicate with their surrounding ECM. This family of proteins includes connective tissue growth factor (CTGF), also known as CCN2, thrombospondins (TSPs), secreted protein acidic and rich in cysteine (SPARC), periostin, osteonectin, and Tenascin-C and -X and other ECM proteins. All members appear to play a role in fibrosis and increased ECM deposition. Most are widely expressed in tissues particularly in the TM and ONH and deficiency of TSP1 and SPARC have been shown to lower IOP in mouse models of glaucoma through enhanced outflow facility. The role of these proteins in glaucoma is emerging as some have an association with the pathophysiology of the TM and LC regions and might therefore be potential targets for therapeutic intervention in glaucoma.

11 Review Aniridia: current pathology and management. 2008

Lee, Helena / Khan, Rizwana / O'Keefe, Michael. ·Department of Paediatric Ophthalmology, Children's University Hospital, Dublin, Ireland. ·Acta Ophthalmol · Pubmed #18937825.

ABSTRACT: Aniridia is a rare panocular disorder affecting the cornea, anterior chamber, iris, lens, retina, macula and optic nerve. It occurs because of mutations in PAX6 on band p13 of chromosome 11. It is associated with a number of syndromes, including Wilm's tumour, bilateral sporadic aniridia, genitourinary abnormalities and mental retardation (WAGR) syndrome. PAX6 mutations result in alterations in corneal cytokeratin expression, cell adhesion and glycoconjugate expression. This, in addition to stem-cell deficiency, results in a fragile cornea and aniridia-associated keratopathy (AAK). It also results in abnormalities in the differentiation of the angle, resulting in glaucoma. Glaucoma may also develop as a result of progressive angle closure from synechiae. There is cataract development, and this is associated with a fragile lens capsule. The iris is deficient. The optic nerve and fovea are hypoplastic, and the retina may be prone to detachment. Aniridia is a profibrotic disorder, and as a result many interventions--including penetrating keratoplasty and filtration surgery--fail. The Boston keratoprosthesis may provide a more effective approach in the management of AAK. Guarded filtration surgery appears to be effective in glaucoma. Despite our increasing understanding of the genetics and pathology of this condition, effective treatment remains elusive.

12 Article Nutritional supplementation in the treatment of glaucoma: A systematic review. 2019

Loskutova, Ekaterina / O'Brien, Colm / Loskutov, Igor / Loughman, James. ·Centre for Eye Research Ireland, Dublin Institute of Technology, Grangegorman Lower, Dublin, Ireland. Electronic address: losk.katerina@gmail.com. · Centre for Eye Research Ireland, Dublin Institute of Technology, Grangegorman Lower, Dublin, Ireland; Institute of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. · Clinical Research centre, Central Hospital RZD, Moscow, Russia. · Centre for Eye Research Ireland, Dublin Institute of Technology, Grangegorman Lower, Dublin, Ireland; African Vision Research Institute, University of KwaZulu Natal, Durban, South Africa. ·Surv Ophthalmol · Pubmed #30296451.

ABSTRACT: Current treatment strategies for glaucoma are limited to halting disease progression and do not restore lost visual function. Intraocular pressure is the main risk factor for glaucoma, and intraocular pressure-lowering treatment remains the mainstay of glaucoma treatment, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients. We review the literature to determine whether nutritional interventions intended to prevent or delay the progression of glaucoma could prove to be a valuable addition to the mainstay of glaucoma therapy. A total of 33 intervention trials were included in this review, including 21 randomized controlled trials. These suggest that flavonoids exert a beneficial effect in glaucoma, particularly in terms of improving ocular blood flow and potentially slowing progression of visual field loss. In addition, supplements containing forskolin have consistently demonstrated the capacity to reduce intraocular pressure beyond the levels achieved with traditional therapy alone; however, despite the strong theoretical rationale and initial clinical evidence for the beneficial effect of dietary supplementation as an adjunct therapy for glaucoma, the evidence is not conclusive. More and better quality research is required to evaluate the role of nutritional supplementation in glaucoma.

