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Kaya S, Khamees A, Geerling G, Strzalkowski P, Gontscharuk V, Szendroedi J, Müssig K, Ziegler D, Roden M, Guthoff R. Macular perfusion alterations in people with recent-onset diabetes and novel diabetes subtypes. Diabetologia 2025; 68:1140-1156. [PMID: 40164944 PMCID: PMC12069482 DOI: 10.1007/s00125-025-06407-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 01/27/2025] [Indexed: 04/02/2025]
Abstract
AIMS/HYPOTHESIS Our aim was to detect early structural and functional changes in the macular capillaries using optical coherence tomography angiography during the course of type 1 or 2 diabetes mellitus. METHODS In this cross-sectional study, individuals with type 1 diabetes (n=143) or type 2 diabetes (n=197) from the German Diabetes Study (ClinicalTrials.gov registration no. NCT01055093) underwent clinical examination and cluster analysis to identify phenotype-based diabetes subtypes, using BMI, age, HbA1c, homoeostasis model estimates and islet autoantibodies. Colour fundus photography, optical coherence tomography and optical coherence tomography angiography were performed within the first year of diabetes diagnosis (baseline) and at 5 year intervals up to year 10. Age- and sex-adjusted participants served as control participants (n=105). Perfusion density, vessel density, presence of retinal microaneurysms in superficial, intermediate and deep capillary plexus (SCP, ICP, DCP), choriocapillaris flow deficit density (CC FD) and the foveal avascular zone (FAZ) of the macula as well as retinal layer thickness, visual acuity and contrast sensitivity were analysed. RESULTS Perfusion density and vessel density of SCP were already reduced at baseline in type 2 diabetes (expected difference compared with control participants: -0.0071, p=0.0276, expected difference: -0.0034, p=0.0184, respectively), especially in participants with severe insulin-deficient and mild obesity-related diabetes. At year 10 only perfusion density of the SCP and DCP was reduced in both type 1 and 2 diabetes (p=0.0365, p=0.0062, respectively). The FAZ was enlarged and the CC FD within the first year increased in type 1 (p=0.0327, p=0.0474, respectively) and more markedly in type 2 diabetes (p=0.0006, p<0.0001). The occurrence of microaneurysms in SCP and DCP was significant at year 5 (p=0.0209, p=0.0279, respectively) and year 10 (p=0.0220, p=0.0007). Presence of microaneurysms in SCP and DCP was associated with decreases in perfusion density and vessel density in both SCP and ICP. Furthermore, microaneurysms were associated with decreased ganglion cell layer and inner plexiform layer thickness. CONCLUSIONS/INTERPRETATION Type 2 diabetes already reduces macular perfusion SCP at time of clinical diagnosis, while long-standing diabetes affects both SCP and DCP. The FAZ of the SCP and the CC FD are early indicators of diabetic alterations, with more pronounced changes observed in type 2 diabetes. Microaneurysms in the macular plexus are associated with a decrease of ganglion cell layer and inner plexiform layer. Subclinical microangiopathy occurs prior to manifestation of diabetic retinopathy, disease-related visual acuity impairment or inner retinal layer thinning.
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Affiliation(s)
- Sema Kaya
- Department of Ophthalmology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Ala Khamees
- Department of Ophthalmology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Gerd Geerling
- Department of Ophthalmology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Piotr Strzalkowski
- Department of Ophthalmology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Veronika Gontscharuk
- Institute for Health Services Research and Health Economics, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Institute for Health Services Research and Health Economics, Centre for Health and Society, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
| | - Julia Szendroedi
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
- Department of Internal Medicine I, Medical Faculty, Ruprecht Karls University Heidelberg, Heidelberg, Germany
| | - Karsten Müssig
- Department of Internal Medicine, Gastroenterology and Diabetology, Niels Stensen Hospitals, Franziskus Hospital Harderberg, Georgsmarienhütte, Germany
| | - Dan Ziegler
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michael Roden
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Rainer Guthoff
- Department of Ophthalmology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
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Bodduluri L, Dain SJ, Hameed S, Verge CF, Boon MY. Visual function and retinal thickness in children with type 1 diabetes mellitus. Clin Exp Optom 2024; 107:739-747. [PMID: 38175925 DOI: 10.1080/08164622.2023.2288176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 11/08/2023] [Accepted: 11/20/2023] [Indexed: 01/06/2024] Open
Abstract
CLINICAL RELEVANCE The possibility that changes in blue-yellow visual thresholds and some retinal thickness measures in children with diabetes mellitus may be observed before any visible fundus changes points to the possibility of these measures being a useful predictor that the risks of diabetic retinopathy are higher in some children than in others. INTRODUCTION Previous studies showed mixed results on chromatic and achromatic contrast sensitivity early in the course of diabetes mellitus, and the findings of these studies may have been influenced by a lack of experimental sensitivity to visual deficits, a bias towards tritan-like errors or the cognitive demands of the tests and variations in sample composition. The purpose of this study was to evaluate colour and contrast thresholds and retinal thickness in children with type 1 diabetes mellitus compared with age-matched controls. METHODS A prospective case-control study was carried out on 9-14-year-old children with type 1 diabetes mellitus (49 cases) and age matched controls (49) in which isoluminant red-green and blue-yellow and achromatic luminance contrast thresholds were measured. Fundus photography was used to grade diabetic retinopathy. Retinal thickness parameters were measured using optical coherence tomography. Data on the duration of diabetes mellitus, glycaemic control (HbA1c), blood glucose level, body mass index, blood pressure and blood oxygenation at the time of testing were obtained. RESULTS The cases mostly had poorly controlled diabetes, HbA1c 8.6% (6.4-12.8%), for an average (range) duration of 5 (0.4-12) years. The cases had significantly higher blue-yellow thresholds (p = 0.02) and greater total retinal and inner retinal thickness (p < 0.05) than controls. No cases had diabetic retinopathy. Within the cases, poorer visual function and systemic health measures were associated with thinner retinal structures and greater global loss volume percentage in the ganglion cell complex. CONCLUSION Blue-yellow thresholds of cases were raised compared to normal. Within the cases, higher luminance contrast thresholds were also associated with, mostly, ganglion cell complex reductions.
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Affiliation(s)
- Lakshmi Bodduluri
- School of Optometry and Vision Science, University of New South Wales, Sydney, Australia
| | - Stephen J Dain
- School of Optometry and Vision Science, University of New South Wales, Sydney, Australia
| | - Shihab Hameed
- Endocrinology Department, Sydney Children's Hospital, Randwick, Australia
| | - Charles F Verge
- Endocrinology Department, Sydney Children's Hospital, Randwick, Australia
- Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
| | - Mei Ying Boon
- School of Optometry and Vision Science, University of New South Wales, Sydney, Australia
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Szeto SK, Lai TY, Vujosevic S, Sun JK, Sadda SR, Tan G, Sivaprasad S, Wong TY, Cheung CY. Optical coherence tomography in the management of diabetic macular oedema. Prog Retin Eye Res 2024; 98:101220. [PMID: 37944588 DOI: 10.1016/j.preteyeres.2023.101220] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 10/24/2023] [Accepted: 10/24/2023] [Indexed: 11/12/2023]
Abstract
Diabetic macular oedema (DMO) is the major cause of visual impairment in people with diabetes. Optical coherence tomography (OCT) is now the most widely used modality to assess presence and severity of DMO. DMO is currently broadly classified based on the involvement to the central 1 mm of the macula into non-centre or centre involved DMO (CI-DMO) and DMO can occur with or without visual acuity (VA) loss. This classification forms the basis of management strategies of DMO. Despite years of research on quantitative and qualitative DMO related features assessed by OCT, these do not fully inform physicians of the prognosis and severity of DMO relative to visual function. Having said that, recent research on novel OCT biomarkers development and re-defined classification of DMO show better correlation with visual function and treatment response. This review summarises the current evidence of the association of OCT biomarkers in DMO management and its potential clinical importance in predicting VA and anatomical treatment response. The review also discusses some future directions in this field, such as the use of artificial intelligence to quantify and monitor OCT biomarkers and retinal fluid and identify phenotypes of DMO, and the need for standardisation and classification of OCT biomarkers to use in future clinical trials and clinical practice settings as prognostic markers and secondary treatment outcome measures in the management of DMO.
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Affiliation(s)
- Simon Kh Szeto
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Timothy Yy Lai
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Stela Vujosevic
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Eye Clinic, IRCCS MultiMedica, Milan, Italy
| | - Jennifer K Sun
- Beetham Eye Institute, Harvard Medical School, Boston, USA
| | - SriniVas R Sadda
- Doheny Eye Institute, University of California Los Angeles, Los Angeles, USA
| | - Gavin Tan
- Singapore Eye Research Institute, SingHealth Duke-National University of Singapore, Singapore
| | - Sobha Sivaprasad
- NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Tien Y Wong
- Tsinghua Medicine, Tsinghua University, Beijing, China; Singapore Eye Research Institute, Singapore
| | - Carol Y Cheung
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
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Malakhova AI, Strakhov VV, Malakhova YA. [Objective structural and functional monitoring of polypeptide retinal neuroprotective therapy in diabetic retinopathy]. Vestn Oftalmol 2024; 140:97-104. [PMID: 39569781 DOI: 10.17116/oftalma202414005197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
In recent years, there has been a growing interest in the contribution of neuroretinal degeneration to the pathogenesis of diabetic retinopathy (DR), preceding the classic vascular changes associated with DR. PURPOSE This study evaluated the impact of the polypeptide drug Retinalamin on the structural and functional condition of the retina in patients with DR using optical coherence tomography (OCT) (Topcon OCT 2000 FA, Japan) and the Diopsys Nova vision testing system for electrophysiological studies of the visual organ. MATERIAL AND METHODS The clinical study included 56 patients (112 eyes) with type 1 and type 2 diabetes and DR without macular edema. Of these, 28 patients (56 eyes) comprised the main group receiving intramuscular Retinalamin. The control group consisted of 28 patients (56 eyes) who did not receive Retinalamin treatment. The thickness of the ganglion cell complex was analyzed by OCT imaging performed on the Topcon OCT 2000 FA. Electrophysiological studies of the visual organ were conducted using the Diopsys Nova vision testing system, following the Diopsys PERG24 (pattern ERG) and Diopsys ffERG/Multi-Luminance Flicker (full-field ERG, or flash ERG) protocols. RESULTS The study demonstrated convincing objective evidence of positive changes in the main observation group. CONCLUSION The emergence of two pathogenetically oriented neurodegenerative vectors of DR, involving both the inner and outer retina, significantly expands our understanding of this diabetic complication. This includes the potential for retinal neuroprotective treatment with peptide bioregulators in clinical practice, especially in the early stages of DR.
