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Glaucoma: HELP
Articles from Indianapolis
Based on 90 articles published since 2008
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These are the 90 published articles about Glaucoma that originated from Indianapolis during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Drugs, Inflammation, and the Eye. 2016

Cunningham, Emmett T / London, Nikolas J S / Moorthy, Ramana / Garg, Sunir J / Zierhut, Manfred. ·a California Pacific Medical Center , San Francisco , California , USA . · b The Department of Ophthalmology , Stanford University School of Medicine , Stanford , California , USA . · c The Francis I. Proctor Foundation, UCSF School of Medicine , San Francisco , California , USA . · d West Coast Retina Medical Group , San Francisco , California , USA . · e Retina Consultants San Diego , La Jolla , California , USA . · f Associated Vitreoretinal and Uveitis Consultants, Indiana University School of Medicine , Indianapolis , Indiana , USA . · g MidAtlantic Retina, The Retina Service of Wills Eye Hospital , Philadelphia , Pennsylvania , USA , and. · h Centre for Ophthalmology, University Tuebingen , Tuebingen , Germany. ·Ocul Immunol Inflamm · Pubmed #27074544.

ABSTRACT: -- No abstract --

2 Review Targeting Transforming Growth Factor-β Signaling in Primary Open-Angle Glaucoma. 2017

Wang, Jenny / Harris, Alon / Prendes, Mark A / Alshawa, Loor / Gross, Josh C / Wentz, Scott M / Rao, Ambika B / Kim, Nathaniel J / Synder, Alexander / Siesky, Brent. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN. ·J Glaucoma · Pubmed #28169917.

ABSTRACT: Transforming growth factor-β (TGF-β) may play a role in the pathogenesis of primary open-angle glaucoma (POAG). Elevated levels of TGF-β are found in the aqueous humor and in reactive optic nerve astrocytes in patients with glaucoma. In POAG, aqueous humor outflow resistance at the trabecular meshwork (TM) leads to increased intraocular pressure and retinal ganglion cell death. It is hypothesized that TGF-β increases outflow resistance by altering extracellular matrix homeostasis and cell contractility in the TM through interactions with other proteins and signaling molecules. TGF-β may also be involved in damage to the optic nerve head. Current available therapies for POAG focus exclusively on lowering intraocular pressure without addressing extracellular matrix homeostasis processes in the TM. The purpose of this review is to discuss possible therapeutic strategies targeting TGF-β in the treatment of POAG. Herein, we describe the current understanding of the role of TGF-β in POAG pathophysiology, and examine ways TGF-β may be targeted at the levels of production, activation, downstream signaling, and homeostatic regulation.

3 Review Optical coherence tomography angiography: an overview of the technology and an assessment of applications for clinical research. 2017

Koustenis, Andrew / Harris, Alon / Gross, Josh / Januleviciene, Ingrida / Shah, Aaditya / Siesky, Brent. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Eye Clinic of Lithuanian University of Health Sciences, Kaunas, Lithuania. ·Br J Ophthalmol · Pubmed #27707691.

ABSTRACT: In recent years, ophthalmology has experienced significant developments with respect to imaging modalities. Optical coherence tomography angiography is one such technology that seeks to improve diagnostics for retinal diseases. Using standard structural ocular coherence tomography hardware, optical coherence tomography angiography demonstrates the ability to non-invasively visualise the vasculature in the retina and the choroid with high resolution, allowing greater insight into retinal vascular pathologies. In addition, retinal and choroidal vessel density and blood flow can be quantified, offering potential to assist in the diagnosis of a variety of retinal diseases. To date, numerous retinal diseases, such as open-angle glaucoma, have been found to possess a vascular component. Specifically, ischaemia of the optic nerve head and lamina cribrosa has been theorised as a causative factor in ganglion cell death; however, confirmation of this mechanism has been prohibited by the limitations of currently existing imaging modalities. Optical coherence tomography angiography provides clear imaging of these regions and the possibility to elucidate further understanding of vascular factors that contribute to glaucoma development and progression. Furthermore, this imaging modality may provide insight to neural pathologies with vascular components such as Alzheimer's disease. Herein, the authors discuss the theory of operation for optical coherence tomography angiography and the current findings from pilot studies with a focus on open-angle glaucoma. In addition, speculation is offered for future applications of the technology to study other diseases with microvascular contributions.

