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Glaucoma: HELP
Articles by Donald L. Budenz
Based on 87 articles published since 2008
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Between 2008 and 2019, D. Budenz wrote the following 87 articles about Glaucoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline A clinician's guide to the assessment and management of nonadherence in glaucoma. 2009

Budenz, Donald L. ·Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Florida 33136, USA. dbudenz@med.miami.edu ·Ophthalmology · Pubmed #19837260.

ABSTRACT: PURPOSE: To apply lessons learned in the treatment of systemic hypertension to the problem of nonadherence in glaucoma medical therapy. CLINICAL RELEVANCE: Although physicians recognize that nonadherence with glaucoma medication is a problem, most lack the skill set to identify nonadherent patients, to identify the causes of nonadherence, and to provide solutions to address nonadherence. METHODS: A PubMed search was conducted using the terms "adherence" OR "compliance" AND "hypertension," with the following limitations: title, English language, humans, from 2000 through 2009. Other studies identified outside of the PubMed search were included if relevant. RESULTS: Studies from the systemic hypertension literature suggest that simplifying medication regimens, lowering costs, and patient education about the disease and the importance of taking medications are successful strategies for improving adherence. In addition, good family or social support, frequent physician visits, and pairing medication administration with specific activities (such as meals or brushing one's teeth) can help improve adherence. CONCLUSIONS: The body of literature on adherence interventions in chronic diseases such as systemic hypertension shows that although many interventions have been tested and evaluated, only some are successful. Paradigms derived from behavioral medicine and nursing offer valuable lessons on how to motivate patients to change behavior, but these activities require skill sets not traditionally taught in medical school. Just as there are myriad causes of nonadherence, the interventions most likely will need to be multifaceted and tailored to the individual patient. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

2 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.

3 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.

4 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.

5 Review Glaucoma Drainage Implant Surgery. 2017

Aref, Ahmad A / Gedde, Steven J / Budenz, Donald L. · ·Dev Ophthalmol · Pubmed #28442686.

ABSTRACT: Glaucoma drainage implant (GDI) surgery represents a significant advance in the treatment of refractory glaucomas. Recent randomized clinical trials have compared the efficacy and safety of this technique to standard trabeculectomy. Several types of implant are currently available and differ in surface area, shape, composition, and the presence or absence of a flow-restricting valve. Two separate prospective, randomized clinical trials comparing 2 types of GDI have reported results after 5 years of follow-up. GDIs may be placed in the anterior chamber, ciliary sulcus, or pars plana. Several types of patch graft material may be utilized to prevent tube erosion. Potential complications of GDI surgery may relate to immediate or late-onset hypotony, motility disturbances, corneal decompensation, or tube erosion.

6 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.

7 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.

8 Review Glaucoma drainage implant surgery. 2012

Aref, Ahmad A / Gedde, Steven J / Budenz, Donald L. ·Illinois Eye & Ear Infirmary, University of Illinois at Chicago School of Medicine, Chicago, Ill., USA. ·Dev Ophthalmol · Pubmed #22517172.

ABSTRACT: Glaucoma drainage implant (GDI) surgery represents a significant advance in the treatment of refractory glaucomas. Recent randomized clinical trials have compared the efficacy and safety of this technique to standard trabeculectomy. Several types of implants are currently available and differ in surface area, shape, composition, and presence or absence of a flow-restricting valve. A prospective, randomized clinical trial comparing two types of GDIs is ongoing. GDIs may be placed in the anterior chamber, ciliary sulcus, or pars plana. Several types of patch graft material may be utilized to prevent tube erosion. Potential complications of GDI surgery may relate to immediate or late-onset hypotony, motility disturbances, corneal decompensation, or tube erosion.

9 Review Ocular perfusion pressure and glaucoma. 2011

Grover, Davinder S / Budenz, Donald L. · ·Int Ophthalmol Clin · Pubmed #21633235.

ABSTRACT: -- No abstract --

10 Review Update on aqueous shunts. 2011

Gedde, Steven J / Parrish, Richard K / Budenz, Donald L / Heuer, Dale K. ·Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USA. ·Exp Eye Res · Pubmed #21443872.

ABSTRACT: Medicare claims data and surveys of the American Glaucoma Society membership show that aqueous shunts are being increasingly utilized in the surgical management of glaucoma. New clinical trials data have identified differences in the efficacy and safety of shunts in common use. Recent studies have reported comparable results with trabeculectomy and aqueous shunts in similar patient groups. Intraoperative and postoperative complications may develop with aqueous shunt surgery related to the implantation of a foreign material. Several modifications in surgical technique have been directed toward improving surgical success, reducing complications, and optimizing efficiency and cost.

