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Heritability of Retinal Vascular Morphology
in a Danish Twin Population


Nina Taarnhøj  


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Accepted by: The Faculty of Health Science University of Copenhagen
Defended on: March 11, 2008
Official opponents: Fridbert Jonasson, Professor, MD, Reykjavik, Iceland , Peter Bjerre Toft, Associate professor, MD, Department of Ophthalmology, Rigshospitalet, Denmark , Hans Ibsen, Professor, MD, Medicinsk afdeling, Holbæk, Denmark
Tutors: Michael Larsen, Professor, MD, Department of Ophthalmology, Glostrup Hospital , Line Kessel, MD, Ph.D. Department of Ophthalmology, Glostrup Hospital , Knut Borch-Johnsen, Professor, MD, Steno Diabetes Centre

Published in the PhD Database: August 6, 2008


English abstract
The clinical signs of many systemic vascular diseases, such as hypertension and diabetes mellitus, are reflected in the fundus of the eye. Vascular abnormalities are easily observed by ophthalmoscopy and the eye is like a window to the systemic vasculature. Large epidemiologic studies have demonstrated the association between retinal vessel abnormalities and hypertension, cardiovascular disease, diabetes mellitus, stroke and ocular diseases. These associations explain only a small part of the variation in retinal blood vessels. Given, the association between retinal vessel morphology and complex systemic diseases, understanding the genetic and environmental determinants of vessel morphology may provide additional insights into the aetiology and pathogenesis of these complex diseases. The classic twin study is superb at finding out if a trait is genetically influenced ¿ if it can demonstrate that monozygotic (MZ) twins are more similar for the trait than dizygotic (DZ) twins, especially when using structural equation modelling. We wanted to examine how much of the variation in retinal vessel morphology was explained by genetic and environmental factors in a Danish twin population.
The thesis is based on four papers, of which one is a review of twin studies in ophthalmology and the other three cover heritability analyses of retinal blood vessel calibres, retinal arterial tortuosity and the presence of cilioretinal arteries in digital red-free fundus images from 58 MZ and 54 DZ same-sex healthy normotensive twin pairs aged 20 to 46 years. This thesis demonstrated that genetic factors influenced the variation in retinal arterial tortuosity, retinal vessel calibre, and the presence of cilioretinal arteries. Straight arteries were associated with increasing body mass index and mean arterial blood pressure. Narrow retinal veins were associated with increasing age, and narrow retinal arteries were associated with increasing age and mean arterial blood pressure. There was evidence of a weak genetic association between retinal artery calibre and blood pressure, indicating that a genetic and mechanistic link may be present between the two. The data from these studies suggest that a single fundus photograph cannot yet be used in the evaluation of an individual patients¿ risk of cardiovascular disease because individual predictive values of risk estimates for cardiovascular disease have yet to be defined. Longitudinal studies based on repeated fundus photographs over many years, are likely to be more sensitive than cross sectional population studies in showing effects of systemic health parameters on vascular morphology.



Danish abstract
I øjets nethinde kan man observere kliniske tegn på systemiske sygdomme, som for eksempel forhøjet blodtryk og diabetes mellitus ved hjælp af oftalmoskop. Øjet kan betragtes som et vindue ind til de systemiske kar, da mange abnormiteter i systemiske kar reflekteres i nethindens kar. Store epidemiologiske studier har vist sammenhænge mellem nethinde arterie forsnævring/vene dilatation og forhøjet blodtryk, hjertesygdom, diabetes mellitus og slagtilfælde. Sammenhæng mellem arterie tortuositet i nethinden og forhøjet blodtryk og død pga. iskæmisk hjertesygdom er også blevet påvist. Disse sammenhænge forklarer dog kun en brøkdel af variationen i nethindens kar. Vi ønskede at finde ud af hvor meget af variationen som skyldtes genetiske og miljømæssige faktorer, for at få en dybere forståelse af patogenesen til disse komplekse vaskulære sygdomme. Klassiske tvillingstudier er fremragende til at finde ud af om en fænotype eller en sygdom er genetisk bestemt, hvis de kan demonstrere at monozygote (MZ) tvillinger er signifikant mere ens end dizygote (DZ) tvillinger, specielt ved brug af moderne tvillingstatistiske analysemetoder. Vi ønskede at undersøge hvor stor del af variationen i tre forskellige typer af karmorfologi, som skyldtes genetiske og miljømæssige faktorer i en dansk tvillingpopulation.
Afhandlingen er baseret på fire artikler, hvoraf de tre af dem er arveligheds analyser af henholdsvis kardiameter, arterie tortuositet og tilstedeværelse og placering af cilioretinale arterier. Disse karakteristika er undersøgt på digitale fundus fotografier fra 58 MZ og 54 DZ raske, normotensive tvillingepar af samme køn i alderen 20-46 år. Studierne viste at variationen i kardiameter, arterie tortuositet og tilstedeværelse og placering af cilioretinale arterier var hovedsagelig bestemt af genetiske faktorer i denne population. Desuden var mindre arterie diameter associeret med stigende blodtryk og stigende alder og mindre vene diameter var associeret med stigende alder. Nedsat tortuositet var associeret med øget middel arterie blodtryk og body mass index.
Det er ikke endnu muligt at forudsige noget om en individuel patients risiko for udvikling af hjertekarsygdom baseret på karmål fra et enkelt fundus fotografi, fordi individuelle prædiktive værdier og risk estimater for hjertekarsygdom mangler at blive defineret i større epidemiologiske studier. Longitudinelle studier baseret på gentagne fundus fotografier over mange år, er muligvis mere sensitive end tværsnits studier som dette, til at vise effekten af systemiske parametre på nethindens kar morfologi.