Increased incidence of severe retinopathy of prematurity following a new national guideline
Editor,
The NEDROP-study, a national inventory on Retinopathy of Prematurity (ROP) in the Netherlands (2009), showed that early treatment criteria for ROP (ETROP) were not yet widely implemented1, 2.
ROP was found in 19.2% of which 5.2% required treatment and 1.8% developed an end-stage ROP (stage 4 or 5). Subsequently, a new ROP- guideline was introduced in 2013 emphasizing the use of ETROP-criteria3. To investigate the influence of the new guideline on incidence of severe ROP and
outcome of ROP-treatment, a retrospective investigation was conducted using anonymized data of infants treated in three Dutch teaching hospitals between 2010 and 2016. In total, 57 subjects were identified and divided into group A (A): 16 infants (32 eyes) treated from January 1st 2010-April 1st
2013 and group B (B): 41 infants (79 eyes), from April 1st 2013-July 1st 2016. After correction for the
duration of inclusion, a 2.7-fold increase in ROP-treatments was found. The groups were comparable regarding median (inter quartile range) gestational age (A: 25.2 (1.4), B:26.2 (2.1) weeks, p=0.204), median birth weight (A: 715 (184) and B: 730 (205) grams, p=0.972), neonatal interventions and comorbidities associated with ROP (table 1). Time and stage of ROP at first detection and treatment decision did not differ significantly between the groups, with the exception ofmedian post
menstrual age (PMA) at treatment decision being higher in B than in A (p=0.025, table 1). In A, ROP recurred and required retreatment with laser in two eyes in two infants, vs. 8 eyes in five infants in B (p=0.429). Apart from one patient (B) developing stage 5 ROP unilaterally, all infants had a
favourable anatomical outcome at median follow-up age of 42 (33) (A) and 18 (12) (B) months. Conceivably explaining the difference in PMA at treatment decision was the adoption of higher oxygen saturation target levels during the first phase of ROP following a meta-analysis on optimal oxygenation of extremely preterm infants, applied in 2 of the 3 hospitals from 2014 onwards (NeOProM)4. Considering the two-phased ROP-pathogenesis, the first (vaso-obliterative) phase is
extra-uterine environment due to higher oxygen saturation levels can lead to its decrease during the first weeks of life. Low VEGF-levels suppress the impulse for vascular outgrowth and moreover, cause obliteration of yet formed vessels. As the metabolic activity of the maturing neuroretina increases, oxygen deficit due to vascular incompetence leads to areas of hypoxia increasing VEGF-release. This in turn promotes the second, vaso-proliferative phase, defined by emerging neovascularisations on the verge of the vascularised and avascularised retina, forming the most important risk factor for permanent visual impairment due to retinal detachment. We hypothesize that higher oxygen targets in phase 1 in group B resulted in delayed onset of phase 2 due to a lag in VEGF-release. Another reason for the increase in ROP-treatments could be the adoption of ETROP-criteria, advising treatment in earlier ROP-stages. In A, ROP-stage>3 was found in 73.3%% vs. 64.9% in B (p=0.555), carefully suggesting a small trend towards better adherence to the new treatment criteria.
Nevertheless, our cohort represents a subgroup of treated infants. For a more conclusive statement on the influence of our new guideline, extension to a national cohort is necessary. To conclude, more infants were treated for ROP since the adoption of the new guideline. Better adherence to the ETROP-criteria can partly explain this increase and changes in oxygen regimen presumably
postponed the age at treatment decision.
1. van Sorge AJ et al. Outcome and quality of screening in a nationwide survey on retinopathy of prematurity in The Netherlands. The British journal of ophthalmology 2014; 98:1056-1060. 2. Good WV. Final results of the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc 2004; 102:233-248; discussion 248-250.
3. van Sorge AJ et al. Nationwide inventory of risk factors for retinopathy of prematurity in the Netherlands. The Journal of pediatrics 2014; 164:494-498.e491.