11 Review Spectral domain optical coherence tomography in the diagnosis and management of glaucoma. 2010

Aref, Ahmad A / Budenz, Donald L. ·Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA. ·Ophthalmic Surg Lasers Imaging · Pubmed #21117597.

ABSTRACT: Spectral domain optical coherence tomography (SD-OCT) is a relatively new imaging technology that is being used for the diagnosis and management of glaucoma. This article presents a review of the specific parameters analyzed by SD-OCT and the diagnostic capability, reproducibility, and limitations of the device. SD-OCT parameters useful for diagnosis of glaucoma include retinal nerve fiber layer analysis, optic nerve head analysis, and ganglion cell complex analysis. These parameters have proven to be at least as equivalent to time-domain technology in terms of diagnostic capability and superior in terms of reproducibility. SD-OCT technology may be limited by signal quality, image artifact, and confounding ocular disease.

12 Review Diagnosing glaucoma progression. 2008

Chang, Robert T / Budenz, Donald L. ·Bascom Palmer Eye Institute, Miami, FL 33136, USA. ·Int Ophthalmol Clin · Pubmed #18936634.

ABSTRACT: -- No abstract --

13 Review New developments in optical coherence tomography for glaucoma. 2008

Chang, Robert / Budenz, Donald L. ·Bascom Palmer Eye Institute, Miami, Florida 33136, USA. rchang3@med.miami.edu ·Curr Opin Ophthalmol · Pubmed #18301286.

ABSTRACT: PURPOSE OF REVIEW: Structural imaging is becoming a powerful adjunct for the diagnosis and progression of glaucoma. There are several competing technologies in this arena. Optical coherence tomography continues to evolve at a fast pace, so it can be challenging to keep up with the latest information. This review covers the recent papers relevant to optical coherence tomography for glaucoma. RECENT FINDINGS: Retinal nerve fiber layer imaging by optical coherence tomography is reliable. Age, ethnicity, axial length and optic disc size can affect the machine's normative range. Scan quality can be affected by movement, media opacities, myopia and severity of disease. The sensitivity and specificity are variable across multiple studies. Despite this, the technology is beginning to help us understand the structure-function relationship in glaucoma. SUMMARY: The next generation optical coherence tomography is around the corner. By understanding the current strengths and limitations of this advancing technology, one can better assess its use in clinical practice.

14 Clinical Trial Macular ganglion cell-inner plexiform layer: automated detection and thickness reproducibility with spectral domain-optical coherence tomography in glaucoma. 2011

Mwanza, Jean-Claude / Oakley, Jonathan D / Budenz, Donald L / Chang, Robert T / Knight, O'Rese J / Feuer, William J. ·Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Florida, USA. ·Invest Ophthalmol Vis Sci · Pubmed #21917932.

ABSTRACT: PURPOSE: To demonstrate the capability of SD-OCT to measure macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness and to assess its reproducibility in glaucomatous eyes. METHODS: Fifty-one glaucomatous eyes (26 mild, 11 moderate, 14 severe) of 51 patients underwent macular scanning using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) macula 200×200 acquisition protocol. Five scans were obtained on 5 days within 2 months. The ganglion cell analysis (GCA) algorithm was used to detect the macular GCIPL and to measure the thickness of the overall average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL. The reproducibility of the measurements was evaluated with intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and test-retest standard deviations (TRTSDs). RESULTS: Segmentation and measurement of GCIPL thickness were successful in 50 of 51 subjects. All ICCs ranged between 0.94 and 0.98, but ICCs for average and superior GCIPL parameters (0.97-0.98) were slightly higher than for inferior GCIPL parameters (0.94-0.97). All COVs were <5%, with 1.8% for average GCIPL and COVs for superior GCIPL parameters (2.2%-3.0%) slightly lower than those for inferior GCIPL parameters (2.5%-3.6%). The TRTSD was lowest for average GCIPL (1.16 μm) and varied from 1.43 to 2.15 μm for sectoral GCIPL CONCLUSIONS: The Cirrus HD-OCT GCA algorithm can successfully segment macular GCIPL and measure GCIPL thickness with excellent intervisit reproducibility. Longitudinal monitoring of GCIPL thickness may be possible with Cirrus HD-OCT for assessing glaucoma progression.

