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Correspondence to:
W V Good
Smith-Kettlewell Eye Research Institute, 2318 Fillmore Street, San Francisco, CA 94115, USA; Good@Ski.org
Each time it appears to have been eliminated, it resurfaces
Keywords: threshold retinopathy; low birthweight infants; renal insufficiency; morbidity
Old Deuteronomy’s lived a long time;
He’s a Cat who has lived many lives in succession.
He was famous in proverb and famous in rhyme
A long while before Queen Victoria’s accession.
Old Deuteronomy’s buried nine wives
And more—I am tempted to say, ninety-nine;
And his numerous progeny prospers and thrives
And the village is proud of him in his decline.
At the sight of that placid and bland physiognomy,
When he sits in the sun on the vicarage wall,
The Oldest Inhabitant croaks: "Well, of all . . .
Things. . . Can it be . . . really! . . .
No!. . . Yes!. . .
Ho! hi!
Oh, my eye!
My mind may be wandering, but I confess
I believe it is Old Deuteronomy!"
From TS Eliot’s: Old Possum’s Book of Practical Cats
Life is bracketed by two turbulent periods: birth and death. At both ends, the medical field struggles to expand the lifespan, to promote viability in increasingly premature infants and increasingly aged populations. At the limits of viability there is a price to pay to sustain life. Statistics on viability in preterm infants show that many more low birthweight infants survive, but with substantial morbidity.1 The same is true at the other end of the life spectrum. Most medical costs and morbidities occur during the final days and weeks of life.
In the United States, the premature birth rate for infants born at less than 37 weeks gestational age has increased in the past several years.2 Smaller infants who previously would have succumbed to prematurity now survive. Morbidity has not declined. Neurodevelopmental damage, chronic lung disease, liver and heart disease remain important problems. Recent evidence suggests that many low birthweight infants suffer CNS damage, at least when brain volume is assessed.3 Despite wonderful advances in our ability to sustain life, too many premature infants graduate from the nursery with significant and often permanent medical problems.
In this issue of the BJO (p 239) Allegaert and colleagues from the EpiBel Study Group give us some insight into the risk of severe retinopathy of prematurity (ROP) in the youngest of survivors—those born at gestational ages 26 weeks. A lively debate has erupted over the past decade as to whether ROP remains a significant healthcare problem, at least in western countries. Some studies suggest that the incidence of ROP has been reduced,4 but not all agree that this is the case.5 The argument goes something like this. Children born 15 years ago were managed differently and therefore cannot rightly be compared to current day infants. Neonatal advances may have reduced the incidence of ROP. Laser treatment has replaced cryoablation and is more effective. Therefore we don’t see as much ROP, and severe cases of ROP are managed in ways that dramatically improve structural and functional outcomes.
The answer to the debate about the significance and modern incidence of ROP will be unknown until larger scale studies are completed,6 but the findings from the EpiBel Group suggest that ROP remains an important problem, at least in the youngest gestational age infants. The EpiBel study found threshold ROP in 19.8% of infants born between 22 and 26 weeks gestational age, and severe ROP (stage 3) in 25.5%. It is difficult to compare these findings to other studies, since other studies have used different criteria for study entry (for example, 1250 g), but the risk of severe ROP in the EpiBel Study is high by any standard. The risk is particularly high at the limit of viability. Ineluctably, ROP will remain a significant problem as smaller infants survive, because ROP is a disease of the smallest and youngest; those on the edge of life.
For argument’s sake, taking the position that ROP is curable with laser or cryotherapy, there might be no reason for concern, despite the findings reported in this issue. This argument ignores the important findings from the CRYO-ROP study, that ocular morbidity is significant in infants with threshold ROP. Visual acuity is frequently worse than 6/12 in infants with threshold ROP,7 and myopia, amblyopia, and strabismus are common. Also overlooked in this debate is the risk of cerebral (cortical) visual impairment, a problem which also often resides on the margins of viability.
This report from the EpiBel Group demonstrates a new finding, that renal insufficiency is associated with ROP. While the significance of this finding is unclear, it demonstrates again that the smallest and sickest infants are most likely to develop significant ROP. Another intriguing finding is the association between CRIB and Apgar scores and significant ROP. These scores could identify infants at risk for ophthalmic morbidity, although a prospective study of this issue seems advisable before drawing this conclusion. To the extent that Apgar and CRIB scores can be modified, the incidence and severity of ROP and other diseases of preterm infants might be reduced. On the other hand, these scores could simply be markers for the sickest, smallest, and youngest infants.
The authors also remind us that infants with severe ROP usually sustain damage to other organ systems. Threshold ROP was the sole marker for morbidity at discharge in only 8% of infants in this study. This finding is familiar to paediatricians and ophthalmologists who care for children with advanced ROP. These children and their caregivers face complicated challenges caused by ophthalmic and neurological morbidity.
Is ROP a disease of the past? As long as infants survive on the margins of viability it is not. ROP has been declared dead on many previous occasions, only to be resurrected as viability at the margins of life improves. ROP is like the cat with nine lives. Each time it appears to have been eliminated, it resurfaces. We should thank Allegaert and colleagues for their important report, which reminds us of the limitations we face as physicians involved in the care of the youngest, most fragile, infants.
REFERENCES
Harper RG, Rehman KU, Sia C, et al. Neonatal outcome of infants born at 500 to 800 grams from 1990 through 1998 in a tertiary care center. J Perinatol 2002;22:555–62.
Goldenberg RL, Jobe AH. Prospects for research in reproductive health and birth outcomes. JAMA 2001;285:633–9.
Peterson BS, Anderson AW, Ehrenkranz R, et al. Regional brain volumes and their later neurodevelopmental correlates in term and preterm infants. Pediatrics 2003;111:939–48.
Bullard SR, Donahue SP, Feman SS, et al. The decreasing incidence and severity of retinopathy of prematurity. J AAPOS 1999;3:46–52.
Termote J, Schalij-Delfos NE, Donders AR, et al. The incidence of visually impaired children with retinopathy of prematurity and their concomitant disabilities. J AAPOS 2003;7:131–6.
Good WV, Hardy RJ. The Multicenter Study of Early Treatment for Retinopathy of Prematurity (ETROP). Ophthalmology 2001;108:1013–14.
Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Ophthalmological outcomes at 10 years. Arch Ophthalmol 2001;119:1110–18.