Key points

Introduction

Retinopathy of prematurity (ROP) is a potentially blinding retinal vascular disease that occurs in very low birth weight (VLBW) (<1500 g) premature infants. Originally called retrolental fibroplasia (RLF), the disease was first described in 1942. In 1950, RLF was responsible for 21.5% to 41.7% of all childhood blindness. High supplemental oxygen and lower birth weight were discovered to be the major risk factors in RLF. Nevertheless, even with monitoring oxygen saturations in the 1980s, 5% of infants with ROP became totally blind. Screening for ROP, close monitoring of prethreshold disease, treatment of threshold disease with laser photoablation along with prevention of ROP and prematurity have become the foundations for preventing blindness.

Introduction

Retinopathy of prematurity (ROP) is a potentially blinding retinal vascular disease that occurs in very low birth weight (VLBW) (<1500 g) premature infants. Originally called retrolental fibroplasia (RLF), the disease was first described in 1942. In 1950, RLF was responsible for 21.5% to 41.7% of all childhood blindness. High supplemental oxygen and lower birth weight were discovered to be the major risk factors in RLF. Nevertheless, even with monitoring oxygen saturations in the 1980s, 5% of infants with ROP became totally blind. Screening for ROP, close monitoring of prethreshold disease, treatment of threshold disease with laser photoablation along with prevention of ROP and prematurity have become the foundations for preventing blindness.

Extent of the problem

According to the 2010 US census, the preterm birth rate (<37 weeks) was 11.99% of all births and the low birth weight rate (<2500 g) comprised 8.15% of all births. VLBW (<1500 g) birth rate was 1.45% and was unchanged compared with the previous year census. In 2008, 24% of VLBW infants died within the first year of life. From 1997 to 2005, 0.17% of total newborns born in the United States had some form of ROP. It is the third leading cause of childhood blindness in the United States (14%). In highly developed countries such as the United States, only the smallest, youngest babies are likely to have ROP, because of improved control of risk factors and more aggressive management of unstable infants. By comparison, in Latin America and Eastern Europe, there are higher rates of severe ROP and blindness, and the disease occurs in older and larger infants compared with the United States. In poorly developed nations, preterm infants do not survive long enough to develop ROP. In 2010, it was estimated that globally 184,700 premature infants would develop ROP, and of those, 20,000 would become blind or severely visually impaired.

Cause/contributory or risk factors

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  Risk factors:

  
  
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  Birth weight

  
  
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  Gestational age

  
  
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  Poor weight gain

  
  
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  Low cortisol concentration

  
  
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  Dopamine-resistant hypotension

  
  
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  White race

  
  
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  Birth at an outlying hospital

  
  
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  Low insulinlike growth factor binding protein 3, low insulin growth factor, and low urine vascular endothelial growth factor (VEGF)

  
  
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  Hyperglycemia

  
  
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  Insulin treatment

  
  
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  Corticosteroid treatment

  
  
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  Insufficient intake of docosahexaenoic acid

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  Associated conditions:

  
  
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  Respiratory conditions such as bronchopulmonary dysplasia

  
  
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  Fetal hemorrhage

  
  
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  Intraventricular hemorrhage

  
  
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  Blood transfusion

  
  
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  Sepsis

  
  
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  Respiratory tract colonization with Ureaplasma urealyticum

  
  
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  Patent ductus arteriosis

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  Protective conditions:

  
  
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  Hypoxia

  
  
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  Necrotizing enterocolitis

  
  
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  Hemolytic disease

  
  
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  Breast milk

  
  
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  Improved nutrition (lipids and total calories)

  
  
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  Maternal preeclampsia

Sequelae

Infants with regressed or treated ROP along with premature infants who never developed ROP should be appropriately referred to a pediatric ophthalmologist at a young age, preferably in the first 1 to 3 years of life, to evaluate for the following ophthalmic conditions related to both ROP and prematurity:

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  Blindness

  
  
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  Retinal detachment

  
  
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  Cataracts

  
  
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  Glaucoma

  
  
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  High refractive errors, including high myopia

  
  
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  Amblyopia

  
  
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  Anisometropia

  
  
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  Strabismus

  
  
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  Astigmatism

  
  
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  Nystagmus

  
  
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  Microphthalmos

  
  
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  Cortical visual impairment

  
  
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  Developmental, educational, and social challenges

Clinical assessment

Screening preterm infants for ROP should include those with birth weight of 1500 g or less or a gestational age of 30 weeks or less. In addition, infants with a birth weight between 1500 g and 2000 g or gestational age greater than 30 weeks with an unstable clinical course may be examined if they are believed by the neonatologist or pediatrician to be at risk for ROP. The initial examination is based on the infant’s age. Infants born at 24 to 27 weeks postmenstrual age should start ROP screening examinations at 31 weeks postmenstrual age. Infants born after 27 weeks of age should be screened at 4 weeks after birth.

