Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank

Siegfried Karl Wagner, Vasiliki Bountziouka, Pirro Hysi, Jugnoo Sangeeta Rahi*, Naomi Allen, Tariq Aslam, Denize Atan, Konstantinos Balaskas, Sarah Barman, Jenny Barrett, Paul Bishop, Graeme Black, Tasanee Braithwaite, Roxana Carare, Usha Chakravarthy, Michelle Chan, Sharon Chua, Alexander Day, Parul Desai, Bal DhillonAndrew Dick, Alexander Doney, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John Gallacher, David (Ted) Garway-heath, Jane Gibson, Jeremy Guggenheim, Chris Hammond, Alison Hardcastle, Simon Harding, Ruth Hogg, Pearse Keane, Sir Peng Tee Khaw, Anthony Khawaja, Gerassimos Lascaratos, Thomas Littlejohns, Andrew Lotery, Robert Luben, Phil Luthert, Tom Macgillivray, Sarah Mackie, Bernadette Mcguinness, Gareth Mckay, Euan Paterson, Tunde Peto, David Steel, Jayne Woodside, UK Biobank Eye & Vision Consortium

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Amblyopia is a common neurodevelopmental condition and leading cause of childhood visual impairment. Given the known association between neurodevelopmental impairment and cardiometabolic dysfunction in later life, we investigated whether children with amblyopia have increased risk of cardiometabolic disorders in adult life. 

Methods: This was a cross-sectional and longitudinal analysis of 126,399 United Kingdom Biobank cohort participants who underwent ocular examination. A subset of 67,321 of these received retinal imaging. Data analysis was conducted between November 1st 2021 and October 15th 2022. Our primary objective was to investigate the association between amblyopia and a number of components of metabolic syndrome and individual cardiometabolic diseases. Childhood amblyopia, dichotomised as resolved or persisting by adulthood, cardiometabolic disease and mortality were defined using ophthalmic assessment, self-reported, hospital admissions and death records. Morphological features of the optic nerve and retinal vasculature and sublayers were extracted from retinal photography and optical coherence tomography. Associations between amblyopia and cardiometabolic disorders as well as retinal markers were investigated in multivariable-adjusted regression models. 

Findings: Individuals with persisting amblyopia (n = 2647) were more likely to be obese (adjusted odds ratio (95% confidence interval): 1.16 (1.05; 1.28)), hypertensive (1.25 (1.13; 1.38)) and diabetic (1.29 (1.04; 1.59)) than individuals without amblyopia (controls, (n = 18,481)). Amblyopia was also associated with an increased risk of myocardial infarction (adjusted hazard ratio: 1.38 (1.11; 1.72)) and death (1.36 (1.15; 1.60)). On retinal imaging, amblyopic eyes had significantly increased venular caliber (0.29 units (0.21; 0.36)), increased tortuosity (0.11 units (0.03; 0.19)), but lower fractal dimension (−0.23 units (−0.30; −0.16)) and thinner ganglion cell-inner plexiform layer (mGC-IPL, −2.85 microns (−3.47; −2.22)). Unaffected fellow eyes of individuals with amblyopia also had significantly lower retinal fractal dimension (−0.08 units (−0.15; −0.01)) and thinner mGC-IPL (−1.14 microns (−1.74; −0.54)). Amblyopic eyes with a persisting visual deficit had smaller optic nerve disc height (−0.17 units (−0.25; −0.08)) and width (−0.13 units (−0.21; −0.04)) compared to control eyes. 

Interpretation: Although further research is needed to understand the basis of the observed associations, healthcare professionals should be cognisant of greater cardiometabolic dysfunction in adults who had childhood amblyopia. Differences in retinal features in both the amblyopic eye and the unaffected non-amblyopic suggest generalised versus local processes. 

Original languageEnglish
Article number102493
JournaleClinicalMedicine
Volume70
DOIs
Publication statusPublished - 18 Apr 2024

Keywords

  • Amblyopia
  • Cardiometabolic dysfunction
  • Neurodevelopment
  • Oculomics
  • Retina

ASJC Scopus subject areas

  • General Medicine

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