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Affiliation(s)
- A I Malakhova
- Smolensk Regional Clinical Hospital, Smolensk, Russia
| | - V V Strakhov
- Yaroslavl State Medical University, Yaroslavl, Russia
| | - Yu A Malakhova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
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Hashemi H, Shahidi A, Hashemi A, Jamali A, Mortazavi A, Khabazkhoob M. The prevalence of red-green color vision deficiency and its related factors in an elderly population above 60 years of age. Int J Ophthalmol 2023; 16:1535-1541. [PMID: 37724279 PMCID: PMC10475627 DOI: 10.18240/ijo.2023.09.22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 06/12/2023] [Indexed: 09/20/2023] Open
Abstract
AIM To determine the prevalence of red-green (RG) color vision deficiency (CVD) in an elderly population and its related factors. METHODS This report is a part of the Tehran Geriatric Eye Study: a cross-sectional population-based study that was conducted on the elderly population (≥60y) of Tehran, Iran using multi-stage stratified random cluster sampling. All study participants underwent complete ocular examination, including the measurement of uncorrected and best-corrected visual acuity, objective and subjective refraction, and slit-lamp biomicroscopy. The color vision was tested using Ishihara plates with the near optical correction in place. RESULTS Of the 3791 invitees, 3310 participated in the study. The data of 2164 individuals were analyzed after applying the exclusion criteria. The prevalence of R-G CVD was 3.73% (95%CI: 2.37%-5.09%) in the whole sample; the prevalence of protanomaly, protanopia, and deuteranopia was 1.51%, 1.76%, and 0.45%, respectively. The prevalence of R-G CVD was significantly higher in males than in females. The prevalence of RG CVD increased with advancing age from 2.91% in the age group 60-64y to 5.8% in the age group ≥80y (P=0.070). According to the multiple logistic regression model, male sex, and glaucoma were significantly related to RG CVD. Older age and hypertension also had a marginally significant relationship with RG CVD. CONCLUSION Changes in color vision occur in the elderly due to the aging process and some physiological and pathological factors. Since the change in visual perception may affect the person's performance, this aspect of the visual system's function should also be taken into consideration in the examinations of the elderly.
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Affiliation(s)
- Hassan Hashemi
- Noor Research Center for Ophthalmic Epidemiology, Noor Eye Hospital, Tehran 1983963113, Iran
| | - Aida Shahidi
- Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran 1983963113, Iran
| | - Alireza Hashemi
- Noor Research Center for Ophthalmic Epidemiology, Noor Eye Hospital, Tehran 1983963113, Iran
| | - Alireza Jamali
- Rehabilitation Research Center, Department of Optometry, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran 1545913487, Iran
| | - Abolghasem Mortazavi
- Department of Neurosurgery, Sina Hospital, Tehran University of Medical Sciences, Tehran 1416753955, Iran
| | - Mehdi Khabazkhoob
- Department of Basic Sciences, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran 1968653111, Iran
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Amorim M, Martins B, Fernandes R. Immune Fingerprint in Diabetes: Ocular Surface and Retinal Inflammation. Int J Mol Sci 2023; 24:9821. [PMID: 37372968 DOI: 10.3390/ijms24129821] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 05/29/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye's immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system's main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.
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Affiliation(s)
- Madania Amorim
- Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Beatriz Martins
- Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-531 Coimbra, Portugal
| | - Rosa Fernandes
- Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-531 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal
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Hernández C, Simó-Servat O, Porta M, Grauslund J, Harding SP, Frydkjaer-Olsen U, García-Arumí J, Ribeiro L, Scanlon P, Cunha-Vaz J, Simó R. Serum glial fibrillary acidic protein and neurofilament light chain as biomarkers of retinal neurodysfunction in early diabetic retinopathy: results of the EUROCONDOR study. Acta Diabetol 2023; 60:837-844. [PMID: 36959506 DOI: 10.1007/s00592-023-02076-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/11/2023] [Indexed: 03/25/2023]
Abstract
AIMS Neurodegeneration and glial activation are primary events in the pathogenesis of diabetic retinopathy. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of underlying neuroinflammatory and neurodegenerative disease processes. The aim of the present study was to assess the usefulness of these serum biomarkers for the identification and monitoring of retinal neurodysfunction in subjects with type 2 diabetes. METHODS A case-control study was designed including 38 patients from the placebo arm of the EUROCONDOR clinical trial: 19 with and 19 without retinal neurodysfunction assessed by multifocal electroretinography. GFAP and NfL were measured by Simoa. RESULTS Serum levels of GFAP and NfL directly correlated with age (r = 0.37, p = 0.023 and r = 0.54, p < 0.001, respectively). In addition, a direct correlation between GFAP and NfL was observed (r = 0.495, p = 0.002). Serum levels of GFAP were significantly higher at baseline in those subjects in whom neurodysfunction progressed after the 2 years of follow-up (139.1 ± 52.5 pg/mL vs. 100.2 ± 54.6 pg/mL; p = 0.04). CONCLUSIONS GFAP could be a useful serum biomarker for retinal neurodysfunction. Monitoring retinal neurodysfunction using blood samples would be of benefit in clinical decision-making. However, further research is needed to validate this result as well as to establish the best cutoff values.
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Affiliation(s)
- Cristina Hernández
- Diabetes and Metabolism Research Unit and CIBERDEM, Vall d'Hebron Research Institute, Vall d'Hebron Barcelona Hospital Campus, Passeig de La Vall d'Hebron, 119-129, 08035, Barcelona, Spain.
| | - Olga Simó-Servat
- Diabetes and Metabolism Research Unit and CIBERDEM, Vall d'Hebron Research Institute, Vall d'Hebron Barcelona Hospital Campus, Passeig de La Vall d'Hebron, 119-129, 08035, Barcelona, Spain
| | - Massimo Porta
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Jakob Grauslund
- Research Unit of Ophthalmology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Simon P Harding
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, and St. Paul's Eye Unit. Liverpool University Hospitals, Liverpool, UK
| | - Ulrik Frydkjaer-Olsen
- Research Unit of Ophthalmology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - José García-Arumí
- Department of Ophthalmology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Luísa Ribeiro
- Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal
| | - Peter Scanlon
- Gloucestershire Hospitals National Health Service Foundation Trust, Cheltenham, UK
| | - José Cunha-Vaz
- Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal
| | - Rafael Simó
- Diabetes and Metabolism Research Unit and CIBERDEM, Vall d'Hebron Research Institute, Vall d'Hebron Barcelona Hospital Campus, Passeig de La Vall d'Hebron, 119-129, 08035, Barcelona, Spain
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Allen RS, Khayat CT, Feola AJ, Win AS, Grubman AR, Chesler KC, He L, Dixon JA, Kern TS, Iuvone PM, Thule PM, Pardue MT. Diabetic rats with high levels of endogenous dopamine do not show retinal vascular pathology. Front Neurosci 2023; 17:1125784. [PMID: 37034167 PMCID: PMC10073440 DOI: 10.3389/fnins.2023.1125784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 02/21/2023] [Indexed: 04/11/2023] Open
Abstract
Purpose Limited research exists on the time course of long-term retinal and cerebral deficits in diabetic rodents. Previously, we examined short term (4-8 weeks) deficits in the Goto-Kakizaki (GK) rat model of Type II diabetes. Here, we investigated the long-term (1-8 months) temporal appearance of functional deficits (retinal, cognitive, and motor), retinal vascular pathology, and retinal dopamine levels in the GK rat. Methods In GK rats and Wistar controls, retinal neuronal function (electroretinogram), cognitive function (Y-maze), and motor function (rotarod) were measured at 1, 2, 4, 6, and 8 months of age. In addition, we evaluated retinal vascular function (functional hyperemia) and glucose and insulin tolerance. Retinas from rats euthanized at ≥8 months were assessed for vascular pathology. Dopamine and DOPAC levels were measured via HPLC in retinas from rats euthanized at 1, 2, 8, and 12 months. Results Goto-Kakizaki rats exhibited significant glucose intolerance beginning at 4 weeks and worsening over time (p < 0.001). GK rats also showed significant delays in flicker and oscillatory potential implicit times (p < 0.05 to p < 0.001) beginning at 1 month. Cognitive deficits were observed beginning at 6 months (p < 0.05), but no motor deficits. GK rats showed no deficits in functional hyperemia and no increase in acellular retinal capillaries. Dopamine levels were twice as high in GK vs. Wistar retinas at 1, 2, 8, and 12 months (p < 0.001). Conclusion As shown previously, retinal deficits were detectable prior to cognitive deficits in GK rats. While retinal neuronal function was compromised, retinal vascular pathology was not observed, even at 12+ months. High endogenous levels of dopamine in the GK rat may be acting as an anti-angiogenic and providing protection against vascular pathology.
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Affiliation(s)
- Rachael S. Allen
- Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States
- Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States
| | - Cara T. Khayat
- Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States
| | - Andrew J. Feola
- Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States
- Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States
- Department of Ophthalmology, Emory University, Atlanta, GA, United States
| | - Alice S. Win
- Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States
- Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States
| | - Allison R. Grubman
- Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States
- Department of Ophthalmology, Emory University, Atlanta, GA, United States
| | - Kyle C. Chesler
- Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States
- Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States
| | - Li He
- Department of Ophthalmology, Emory University, Atlanta, GA, United States
- Department of Pharmacology and Chemical Biology, Emory University, Atlanta, GA, United States
| | - Jendayi A. Dixon
- Department of Ophthalmology, Emory University, Atlanta, GA, United States
| | - Timothy S. Kern
- Department of Pharmacology, Case Western Reserve University, Cleveland, OH, United States
- Veterans Administration Medical Center Research Service, Cleveland, OH, United States
- Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA, United States
| | - P. Michael Iuvone
- Department of Ophthalmology, Emory University, Atlanta, GA, United States
- Department of Pharmacology and Chemical Biology, Emory University, Atlanta, GA, United States
| | - Peter M. Thule
- Section Endocrinology and Metabolism, Atlanta VA Medical Center, Emory University School of Medicine, Decatur, GA, United States
| | - Machelle T. Pardue
- Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA, United States
- Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States
- Department of Ophthalmology, Emory University, Atlanta, GA, United States
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Trukša R, Fomins S, Jansone-Langina Z, Dzenis J. Modeling D15 test sequences in red-green anomalous trichromacy. JOURNAL OF THE OPTICAL SOCIETY OF AMERICA. A, OPTICS, IMAGE SCIENCE, AND VISION 2023; 40:A85-A90. [PMID: 37133012 DOI: 10.1364/josaa.479848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Color arrangement tests such as the D15 test can be used to detect congenital and acquired color vision defects. However, the D15 test cannot be used as the only test to assess color vision because of its relatively low sensitivity in less severe cases of color vision deficiency. In this study, we attempted to determine D15 cap arrangements for red/green anomalous trichromats with varying degrees of severity of color vision deficiency. The color coordinates of D15 test caps corresponding to a particular type and severity of color vision deficiency were determined using the model proposed by Yaguchi et al. [J. Opt. Soc. Am. A35, B278 (2018)JOAOD60740-323210.1364/JOSAA.35.00B278]. The arrangement of the color caps was modeled by assuming that individuals with color vision deficiency would arrange the D15 test caps judging by color differences perceived by them. The proposed simulation correctly predicts the increase in severity of color vision deficiency with spectral reduction between the L- and M-cone photopigments. The type of color vision deficiency is correctly predicted with few exceptions in protanomalous trichromats.