4 Review Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. 2017

Fini, M Elizabeth / Schwartz, Stephen G / Gao, Xiaoyi / Jeong, Shinwu / Patel, Nitin / Itakura, Tatsuo / Price, Marianne O / Price, Francis W / Varma, Rohit / Stamer, W Daniel. ·USC Institute for Genetic Medicine and Department of Cell & Neurobiology, Keck School of Medicine of USC, University of Southern California, 2250 Alcatraz St., Suite 240, Los Angeles, CA, 90089, USA. Electronic address: efini@med.usc.edu. · Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 3880 Tamiami Trail North, Naples, FL, 34103, USA. Electronic address: sschwartz2@med.miami.edu. · Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1905 W Taylor St., Suite 235, Chicago, IL, 60612, USA. Electronic address: rgao@uic.edu. · USC Institute for Genetic Medicine, USC Roski Eye Institute and Department of Ophthalmology, Keck School of Medicine of USC, University of Southern California, 2250 Alcatraz St., Suite 240, Los Angeles, CA, 90089, USA. Electronic address: shinwuje@med.usc.edu. · USC Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, 2250 Alcatraz St., Suite 240, Los Angeles, CA, 90089, USA. Electronic address: nitinusc@gmail.com. · USC Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, 2250 Alcatraz St., Suite 240, Los Angeles, CA, 90089, USA. Electronic address: itakura@med.usc.edu. · Cornea Research Foundation of America, 9002 North Meridian Street, Indianapolis, IN, 46260, USA. Electronic address: marianneprice@cornea.org. · Price Vision Group, 9002 North Meridian Street, Indianapolis, IN, 46260, USA. Electronic address: francisprice@pricevisiongroup.net. · Office of the Dean, USC Roski Eye Institute and Department of Ophthalmology, Keck School of Medicine of USC, University of Southern California, 1975 Zonal Ave., KAM 500, Los Angeles, CA, 90089, USA. Electronic address: Rohit.Varma@med.usc.edu. · Department of Ophthalmology and Department of Biomedical Engineering, Duke University, AERI Room 4008, 2351 Erwin Rd, Durham, NC, 27705, USA. Electronic address: dan.stamer@duke.edu. ·Prog Retin Eye Res · Pubmed #27666015.

ABSTRACT: Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative

5 Review Autoregulation and neurovascular coupling in the optic nerve head. 2016

Prada, Daniele / Harris, Alon / Guidoboni, Giovanna / Siesky, Brent / Huang, Amelia M / Arciero, Julia. ·Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis (IUPUI), Indianapolis, Indiana, USA. Electronic address: dprada@iupui.edu. · Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis (IUPUI), Indianapolis, Indiana, USA; Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA; LabEx IRMIA, University of Strasbourg, Strasbourg, Alsace, France. · Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis (IUPUI), Indianapolis, Indiana, USA. ·Surv Ophthalmol · Pubmed #26498862.

ABSTRACT: Impairments of autoregulation and neurovascular coupling in the optic nerve head play a critical role in ocular pathologies, especially glaucomatous optic neuropathy. We critically review the literature in the field, integrating results obtained in clinical, experimental, and theoretical studies. We address the mechanisms of autoregulation and neurovascular coupling in the optic nerve head, the current methods used to assess autoregulation--including measurements of optic nerve head blood flow (or volume and velocity)--blood flow data collected in the optic nerve head as pressure or metabolic demand is varied in healthy and pathologic conditions, and the current status and potential of mathematical modeling work to further the understanding of the relationship between ocular blood flow mechanisms and diseases such as glaucoma.

6 Review Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma. 2015

Siaudvytyte, L / Januleviciene, I / Daveckaite, A / Ragauskas, A / Bartusis, L / Kucinoviene, J / Siesky, B / Harris, A. ·Eye Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Health Telematics Science Centre of Kaunas University of Technology, Kaunas, Lithuania. · Glaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN, USA. ·Eye (Lond) · Pubmed #26183286.

ABSTRACT: There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.

