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Retinopathy of prematurity

Increasing rates of ROP and new treatments call for new guidelines

Roibeard O’hEineachain

Posted: Sunday, September 1, 2019

Ms Patricia Logan (left) pictured with Ms Claire Hartnett, Consultant Ophthalmic Surgeon, Temple Street Children’s University Hospital, Dublin at the Annual Conference of the Irish College of Ophthalmologists at the Galway Bay Hotel, Salthill, Ireland

As care of pre-term infants improves the incidence of retinopathy of prematurity (ROP) is rising, and as new treatments become available new guidelines are necessary, said Claire Hartnett MD, Temple Street Children’s University Hospital, Dublin, Ireland.

“ROP is a potentially blinding condition. Worldwide, in 2010 an estimated 53,000 infants required ROP treatment and 20,000 infants became blind or severely sight-impaired because of the disease. Two-thirds of those infants suffering sight loss live in middle-income countries,” Dr Hartnett told the Annual Conference of the Irish College of Ophthalmologists in Galway Ireland.

She noted that in high-income countries, the incidence of blindness from ROP is 3-to-13%. The rate is rising because more infants are surviving when born at gestational ages as low as 23 weeks, with birth weights as low as 600g. Infants born at that age are more likely to develop posterior ROP and a more aggressive disease.

Meanwhile, in middle-income countries, increased survival of profoundly premature infants has led to high rates of ROP because the neonatal intensive care units (NICUs) in those regions often lack sophisticated technology for monitoring oxygen delivery.

WHEN TO TREAT, HOW TO TREAT
The Royal College of Ophthalmology established guidelines in 2008 regarding when treatment should be considered and when it is unequivocally indicated. They advise that treatment is indicated in any ROP in zone I with plus disease, stage 3 ROP in zone I with or without plus disease and in zone II stage 3 with plus disease. Treatment should be considered in eyes with stage 2 ROP in zone II, although studies have shown that around half of eyes in this category of ROP will go on to show regression of the condition without any treatment.

The current guidelines predate the evidence-based use of bevacizumab and other anti-VEGF agents and therefore do not include it in their protocol. They recommend transpupillary diode laser therapy as first-line therapy and argon laser as second-line therapy.

Introduced in the 1990s, laser treatment provides a predictable regression pattern and in almost all eyes treatment will either succeed or fail within nine weeks. Failure rates are especially low in specialised treatment centres. However, laser treatment is difficult to apply in eyes with media opacities. It also requires the co-ordination of a multi-disciplinary team. Moreover, the treatment causes permanent loss of the peripheral visual field and often induces clinically significant myopia.

ADVENT OF ANTI-VEGF
Since the Royal College of Ophthalmology published their guidelines in 2008, the results of the BEAT-ROP study have demonstrated that intravitreal injection of bevacizumab produced significantly better outcomes in eyes with stage 3 ROP disease in zone 1 but not zone II. However, there was a 4% risk of delayed recurrence at a mean 16 weeks’ follow-up (Mintz-Hittner et al N Engl J Med 2011; 364:603-615), Dr Hartnett said.

Intravitreal anti-VEGF agents have several practical advantages over laser treatment, she noted. They do not require intubation, they are easy to administer and the agents are readily available. In addition, they provide a rapid regression of neovascularisation. They also allow for further non-pathological retinal vascularisation, thereby preserving the peripheral visual field.

Anti-VEGF treatment can be a better option than laser treatment in eyes with ROP in a number of circumstances, Dr Hartnett said. First, there are eyes with stage 3 zone I disease. Other indications include eyes where poor fundus visualisation precludes laser treatment and cases where an infant is unstable and the anaesthetic risk is too high.

However, anti-VEGF may be contraindicated in infants whose parents will be unlikely to return for the frequent follow-up visits required because of the risk of early and late reactivation. Other potential anti-VEGF sequelae include persistent vascular abnormalities. They, in turn, can lead to contraction of the retinal fibrovascular membrane resulting in circumferential and prepapillary types of retinal detachment.

An unanswered question is the effect of systemic exposure of anti-VEGF agents in pre-term infants. The agents persist systemically for several weeks with demonstrable VEGF inhibition. She noted that VEGF is important in organogenesis and microvascular maintenance. In foetal development it plays a critical role in lung maturation, cardiac, renal and pancreatic development, bone growth and neurogenesis.

Claire Hartnett: drchartnett@gmail.com