13 Article Difference in intraocular pressure measurements between non-contact tonometry and Goldmann applanation tonometry and the role of central corneal thickness in affecting glaucoma referrals. 2019

Kamel, Khalid / Dervan, Edward / Falzon, Kevin / O'Brien, Colm. ·Institute of Ophthalmology, Mater Misericordiae University Hospital, 60 Eccles Street, Dublin 7, Republic of Ireland. kholod8383@hotmail.com. · Institute of Ophthalmology, Mater Misericordiae University Hospital, 60 Eccles Street, Dublin 7, Republic of Ireland. · Ophthalmology Department, York Hospital, York, UK. ·Ir J Med Sci · Pubmed #29616408.

ABSTRACT: BACKGROUND: Patients at glaucoma risk are commonly identified by optometrists and subsequently referred to glaucoma specialists. Optometrists mainly use non-contact tonometry (NCT) for intraocular pressure (IOP) measurement. AIMS: To investigate the role of differences in IOP measurement between NCT and Goldmann applanation tonometry (GAT) and the effect of central corneal thickness (CCT) on these differences in optometrist referrals METHODS: Details of the initial clinical visit of patients referred with IOP > 21 mmHg in either eye as measured by NCT to a consultant glaucoma specialist were retrospectively reviewed. Demographic and referral data, IOP, CCT, and glaucoma diagnosis were obtained. The main outcome measure was the IOP measurement differences between NCT and GAT. RESULTS: Of the 98 patients referred, only 23% had IOP > 21 mmHg when measured by GAT. NCT (Nidek NT400, Reichert Puff, Pulsair Easy Eye) measured the IOP greater than GAT by a mean of 5.8 mmHg (NCT 24.1 ± 3.5, GAT 18.3 ± 3.0). The effect of CCT on IOP measurement was less for GAT (R CONCLUSIONS: The difference in IOP measurement between NCT and GAT leads to a possible increase in glaucoma referrals, particularly in patients with thicker corneas. Repeat IOP using GAT and CCT measurement would help in triaging referrals.

14 Article Macular Pigment and Visual Function in Patients With Glaucoma: The San Diego Macular Pigment Study. 2018

Daga, Fábio B / Ogata, Nara G / Medeiros, Felipe A / Moran, Rachel / Morris, Jeffrey / Zangwill, Linda M / Weinreb, Robert N / Nolan, John M. ·Hamilton Glaucoma Center and Shiley Eye Institute and Department of Ophthalmology, University of California San Diego, La Jolla, California, United States. · Department of Ophthalmology, Duke Eye Center, Duke University, Durham, North Carolina, United States. · Nutrition Research Centre Ireland, School of Health Sciences, Carriganore House, Waterford Institute of Technology, West Campus, Carriganore, Waterford, Ireland. · Morris Eye Group, Encinitas, Vista, California, United States. ·Invest Ophthalmol Vis Sci · Pubmed #30193322.

ABSTRACT: Purpose: Although recent studies have shown that macular pigment (MP) is significantly lower in glaucoma patients, this relationship merits further investigation. Methods: This cross-sectional study included 85 glaucoma patients and 22 controls. All subjects had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements. Intake of lutein (L) and zeaxanthin (Z) was estimated using a novel dietary screener. The Heidelberg Spectralis dual-wavelength autofluorescence (AF) technology was employed to study the relationship between MP and glaucoma. The association between MP volume and glaucoma was investigated using linear regression models accounting for potential confounding factors. Results: Glaucoma patients had significantly worse SAP mean deviation (MD) and lower RNFL thickness in the study eye compared to control subjects (P < 0.001 for both). MP (volume) was comparable between groups (P = 0.436). In the univariable model, diagnosis of glaucoma was not associated with MP volume (R2 = 1.22%; P = 0.257). Dietary intake of L and Z was positively and significantly related to MP in the univariable (P = 0.022) and multivariable (P = 0.020) models. Conclusions: These results challenge previous studies that reported that glaucoma is associated with low MP. Dietary habits were found to be the main predictor of MP in this sample. Further research is merited to better understand the relationship between glaucoma, MP, and visual performance in these patients.

