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      Association of macular pigment optical density with retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma

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      BMJ Open Ophthalmology
      BMJ Publishing Group
      glaucoma, epidemiology, optic nerve, retina, imaging

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          Abstract

          Objective

          To investigate associations between baseline macular pigment optical density (MPOD) and retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma (POAG) in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2).

          Methods and analysis

          MPOD was measured at CAREDS baseline (2001–2004) via heterochromatic flicker photometry (0.5° from foveal centre). Peripapillary retinal nerve fibre layer (RNFL), macular ganglion cell complex (GCC), ganglion cell layer (GCL), inner plexiform layer (IPL), and RNFL thicknesses were measured at CAREDS2 (2016–2019) via spectral-domain optical coherence tomography. Associations between MPOD and retinal thickness were assessed using multivariable linear regression.

          Results

          Among 742 eyes (379 participants), manifest POAG was identified in 50 eyes (32 participants). In eyes without manifest POAG, MPOD was positively associated with macular GCC, GCL and IPL thicknesses in the central subfield (P-trend ≤0.01), but not the inner or outer subfields. Among eyes with manifest POAG, MPOD was positively associated with macular GCC, GCL, IPL and RNFL in the central subfield (P-trend ≤0.03), but not the inner or outer subfields, and was positively associated with peripapillary RNFL thickness in the superior and temporal quadrants (P-trend≤0.006).

          Conclusion

          We observed a positive association between MPOD and central subfield GCC thickness 15 years later. MPOD was positively associated with peripapillary RNFL superior and temporal quadrant thicknesses among eyes with manifest POAG. Our results linking low MPOD to retinal layers that are structural indicators of early glaucoma provide further evidence that carotenoids may be protective against manifest POAG.

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          Most cited references34

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          Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis.

          Glaucoma is the leading cause of global irreversible blindness. Present estimates of global glaucoma prevalence are not up-to-date and focused mainly on European ancestry populations. We systematically examined the global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and projected the number of affected people in 2020 and 2040. Systematic review and meta-analysis. Data from 50 population-based studies (3770 POAG cases among 140,496 examined individuals and 786 PACG cases among 112 398 examined individuals). We searched PubMed, Medline, and Web of Science for population-based studies of glaucoma prevalence published up to March 25, 2013. Hierarchical Bayesian approach was used to estimate the pooled glaucoma prevalence of the population aged 40-80 years along with 95% credible intervals (CrIs). Projections of glaucoma were estimated based on the United Nations World Population Prospects. Bayesian meta-regression models were performed to assess the association between the prevalence of POAG and the relevant factors. Prevalence and projection numbers of glaucoma cases. The global prevalence of glaucoma for population aged 40-80 years is 3.54% (95% CrI, 2.09-5.82). The prevalence of POAG is highest in Africa (4.20%; 95% CrI, 2.08-7.35), and the prevalence of PACG is highest in Asia (1.09%; 95% CrI, 0.43-2.32). In 2013, the number of people (aged 40-80 years) with glaucoma worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020 and 111.8 million in 2040. In the Bayesian meta-regression model, men were more likely to have POAG than women (odds ratio [OR], 1.36; 95% CrI, 1.23-1.52), and after adjusting for age, gender, habitation type, response rate, and year of study, people of African ancestry were more likely to have POAG than people of European ancestry (OR, 2.80; 95% CrI, 1.83-4.06), and people living in urban areas were more likely to have POAG than those in rural areas (OR, 1.58; 95% CrI, 1.19-2.04). The number of people with glaucoma worldwide will increase to 111.8 million in 2040, disproportionally affecting people residing in Asia and Africa. These estimates are important in guiding the designs of glaucoma screening, treatment, and related public health strategies. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            The pathophysiology and treatment of glaucoma: a review.

            Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.
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              Glaucomatous damage of the macula.

