Sections

Workup

Approach Considerations

The evaluation of premature infants at risk for retinopathy of prematurity (ROP) should be limited to practitioners who are facile with binocular indirect ophthalmoscopy and scleral depression, and who have significant experience with ROP.

Ocular ultrasonography is an important tool when there is a media opacity (eg, cataract, vitreous hemorrhage) that precludes a view of the retina.

Some center utilize fundus photography with remote image reading.^[21]There have been encouraging results with this approach.

Ophthalmologic evaluation in retinopathy of prematurity (ROP)

Record the vascular maturity (how far out the vessels have grown), as indicated by zone, stage of disease, and the presence or absence of plus disease or preplus disease.

Quantify the extent of ROP on the basis of number and contiguity of clock hours (meridians) in which the disease is present in the retina.

Staging

The International Classification of Retinopathy of Prematurity (ICROP) describes five stages of ROP, as follows^[17]:

Stage I is characterized by a line of demarcation between the vascular and avascular retina. Branching or arborization can be seen growing at the leading edge of the retinal vasculature. (See the image below.)
Retinopathy of Prematurity. Stage I retinopathy of prematurity.
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Stage II is characterized by an elevated ridge, rather than a flat demarcation line. Flat neovascularization may be present but is posterior to the ridge. (See the following image.)
Retinopathy of Prematurity. Stage II retinopathy of prematurity.
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Stage 3 is extraretinal neovascularization, or vessels that grow off the ridge into the vitreous toward the examiner. (See the image below.)
Retinopathy of Prematurity. Stage III retinopathy of prematurity.
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Stage IV refers to partial retinal detachment. Stage IV-A is outside the macula; stage IV-B involves the macula.
Stage IV is total retinal detachment. (See the following image.)
Retinopathy of Prematurity. A comparison between attached and detached retina.
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Some ophthalmologists describe an immature or avascular retina as stage 0 ROP.

Plus disease is an important marker of disease activity/severity; plus refers to severe tortuosity of vessels in the posterior pole. Rapidly progressing plus disease is sometimes referred to as Rush disease. Preplus disease is defined as vascular abnormalities of the posterior pole characterized by more arterial tortuosity and more venous dilatation than normal but not severe enough to be classified as plus disease.

Zones of disease

Zone I is the innermost area of the retina surrounding the macula (see the image below).

Retinopathy of Prematurity. Zone I retinopathy of prematurity.

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Zone II is the middle third of the retina, nasally extending to the edge of the retina (see the following image).

Retinopathy of Prematurity. Zone II retinopathy of prematurity.

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Zone III is the most peripheral area of the retina on the temporal side (see the image below).

Retinopathy of Prematurity. Zone III retinopathy of prematurity.

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Types

As of the publication of the Early Treatment for Retinopathy of Prematurity (ETROP) study, more ophthalmologists are describing eyes with ROP into two types (see the image below):

Retinopathy of Prematurity. Treatment guidelines, according to the Early Treatment for Retinopathy of Prematurity (ET-ROP) study.

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Type 1 ROP requires treatment and includes the following:

Eyes with zone I, stage III ROP without plus disease, or
Eyes with zone II, stage II or stage III ROP with plus disease

Type 2 ROP requires observation and includes the following:

Eyes with zone I, stage I or stage III ROP without plus disease, or
Eyes with zone II, stage III ROP without plus disease

Procedures

A proper examination of the fundus requires adequate pupillary dilation. Typically, the infant's nurse will instill a combination of 0.2% cyclopentolate hydrochloride (HCl)/1% phenylephrine HCl) (Cyclogyl) ophthalmic solution 2-3 times in the hour before the scheduled examination. Mydriatic agents can cause blanching of the skin of the lids and increased blood pressure,

Infants examined in the neonatal intensive care unit should be relatively medically stable. They should be swaddled, and the attending nurse should assist the examination by stabilizing the head and upper body of the baby.

Wire lid speculums are used to hold the lids open. Most examiners will instill a topical anesthetic to reduce the discomfort of the speculum and the scleral depression (gentle pressing on the sclera to bring the peripheral retina into better view).

The examination can cause bradycardia, apnea, and hypertension (in response to pain) and, rarely, seizures and arrhythmia. Examiners should be able to examine each eye in a few minutes to reduce the risk of these complications. Medications and equipment for cardiovascular support should be at hand.