15 Article Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. 2018

Shiga, Yukihiro / Akiyama, Masato / Nishiguchi, Koji M / Sato, Kota / Shimozawa, Nobuhiro / Takahashi, Atsushi / Momozawa, Yukihide / Hirata, Makoto / Matsuda, Koichi / Yamaji, Taiki / Iwasaki, Motoki / Tsugane, Shoichiro / Oze, Isao / Mikami, Haruo / Naito, Mariko / Wakai, Kenji / Yoshikawa, Munemitsu / Miyake, Masahiro / Yamashiro, Kenji / Anonymous391123 / Kashiwagi, Kenji / Iwata, Takeshi / Mabuchi, Fumihiko / Takamoto, Mitsuko / Ozaki, Mineo / Kawase, Kazuhide / Aihara, Makoto / Araie, Makoto / Yamamoto, Tetsuya / Kiuchi, Yoshiaki / Nakamura, Makoto / Ikeda, Yasuhiro / Sonoda, Koh-Hei / Ishibashi, Tatsuro / Nitta, Koji / Iwase, Aiko / Shirato, Shiroaki / Oka, Yoshitaka / Satoh, Mamoru / Sasaki, Makoto / Fuse, Nobuo / Suzuki, Yoichi / Cheng, Ching-Yu / Khor, Chiea Chuen / Baskaran, Mani / Perera, Shamira / Aung, Tin / Vithana, Eranga N / Cooke Bailey, Jessica N / Kang, Jae H / Pasquale, Louis R / Haines, Jonathan L / Anonymous401123 / Wiggs, Janey L / Burdon, Kathryn P / Gharahkhani, Puya / Hewitt, Alex W / Mackey, David A / MacGregor, Stuart / Craig, Jamie E / Allingham, R Rand / Hauser, Micheal / Ashaye, Adeyinka / Budenz, Donald L / Akafo, Stephan / Williams, Susan E I / Kamatani, Yoichiro / Nakazawa, Toru / Kubo, Michiaki. ·Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. · Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan. · Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan. · Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan. · Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan. · Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan. · Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. · Institute of Medical Science, The University of Tokyo, Tokyo, Japan. · Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan. · Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. · Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan. · Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Department of Ophthalmology, Otsu Red-Cross Hospital, Otsu, Japan. · Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. · Division of Molecular and Cellular Biology, National Institute of Sensory Organs, Tokyo Medical Center, National Hospital Organization, Tokyo, Japan. · Department of Ophthalmology, University of Tokyo, Tokyo, Japan. · Ozaki Eye Hospital, Hyuga, Miyazaki, Japan. · Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. · Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan. · Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan. · Department of Ophthalmology and Visual Sciences, Hiroshima University, Hiroshima, Japan. · Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Fukuiken Saiseikai Hospital, Fukui, Japan. · Tajimi Iwase Eye Clinic, Tajimi, Japan. · Yotsuya Shirato Eye Clinic, Tokyo, Japan. · Oka Eye Clinic, Fukuoka, Japan. · Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan. · Department of Integrative Genomics, Tohoku Medical Megabank Organization, Miyagi, Japan. · Department of Education and Training, Tohoku Medical Megabank Organization, Miyagi, Japan. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Genome Institute of Singapore, Singapore. · Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. · Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia. · Department of Ophthalmology, Flinders University, Adelaide, SA, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. · Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia. · Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, WA, Australia. · Department of Ophthalmology, Duke University, Durham, NC, USA. · Duke University Medical Center, Durham, NC, USA. · Department of Ophthalmology, College of Medicine, University of Ibadan, Ibadan, Nigeria. · Department of Ophthalmology, University of North Carolina at Chapel Hill, USA. · University of Ghana School of Medicine and Dentistry, Ghana. · Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, South Africa. · Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ·Hum Mol Genet · Pubmed #29452408.

