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      Variation in the Three-Dimensional Histomorphometry of the Normal Human Optic Nerve Head With Age and Race: Lamina Cribrosa and Peripapillary Scleral Thickness and Position

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          Abstract

          Purpose

          This study quantified the thickness and depth of the lamina cribrosa (LC) and peripapillary scleral thickness in high-resolution three-dimensional (3D) fluorescent reconstructions of the optic nerve head (ONH) in eyes from donors of African (AD) and European descent (ED).

          Methods

          A total of 64 eyes (45 ED, 19 AD) from 51 normal donors were obtained within 6 hours of death and fixed at 10 mm Hg of pressure. The optic nerve head was trephined from the globe and digitally reconstructed at 1.5 × 1.5 × 1.5 μm voxel resolution with an automated episcopic fluorescence technique. The load-bearing ONH connective tissue surfaces were manually delineated in 3D using custom software.

          Results

          The lamina cribrosa and peripapillary sclera were significantly thinner in AD eyes adjusting for age and sex (LC was 24 ± 11 μm thinner; P = 0.0350; scleral was 56 ± 22 μm thinner; P = 0.0097). The lamina cribrosa was significantly thinner in females (23 ± 11 μm thinner; P = 0.0425). Age was not significantly associated with any morphologic parameter in the ED group. However, increasing age was associated with an increase in scleral thickness (1.3 μm/year, P = 0.0499) and an increase in LC depth (2.3 μm/year, P = 0.0035) in the AD group. The sclera was thickest in the superior and temporal regions while the LC was thinnest superiorly.

          Conclusions

          Substantial sectorial and racial differences in LC and scleral morphology were observed, as well as increasing LC depth and scleral thickness with age in the AD group. Results suggest greater age-related remodeling of the load-bearing ONH connective tissues in eyes from AD individuals that could explain, in part, the greater predilection to glaucomatous injury seen in aged AD populations.

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          Most cited references52

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          Risk factors for progression of visual field abnormalities in normal-tension glaucoma.

          To uncover risk factors for the highly variable individual rates of progression in cases of untreated normal-tension glaucoma. Visual field data were assembled from 160 subjects (160 eyes) enrolled in the collaborative normal-tension glaucoma study during intervals in which the eye under study was not receiving intraocular pressure-lowering treatment during prerandomization and postrandomization intervals. Analyses included multivariate analysis of time-dependent Cox proportional hazard, Kaplan-Meier analysis of "survival" without an increment of visual field worsening, and comparison of slopes of change in mean deviation global index over time. Most migraine occurred in women, but analysis demonstrated that gender and presence of migraine contribute separately to the overall risk. The risk ratio for migraine, adjusted for the other variables was 2.58 (P =.0058), for disk hemorrhage was 2.72 (P =.0036), and for female gender 1.85 (P =.0622). The average fall in the mean deviation index was faster in nonmigrainous women than in nonmigrainous men (P =.05). Suggesting genetic influence, Asians had a slower rate of progression (P =.005), and the few black patients enrolled had a tendency for faster progression. However, self-declared history of family with glaucoma or treated for glaucoma did not affect the rate of progression. Neither age nor the untreated level of intraocular pressure affected the rate of untreated disease progression, despite their known influence on prevalence. Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.
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            Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study.