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McAnany JJ, Park JC, Lim JI. Visual Field Abnormalities in Early-Stage Diabetic Retinopathy Assessed by Chromatic Perimetry. Invest Ophthalmol Vis Sci 2023; 64:8. [PMID: 36734963 PMCID: PMC9907378 DOI: 10.1167/iovs.64.2.8] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Purpose The purpose of this study was to define the nature and extent of sensitivity loss using chromatic perimetry in diabetics who have mild or no retinopathy. Methods Thirty-four individuals with type II diabetes mellitus who have mild nonproliferative diabetic retinopathy (MDR; N = 17) or no diabetic retinopathy (NDR; N = 17) and 15 visually normal, non-diabetic controls participated. Sensitivity was assessed along the horizontal visual field meridian using an Octopus 900 perimeter. Measurements were performed under light- and dark-adapted conditions using long-wavelength (red) and short-wavelength (blue) Goldmann III targets. Cumulative defect curves (CDCs) were constructed to determine whether field sensitivity loss was diffuse or localized. Results Sensitivity was reduced significantly under light-adapted conditions for both stimulus colors for the NDR (mean defect ± SEM = -2.1 dB ± 0.6) and MDR (mean defect ± SEM = -4.0 dB ± 0.7) groups. Sensitivity was also reduced under dark-adapted conditions for both stimulus colors for the NDR (mean defect ± SEM = -1.9 dB ± 0.7) and MDR (mean defect ± SEM = -4.5 ± 1.0 dB) groups. For both diabetic groups, field loss tended to be diffuse under light-adapted conditions (up to 6.9 dB loss) and localized under dark-adapted conditions (up to 15.4 dB loss). Conclusions Visual field sensitivity losses suggest neural abnormalities in early stage diabetic eye disease and the pattern of the sensitivity losses differed depending on the adaptation conditions. Chromatic perimetry may be useful for subtyping individuals who have mild or no diabetic retinopathy and for better understanding their neural dysfunction.
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Affiliation(s)
- J. Jason McAnany
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States,Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, United States
| | - Jason C. Park
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
| | - Jennifer I. Lim
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
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11
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Mayes HS, Navarro M, Satchell LP, Tipton MJ, Ando S, Costello JT. The effects of manipulating the visual environment on thermal perception: A structured narrative review. J Therm Biol 2023; 112:103488. [PMID: 36796929 DOI: 10.1016/j.jtherbio.2023.103488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 01/14/2023] [Accepted: 01/15/2023] [Indexed: 01/26/2023]
Abstract
When exposed to ambient temperatures that cause thermal discomfort, a human's behavioral responses are more effective than autonomic ones at compensating for thermal imbalance. These behavioral thermal responses are typically directed by an individual's perception of the thermal environment. Perception of the environment is a holistic amalgamation of human senses, and in some circumstances, humans prioritize visual information. Existing research has considered this in the specific case of thermal perception, and this review investigates the state of the literature examining this effect. We identify the frameworks, research rationales, and potential mechanisms that underpin the evidence base in this area. Our review identified 31 experiments, comprising 1392 participants that met the inclusion criteria. Methodological heterogeneity was observed in the assessment of thermal perception, and a variety of methods were employed to manipulate the visual environment. However, the majority of the included experiments (80%) reported a difference in thermal perception after the visual environment was manipulated. There was limited research exploring any effects on physiological variables (e.g. skin and core temperature). This review has wide-ranging implications for the broad discipline of (thermo)physiology, psychology, psychophysiology, neuroscience, ergonomics, and behavior.
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Affiliation(s)
- Harry S Mayes
- School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, England, UK
| | - Martina Navarro
- School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, England, UK
| | - Liam P Satchell
- Department of Psychology, University of Winchester, Winchester, UK
| | - Michael J Tipton
- School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, England, UK
| | - Soichi Ando
- Graduate School of Informatics and Engineering, The University of Electro-Communications, Tokyo, Japan
| | - Joseph T Costello
- School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, England, UK.
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12
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Emade N, Nyamori J, Njuguna M, Njambi L, Gichuhi S. Vision-Related Quality of Life among Patients Attending the Diabetes and Eye Clinics in Kenyatta National Hospital, Kenya. J Ophthalmol 2023; 2023:7809692. [PMID: 36703703 PMCID: PMC9873415 DOI: 10.1155/2023/7809692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 12/19/2022] [Accepted: 12/30/2022] [Indexed: 01/19/2023] Open
Abstract
Objective Our main objective was to determine the overall vision-related quality of life (VRQoL) among patients with diabetes mellitus attending the diabetes and eye clinics in Kenyatta National Hospital, Kenya. Design Analytical cross-sectional study conducted in December 2020 setting: This study was performed at the Diabetes and Eye Clinics in Kenyatta National Hospital, the main national referral centre in Nairobi, Kenya. Participants. Using a purposive consecutive sampling method, we enrolled 100 participants, 50 with diabetic retinopathy and 50 without diabetic retinopathy. Main Outcomes and Measures. We compared the VRQoL of participants with diabetic retinopathy with those without diabetic retinopathy and assessed whether VRQoL worsened with increasing the severity of diabetic retinopathy. VRQoL was assessed using the World Health Organization/Prevention of Blindness and Deafness Vision Function-20 Questionnaire (VF-20). With this tool, the higher the mean score, the worse the quality of life. Diabetic retinopathy was graded using the Early Treatment of Diabetic Retinopathy Study. VRQoL trend with DR were analysed using the worse eye. Results Participants with diabetic retinopathy had worse overall total VRQoL mean score (33.4, SD11.5) than those without (26.9, SD 4.7) in all domains; overall self-rating, 2.6 vs. 2.2, p < 0.001; general functioning, 18.0 vs. 14.7, p=0.005; psychosocial, 6.7 vs. 5.3, p < 0.001; and visual symptoms, 6.1 vs. 4.8, p < 0.001. VRQoL was worse with increasing severity of diabetic retinopathy in all domains moving from mild NPDR to moderate NPDR, severe NPDR and PDR, overall self-rating (2.2, 2.5, 3.5, 3.3; p < 0.001); visual symptoms (5.6, 5.6, 7.5, 7.4; p=0.002); psychosocial (5.7, 6.5, 6.0 8.8; p=0.004); and general functioning (15.7, 16.9, 17.5 23.6; p=0.014). Presence of DR, distance vision impairment, and diabetic macula oedema were associated with low overall self-rating. Conclusion and Relevance. Our findings underscore the need for interventions for early detection and management of diabetic retinopathy to prevent developing more advanced DR and its associated deterioration of VRQoL.
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Affiliation(s)
- Nerice Emade
- MMed Ophthal, University of Nairobi, Nairobi, Kenya
| | - Joseph Nyamori
- Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
| | - Margaret Njuguna
- Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
| | - Lucy Njambi
- Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
| | - Stephen Gichuhi
- Head Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
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13
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Simó R, Simó-Servat O, Bogdanov P, Hernández C. Diabetic Retinopathy: Role of Neurodegeneration and Therapeutic Perspectives. Asia Pac J Ophthalmol (Phila) 2022; 11:160-167. [PMID: 35533335 DOI: 10.1097/apo.0000000000000510] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
ABSTRACT Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy, the leading cause of preventable blindness. The hallmarks of diabetes-induced neurodegeneration are neural cell apoptosis and glial activation, which seem even before vascular lesions can be detected by ophthalmoscopic examination. The molecular mediators of retinal neurodegeneration include proinflamma- tory cytokines, oxidative stress, mitochondrial dysfunction, and the molecular pathways closely related to chronic hyperglycemia. In this article, an overview of the main components of neurodegeneration, its key underlying mechanisms, and the more useful experimental models for investigative purposes will be given. In addition, the results of most relevant treatments based on neuroprotection, and the research gaps that should be filled will be critically reviewed.
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Affiliation(s)
- Rafael Simó
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
- Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
| | - Olga Simó-Servat
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
- Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
| | - Patricia Bogdanov
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
- Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
| | - Cristina Hernández
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
- Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
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14
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Chai S, Ge Y, Wan Y, Xia H, Dong R, Ren X, Yuan H, Hou Q, Yang J, Li X. Visual functional defects in patients with type 2 diabetes mellitus: a questionnaire based cross-sectional study. Int Ophthalmol 2022; 42:2205-2218. [PMID: 35119607 DOI: 10.1007/s10792-022-02220-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 01/06/2022] [Indexed: 11/24/2022]
Abstract
PURPOSE To determine the impact of type 2 diabetes mellitus (T2DM) on visual functions, identify different modifiers as risk or protective factors, and find out how these factors affect patients' visual symptoms and visual functions as a whole. METHODS We performed an online survey among 1030 participants (400 patients, 630 non-patients). Demographic features and severity of disease were documented, while visual functions were evaluated using National Eye Institute Visual Functioning questionnaire-25 (NEI VFQ-25). Independent t-test, analysis of variance, linear and nonlinear regression models were used to assess all data. RESULTS Scores other than color vision among T2DM patients were significantly lower compared with non-T2DM participants. There was significant difference after stratification of age and education, but no significant difference between different genders was observed. Parameters including duration of T2DM, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) negatively impacted on the scores, with 20 years' of diabetic duration, 10 mmol/L of FPG, 7.5% of HbA1c being potential cut-off points. Poorer best corrected visual acuity (BCVA) and diagnosis of diabetic retinopathy were risk factors, while they simultaneously produced mediation effect, contributing 5%-78% of effect in the deterioration of visual functions caused by longer diabetic duration and higher blood glucose. CONCLUSION Significant visual impairments and faster deterioration in visual functions were seen in T2DM patients, with older age, lower educational level, longer diabetic duration, poorer blood glucose administration, limited BCVA, and the presence of diabetic retinopathy identified as risk factors. Average BCVA and diabetic retinopathy also yielded mediation effect as diabetic duration lengthened and blood glucose elevated.
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Affiliation(s)
- Sanbao Chai
- Department of Endocrinology and Metabolism, Peking University International Hospital, Beijing, 102206, People's Republic of China
| | - Yimeng Ge
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China
| | - Yu Wan
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China
| | - Huaqin Xia
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China
| | - Ruilan Dong
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China
| | - Xiaotong Ren
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China
| | - Hao Yuan
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China
| | - Qingyi Hou
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China
| | - Jiarui Yang
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China.
| | - Xuemin Li
- Department of Opthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Peking University Third Hospital Haidian District, 49 North Garden Road, Beijing, 100191, People's Republic of China.
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15
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Yokoyama S, Tanaka Y, Kojima T, Horai R, Kato Y, Nakamura H, Sato H, Mitamura M, Tanaka K, Ichikawa K. Age-related changes of color visual acuity in normal eyes. PLoS One 2021; 16:e0260525. [PMID: 34843576 PMCID: PMC8629265 DOI: 10.1371/journal.pone.0260525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 10/26/2021] [Indexed: 11/22/2022] Open
Abstract
Purpose To evaluate the age-related change in color visual acuity (CVA) in normal eyes. Methods In total, 162 normal eyes (162 subjects, women: 52, men: 110, age range: 15–68 years) with best-corrected visual acuity (BCVA) ≥20/13 were enrolled. Fifteen colors from the New Color Test (chroma 6) were applied to Landolt “C” rings, white point D65 was applied as background, and a luminance of 30 cd/m2 was set for both the rings and the background. These rings were used to measure the chromatic spatial discrimination acuity as the CVA value, while changing the stimulus size. Correlations of the CVA value of each color and age were evaluated. Mean CVA values of all 15 colors (logarithm of the minimum angle of resolution) were compared between age groups in 10-year increments. Results Nine CVA values (red, yellow-red, red-yellow, green, blue-green, green-blue, purple, red-purple, and purple-red) were negatively correlated with age (all p<0.05); the remaining six (yellow, green-yellow, yellow-green, blue, purple-blue, and blue-purple), as well as BCVA were not. The age groups with the best to worst mean CVA values of 15 colors were as follows: 20–29 (mean ± standard deviation, 0.303 ± 0.113), 30–39 (0.324 ± 0.096), 10–19 (0.333 ± 0.022), 50–59 (0.335 ± 0.078), 40–49 (0.339 ± 0.096), and 60–69 (0.379 ± 0.125) years. There were statistically significant differences between mean CVA values of the following groups: 20–29 and 40–49 years; 20–29 and 60–69 years; 30–39 and 60–69 years (all p<0.01). Conclusions The CVA values related to the medium/long-wavelength-sensitive cones were more susceptible to aging than those related to the short-wavelength-sensitive cones. This differed from previous reports, and may be related to the difference in the range of foveal cone function evaluated with each examination.
