For ophthalmologists, the long-term imprint of preterm birth is becoming increasingly relevant as survival rates of extremely preterm infants continue to rise. Yet a central question remains: how does early disruption of retinal vascular development manifest decades later — especially in individuals who never had diagnosed or treated retinopathy of prematurity (ROP)?
Now, new research from Finland and Norway has taken data from the Helsinki Study of Very Low Birth Weight Adults (HeSVA) to provide the clearest picture to date of this “silent legacy,” revealing persistent vascular anomalies into adulthood—even in eyes with normal vision.
In this Retina-published birth-cohort analysis of 64 adults born preterm with very low birth weight and 81 term-born controls, participants underwent detailed optical coherence tomography (OCT), OCT angiography (OCTA), and ultra-widefield imaging at a mean age of 38 years. None had received ROP treatment at birth, and neonatal retinal status had not been routinely documented — making the findings especially relevant for understanding the natural history of preterm retinal vascularization.
One of the most striking findings was the frequency of abnormal foveal avascular zone (FAZ) morphology. Over half of VLBW eyes (57%) had FAZ areas below the fifth percentile of controls, while 14% had a completely vascularized fovea. These abnormalities correlated strongly with macular developmental arrest (MDA) — present in 47% of VLBW eyes — and yet visual acuity remained excellent across the cohort, underscoring the dissociation between structural immaturity and functional outcome.
Ultra-widefield imaging revealed that 23% of VLBW eyes had persistent avascular retina (PAR). But importantly, these eyes showed no degenerative complications. Subtle regressed-ROP-like features — including temporal notching, demarcation remnants, or vascular tortuosity — were present in around 20% of VLBW eyes, particularly among those with MDA or extremely preterm birth.
An intriguing and clinically relevant association emerged: hypertension in adulthood increased the odds of PAR nearly fourfold. This suggests that cardiovascular risk factors may amplify early microvascular vulnerability — a point reinforced by the authors’ broader cardiometabolic assessment.
The study findings challenge the binary assumption that eyes without clinically apparent ROP in infancy necessarily follow a “normal” developmental trajectory. Instead, preterm birth appears to imprint a spectrum of stable, non-progressive vascular variants that persist well into adulthood.
This matters for several reasons. First, clinicians interpreting OCT/OCTA in adults must recognize that a small or absent FAZ, foveal ectopia, or mild peripheral avascularity could represent benign developmental sequelae — not pathology. Second, as anti-VEGF therapy for ROP becomes more widespread, understanding the baseline natural history of PAR is crucial for differentiating treatment-related anomalies from preterm-related ones.
For the ophthalmologist, this study highlights a key message: the retina remembers prematurity, even when vision is preserved and ROP was never diagnosed. Awareness of these characteristic patterns — central and peripheral — will improve interpretation, reduce unnecessary concern, and prompt targeted monitoring where appropriate. As survival of extremely preterm infants continues to rise, these developmental footprints will become increasingly visible in the clinic.