ABSTRACT: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

16 Article Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. 2018

Bailey, Jessica N Cooke / Gharahkhani, Puya / Kang, Jae H / Butkiewicz, Mariusz / Sullivan, David A / Weinreb, Robert N / Aschard, Hugues / Allingham, R Rand / Ashley-Koch, Allison / Lee, Richard K / Moroi, Sayoko E / Brilliant, Murray H / Wollstein, Gadi / Schuman, Joel S / Fingert, John H / Budenz, Donald L / Realini, Tony / Gaasterland, Terry / Scott, William K / Singh, Kuldev / Sit, Arthur J / Igo, Robert P / Song, Yeunjoo E / Hark, Lisa / Ritch, Robert / Rhee, Douglas J / Vollrath, Douglas / Zack, Donald J / Medeiros, Felipe / Vajaranant, Thasarat S / Chasman, Daniel I / Christen, William G / Pericak-Vance, Margaret A / Liu, Yutao / Kraft, Peter / Richards, Julia E / Rosner, Bernard A / Hauser, Michael A / Craig, Jamie E / Burdon, Kathryn P / Hewitt, Alex W / Mackey, David A / Haines, Jonathan L / MacGregor, Stuart / Wiggs, Janey L / Pasquale, Louis R / Anonymous8431162. ·Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States. · Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States. · Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia. · Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States. · Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States. · Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, University of California at San Diego, La Jolla, California, United States. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, United States. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States. · Center for Human Genetics, Marshfield Clinic Research Institute, Marshfield, Wisconsin, United States. · Department of Ophthalmology, NYU Langone Medical Center, NYU School of Medicine, New York, New York, United States. · Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, Iowa, United States. · Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, United States. · Department of Ophthalmology, WVU Eye Institute, Morgantown, West Virginia, United States. · Scripps Genome Center, University of California at San Diego, San Diego, California, United States. · Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology, Stanford University, Palo Alto, California, United States. · Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States. · Wills Eye Hospital, Glaucoma Research Center, Philadelphia, Pennsylvania, United States. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, United States. · Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States. · Department of Genetics, Stanford University, Palo Alto, California, United States. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, United States. · Department of Ophthalmology, University of Illinois College of Medicine at Chicago, Chicago, Illinois, United States. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States. · Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States. · Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, United States. · Department of Ophthalmology, Flinders University, Adelaide, SA, Australia. · School of Medicine, Menzies Research Institute of Tasmania, Hobart, Australia. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia. · Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States. ·Invest Ophthalmol Vis Sci · Pubmed #29392307.

ABSTRACT: Purpose: Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods: We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results: In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions: Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.

17 Article Longitudinal Change in Central Corneal Thickness in the Tema Eye Survey. 2018

Mwanza, Jean-Claude / Tulenko, Samantha E / Budenz, Donald L / Mathenge, Elizabeth / Herndon, Leon H / Kim, Hanna Y / Hall, Alyson / Hay-Smith, Graham / Spratt, Alexander / Barton, Keith. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. · Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: donald_budenz@med.unc.edu. · Duke Eye Center, Duke University, Durham, North Carolina. · Department of Ophthalmology, Kaiser Permanente Woodland Hills Medical Center, Woodland Hills, California. · Department of Ophthalmology, The Glaucoma Center, Bowie, Maryland. · The Moreton Eye Group, Brisbane, Queensland, Australia. · South Florida Eye Health, Hollywood, Florida. · Moorefields Eye Hospital and Department of Epidemiology and Genetics, Institute of Ophthalmology, University College of London, London, United Kingdom. ·Am J Ophthalmol · Pubmed #29141198.

ABSTRACT: PURPOSE: To determine the change and rate of change in central corneal thickness (CCT) and their determinants. DESIGN: Longitudinal observational population-based study. METHODS: A total of 758 normal and 58 glaucomatous subjects underwent complete eye examination, with CCT measurements at 2 separate visits. Change and rate of change in CCT were determined. Univariate and multivariate linear regression analyses were performed to determine the factors associated with change and rate of change. RESULTS: The mean follow-up duration was 8.4 ± 0.7 years. The overall change was -8.9 ± 16.7 μm in OD and -9.8 ± 16.2 μm in OS, both P < .0001. Changes in glaucomatous and normal subjects were -14.1 ± 2.2 μm vs -8.6 ± 0.6 μm in OD (P = .02) and -14.5 ± 2.2 μm vs -9.5 ± 0.6 μm in OS (P = .03), respectively. The overall rate of thinning was -1.1 μm/year (OD) and -1.2 μm/year (OS). Rates in glaucomatous and normal eyes were -1.7 ± 0.3 μm/year vs -1.0 ± 0.1 μm/year in OD (P = .02) and -1.7 ± 0.3 μm/year vs -1.1 ± 0.1 μm/year in OS (P = .03), respectively. Change and rate of change were associated with baseline CCT (ß = -0.1 to -0.09 and -0.011, respectively, all P < .001) and glaucoma (ß = -6.8 to -5.6, P ≤ .009, and -0.75 to -0.69, P ≤ .007, respectively). CONCLUSION: CCT decreased significantly over time. The change and rate of change were greater in glaucomatous than normal eyes, and were greater than described in cross-sectional studies.