15 Article Associations between factors related to atopic disease and glaucoma in the National Health and Nutrition Examination Survey. 2018

Tseng, Victoria L / Lee, Janet / Yu, Fei / Sirsy, Omar / Coleman, Anne L. ·1 Stein Eye Institute, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA, USA. · 2 Department of Biostatistics, Fielding School of Public Health, University of California - Los Angeles, Los Angeles, CA, USA. · 3 Royal College of Surgeons in Ireland, Dublin, Ireland. · 4 Department of Epidemiology, Fielding School of Public Health, University of California - Los Angeles, Los Angeles, CA, USA. ·Eur J Ophthalmol · Pubmed #29756485.

ABSTRACT: INTRODUCTION: Previous studies have suggested associations between glaucoma and serum sensitization to specific allergens. The purpose of this study was to examine associations between inciting factors for atopic disease, atopic diseases and symptoms, and glaucoma in the 2005-2006 National Health and Nutrition Examination Survey. METHODS: The study population included adult participants of National Health and Nutrition Examination Survey 2005-2006. Inciting factors for atopic disease included pet ownership, mildew/musty smell in home, cockroaches in home, use of water treatment devices, and crowded living conditions. Atopic diseases and symptoms included hay fever, eczema, any allergy, sneezing problems, and sinus infections. The outcome was glaucoma defined by the Rotterdam criteria. Covariates included age, gender, ethnicity, and allergy-related medication use. Logistic regression was used to examine associations between each exposure and glaucoma prevalence, controlling for all covariates. Statistical analyses were weighted by the National Health and Nutrition Examination Survey multistage sampling design. RESULTS: The weighted study population included 83,205,587 subjects, of whom 2,657,336 (3.2%) had glaucoma. After adjusting for covariates, factors associated with increased glaucoma included cat ownership (odds ratio =1.99, 95% confidence interval = 1.02-3.87) and mildew/musty smell in home (odds ratio = 1.95, 95% confidence interval = 0.99-3.84; borderline significance), while history of eczema was associated with decreased glaucoma (odds ratio = 0.27, 95% confidence interval = 0.02-0.99). CONCLUSION: In National Health and Nutrition Examination Survey, self-reported cat ownership is associated with increased glaucoma prevalence, while a mildew/musty smell in home may have a borderline association with increased glaucoma prevalence. These findings are possibly related to laboratory associations identified in the same population and further studies are needed to identify potential mechanisms to explain these associations.

16 Article Expanding the traditional role of optometry: Current practice patterns and attitudes to enhanced glaucoma services in Ireland. 2018

Barrett, Catriona / Loughman, James. ·Dublin Institute of Technology, 19A Lower Kevin Street, Dublin 8, Ireland; DIT Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Dublin, Ireland. Electronic address: catriona.barrett@dit.ie. · Dublin Institute of Technology, 19A Lower Kevin Street, Dublin 8, Ireland; DIT Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Dublin, Ireland; African Vision Research Institute, University of KwaZulu Natal, South Africa. ·J Optom · Pubmed #29650469.

ABSTRACT: PURPOSE: To investigate current diagnostic equipment availability and usage for glaucoma case-finding within community optometric practice, and to explore optometrists' attitudes towards an enhanced scope of clinical practice. METHODS: An anonymous survey was developed, validated, and distributed to all optometrists in Ireland. RESULTS: 199 optometrists (27% of registrants) responded to the survey. 87% had access to the traditional triad of tests necessary to conduct adequate glaucoma case finding. Standard automated perimetry was the most commonly absent (13%) of the three essential screening tests. 64% of respondents indicated that monocular direct ophthalmoscopy was their first choice technique for fundus examination. 47% of respondents had access to contact applanation tonometry, though just 14% used it as first choice during routine eye examinations. Among the 73 participants with access to both contact and non-contact tonometry (NCT), 80.8%, used NCT preferentially. The significant majority (98%) indicated an interest in enhanced glaucoma services with 57% agreeing that postgraduate training was an essential prerequisite to any increase in scope of practice. CONCLUSION: Irish optometrists are well equipped with the traditional tests used in glaucoma detection. However, implementation of enhanced referral schemes or glaucoma monitoring or management services would require equipment upgrades and associated training in at least half of the surveyed practices. There is strong interest in furthering optometric professional development and expanding the traditional role boundaries of optometrists, incorporating further education as an essential prerequisite to an enhanced scope of practice.

