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Glaucoma: HELP
Articles from University of North Carolina Chapel Hill
Based on 141 articles published since 2009
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These are the 141 published articles about Glaucoma that originated from University of North Carolina Chapel Hill during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Review Current concepts of cerebrospinal fluid dynamics and the translaminar cribrosa pressure gradient: a paradigm of optic disk disease. 2019

Liu, Katy C / Fleischman, David / Lee, Andrew G / Killer, Hanspeter E / Chen, John J / Bhatti, M Tariq. ·Department of Ophthalmology, Duke Eye Center, Durham, North Carolina, USA. · Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, USA. · Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, USA; Department of Ophthalmology, Weill Cornell Medicine, New York, NY, USA; Department of Neurology, Weill Cornell Medicine, New York, NY, USA; Department of Neurosurgery, Weill Cornell Medicine, New York, NY, USA. · Department of Ophthalmology, Kantonsspital Aarau, Aarau, Switzerland; Center of Biomedicine University of Basel, Basel, Switzerland. · Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA. · Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA. Electronic address: bhatti.muhammad@mayo.edu. ·Surv Ophthalmol · Pubmed #31449832.

ABSTRACT: Modern advances in measuring and studying cerebrospinal fluid dynamics have furthered our understanding of intracranial pressure and its pathophysiological effects on the eye. In particular, the cerebrospinal fluid pressure and composition within the optic nerve subarachnoid space are key factors in diseases of the optic disk. Intracranial pressure and intraocular pressure establish a pressure gradient across the lamina cribrosa. Alterations in this translaminar cribrosa pressure difference induce structural deformations in the lamina cribrosa manifested clinically by the appearance of optic disk edema or optic disk cupping. Much has been learned about papilledema (i.e., optic disk edema due to elevated intracranial pressure) from clinical observations and studies on patients with idiopathic intracranial hypertension. Furthermore, optic nerve subarachnoid space hydrodynamics and translaminar cribrosa pressure difference are postulated to contribute to the pathogenesis of optic disk edema observed in spaceflight-associated neuroocular syndrome. Recently, a substantial body of literature has accumulated suggesting low intracranial pressure may be a risk factor for the development of glaucomatous optic disk cupping within the context of the translaminar cribrosa pressure difference and posterior scleral biomechanics.

2 Review A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome. 2018

De la Torre, Alejandro J / Luat, Aimee F / Juhász, Csaba / Ho, Mai Lan / Argersinger, Davis P / Cavuoto, Kara M / Enriquez-Algeciras, Mabel / Tikkanen, Stephanie / North, Paula / Burkhart, Craig N / Chugani, Harry T / Ball, Karen L / Pinto, Anna Lecticia / Loeb, Jeffrey A. ·Department of Neurology, Northwestern University, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. · Department of Pediatrics and Neurology, Wayne State University, Children's Hospital of Michigan, Detroit, Michigan. · Department of Radiology, Mayo Clinic, Rochester, Minnesota. · Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. · School of Communication Studies, Ohio University, Athens, Ohio. · Department of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin. · Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina. · Department of Neurology, Nemours DuPont Hospital for Children, Wilmington, Delaware. · The Sturge-Weber Foundation, Houston, Texas. · Department of Neurology, Harvard Medical School, Children's Hospital Boston, Boston, Massachusetts. · Department of Neurology and Rehabilitation, University of Illinois, Chicago, Illinois. Electronic address: jaloeb@uic.edu. ·Pediatr Neurol · Pubmed #29803545.

ABSTRACT: BACKGROUND: Sturge-Weber syndrome is a neurocutaneous disorder associated with port-wine birthmark, leptomeningeal capillary malformations, and glaucoma. It is associated with an unpredictable clinical course. Because of its rarity and complexity, many physicians are unaware of the disease and its complications. A major focus moving ahead will be to turn knowledge gaps and unmet needs into new research directions. METHODS: On October 1-3, 2017, the Sturge-Weber Foundation assembled clinicians from the Clinical Care Network with patients from the Patient Engagement Network of the Sturge-Weber Foundation to identify our current state of knowledge, knowledge gaps, and unmet needs. RESULTS: One clear unmet need is a need for consensus guidelines on care and surveillance. It was strongly recommended that patients be followed by multidisciplinary clinical teams with life-long follow-up for children and adults to monitor disease progression in the skin, eye, and brain. Standardized neuroimaging modalities at specified time points are needed together with a stronger clinicopathologic understanding. Uniform tissue banking and clinical data acquisition strategies are needed with cross-center, longitudinal studies that will set the stage for new clinical trials. A better understanding of the pathogenic roles of cerebral calcifications and stroke-like symptoms is a clear unmet need with potentially devastating consequences. CONCLUSIONS: Biomarkers capable of predicting disease progression will be needed to advance new therapeutic strategies. Importantly, how to deal with the emotional and psychological effects of Sturge-Weber syndrome and its impact on quality of life is a clear unmet need.

3 Review Utility of combining spectral domain optical coherence tomography structural parameters for the diagnosis of early Glaucoma: a mini-review. 2018

Mwanza, Jean-Claude / Warren, Joshua L / Budenz, Donald L. ·1Department of Ophthalmology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC USA. · 0000000122483208 · grid.10698.36 · 2Department of Biostatistics, Yale University, New Haven, CT USA. · 0000000419368710 · grid.47100.32 ·Eye Vis (Lond) · Pubmed #29725607.