18 Article Differences in Optical Coherence Tomography Assessment of Bruch Membrane Opening Compared to Stereoscopic Photography for Estimating Cup-to-Disc Ratio. 2017

Mwanza, Jean-Claude / Huang, Linda Y / Budenz, Donald L / Shi, Wei / Huang, Gintien / Lee, Richard K. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. · Bascom Palmer Eye Institute, University of Miami, Miami, Florida. · Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: donald_budenz@med.unc.edu. · Bascom Palmer Eye Institute, University of Miami, Miami, Florida. Electronic address: rlee@med.miami.edu. ·Am J Ophthalmol · Pubmed #28964804.

ABSTRACT: PURPOSE: To compare the vertical and horizontal cup-to-disc ratio (VCDR, HCDR) by an updated optical coherence tomography (OCT) Bruch membrane opening (BMO) algorithm and stereoscopic optic disc photograph readings by glaucoma specialists. DESIGN: Reliability analysis. METHODS: A total of 195 eyes (116 glaucoma and 79 glaucoma suspect) of 99 patients with stereoscopic photographs and OCT scans of the optic discs taken during the same visit were compared. Optic disc photographs were read by 2 masked glaucoma specialists for VCDR and HCDR estimation. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess the agreement between photograph reading and OCT in estimating CDR. RESULTS: OCT images computed significantly larger VCDR and HCDR than photograph reading before and after stratifying eyes based on disc size (P < .001). The difference in CDR estimates between the 2 methods was equal to or greater than 0.2 in 29% and 35% of the eyes for VCDR and HCDR, respectively, with a mean difference of 0.3 in each case. The ICCs between the readers and OCT ranged between 0.50 and 0.63. The size of disagreement in VCDR correlated weakly with cup area in eyes with medium (r CONCLUSIONS: OCT and photograph reading by clinicians agree poorly in CDR assessment. The difference in VCDR between the 2 methods was depended on cup area in medium and large discs. These differences should be considered when making conclusions regarding CDRs in clinical practice.

19 Article Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis. 2017

Aschard, Hugues / Kang, Jae H / Iglesias, Adriana I / Hysi, Pirro / Cooke Bailey, Jessica N / Khawaja, Anthony P / Allingham, R Rand / Ashley-Koch, Allison / Lee, Richard K / Moroi, Sayoko E / Brilliant, Murray H / Wollstein, Gadi / Schuman, Joel S / Fingert, John H / Budenz, Donald L / Realini, Tony / Gaasterland, Terry / Scott, William K / Singh, Kuldev / Sit, Arthur J / Igo, Robert P / Song, Yeunjoo E / Hark, Lisa / Ritch, Robert / Rhee, Douglas J / Gulati, Vikas / Haven, Shane / Vollrath, Douglas / Zack, Donald J / Medeiros, Felipe / Weinreb, Robert N / Cheng, Ching-Yu / Chasman, Daniel I / Christen, William G / Pericak-Vance, Margaret A / Liu, Yutao / Kraft, Peter / Richards, Julia E / Rosner, Bernard A / Hauser, Michael A / Anonymous6180917 / Klaver, Caroline C W / vanDuijn, Cornelia M / Haines, Jonathan / Wiggs, Janey L / Pasquale, Louis R. ·Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA. · Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · Department of Epidemiology, Genetic Epidemiology Unit, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA. · Department of Medicine, Duke University Medical Center, Durham, NC, USA. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA. · Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA. · Department of Ophthalmology, NYU Langone Medical Center, NYU School of Medicine, New York, NY, USA. · Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IO, USA. · Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, USA. · Department of Ophthalmology, WVU Eye Institute, Morgantown, WV, USA. · Scripps Genome Center, University of California at San Diego, San Diego, CA, USA. · Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Ophthalmology, Stanford University, Palo Alto, CA, USA. · Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA. · Wills Eye Hospital, Glaucoma Research Center, Philadelphia, PA, USA. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA. · Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Department of Ophthalmology &Visual Sciences, University of Nebraska Medical Center, Omaha, NE, USA. · Department of Genetics, Stanford University, Palo Alto, CA, USA. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD, USA. · Department of Ophthalmology, Hamilton Eye Center, University of California at San Diego, San Diego, CA, USA. · Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore. · Ophthalmology &Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Department of Cellular Biology &Anatomy, Augusta University, Augusta, GA, USA. · Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA. · Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. ·Eur J Hum Genet · Pubmed #28853718.