17 Article Glaucoma referral refinement in Ireland: managing the sensitivity-specificity paradox in optometric practice. 2018

Barrett, Catriona / O'Brien, Colm / Loughman, James. ·Department of Optometry, Dublin Institute of Technology (DIT), Dublin, Ireland. · DIT Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Dublin, Ireland. · Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. · African Vision Research Institute, University of KwaZulu Natal, Durban, South Africa. ·Ophthalmic Physiol Opt · Pubmed #29492992.

ABSTRACT: PURPOSE: Glaucoma referral refinement (GRR) has proven a successful demand management strategy for glaucoma suspect cases in the United Kingdom (UK). A GRR clinic was established in Dublin, Ireland to investigate the clinical viability of this pathway outside the UK's National Health Service (NHS) structures, and away from the influence of National Institute for Clinical Excellence (NICE) guidance. METHODS: Glaucoma suspect patients were recruited into the scheme following referral from community optometrists in the greater Dublin area. The GRR exam protocol was designed in consultation with the participating ophthalmology department. The refinement scheme optometrist, trained through apprenticeship style experience at a hospital outpatient clinic, made a tentative management decision after carrying out the GRR exam. The final management decision was made in a 'virtual clinic' by a glaucoma specialist consultant ophthalmologist. RESULTS: Two hundred and twenty-five glaucoma suspect patients were seen in the scheme. After their first GRR visit, 28% were discharged back to their own optometrist, 42% were monitored in the GRR clinic, and 30% were referred to ophthalmology. After this monitoring cohort were further assessed, a total of 38% of the patients seen within the scheme required referral to ophthalmology. Sixteen percent of the total participant group (n = 225) were lost to follow up. Cohen's κ was used to determine the level of agreement between the scheme optometrist and ophthalmologist. There was substantial agreement, with κ = 0.63 for the first visit management decisions (n = 225). Agreement increased for subsequent monitoring visits with κ = 0.85 for second visits (n = 65), and κ = 0.69 for all management decisions within the scheme (n = 301). We received management outcomes for 44 of the 86 patients referred to ophthalmology. Of these 44, 57% received medical treatment for glaucoma, 34% were monitored without treatment, 2% were discharged, and 7% had comorbidities that were assessed and managed. CONCLUSION: Of the patients seen within the scheme, 62% did not require referral onward to ophthalmology, thus releasing the significant majority of hospital clinic slots that would previously have been required to examine such patients. The high level of inter-professional decision agreement likely reflects the benefits of pre-scheme apprenticeship style training and ongoing hospital clinic participation by the scheme optometrist. The rate of loss to follow up compares favourably with ophthalmology led, hospital based, glaucoma clinics. Nevertheless, the losses indicate that patient education remains a key priority for future planning.

18 Article Activation of the NFAT-Calcium Signaling Pathway in Human Lamina Cribrosa Cells in Glaucoma. 2018

Irnaten, Mustapha / Zhdanov, Alexander / Brennan, Deirdre / Crotty, Thomas / Clark, Abbot / Papkovsky, Dmitri / O'Brien, Colm. ·Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. · School of Biochemistry & Cell Biology, University College Cork, Cork, Ireland. · Department of Anatomy, University College Dublin School of Medicine, Health Sciences Centre, University College Dublin, Belfield, Dublin, Ireland. · School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. · The North Texas Eye Research Institute, University of North Texas, Health Science Center, Fort Worth, Texas, United States. ·Invest Ophthalmol Vis Sci · Pubmed #29411011.