ABSTRACT: Optical coherence tomography (OCT) has moved to the forefront of imaging modalities in the management of glaucoma and retinal diseases. It is modifying how glaucoma and glaucoma progression are diagnosed clinically and augmenting our understanding of the disease. OCT provides multiple parameters from various anatomic areas for glaucoma diagnosis, evaluation of treatment efficacy, and progression monitoring. While the use of multiple parameters has increased the likelihood of detecting early structural changes, diagnosing glaucoma in early stages is often challenging when the damages are subtle and not apparent on OCT scans, in addition to the fact that assessment of OCT parameters often yields conflicting findings. One promising approach is to combine multiple individual parameters into a composite parameter from the same test to improve diagnostic accuracy, sensitivity, and specificity. This review presents current evidence regarding the value of spectral domain OCT composite parameters in diagnosing early glaucoma.

4 Review Consensus recommendations for trabecular meshwork cell isolation, characterization and culture. 2018

Keller, Kate E / Bhattacharya, Sanjoy K / Borrás, Theresa / Brunner, Thomas M / Chansangpetch, Sunee / Clark, Abbott F / Dismuke, W Michael / Du, Yiqin / Elliott, Michael H / Ethier, C Ross / Faralli, Jennifer A / Freddo, Thomas F / Fuchshofer, Rudolf / Giovingo, Michael / Gong, Haiyan / Gonzalez, Pedro / Huang, Alex / Johnstone, Murray A / Kaufman, Paul L / Kelley, Mary J / Knepper, Paul A / Kopczynski, Casey C / Kuchtey, John G / Kuchtey, Rachel W / Kuehn, Markus H / Lieberman, Raquel L / Lin, Shan C / Liton, Paloma / Liu, Yutao / Lütjen-Drecoll, Elke / Mao, Weiming / Masis-Solano, Marisse / McDonnell, Fiona / McDowell, Colleen M / Overby, Darryl R / Pattabiraman, Padmanabhan P / Raghunathan, Vijay K / Rao, P Vasanth / Rhee, Douglas J / Chowdhury, Uttio Roy / Russell, Paul / Samples, John R / Schwartz, Donald / Stubbs, Evan B / Tamm, Ernst R / Tan, James C / Toris, Carol B / Torrejon, Karen Y / Vranka, Janice A / Wirtz, Mary K / Yorio, Thomas / Zhang, Jie / Zode, Gulab S / Fautsch, Michael P / Peters, Donna M / Acott, Ted S / Stamer, W Daniel. ·Oregon Health and Science University, United States. · University of Miami, United States. · University of North Carolina-Chapel Hill, United States. · Glaucoma Research Foundation, United States. · University of California, San Francisco, United States. · University of North Texas Health Sciences Center, United States. · Aerie Pharmaceuticals, United States. · University of Pittsburgh, United States. · University of Oklahoma, United States. · Georgia Institute of Technology, United States. · University of Wisconsin, United States. · Massachusetts College of Pharmacy and Health Sciences, United States. · University of Regensburg, Germany. · John H. Stroger, Jr. Hospital of Cook County, United States. · Boston University, United States. · Duke University, United States. · University of California, Los Angeles, United States. · University of Washington, United States. · University of Illinois at Chicago, United States. · Vanderbilt University, United States. · University of Iowa, United States. · Augusta University, United States. · University of Erlangen-Nuremberg, Germany. · Imperial College, London, United Kingdom. · Case Western Reserve University, United States. · University of Houston, United States. · Mayo Clinic, United States. · University of California, Davis, United States. · Western Glaucoma Foundation, United States. · EyeSonix, United States. · Loyola University, Chicago, United States. · University of Southern California, United States. · Glauconix, United States. · Department of Ophthalmology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, United States. Electronic address: fautsch.michael@mayo.edu. · Department of Pathology & Laboratory Medicine, University of Wisconsin, 1300 University Ave, Madison, WI 53706, United States. Electronic address: dmpeter2@wisc.edu. · Department of Ophthalmology, Department of Biochemistry & Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, United States. Electronic address: acott@ohsu.edu. · Department of Ophthalmology, Duke University, DUMC 3802, Durham, NC 27705, United States. Electronic address: dan.stamer@duke.edu. ·Exp Eye Res · Pubmed #29526795.

ABSTRACT: Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and their dysfunction resulting in ocular hypertension. In this review, we describe the standard procedures used for the isolation of TM cells from several animal species including humans, and the methods used to validate their identity. Having a set of standard practices for TM cells will increase the scientific rigor when used as a model, and enable other researchers to replicate and build upon previous findings.

5 Review Growth Factors, Oxidative Damage, and Inflammation in Exfoliation Syndrome. 2018

Borrás, Teresa. ·Department of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, NC. ·J Glaucoma · Pubmed #29401156.

ABSTRACT: Exfoliation syndrome (XFS) produces deleterious ocular aging and has protean systemic manifestations. Local ocular production of TGFβ1 is of central importance in XFS. TGFβ1 appears to induce the expression of LOXL1 and the production of other extracellular matrix components which are known to be present in exfoliation material. Furthermore, results from several studies find that the aqueous humor of exfoliation glaucoma patients exhibits a decreased antioxidant defense and increased oxidative stress systems. Finally, studies show that the levels of interleukin-6 and interleukin-8 in the aqueous humor of XFS patients were 3-fold higher than in controls. Overall TGFβ1, as well as a prooxidative and proinflammatory environment seems to play an important role in XFS.