Examinations can be performed in the hospital or as an outpatient. After pupillary dilation, an experienced ophthalmologist performs the examination with a lid speculum, scleral depressor, and binocular indirect ophthalmoscopy. Description of ROP depends on location, staging, extent, and presence of preplus or plus disease :

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  Location:

  
  
  
  
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    Zone I: radius of which subtends an angle of 30° and extends from the disk to twice the center of the macula

    
    
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    Zone II: edge of zone I to the nasal ora serrata and around to an area near the temporal equator

    
    
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    Zone III: the remaining temporal crescent anterior to zone II

  
  
  
  
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  Staging:

  
  
  
  
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    Immature: before the development of ROP

    
    
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    Stage 1: demarcation line between vascular and avascular retina

    
    
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    Stage 2: ridge (line acquires width and height)

    
    
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    Stage 3: extraretinal fibrovascular proliferation ( Fig. 1 )

    
    

    
    

    
    

    

    
    

    
    

    Zone II, stage 3 with plus.

    
    
    
    
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    Stage 4:

    
    
    
    
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      4a: extrafoveal retinal detachment

      
      
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      4b: foveal retinal detachment

    
    
    
    
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    Stage 5: total retinal detachment

  
  
  
  
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  Plus disease (see Fig. 1 ):

  
  
  
  
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    Increase in venous dilation and arteriolar tortuosity, poor pupillary dilation and vitreous haze

    
    
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    Present in at least 2 quadrants

  
  
  
  
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  Preplus: abnormal dilation and tortuosity of the posterior pole vessels (<2 quadrants)

  
  
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  Aggressive posterior ROP (AP-ROP) ( Fig. 2 )

  
  
  
  
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    Most commonly in zone I but also in zone II

    
    
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    If left untreated, progresses to stage 5

    
    
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    Can be seen on the initial examination

  
  

  
  

  
  

  
  

  
  

  AP-ROP.

  
  
  
  
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  Regression of ROP

  
  
  
  
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    Resolution without sequelae

    
    
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    Involution of the vasoproliferative phase to a fibrotic phase

    
    
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    Vascular abnormalities

    
    
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    Pigmentary changes

    
    
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    Temporal dragging of the macula

    
    
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    Traction and retinal detachment

  
  

Follow-up examinations depend on severity of the eye examination, with more severe examinations scheduled in 1 week or less and more stable examinations extended to 2 to 3 weeks. Examinations are terminated when retinal vascularization reaches zone III without previous zone I or zone II ROP, with full retinal vascularization within at least 1 disk diameter of the ora serrata, at postmenstrual age 50 weeks without previous prethreshold disease or with regression of ROP.

In general, the screening examinations are safe and effective if performed by an experienced ophthalmologist. Even although these infants can decrease their heart rate and oxygen saturations in response to the screening examinations, there are not any clinically significant systemic complications directly attributable to ROP examinations. These examinations can be made more comfortable by topical anesthetics, pacifier sucking, or sucrose.

A carefully designed protocol to ensure appropriate screening and follow-up of infants at risk is a necessary component of ROP screening programs. Not only is there a grave risk of blindness when there is a delay in screening, referral, follow-up, diagnosis, or treatment, there is also a significant medicolegal risk to the physician and responsible hospital. Evidence has shown that regional hospitals and higher-level neonatal intensive care units (NICUs) with such a protocol in place have fewer missed ROP examinations. Maintaining a rigorous and safe ROP screening program is labor intensive. The increase in premature survival rates in developing countries, combined with the lack of fewer skilled ophthalmologists who can screen in moderately developed areas in Latin America and Asia, has led to an increasing incidence of ROP blindness. New investigations into telemedicine screening to aid in these areas have shown promise. A recent study, telemedicine approaches to evaluating acute-phase ROP (E-ROP), had just been completed; however, results have not yet been published. Telemedicine involves training nonphysicians to take images with a retinal camera. The images are sent to an experienced ophthalmologist for interpretation. There is evidence that telemedicine may be more cost-effective, but binocular indirect ophthalmoscopy is the gold standard for screening ROP when there is an ophthalmologist to perform examinations. Recent studies might show that telemedicine is equally effective in diagnosing threshold disease, and this might become the standard in neonatal units that do not have a local pediatric ophthalmologist who can examine babies weekly. It is crucial that (1) all babies are tracked closely in the NICU, (2) babies are referred for immediate transfer if they have threshold disease requiring treatment, and (3) babies are referred for follow-up on discharge from the hospital. Ideally, the ophthalmologist reading the photographs should be the ophthalmologist who will follow the baby up for treatment if indicated. This practice helps expedite the process and decrease the chances for delay in transferring the infant to a center at which treatment can be performed.