7 Review Vascular Dysfunction in Diabetes and Glaucoma: A Complex Relationship Reviewed. 2015

Gerber, Austin L / Harris, Alon / Siesky, Brent / Lee, Eric / Schaab, Tara J / Huck, Andrew / Amireskandari, Annahita. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN. ·J Glaucoma · Pubmed #25264988.

ABSTRACT: Open-angle glaucoma (OAG) is a multifactorial disease characterized by progressive retinal ganglion cell death and visual field loss. Intraocular pressure, ocular perfusion pressure, and systemic vascular irregularities have all been identified as contributing factors for glaucoma onset and progression. Focal and systemic vascular abnormalities have also been well documented in diabetic patients. The relationship between diabetes mellitus and OAG remains enigmatic in the literature. As the pathogenesis of both diabetes mellitus and OAG involves compromised vascular regulation, this review was undertaken to further investigate their precise relationship. A literature review of published population-based studies was performed, with a focus on studies regarding blood flow abnormalities. Although current studies support the role of vascular contributions to both diseases, the association between glaucoma and diabetes yields contrasting results.

8 Review Vascular considerations in glaucoma patients of African and European descent. 2014

Huck, Andrew / Harris, Alon / Siesky, Brent / Kim, Nathaniel / Muchnik, Michael / Kanakamedala, Priyanka / Amireskandari, Annahita / Abrams-Tobe, Leslie. ·Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, University School of Medicine, Indianapolis, IN, USA. ·Acta Ophthalmol · Pubmed #24460758.

ABSTRACT: Glaucoma is the leading cause of blindness in individuals of African descent (AD). While open-angle glaucoma (OAG) disproportionately affects individuals of AD compared with persons of European descent (ED), the physiological mechanisms behind this disparity are largely unknown. The more rapid progression and greater severity of the disease in persons of AD further raise the concern for identifying these underlying differences in disease pathophysiology between AD and ED glaucoma patients. Ocular structural differences between AD and ED patients, including larger optic disc area, cup:disc ratio and thinner corneas, have been found. AD individuals are also disproportionately affected by systemic vascular diseases, including hypertension, cardiovascular disease, stroke and diabetes mellitus. Abnormal ocular blood flow has been implicated as a risk factor for glaucoma, and pilot research is beginning to identify localized ocular vascular differences between AD and ED OAG patients. Given the known systemic vascular deficits and the relationship between glaucoma and ocular blood flow, exploring these concepts in terms of glaucoma risk factors may have a significant impact in elucidating the mechanisms behind the disease disparity in the AD population.

9 Review Cerebrospinal fluid pressure and glaucoma: regulation of trans-lamina cribrosa pressure. 2014

Marek, Brian / Harris, Alon / Kanakamedala, Priyanka / Lee, Eric / Amireskandari, Annahita / Carichino, Lucia / Guidoboni, Giovanna / Tobe, Leslie Abrams / Siesky, Brent. ·Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indianapolis, Indiana, USA. · Department of Mathematical Sciences, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA. · Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indianapolis, Indiana, USA Department of Mathematical Sciences, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA. ·Br J Ophthalmol · Pubmed #24307714.

ABSTRACT: Increased trans-lamina cribrosa pressure difference (TLCPD), the difference of intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSF-P), has been investigated as a possible risk factor in glaucoma pathogenesis. In fact, lower CSF-P in the setting of normal IOP has been implicated as a potential risk factor for normal tension glaucoma. Increased TLCPD has been associated with decreased neuroretinal rim area and increased visual field defects. Furthermore, dysregulation of systemic blood pressure has been associated with changes in IOP. Recent studies have also suggested that increased body mass index (BMI) is associated with decreased prevalence of glaucoma, which may be due to an increased CSF-P with increased BMI found in many studies. Given the interaction of various pressures, their role in glaucoma pathophysiology has come under investigation and warrants further study in order to better understand the aetiology and progression of glaucoma.

10 Review Nanotechnology and glaucoma: a review of the potential implications of glaucoma nanomedicine. 2014

Kim, Nathaniel J / Harris, Alon / Gerber, Austin / Tobe, Leslie Abrams / Amireskandari, Annahita / Huck, Andrew / Siesky, Brent. ·Department of Ophthalmology, Indiana University School of Medicine, , Indianapolis, Indiana, USA. ·Br J Ophthalmol · Pubmed #24246373.