ABSTRACT: Purpose: Optic nerve cupping in glaucoma is characterized by remodeling of the extracellular matrix (ECM) and fibrosis in the lamina cribrosa (LC). We have previously shown that glaucoma LC cells express raised levels of ECM genes and have elevated intracellular calcium ([Ca2+]i). Raised [Ca2+]i is known to promote proliferation, activation, and contractility in fibroblasts via the calcineurin-NFAT (nuclear factor of activated T-cells) signaling pathway. In this study, we examine NFAT expression in normal and glaucoma LC cells, and investigate the effect of cyclosporin A (CsA, a known inhibitor of NFAT activity) on [Ca2+]i and ECM gene expression in normal and glaucoma LC cells. Methods: [Ca2+]i was measured with dual-wavelength Ca2+ imaging and confocal microscopy using Fura-2-AM and Fluo-4 under physiological isotonic and hypotonic cell stretch treatment. Human donor LC cells were cultured under normal physiological conditions or using a glaucoma-related stimulus, oxidative stress (H2O2, 100 μM), for 6 hours with or without CsA. NFATc3 protein levels were examined using Western blot analysis. Profibrotic ECM gene transcription (including transforming growth factor-β1 [TGFβ1], collagen 1A1 [Col1A1], and periostin) was analyzed using quantitative real time RT-PCR. Results: Basal and hypotonic cell membrane stretch-induced [Ca2+]i were significantly (P < 0.05) elevated in glaucoma LC cells compared to normal controls. There was a significant delay in [Ca2+]i reuptake into internal stores in the glaucoma LC cells. NFATc3 protein levels were increased in glaucoma LC cells. CsA (10 μM) significantly inhibited the H2O2-induced expression of NFATc3 in normal and glaucoma LC cells. CsA also reduced the H2O2-induced NFATc3 dephosphorylation (and nuclear translocation), and also suppressed the H2O2-induced elevation in profibrotic ECM genes (TGFβ1, Col1A1, and periostin), both in normal and in glaucoma LC cells. Conclusions: Intracellular Ca2+ and NFATc3 expression were significantly increased in glaucoma LC cells. CsA reduced the H2O2-induced enhancement in NFATc3 protein expression and nuclear translocation and the profibrotic gene expression both in normal and in glaucoma LC cells. Therefore, targeting the calcineurin-NFATc3 signaling pathway may represent a potential avenue for treating glaucoma-associated LC fibrosis.

19 Article Increased Substrate Stiffness Elicits a Myofibroblastic Phenotype in Human Lamina Cribrosa Cells. 2018

Liu, Baiyun / Kilpatrick, Jason I / Lukasz, Bartlomiej / Jarvis, Suzanne P / McDonnell, Fiona / Wallace, Deborah M / Clark, Abbot F / O'Brien, Colm J. ·School of Physics, Conway Institute, University College Dublin, Belfield, Dublin, Ireland. · Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland. · School of Medicine, University College Dublin, Belfield, Dublin, Ireland. · North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, United States. · Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. ·Invest Ophthalmol Vis Sci · Pubmed #29392327.

ABSTRACT: Purpose: Alteration in the extracellular matrix (ECM) of the optic nerve head (ONH) causes lamina cribrosa (LC) fibrosis and affects the mechanical integrity of the ONH. Increased ECM tissue stiffness drives myofibroblast activation leading to tissue fibrosis throughout the body. Here using primary human LC cells, we investigate the effect of substrate stiffness on profibrotic changes, which might be a key molecular mechanism driving ECM remodeling of the LC in primary open-angle glaucoma (POAG) glaucoma. Methods: Primary human LC cells from normal and age-matched POAG glaucoma donors were cultured on substrates with defined mechanical properties of 5 and 100 kPa to replicate the range of mechanical microenvironments that cells may experience in vivo. Cell morphology, spread area, actin stress fibers, vinculin-focal adhesion formation, and α-smooth muscle actin (α-SMA) signal were examined using immunofluorescence staining. The elastic modulus of cells was measured using atomic force microscopy (AFM). Results: Significantly greater cell spread area along with increased actin filament development, and vinculin-focal adhesion formation (number and size) were found in both normal and glaucoma LC cells cultured on stiff substrates. These changes were positively associated with elevated cell stiffness measured by AFM. Changes in spreading and cytoskeleton organization of glaucoma LC cells were significantly more pronounced than those in normal cells. The transformation to a myofibroblast-like cell phenotype was identified in both LC cells exposed to stiffer substrates, as indicated by an increased α-SMA signal and its colocalization with the actin stress fibers. Conclusions: These findings demonstrated that a stiffer cell microenvironment activates a myofibroblastic transformation in human LC cells, and therefore contributes to LC remodelling and fibrosis in glaucoma.