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Affiliation(s)
- Sho Yokoyama
- Department of Ophthalmology, Japan Community Healthcare Organization Chukyo Hospital, Nagoya, Japan
| | | | - Takashi Kojima
- Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
- * E-mail:
| | | | | | | | | | | | - Kiyoshi Tanaka
- Faculty of Engineering, Shinshu University, Nagano, Japan
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16
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Yang M, Chen Y, Vagionitis S, Körtvely E, Ueffing M, Schmachtenberg O, Hu Z, Jiao K, Paquet-Durand F. Expression of glucose transporter-2 in murine retina: Evidence for glucose transport from horizontal cells to photoreceptor synapses. J Neurochem 2021; 160:283-296. [PMID: 34726780 DOI: 10.1111/jnc.15533] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/12/2021] [Accepted: 10/18/2021] [Indexed: 01/30/2023]
Abstract
The retina has the highest relative energy consumption of any tissue, depending on a steady supply of glucose from the bloodstream. Glucose uptake is mediated by specific transporters whose regulation and expression are critical for the pathogenesis of many diseases, including diabetes and diabetic retinopathy. Here, we used immunofluorescence to show that glucose transporter-2 (GLUT2) is expressed in horizontal cells of the mouse neuroretina in proximity to inner retinal capillaries. To study the function of GLUT2 in the murine retina, we used organotypic retinal explants, cultivated under entirely controlled, serum-free conditions and exposed them to streptozotocin, a cytotoxic drug transported exclusively by GLUT2. Contrary to our expectations, streptozotocin did not measurably affect horizontal cell viability, while it ablated rod and cone photoreceptors in a concentration-dependent manner. Staining for poly-ADP-ribose (PAR) indicated that the detrimental effect of streptozotocin on photoreceptors may be associated with DNA damage. The negative effect of streptozotocin on the viability of rod photoreceptors was counteracted by co-administration of either the inhibitor of connexin-formed hemi-channels meclofenamic acid or the blocker of clathrin-mediated endocytosis dynasore. Remarkably, cone photoreceptors were not protected from streptozotocin-induced degeneration by neither of the two drugs. Overall, these data suggest the existence of a GLUT2-dependent glucose transport shuttle, from horizontal cells into photoreceptor synapses. Moreover, our study points at different glucose uptake mechanisms in rod and cone photoreceptors.
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Affiliation(s)
- Ming Yang
- Affiliated Hospital of Yunnan University & 2nd People's Hospital of Yunnan Province, Kunming, China.,Yunnan Eye Institute & Key Laboratory of Yunnan Province, Kunming, China.,1st Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yiyi Chen
- Institute for Ophthalmic Research, Eberhard-Karls-Universität, Tübingen, Germany
| | - Stavros Vagionitis
- Institute of Neuronal Cell Biology, Technical University of Munich, Munich, Germany
| | - Elöd Körtvely
- Roche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I2O), Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland
| | - Marius Ueffing
- Institute for Ophthalmic Research, Eberhard-Karls-Universität, Tübingen, Germany
| | - Oliver Schmachtenberg
- CINV, Instituto de Biología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Zhulin Hu
- Affiliated Hospital of Yunnan University & 2nd People's Hospital of Yunnan Province, Kunming, China.,Yunnan Eye Institute & Key Laboratory of Yunnan Province, Kunming, China
| | - Kangwei Jiao
- Affiliated Hospital of Yunnan University & 2nd People's Hospital of Yunnan Province, Kunming, China.,Yunnan Eye Institute & Key Laboratory of Yunnan Province, Kunming, China
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17
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Simó R, Simó-Servat O, Bogdanov P, Hernández C. Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy. Pharmaceutics 2021; 13:pharmaceutics13081320. [PMID: 34452281 PMCID: PMC8399715 DOI: 10.3390/pharmaceutics13081320] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/18/2021] [Accepted: 08/19/2021] [Indexed: 01/02/2023] Open
Abstract
The concept of diabetic retinopathy as a microvascular disease has evolved and is now considered a more complex diabetic complication in which neurovascular unit impairment plays an essential role and, therefore, can be considered as a main therapeutic target in the early stages of the disease. However, neurodegeneration is not always the apparent primary event in the natural story of diabetic retinopathy, and a phenotyping characterization is recommendable to identify those patients in whom neuroprotective treatment might be of benefit. In recent years, a myriad of treatments based on neuroprotection have been tested in experimental models, but more interestingly, there are drugs with a dual activity (neuroprotective and vasculotropic). In this review, the recent evidence concerning the therapeutic approaches targeting neurovascular unit impairment will be presented, along with a critical review of the scientific gaps and problems which remain to be overcome before our knowledge can be transferred to clinical practice.
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Affiliation(s)
- Rafael Simó
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
- Correspondence:
| | - Olga Simó-Servat
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
| | - Patricia Bogdanov
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
| | - Cristina Hernández
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
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18
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Adornetto A, Gesualdo C, Laganà ML, Trotta MC, Rossi S, Russo R. Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy. Front Pharmacol 2021; 12:695267. [PMID: 34234681 PMCID: PMC8256993 DOI: 10.3389/fphar.2021.695267] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/09/2021] [Indexed: 01/18/2023] Open
Abstract
Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches.
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Affiliation(s)
- Annagrazia Adornetto
- Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
| | - Carlo Gesualdo
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Maria Luisa Laganà
- Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
| | - Maria Consiglia Trotta
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Settimio Rossi
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Rossella Russo
- Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
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19
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Énzsöly A, Hajdú RI, Turóczi Z, Szalai I, Tátrai E, Pálya F, Nagy ZZ, Mátyás C, Oláh A, Radovits T, Szabó K, Dékány B, Szabó A, Kusnyerik Á, Soltész P, Veres DS, Somogyi A, Somfai GM, Lukáts Á. The Predictive Role of Thyroid Hormone Levels for Early Diabetic Retinal Changes in Experimental Rat and Human Diabetes. Invest Ophthalmol Vis Sci 2021; 62:20. [PMID: 34010957 PMCID: PMC8142702 DOI: 10.1167/iovs.62.6.20] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Purpose In diabetic subjects, early visual functional alterations such as color vision deficiencies (CVDs) are known to precede clinically apparent diabetic retinopathy. Prominent photoreceptor outer segment degeneration and an increase in the number of retinal dual cones (co-expressing S- and M-opsins simultaneously) have been described in diabetic rat models, suggesting a connection with the development of CVDs. As cone opsin expression is controlled by thyroid hormones, we investigated the diabetic retina in association with thyroid hormone alterations. Methods In rat models of type 1 and 2 diabetes, dual cones were labeled by immunohistochemistry, and their numbers were analyzed in relation to free triiodothyronine (fT3) and free thyroxine (fT4) levels. Quantification of dual cones was also performed in human postmortem retinas. Additionally, a cross-sectional case–control study was performed where thyroid hormone levels were measured and color vision was assessed with Lanthony desaturated D15 discs. Results A higher number of dual cones was detectable in diabetic rats, correlating with fT4 levels. Dual cones were also present in postmortem human retinas, with higher numbers in the three diabetic retinas. As expected, age was strongly associated with CVDs in human patients, and the presence of diabetes also increased the risk. However, the current study failed to detect any effect of thyroid hormones on the development of CVDs. Conclusions Our results point toward the involvement of thyroid homeostasis in the opsin expression changes in diabetic rats and human samples. The evaluation of the possible clinical consequences warrants further research.
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Affiliation(s)
- Anna Énzsöly
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Rozina I Hajdú
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary.,Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
| | - Zsolt Turóczi
- 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - Irén Szalai
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Erika Tátrai
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Fanni Pálya
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Zoltán Z Nagy
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Csaba Mátyás
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Attila Oláh
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Tamás Radovits
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Klaudia Szabó
- Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
| | - Bulcsú Dékány
- Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
| | - Arnold Szabó
- Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
| | - Ákos Kusnyerik
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Petra Soltész
- 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - Dániel S Veres
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
| | - Anikó Somogyi
- 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - Gábor M Somfai
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary.,Eye Clinic, Stadtspital Waid and Triemli, Zürich, Switzerland.,Werner H. Spross Foundation for the Advancement of Research and Teaching in Ophthalmology, Zürich, Switzerland
| | - Ákos Lukáts
- Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
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20
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Ţălu Ş, Nicoara SD. Malfunction of outer retinal barrier and choroid in the occurrence and progression of diabetic macular edema. World J Diabetes 2021; 12:437-452. [PMID: 33889289 PMCID: PMC8040083 DOI: 10.4239/wjd.v12.i4.437] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/23/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy, affecting 1 in 15 patients with diabetes mellitus (DM). The disruption of the inner blood-retina barrier (BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris, in the occurrence and evolution of DME. The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition. In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.
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Affiliation(s)
- Ştefan Ţălu
- Directorate of Research, Development and Innovation Management (DMCDI), Technical University of Cluj-Napoca, Cluj-Napoca 400020, Romania
| | - Simona Delia Nicoara
- Department of Ophthalmology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania
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21
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González-Casanova J, Schmachtenberg O, Martínez AD, Sanchez HA, Harcha PA, Rojas-Gomez D. An Update on Connexin Gap Junction and Hemichannels in Diabetic Retinopathy. Int J Mol Sci 2021; 22:ijms22063194. [PMID: 33801118 PMCID: PMC8004116 DOI: 10.3390/ijms22063194] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 03/06/2021] [Accepted: 03/10/2021] [Indexed: 01/10/2023] Open
Abstract
Diabetic retinopathy (DR) is one of the main causes of vision loss in the working age population. It is characterized by a progressive deterioration of the retinal microvasculature, caused by long-term metabolic alterations inherent to diabetes, leading to a progressive loss of retinal integrity and function. The mammalian retina presents an orderly layered structure that executes initial but complex visual processing and analysis. Gap junction channels (GJC) forming electrical synapses are present in each retinal layer and contribute to the communication between different cell types. In addition, connexin hemichannels (HCs) have emerged as relevant players that influence diverse physiological and pathological processes in the retina. This article highlights the impact of diabetic conditions on GJC and HCs physiology and their involvement in DR pathogenesis. Microvascular damage and concomitant loss of endothelial cells and pericytes are related to alterations in gap junction intercellular communication (GJIC) and decreased connexin 43 (Cx43) expression. On the other hand, it has been shown that the expression and activity of HCs are upregulated in DR, becoming a key element in the establishment of proinflammatory conditions that emerge during hyperglycemia. Hence, novel connexin HCs blockers or drugs to enhance GJIC are promising tools for the development of pharmacological interventions for diabetic retinopathy, and initial in vitro and in vivo studies have shown favorable results in this regard.