6 Review Drop instillation and glaucoma. 2018

Davis, Scott A / Sleath, Betsy / Carpenter, Delesha M / Blalock, Susan J / Muir, Kelly W / Budenz, Donald L. ·Division of Pharmaceutical Outcomes and Policy, University of North Carolina Eshelman School of Pharmacy. · Cecil G. Sheps Center for Health Services Research, Chapel Hill, North Carolina. · Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina. · Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. ·Curr Opin Ophthalmol · Pubmed #29140818.

ABSTRACT: PURPOSE OF REVIEW: To describe the current state of knowledge regarding glaucoma patients' eye drop technique, interventions attempting to improve eye drop technique, and methods for assessing eye drop technique. RECENT FINDINGS: In observational studies, between 18.2 and 80% of patients contaminate their eye drop bottle by touching their eye or face, 11.3-60.6% do not instill exactly one drop, and 6.8-37.3% miss the eye with the drop. Factors significantly associated with poorer technique include older age, lack of instruction on eye drop technique, female sex, arthritis, more severe visual field defect, lack of positive reinforcement to take eye drops, lower educational level, low self-efficacy, and being seen at a clinic rather than a private practice. Among intervention studies, four of five studies using a mechanical device and three of four studies using educational interventions to improve technique showed positive results, but none of the studies were randomized controlled trials. SUMMARY: Poor eye drop technique is a significant impediment to achieving good control of intraocular pressure in glaucoma. Both mechanical device interventions and educational interventions offer promise to improve patients' technique, but studies with stronger designs need to be done followed by introduction into clinical practice.

7 Review New developments in optical coherence tomography imaging for glaucoma. 2018

Mwanza, Jean-Claude / Budenz, Donald L. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. ·Curr Opin Ophthalmol · Pubmed #29140817.

ABSTRACT: PURPOSE OF REVIEW: Since its introduction in ophthalmology, optical coherence tomography (OCT) has undergone significant advances in imaging protocols, algorithms, and addition of new parameters which have maximized its potential for diagnosing, evaluating the response to treatment, and assessing the progression of various ocular diseases, including glaucoma. This review provides an update on recent developments in OCT with respect to the management of glaucoma. RECENT FINDINGS: Most recent notable developments include the introduction of the minimum distance band, which is a three-dimensional optic nerve head parameter, and Swept-Source OCT with its single wide-field scanning capability. The introduction of OCT angiography provides additional structural and functional measures for glaucoma management. Adaptive optics helps visualize individual RNFL bundles and measure their widths. SUMMARY: Continued improvements in OCT technology is both enhancing our understanding of glaucoma and improving our ability to manage the disease.

8 Review Detecting Visual Field Progression. 2017

Aref, Ahmad A / Budenz, Donald L. ·Illinois Eye & Ear Infirmary, University of Illinois at Chicago College of Medicine, Chicago, Illinois. · Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: donald_budenz@med.unc.edu. ·Ophthalmology · Pubmed #29157362.

ABSTRACT: Timely detection of glaucomatous progression is crucial in the delivery of glaucoma care. Clinical judgment may be used to make this assessment, but relatively modest agreement among practitioners supports the use of complementary methods. Event-based analyses take into account expected localized test-retest variabilities in sensitivity, and trend-based analyses are helpful for determining and predicting overall visual function. Landmark clinical trials have used various visual field progression criteria as end points with variable performances. Short- and long-term fluctuations as well as inadequate testing frequency are limitations in visual field analysis for glaucomatous progression. Ongoing improvements in statistical techniques as well as incorporation of functional and structural measures into a single model likely will lead to an enhanced ability to detect glaucomatous progression and will allow for more timely and appropriate therapy.

9 Review Injectable hydrogels for ophthalmic applications. 2017

Wang, Kai / Han, Zongchao. ·Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 27599, USA. · Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 27599, USA; Carolina Institute for Nano Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: zongchao@med.unc.edu. ·J Control Release · Pubmed #29061512.

ABSTRACT: The demand for effective eye therapies is driving the development of injectable hydrogels as new medical devices for controlled delivery and filling purposes. This article introduces the properties of injectable hydrogels and summarizes their versatile application in the treatment of ophthalmic diseases, including age-related macular degeneration, cataracts, diabetic retinopathy, glaucoma, and intraocular cancers. A number of injectable hydrogels are approved by FDA as surgery sealants, tissue adhesives, and are now being investigated as a vitreous humor substitute. Research on hydrogels for drug, factor, nanoparticle, and stem cell delivery is still under pre-clinical investigation or in clinical trials. Although substantial progress has been achieved using injectable hydrogels, some challenging issues must still be overcome before they can be effectively used in medical practice.

10 Review The Pathway From Genes to Gene Therapy in Glaucoma: A Review of Possibilities for Using Genes as Glaucoma Drugs. 2017

Borrás, Teresa. ·Department of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, North Carolina. ·Asia Pac J Ophthalmol (Phila) · Pubmed #28161916.

ABSTRACT: Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration.

11 Review A single gene connects stiffness in glaucoma and the vascular system. 2017

Borrás, Teresa. ·Department of Ophthalmology, University of North Carolina School of Medicine, 4109C Neuroscience Research Building CB 7041, 105 Mason Farm Road, Chapel Hill, NC 27599-7041, USA. Electronic address: tborras@med.unc.edu. ·Exp Eye Res · Pubmed #27593913.

