The Retina as a Biomarker for Brain Development


The retina, visible during an eye examination, is part of the brain.  That fact was elegantly stated by Dr. David Hubel of Harvard, co-recipient of the Nobel Prize for his work on the visual system, who wrote: “The retina is part of the brain, having been sequestered from it early in development but having kept its connections with the brain proper through a bundle of fibers—the optic nerve.”  A white paper published by the American Optometric Association on vision as a collaboration between the eyes and brain reinforced this structural fact from a functional point of view.

An intriguing new article from a research group in Spain considers retinal structure assessed by optical coherence tomography (OCT) as a biomarker of brain development in children born small for gestational age (SGA).  As the authors note, compelling evidence supports that children born SGA have poorer neurobehavioral outcomes, including learning, cognitive and attentional problems, than do AGA (appropriate for gestational age) infants.  Their research group previously reported that thinning in the retinal nerve fibre layer (RNFL) is associated with impaired performance intelligence scores in school-age children born SGA, due to exposition to chronic hypoxia and undernutrition in fetal life.

Given that children born SGA account for around 10% of all deliveries, early and accurate biomarkers of suboptimal neurodevelopment are required to identify children at increased risk of neurological impairments among these infants.  Because OCT measurements have been utilized as an accurate biomarker of neuronal changes in the central nervous system in certain neurodegenerative conditions such as MS and Parkinson’s, the authors speculated about an analogous use for neurodevelopmental delays.

OCT measurements analyzed in this study included average RNFL thickness, thickness in the four quadrants, disc area, C/D ratio, average ganglion cell and inner plexiform layers (GCL-IPL), and minimum GCL-IPL.  Outcomes were classified as abnormal when they were below the 5th centile of  normal pediatric values for each measurement.  These values were compared to brain area volume as assessed by MRI.  Their results are illustrated here:



Comparative representation of MRI brain images and retinal structure (ganglion cell-inner plexiform complex (GCL-IPL)). (Left, A) Brain images of a child born with an appropriate birth weight (top, A1) and a child born small for gestational age (bottom, A2). (Right, B) Retinal measurements of a child born with an appropriate birth weight (top, B1) and a child born small for gestational age (bottom, B2).

Quoting from the paper’s discussion section:  “Primary injuries in immature optic radiation are frequently associated with structural changes in the retina. Lennartsson et al performed brain MRI and OCT in seven cases of young adults born preterm with known white matter damage due to immaturity and concluded that RNFL loss was more pronounced in subjects with more extensive lesions, following the pattern of the optic radiation damage. We propose a double mechanism for neuronal changes in the retina of children born SGA. Although a trans-synaptic degeneration may result in retinal changes in an infant with brain damage due to perinatal adverse events, derived from growth restriction or prematurity, a primary damage may also occur in the retina since neurological insult is taking place in an early stage of neurodevelopment. Chronic exposure to an adverse intrauterine environment in critical stages of pregnancy is likely to cause not only suboptimal development of retinal structures, but also adaptive mechanisms …


And from their conclusion:  “SGA children, both preterm and term born, showed evidence of structural abnormalities in the retinal and brain neuronal tissues at school age, even with no evidence of neurological major impairments. We propose GCL-IPL as a potential biomarker identifying SGA children with the most profound brain reorganisation. An early and non-invasive biomarker would help to identify children with an increased risk of poor neurodevelopment among all SGA born. It would make it possible to perform further studies or to propose early abilitative interventions. Although retinal measurements should not be considered as an isolated biomarker of brain damage in SGA children, they could be helpful in combination with other biological or cognitive assessments.”

3 thoughts on “The Retina as a Biomarker for Brain Development

  1. Great to know! This justifies the use of OCT in younger children. Now, will insurance accept this as a reason to test?

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