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Affiliation(s)
- Jorge González-Casanova
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910060, Chile;
| | - Oliver Schmachtenberg
- Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Biología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile;
| | - Agustín D. Martínez
- Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile; (A.D.M.); (H.A.S.); (P.A.H.)
| | - Helmuth A. Sanchez
- Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile; (A.D.M.); (H.A.S.); (P.A.H.)
| | - Paloma A. Harcha
- Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile; (A.D.M.); (H.A.S.); (P.A.H.)
| | - Diana Rojas-Gomez
- Escuela de Nutrición y Dietética, Facultad de Medicina, Universidad Andres Bello, Santiago 8370146, Chile
- Correspondence: ; Tel.: +56-2-26618559
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22
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Pan WW, Gardner TW, Harder JL. Integrative Biology of Diabetic Retinal Disease: Lessons from Diabetic Kidney Disease. J Clin Med 2021; 10:1254. [PMID: 33803590 PMCID: PMC8003049 DOI: 10.3390/jcm10061254] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/09/2021] [Accepted: 03/12/2021] [Indexed: 01/13/2023] Open
Abstract
Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models-a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual's specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.
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Affiliation(s)
- Warren W. Pan
- Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105, USA; (W.W.P.); (T.W.G.)
| | - Thomas W. Gardner
- Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105, USA; (W.W.P.); (T.W.G.)
- Department of Internal Medicine (Metabolism, Endocrinology and Diabetes), University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Jennifer L. Harder
- Department of Internal Medicine (Nephrology), University of Michigan Medical School, Ann Arbor, MI 48109, USA
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23
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The innate immune system in diabetic retinopathy. Prog Retin Eye Res 2021; 84:100940. [PMID: 33429059 DOI: 10.1016/j.preteyeres.2021.100940] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/24/2020] [Accepted: 01/03/2021] [Indexed: 12/20/2022]
Abstract
The prevalence of diabetes has been rising steadily in the past half-century, along with the burden of its associated complications, including diabetic retinopathy (DR). DR is currently the most common cause of vision loss in working-age adults in the United States. Historically, DR has been diagnosed and classified clinically based on what is visible by fundoscopy; that is vasculature alterations. However, recent technological advances have confirmed pathology of the neuroretina prior to any detectable vascular changes. These, coupled with molecular studies, and the positive impact of anti-inflammatory therapeutics in DR patients have highlighted the central involvement of the innate immune system. Reminiscent of the systemic impact of diabetes, immune dysregulation has become increasingly identified as a key element of the pathophysiology of DR by interfering with normal homeostatic systems. This review uses the growing body of literature across various model systems to demonstrate the clear involvement of all three pillars of the immune system: immune-competent cells, mediators, and the complement system. It also demonstrates how the relative contribution of each of these requires more extensive analysis, including in human tissues over the continuum of disease progression. Finally, although this review demonstrates how the complex interactions of the immune system pose many more questions than answers, the intimately connected nature of the three pillars of the immune system may also point to possible new targets to reverse or even halt reverse retinopathy.
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24
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Ichikawa K, Yokoyama S, Tanaka Y, Nakamura H, Smith RT, Tanabe S. The Change in Color Vision with Normal Aging Evaluated on Standard Pseudoisochromatic Plates Part-3. Curr Eye Res 2020; 46:1038-1046. [PMID: 33190542 DOI: 10.1080/02713683.2020.1843683] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Purpose: To evaluate the influence of aging on color vision in a large normal population using Standard Pseudoisochromatic Plates part-3 (SPP-3), which is a pseudoisochromatic plate test used to detect congenital or acquired color vision deficiency (CVD).Materials and methods: We retrospectively reviewed SPP-3 test results of 23,565 normal eyes of 23,565 subjects (women: 12,035; men: 11,530), who were examined between July 1993 and December 2010. The subjects had a mean age of 46.9 ± 18.5 years, ranging from 5 to 89 years, and they were evaluated following categorization into age groups with five-year increments. Subjects whose best-corrected visual acuity (BCVA) was 20/20 or better, with no history of ocular diseases, were included. Subjects with congenital CVD were excluded.Results: We found a negative correlation between age and the total number of correct answers in SPP-3 (Spearman's correlation coefficient, r = -0.5743; p < .0001). The total number of correct answers was the highest in subjects aged 10-14, 15-19, and 20-24 years (17.2 ± 0.9 [mean ±SD]). The total number of correct answers of these groups had significant differences from those in the 5-9 years age group and those aged >30 years (Dunn's post-hoc test: p < .0001). Among the 19 detection numerals in SPP-3, we found that the correct answer rates of six numerals decreased with aging, and the colors of the numerals and their backgrounds all located parallel to the tritanopic confusion line.Conclusions: Using SPP-3, we confirmed that aging influenced color vision, even in normal eyes with a good BCVA (20/20 or better). The total number of correct answers of SPP-3 was the highest in subjects aged 10-24 years and had already begun to decline in those in their 30s.
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Affiliation(s)
- Kazuo Ichikawa
- Institute of Visual Science, Chukyo Eye Clinic, Nagoya, Japan.,Department of Ophthalmology, Japan Community Health care Organization Chukyo Hospital, Nagoya, Japan
| | - Sho Yokoyama
- Department of Ophthalmology, Japan Community Health care Organization Chukyo Hospital, Nagoya, Japan
| | - Yoshiki Tanaka
- Institute of Visual Science, Chukyo Eye Clinic, Nagoya, Japan
| | - Hideki Nakamura
- Institute of Visual Science, Meito Eye Clinic, Nagoya, Japan
| | - R Theodore Smith
- Department of Ophthalmology, New York Eye & Ear Infirmary of Mount Sinai, New York, USA
| | - Shoko Tanabe
- Institute of Visual Science, Chukyo Eye Clinic, Nagoya, Japan
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25
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Karson N, Smith J, Jones M, Datta A, Richdale K, Harrison WW. Functional retinal outcomes in patients with prediabetes and type 2 diabetes. Ophthalmic Physiol Opt 2020; 40:770-777. [PMID: 32955730 PMCID: PMC7606818 DOI: 10.1111/opo.12733] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 08/25/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE Type 2 diabetes (T2DM) is a leading cause of visual impairment. Its precursor, prediabetes (preDM), is growing in numbers every year. While it is well known that T2DM causes changes in retinal function early in the disease process, it is likely that some of these changes emerge during the preDM stage. This study evaluates retinal function measures in patients with preDM to determine if there are differences in colour vision, contrast sensitivity (CS), and multifocal electroretinogram (mfERG) measures present before T2DM is diagnosed. METHODS The L'Anthony desaturated D-15 test, Mars Chart CS test, and mfERG were administered on the right eye of 43 participants; 15 controls (HbA1c ≤ 5.6%), 17 with preDM (HbA1c 5.7%-6.4%), and 11 with T2DM (either physician diagnosed or with untreated HbA1c ≥ 6.5%). HbA1c values were measured at the time of the other tests. Colour vision confusion scores (CVCS) were calculated from the D-15 using the method developed by Torok. Multivariate regression (which controlled for age differences) was used to evaluate the relationship of HbA1c and functional measures. Kruskal-Wallis tests were also used to evaluate differences between groups with post-hoc analysis. RESULTS CVCSs were significantly different between the three groups (p = 0.009). There was an association between higher CVCS and higher HbA1c values across all groups as well as specifically within the preDM group when controlling for age (R2 = 0.29, p = 0.01 and R2 = 0.39, p = 0.02 respectively). Multivariate regression of all of the functional tests together and HbA1c found only colour vision remained significant, indicating that the functional examination metrics may provide redundant data, with similar changes in prediabetes where colour vision may be the strongest indicator early in the process. CONCLUSIONS Patients with prediabetes have functional changes that can be measured in the retina before the diagnosis of diabetes, with the L'Anthony D-15 colour vision test providing the strongest association with glucose dysregulation in this population. This has important implications for follow up and screening for diabetes within optometric practices. Further studies are needed to follow these patients over time to see how and when these metrics change.
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Affiliation(s)
- Nicole Karson
- University of Houston College of Optometry, Houston, USA
| | | | - Morgan Jones
- University of Houston College of Optometry, Houston, USA
| | - Ananya Datta
- University of Houston College of Optometry, Houston, USA
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26
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Becker S, Carroll LS, Vinberg F. Diabetic photoreceptors: Mechanisms underlying changes in structure and function. Vis Neurosci 2020; 37:E008. [PMID: 33019947 PMCID: PMC8694110 DOI: 10.1017/s0952523820000097] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Based on clinical findings, diabetic retinopathy (DR) has traditionally been defined as a retinal microvasculopathy. Retinal neuronal dysfunction is now recognized as an early event in the diabetic retina before development of overt DR. While detrimental effects of diabetes on the survival and function of inner retinal cells, such as retinal ganglion cells and amacrine cells, are widely recognized, evidence that photoreceptors in the outer retina undergo early alterations in diabetes has emerged more recently. We review data from preclinical and clinical studies demonstrating a conserved reduction of electrophysiological function in diabetic retinas, as well as evidence for photoreceptor loss. Complementing in vivo studies, we discuss the ex vivo electroretinography technique as a useful method to investigate photoreceptor function in isolated retinas from diabetic animal models. Finally, we consider the possibility that early photoreceptor pathology contributes to the progression of DR, and discuss possible mechanisms of photoreceptor damage in the diabetic retina, such as enhanced production of reactive oxygen species and other inflammatory factors whose detrimental effects may be augmented by phototransduction.
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Affiliation(s)
- Silke Becker
- John A. Moran Eye Center, University of Utah, Salt Lake City, Utah
| | - Lara S Carroll
- John A. Moran Eye Center, University of Utah, Salt Lake City, Utah
| | - Frans Vinberg
- John A. Moran Eye Center, University of Utah, Salt Lake City, Utah
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27
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Han W, Wei H, Kong W, Wang J, Yang L, Wu H. Association between retinol binding protein 4 and diabetic retinopathy among type 2 diabetic patients: a meta-analysis. Acta Diabetol 2020; 57:1203-1218. [PMID: 32405713 DOI: 10.1007/s00592-020-01535-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 04/07/2020] [Indexed: 12/23/2022]
Abstract
AIMS The aim of this study was to investigate the association between retinol-binding protein 4 (RBP4) and diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (T2DM). METHODS Databases PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, VIP, and Wangfang were searched to July 30, 2019. The Newcastle-Ottawa Scale was applied to assess the quality of all identified studies, and those qualified were included in the meta-analysis. The Chi squared Q test and I2 statistics were conducted to evaluate heterogeneity. Standardized mean differences (SMD) and 95% confidence intervals (CI) among RBP4 within the DR and T2DM without retinopathy (DWR) groups were pooled using the random effects model depending on the heterogeneity. Subgroup analyses were conducted among the groups having different diabetes duration, detection methods, body mass index, and total cholesterol and triglyceride levels. The funnel plot was used to assess publication bias. RESULTS Nineteen observational studies were included in our meta-analysis. RBP4 was significantly higher in both nonproliferative DR (SMD: 0.72, 95% CI 0.48-0.95, P < 0.00001) and proliferative DR (SMD: 2.68, 95% CI 1.69-3.67, P < 0.00001) groups despite high heterogeneity (I2 = 87 and 97% in DR and PDR groups, respectively). Significant differences were noted among most subgroups (P < 0.05). Among those accompanied by hypercholesterolemia, the association between RBP4 and DR were unclear (P = 0.09). CONCLUSIONS Elevated RBP4 is strongly associated with DR and may play an essential role in its progression. Additional large-scale controlled studies are needed to confirm these findings.