            The purpose of this study was to determine the prevalence of open-angle glaucoma and ocular hypertension in an Australian community whose residents are 49 years of age or older. There were 3654 persons, representing 82.4% of permanent residents from an area west of Sydney, Australia, who were examined. The population was identified by a door-to-door census of all dwellings and by closely matched findings from the national census. All participants received a detailed eye examination, including applanation tonometry, suprathreshold automated perimetry (Humphrey 76-point test), and Zeiss stereoscopic optic disc photography. Glaucoma suspects were asked to return for full threshold fields (Humphrey 30-2 test), gonioscopy, and repeat tonometry. A 5-point hemifield difference on the 76-point test was found in 616 persons (19% of people tested). Humphrey 30-2 tests were performed on 336 glaucoma suspects (9.2% of population), of whom 125 had typical glaucomatous field defects. Two hundred three persons had enlarged or asymmetric cup-disc ratios (> or = 0.7 in 1 or both eyes or a cup-disc ratio difference of > or = 0.3). Open-angle glaucoma was diagnosed when glaucomatous defects on the 30-2 test matched the optic disc changes, without regard to the intraocular pressure level. This congruence was found in 87 participants (2.4%), whereas an additional 21 persons (0.6%) had clinical signs of open-angle glaucoma but incomplete examination findings. Open-angle glaucoma was thus found in 108 persons, a prevalence of 3.0% (95% confidence interval [CI], 2.5-3.6), of whom 49% were diagnosed previously. An exponential rise in prevalence was observed with increasing age. Ocular hypertension, defined as an intraocular pressure in either eye greater than 21 mmHg, without matching disc and field changes, was present in 3.7% of this population (95% CI, 3.1-4.3), but there was no significant age-related increase in prevalence. The prevalence of glaucoma was higher in women after adjusting for age (odds ratio, 1.5; CI, 1.0-2.2). There was no sex difference in the age-adjusted prevalence of ocular hypertension. These data provide detailed age and sex-specific prevalence rates for open-angle glaucoma and ocular hypertension in an older Australian population.
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              A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma.

              This article is dedicated to Rosario Hernandez for her warm support of my own work and her genuine enthusiasm for the work of her colleagues throughout her career. I first met Rosario as a research fellow in Harry Quigley's laboratory between 1991 and 1993. Along with Harry, John Morrison, Elaine Johnson, Abe Clark, Colm O'Brien and many others, Rosario's work has provided lamina cribrosa astrocyte cellular mechanisms that are biomechanically plausible and in so doing provided credibility to early notions of the optic nerve head (ONH) as a biomechanical structure. We owe a large intellectual debt to Rosario for her dogged persistence in the characterization of the ONH astrocyte and lamina cribrosacyte in age and disease. Two questions run through her work and remain of central importance today. First, how do astrocytes respond to and alter the biomechanical environment of the ONH and the physiologic stresses created therein? Second, how do these physiologic demands on the astrocyte influence their ability to deliver the support to retinal ganglion cell axon transport and flow against the translaminar pressure gradient? The purpose of this article is to summarize what is known about the biomechanical determinants of retinal ganglion cell axon physiology within the ONH in the optic neuropathy of aging and Glaucoma. My goal is to provide a biomechanical framework for this discussion. This framework assumes that the ONH astrocytes and glia fundamentally support and influence both the lamina cribrosa extracellular matrix and retinal ganglion cell axon physiology. Rosario Hernandez was one of the first investigators to recognize the implications of this unique circumstance. Many of the ideas contained herein have been initially presented within or derived from her work (Hernandez, M.R., 2000. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 19, 297-321.; Hernandez, M.R., Pena, J.D., 1997. The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol. 115, 389-395.). Copyright © 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                July 2017
                : 58
                : 9
                : 3759-3769
                Affiliations
                [1 ]Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
                [2 ]Department of Biomedical Engineering, School of Engineering, University of Alabama at Birmingham, Birmingham, Alabama, United States
                [3 ]Devers Eye Institute, Legacy Health System, Portland, Oregon, United States
                Author notes
                Correspondence: Christopher A. Girkin, Department of Ophthalmology, UAB Callahan Eye Hospital, 1700 South 18th Street, Suite 601, Birmingham, AL 35213, USA; cgirkin@ 123456uab.edu .

                CAG and MAF contributed equally to the work presented here and therefore should be considered equivalent authors.

                Article
                iovs-58-09-17 IOVS-17-21842
                10.1167/iovs.17-21842
                5525554
                28738420
                3fedab83-33c6-4477-8013-8d4899b623c2
                Copyright 2017 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 13 March 2017
                : 13 June 2017
                Categories
                Glaucoma

                lamina cribrosa,race,optic nerve head,morphometry
                lamina cribrosa, race, optic nerve head, morphometry

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