ABSTRACT: The purpose of this review is to discuss the evolution of nanotechnology and its potential diagnostic and therapeutic applications in the field of ophthalmology, particularly as it pertains to glaucoma. We reviewed literature using MEDLINE and PubMed databases with the following search terms: glaucoma, nanotechnology, nanomedicine, nanoparticles, ophthalmology and liposomes. We also reviewed pertinent references from articles found in this search. A brief history of nanotechnology and nanomedicine will be covered, followed by a discussion of the advantages and concerns of using this technology in the field of glaucoma. We will look at various studies concerning the development of nanomedicine, its potential applications in ocular drug delivery, diagnostic and imaging modalities and, surgical techniques. In particular, the challenges of assuring safety and efficacy of nanomedicine will be examined. We conclude that nanotechnology offers a novel approach to expanding diagnostic, imaging and surgical modalities in glaucoma and may contribute to the knowledge of disease pathogenesis at a molecular level. However, more research is needed to better elucidate the mechanism of cellular entry, the potential for nanoparticle cytotoxicity and the assurance of clinical efficacy.

11 Review Cerebral blood flow in glaucoma patients. 2013

Harris, Alon / Siesky, Brent / Wirostko, Barbara. ·Department of Ophthalmology, Glick Eye Institute, Indiana University Medical Center, Indianapolis, IN, USA. ·J Glaucoma · Pubmed #23733128.

ABSTRACT: Glaucomatous damage has been described as a slowly progressive neuronal degenerative process along the visual pathway. Decreased cerebral and ocular blood flow as well as impaired vascular autoregulation has been identified in glaucoma and have been shown to correlate with visual field loss. In low-tension glaucoma patients, diffuse cerebral ischemic changes have been detected through magnetic resonance imaging. Given these findings, it seems that for some patients, glaucomatous damage may be the ocular manifestation of a more widespread vascular abnormality involving the brain rather than a separate process isolated only to the eye and its immediate vasculature.

12 Review Retinal oxygen saturation and metabolism: how does it pertain to glaucoma? An update on the application of retinal oximetry in glaucoma. 2013

Tobe, Leslie A / Harris, Alon / Schroeder, Anne / Gerber, Austin / Holland, Stephen / Amireskandari, Annahita / Kim, Nathaniel J / Siesky, Brent. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, USA. ·Eur J Ophthalmol · Pubmed #23640511.

ABSTRACT: PURPOSE: To discuss the techniques and mechanisms of retinal oximetry with a focus on utilization of retinal oximetry in the assessment of retinal oxygen saturation in glaucoma. METHODS: We reviewed recent literature found by searching combinations of the following search terms: glaucoma, retinal oximetry, ocular blood flow, retinal blood flow, oxygen saturation. We also reviewed pertinent references from articles found in this search. RESULTS: Retinal oximetry offers the potential for directly assessing oxygen saturation in retinal tissue. This capability can contribute to the knowledge of ocular blood flow and its role in the pathogenesis of glaucoma. CONCLUSIONS: Recent research has shown that retinal oximetry could become an important clinical tool in glaucoma. However, more research is needed to validate the reliability and reproducibility of retinal oximetry, and to fully deduce its clinical role in ocular diseases.

13 Review Ocular hemodynamics and glaucoma: the role of mathematical modeling. 2013

Harris, Alon / Guidoboni, Giovanna / Arciero, Julia C / Amireskandari, Annahita / Tobe, Leslie A / Siesky, Brent A. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, USA. alharris@indiana.edu ·Eur J Ophthalmol · Pubmed #23413108.

ABSTRACT: PURPOSE: To discuss the role of mathematical modeling in studying ocular hemodynamics, with a focus on glaucoma. METHODS: We reviewed recent literature on glaucoma, ocular blood flow, autoregulation, the optic nerve head, and the use of mathematical modeling in ocular circulation. RESULTS: Many studies suggest that alterations in ocular hemodynamics play a significant role in the development, progression, and incidence of glaucoma. Although there is currently a limited number of studies involving mathematical modeling of ocular blood flow, regulation, and diseases (such as glaucoma), preliminary modeling work shows the potential of mathematical models to elucidate the mechanisms that contribute most significantly to glaucoma progression. CONCLUSION: Mathematical modeling is a useful tool when used synergistically with clinical and laboratory data in the study of ocular blood flow and glaucoma. The development of models to investigate the relationship between ocular hemodynamic alterations and glaucoma progression will provide a unique and useful method for studying the pathophysiology of glaucoma.