20 Article Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels. 2018

Mulvihill, John J E / Raykin, Julia / Snider, Eric J / Schildmeyer, Lisa A / Zaman, Irsham / Platt, Manu O / Kelly, Daniel J / Ethier, C Ross. ·Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Dr. NW, Atlanta, GA, 30332, USA. · Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland. · Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Dr. NW, Atlanta, GA, 30332, USA. ross.ethier@bme.gatech.edu. · George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA. ross.ethier@bme.gatech.edu. ·Ann Biomed Eng · Pubmed #29181720.

ABSTRACT: Glaucoma is a common optic neuropathy characterized by retinal ganglion cell death. Elevated intraocular pressure (IOP), a key risk factor for glaucoma, leads to significant biomechanical deformation of optic nerve head (ONH) cells and tissues. ONH astrocytes respond to this deformation by transforming to a reactive, proliferative phenotype, which has been implicated in the progression of glaucomatous vision loss. However, little is known about the mechanisms of this transformation. In this study, we developed a 3D collagen gel culture system to mimic features of ONH deformation due to elevated IOP. Compressive loading of astrocyte-seeded collagen gels led to cell alignment perpendicular to the direction of strain, and increased astrocyte activation, as assayed by GFAP, vimentin, and s100β levels, as well as MMP activity. This proof-of-concept study shows that this system has potential for studying mechanisms of astrocyte mechanobiology as related to the pathogenesis of glaucoma. Further work is needed to establish the possible interplay of mechanical stimulation, matrix properties, and hypoxia on the observed response of astrocytes.

21 Article Macular pigment is associated with glare-affected visual function and central visual field loss in glaucoma. 2018

Siah, We Fong / O'Brien, Colm / Loughman, James J. ·Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. · School of Medicine, University College Dublin, Dublin, Ireland. · School of Physics, Clinical and Optometric Sciences, College of Sciences and Health, Dublin Institute of Technology, Dublin, Ireland. · Faculty of Health Sciences, African Vision Research Institute, University of KwaZulu-Natal, Durban, South Africa. ·Br J Ophthalmol · Pubmed #28982957.

ABSTRACT: AIM: To evaluate the relationship between macular pigment optical density (MPOD) and glare disability in open-angle glaucoma. METHODS: A cross-sectional analysis of baseline data (88 subjects; median age, 67 (range 36-84) years) collected during the Macular Pigment and Glaucoma Trial (ISRCTN registry number: 56985060). MPOD at 0.25°, 0.5° and 1° of retinal eccentricity was measured using customised heterochromatic flicker photometry. Mesopic contrast sensitivity with glare (mCSg), photostress recovery time (PRT) and self-reported glare symptoms were evaluated. Fourier-domain optical coherence tomography was used to analyse ganglion cell complex (GCC) and identify foveal involvement. RESULTS: Low spatial frequency ( CONCLUSIONS: Macular pigment level may be an important consideration among those experiencing disability glare in glaucoma, including those with foveal involvement. TRIAL REGISTRATION NUMBER: ISRCTN56985060, Post-results.

22 Article Barriers to glaucoma case finding as perceived by optometrists in Ireland. 2018

Barrett, Catriona / O'Brien, Colm / Butler, John S / Loughman, James. ·School of Physics and Clinical and Optometric Sciences, Dublin Institute of Technology, Dublin, Ireland. · Mater Misericordiae University Hospital, Dublin, Ireland. · School of Mathematical Sciences, Dublin Institute of Technology, Dublin, Ireland. · African Vision Research Institute, University of KwaZulu Natal, Durban, South Africa. ·Clin Exp Optom · Pubmed #28718219.

