Lotta Gränse, ophthalmologist and researcher Lund University and Skåne University Hospital has demonstrated that eye drops containing cortisone can prevent the development of the very serious eye disease ROP in infants. This has revolutionised treatment and means that the majority of children in Sweden's Southern Healthcare Region with severe ROP do not need conventional treatment under anaesthesia to avoid serious visual impairment or blindness. The study has been published in the highly ranked journal Ophthalmology.
ROP (retinopathy of prematurity) is one of the most common causes of severe visual impairment and blindness in children worldwide. Because the blood vessels in the retina are not fully developed, changes in oxygen levels after birth can disrupt normal vascular growth, which may lead to abnormal blood vessels, bleeding, scarring, retinal detachment and, in severe cases, blindness. The conventional treatment is laser therapy on the retina or administering injections of a vascular inhibitor into the eye. Both treatments entail various risks and require anaesthesia, which should preferably be avoided for premature babies.
Development of diagnostics and treatment for severe ROP
Lotta Gränse is a docent and project manager for the Retinopathy of Prematurity research team at Lund University and senior ophthalmology consultant at Skåne University Hospital. At Skåne University Hospital, she has been responsible for ROP activities since 2012 and is a unit representative for national specialised medical care relating to certain types of ROP. She is responsible for the screening of premature babies, assessing screening images received from other clinics and determining if and when treatment under anaesthesia is required. Since 2016, she has also been carrying out treatment.
It was absolutely fantastic to see how babies who previously used to get worse and undergo destructive laser surgery, now, with usually only one drop cortisone a day, sailed past that treatment and healed. It seemed inconceivable that no one had thought of introducing cortisone drops before.
"Over the past ten years, the diagnosis of ROP in the Southern Healthcare Region has been improved by using digital wide-angle photography. The technique has made it possible for us to compare images and follow the course of the disease in a way that was not possible previously," says Lotta Gränse.
In severe ROP, the eye is very inflamed and it is difficult for the pupil to dilate, but it is important to have a large pupil for the laser therapy to be as effective as possible. To facilitate treatment, Lotta Gränse began administering a dose of cortisone drops (dexamethasone) a few days before the operation. This dose was the same as that recommended in international guidelines for post-operative treatment. She then observed that the eye inflammation had subsided and when she compared the images before and during treatment, she could also see that the ROP disease had decreased. In one case, the child could even avoid laser therapy altogether.
"This sparked the idea of starting to administer a lower dose of cortisone drops at an earlier stage before the disease had progressed too far. It was absolutely fantastic to see how babies who previously used to get worse and undergo destructive laser surgery, now, with usually only one drop cortisone a day, sailed past that treatment and healed. It seemed inconceivable that no one had thought of introducing cortisone drops before."
According to Lotta Gränse, the connection may have gone unnoticed because different professional groups work in separate clinical pathways: paediatric ophthalmologists perform the screening, while retinal surgeons handle the treatment. Previously, there were also no images available during screening and treatment, which made it difficult to get an overview of the disease.
Far fewer children required treatment
Lotta Gränse first published a report on her findings from Skåne University Hospital, but in order to provide greater scientific evidence for the treatment, a national collaborative project was initiated. Lotta Gränse and her research team, along with the neonatal clinic and the Department of Statistics and Epidemiology at Skåne University Hospital, compared the results from the Southern Healthcare Region with three large screening centres in Sweden. The project included a total of 2,017 babies born before week 30 of the pregnancy who were screened for ROP during the periods 2015-2018 and 2020-2021, before and after the introduction of dexamethasone eyedeops in the the Southern Healthcare Region when diagnosis of severe ROP.
"Using data from the national quality register for ROP, SWEDROP, we compared the conventional treatment frequency of severe ROP under anaesthesia at the three screening centres with the Southern Healthcare Region."
Between 2015 and 2018, 72 per cent (23 out of 32) of babies with severe ROP required conventional treatment under anaesthetic in the Southern Healthcare Region. At the three other hospitals, the corresponding figure was 47 per cent (82 out of 175).
In 2020-2021, cortisone drops began to be administered in the Southern Healthcare Region. This led to a clear reduction in the need for conventional treatment with only 13 per cent (4 out of 32) of babies with severe ROP requiring conventional treatment. The three other hospitals continued with unchanged standard treatment and therefore serve as a control group, where 56 per cent (32 out of 57) of the babies received conventional treatment.
Further research on long-term effects
Now Lotta Gränse wants to continue her research to investigate the factors that play a role for babies who still need conventional treatment, and to study the effects of the drops in long-term follow-ups on the development of the eye and the child as a whole.
"According to international guidelines, the ROP disease is currently monitored until it becomes so severe that it must be treated with destructive or invasive treatment under anaesthesia. This new strategy, using low-dose cortisone eye drops, is an active treatment to prevent this. It makes a huge difference for the children affected and their families, but also in socio-economic terms. Cortisone drops are inexpensive, whereas surgery is very resource-intensive."
