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      Cytokine biomarkers in tear film for primary open-angle glaucoma

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          Abstract

          Purpose

          To determine the utility of tear film cytokines as biomarkers for early primary open-angle glaucoma (POAG).

          Methods

          Patients without POAG and eye drop-naïve patients with newly diagnosed POAG were recruited from an academic hospital-based glaucoma practice. Tear films of recruited patients were obtained and analyzed using a multiplex, high-sensitivity electrochemiluminescent enzyme-linked immunosorbent assay for proinflammatory cytokines (IFNγ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, and TNFα).

          Results

          Mean concentrations of tear film cytokines were lower in the glaucoma group for 8 of 10 cytokines tested. IL-12p70 (3.94±2.19 pg/mL in control vs 2.31±1.156 pg/mL in POAG; P=0.035) was significantly lower in the tear film of patients with newly diagnosed POAG.

          Conclusion

          Proinflammatory cytokines were lower in eye drop-naïve newly diagnosed glaucoma patients. Tear film cytokine profiles may be used as biomarkers of early POAG.

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          Most cited references21

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          Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons.

          To compare the number of retinal ganglion cells (RGCs) topographically mapped with specific visual field threshold test data in the same eyes among glaucoma patients. Seventeen eyes of 13 persons with well-documented glaucoma histories and Humphrey threshold visual field tests (San Leandro, CA) were obtained from eye banks. RGC number was estimated by histologic counts of retinal sections and by counts of remaining axons in the optic nerves. The locations of the retinal samples corresponded to specific test points in the visual field. The data for glaucoma patients were compared with 17 eyes of 17 persons who were group matched for age, had no ocular history, and had normal eyes by histologic examination. The mean RGC loss for the entire retina averaged 10.2%, indicating that many eyes had early glaucoma damage. RGC body loss averaged 35.7% in eyes with corrected pattern SD probability less than 0.5%. When upper to lower retina RGC counts were compared with their corresponding visual field data within each eye, a 5-dB loss in sensitivity was associated with 25% RGC loss. For individual points that were abnormal at a probability less than 0.5%, the mean RGC loss was 29%. In control eyes, the loss of RGCs with age was estimated as 7205 cells per year in persons between 55 and 95 years of age. In optic nerves from glaucoma subjects, smaller axons were significantly more likely to be present than larger axons (R2 = 0.78, P<0.001). At least 25% to 35% RGC loss is associated with statistical abnormalities in automated visual field testing. In addition, these data corroborate previous findings that RGCs with larger diameter axons preferentially die in glaucoma.
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            Prevalence of open-angle glaucoma among adults in the United States.

            To estimate the prevalence and distribution of open-angle glaucoma (OAG) in the United States by age, race/ethnicity, and gender. Summary prevalence estimates of OAG were prepared separately for black, Hispanic, and white subjects in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US census data and to projected US population figures for 2020 to estimate the number of the US population with OAG. The overall prevalence of OAG in the US population 40 years and older is estimated to be 1.86% (95% confidence interval, 1.75%-1.96%), with 1.57 million white and 398 000 black persons affected. After applying race-, age-, and gender-specific rates to the US population as determined in the 2000 US census, we estimated that OAG affects 2.22 million US citizens. Owing to the rapidly aging population, the number with OAG will increase by 50% to 3.36 million in 2020. Black subjects had almost 3 times the age-adjusted prevalence of glaucoma than white subjects. Open-angle glaucoma affects more than 2 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to more than 3 million by 2020.
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              Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey.

              A detailed ocular examination, including perimetry, was conducted on 5308 black and white subjects aged 40 years and older in a population-based prevalence survey in east Baltimore, Md. Repeated, detailed examinations were carried out on selected subjects. Roughly half of all subjects with optic nerve damage from primary open angle glaucoma, regardless of race, were unaware that they had the condition. The average intraocular pressure (IOP) among black patients with glaucoma who were receiving treatment was virtually identical to that in those black patients who were not receiving treatment (median IOP, 20 mm Hg); treated eyes of white patients had a lower IOP than those eyes of white patients who were not receiving treatment (mean [+/- SD] IOP, 18.69 +/- 3.23 mm Hg vs 24.15 +/- 5.23 mm Hg; P less than .001). The risk of glaucomatous optic nerve damage increased with the height of the screening IOP, particularly at levels of 22 to 29 and 30 mm Hg and above (relative rate compared with IOP of 15 mm Hg or lower, 12.8 and 40.1 mm Hg, respectively). More than half of all glaucomatous eyes had a screening IOP below 21 mm Hg, whether these eyes were receiving treatment or not. The IOP in glaucomatous eyes tended to rise on follow-up, in contrast with nonglaucomatous eyes in which the IOP was as likely to rise as to fall. Results confirmed that IOP is an important factor in glaucoma, but did not support the traditional distinction between "normal" and "elevated" pressure, nor its corollaries, "low-tension" glaucoma and "high-tension" glaucoma.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clin Ophthalmol
                Clinical Ophthalmology
                Clinical Ophthalmology (Auckland, N.Z.)
                Dove Medical Press
                1177-5467
                1177-5483
                2017
                22 February 2017
                : 11
                : 411-416
                Affiliations
                [1 ]Department of Ophthalmology, Duke University Medical Center, Durham, NC
                [2 ]Department of Ophthalmology, University of Washington, Seattle, WA
                [3 ]Duke Molecular Physiology Institute
                [4 ]Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
                Author notes
                Correspondence: Divakar Gupta, Department of Ophthalmology, Duke University Medical Center, 2351 Erwin Rd, Durham, NC 27703, USA, Tel +1 919 684 6611, Fax +1 919 681 8267, Email divakar.gupta@ 123456duke.edu
                [*]

                These authors contributed equally to this work

                Article
                opth-11-411
                10.2147/OPTH.S125364
                5328319
                46dc67da-8ada-4d4b-9e6f-b8efb13d1140
                © 2017 Gupta et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Ophthalmology & Optometry
                glaucoma,biomarkers,tear film,cytokines,glaucoma diagnosis,lower limit of detection

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