Premature Infant and Retinopathy of Prematurity

Diagnosis and follow-up for infants with retinopathy

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

ROP (Retinopathy of Prematurity)

Key Points

Phases of ROP
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]

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
*[Bharwani: 2008] [Carlo: 2010] [Hagadorn: 2007] [Hellström: 2009] [Kaempf: 2011] [Lad: 2009] [Löfqvist: 2006] [Noyola: 2002] [Seiberth: 2000]


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].

Screening & Diagnostic Testing

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).

Co-occurring Conditions

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 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.


Information & Support

Related Portal Content

For Professionals

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)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

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: March 2024
Current Authors and Reviewers:
Author: Sarah Winter, MD
Reviewer: Griffin J Jardine, MD
Authoring history
2020: update: Jennifer Goldman, MD, MRP, FAAPA; Sarah Winter, MDA
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

Araz-Ersan B, Kir N, Tuncer S, Aydinoglu-Candan O, Yildiz-Inec D, Akdogan B, Ekici B, Demirel A, Ozmen M.
Preliminary anatomical and neurodevelopmental outcomes of intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity.
Curr Eye Res. 2015;40(6):585-91. PubMed abstract

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

Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz ID 3rd, Piazza AJ, Sánchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD.
Target ranges of oxygen saturation in extremely preterm infants.
N Engl J Med. 2010;362(21):1959-69. PubMed abstract / Full Text

Chen J, Stahl A, Hellstrom A, Smith LE.
Current update on retinopathy of prematurity: screening and treatment.
Curr Opin Pediatr. 2011;23(2):173-8. PubMed abstract / Full Text

Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Paul Chan RV, Berrocal A, Binenbaum G, Blair M, Peter Campbell J, Capone A Jr, Chen Y, Dai S, Ells A, Fleck BW, Good WV, Elizabeth Hartnett M, Holmstrom G, Kusaka S, Kychenthal A, Lepore D, Lorenz B, Martinez-Castellanos MA, Özdek Ş, Ademola-Popoola D, Reynolds JD, Shah PK, Shapiro M, Stahl A, Toth C, Vinekar A, Visser L, Wallace DK, Wu WC, Zhao P, Zin A.
International Classification of Retinopathy of Prematurity, Third Edition.
Ophthalmology. 2021;128(10):e51-e68. PubMed abstract

Cryotherapy for Retinopathy of Prematurity Cooperative Group.
Multicenter trial of cryotherapy for retinopathy of prematurity: natural history ROP: ocular outcome at 5(1/2) years in premature infants with birth weights less than 1251 g.
Arch Ophthalmol. 2002;120(5):595-9. PubMed abstract / Full Text

Early Treatment For Retinopathy Of Prematurity Cooperative Group.
Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.
Arch Ophthalmol. 2003;121(12):1684-94. PubMed abstract / Full Text

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

Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, Quintos M, Tung B.
The incidence and course of retinopathy of prematurity: findings from the early treatment for retinopathy of prematurity study.
Pediatrics. 2005;116(1):15-23. PubMed abstract

Hagadorn JI, Richardson DK, Schmid CH, Cole CH.
Cumulative illness severity and progression from moderate to severe retinopathy of prematurity.
J Perinatol. 2007;27(8):502-9. PubMed abstract / Full Text

Hartnett ME.
Retinopathy of Prematurity: Evolving Treatment With Anti-Vascular Endothelial Growth Factor.
Am J Ophthalmol. 2020;218:208-213. PubMed abstract / Full Text

Hellström A, Hård AL, Engström E, Niklasson A, Andersson E, Smith L, Löfqvist C.
Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening.
Pediatrics. 2009;123(4):e638-45. PubMed abstract

Kaempf JW, Kaempf AJ, Wu Y, Stawarz M, Niemeyer J, Grunkemeier G.
Hyperglycemia, insulin and slower growth velocity may increase the risk of retinopathy of prematurity.
J Perinatol. 2011;31(4):251-7. PubMed abstract

Lad EM, Hernandez-Boussard T, Morton JM, Moshfeghi DM.
Incidence of retinopathy of prematurity in the United States: 1997 through 2005.
Am J Ophthalmol. 2009;148(3):451-8. PubMed abstract

Löfqvist C, Andersson E, Sigurdsson J, Engström E, Hård AL, Niklasson A, Smith LE, Hellström A.
Longitudinal postnatal weight and insulin-like growth factor I measurements in the prediction of retinopathy of prematurity.
Arch Ophthalmol. 2006;124(12):1711-8. PubMed abstract / Full Text

Ng EY, Connolly BP, McNamara JA, Regillo CD, Vander JF, Tasman W.
A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years: part 1. Visual function and structural outcome.
Ophthalmology. 2002;109(5):928-34; discussion 935. PubMed abstract

Noyola DE, Bohra L, Paysse EA, Fernandez M, Coats DK.
Association of candidemia and retinopathy of prematurity in very low birthweight infants.
Ophthalmology. 2002;109(1):80-4. PubMed abstract

Quinn GE, Ying GS, Daniel E, Hildebrand PL, Ells A, Baumritter A, Kemper AR, Schron EB, Wade K.
Validity of a telemedicine system for the evaluation of acute-phase retinopathy of prematurity.
JAMA Ophthalmol. 2014;132(10):1178-84. PubMed abstract / Full Text

Seiberth V, Linderkamp O.
Risk factors in retinopathy of prematurity. a multivariate statistical analysis.
Ophthalmologica. 2000;214(2):131-5. PubMed abstract

Wang J, Liu C, Wu H, Ng TK, Zhang M.
Diagnostic Accuracy of Wide-Field Digital Retinal Images in Retinopathy of Prematurity Detection: Systematic Review and Meta-Analysis.
Curr Eye Res. 2022;47(7):1024-1033. PubMed abstract