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      Evidence for Structural and Functional Damage of the Inner Retina in Diabetes With No Diabetic Retinopathy

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          Abstract

          Purpose

          To provide structural and functional evidence of inner retinal loss in diabetes prior to vascular changes and interpret the structure-function relationship in the context of an established neural model.

          Methods

          Data from one eye of 505 participants (134 with diabetes and no clinically evident vascular alterations of the retina) were included in this analysis. The data were collected as part of a large population-based study. Functional tests included best-corrected visual acuity, Pelli-Robson contrast sensitivity, mesopic microperimetry, and frequency doubling technology perimetry (FDT). Macular optical coherence tomography volume scans were collected for all participants. To interpret the structure-function relationship in the context of a neural model, ganglion cell layer (GCL) thickness was converted to local ganglion cell (GC) counts.

          Results

          The GCL and inner plexiform layer were significantly thinner in participants with diabetes ( P < 0.05), with no significant differences in the macular retinal nerve fiber layer or the outer retina. All functional tests except microperimetry showed a significant loss in diabetic patients ( P < 0.05). Both FDT and microperimetry showed a significant relationship with the GC count ( P < 0.05), consistent with predictions from a neural model for partial summation conditions. However, the FDT captured additional significant damage ( P = 0.03) unexplained by the structural loss.

          Conclusions

          Functional and structural measurements support early neuronal loss in diabetes. The structure-function relationship follows the predictions from an established neural model. Functional tests could be improved to operate in total summation conditions in the macula, becoming more sensitive to early loss.

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          Most cited references63

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          Global Prevalence and Major Risk Factors of Diabetic Retinopathy

          OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.
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            Diabetic retinopathy.

            Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising. Copyright 2010 Elsevier Ltd. All rights reserved.
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              A simple sequentially rejective multiple test procedure

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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest Ophthalmol Vis Sci
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                24 March 2021
                March 2021
                : 62
                : 3
                : 35
                Affiliations
                [1 ]Optometry and Visual Sciences, City, University of London, London, United Kingdom
                [2 ]NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
                [3 ]Centre for Public Health, Queen's University Belfast, Block B, Royal Hospital, Belfast, Northern Ireland
                Author notes
                [* ]Correspondence: Giovanni Montesano, Optometry and Visual Sciences, City, University of London, Northampton Square, London, EC1V 0HB, UK; giovmontesano@ 123456gmail.com.
                Article
                IOVS-20-31957
                10.1167/iovs.62.3.35
                7995918
                33760040
                c2643153-4f68-494f-9a72-20be222247d8
                Copyright 2021 The Authors

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

                History
                : 26 February 2021
                : 10 December 2020
                Page count
                Pages: 13
                Categories
                Retina
                Retina

                diabetes,retinal ganglion cells,microperimetry,oct,spatial summation

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