ABSTRACT: BACKGROUND: This research was designed to provide an in-depth exploration of the perceptions of optometrists relating to the challenges of glaucoma case finding in the Irish health-care system. METHODS: A survey was developed, piloted and distributed for anonymous completion by optometrists registered to practise in Ireland. The survey included 10 five-level Likert items exploring potential barriers to glaucoma detection and a free-text box for participants to comment more broadly. RESULTS: One hundred and ninety-nine optometrists (27 per cent of registrants) responded to the survey. Among the barriers identified, there was notable agreement (71 per cent) with the need for extra training on glaucoma detection. Logistic regression showed that optometrists without postgraduate qualifications were more likely to agree with the need for extra training (OR 3.2, 95 per cent CI 1.3-8.1). Respondents largely agreed (61 per cent) that patient unwillingness to pay additional fees for supplementary glaucoma-specific tests was also a barrier. Appointment times of less than 30 minutes were significantly associated with six of the 10 proposed barriers to glaucoma detection. A logistic regression analysis (n = 179) confirmed that the time allotted per appointment was a significant predictor of the agreement time of optometrists as a barrier (χ CONCLUSION: The strong link found between postgraduate education and the confidence of optometrists in detecting glaucoma indicates that optometrists wishing to increase their scope of practice in the new legislative environment in Ireland may more actively seek training in areas of interest. The responses also indicate a lack of funding for the level of diagnostic testing required for accurate glaucoma diagnosis. Recent increases in the state's eye examination fees look likely to address the identified time and financial barriers to glaucoma detection in Ireland. Future work should look to analyse the effects of increased funding on optometric case finding for glaucoma.

23 Article Optical Coherence Tomography Angiography Macular and Peripapillary Vessel Perfusion Density in Healthy Subjects, Glaucoma Suspects, and Glaucoma Patients. 2017

Triolo, Giacinto / Rabiolo, Alessandro / Shemonski, Nathan D / Fard, Ali / Di Matteo, Federico / Sacconi, Riccardo / Bettin, Paolo / Magazzeni, Stephanie / Querques, Giuseppe / Vazquez, Luis E / Barboni, Piero / Bandello, Francesco. ·Department of Ophthalmology, University Vita-Salute, San Raffaele Scientific Institute, Milan, Italy. · Carl Zeiss Meditec, Inc., Dublin, California, United States. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States. ·Invest Ophthalmol Vis Sci · Pubmed #29114838.

ABSTRACT: Purpose: To evaluate macular and peripapillary vessel perfusion density (VD) in glaucoma suspects (GS) and glaucoma patients; to correlate ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses with macular and peripapillary VD; and to evaluate the diagnostic accuracy of the structural and vascular parameters. Methods: A consecutive series of GS, glaucoma patients, and healthy subjects was prospectively recruited from July 1, 2016, to January 31, 2017. All subjects underwent standard automated perimetry, spectral-domain optical coherence tomography (OCT), and 6 × 6-mm optical coherence tomography angiography (OCT-A) centered on the fovea and optic nerve. Results: Forty controls, 40 GS, and 40 glaucoma patients were enrolled. Peripapillary RNFL, GCIPL, and macular RNFL thicknesses significantly decreased in the glaucoma group compared to controls and GS (P < 0.01). Peripapillary VD in average and in the superior and inferior quadrants decreased in the glaucoma group (P ≤ 0.001); conversely, macular VD was not statistically different across groups (P > 0.05). At the peripapillary area, a correlation between RNFL thickness and VD was found; conversely, no statistically significant correlation was found between GCIPL thicknesses and macular VD (all P > 0.05) in all groups. Peripapillary RNFL and GCIPL showed higher diagnostic capacity compared to peripapillary and macular VDs. Conclusions: Structural damage is evident both in the peripapillary and in macular areas. Vascular damage seems to be less prominent, as it was seen only for the glaucoma group and at the radial peripapillary plexus. Diagnostic abilities are excellent for structural variables, less so but still good for peripapillary VD, and poor for macular VD.