              There is a growing body of evidence that early glaucomatous damage involves the macula. The anatomical basis of this damage can be studied using frequency domain optical coherence tomography (fdOCT), by which the local thickness of the retinal nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy controls and patients, we show that: 1. For healthy controls, the average RGC+ layer thickness closely matches human histological data; 2. For glaucoma patients and suspects, the average RGC+ layer shows greater glaucomatous thinning in the inferior retina (superior visual field (VF)); and 3. The central test points of the 6° VF grid (24-2 test pattern) miss the region of greatest RGC+ thinning. Based upon fdOCT results from individual patients, we have learned that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as the displacement of RGCs from the foveal center is taken into consideration; and 2. Macular damage is typically arcuate in nature and often associated with local RNFL thinning in a narrow region of the disc, which we call the macular vulnerability zone (MVZ). According to our schematic model of macular damage, most of the inferior region of the macula projects to the MVZ, which is located largely in the inferior quadrant of the disc, a region that is particularly susceptible to glaucomatous damage. A small (cecocentral) region of the inferior macula, and all of the superior macula (inferior VF), project to the temporal quadrant, a region that is less susceptible to damage. The overall message is clear; clinicians need to be aware that glaucomatous damage to the macula is common, can occur early in the disease, and can be missed and/or underestimated with standard VF tests that use a 6° grid, such as the 24-2 VF test. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                BMJ Open Ophthalmol
                BMJ Open Ophthalmol
                bmjophth
                bmjophth
                BMJ Open Ophthalmology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2397-3269
                2023
                27 October 2023
                : 8
                : 1
                : e001331
                Affiliations
                [1 ]departmentDepartment of Nutritional Sciences, College of Agricultural & Life Sciences , University of Wisconsin , Madison, Wisconsin, USA
                [2 ]departmentDepartment of Ophthalmology and Visual Sciences , University of Wisconsin , Madison, Wisconsin, USA
                [3 ]departmentOphthalmology & Visual Sciences , Ringgold_5506Medical College of Wisconsin , Milwaukee, Wisconsin, USA
                [4 ]departmentDepartment of Ophthalmology & Visual Sciences , University of Illinois , Chicago, Illinois, USA
                [5 ]departmentDepartment of Psychology , Ringgold_1355University of Georgia , Athens, Georgia, USA
                [6 ]departmentDepartment of Epidemiology , University of Iowa , Iowa City, Iowa, USA
                [7 ]departmentDepartment of Cancer Prevention , Fred Hutchinson Cancer Center , Seattle, Washington, USA
                Author notes
                [Correspondence to ] Dr Yao Liu; yao.liu2@ 123456wisc.edu
                Author information
                http://orcid.org/0000-0003-0604-5333
                http://orcid.org/0000-0002-0700-0148
                Article
                bmjophth-2023-001331
                10.1136/bmjophth-2023-001331
                10619120
                37890895
                95a7f08f-76c4-4356-a02f-626247f1e223
                © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 08 May 2023
                : 06 October 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: HHSN268201600003C, HHSN268201600004C
                Award ID: HHSN268201600018C, HHSN268201600001C, HHSN26820160
                Funded by: Research to Prevent Blindness, Inc.;
                Award ID: Unrestricted grant to UW-Madison
                Funded by: FundRef http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: T32 DK007665
                Funded by: FundRef http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: EY013018
                Award ID: EY016886
                Award ID: EY025292
                Award ID: EY025292-01S1
                Award ID: P30 EY016665
                Funded by: McPherson Eye Research Institute;
                Award ID: Dan and Ellie Albert Medical Student Scholarship
                Funded by: FundRef http://dx.doi.org/10.13039/100006108, National Center for Advancing Translational Sciences;
                Award ID: UL1 TR002373
                Funded by: American Glaucoma Society;
                Award ID: MAPS Award
                Funded by: University of Wisconsin (UW) School of Medicine and Public Health;
                Award ID: Shapiro Fellowship
                Funded by: Lions Eye Bank of Wisconsin Gift of Sight Discovery Fund;
                Categories
                Glaucoma
                1506
                2348
                Original research
                Custom metadata
                unlocked

                glaucoma,epidemiology,optic nerve,retina,imaging
                glaucoma, epidemiology, optic nerve, retina, imaging

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