14 Review The role of transforming growth factor β in glaucoma and the therapeutic implications. 2013

Prendes, Mark A / Harris, Alon / Wirostko, Barbara M / Gerber, Austin L / Siesky, Brent. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. ·Br J Ophthalmol · Pubmed #23322881.

ABSTRACT: Glaucoma is a progressive optic neuropathy frequently associated with elevated intraocular pressure, ocular vascular changes and extracellular matrix remodelling at the optic nerve head and in the trabecular meshwork. The pathogenesis is multifactorial and complex, but many recent studies have suggested that transforming growth factor-β (TGF-β) plays a major role in the process. Significantly elevated levels of TGF-β have been identified in the anterior chamber of glaucomatous eyes. TGF-β has also been shown to directly cause increased intraocular pressure. It is believed that this occurs through complex interaction with the trabecular meshwork, leading to decreased aqueous humour outflow. These processes occur through specific interactions with various proteins and signalling molecules also present in ocular tissues. By understanding the role that TGF-β plays in the pathogenesis of glaucoma, alternative therapeutic agents can be developed, which target these pathways and improve and assist in the management of disease. This review will cover previous investigative studies and discuss the current understanding of TGF-β's role in glaucoma and how it may serve as a potential therapeutic target.

15 Review Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma. 2012

Shoshani, Yochai Z / Harris, Alon / Shoja, Mohammadali M / Rusia, Deepam / Siesky, Brent / Arieli, Yoel / Wirostko, Barbara. ·Department of Ophthalmology, Indiana School of Medicine, Indianapolis, Indiana 46202, USA. ·Curr Eye Res · Pubmed #22029631.

ABSTRACT: PURPOSE: To review the role of endothelin in intraocular pressure control, its effect on the trabecular meshwork (TM) and the outflow facility, effect on ocular blood flow and vascular regulation and the potential role of endothelin-1 (ET-1) antagonism in the therapeutic paradigm of glaucoma. METHODS: A thorough review of the medical literature and a meta-analysis on the level of ET-1 in OAG patients in an attempt to demonstrate the evolving importance of endothelin in glaucoma. RESULTS: ET-1 has been identified in the plasma in concentrations that are markedly increased in a number of systemic as well as ocular pathologies such as glaucoma where underlying vascular dysfunction and pathology play a role. It has been shown that ET-1 induces human TM cell contraction in culture and that it can affect the outflow facility. Evidence indicates that systemic ET-1 regulatory mechanisms and vascular responses to it are also altered in glaucoma. Recently, several endothelin antagonists have been shown to have a potential role in glaucoma therapy. In our meta-analysis, only patients with normal tension glaucoma (NTG) (as opposed to patients with high tension glaucoma (HTG)) had significantly higher plasma ET-1 levels compared to non-glaucomatous control. High tension glaucomaHTG patients had significant higher levels of ET-1 in the aqueous humor. CONCLUSIONS: The potential role of ET-1 antagonism in the therapeutic paradigm of glaucoma is an exciting possible new approach in the treatment of OAG patients. In NTG, ET-1 may have both a local and systemic component of vascular dysregulation, while whereas in HTG, the role of ET-1 may be dominantly localized to ocular tissue.

16 Review Update on the role of alpha-agonists in glaucoma management. 2011

Arthur, Stella / Cantor, Louis B. ·Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA. ·Exp Eye Res · Pubmed #21524649.