ABSTRACT: Arterial calcification results in arterial stiffness and higher systolic blood pressure. Arterial calcification is prevented by the high expression of the Matrix-Gla gene (MGP) in the vascular smooth muscle cells (VSMC) of the arteries' tunica media. Originally, MGP, a gene highly expressed in cartilage and VSMC, was found to be one of the top expressed genes in the trabecular meshwork. The creation of an Mgp-lacZ Knock-In mouse and the use of mouse genetics revealed that in the eye, Mgp's abundant expression is localized and restricted to glaucoma-associated tissues from the anterior and posterior segments. In particular, it is specifically expressed in the regions of the trabecular meshwork and of the peripapillary sclera that surrounds the optic nerve. Because stiffness in these tissues would significantly alter outflow facility and biomechanical scleral stress in the optic nerve head (ONH), we propose MGP as a strong candidate for the regulation of stiffness in glaucoma. MGP further illustrates the presence of a common function affecting key glaucomatous parameters in the front and back of the eye, and thus offers the possibility for a sole therapeutic target for the disease.

12 Review Optical coherence tomography platforms and parameters for glaucoma diagnosis and progression. 2016

Mwanza, Jean-Claude / Budenz, Donald L. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. ·Curr Opin Ophthalmol · Pubmed #26569530.

ABSTRACT: PURPOSE OF REVIEW: Optical coherence tomography (OCT) aids in the diagnosis and long-term monitoring of various ocular diseases, including glaucoma. Initially, the retinal nerve fiber layer was the only OCT structural parameter used in glaucoma. Subsequent research has resulted in more retinal and optic nerve head parameters. In addition, OCT is being investigated for its ability to assess ocular hemodynamics. This review summarizes these spectral domain-optical coherence tomography (SDOCT) parameters in the context of glaucoma. RECENT FINDINGS: Several new SDOCT retinal nerve fiber layer, optic nerve head, and macular parameters with good glaucoma diagnostic ability have been added to existing ones recently. The combination of SDOCT and Doppler or angiography has also resulted in hemodynamic parameters that may prove to be useful in the functional assessment in glaucoma. SUMMARY: OCT technology is advancing not only as a tool for structural assessment, but also as a multimodality tool to assess both structure and function to enhance our understanding of glaucoma, and ultimately clinical decisions.

13 Review The cellular and molecular biology of the iris, an overlooked tissue: the iris and pseudoexfoliation glaucoma. 2014

Borrás, Terete. ·Department of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, NC. ·J Glaucoma · Pubmed #25275904.

ABSTRACT: Located between the cornea and the lens, the Iris is fully immersed in aqueous humor. During exfoliation syndrome, a disorder of the elastic fibers, an abnormal fibrillar material (XFM) is deposited on the anterior lens capsule underneath the pigment epithelium of the Iris. Release of this material to the aqueous humor reaches the trabecular meshwork where its presence is associated with elevated intraocular pressure. Ultrastructural studies suggest that the XFM material is produced by the lens capsule, lens epithelial and iris pigment epithelial cells (IPE). The involvement of the IPE in pseudoexfoliation glaucoma has not been extensively addressed. Immunohistochemistry studies have shown higher levels of LOXL1 and clusterin in the IPE extracellular space of specimens from exfoliation patients. But studies using IPE cells to understand the formation of the XFM in vitro and/or in vivo are scarce. A focus on the Iris and its IPE cells would be key for the elucidation of XFM and the understanding of the development of pseudoexfoliation glaucoma.

14 Review The effects of myocilin expression on functionally relevant trabecular meshwork genes: a mini-review. 2014

Borrás, Teresa. ·Department of Ophthalmology, University of North Carolina School of Medicine , Chapel Hill, North Carolina. ·J Ocul Pharmacol Ther · Pubmed #24564495.

ABSTRACT: Myocilin is a secreted glaucoma-associated protein, specifically induced by dexamethasone in human trabecular meshwork cells, where it was discovered. Myocilin is expressed in several tissues of the body, but it causes disease only in the eye. The protein contains two domains: an N-terminal region with significant homologies to nonmuscle myosin, and a C-terminal region, which is similar to the olfactomedin proteins. Forty percent of myocilin undergoes an intracellular endoproteolytic cleavage by calpain II, a calcium-dependent cysteine protease, which releases the 2 domains. The protein is known to interact with intracellular and extracellular matrix proteins, and some is released into the extracellular space associated with exosomes. Myocilin mutations are linked to glaucoma and induce elevated intraocular pressure. Most of the glaucoma-causative mutations map to the olfactomedin domain, which appears to be a critical domain for the function of the protein. Myocilin mutants are misfolded, aggregate in the endoplasmic reticulum, and are not secreted. Overexpression of myocilin and of its mutants in primary human trabecular meshwork cells triggers changes in the expression of numerous genes, many of which have been known to be involved in mechanisms important for the physiology and pathology of the tissue. Here we review recent studies from our laboratory and those of others that deal with trabecular meshwork genes, which are altered by the overexpression of wild-type and glaucoma-causative mutant myocilin genes.

15 Review Sustained drug delivery in glaucoma. 2014

Knight, O'Rese J / Lawrence, Scott D. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. ·Curr Opin Ophthalmol · Pubmed #24463419.