24 Article Measurement of Gamma-Irradiated Corneal Patch Graft Thickness After Aqueous Drainage Device Surgery. 2017

de Luna, Regina A / Moledina, Ameera / Wang, Jiangxia / Jampel, Henry D. ·Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland. · Royal College of Surgeons in Ireland, Dublin, Ireland. · Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. ·JAMA Ophthalmol · Pubmed #28772298.

ABSTRACT: Importance: Exposure of the tube of an aqueous drainage device (ADD) through the conjunctiva is a serious complication of ADD surgery. Although placement of gamma-irradiated sterile cornea (GISC) as a patch graft over the tube is commonly performed, exposures still occur. Objectives: To measure GISC patch graft thickness as a function of time after surgery, estimate the rate of graft thinning, and determine risk factors for graft thinning. Design, Setting, and Participants: Cross-sectional study of graft thickness using anterior segment optic coherence tomography (AS-OCT) was conducted at the Wilmer Eye Institute at Johns Hopkins Hospital. A total of 107 patients (120 eyes, 120 ADDs) 18 years or older who underwent ADD surgery at Johns Hopkins with GISC patch graft between July 1, 2010, and October 31, 2016, were enrolled. Intervention: Implantation of ADD with placement of GISC patch graft over the tube. Main Outcomes and Measures: Graft thickness vs time after ADD surgery and risk factors for undetectable graft. Results: Of the 107 patients included in the analysis, the mean (SD) age of the cohort was 64 (16.2) years, 49 (45.8%) were male, and 43 (40.2%) were African American. The mean time of measurement after surgery was 1.7 years (range, 1 day to 6 years). Thinner grafts were observed as the time after surgery lengthened (β regression coefficient, -60 µm per year since surgery; 95% CI, -80 µm to -40 µm). The odds ratio of undetectable grafts per year after ADD surgery was 2.1 (95% CI, 1.5-3.0; P < .001). Age, sex, race, type of ADD, quadrant of ADD placement, diagnosis of uveitis or dry eye, and prior conjunctival surgery were not correlated with the presence or absence of the graft. Conclusions and Relevance: Gamma-irradiated sterile corneal patch grafts do not always retain their integrity after ADD surgery. Data from this cross-sectional study showed that on average, the longer the time after surgery, the thinner the graft. These findings suggest that placement of a GISC patch graft is no guarantee against tube exposure, and that better strategies are needed for preventing this complication.

25 Article I Still Haven't Found What I'm Looking For... Bono, Google and Glaucoma Awareness. 2017

Lyons, C / Ellard, R / McElnea, E / Townley, D. ·Department of Ophthalmology, University Hospital Galway, University Road, Galway, Ireland. ·Ir Med J · Pubmed #28737309.

ABSTRACT: The effect of celebrity diagnosis on public awareness of health conditions has already been well documented. In October 2014, Bono, the lead singer with U2, revealed publicly for the first time that he has glaucoma. This study aimed to analyze the impact of Bono's announcement on public awareness of glaucoma using Google Search trends as an indicator of public interest in the disease. Google Trends was used to examine Google Search activity for the term 'Glaucoma' between 2009 and 2015 in both Ireland and the United Kingdom. Trend analyses were performed using Microsoft Excel Version 14.3.5. Increased Google Search activity for 'Glaucoma' in October 2014 was found in both Ireland and the United Kingdom. A five-fold increase from the mean Google Search activity for this term was found in Ireland and a two-fold increase from the mean Google Search activity for this term was found in the United Kingdom. No such increase in Google Search activity occurred during each country's 2014 Glaucoma Awareness week. Google Trends is useful in medical research as a means of assessing public awareness of, and/or interest in, health related topics. Current approaches to glaucoma related health promotion in both Ireland and the United Kingdom have failed to yield an increase in on-line Google Search activity. While there was an increase in interest in glaucoma it is unclear whether this led to an increase in health seeking behaviour.

Next