Laser or anti-VEGF?

A panel discussion examined the best options for treating retinopathy of prematurity

TBC Soosan Jacob

Posted: Friday, June 1, 2018

Dr Shira Robbins examines a premature infant in the neonatal intensive care unit. Picture by Peter Durdaller

Shira L. Robbins MD

The use of anti-VEGF agents for the treatment of severe retinopathy of prematurity (ROP) appears to provide many benefits, but questions remain about the optimal regimen and longer-term follow-up issues.

Shira L. Robbins MD argued in favour of anti-VEGF therapy for ROP in a session of the World Congress of Paediatric Ophthalmology and Strabismus in Hyderabad, India. She credited Dr Helen Mintz-Hittner, director of the landmark BEAT-ROP study that first showed the value of this approach compared with conventional laser treatment in a large cohort.

The general benefits of anti-VEGF treatment include continuity of ocular development with encouragement of both short- and long-term development of the eye through progress towards normalisation of growth factors. Other benefits include better efficacy and successful treatment of more patients regardless of large areas of avascular retina. Previously, these cases of posterior disease with large avascular areas portended a strong possibility of poor outcome with traditional laser treatment.

Anti-VEGF treatment also creates a potentially larger functional and structural visual field secondary to intact peripheral retina, with continued retinal vascular development and decreased chances of high myopia, said Dr Robbins, Ratner Children’s Eye Center at the Shiley Eye Institute, University of California – San Diego.

Following anti-VEGF therapy, the macula also develops differently than in post-laser infants, resulting in more typical macular development. This leads to better structure on macular OCT configuration and better visual acuity, as shown in a study by Mohsenin et al. 2017, she reported. Avoiding laser reduces possible associated complications such as cataract, irregular pupils, acute angle-closure glaucoma, retinal dragging and detachment, microphthalmia and phthisis. Lasers can also lead to greater anterior segment changes with steeper corneal curvature, shallower AC and thicker lenses.

Sharing Dr Mintz-Hittner’s data, she reported that in Zone 1 ROP, recurrences occurred later in the intravitreal anti-VEGF group compared to lasers alone. Recurrence clinically manifests as slow advance of retinal vessels, reappearance of plus disease and extraretinal fibrovascular proliferation. Long-term risks relate to systemic problems but these remain unproven she said, adding that further follow-up is required.

However, risks of lenticular and retinal trauma and endophthalmitis do exist, as well as short-term risk of aggressive recurrence, especially with the aggressive form of posterior ROP. Recurrence is also seen in patients with prolonged hospitalisation, e.g. in patients with necrotising entero-colitis, broncho-pulmonary dysplasia, intravitreal haemorrhages, patent ductus arteriosus, low birth weight and low gestational age.

In a panel discussion, Drs Shira Robbins, Subhadra Jalali and Lingam Gopal discussed various aspects of anti-VEGF therapy including concerns of deleterious effects on the rest of the organs, the need for randomised controlled trials, the appropriate dose and other clinical issues.

Dr Gopal stated that he preferred lasers, reserving anti-VEGF treatment for cases not salvageable with laser, or for aggressive posterior ROP. He used half the adult dose of ranibizumab as it affects serum levels of VEGF minimally. He also spaced injections between the two eyes to decrease both total cumulative dose and risk of infection.

Dr Robbins preferred bevacizumab for treating very posterior disease as the amount of salvaged or usable retina is typically more after treatment as compared to initial laser treatments that often have poor structural and functional outcomes. She phrased this as “buying more retina real estate for an infant”. She suggested that the dose could differ between initial treatment and treatment of recurrence and preferred simultaneous injections for bilateral disease.

Dr Jalali preferred to use one-third the adult dose of bevacizumab, as it circulated in serum for longer, thus treating disease for longer periods with less recurrence.

Discussing long-term safety issues of intravitreal injections, Dr Robbins noted that she had not seen any case report to date reporting any physical malformation or other organ system damage secondary to treatment. Larger studies showed contrasting reports, with one study showing effect on neurodevelopment, while the other did not show any. Panellists noted some of these babies would have neurodevelopmental disease secondary to the natural course of prematurity itself, and it is sometimes difficult to determine if any effects are secondary to treatment or prematurity.

There was universal agreement that parental counselling was important to maintaining a balanced representation of information regarding benefits and possible side-effects, per available scientific evidence. It is also important to stress to parents the need for close and diligent follow-up. Parents in the US also need to know that anti-VEGF treatment of ROP is not yet FDA approved.

During the adjusted age of 45-55 weeks, close follow-up was recommended every week in the active phase, as that is when most recurrences happen. Longer follow-up is required as recurrences have been reported even later than with laser treatment. The subtlety of recurrences and possibility of their being missed in the absence of angiography, the importance of careful examination, and issues that may arise with repeated exposure to general anaesthesia are also factors to consider in ROP.

Shira L. Robbins: