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The Eyes Have it – Time to Examine Pain Management for ROP :

June 18, 2018

Their work is timely and important: the reported rate of ROP is at least 15% among premature infants and appears to be rising, with protocols absolutely mandating screening for all infants born at a gestational age of <30 weeks.

In a recently released article in Pediatrics, Dr. Timothy Disher and colleagues conducted a systematic review and meta-analysis (10.1542/peds.2018-0401) of randomized trials of pain-relieving interventions for premature infants undergoing exams to detect or treat ROP (retinopathy of prematurity). Their work is timely and important: the reported rate of ROP is at least 15% among premature infants and appears to be rising, with protocols absolutely mandating screening for all infants born at a gestational age of <30 weeks.1,2 In ROP disease, risk of blindness is meaningfully increased without treatment, and screening identifies those with disease. Although there is clear agreement about the need for screening, eye exams, which often must be repeated multiple times and even weekly, have long been recognized as extremely painful for the infant. Shorter term effects of painful eye exams include clinically significant increases in apneic events in the 24-28 hours following an ROP examination.3 Longer term effects of repeated procedural pain in preterm infants are likely underestimated and mainly unknown, but there is growing evidence of their impact: Valeri and colleagues reported a higher number of painful procedures in infants of gestational age <29 weeks was associated with poorer growth, “poor quality of cognitive and motor development at 1 year of age,” and cortical changes at age 7 years.4 While this field of study is in its infancy, pain management for humanitarian and ethical reasons alone is sufficient cause to pursue best practices and optimal pain treatment.

A total of 29 studies were included in this review. Clinicians may find it helpful to begin by reading Appendix 2, Supplementary eTable 2.1, which describes all of the many interventions that were used in the reviewed studies.  The interventions are grouped by those that included anesthetic eye drops versus those that did not. The range of interventions trialed included sweet taste, expressed breastmilk, rocking, singing, non-nutritive sucking, swaddling, and acetaminophen.  Following the approach of a recent Cochrane review, the primary outcome included one pain score during the procedure (pain reactivity) and one after the procedure (pain regulation); all pain scores were converted to the validated Premature Infant Pain Profile (PIPP) which was most frequently used to measure ROP-procedure related pain.

Two points stood out in my mind. One is that despite evidence that multi-sensory pain treatments appear to have an impact, there was no treatment that worked completely.  In fact, worrisomely, almost 2/3 of trial arms had a mean PIPP score >12 (a PIPP score of 7-12 is mild pain, and >12 represents moderate to severe pain). Thus even among infants who were enrolled in trials to treat pain, most were experiencing severe pain. Second, the authors found clues in several studies that avoiding speculum use may be an important pain-mitigating intervention, but the barrier to change is worry about missed findings. Are there technical procedural changes that can be envisioned here that could make specula obsolete?  The review on infant pain of Dr. Disher and colleagues is thought-provoking and touches a raw nerve for me. This area is a huge missed opportunity at present, and I agree with the authors that research exploring new and different approaches is urgently needed. 


  1. Owen LA, Morrison MA, Hoffman RO, Yoder BA, DeAngelis MM (2017) Retinopathy of prematurity: A comprehensive risk analysis for prevention and prediction of disease. PLoS ONE 12(2): e0171467.
  2. Jefferies AL, Canadian Paediatric Society, Fetus and Newborn Committee. Retinopathy of prematurity: An update on screening and management. Paediatrics & Child Health. 2016;21(2):101-104.
  3. Mitchell AJ, Green A, Jeffs DA, Roberson PK. Physiologic Effects of Retinopathy of Prematurity Screening Examinations. Advances in neonatal care : official journal of the National Association of Neonatal Nurses. 2011;11(4):291-297. doi:10.1097/ANC.0b013e318225a332.
  4. Valeri BO, Holsti L, Linhares MBMM. Neonatal Pain and Developmental Outcomes in Children Born Preterm: A Systematic Review. Clin J Pain. 2015;31(4):355-362.
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