Retinopathy of Prematurity Not Associated With Brain Maturation Delay

Chinese mom is trying to keep her daughter calm during her MRI check-up on a fine day in Oslo, Norway. Mom is very anxious about her sick daughter but still puts on a brave face so they can power through this ordeal. Magnetic Resonance Imaging (MRI) is a non-invasive imaging technology that uses strong magnetic fields and radio waves to produce detailed images of organs inside our body.
Researchers say delayed development of white matter pathways are not more likely in patients born with the retinal condition.

Neither retinopathy of prematurity (ROP) nor severe ROP is significantly associated with a delay in maturation of white matter pathways, according to research published in Investigative Ophthalmology & Visual Science. 

Researchers conducted a prospective, observational cohort study of 84 preterm infants to investigate the microstructural alteration of brain white matter and compare microstructural parameters between infants with and without ROP or severe ROP.  

All infants with a gestational age of 31 weeks or fewer or a birth weight of 1500 g or less were screened for retinopathy of prematurity. Disease classification was performed for ROP zone and stage, and maximal ROP stage was used for the study analyses. 

Researchers identified mean gestational ages of infants with and without ROP (26.9 weeks ± 1.7 weeks and 30.3 weeks ± 2.6 weeks, respectively), and mean birth weights (964.1 g ± 276.3 g and 1387.5 g ± 348.2 g, respectively). Significant differences in gestational age, birth weight, length at birth, head circumference, 1-minute and 5-minute Apgar scores, and mechanical duration ventilation and oxygen therapy were found between the groups (all P <.01). 

No significant differences in mean diffusivity (MD) or fractional anisotropy values between infants with and without ROP were noted (all P >.05). Fractional anisotropy values were significantly different between infants with and without severe ROP in the body of the corpus callosum, the right corticospinal tract, the pathway connecting the V1/V2 and V4 in the left and right hemispheres hemisphere, the pathway connecting the V1/V2 and V5/MT, and the pathway connecting the thalamus and primary somatosensory cortex. MD values were not significantly different in the severe ROP group. 

After adjusting for confounders, the parameters of other white matter pathways that showed either statistically significant or marginally significant differences in fractional anisotropy or MD values did not have a statistically significant association with either ROP or severe ROP. 

Developmental outcomes for cognitive, motor, and language functions were evaluated in 81 infants. Investigators found marginally significant differences in mean cognitive scores between infants with and without ROP, but no significant differences in mean language or motor scores. In the severe ROP group, there were no statistically significant differences in any of the developmental scores, and no statistically significant differences in the frequency of developmental delay in those with or without ROP or severe ROP. 

Multiple regression analyses were performed to examine the association between white matter pathway fractional anisotropy or MD values and Bayley Scales of Infant and Toddler Development (BSID-III) scores. In multivariate analyses inclusive of sex, gestational age, gestational age at MRI scan, BPD, sepsis, and maternal education, cognitive scores were significantly associated with fractional anisotropy values of the left corticospinal tract and middle cerebellar peduncle and MD values of the left and right corticospinal tracts, middle cerebellar peduncle, left uncinate fasciculus, and primary motor cortices, as well as left and right auditory radiation. 

Finally, the investigators compared BSID-III scores between infants with ROP treated with and without intravitreal bevacizumab therapy. Between these 2 groups, there were no significant differences in developmental scores or frequencies of developmental delay in cognitive, motor, or language functions. Significant associations were noted between intravitreal bevacizumab therapy and MD values for the pathway between the pre- and primary motor cortices in the left hemisphere, present in multiple regression analyses. 

Study limitations include challenges associated with performing MRI on infants, particularly in cases that require sedation which may pose medical risks, the short follow-up period, and the limited accuracy of language function assessment at such a young age. Visual acuity was not evaluated in this patient population. 

“Developmental outcomes were similar between preterm infants with and without ROP or severe ROP, and also between ROP infants with and without anti-vascular endothelial growth factor therapy,” according to the researchers. “Although future studies should investigate long-term developmental outcomes and white matter maturation in infants treated with anti-VEGF therapy for ROP, our study suggests a potential association between the therapy and maturation of the motor-associated white matter pathways.”


Ahn SJ, Lee JY, Lee JY, et al. Brain white matter maturation and early developmental outcomes in preterm infants with retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2021;62(2):2. doi:10.1167/iovs.62.2.2.