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      Age-related change in flicker thresholds with rod- and cone-enhanced stimuli

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          Abstract

          Purpose

          Rod and cone photoreceptor-specific tests can be time-consuming. A new non-invasive test is described. The test is based on the measurement of flicker modulation thresholds with rod- and cone-enhanced visual stimuli, which requires only minimum adaptation time. Here, we investigated how the rod-and cone-mediated flicker thresholds vary with age.

          Methods

          Monocular thresholds with rod and cone–enhanced stimuli were measured in 140 healthy adults, (age range: 18–75 years), foveally (0°) and at four parafoveal locations, at an eccentricity of 5° in each of the four quadrants using five, adaptive, interleaved staircases. Temporal frequencies, stimulus sizes, background luminance and spectral composition, were adjusted appropriately to achieve approximately 1 log unit separation in sensitivity between the rod- and cone-enhanced stimuli. Spectrally calibrated, ‘neutral density’ filters were used to enable adequate control of display luminance for rod enhanced stimuli.

          Results

          The magnitude of central and parafoveal rod thresholds was significantly higher than the central and parafoveal cone thresholds, respectively (p < 0.001) in both the age groups. However, the rate of increase in central rod thresholds (y = 0.45x—12.79; linear regression equation) was not significantly steeper than the rate of increase in central (y = 0.29x—8.53) cone thresholds (p = 0.15). Centrally, cone thresholds showed a better correlation with rod central thresholds for the age > 45 years (Spearman correlation, ρ = 0.74, p < 0.001) compared to age ≤ 45 years (ρ = 0.41, p < 0.001).

          Conclusions

          Thresholds with rod- and cone-enhanced stimuli are largely invariant below 45 years of age and increase rapidly above this age. This age-wise normative database can be used as an effective functional-marker to assess photoreceptor sensitivities in retinal diseases.

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          Most cited references65

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          The Lens Opacities Classification System III

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            Photoreceptor loss in age-related macular degeneration.

            The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the fundus. If so, AMD must have a predilection for rods over cones. The authors tested this hypothesis by determining the relative numbers of cones and rods in donor eyes with mid-to late-stage AMD and in age-matched controls. Thirteen eyes (from seven donors) with grossly visible macular drusen and pigmentary disturbances were either wholemounted for photoreceptor counts or sectioned through the fovea for histopathology and carbonic anhydrase histochemistry to label red-green cones. Eyes were assigned to AMD or control groups on the basis of histopathology and clinical history. Five nonexudative AMD (NE-AMD) eyes from three donors showed sparing of foveal cones and loss of rods and cones in the parafovea. In two donors, rod loss exceeded cone loss at most parafoveal locations, and in one donor, rod density was normal and cone density was reduced. In eight exudative AMD (EX-AMD) eyes from five donors, photoreceptors surviving along the margins of and overlying disciform scars were largely cones. Photoreceptors are lost in NE-AMD as well as in the more severe exudative form, consistent with functional and clinical studies. The authors propose that rods die in older eyes without evidence of overt retinal pigment epithelial disease. In persons susceptible to AMD, the retinal pigment epithelium becomes dysfunctional. Secondarily, rod loss continues and cones begin to degenerate. Eventually, only degenerate cones remain; ultimately, all photoreceptors may disappear.
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              Aging and vision.

              Given the increasing size of the older adult population in many countries, there is a pressing need to identify the nature of aging-related vision impairments, their underlying mechanisms, and how they impact older adults' performance of everyday visual tasks. The results of this research can then be used to develop and evaluate interventions to slow or reverse aging-related declines in vision, thereby improving quality of life. Here we summarize salient developments in research on aging and vision over the past 25 years, focusing on spatial contrast sensitivity, vision under low luminance, temporal sensitivity and motion perception, and visual processing speed. Copyright © 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: Visualization
                Role: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 July 2020
                2020
                : 15
                : 7
                : e0232784
                Affiliations
                [1 ] Brien Holden Institute of Optometry and Vision Science, L V Prasad Eye Institute, Hyderabad, India
                [2 ] Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India
                [3 ] Centre for Applied Vision Research, School of Health Sciences, City, University of London, London, England, United Kingdom
                [4 ] Human Performance, QinetiQ, Hampshire, England, United Kingdom
                University of Massachusetts Medical School, UNITED STATES
                Author notes

                Competing Interests: AH and SRB received support in the form of salaries from the Hyderabad Eye Research Foundation. AS, JB, and JRES received support in the form of salaries from City University of London. JRES received support in the form of a salary from QinetiQ. The authors would like to declare the following patents/patent applications associated with this research: EU- EP08762401.1; US- US8,322,857: 'Vision testing apparatus and method.' This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-6087-2690
                http://orcid.org/0000-0002-2187-5004
                Article
                PONE-D-20-02487
                10.1371/journal.pone.0232784
                7343165
                32639956
                70ae23b9-fe65-4b54-90aa-436203203765
                © 2020 Hathibelagal 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
                : 27 January 2020
                : 21 April 2020
                Page count
                Figures: 6, Tables: 2, Pages: 15
                Funding
                "John L Barbur is an inventor of AVOT tests (some employed in this study); an employee of City, University of London; and a director of City Occupational Ltd. (a City University spin out company setup to manufacture and supply AVOT tests). The funder provided support in the form of salaries for author [JS], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
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