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Affiliation(s)
- Wentao Han
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, People's Republic of China
| | - Huagen Wei
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, People's Republic of China
| | - Weizheng Kong
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, People's Republic of China
| | - Jing Wang
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, People's Republic of China
| | - Luqian Yang
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, People's Republic of China
| | - Huiqun Wu
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, People's Republic of China.
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28
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A critical review: Psychophysical assessments of diabetic retinopathy. Surv Ophthalmol 2020; 66:213-230. [PMID: 32866468 DOI: 10.1016/j.survophthal.2020.08.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 08/23/2020] [Accepted: 08/24/2020] [Indexed: 02/08/2023]
Abstract
Diabetic retinal disease remains a leading cause of vision loss despite currently available screening methods, ocular treatments, and efforts to control metabolic dysfunction. It is now understood that diabetes damages the entire retina and the cellular components of the neurovascular unit. Multiple studies have demonstrated impairment of various aspects of retinal function across the spectrum of retinopathy severity. Here we review these tests, the principles underlying their use, clinical data from multiple publications, the strengths and limitations of the studies, and prospects for their application to understand the pathophysiology of diabetic retinal disease and monitor its response to therapy. We focus on visual acuity, contrast sensitivity, color vision, visual field, and dark adaptation and their use to understand the pathophysiology of diabetic retinopathy and as potential endpoints for clinical trials.
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29
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Schnichels S, Paquet-Durand F, Löscher M, Tsai T, Hurst J, Joachim SC, Klettner A. Retina in a dish: Cell cultures, retinal explants and animal models for common diseases of the retina. Prog Retin Eye Res 2020; 81:100880. [PMID: 32721458 DOI: 10.1016/j.preteyeres.2020.100880] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Revised: 06/23/2020] [Accepted: 06/26/2020] [Indexed: 12/11/2022]
Abstract
For many retinal diseases, including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), the exact pathogenesis is still unclear. Moreover, the currently available therapeutic options are often unsatisfactory. Research designed to remedy this situation heavily relies on experimental animals. However, animal models often do not faithfully reproduce human disease and, currently, there is strong pressure from society to reduce animal research. Overall, this creates a need for improved disease models to understand pathologies and develop treatment options that, at the same time, require fewer or no experimental animals. Here, we review recent advances in the field of in vitro and ex vivo models for AMD, glaucoma, and DR. We highlight the difficulties associated with studies on complex diseases, in which both the initial trigger and the ensuing pathomechanisms are unclear, and then delineate which model systems are optimal for disease modelling. To this end, we present a variety of model systems, ranging from primary cell cultures, over organotypic cultures and whole eye cultures, to animal models. Specific advantages and disadvantages of such models are discussed, with a special focus on their relevance to putative in vivo disease mechanisms. In many cases, a replacement of in vivo research will mean that several different in vitro models are used in conjunction, for instance to analyze and validate causative molecular pathways. Finally, we argue that the analytical decomposition into appropriate cell and tissue model systems will allow making significant progress in our understanding of complex retinal diseases and may furthermore advance the treatment testing.
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Affiliation(s)
- Sven Schnichels
- University Eye Hospital, Centre for Ophthalmology, University of Tübingen, Germany.
| | - François Paquet-Durand
- Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany
| | - Marina Löscher
- University Eye Hospital, Centre for Ophthalmology, University of Tübingen, Germany
| | - Teresa Tsai
- Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Germany
| | - José Hurst
- University Eye Hospital, Centre for Ophthalmology, University of Tübingen, Germany
| | - Stephanie C Joachim
- Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Germany
| | - Alexa Klettner
- Department of Ophthalmology, University Medical Center, University of Kiel, Kiel, Germany
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30
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López-Bernal Á, García-Tejera O, Testi L, Villalobos FJ. Genotypic variability in radial resistance to water flow in olive roots and its response to temperature variations. TREE PHYSIOLOGY 2020; 40:445-453. [PMID: 32031664 DOI: 10.1093/treephys/tpaa010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 12/30/2019] [Accepted: 01/23/2020] [Indexed: 06/10/2023]
Abstract
As radial root resistance (Rp) represents one of the key components of the soil-plant-atmosphere continuum resistance catena modulating water transport, understanding its control is essential for physiologists, modelers and breeders. Reports of Rp, however, are still scarce and scattered in the scientific literature. In this study, we assessed genetic variability in Rp and its dependence on temperature in five widely used olive cultivars. In a first experiment, cultivar differences in Rp at 25 °C were evaluated from flow-pressure measurements in excised roots and subsequent analysis of root traits. In a second experiment, similar determinations were performed continually over a 5-h period in which temperature was gradually increased from 12 to 32 °C, enabling the assessment of Rp response to changing temperature. Despite some variability, our results did not show statistical differences in Rp among cultivars in the first experiment. In the second, cultivar differences in Rp were not significant at 12 °C, but they became so as temperature increased. Furthermore, the changes in Rp between 12 and 32 °C were higher than those expected by the temperature-driven decrease in water viscosity, with the degree of that change differing among cultivars. Also, Rp at 25 °C reached momentarily in the second experiment was consistently higher than in the first at that same, but fixed, temperature. Overall, our results suggest that there is limited variability in Rp among the studied cultivars when plants have been exposed to a given temperature for sufficient time. Temperature-induced variation in Rp might thus be partly explained by changes in membrane permeability that occur slowly, which explains why our values at 25 °C differed between experiments. The observed cultivar differences in Rp with warming also indicate faster acclimation of Rp to temperature changes in some cultivars than others.
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Affiliation(s)
- Á López-Bernal
- Departamento de Agronomía, Universidad de Córdoba, Campus de Rabanales, Edificio C4, 14071 Córdoba, Spain
| | - O García-Tejera
- Efficient Use of Water Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Parc de Gardeny, Edifici Fruitcentre, 25003 Lleida, Spain
| | - L Testi
- Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Av. Menéndez Pidal s/n, 14080 Córdoba, Spain
| | - F J Villalobos
- Departamento de Agronomía, Universidad de Córdoba, Campus de Rabanales, Edificio C4, 14071 Córdoba, Spain
- Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Av. Menéndez Pidal s/n, 14080 Córdoba, Spain
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31
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Faraji M, Kangari H, Majidi A, Tabatabaee SM. Stereopsis in Early Diabetic Retinopathy. CLINICAL OPTOMETRY 2020; 12:1-7. [PMID: 32021531 PMCID: PMC6959501 DOI: 10.2147/opto.s232312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 12/16/2019] [Indexed: 06/10/2023]
Abstract
PURPOSE The present study was undertaken to compare the stereoacuities measured by TNO and Titmus tests, in diabetic patients with early retinopathies and those without diabetes (control group). METHODS In this study, 139 participants (43 with diabetes mellitus, and 96 age-matched controls) were recruited from a retina subspecialist clinic in Qazvin, Iran, from September 2016 to March 2017. The stereo-acuities were measured following subjective refraction by Titmus and TNO tests at 40 cm. The patients with diabetes whose retinal exam revealed no background retinopathy or only microaneurysms (very mild diabetic retinopathy) in the worse eye were enrolled into this study. RESULTS In the diabetic group, with TNO, the stereoacuity levels in 95.3% of the subjects were in 120, 240, and 480 levels, while in the non-diabetic group, 86.4% of the subjects were in 30, 60, and 120 levels. In the diabetic group, with Titmus, 86.1% of the subjects were in 40, 50, and 60 levels, while in the nondiabetic group 91.7% of the subjects were in 40 levels. The correlation between TNO and Titmus was statistically significant (r = 0.338, P<0.001) for the non-diabetic group, while it was not statistically significant (r = -0.034, P= 0.827) for the diabetic group. CONCLUSION In the early stages of diabetic retinopathy, the global pathway of stereopsis is damaged more than the local. The difference in severity of damage to local and global pathways in patients with diabetes indicates that there may be different underlying mechanisms for these two pathways.
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Affiliation(s)
- Mohadeceh Faraji
- Department of Optometry, School of Rehabilitation, (Student Research Office), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Haleh Kangari
- Department of Optometry, School of Rehabilitation, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Xia Z, Chen H, Zheng S. Alterations of Retinal Pigment Epithelium-Photoreceptor Complex in Patients with Type 2 Diabetes Mellitus without Diabetic Retinopathy: A Cross-Sectional Study. J Diabetes Res 2020; 2020:9232157. [PMID: 32215275 PMCID: PMC7079236 DOI: 10.1155/2020/9232157] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 02/20/2020] [Indexed: 11/18/2022] Open
Abstract
AIM A cross-sectional study was performed to examine the alterations of the retinal pigment epithelium- (RPE-) photoreceptor complex layer in type 2 diabetes mellitus (DM) without diabetic retinopathy (DR), using spectral-domain optical coherence tomography (SD-OCT). METHODS Patients with type 2 DM without DR and healthy controls without DM were recruited. All participants underwent examinations including SD-OCT. The thickness measurements of the retinal neural layers were calculated after automatic segmentation. An independent-sample t-test was used to compare the means of the thickness of retinal neural layers in patients with DM and healthy controls. RESULTS Sixty-seven eyes from 67 patients with DM and 30 eyes from 30 healthy controls were included in this study. No significant differences were found in age (P = 0.601), gender (P = 0.601), gender (P = 0.601), gender (P = 0.601), gender (P = 0.601), gender (P = 0.601), gender (P = 0.601), gender (P = 0.601), gender (. CONCLUSION Lesions in the RPE-photoreceptor complex are present without vascular abnormalities, which may precede the alterations of ganglion cells in patients with type 2 DM.
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Affiliation(s)
- Zheren Xia
- Department of Ophthalmology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hao Chen
- Department of Ophthalmology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Suilian Zheng
- Department of Ophthalmology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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Pillar S, Moisseiev E, Sokolovska J, Grzybowski A. Recent Developments in Diabetic Retinal Neurodegeneration: A Literature Review. J Diabetes Res 2020; 2020:5728674. [PMID: 34151902 PMCID: PMC7787838 DOI: 10.1155/2020/5728674] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 10/11/2020] [Accepted: 11/24/2020] [Indexed: 02/08/2023] Open
Abstract
Neurodegeneration plays a significant role in the complex pathology of diabetic retinopathy. Evidence suggests the onset of neurodegeneration occurs early on in the disease, and so a greater understanding of the process is essential for prompt detection and targeted therapies. Neurodegeneration is a common pathway of assorted processes, including activation of inflammatory pathways, reduction of neuroprotective factors, DNA damage, and apoptosis. Oxidative stress and formation of advanced glycation end products amplify these processes and are elevated in the setting of hyperglycemia, hyperlipidemia, and glucose variability. These key pathophysiologic mechanisms are discussed, as well as diagnostic modalities and novel therapeutic avenues, with an emphasis on recent discoveries. The aim of this article is to highlight the crucial role of neurodegeneration in diabetic retinopathy and to review the molecular basis for this neuronal dysfunction, its diagnostic features, and the progress currently made in relevant therapeutic interventions.
