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      Influence of Clinical Factors and Magnification Correction on Normal Thickness Profiles of Macular Retinal Layers Using Optical Coherence Tomography

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          Abstract

          Purpose

          To identify the factors which significantly contribute to the thickness variabilities in macular retinal layers measured by optical coherence tomography with or without magnification correction of analytical areas in normal subjects.

          Methods

          The thickness of retinal layers {retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCLIPL), RNFL plus GCLIPL (ganglion cell complex, GCC), total retina, total retina minus GCC (outer retina)} were measured by macular scans (RS-3000, NIDEK) in 202 eyes of 202 normal Asian subjects aged 20 to 60 years. The analytical areas were defined by three concentric circles (1-, 3- and 6-mm nominal diameters) with or without magnification correction. For each layer thickness, a semipartial correlation (sr) was calculated for explanatory variables including age, gender, axial length, corneal curvature, and signal strength index.

          Results

          Outer retinal thickness was significantly thinner in females than in males (sr 2, 0.07 to 0.13) regardless of analytical areas or magnification correction. Without magnification correction, axial length had a significant positive sr with RNFL (sr 2, 0.12 to 0.33) and a negative sr with GCLIPL (sr 2, 0.22 to 0.31), GCC (sr 2, 0.03 to 0.17), total retina (sr 2, 0.07 to 0.17) and outer retina (sr 2, 0.16 to 0.29) in multiple analytical areas. The significant sr in RNFL, GCLIPL and GCC became mostly insignificant following magnification correction.

          Conclusions

          The strong correlation between the thickness of inner retinal layers and axial length appeared to result from magnification effects. Outer retinal thickness may differ by gender and axial length independently of magnification correction.

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          Most cited references40

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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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            Improvements on Littmann's method of determining the size of retinal features by fundus photography.

            Littmann's formula relating the size of a retinal feature to its measured image size on a telecentric fundus camera film is widely used. It requires only the corneal radius, ametropia, and Littmann's factor q obtained from nomograms or tables. These procedures are here computerized for practitioners' convenience. Basic optical principles are discussed, showing q to be a constant fraction of the theoretical ocular dimension k', the distance from the eye's second principal point to the retina. If the eye's axial length is known, three new methods of determining q become available: (a) simply reducing the axial length by a constant 1.82 mm; (b) constructing a personalized schematic eye, given additional data; (c) ray tracing through this eye to extend calculations to peripheral retinal areas. Results of all these evaluations for 12 subjects of known ocular dimensions are presented for comparison. Method (a), the simplest, is arguably the most reliable. It shows good agreement with Littmann's supplementary procedure when the eye's axial length is known.
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              Effect of myopia on the thickness of the retinal nerve fiber layer measured by Cirrus HD optical coherence tomography.

              To evaluate the effect of myopia on the peripapillary retinal nerve fiber layer (RNFL) thickness measured by Cirrus HD optical coherence tomography (OCT). Comprehensive ophthalmic examinations were performed, including measurement of visual acuity, refraction, and axial length on 269 subjects (age, 19-26 years) with no ophthalmic abnormality. Further, 200 x 200-cube optic disc scans of the subjects' eyes were obtained with Cirrus HD OCT. The RNFL thickness at 256 points of the RNFL thickness profile and the average RNFL thickness were recorded. The correlations between these values and the axial length and spherical equivalent (SE) of refractive errors were then analyzed by simple linear regression, before and after adjustment of the ocular magnification. Before ocular magnification adjustment, the uncorrected average RNFL thickness decreased as the axial length increased and as the SE decreased. However, after the adjustment, the corrected average RNFL thickness exhibited no correlation with the spherical equivalent and a weak positive correlation with the axial length. Myopia also affected the RNFL thickness distribution. As the axial length increased and the spherical equivalent decreased, the thickness of the temporal peripapillary RNFL increased and that of the superior, superior nasal, inferior, and inferior nasal peripapillary RNFL decreased. The axial length affected the average RNFL thickness, and myopia affected the RNFL thickness distribution. High myopes are likely to exhibit different RNFL distribution patterns. Since ocular magnification significantly affects the RNFL measurement in such patients, it should be considered in diagnosing glaucoma.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 January 2016
                2016
                : 11
                : 1
                : e0147782
                Affiliations
                [1 ]Department of Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
                [2 ]Department of Ophthalmology, Saitama Medical University, Saitama, Japan
                [3 ]Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [4 ]Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan
                [5 ]Department of Ophthalmology, National University Hospital, National University Health System, Singapore, Singapore
                [6 ]Department of Ophthalmology, United Christian Hospital and Tseung Kwan O Hospital, Hong Kong, China
                [7 ]Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
                University of Florida, UNITED STATES
                Author notes

                Competing Interests: The authors of this manuscript have the following competing interests: F, NIDEK (MH, HT), Canon (HT, NY), C, Santen (SO), JAPAN FOCUS (SO), NIDEK (SO, MH, KS, NY), Canon (NY), R, Carl Zeiss (HT), NIDEK (HT, KL, NY), Canon (NY). This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: TH SO MH YI NS KOM HT KS PC KL NY. Performed the experiments: TH. Analyzed the data: TH. Contributed reagents/materials/analysis tools: TH SO MH YI NS KOM HT KS PC KL NY. Wrote the paper: TH SO MH YI NS KOM HT KS PC KL NY.

                Article
                PONE-D-15-46440
                10.1371/journal.pone.0147782
                4729678
                26814541
                ef003b1c-6fc6-4e8a-882f-e34482563eae
                © 2016 Higashide et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 October 2015
                : 10 January 2016
                Page count
                Figures: 7, Tables: 3, Pages: 17
                Funding
                This work was supported by a Grant-in-Aid for Scientific Research (26462632) from the Japan Society for the Promotion of Science (KS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Retina
                Medicine and Health Sciences
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                Ocular System
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                Retina
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                Eyes
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                Cell Biology
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                Ophthalmology
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