ABSTRACT: Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10

20 Article A comparison of cup-to-disc ratio estimates by fundus biomicroscopy and stereoscopic optic disc photography in the Tema Eye Survey. 2017

Mwanza, J C / Grover, D S / Budenz, D L / Herndon, L W / Nolan, W / Whiteside-de Vos, J / Hay-Smith, G / Bandi, J R / Bhansali, K A / Forbes, L A / Feuer, W J / Barton, K. ·Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Glaucoma Associates of Texas, Dallas, TX, USA. · Duke University Eye Center, Durham, NC, USA. · Moorfields Eye Hospital, London, UK. · Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Peninsula Eye Hospital, Redcliffe, Queensland, Australia. · Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA. · National Institute for Health Research, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital, London, UK. ·Eye (Lond) · Pubmed #28387768.

ABSTRACT: PurposeTo determine if there are systematic differences in cup-to-disc ratio (CDR) grading using fundus biomicroscopy compared to stereoscopic disc photograph reading.MethodsThe vertical cup-to-disc ratio (VCDR) and horizontal cup-to-disc ratio (HCDR) of 2200 eyes (testing set) were graded by glaucoma subspecialists through fundus biomicroscopy and by a reading center using stereoscopic disc photos. For validation, the glaucoma experts also estimated VCDR and HCDR using stereoscopic disc photos in a subset of 505 eyes that they had assessed biomicroscopically. Agreement between grading methods was assessed with Bland-Altman plots.ResultsIn both sets, photo reading tended to yield small CDRs marginally larger, but read large CDRs marginally smaller than fundus biomicroscopy. The mean differences in VCDR and HCDR were 0.006±0.18 and 0.05±0.18 (testing set), and -0.053±0.23 and -0.028±0.21 (validation set), respectively. The limits of agreement were ~0.4, which is twice as large as the cutoff of clinically significant CDR difference between methods. CDR estimates differed by 0.2 or more in 33.8-48.7% between methods.ConclusionsThe differences in CDR estimates between fundus biomicroscopy and stereoscopic optic disc photo reading showed a wide variation, and reached clinically significance threshold in a large proportion of patients, suggesting a poor agreement. Thus, glaucoma should be monitored by comparing baseline and subsequent CDR estimates using the same method rather than comparing photographs to fundus biomicroscopy.

21 Article Five-Year Pooled Data Analysis of the Ahmed Baerveldt Comparison Study and the Ahmed Versus Baerveldt Study. 2017

Christakis, Panos G / Zhang, Dongyu / Budenz, Donald L / Barton, Keith / Tsai, James C / Ahmed, Iqbal I K / Anonymous950894. ·Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine, Toronto, Canada. · Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina. · Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina; Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: dbudenz@med.unc.edu. · NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital, London, United Kingdom. · Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York Eye and Ear Infirmary of Mount Sinai, New York, New York. ·Am J Ophthalmol · Pubmed #28104418.

ABSTRACT: PURPOSE: To determine the relative efficacy of the Ahmed-FP7 and Baerveldt BG101-350 implants. DESIGN: Pooled analysis of 2 multicenter, randomized clinical trials. METHODS: A total of 514 patients aged 18 or older with uncontrolled glaucoma that had failed or were at high risk of failing trabeculectomy were randomized to receive an Ahmed implant (n = 267) or Baerveldt implant (n = 247). Cumulative failure rates (using an intraocular pressure [IOP] target of 6-18 mm Hg inclusive), de novo glaucoma surgery rates, mean IOP, mean glaucoma medication use, and visual acuity were compared. RESULTS: Baseline characteristics were similar between groups. Mean preoperative IOP of the study population was 31.5 ± 11.3 mm Hg on an average of 3.3 ± 1.1 glaucoma medications. At 5 years, mean IOP was 15.8 ± 5.2 mm Hg in the Ahmed group and 13.2 ± 4.7 mm Hg in the Baerveldt group (P < .001). Mean glaucoma medication use was 1.9 ± 1.5 in the Ahmed group and 1.5 ± 1.4 in the Baerveldt group (P = .007). The cumulative failure rate at 5 years was 49% in the Ahmed group and 37% in the Baerveldt group (P = .007). High IOP was the most common reason for failure in both groups, and de novo glaucoma surgery was required in 16% of the Ahmed group and 8% of the Baerveldt group (P = .006). Failure owing to hypotony occurred in 0.4% of the Ahmed group and 4.5% of the Baerveldt group (P = .002). Visual outcomes were similar between groups (P = .90). CONCLUSIONS: The Baerveldt group had a lower failure rate, lower rate of de novo glaucoma surgery, and lower mean IOP on fewer medications than the Ahmed group. Baerveldt implantation carried a higher risk of hypotony.

