Published 3 December 2008, doi:10.1136/bmj.a2648
Cite this as: BMJ 2008;337:a2648

Endgames

Picture quiz

Retinopathy of prematurity

¹ Department of Optometry and Visual Science, City University, London EC1V 0HB

The figure is a wide field image taken with a RetCam (Clarity Inc, Pleasanton, CA, USA) at 39⁺⁴ weeks’ postmenstrual age from a baby born at 27⁺⁵ weeks’ gestation (birth weight 940 g). He needed prolonged ventilation for respiratory distress syndrome, and he underwent surgery for necrotising enterocolitis. Now aged 5, he is seen regularly at the eye clinic for myopia and intermittent exotropia, which his mother reports is most obvious at the end of the day.

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Questions

1 Which preterm babies are screened for retinopathy of prematurity in the United Kingdom?

2 What stage of retinopathy of prematurity does this baby have and how should he be managed?

3 What other ophthalmic sequelae are common in children born prematurely?

Answers

Short answers

1 In the UK all babies weighing less than 1501 g or born before 32 weeks’ gestation should be screened for retinopathy of prematurity.

2 This baby has stage 3 retinopathy of prematurity with "plus disease" (fig 2) and should have 360° peripheral laser treatment anterior to the lesion within 48-72 hours. The right eye is similarly affected and needs to be treated—retinopathy of prematurity is typically bilateral and symmetrical.

View larger version (92K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2 Retinopathy of prematurity pathology visible on image

 

3 Refractive errors, in particular myopia, strabismus with an unusually high rate of exotropia, amblyopia, and cerebral visual impairment.

Long answers
1 Which preterm babies should be screened?
Retinopathy of prematurity is a potentially preventable cause of blindness in children. The proportion of childhood blindness caused by retinopathy of prematurity fell from 8% between 1985 and 1990¹ to 3% in 2000.² This decrease may partly be the result of increased awareness and the implementation of combined college screening guidelines. The most recent UK guideline was published in May 2008 and provides an evidence based approach to screening and treatment. The key recommendations state that all babies of less than 32 weeks’ gestation or less than 1501 g birth weight should be screened for retinopathy of prematurity, and that all babies of less than 31 weeks’ gestation or less than 1251 g birth weight must be screened.^{3 4} This guideline is specific for the UK and inappropriate for other countries because of the geographical diversity of the disease. Guidelines from the United States^{5 6} and Canada⁷ differ slightly from one another and from UK guidelines.³ Most importantly, guidelines from countries with high development rankings should not be applied in countries with low and middle development rankings, where more mature babies are at risk of retinopathy of prematurity.^{8 9} Brazil is one of the first of such countries to publish proposed guidelines on retinopathy of prematurity.¹⁰

2 Stage and management
Retinopathy of prematurity is a disease that affects the developing neural retina and its vasculature. The retina and its blood supply develop in a centrifugal direction from the optic nerve head. By full term the neural retina has reached the ora serrata and, at their most peripheral extent, the vessels are 2 mm away from the ora serrata. However, if the baby is born early, abnormal expression of growth factors disrupts this developmental pattern. Pathological effects—largely in response to overexpression of vascular endothelial growth factor—are seen at the leading retinal edge and in the vasculature at the posterior pole.

The abnormalities at the leading retinal edge in retinopathy of prematurity are divided into five stages (box) and the position of these stages is documented according to retinal zoning (fig 3). The first three stages and a fourth stage encompassing all retinal detachments associated with retinopathy of prematurity were first described by the first meeting of the committee for the classification of retinopathy of prematurity in 1984.¹¹ The committee also introduced the term "plus disease" to describe the characteristic vascular changes of congestion and tortuosity at the posterior pole. This staging was updated in 2005 and now includes a description of an intermediate level of plus disease (preplus) and a breakdown of retinal detachments associated with retinopathy of prematurity into two distinct stages—stage 4 for partial detachments and stage 5 for total retinal detachments. The concept of a more virulent form of the disease specific to smaller more vulnerable babies, named aggressive posterior retinopathy of prematurity was also heralded—in effect, a sixth acute phase stage.¹²

The five (six) stages of retinopathy of prematurity Stage 1: Demarcation line Stage 2: Formation of three dimensional ridge Stage 3: Fibrovascular proliferation at ridge Stage 4: Partial retinal detachment macula on macula off Stage 5: Total retinal detachment (Stage 6: Aggressive posterior retinopathy of prematurity)

View larger version (31K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 3 The zones of retinopathy of prematurity. Reproduced, with permission, from the UK guideline3

 
The recommendations in the Multicentre Trial of Cryotherapy for Retinopathy of Prematurity for treating retinopathy of prematurity at "threshold" (defined as five contiguous or eight cumulative clock hours of stage 3 retinopathy of prematurity in zone I or II in the presence of plus disease) have since been replaced.¹³ After 10 years of follow-up, children treated with cryotherapy had better visual outcomes compared with controls, but 44.4% of children still had an unfavourable visual outcome.¹⁴ The Early Treatment of Retinopathy of Prematurity (ETROP) randomised trial provides evidence to support treating babies with laser at an earlier stage than threshold to improve visual outcome.¹⁵ Current UK guidelines advocate treating any stage of retinopathy of prematurity in zone 1 associated with plus disease, any zone 1 stage 3 disease with or without plus disease, and zone II stage 2 or 3 retinopathy of prematurity with plus disease. The importance of plus disease in diagnosing treatable retinopathy of prematurity has been highlighted by ETROP. The alarmingly low rates of agreement between clinicians when diagnosing plus disease^{16 17} have stimulated research into a more quantified approach to the vascular changes associated with the disease.¹⁸ A more quantified approach also lends itself to automated analysis techniques and telemedicine applications, both realistic screening and diagnostic tools for retinopathy of prematurity in the future.

3 Associated conditions
Retinopathy of prematurity is the ophthalmic condition most commonly associated with preterm birth, but these infants may have many other visual impairments.¹⁹ Prematurity predisposes to refractive errors. Babies born at term have a tendency to hypermetropia,²⁰ but the refractive error settles in the first years of life by the process of emmetropisation secondary to an increase in axial length and flattening of the lens. Preterm infants have shorter axial lengths,²¹ although preterm infants with severe retinopathy of prematurity have slightly longer axial lengths than those without the condition.²² Despite this, the eyes of children born preterm paradoxically have a tendency towards myopia, and these children are also more likely to have astigmatism and anisometropia.^{23 24 25 26} Strabismus and exotropia are also more common in infants born preterm.^{27 28 29} Preterm infants may also have visual disability as a result of neurological damage, such as ischaemic brain lesions³⁰ and intraventricular haemorrhage.³¹

Although retinopathy of prematurity is the most common ocular problem associated with prematurity, the major cause of visual disability in these children is cerebral visual impairment.

Cite this as: BMJ 2008;337:a2648

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient consent not required (patient anonymised, dead, or hypothetical).

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