ABSTRACT: PURPOSE OF REVIEW: This article reviews recently published studies and important clinical trials of novel drug delivery systems for glaucoma and evaluates the potential of these systems to provide sustained therapeutic benefits. RECENT FINDINGS: The efficacy of topical medications to lower intraocular pressure (IOP) is limited by poor patient adherence, low bioavailability of drug and the potential for local and systemic side effects. Recent studies highlight the potential for sustained drug delivery through innovative delivery platforms. Nanoparticle-based formulations, drug-eluting contact lenses, punctum inserts and bioadhesive matrices placed in the conjunctival sac can enhance drug delivery by increasing precorneal residence time, enhancing corneal permeation and lowering the systemic absorption of drug. Periocular injections and surgically implanted drug reservoirs could offer even greater duration of drug delivery, particularly when the drug is packaged within stable vehicles. SUMMARY: Novel platforms for providing sustained drug delivery in glaucoma continue to evolve. The ability to incorporate effective commercially available drugs into more stable compounds is an important element. Although more research is needed to establish their clinical efficacy, novel delivery systems will allow for more targeted medical therapy and for the opportunity to further explore neuroprotective and gene-based therapies.

16 Review New options for combined cataract and glaucoma surgery. 2014

Budenz, Donald L / Gedde, Steven J. ·aDepartment of Ophthalmology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina bBascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA. ·Curr Opin Ophthalmol · Pubmed #24389806.

ABSTRACT: PURPOSE OF REVIEW: To review the current literature regarding the effectiveness and risks of new surgeries that can be combined with phacoemulsification in the management of cataract and glaucoma. RECENT FINDINGS: Surgical options for concurrently managing cataract and glaucoma have expanded in recent years. Endoscopic cyclophotocoagulation, trabecular micro-bypass stent, ab interno trabeculectomy, and canaloplasty may be performed in conjunction with cataract extraction to provide additional intraocular pressure (IOP) reduction. Studies evaluating these new glaucoma procedures combined with phacoemulsification generally include retrospective case series without a comparison group. Because cataract surgery alone is associated with IOP reduction, the relative contribution of the glaucoma procedure in lowering IOP cannot be determined in these studies. Randomized clinical trials are needed to better evaluate the efficacy and safety of newer glaucoma procedures in combination with cataract surgery. SUMMARY: The newer glaucoma procedures appear less effective than trabeculectomy, but they are associated with a lower risk of surgical complications.

17 Review The role of cerebrospinal fluid pressure in glaucoma and other ophthalmic diseases: A review. 2013

Fleischman, David / Allingham, R Rand. ·Department of Ophthalmology, University of North Carolina Hospitals, Chapel Hill, NC, USA. ·Saudi J Ophthalmol · Pubmed #24227969.

ABSTRACT: Glaucoma is one of the most common causes of blindness in the world. Well-known risk factors include age, race, a positive family history and elevated intraocular pressures. A newly proposed risk factor is decreased cerebrospinal fluid pressure (CSFP). This concept is based on the notion that a pressure differential exists across the lamina cribrosa, which separates the intraocular space from the subarachnoid fluid space. In this construct, an increased translaminar pressure difference will occur with a relative increase in elevated intraocular pressure or a reduction in CSFP. This net change in pressure is proposed to act on the tissues within the optic nerve head, potentially contributing to glaucomatous optic neuropathy. Similarly, patients with ocular hypertension who have elevated CSFPs, would enjoy a relatively protective effect from glaucomatous damage. This review will focus on the current literature pertaining to the role of CSFP in glaucoma. Additionally, the authors examine the relationship between glaucoma and other known CSFP-related ophthalmic disorders.

18 Review Ocular disease, knowledge and technology applications in patients with diabetes. 2013

Threatt, Jennifer / Williamson, Jennifer F / Huynh, Kyle / Davis, Richard M / Hermayer, Kathie. ·East Carolina University, Greenville, North Carolina. · The University of North Carolina at Chapel Hill (JFW, KH, RMD), Chapel Hill, North Carolina. · The University of North Carolina at Chapel Hill (JFW, KH, RMD), Chapel Hill, North Carolina. Electronic address: richdavis@unc.edu. · School of Medicine and Health Sciences, George Washington University, Washington DC. ·Am J Med Sci · Pubmed #23531956.

ABSTRACT: An estimated 25.8 million children and adults in the United States, approximately 8.3% of the population, have diabetes. Diabetes prevalence varies by race and ethnicity. African Americans have the highest prevalence (12.6%), followed closely by Hispanics (11.8%), Asian Americans (8.4%) and whites (7.1%). The purpose of this article was to discuss the ocular complications of diabetes, the cultural and racial differences in diabetes knowledge and the role of telemedicine as a means to reach the undeserved who are at risk of complications. Information on the pathophysiology of ocular disease in patients with diabetes and the role of telemedicine in diabetes care was derived from a literature review. National Institutes of Health online resources were queried to present data on the racial and cultural understandings of diabetes and diabetes-related complications. The microvascular ocular complications of diabetes are discussed for retinopathy, cataracts, glaucoma and ocular surface disease. Racial and cultural differences in knowledge of recommended self-care practices are presented. These differences, in part, may explain health disparities and the increased risk of diabetes and its complications in rural minority communities. Finally, advances in telemedicine technology are discussed that show improvements in metabolic control and cardiovascular risk in adults with type 2 diabetes. Improving provider and patient understanding of diabetes complications may improve management and self-care practices that are important for diabetes control. Telemedicine may improve access to diabetes specialists and may improve self-management education and diabetes control particularly in rural and underserved communities.