22 Article Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample. 2017

Pasquale, Louis R / Aschard, Hugues / Kang, Jae H / Bailey, Jessica N Cooke / Lindström, Sara / Chasman, Daniel I / Christen, William G / Allingham, R Rand / Ashley-Koch, Allison / Lee, Richard K / Moroi, Sayoko E / Brilliant, Murray H / Wollstein, Gadi / Schuman, Joel S / Fingert, John / Budenz, Donald L / Realini, Tony / Gaasterland, Terry / Gaasterland, Douglas / Scott, William K / Singh, Kuldev / Sit, Arthur J / Igo, Robert P / Song, Yeunjoo E / Hark, Lisa / Ritch, Robert / Rhee, Douglas J / Gulati, Vikas / Havens, Shane / Vollrath, Douglas / Zack, Donald J / Medeiros, Felipe / Weinreb, Robert N / Pericak-Vance, Margaret A / Liu, Yutao / Kraft, Peter / Richards, Julia E / Rosner, Bernard A / Hauser, Michael A / Haines, Jonathan L / Wiggs, Janey L. ·1 Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA · 2 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA · 3 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard Medical School, Boston, MA · 4 Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH · 5 Institute of Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH · 6 Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA · 7 Department of Ophthalmogy, Duke University, Duke University Medical Center, Durham, NC · 8 Department of Medicine, Duke University, Duke University Medical Center, Durham, NC · 9 Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL · 10 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI · 11 Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI · 12 Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA · 13 Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IO · 14 Department of Ophthalmology, University of North Carolina, Chapel Hill, NC · 15 Department of Ophthalmology, WVU Eye Institute, Morgantown, WV · 16 Scripps Genome Center, University of California at San Diego, San Diego, CA · 17 Emmes Corporation, Chevy Chase, MD · 18 Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL · 19 Department of Ophthalmology, Stanford University, Palo Alto, CA · 20 Department of Ophthalmology, Mayo Clinic, Rochester, MN · 21 Wills Eye Institute, Philadelphia, PA · 22 Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY · 23 Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH · 24 Department of Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, NE · 25 Department of Genetics; Stanford University, Palo Alto, CA · 26 Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD · 27 Department of Ophthalmology, Hamilton Eye Center; University of California at San Diego, San Diego, CA · 28 Department of Cellular Biology & Anatomy, Augusta University, Augusta, GA. ·Menopause · Pubmed #27760082.

ABSTRACT: OBJECTIVE: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. METHODS: Using data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. RESULTS: The genetic risk score was associated with self-reported ANM (P = 2.2 × 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). CONCLUSIONS: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.

23 Article A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium. 2016

Liu, Yutao / Bailey, Jessica Cooke / Helwa, Inas / Dismuke, W Michael / Cai, Jingwen / Drewry, Michelle / Brilliant, Murray H / Budenz, Donald L / Christen, William G / Chasman, Daniel I / Fingert, John H / Gaasterland, Douglas / Gaasterland, Terry / Gordon, Mae O / Igo, Robert P / Kang, Jae H / Kass, Michael A / Kraft, Peter / Lee, Richard K / Lichter, Paul / Moroi, Sayoko E / Realini, Anthony / Richards, Julia E / Ritch, Robert / Schuman, Joel S / Scott, William K / Singh, Kuldev / Sit, Arthur J / Song, Yeunjoo E / Vollrath, Douglas / Weinreb, Robert / Medeiros, Felipe / Wollstein, Gadi / Zack, Donald J / Zhang, Kang / Pericak-Vance, Margaret A / Gonzalez, Pedro / Stamer, W Daniel / Kuchtey, John / Kuchtey, Rachel W / Allingham, R Rand / Hauser, Michael A / Pasquale, Louis R / Haines, Jonathan L / Wiggs, Janey L. ·Department of Cellular Biology and Anatomy Augusta University, Augusta, Georgia, United States 2James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States 3Center for Biotechnology and Genomic Medicine, Augusta Uni. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States. · Department of Cellular Biology and Anatomy Augusta University, Augusta, Georgia, United States. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States. · Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States. · Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, United States. · Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States. · Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States. · The Emmes Corporation, Rockville, Maryland, United States. · Scripps Genome Center, University of California at San Diego, San Diego, California, United States. · Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States. · School of Public Health, Harvard University, Boston, Massachusetts, United States. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States. · Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, United States. · Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. · Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology, Stanford University, Palo Alto, California, United States. · Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States. · Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, California, United States. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, United States. · Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States 26Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States 27Department of Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States. · Department of Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States. ·Invest Ophthalmol Vis Sci · Pubmed #27537254.