ABSTRACT: Glaucoma is the second most common cause of world blindness (following cataract) with estimated cases reaching 79.6 million by 2020. Although the etiology of glaucoma is multi-factorial, intraocular pressure (IOP) is the only modifiable factor in glaucoma management proven to alter the natural course of the disease. Among various classes of IOP-lowering medications currently available, alpha-adrenergic receptor agonists are used either as monotherapy, as second-line therapy, or in fixed combination with beta-blockers. Non-selective adrenergic agonists such as epinephrine and dipivefrin are infrequently used today for the treatment of glaucoma or ocular hypertension, and have been replaced by the alpha-2-selective agonists. The use of apraclonidine for IOP reduction in glaucoma or OHT is limited due to a high rate of follicular conjunctivitis. The alpha-2-selective agonist in use today is brimonidine. The brimonidine-purite formulations are preferred to brimonidine-benzalkonium chloride (BAC) formulations due better tolerability while maintaining similar efficacy. Brimonidine is also effective when used in combination with a beta-blocker. Using brimonidine-timolol fixed combination (BTFC) as first-line therapy has an added potential for neuroprotection. This would be a valuable strategy for glaucoma treatment, for patients who are intolerant of prostaglandin analogs, or for patients where prostaglandin analogues are contraindicated as first-line therapy, such as in patients with inflammatory glaucoma.

17 Review Feasibility of creating a normative database of colour Doppler imaging parameters in glaucomatous eyes and controls. 2011

Rusia, Deepam / Harris, Alon / Pernic, Allison / Williamson, Kathleen M / Moss, Adam M / Shoshani, Yochai Z / Siesky, Brent. ·Letzter Professor of Ophthalmology, Professor of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ·Br J Ophthalmol · Pubmed #21106991.

ABSTRACT: BACKGROUND AND AIMS: Colour Doppler imaging (CDI) is a frequently cited methodology for quantifying ocular blood flow velocities. This investigation reviews the feasibility of creating a normative database of CDI parameters in glaucoma patients and controls. A literature search was conducted for CDI studies involving glaucomatous eyes. Using data from these studies, a weighted mean was derived for the peak systolic velocity, end diastolic velocity and Pourcelot's resistive index in the ophthalmic, central retinal and posterior ciliary arteries. A multivariate analysis was performed to identify whether methodological characteristics contributed to the inter-study variance in CDI values. Data from 3061 glaucoma patients and 1072 controls were included. The mean values for glaucomatous eyes were within one standard deviation of the values for controls for most CDI parameters. Gender mix (p=0.043), intraocular pressure status (p=0.017), frequency of the ultrasound transducer (p=0.02) and whether the patients were on antihypertensive therapy (p=0.004) contributed to the variance. Methodological differences create inter-study variance in CDI values, complicating the construction of a normative database and limiting its utility. Because the mean values for glaucomatous and normal eyes have overlapping ranges, caution should be used when classifying glaucoma status based on a single CDI measurement.

18 Review Effects of exercise on intraocular pressure and ocular blood flow: a review. 2009

Risner, David / Ehrlich, Rita / Kheradiya, Nisha S / Siesky, Brent / McCranor, Lynne / Harris, Alon. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA. ·J Glaucoma · Pubmed #19680049.

ABSTRACT: Glaucoma is a disease characterized by progressive optic neuropathy resulting in retinal ganglion cell death, which affects approximately 68 million people worldwide. Risk factors include intraocular pressure (IOP), genetics, race, age, and vascular factors. Exercise is known to affect IOP and systemic cardiovascular factors and, therefore, may affect glaucoma pathophysiology. This review discusses the results of articles relevant to glaucoma, IOP, ocular blood flow (OBF), and exercise. Isometric and dynamic exercises have been studied with respect to effects on IOP and OBF. Isometric exercise results in an acute decrease in IOP, which correlates with hypocapnia. Dynamic exercise results in a more pronounced but also short duration decrease in IOP. Physical fitness is associated with lower baseline IOP but diminished acute IOP-lowering response to exercise. Upon cessation of exercise, values return to pretrained levels within 1 month. In glaucoma patients, these IOP-lowering effects are greater than in healthy subjects. In healthy subjects, OBF is unchanged during exercise due to vascular autoregulation. This autoregulation fails at ocular perfusion pressures greater than 70% above baseline. In conclusion exercise in glaucoma patients results in acutely lowered IOP and lower baseline IOP. The effects of exercise on the prevention of glaucoma and glaucomatous progression remain unknown. The role of exercise in glaucoma management should be investigated.