19 Review Review: a meta-analysis of GWAS and age-associated diseases. 2012

Jeck, William R / Siebold, Alex P / Sharpless, Norman E. ·Department of Genetics, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, NC, USA. ·Aging Cell · Pubmed #22888763.

ABSTRACT: Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SNPs associated with many important human diseases, including diseases associated with aging. In an effort to understand the genetics of broad resistance to age-associated diseases (i.e., 'wellness'), we performed a meta-analysis of human GWAS. Toward that end, we compiled 372 GWAS that identified 1775 susceptibility SNPs to 105 unique diseases and used these SNPs to create a genomic landscape of disease susceptibility. This map was constructed by partitioning the genome into 200 kb 'bins' and mapping the 1775 susceptibility SNPs to bins based on their genomic location. Investigation of these data revealed significant heterogeneity of disease association within the genome, with 92% of bins devoid of disease-associated SNPs. In contrast, 10 bins (0.06%) were significantly (P < 0.05) enriched for susceptibility to multiple diseases, 5 of which formed two highly significant peaks of disease association (P < .0001). These peaks mapped to the Major Histocompatibility (MHC) locus on 6p21 and the INK4/ARF (CDKN2a/b) tumor suppressor locus on 9p21.3. Provocatively, all 10 significantly enriched bins contained genes linked to either inflammation or cellular senescence pathways, and SNPs near regulators of senescence were particularly associated with disease of aging (e.g., cancer, atherosclerosis, type 2 diabetes, glaucoma). This analysis suggests that germline genetic heterogeneity in the regulation of immunity and cellular senescence influences the human healthspan.

20 Review What's new in laser treatment for glaucoma? 2012

Meyer, Jay J / Lawrence, Scott D. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7040, USA. ·Curr Opin Ophthalmol · Pubmed #22186007.

ABSTRACT: PURPOSE OF REVIEW: This review highlights recently published studies on prevailing and newer laser therapies in glaucoma and critically evaluates their roles in the treatment algorithm. RECENT FINDINGS: Recently published studies suggest a role for selective laser trabeculoplasty (SLT) as initial therapy for open-angle glaucoma and ocular hypertension and have demonstrated efficacy in other glaucoma subtypes. Novel laser applications (micropulse diode laser trabeculoplasty, titanium sapphire laser trabeculoplasty and excimer laser trabeculotomy) have shown favorable early results. Endoscopic and transscleral cyclophotocoagulation (ECP, TCP) are generally reserved for refractory glaucomas, although some recent studies report its use in patients with good visual acuity. The effectiveness of laser iridotomy with or without iridoplasty for long-term prevention of primary angle closure glaucoma is undetermined. Laser goniopuncture is an important adjunct to nonpenetrating surgery, but wide adoption of the procedure is lacking. SUMMARY: The use of lasers in glaucoma continues to evolve, with a trend towards primary and earlier intervention. SLT is assuming an expanded role in the treatment of additional subtypes of glaucoma, whereas ECP and TCP are generally reserved for refractory glaucomas. Newer laser modalities show promise as alternatives and adjuncts to topical medications and nonpenetrating surgery. Additional research is needed to better define their safety and efficacy.

21 Review Predisease: when does it make sense? 2011

Viera, Anthony J. ·Department of Family Medicine, 590 Manning Drive, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7595, USA. anthony_viera@med.unc.edu ·Epidemiol Rev · Pubmed #21624963.

ABSTRACT: Screening often leads to finding conditions that are not at the stage or level that would classify them as disease but, at the same time, are not at a stage or level at which people can be declared entirely disease free. These "in-between" states have sometimes been designated as "predisease." Examples include precancerous lesions, increased intraocular pressure ("preglaucoma"), prediabetes, and prehypertension. When the goal of preventing adverse health outcomes is kept in mind, this review poses the idea that "predisease" as a category on which to act makes sense only if the following 3 conditions are met. First, the people designated as having predisease must be far more likely to develop disease than those not so designated. Second, there must be a feasible intervention that, when targeted to people with predisease, effectively reduces the likelihood of developing disease. Third, the benefits of intervening on predisease must outweigh the harms in the population. A systematic review of screening guidelines (published in 2003-2010) for 4 sample conditions (cervical cancer, glaucoma, diabetes, and hypertension) is included to assess whether they address these issues, followed by a discussion of the framework questions as they pertain to each condition.

22 Article A Novel Porcine Model for the Study of Cerebrospinal Fluid Dynamics: Development and Preliminary Results. 2019

Fleischman, David / Kaskar, Omkar / Shams, Rayad / Zhang, Xinxin / Olson, Daniel / Zdanski, Carlton / Thorp, Brian D / Kuznetsov, Andrey V / Grace, Landon / Lee, Yueh Z. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. · Department of Mechanical and Aerospace Engineering, NC State University, Raleigh, NC, United States. · Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. · Department of Otolaryngology, Head & Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. ·Front Neurol · Pubmed #31708863.