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Affiliation(s)
- Shani Pillar
- Department of Ophthalmology, Meir Medical Center, Kfar Saba, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Elad Moisseiev
- Department of Ophthalmology, Meir Medical Center, Kfar Saba, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Andrzej Grzybowski
- Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland
- Institute for Research in Ophthalmology, Foundation for Ophthalmology Development, Poznan, Poland
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Wang TT, Lio CK, Huang H, Wang RY, Zhou H, Luo P, Qing LS. A feasible image-based colorimetric assay using a smartphone RGB camera for point-of-care monitoring of diabetes. Talanta 2020; 206:120211. [DOI: 10.1016/j.talanta.2019.120211] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/23/2019] [Accepted: 07/31/2019] [Indexed: 01/11/2023]
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Simó R, Hernández C, Porta M, Bandello F, Grauslund J, Harding SP, Aldington SJ, Egan C, Frydkjaer-Olsen U, García-Arumí J, Gibson J, Lang GE, Lattanzio R, Massin P, Midena E, Ponsati B, Ribeiro L, Scanlon P, Lobo C, Costa MÂ, Cunha-Vaz J. Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial. Diabetes 2019; 68:457-463. [PMID: 30389750 DOI: 10.2337/db18-0682] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 10/21/2018] [Indexed: 12/25/2022]
Abstract
The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit.
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Affiliation(s)
- Rafael Simó
- Diabetes and Metabolism Research Unit and CIBERDEM, Vall d'Hebron Research Institute, Barcelona, Spain
| | - Cristina Hernández
- Diabetes and Metabolism Research Unit and CIBERDEM, Vall d'Hebron Research Institute, Barcelona, Spain
| | - Massimo Porta
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Francesco Bandello
- Department of Ophthalmology, University Vita-Salute, Scientific Institute San Raffaele, Milano, Italy
| | - Jakob Grauslund
- Research Unit of Ophthalmology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Simon P Harding
- Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, U.K
| | - Stephen J Aldington
- Gloucestershire Hospitals National Health Service Foundation Trust, Cheltenham, U.K
| | - Catherine Egan
- Moorfields Eye Hospital National Health Service Foundation Trust, Institute of Ophthalmology/University College London, London, U.K
| | - Ulrik Frydkjaer-Olsen
- Research Unit of Ophthalmology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - José García-Arumí
- Department of Ophthalmology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Jonathan Gibson
- Department of Vision Sciences, Aston University, Birmingham, U.K
| | - Gabriele E Lang
- Department of Ophthalmology, University of Ulm, Ulm, Germany
| | - Rosangela Lattanzio
- Department of Ophthalmology, University Vita-Salute, Scientific Institute San Raffaele, Milano, Italy
| | - Pascale Massin
- Department of Ophthalmology, Lariboisière Hospital, Paris, France
| | - Edoardo Midena
- Department of Ophthalmology, University of Padova, Padova, Italy
| | | | - Luísa Ribeiro
- Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal, and Faculty of Medicine, University of Coimbra, Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal
| | - Peter Scanlon
- Gloucestershire Hospitals National Health Service Foundation Trust, Cheltenham, U.K
| | - Conceição Lobo
- Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal, and Faculty of Medicine, University of Coimbra, Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal
| | - Miguel Ângelo Costa
- Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal, and Faculty of Medicine, University of Coimbra, Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal
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Elisha R. The curious case of Patient K. Med J Aust 2018; 209:501-502. [PMID: 30521445 DOI: 10.5694/mja18.00962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 10/09/2018] [Indexed: 11/17/2022]
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Simó R, Stitt AW, Gardner TW. Neurodegeneration in diabetic retinopathy: does it really matter? Diabetologia 2018; 61:1902-1912. [PMID: 30030554 PMCID: PMC6096638 DOI: 10.1007/s00125-018-4692-1] [Citation(s) in RCA: 384] [Impact Index Per Article: 54.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 06/19/2018] [Indexed: 02/07/2023]
Abstract
The concept of diabetic retinopathy as a microvascular disease has evolved, in that it is now considered a more complex diabetic complication in which neurodegeneration plays a significant role. In this article we provide a critical overview of the role of microvascular abnormalities and neurodegeneration in the pathogenesis of diabetic retinopathy. A special emphasis is placed on the pathophysiology of the neurovascular unit (NVU), including the contributions of microvascular and neural elements. The potential mechanisms linking retinal neurodegeneration and early microvascular impairment, and the effects of neuroprotective drugs are summarised. Additionally, we discuss how the assessment of retinal neurodegeneration could be an important index of cognitive status, thus helping to identify individuals at risk of dementia, which will impact on current procedures for diabetes management. We conclude that glial, neural and microvascular dysfunction are interdependent and essential for the development of diabetic retinopathy. Despite this intricate relationship, retinal neurodegeneration is a critical endpoint and neuroprotection, itself, can be considered a therapeutic target, independently of its potential impact on microvascular disease. In addition, interventional studies targeting pathogenic pathways that impact the NVU are needed. Findings from these studies will be crucial, not only for increasing our understanding of diabetic retinopathy, but also to help to implement a timely and efficient personalised medicine approach for treating this diabetic complication.
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Affiliation(s)
- Rafael Simó
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
| | - Alan W Stitt
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, UK
| | - Thomas W Gardner
- Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA
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Klein BEK, Horak KL, Lee KE, Meuer SM, Abramoff MD, Soliman EZ, Rechek M, Klein R. Neural dysfunction and retinopathy in persons with type 1 diabetes. Ophthalmic Epidemiol 2018; 25:373-378. [PMID: 29985712 DOI: 10.1080/09286586.2018.1489971] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
OBJECTIVE To determine associations of microvascular and neuropathic complications of diabetes cross-sectionally and longitudinally in persons with long-term type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Persons receiving care for T1D in South Central Wisconsin were identified in 1979-1980 and examined approximately every 5 years. Associations between neuropathic and microvascular complications were examined at most prior visits, when information on several neuropathic complications was collected. Temporal relationships were examined by modeling incidence between examinations across the visits. RESULTS Adjusting for duration of diabetes, glycated hemoglobin, and systolic blood pressure, the following were cross-sectionally associated with prevalent PDR (proliferative diabetic retinopathy): the presence of sensory neuropathy (SN) as reported at each Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) examination (odds ratio (OR) = 2.76, confidence interval (CI) = 1.71, 4.48) and the heartrate variability measures RMSD (square root of the mean of squared differences of successive RR intervals) (OR = 0.24, CI = 0.16, 0.37) and SDNN (standard deviation of successive RR intervals) (OR = 0.26, CI = 0.17, 0.39). Findings were similar for prevalent ME (macular edema) as assessed from spectral-domain optical coherence tomography (SD-OCT). The presence of PDR (OR = 2.13, CI = 1.63, 2.78) and ME (OR = 2.36, CI = 1.66, 3.34) were both significantly associated with incident WESDR SN. WESDR SN was associated with incident PDR (OR = 1.53, CI = 1.09, 2.15) but not incident ME (OR = 1.31, CI = 0.92, 1.87). CONCLUSIONS Sensory neuropathy and heartrate variability were significantly associated with prevalent PDR and ME in people with long-term T1D. PDR and ME were significantly associated with incident sensory neuropathy, and sensory neuropathy was significantly associated with incident PDR. Studies using earliest detectable markers of microvascular and neurologic abnormalities are needed to determine which of the two systems 'fails' first. Such information might suggest a temporal sequence of diabetes complications.
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Affiliation(s)
- Barbara E K Klein
- a Ophthalmology & Visual Sciences , University of Wisconsin-Madison , Madison , WI , USA
| | - Kayla L Horak
- a Ophthalmology & Visual Sciences , University of Wisconsin-Madison , Madison , WI , USA
| | - Kristine E Lee
- a Ophthalmology & Visual Sciences , University of Wisconsin-Madison , Madison , WI , USA
| | - Stacy M Meuer
- a Ophthalmology & Visual Sciences , University of Wisconsin-Madison , Madison , WI , USA
| | - Michael D Abramoff
- b Electrical and Computer Engineering , University of Iowa , Iowa City , IA , USA.,c Biomedical Engineering , University of Iowa , Iowa City , IA , USA
| | - Elsayed Z Soliman
- d Epidemiology & Prevention EpiCare , Wake Forest University , Winston-Salem , NC , USA
| | - Mary Rechek
- a Ophthalmology & Visual Sciences , University of Wisconsin-Madison , Madison , WI , USA
| | - Ronald Klein
- a Ophthalmology & Visual Sciences , University of Wisconsin-Madison , Madison , WI , USA
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Trifunović D, Arango-Gonzalez B, Comitato A, Barth M, Del Amo EM, Kulkarni M, Sahaboglu A, Hauck SM, Urtti A, Arsenijevic Y, Ueffing M, Marigo V, Paquet-Durand F. HDAC inhibition in the cpfl1 mouse protects degenerating cone photoreceptors in vivo. Hum Mol Genet 2018; 25:4462-4472. [PMID: 28172811 DOI: 10.1093/hmg/ddw275] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 08/05/2016] [Accepted: 08/11/2016] [Indexed: 12/21/2022] Open
Abstract
Cone photoreceptor cell death as it occurs in certain hereditary retinal diseases is devastating, with the affected patients suffering from a loss of accurate and colour vision. Regrettably, these hereditary cone diseases are still untreatable to date. Thus, the identification of substances able to block or restrain cone cell death is of primary importance. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cpfl1 cones in vitro, in retinal explant cultures. More importantly, in vivo, a single intravitreal TSA injection significantly increased cone survival for up to 16 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and retinal diseases associated with impaired cone migration.
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Affiliation(s)
- Dragana Trifunović
- Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
| | | | - Antonella Comitato
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Melanie Barth
- Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
| | - Eva M Del Amo
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Manoj Kulkarni
- Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
| | - Ayse Sahaboglu
- Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
| | - Stefanie M Hauck
- Research Unit Protein Science, Helmholtz Center Munich, Neuherberg, Germany
| | - Arto Urtti
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland.,Centre for Drug Research, Division of Pharmaceutical Bioscience, University of Helsinki, Helsinki, Finland
| | - Yvan Arsenijevic
- Unit of Gene Therapy & Stem Cell Biology, Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland
| | - Marius Ueffing
- Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
| | - Valeria Marigo
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
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Sawides L, Sapoznik KA, de Castro A, Walker BR, Gast TJ, Elsner AE, Burns SA. Alterations to the Foveal Cone Mosaic of Diabetic Patients. Invest Ophthalmol Vis Sci 2017; 58:3395-3403. [PMID: 28687853 PMCID: PMC5501497 DOI: 10.1167/iovs.17-21793] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Purpose We measured localized changes occurring in the foveal cone photoreceptors and related defects in the cone mosaic to alterations in the nearby retinal vasculature. Methods The central 4° of the retina of 54 diabetic (53.7 ± 12.5 years) and 85 control (35.8 ± 15.2 years) participants were imaged with the Indiana adaptive optics scanning laser ophthalmoscope. Foveal cones and overlying retinal capillaries were imaged and infrared scanning laser ophthalmoscopy (IR SLO) images and optical coherence tomography (OCT) B-scans were obtained. Follow-up imaging sessions were performed with intervals from 4 to 50 months for 22 of the 54 diabetic participants. Results The foveal cone mosaics of 49 of 54 diabetic participants were of sufficient quality to assess the absence or presence of small localized defects in the cone mosaic. In 13 of these 49 diabetic participants we found localized defects, visualized as sharp-edged areas of cones with diminished reflectivity. These small, localized areas ranged in size from 10 × 10 μm to 75 × 30 μm. Of these 13 participants with cone defects, 11 were imaged over periods from 4 to 50 months and the defects remained relatively stable. These dark regions were not shadows of overlying retinal vessels, but all participants with these localized defects had alterations in the juxtafoveal capillary network. Conclusions The foveal cone mosaic can show localized areas of dark cones that persist over time, that apparently correspond to either missing or nonreflecting cones, and may be related to local retinal ischemia.
