Amblyopia, known as 'lazy eye', is a very common neurodevelopmental defect and a cause of visual impairment, affecting between 1 and 3% of children worldwide.
David H. Hubel and Torsten Wiesel, the two scientists who won the 1981 Nobel Prize in Medicine for their research on the neurophysiological mechanisms of vision, have always maintained that amblyopia constitutes an important model for understanding neuroplasticity and neurodevelopment.
Primary amblyopia is determined by an aberrant competitive interaction between the cortical afferent fibres of the two eyes, this condition results in one of the eyes becoming dominant and the other 'lagging' and losing visus.
Significant progress has been made in the current era, thanks to increasingly widespread screening programmes in the school population and the subsequent corrective ophthalmic intervention - consisting of refractive correction and optical penalisation of the dominant contralateral optic - but unfortunately many children still develop a persistent unilateral visual impairment, which persists into adulthood.
Since the 1990s, numerous studies have investigated the relationship between intrauterine development, neurodevelopment and non-communicable diseases such as Alzheimer's disease, Parkinson's disease, stroke, cancer, diabetes, chronic kidney disease, osteoporosis and osteoarthritis. More recently, studies have also focused on the link between neurodevelopment and cardio-metabolic syndromes and, in this area, research has examined amblyopia, a visual impairment that has been directly or indirectly linked to parent-related risk factors - mainly the mother - such as advanced age of conception, cigarette smoking and alcohol consumption. Experimental evidence shows an association between these perinatal risk factors and the development of cardio-metabolic diseases in adulthood. Furthermore, recent studies show that apparently normal eyes in patients with amblyopia present morphological differences at the retinal level, which seem to suggest systemic structural dysregulation in the brain and visual pathways.
The association between amblyopia and cardio-metabolic disorders has now, for the first time, been the subject of a systematic study by British researchers at University College London and published in The Lancet. The aim of the research team was to investigate 'whether' individuals with childhood amblyopia are more likely to develop cardio-metabolic disorders in later adult life than individuals without amblyopia.
The study included data from 126,000 individuals, aged between 40 and 69 years, drawn from the United Kingdom Biobank. All recruited subjects underwent a comprehensive eye examination. During the recruitment process, participants were also asked about the diagnosis and treatment of their amblyopia condition as children, about the persistence of amblyopia in adulthood, and about any diagnoses of diabetes, high blood pressure, and cardiological and cerebrovascular diseases.
The researchers also measured body mass index, blood glucose and cholesterol levels and tracked the participants' mortality.
The results showed that a high percentage, 82.2%, of the 3,238 participants who had suffered from amblyopia in childhood had persistent visual impairment in one eye as adults.
Moreover, subjects with childhood amblyopia were more likely to develop diabetes (+29%), hypertension (+25%) and obesity (+16%). The risk of heart attack was also higher, although the presence of other pathologies, ethnicity and social class of membership also had to be considered as related competing risk factors.
On retinal imaging the amblyopic eyes had an increased venular calibre, increased tortuosity, a smaller fractal dimension and a thinner inner plexiform layer of ganglion cells. The healthy (i.e. non-amblyopic) eyes of the amblyopia subjects also had a significantly smaller retinal fractal dimension and a thinner inner plexiform layer. Finally, amblyopic eyes with persistent visual impairment had reduced optic nerve height and width compared to control eyes.
What meaning should be attached to these results?
A causal correlation, whereby amblyopia can be considered the direct cause of cardio-metabolic disorders, can clearly be ruled out and, in addition, further research will be needed to understand the basis of the association that has been identified between cardio-metabolic dysfunction in adults and childhood amblyopia.
Moreover, as pointed out by experts in preventive medicine, it is very rare to find a 'marker' in a child that is associated with the risk of serious diseases in adulthood, and even rarer when it is a parameter that can be measured in all children at screening visits organised in schools.
On the subject of refractive defects in paediatric age, see also:
- Paediatric vision screening - Oculista Italiano
- Refractive defects in children - Oculista Italiano
- Convergence insufficiency in children: how to intervene - Oculista Italiano
- Dyslexia and impaired eye movements - Oculist Italiano
- Upton E, Doogan C, Fleming V, et al. Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank. 2024; eClinicalMedicine;10.1016/j.eclinm.2024.102493
- Fu Z, Hong H, Su Z, Lou B, Pan CW, Liu H. Global prevalence of amblyopia and disease burden projections through 2040: a systematic review and meta-analysis. Br J Ophthalmol. 2020 Aug;104(8):1164-1170. doi: 10.1136/bjophthalmol-2019-314759. Epub 2019 Nov 8. PMID: 31704700.
- Holmes JM, Clarke MP. Amblyopia. Lancet. 2006 Apr 22;367(9519):1343-51. doi: 10.1016/S0140-6736(06)68581-4. PMID: 16631913.
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