ABSTRACT: PURPOSE: Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG). METHODS: Using the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls. RESULTS: Only rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11-1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment. CONCLUSIONS: Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

24 Article Central Corneal Thickness and its Associations With Ocular and Systemic Factors in an Urban West African Population. 2016

Sng, Chelvin / Barton, Keith / Kim, Hanna / Yuan, Shi / Budenz, Donald L. ·Glaucoma Service and National Institute for Health Research Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital, London, United Kingdom; Department of Ophthalmology, National University Health System, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Glaucoma Service and National Institute for Health Research Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital, London, United Kingdom; Department of Epidemiology and Genetics, Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: keith@keithbarton.co.uk. · Department of Ophthalmology, Kaiser Permanente, Woodland Hills, California. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Department of Ophthalmology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. ·Am J Ophthalmol · Pubmed #27423792.

ABSTRACT: PURPOSE: To assess the associations of central corneal thickness (CCT) with ocular and systemic factors in a West African population. DESIGN: Population-based cross-sectional study. METHODS: Participants aged ≥40 years in the Tema Eye Survey who had clinically normal corneas were included in this study. CCT was determined bilaterally using handheld ultrasound pachymetry. The association between CCT and ocular or systemic factors was analyzed with univariable linear regression. Multivariable linear regression analysis was performed for variables significantly associated with CCT in the univariable analysis. Main outcome measures were CCT (μm) and its associations with age, sex, IOP, cup-to-disc ratio (CDR), glaucoma, hypertension, and diabetes. RESULTS: A total of 6806 eligible subjects were identified, of whom 5603 (82.3%) participated in the Tema Eye Survey. A total of 4737 participants (84.5% of participants) of West African descent and clinically normal corneas were included. The mean age ± standard deviation (SD) of participants was 51.2 ± 9.7 years and 38.7% were male. The mean ± SD CCT in the population was 533.9 ± 34.0 μm. In the multivariable linear regression analysis, increased CCT was significantly associated with younger age, male sex, and higher IOP (all P < .001). There were no significant associations between CCT and CDR, glaucoma, hypertension, and diabetes. CONCLUSIONS: This population-based cross-sectional survey of West African adults found a significant association between increased CCT and younger age, male sex, and higher IOP but not glaucoma or CDR. Variations in corneal thickness may influence the accuracy of IOP measurements in African persons.

25 Article Ocular hypotensive effect of fixed-combination brinzolamide/brimonidine adjunctive to a prostaglandin analog: a randomized clinical trial. 2016

Fechtner, R D / Myers, J S / Hubatsch, D A / Budenz, D L / DuBiner, H B. ·Department of Ophthalmology, SUNY Upstate Medical University, Syracuse, NY, USA. · Wills Eye Hospital, Philadelphia, PA, USA. · Alcon Laboratories, Inc., Fort Worth, TX, USA. · Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, USA. · Clayton Eye Center, Morrow, GA, USA. ·Eye (Lond) · Pubmed #27367743.

ABSTRACT: PurposeTo determine whether intraocular pressure (IOP) lowering with fixed-combination brinzolamide/brimonidine (BBFC) adjunctive to a prostaglandin analog (PGA) was superior to that of vehicle+PGA in patients with open-angle glaucoma or ocular hypertension who were inadequately controlled with PGA monotherapyMethodsThis 6-week, multicenter, randomized, double-masked, parallel-group trial was conducted at 30 clinical sites in the United States between October 2013 and May 2014. Eligible patients were adults with open-angle glaucoma or ocular hypertension and with mean IOP ≥21 and <32 mm Hg, whereas receiving an open-label PGA (latanoprost, bimatoprost, or travoprost). Patients instilled a PGA once-daily in a run-in phase before randomization to masked BBFC or vehicle adjunctive treatment. Masked treatments were instilled 3 times daily for 6 weeks, and patients continued once-daily use of their PGA. The primary efficacy end point was the between-group difference in mean diurnal IOP (average of 0800, 1000, 1500, and 1700 hours time points) at week 6.ResultsAt week 6, mean diurnal IOP with BBFC+PGA was lower than with vehicle+PGA (17.1±0.4 mm Hg vs 20.5±0.4 mm Hg; between-group difference, -3.4±0.5 mm Hg; P<0.0001; 95% confidence interval, -4.5 to -2.4 mm Hg). BBFC+PGA reduced mean diurnal IOP by 5.7 mm Hg (25%) from the baseline IOP achieved with PGA monotherapy.ConclusionsTherapy with BBFC produced an additive IOP-lowering effect compared with a PGA alone or in conjunction with vehicle. BBFC may provide an effective treatment option for patients receiving PGA monotherapy who require additional IOP reduction.

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