New criteria for examining premature infants for retinopathy of prematurity (ROP) have been found to be more sensitive and specific than current screening guidelines.1 The study group known as G-ROP reaffirmed that the new criteria are 100% sensitive for predicting type 1 ROP. Moreover, the new guidelines have the potential to reduce the number of infants receiving examinations by a third.
The new screening criteria have both clinical and cost-saving implications. Fewer at-risk babies will have to endure stressful retinal examinations in the neonatal ICU, and those who would benefit from an examination are less likely to slip through the cracks.
“We were happy that the criteria maintained such high sensitivity,” said study group chair Gil Binenbaum, MD, MSCE, at the Children’s Hospital of Philadelphia. “Even though they were developed using data from a very large cohort, there was still a chance that some overfitting could have occurred or that changes in neonatal care, such as oxygen saturation targets, may have resulted in changes in the characteristics of infants who developed severe ROP. Fortunately, the G-ROP criteria still performed well.”
ROP. The now validated G-ROP criteria include measures of slow growth as well as birth weight and gestational age.
Expanding the criteria to improve screening. Currently recommended guidelines are based on birth weight (BW) of less than 1,501 g or a gestational age (GA) of 30 weeks or less.
The new G-ROP guidelines use six criteria, any one of which leads to an examination for ROP. These criteria include a BW of less than 1,051 g; a GA of less than 28 weeks; three measures of slow postnatal weight gain; or the presence of hydrocephalus.
The postnatal weight gain measures capture infants with higher BW and older GA who develop type 1 ROP. Weight gain is a proposed surrogate measure for factors that result in decreased VEGF activity and poor retinal vessel development.
Generalizability of the G-ROP criteria. The validation study applied the G-ROP criteria to a new cohort of premature babies (N = 3,981), who were examined between 2015-2017 at 25 of the original G-ROP hospitals and 16 new hospitals in the United States and Canada.
In the current study, the criteria predicted 219 of 219 cases of type 1 ROP (100% sensitivity). And the percentage of infants undergoing exams fell by 35.6% (n = 1,418). In a pooled cohort of 11,463 infants from this study and an earlier cohort, the criteria predicted 677 of 677 cases of type 1 ROP (100% sensitivity) and yielded a 32.5% reduction in examinations (n = 3,730).
A caveat. The validation study applies only to countries with highly developed neonatal care systems. It is not generalizable to countries in which excessive oxygen supplementation is the primary cause of ROP and postnatal weight gain is not reliably predictive of ROP. Dr. Binenbaum said that each new setting will require separate validation.
Toward a new standard. The case for adopting a new set of national guidelines is strong, Dr. Binenbaum said. In the pooled cohort analysis, for example, currently recommended guidelines pre-dicted 674 of 677 type 1 cases (99.6% sensitivity), compared to 100% sen-sitivity screening with the newer G-ROP criteria.
“Even a 0.4% decrease in sensitivity is not acceptable,” Dr. Binenbaum said, as this represents about 25 babies a year nationally being missed and possibly going blind.
“If the difference were reversed and the G-ROP criteria had the slightly lower sensitivity, there would be no chance anyone would use them to decide who to examine. But the situation is not reversed. So, the argument to keep using the current criteria is not a strong one, because the G-ROP criteria are actually more sensitive,” he said.
“With validation, we now have criteria with higher sensitivity and much greater specificity than the current guidelines, so we think it is appropriate to use these criteria for screening decisions.”
1 Binenbaum G et al. JAMA Ophthalmol. Published online Nov. 14, 2019.
Relevant financial disclosures—Dr. Binenbaum: None. This study was funded by the NIH and by an endowed chair at the Children’s Hospital of Philadelphia.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Bharti None.
Dr. Binenbaum Luminopia: C,O; NEI: S; Natus Medical: L; X Biomedical: O,P.
Dr. Digre None.
Dr. Ozudogru None.
Dr. Yoon Alcon: C,L; Allergan: C,L,S; Bayer Pharmaceuticals: C,L,S; Boehringer Ingelheim: C.
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||Employed by a commercial company.
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||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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