19 Review Literature review and meta-analysis of topical carbonic anhydrase inhibitors and ocular blood flow. 2009

Siesky, Brent / Harris, Alon / Brizendine, Edward / Marques, Clarice / Loh, Jennifer / Mackey, Joseph / Overton, Jennifer / Netland, Peter. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. ·Surv Ophthalmol · Pubmed #19171209.

ABSTRACT: The purpose of this literature review and meta-analysis was to determine what, if any, effects topical carbonic anhydrase inhibitors have on ocular hemodynamics in humans. A literature review and meta-analysis was conducted to investigate the effects of topical carbonic anhydrase inhibitors on ocular blood flow. Thirty-five articles were evaluated according to the inclusion criteria with 13 manuscripts meeting requirements for statistical analysis. Each study's effect size, defined as the change in blood flow measures after treatment with topical carbonic anhydrase inhibitors, was estimated using the weighted mean difference. Based on this meta-analysis, we conclude that topical carbonic anhydrase inhibitors increase ocular blood flow velocities in the retinal circulation, central retinal and short posterior ciliary arteries, but not in the ophthalmic artery.

20 Review Age-related ocular vascular changes. 2009

Ehrlich, Rita / Kheradiya, Nisha S / Winston, Diana M / Moore, Daniel B / Wirostko, Barbara / Harris, Alon. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA. ·Graefes Arch Clin Exp Ophthalmol · Pubmed #19084984.

ABSTRACT: BACKGROUND: The global society is aging at an increasing rate, with a continually larger proportion of the population consisting of those over the age of 65. Age-related vascular changes have been demonstrated in ocular tissue, and the incidence and prevalence of diseases such as macular degeneration, glaucoma and vascular occlusive diseases increase significantly with age. METHODS: This article reviews the current body of literature examining age-associated ocular vascular changes, and summarizes the aggregate findings. We discuss the potential role of the aging vasculature in the etiology of age-associated ocular disease, focusing on glaucoma. RESULTS: Our working hypothesis is that although advancing age is a physiological phenomenon, there are stepwise hemodynamic and vascular changes that occur, predisposing the eye and other tissue beds to pathological conditions. Advancing age does not independently give rise to disease, but does generate increasingly vulnerable vascular beds that are susceptible to further insults. CONCLUSIONS: These results compel a need for further investigation of age-related changes in ocular physiology and pathophysiology.

21 Review Mechanobiology of trabecular meshwork cells. 2009

WuDunn, Darrell. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. dwudunn@iupui.edu ·Exp Eye Res · Pubmed #19071113.

ABSTRACT: Trabecular meshwork (TM) cells likely play a key role in regulating outflow facility and hence intraocular pressure. They function in a dynamic environment subjected to variations in mechanical and fluid shear forces. Because the extent of mechanical stress on the trabecular meshwork is dependent on the intraocular pressure, the behavior of TM cells under mechanical strain may suggest mechanisms for how outflow facility is regulated. Studies have demonstrated that TM cells respond in a variety of ways to mechanical loads, including increased extracellular matrix turnover, altered gene expression, cytokine release, and altered signal transduction. This review highlights some of the considerations and limitations of studying the mechanobiology of TM cells.

22 Review [An updated review of methods for human retinal oximetry measurements and current applications]. 2008

Ben-Zion, Itay / Harris, Alon / Weizman, Yosi / Ehrlich, Rita / Rechtman, Ehud. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. ·Harefuah · Pubmed #19039914.

ABSTRACT: The concept of retinal oximetry is based on physical properties that have been recognized since the 18th century. Attempts to non-invasively quantify the oxygen saturation of blood within the retinal vasculature date back to the 1950's. There are different techniques in existence for the measurement of retinal oxygenation, the leading ones are: photographic, digital, spectroscopy and the pulse methods. Each method has its advantages and disadvantages. Current data from studies on retinal oximetry is presented, for both the healthy retina and in diseases such as glaucoma, diabetic retinopathy and age-related macular degeneration. It is clear that a thorough understanding of retinal oxygen tension is vital to our understanding of normal retinal physiology and the pathophysiology of degenerative eye diseases.

23 Review The circadian variations in systemic blood pressure, ocular perfusion pressure, and ocular blood flow: risk factors for glaucoma? 2008

Werne, Adam / Harris, Alon / Moore, Danny / BenZion, Itay / Siesky, Brent. ·Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. ·Surv Ophthalmol · Pubmed #19026319.

