Premature Infant and Retinopathy of Prematurity


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. [Section: 2006] [Fierson: 2018]
ROP, characterized by abnormal retinal vascularization in preterm infants, occurs in 2 phases:
  1. Inhibited vascularization leading to retinal hypoxia (~30 - 32 weeks postmenstrual age)
  2. Hypoxia-driven neovascularization (begins ~32 - 34 weeks postmenstrual age) [Chen: 2011]
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
*[Bharwani: 2008] [Carlo: 2010] [Hagadorn: 2007] [Hellström: 2009] [Kaempf: 2011] [Lad: 2009] [Löfqvist: 2006] [Löfqvist: 2009] [Noyola: 2002] [PATZ: 1952] [Seiberth: 2000]


Evaluation is completed by an ophthalmologist specialized in neonatal disorders. The pupil is dilated in order 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 [International: 2005].
An alternative approach is being investigated using digital photographic retinal images that are captured and then 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 is still forthcoming. [Quinn: 2014]
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:

Recommended Follow-Up

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 (PDF Document 100 KB).
Regardless of whether at-risk infants develop treatment-requiring ROP, pediatricians and other physicians who care for infants who have had ROP should be aware that these infants are at increased risk for other seemingly unrelated visual disorders, such as strabismus, amblyopia, high refractive errors, cataracts, and glaucoma. Ophthalmologic follow-up for these potential problems after discharge from the NICU is indicated within 4 to 6 months after discharge.


Treatment is recommended for type 1 ROP, or pre-threshold, which is aggressive. Preterm infants who are 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, visual and developmental outcomes. [Quinn: 2016] 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.


Information & Support

For Professionals

Best Evidence Statement (BESt) Screening for Retinopathy of Prematurity (PDF Document 100 KB)
Provides detailed on screening and follow-up for ROP; Cincinnati Children's Hospital Medical Center (2007).

For Parents and Patients


Retinopathy of Prematurity (NEI)
General information for patients and their families about retinopathy of prematurity (ROP); National Eye Institute.


The International Classification of Retinopathy of Prematurity Revisited (JAMA)
A revised consensus statement (2007) of an international group of retinopathy of prematurity experts.

Services for Patients & Families in Nevada (NV)

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Helpful Articles

Fierson WM.
Screening Examination of Premature Infants for Retinopathy of Prematurity.
Pediatrics. 2018;142(6). PubMed abstract

Authors & Reviewers

Initial publication: July 2015; last update/revision: January 2020
Current Authors and Reviewers:
Authors: Jennifer Goldman, MD, MRP, FAAP
Sarah Winter, MD
Authoring history
2015: first version: Jennifer Goldman, MD, MRP, FAAPA; Jeniel L. Jacobs, DNP, APRN, NNP-BCSA; Sarah Winter, MDA; Sherrily Brown, FNPA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

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Bharwani SK, Dhanireddy R.
Systemic fungal infection is associated with the development of retinopathy of prematurity in very low birth weight infants: a meta-review.
J Perinatol. 2008;28(1):61-6. PubMed abstract / Full Text

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Fierson WM.
Screening Examination of Premature Infants for Retinopathy of Prematurity.
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Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, Quintos M, Tung B.
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Hellström A, Hård AL, Engström E, Niklasson A, Andersson E, Smith L, Löfqvist C.
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Kaempf JW, Kaempf AJ, Wu Y, Stawarz M, Niemeyer J, Grunkemeier G.
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Arch Ophthalmol. 2006;124(12):1711-8. PubMed abstract / Full Text

Löfqvist C, Hansen-Pupp I, Andersson E, Holm K, Smith LE, Ley D, Hellström A.
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Ng EY, Connolly BP, McNamara JA, Regillo CD, Vander JF, Tasman W.
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Screening examination of premature infants for retinopathy of prematurity.
Pediatrics. 2006;117(2):572-6. PubMed abstract / Full Text
From the Section on Ophthalmology American Academy of Pediatrics, American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus.

Seiberth V, Linderkamp O.
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