ABSTRACT: Idiopathic intracranial hypertension, space-flight associated neuro-ocular syndrome (SANS), and glaucoma are conditions that are among a spectrum of cerebrospinal fluid (CSF)-related ophthalmologic disease. This implies that local CSF pressures at the level of the optic nerve are involved to variable extent in these disease processes. However, CSF pressure measurements are problematic due to invasiveness and interpretation. The pressure measured by a lumbar puncture is likely not the same as the orbital CSF pressure. It is believed this is at least in part due to the flow restrictive properties of the optic canal. To investigate CSF flow within the orbit, a model for CSF dynamics was created using three medium-sized pigs. Contrast was administered through a lumbar subarachnoid space access. The contrast front was imaged with repeated computed tomographic (CT) imaging. Once contrast entered the orbit, rapid, sequential CT imaging was performed until the contrast reached the posterior globe. Head tilting was performed to highlight the role of gravitational dependence within the subarachnoid space.

23 Article Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry. 2019

Anonymous1711607 / Hauser, Michael A / Allingham, R Rand / Aung, Tin / Van Der Heide, Carly J / Taylor, Kent D / Rotter, Jerome I / Wang, Shih-Hsiu J / Bonnemaijer, Pieter W M / Williams, Susan E / Abdullahi, Sadiq M / Abu-Amero, Khaled K / Anderson, Michael G / Akafo, Stephen / Alhassan, Mahmoud B / Asimadu, Ifeoma / Ayyagari, Radha / Bakayoko, Saydou / Nyamsi, Prisca Biangoup / Bowden, Donald W / Bromley, William C / Budenz, Donald L / Carmichael, Trevor R / Challa, Pratap / Chen, Yii-Der Ida / Chuka-Okosa, Chimdi M / Cooke Bailey, Jessica N / Costa, Vital Paulino / Cruz, Dianne A / DuBiner, Harvey / Ervin, John F / Feldman, Robert M / Flamme-Wiese, Miles / Gaasterland, Douglas E / Garnai, Sarah J / Girkin, Christopher A / Guirou, Nouhoum / Guo, Xiuqing / Haines, Jonathan L / Hammond, Christopher J / Herndon, Leon / Hoffmann, Thomas J / Hulette, Christine M / Hydara, Abba / Igo, Robert P / Jorgenson, Eric / Kabwe, Joyce / Kilangalanga, Ngoy Janvier / Kizor-Akaraiwe, Nkiru / Kuchtey, Rachel W / Lamari, Hasnaa / Li, Zheng / Liebmann, Jeffrey M / Liu, Yutao / Loos, Ruth J F / Melo, Monica B / Moroi, Sayoko E / Msosa, Joseph M / Mullins, Robert F / Nadkarni, Girish / Napo, Abdoulaye / Ng, Maggie C Y / Nunes, Hugo Freire / Obeng-Nyarkoh, Ebenezer / Okeke, Anthony / Okeke, Suhanya / Olaniyi, Olusegun / Olawoye, Olusola / Oliveira, Mariana Borges / Pasquale, Louise R / Perez-Grossmann, Rodolfo A / Pericak-Vance, Margaret A / Qin, Xue / Ramsay, Michele / Resnikoff, Serge / Richards, Julia E / Schimiti, Rui Barroso / Sim, Kar Seng / Sponsel, William E / Svidnicki, Paulo Vinicius / Thiadens, Alberta A H J / Uche, Nkechinyere J / van Duijn, Cornelia M / de Vasconcellos, José Paulo Cabral / Wiggs, Janey L / Zangwill, Linda M / Risch, Neil / Milea, Dan / Ashaye, Adeyinka / Klaver, Caroline C W / Weinreb, Robert N / Ashley Koch, Allison E / Fingert, John H / Khor, Chiea Chuen. ·Department of Medicine, Duke University, Durham, North Carolina. · Department of Ophthalmology, Duke University, Durham, North Carolina. · Singapore Eye Research Institute, Singapore. · Duke-NUS Medical School, Signapore. · Singapore National Eye Center, Singapore. · Department of Ophthalmology, Young Loo Lin School of Medicine, Singapore. · Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City. · The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California. · Department of Pediatrics, Harbor-University of California, Los Angeles Medical Center, Torrance. · Department of Pathology, Duke University, Durham, North Carolina. · Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. · Rotterdam Eye Hospital, Rotterdam, the Netherlands. · Department of Ophthalmology, Erasmus MC, Rotterdam, the Netherlands. · Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa. · National Eye Centre, Kaduna, Nigeria. · Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. · Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana. · Department of Ophthalmology, ESUT Teaching Hospital Parklane, Enugu, Nigeria. · Shiley Eye Institute, Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, La Jolla. · Institut d'Ophtalmologie Tropicale de l'Afrique, Bamako, Mali. · Université des Sciences des Techniques et des Technologies de Bamako, Bamako, Mali. · Service Spécialisé d'ophtalmologie, Hôpital Militaire de Région No1 de Yaoundé, Yaoundé, Cameroun. · Center for Diabetes Research, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina. · Center for Human Genetics, Bar Harbor, Maine. · Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. · University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria. · Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio. · Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio. · Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil. · Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina. · Clayton Eye Care Center Management Inc, Marrow, Georgia. · Kathleen Price Bryan Brain Bank and Biorepository, Department of Neurology, Duke University, Durham, North Carolina. · McGovern Medical School, Ruiz Department of Ophthalmology & Visual Science, The University of Texas Health Science Center at Houston, Houston. · The Emmes Corporation, Rockville, Maryland. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor. · Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham. · Section of Academic Ophthalmology, School of Life Course Sciences, FoLSM, King's College London, London, United Kingdom. · Department of Epidemiology and Biostatistics, University of California at San Francisco. · Institute for Human Genetics, University of California at San Francisco. · Sheikh Zayed Regional Eye Care Centre, Kanifing, The Gambia. · Division of Research, Kaiser Permanente Northern California, Oakland. · Department of Ophthalmology, St Joseph Hospital, Kinshasa, Limete, Democratic Republic of the Congo. · The Eye Specialists Hospital, Enugu, Nigeria. · Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee. · Clinique Spécialisée en Ophtalmologie Mohammedia, Mohammedia, Morocco. · Genome Institute of Singapore, Singapore. · Bernard and Shirlee Brown Glaucoma Research Laboratory, Harkness Eye Institute, Columbia University Medical Center, New York, New York. · Cellular Biology and Anatomy, Augusta University, Augusta, Georgia. · James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia. · Center for Biotechnology & Genomic Medicine, Augusta University, Augusta, Georgia. · The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. · The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York. · Center for Molecular Biology and Genetic Engineering, University of Campinas, Campinas, Brazil. · Lions Sight-First Eye Hospital, Kamuzu Central Hospital, Lilongwe, Malawi. · Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. · Nigerian Navy Reference Hospital, Ojo, Lagos, Nigeria. · Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria. · Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts. · Instituto de Glaucoma y Catarata, Lima, Peru. · John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida. · Duke Molecular Physiology Institute, Duke University, Durham, North Carolina. · Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. · Brien Holden Vision Institute, Sydney, Australia. · School of Optometry and Vision Science, University of New South Wales, Sydney, Australia. · Department of Epidemiology, University of Michigan, Ann Arbor. · Hoftalon Hospital, Londrina, Brazil. · San Antonio Eye Health, San Antonio, Texas. · Eyes of Africa, Child Legacy International (CLI) Hospital, Msundwe, Malawi. · Nuffield Department of Public Health, University of Oxford, Oxford, United Kingdom. · Harvard University Medical School, Boston, Massachusetts. · Massachusetts Eye and Ear Hospital, Boston. · Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands. ·JAMA · Pubmed #31688885.