ABSTRACT: Intraocular pressure, a major risk factor for glaucoma, is known to vary throughout the day, yet glaucoma continues to progress in some patients despite it being well controlled. It is important to understand how other glaucomatous risk factors are affected by circadian variations. The purpose of this review is to analyze the literature concerning circadian variations in systemic blood pressure, ocular perfusion pressure, and ocular blood flow and to identify consensus findings regarding their impact on glaucoma. This review suggests that nonphysiologic nocturnal blood pressure dipping and wider circadian fluctuations in ocular perfusion pressure are linked with the development and progression of glaucoma. No consensus concerning circadian variations in ocular blood flow exists in the current literature, and future investigations of nocturnal changes in blood flow and glaucoma progression are required.

24 Review Measuring and interpreting ocular blood flow and metabolism in glaucoma. 2008

Harris, Alon / Kagemann, Larry / Ehrlich, Rita / Rospigliosi, Carlos / Moore, Danny / Siesky, Brent. ·Department of Ophthalmology, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA. alharris@indiana.edu ·Can J Ophthalmol · Pubmed #18443609.

ABSTRACT: There is a growing body of evidence suggesting that vascular dysfunction is related to several prominent ophthalmic diseases, including glaucoma. The vast majority of studies providing data on ocular circulation and disease pathophysiology use a relatively small number of complicated ocular blood flow imaging techniques. Although these imaging technologies are not commonly used in clinical settings, understanding the medical literature characterizing ocular blood flow requires familiarity with their methodology and function. This review highlights the imaging technologies most commonly used to investigate ocular blood flow, including color Doppler imaging, confocal scanning laser ophthalmoscopic angiography with fluorescein and indocyanine green dye, Canon laser blood flowmetry, scanning laser Doppler flowmetry, and retinal photographic oximetry. Each imaging technique's ability to define vascular function and reveal pathology is discussed as are limitations inherent to each technology. The ultimate goal of this review is to provide the physician with a clinically relevant foundation for differentiating the various ocular blood flow outcome measures often presented in the literature and determine how they are related to ocular health and disease.

25 Clinical Trial Ocular hypotensive effect of the novel EP3/FP agonist ONO-9054 versus Xalatan: results of a 28-day, double-masked, randomised study. 2017

Miller Ellis, Eydie / Berlin, Michael S / Ward, Caroline L / Sharpe, John A / Jamil, Alam / Harris, Alon. ·Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Glaucoma Institute of Beverly Hills & Jules Stein Eye Institute, UCLA, Los Angeles, California, USA. · Ono Pharma UK, London, UK. · Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA. ·Br J Ophthalmol · Pubmed #27649982.

ABSTRACT: BACKGROUND/AIMS: ONO-9054 is being developed for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) and open-angle glaucoma (OAG). This study compared the novel dual EP3/FP agonist ONO-9054 with the FP agonist Xalatan. METHODS: Adults (n=123) with bilateral mild/moderate OAG or OHT, with unmedicated IOP of ≥24 mm Hg at 8:00 hours, ≥21 mm Hg at 10:00 hours and ≤36 mm Hg, were randomised 1:1 to receive ONO-9054 (0.003%, 30 μg/mL) or Xalatan (0.005%, 50 μg/mL) once daily for 28 days. RESULTS: Day 29 mean diurnal IOP was -7.2 mm Hg for ONO-9054 vs -6.6 mm Hg for Xalatan. At 08:00 hours, the IOPs were comparable, and at all later time points the decrease in IOP was greater for ONO-9054. On day 29, the odds of a mean IOP reduction of ≤-25%, ≤-30% and ≤-35% for ONO-9054 were 2.39, 2.37 and 4.85 times more, respectively, than the odds for Xalatan (p<0.05, CONCLUSIONS: Subjects randomised to receive ONO-9054 were more likely to achieve a greater per cent reduction in IOP and were more likely to achieve target IOPs than those receiving Xalatan. The effects of ONO-9054 in reducing IOP appear to persist longer than those of Xalatan. TRIAL REGISTRATION NUMBER: NCT02083289, Results.

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