According to the National Eye Institute, about 15,000 infants develop retinopathy of prematurity (ROP) annually in the United States. Of these infants, about 520 become legally blind every year. ROP has increased in prevalence as advances in medical care have increased the survival of extremely premature infants. All infants with a birth weight of ≤1500 g or a gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or a gestational age of >30 weeks who are believed by their attending pediatrician or neonatologist to be at risk for ROP should be screened for ROP. [Fierson: 2018]

Other Names

Phases of ROP
ROP, characterized by abnormal retinal vascularization in preterm infants, occurs in 2 phases:

Risk factors for ROP
Of the 50 identified risk factors for ROP, prematurity is primary. *Other risk factors include:

• Low-birth weight
• Greater than a week of assisted ventilation
• Surfactant administration
• Large blood transfusion volume
• Illness acuity
• Hyperglycemia
• Insulin administration
• Sepsis
• Blood gas fluctuation
• Intraventricular hemorrhage
• Bronchopulmonary dysplasia
• Fungal infection
• Early erythropoietin administration
• High arterial oxygen tension
• Slow longitudinal growth
• Low insulin-like growth factor binding protein 1 and 3

Evaluation is completed by an ophthalmologist specialized in neonatal disorders. The pupil is dilated to visualize the retina and vitreous by indirect ophthalmoscope examination. The ophthalmologist should have knowledge and experience in accurately identifying the location and sequential retinal changes of ROP. The findings should be recorded using the International Classification of ROP Revisited at [Chiang: 2021].

An alternative approach is being investigated using digital photographic retinal images sent for review and interpretation. The ophthalmologists who read these images should have the same clinical expertise in ROP as the bedside examiners, plus expertise in reading the digital images. The outcome of comparisons between large-scale digital retinal imaging and direct ophthalmoscopic ROP screenings shows promise. [Wang: 2022]

Some neonatal centers are using this new technology. It is recommended that these centers should, at minimum, use the timing for screening as recommended in guidelines and have the ability to obtain bedside examinations when the digital recording results are ambiguous, either by having the ophthalmologist come to the bedside or transferring the patient to a facility that provides this exam. [Quinn: 2014]

The classification of retinal findings dictates the follow-up exams. These are described in [Chiang: 2021].

Initial ROP screening should be completed at 32 weeks postmenstrual age or 5 weeks postnatal age, whichever comes second. Follow-up assessments are based on initial findings.

See Table 1: Schedule for ROP Screening Frequency or Treatment Based on Examination Findings in Best Evidence Statement (BESt) Screening for Retinopathy of Prematurity ( 100 KB).

Co-occurring Conditions

Treatment is recommended for type 1 ROP, or pre-threshold, which is aggressive. Preterm infants not treated for stage 3+ ROP (especially when in zone 1) have poor visual outcomes. [Cryotherapy: 2002] Early treatment for type I ROP is recommended for the best outcomes. [Early: 2003] [Good: 2005]

Type 1 ROP is defined as follows: [Good: 2005]

• Any stage (less than threshold) ROP in zone 1
• Stage 2 with plus disease in zone 2
• Stage 3 without plus disease in zone 2
• Stage 3 with plus disease in zone 2, but fewer clock hours than threshold

Treatment of ROP in the United States typically involves diode laser photocoagulation. Cryotherapy was the initial form of treatment and is still performed in developing countries. Laser photocoagulation-treated eyes had 5.2 times the visual improvement of cryotherapy-treated eyes. However, laser therapy also can cause complications or adverse outcomes; in 1 study, 2 of 23 laser-treated eyes (8.6%) advanced to stage 5 ROP. [Ng: 2002] The follow-up evaluation excluded infants who had had retinal detachment.

New treatments for ROP that focus on decreasing VEGF, erythropoietin levels, or IGF-1 targeting supplements are in the exploratory stages. A promising new treatment is bevacizumab or other anti-VEGF injections. There are unanswered questions with this therapy about timing, safety, and visual and developmental outcomes. [Hartnett: 2020]

There might be less myopic progression with this therapy than with laser therapy, but long-term outcomes are lacking. [Araz-Ersan: 2015] Follow-up of infants treated with these agents may be longer due to the possibility of late reactivation of proliferative disease.