Associate Professor Leo Hartley (L) and Associate Professor Yoga Kandasamy
By Helen Carter
Optometrists will see more children with retinopathy of prematurity (ROP), and premature babies are receiving eye injections usually given to AMD patients, Associate Professor Leo Hartley says.
Professor Hartley, an optometrist and GP, and neonatologist Professor Yoga Kandasamy, spoke at North Queensland Vision in Cairns in June about the sometimes controversial practice of giving anti-VEGF injections to some premature babies in Australia and overseas to try to prevent blindness.
The treatment is usually given to adults with age-related macular degeneration but Professor Hartley said the injections were being used off-label as a last resort in babies for whom the gold standard treatment of retinal laser could not slow progression of ROP.
He said the American Academy of Pediatrics recommended against routine anti-VEGF injections for premature babies with ROP and America’s Food and Drug Administration, and Australia’s Therapeutic Goods Administration considered it off-label due to risks to the developing organs of neonates.
Anti-vascular endothelial growth factor drugs block the angiogenic protein vascular endothelial growth factor, produced by cells in the retina.
Professor Hartley said anti-VEGFs crossed the blood brain barrier easily so injecting anti-VEGF into the eye meant the treatment ‘leached’ into the rest of the body and brain.
‘For adults it is not so much of a problem. Adults receiving the injections can get kidney damage as evidenced by proteinuria, as well as hypertension via the angiotensin-renin pathway in the kidneys; however, this can be monitored and managed in adults,’ he said.
‘In premature babies who are still developing, how anti-VEGFs affect the rest of the body, especially developing blood vessels in vital organs, is not fully understood.
‘ROP results from abnormal blood vessel growth in the retina which if untreated, can cause the retina to detach from the back of the eye, leading to blindness,’ Professor Hartley said.
‘In one of our studies, we postulated that if VEGF is the main driver of poorly regulated vessel growth, we would expect to see a rise in VEGF at the onset of ROP. However, we did not see any correlation between VEGF levels and ROP in our study.
‘We cannot forget the eyes at the expense of the rest of the body. Our review of studies found anti-VEGF therapy results in systemic effects on serum VEGF levels for up to two months and this could have an effect on neurodevelopmental outcome and vital organ development.
‘As mentioned, the effects both short- and long-term of this on other developing organs is currently unknown. While premature babies are still developing and we do not know the long-term systemic effects of anti-VEGFs, perhaps we shouldn’t be proceeding to use anti-VEGFs routinely.’
Another recent review of ROP treatments also discusses benefits and disadvantages of the therapy.
Royal Australian and New Zealand College of Ophthalmologists Fellow, Dr James Smith, a Paediatric Ophthalmologist at Children’s Hospital Westmead, said that in some specific situations in Australia, anti-VEGF injections were used for premature babies suffering from ROP to try to prevent them from permanently losing their vision.
‘In the most severe cases this is used as a primary treatment and in some other cases, where primary treatment with laser has proved inadequate, it is used as an adjunctive treatment. While this is an off-label use for this treatment, it is undertaken following publication in the New England Journal of Medicine of successful trial results,’ he said.
‘However, it is worth noting that there are potential side-effects, including cataract endophthalmitis and retinal detachment locally, or stroke systemically. As with all treatment decisions, the risk of any side-effects needs to be balanced against the potential positive outcomes and discussed with the patient’s parent or guardian.’
ROP increasing and eye effects
Professor Hartley said that with the westernisation of developing countries, there was a rise in the incidence of premature babies.
‘Women are also having babies later and these pregnancies are riskier and increase the chance of premature birth,’ he said. ‘This of course means there is a rise in the incidence of ROP and there will be more of these children seen by optometrists in the future. Many of these children have ophthalmic conditions linked to ROP that need attention.’
He said premature babies had higher incidences of refractive error, anisometropia and strabismus than normal birth-weight babies born at full-term.
Professor Hartley explained how ROP develops and discussed the traditional treatment using pan-retinal photocoagulation and more recently, anti-VEGFs.
‘Knowing the potential side-effects of anti-VEGFs on the developing premature babies has turned our research towards understanding how VEGF fits into the ROP puzzle as well as future possibilities, if anti-VEGFs are shown to be systemically injurious in follow-up studies,’ he said.
‘The manipulation of non-coding RNA, the puppet masters of the cascade of events leading to ROP, and the use of artificial wombs to grow babies to full term are just two possibilities.’
Professor Kandasamy discussed the future of neonatology and the use of the artificial womb.