ABSTRACT: Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures: Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.

24 Article Diagnosing Glaucoma Progression with Visual Field Data Using a Spatiotemporal Boundary Detection Method. 2019

Berchuck, Samuel I / Mwanza, Jean-Claude / Warren, Joshua L. ·Department of Statistical Science and Forge, Duke University, NC 27708 (sib2@duke.edu). · Department of Ophthalmology, University of North Carolina-Chapel Hill (DO, UNC-CH), NC 27517 (jean-claude_mmwanza@med.unc.edu). · Department of Biostatistics, Yale University, New Haven, CT, 06520 (joshua.warren@yale.edu). ·J Am Stat Assoc · Pubmed #31662589.

ABSTRACT: Diagnosing glaucoma progression is critical for limiting irreversible vision loss. A common method for assessing glaucoma progression uses a longitudinal series of visual fields (VF) acquired at regular intervals. VF data are characterized by a complex spatiotemporal structure due to the data generating process and ocular anatomy. Thus, advanced statistical methods are needed to make clinical determinations regarding progression status. We introduce a spatiotemporal boundary detection model that allows the underlying anatomy of the optic disc to dictate the spatial structure of the VF data across time. We show that our new method provides novel insight into vision loss that improves diagnosis of glaucoma progression using data from the Vein Pulsation Study Trial in Glaucoma and the Lions Eye Institute trial registry. Simulations are presented, showing the proposed methodology is preferred over existing spatial methods for VF data. Supplementary materials for this article are available online and the method is implemented in the R package womblR.

25 Article Transduction optimization of AAV vectors for human gene therapy of glaucoma and their reversed cell entry characteristics. 2019

Rodriguez-Estevez, Laura / Asokan, Priyadarsini / Borrás, Teresa. ·Department of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. · Department of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. tborras@med.unc.edu. ·Gene Ther · Pubmed #31611639.

ABSTRACT: The trabecular meshwork (TM) of the eye is responsible for maintaining physiological intraocular pressure (IOP). Dysfunction of this tissue results in elevated IOP, subsequent optic nerve damage and glaucoma, the world's leading cause of irreversible blindness. IOP regulation by delivering candidate TM genes would offer an enormous clinical advantage to the current daily-drops/surgery treatment. Initially, we showed that a double-stranded AAV2 (scAAV2) transduced the human TM very efficiently, while its single-stranded form (ssAAV2) did not. Here, we quantified transduction and entry of single- and double-strand serotypes 1, 2.5, 5, 6, 8, and 9 in primary, single individual-derived human TM cells (HTM). scAAV2 exhibited highest transduction in all individuals, distantly followed by scAAV2.5, scAAV6, and scAAV5. Transduction of scAAV1, scAAV8, and scAAV9 was negligible. None of the ssAAV serotypes transduced, but their cell entries were significantly higher than those of their corresponding scAAV. Tyrosine scAAV2 capsid mutants increased transduction in HTM cultured cells and all TM-outflow layers of perfused postmortem human eyes. These studies provide the first serotype optimization for gene therapy of glaucoma in humans. They further reveal biological differences between the AAV forms in HTM cells, whose understanding could contribute to the development of gene therapy of glaucoma.

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