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Affiliation(s)
- Lucie Sawides
- School of Optometry, Indiana University, Bloomington, Indiana, United States
| | - Kaitlyn A Sapoznik
- School of Optometry, Indiana University, Bloomington, Indiana, United States
| | - Alberto de Castro
- School of Optometry, Indiana University, Bloomington, Indiana, United States
| | - Brittany R Walker
- School of Optometry, Indiana University, Bloomington, Indiana, United States
| | - Thomas J Gast
- School of Optometry, Indiana University, Bloomington, Indiana, United States
| | - Ann E Elsner
- School of Optometry, Indiana University, Bloomington, Indiana, United States
| | - Stephen A Burns
- School of Optometry, Indiana University, Bloomington, Indiana, United States
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Trento M, Durando O, Lavecchia S, Charrier L, Cavallo F, Costa MA, Hernández C, Simó R, Porta M. Vision related quality of life in patients with type 2 diabetes in the EUROCONDOR trial. Endocrine 2017; 57:83-88. [PMID: 27628581 DOI: 10.1007/s12020-016-1097-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Accepted: 08/17/2016] [Indexed: 11/26/2022]
Abstract
To evaluate vision related quality of life in the patients enrolled in The European Consortium for the Early Treatment of Diabetic Retinopathy, a clinical trial on prevention of diabetic retinopathy. Four-hundred-forty-nine patients, 153 women, with type 2 Diabetes and no or mild diabetic retinopathy were enrolled in a 2-year multicenter randomized controlled trial. The 25-item National Eye Institute Visual Functioning Questionnaire was used to explore 12 subscales of vision related quality of life. The patients were 62.8 ± 6.7 years old and had 11.1 ± 5.6 years known disease duration. Diabetic retinopathy was absent in 193 (43.0 %) and mild in 256 (57.0 %). Patients without diabetic retinopathy were older, had shorter diabetes duration and used less insulin and glucose-lowering agents but did not differ by gender, best corrected visual acuity or any subscale, except vision specific mental health and vision specific role difficulties. Patients with reduced retinal thickness at the ganglion cell layer (n = 36) did not differ for diabetic retinopathy but were older, had lower best corrected visual acuity and worse scores for ocular pain, color vision and peripheral vision. On multivariable analysis, worse scores for general vision remained associated with reduced retinal thickness, diabetes duration and best corrected visual acuity, and scores for visual specific mental health with diabetic retinopathy and lower best corrected visual acuity. Visual specific role difficulties were only associated with reduced best corrected visual acuity. Scores for driving decreased among females, with worsening of Hemoglobin A1c and best corrected visual acuity. Color vision depended only on reduced retinal thickness, and peripheral vision on both reduced thickness and best corrected visual acuity. The National Eye Institute Visual Functioning Questionnaire could detect subtle changes in patients' perception of visual function, despite absent/minimal diabetic retinopathy.
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Affiliation(s)
- Marina Trento
- Laboratory of Clinical Pedagogy, Department of Medical Sciences, University of Turin, Turin, Italy.
| | - Olga Durando
- Laboratory of Clinical Pedagogy, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Sonia Lavecchia
- Laboratory of Clinical Pedagogy, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Lorena Charrier
- Department of Public Health and Paediatrics, University of Turin, Turin, Italy
| | - Franco Cavallo
- Department of Public Health and Paediatrics, University of Turin, Turin, Italy
| | - Miguel Angelo Costa
- Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal
- Diabetic Retinopathy Centre, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Cristina Hernández
- Vall d' Hebron Research Institute and CIBERDEM (ISCIII), Barcelona, Spain
| | - Rafael Simó
- Vall d' Hebron Research Institute and CIBERDEM (ISCIII), Barcelona, Spain
| | - Massimo Porta
- Laboratory of Clinical Pedagogy, Department of Medical Sciences, University of Turin, Turin, Italy
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Khan A, Petropoulos IN, Ponirakis G, Malik RA. Visual complications in diabetes mellitus: beyond retinopathy. Diabet Med 2017; 34:478-484. [PMID: 27917530 DOI: 10.1111/dme.13296] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2016] [Indexed: 11/28/2022]
Abstract
Diabetic retinopathy is the most common cause of vision loss in people with diabetes mellitus; however, other causes of visual impairment/loss include other retinal and non-retinal visual problems, including glaucoma, age-related macular degeneration, non-arteritic anterior ischaemic optic neuropathy and cataracts. Additionally, when a person with diabetes complains of visual disturbance despite a visual acuity of 6/6, abnormalities in refraction, contrast sensitivity, straylight and amplitude of accommodation should be considered. We review and highlight these visual problems for physicians who manage people with diabetes to ensure timely referral and treatment to limit visual disability, which can have a significant impact on daily living, especially for those participating in sports and driving.
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Affiliation(s)
- A Khan
- Weill Cornell Medicine-Qatar, Doha, Qatar
| | | | | | - R A Malik
- Weill Cornell Medicine-Qatar, Doha, Qatar
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Gast TJ, Fu X, Gens JS, Glazier JA. A Computational Model of Peripheral Photocoagulation for the Prevention of Progressive Diabetic Capillary Occlusion. J Diabetes Res 2016; 2016:2508381. [PMID: 27847828 PMCID: PMC5099465 DOI: 10.1155/2016/2508381] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 08/02/2016] [Accepted: 09/29/2016] [Indexed: 01/17/2023] Open
Abstract
We developed a computational model of the propagation of retinal ischemia in diabetic retinopathy and analyzed the consequences of various patterns and sizes of burns in peripheral retinal photocoagulation. The model addresses retinal ischemia as a phenomenon of adverse local feedback in which once a capillary is occluded there is an elevated probability of occlusion of adjacent capillaries resulting in enlarging areas of retinal ischemia as is commonly seen clinically. Retinal burns of different sizes and patterns, treated as local oxygen sources, are predicted to have different effects on the propagation of retinal ischemia. The patterns of retinal burns are optimized with regard to minimization of the sum of the photocoagulated retina and computer predicted ischemic retina. Our simulations show that certain patterns of retinal burns are effective at preventing the spatial spread of ischemia by creating oxygenated boundaries across which the ischemia does not propagate. This model makes no statement about current PRP treatment of avascular peripheral retina and notes that the usual spot sizes used in PRP will not prevent ischemic propagation in still vascularized retinal areas. The model seems to show that a properly patterned laser treatment of still vascularized peripheral retina may be able to prevent or at least constrain the propagation of diabetic retinal ischemia in those retinal areas with intact capillaries.
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Affiliation(s)
- Thomas J. Gast
- School of Optometry, Indiana University, Bloomington, IN 47405, USA
| | - Xiao Fu
- The Biocomplexity Institute, Indiana University, Bloomington, IN 47405, USA
- Physics Department, Indiana University, Bloomington, IN 47405, USA
| | - John Scott Gens
- The Biocomplexity Institute, Indiana University, Bloomington, IN 47405, USA
- Physics Department, Indiana University, Bloomington, IN 47405, USA
| | - James A. Glazier
- The Biocomplexity Institute, Indiana University, Bloomington, IN 47405, USA
- Physics Department, Indiana University, Bloomington, IN 47405, USA
- School of Informatics and Computing, Indiana University, Bloomington, IN 47408, USA
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Moccia M, Lavorgna L, Lanzillo R, Brescia Morra V, Tedeschi G, Bonavita S. The Dress: Transforming a web viral event into a scientific survey. Mult Scler Relat Disord 2016; 7:41-6. [DOI: 10.1016/j.msard.2016.03.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 03/01/2016] [Indexed: 10/22/2022]
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Relations between Cardiac and Visual Phenotypes in Diabetes: A Multivariate Approach. PLoS One 2016; 11:e0153772. [PMID: 27089510 PMCID: PMC4835099 DOI: 10.1371/journal.pone.0153772] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Accepted: 04/04/2016] [Indexed: 01/07/2023] Open
Abstract
Cardiovascular disease and diabetes represent a major public health concern. The former is the most frequent cause of death and disability in patients with type 2 diabetes, where left ventricular dysfunction is highly prevalent. Moreover, diabetic retinopathy is becoming a dominant cause of visual impairment and blindness. The complex relation between cardiovascular disease and diabetic retinopathy as a function of ageing, obesity and hypertension remains to be clarified. Here, we investigated such relations in patients with diabetes type 2, in subjects with neither overt heart disease nor advanced proliferative diabetic retinopathy. We studied 47 patients and 50 controls, aged between 45 and 65 years, equally distributed according to gender. From the 36 measures regarding visual structure and function, and the 11 measures concerning left ventricle function, we performed data reduction to obtain eight new derived variables, seven of which related to the eye, adjusted for age, gender, body mass index and high blood pressure using both discriminant analysis (DA) and logistic regression (LR). We found moderate to strong correlation between left ventricle function and the eye constructs: minimum correlation was found for psychophysical motion thresholds (DA: 0.734; LR: 0.666), while the maximum correlation was achieved with structural volume density in the neural retina (DA: 0.786; LR: 0.788). Controlling the effect of pairwise correlated visual constructs, the parameters that were most correlated to left ventricle function were volume density in retina and thickness of the retinal nerve fiber layers (adjusted multiple R2 is 0.819 and 0.730 for DA and LR), with additional contribution of psychophysical loss in achromatic contrast discrimination. We conclude that visual structural and functional changes in type 2 diabetes are related to heart dysfunction, when the effects of clinical, demographic and associated risk factors are taken into account, revealing a genuine relation between cardiac and retinal diabetic phenotypes.
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Hernández C, Dal Monte M, Simó R, Casini G. Neuroprotection as a Therapeutic Target for Diabetic Retinopathy. J Diabetes Res 2016; 2016:9508541. [PMID: 27123463 PMCID: PMC4830713 DOI: 10.1155/2016/9508541] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 02/29/2016] [Accepted: 03/16/2016] [Indexed: 02/07/2023] Open
Abstract
Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed.
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Affiliation(s)
- Cristina Hernández
- CIBERDEM (CIBER de Diabetes y Enfermedades Metabolicas Asociadas) and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autonoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain
- *Cristina Hernández: and
| | - Massimo Dal Monte
- Department of Biology, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy
- Interdepartmental Research Center Nutrafood “Nutraceuticals and Food for Health”, University of Pisa, Via del Borghetto 80, 56124 Pisa, Italy
| | - Rafael Simó
- CIBERDEM (CIBER de Diabetes y Enfermedades Metabolicas Asociadas) and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autonoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain
| | - Giovanni Casini
- Department of Biology, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy
- Interdepartmental Research Center Nutrafood “Nutraceuticals and Food for Health”, University of Pisa, Via del Borghetto 80, 56124 Pisa, Italy
- *Giovanni Casini:
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