Visuopathy of prematurity: is retinopathy just the tip of the iceberg?

Abstract

Research on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.

Retinopathy of prematurity

“…Some adverse visual outcomes in individuals born preterm are not due to ROP 55,56 . Instead, they appear to constitute a broader paradigm that includes abnormal vascularization of the retina, alterations in retinal architecture, choroidal degeneration, and abnormalities in the cortico‐visual pathway 57,58 …”

“…55,56 Instead, they appear to constitute a broader paradigm that includes abnormal vascularization of the retina, alterations in retinal architecture, choroidal degeneration, and abnormalities in the corticovisual pathway. 57,58 Although a recent meta-analysis suggested no increased risk for adverse neurodevelopmental outcomes after bevacizumab injection, 59 some large-scale follow-up studies from Canada, 60 the USA, 61 and Japan 62 suggest that infants treated with bevacizumab may have an increased risk for adverse neurodevelopmental outcomes, 60 in particular poor cognitive outcomes as indicated by a percentage of infants with a Bayley cognitive score under 85 of 58% versus 47% (odds ratio 1.7, 95% confidence interval 1.1-2.9) 61 as well as reduced mean developmental quotients, particularly pronounced in the language-social domain. 62 However, one has to keep in mind that these are data from observational studies, not from randomized trials, and that they are prone to selection bias since more infants with very severe (i.e.…”

Visual function correlates with neurodevelopment in a population cohort of school‐aged children born extremely preterm

“…Furthermore, retinal and brain pathologies in extremely preterm infants may be different expressions of neurovascular disease 7 . ROP appears to be the tip of an iceberg of a broader entity of visual problems rooted in neurovascular tissue injury of the retina and brain that we call "visuopathy of prematurity" 9 …”

“…7 ROP appears to be the tip of an iceberg of a broader entity of visual problems rooted in neurovascular tissue injury of the retina and brain that we call "visuopathy of prematurity". 9 In this exploratory study, we wanted to examine the relationship between visual acuity and contrast sensitivity and parent-reported neurodevelopmental problems, neuropsychological testing, and brain MRI in a geographically defined population of school-aged children born extremely preterm in Central Norway. We hypothesized that (1) visual function is subnormal in the whole group and lower in those with ROP, (2) levels of neurodevelopmental challenges are higher compared with average population mean scores, and (3) lower visual function is associated with atypical neurodevelopment.…”

Does prematurity “per se” cause visual deficits in preterm infants without retinopathy of prematurity?

“…It might even lead to the conclusion that it is futile to look beyond ROP in preterm infants because with the baby being born preterm the horse is already out of the barn. Infection and inflammation are one set of candidate contributors to AVO occurrence in both children with and without ROP [19]. There is plenty of room for research designed to further test this and other etiological hypotheses if we refrain from attributing to prematurity "per se" what should be attributed to causes and mechanisms associated with preterm birth.…”