The Academy finds no neurodevelopmental difference between anti-VEGF and laser for ROP

Design

American Academy of Ophthalmology systematic evidence assessment with level-of-evidence ratings

Population

26 studies of infants treated for retinopathy of prematurity 2006 to 2022 across 39 countries

Primary outcome

neurodevelopmental outcomes after intravitreal anti-VEGF versus laser photocoagulation

Effect

20 of 26 studies including all 3 randomised trials found no significant difference; 4 favoured laser, 2 favoured anti-VEGF; no difference in IQ in the 5 studies testing beyond age 4

The question of whether intravitreal anti-VEGF harms the developing brain has shadowed retinopathy of prematurity treatment since bevacizumab entered use — serum VEGF suppression is measurable after intravitreal injection, and the plausibility has been enough to make some units hesitate. An American Academy of Ophthalmology panel searched to December 2025 and included 26 studies covering infants treated between 2006 and 2022 across 39 countries.

Four articles reporting three randomised trials were rated level II; 22 comparative cohorts were level III. There was no level I evidence. Twenty of the 26 studies, including all the randomised trials, found no statistically significant difference in neurodevelopmental outcomes. Four found worse outcomes with intravitreal bevacizumab and two found worse outcomes with laser. Only five studies tested intelligence quotient beyond four years of age, and none of those found a difference.

The panel's own caveat is the important one: no study was powered for neurodevelopmental outcomes or to detect small differences. Half the studies used the Bayley Scales and 54 per cent assessed before 24 months, which is early for a developmental signal in this population. So the honest reading is an absence of demonstrated harm rather than a demonstration of safety — but that absence, across 26 studies and 39 countries, is enough to remove neurodevelopment as the deciding factor when choosing between them.

• Choose between anti-VEGF and laser on retinal indication, zone and follow-up feasibility, not on neurodevelopmental fear
• Tell parents what the evidence is: no demonstrated difference, no trial powered to find a small one
• Where anti-VEGF is used, guarantee the long follow-up it requires before choosing it
• Note the outcome evidence is mostly under 24 months — later assessment is where the gap remains
• Record which agent was used; the four studies favouring laser all involved bevacizumab

Why it matters

It removes the main reason units have hesitated over anti-VEGF, in a disease where the choice often comes down to follow-up capacity.

Don't overread it

No level I evidence and no study powered for neurodevelopment — this is absence of demonstrated harm, not established equivalence.

The statistics, in plain English

'No significant difference' in studies that were never powered to detect one is weak evidence of equivalence, not strong evidence. What raises confidence here is consistency: 20 of 26 studies null, and the six that were not point in both directions, which is the pattern you expect from noise rather than a real effect.

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