Treatment & Management

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Connor KM, SanGiovanni JP, Lofqvist C, et al. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007 Jul. 13(7):868-73. [QxMD MEDLINE Link]. [Full Text].
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Mintz-Hittner HA, Kennedy KA, Chuang AZ. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011 Feb 17. 364(7):603-15. [QxMD MEDLINE Link].
Lorenz B, Stieger K, Jager M, Mais C, Stieger S, Andrassi-Darida M. Retinal vascular development with 0.312 mg intravitreal bevacizumab to treat severe posterior retinopathy of prematurity: a longitudinal fluorescein angiographic study. Retina. 2017 Jan. 37(1):97-111. [QxMD MEDLINE Link].
Stoltz Sjostrom E, Lundgren P, Ohlund I, Holmstrom G, Hellstrom A, Domellof M. Low energy intake during the first 4 weeks of life increases the risk for severe retinopathy of prematurity in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed. 2016 Mar. 101(2):F108-13. [QxMD MEDLINE Link]. [Full Text].
Houston SK, Wykoff CC, Berrocal AM, Hess DJ, Murray TG. Laser treatment for retinopathy of prematurity. Lasers Med Sci. 2013 Feb. 28(2):683-92. [QxMD MEDLINE Link]. [Full Text].
Shalev B, Farr AK, Repka MX. Randomized comparison of diode laser photocoagulation versus cryotherapy for threshold retinopathy of prematurity: seven-year outcome. Am J Ophthalmol. 2001 Jul. 132(1):76-80. [QxMD MEDLINE Link].
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Hwang CK, Hubbard GB, Hutchinson AK, Lambert SR. Outcomes after intravitreal bevacizumab versus laser photocoagulation for retinopathy of prematurity: a 5-year retrospective analysis. Ophthalmology. 2015 May. 122(5):1008-15. [QxMD MEDLINE Link]. [Full Text].
Tolentino M. Systemic and ocular safety of intravitreal anti-VEGF therapies for ocular neovascular disease. Surv Ophthalmol. 2011 Mar-Apr. 56(2):95-113. [QxMD MEDLINE Link].
Hillier RJ, Connor AJ, Shafiq AE. Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series. Br J Ophthalmol. 2018 Feb. 102(2):260-4. [QxMD MEDLINE Link].
Wallace DK, Kraker RT, Freedman SF, et al, for the Pediatric Eye Disease Investigator Group (PEDIG). Assessment of lower doses of intravitreous bevacizumab for retinopathy of prematurity: a phase 1 dosing study. JAMA Ophthalmol. 2017 Jun 1. 135(6):654-6. [QxMD MEDLINE Link]. [Full Text].
Snyder LL, Garcia-Gonzalez JM, Shapiro MJ, Blair MP. Very late reactivation of retinopathy of prematurity after monotherapy with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging Retina. 2016 Mar. 47(3):280-3. [QxMD MEDLINE Link].
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Gunzenhauser RC, Lee YH, Tsui I. Rhegmatogenous retinal detachment after retinopathy of prematurity laser treatment. Am J Ophthalmol Case Rep. 2023 Mar. 29:101785. [QxMD MEDLINE Link]. [Full Text].
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Parry NM. AAP updates screening policy for ROP. Medscape Medical News from WebMD. December 4, 2018. Available at https://www.medscape.com/viewarticle/905930. Accessed: August 12, 2020.
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Media Gallery

Retinopathy of Prematurity. Stage I retinopathy of prematurity.
Retinopathy of Prematurity. Scheme of retina of right eye (RE) and left eye (LE) showing zone borders and clock hours used to describe location and extent of retinopathy of prematurity.
Retinopathy of Prematurity. Zone I retinopathy of prematurity.
Retinopathy of Prematurity. Zone II retinopathy of prematurity.
Retinopathy of Prematurity. Zone III retinopathy of prematurity.
Retinopathy of Prematurity. Stage II retinopathy of prematurity.
Retinopathy of Prematurity. Stage III retinopathy of prematurity.
Retinopathy of Prematurity. Mild extraretinal fibrovascular proliferation.
Retinopathy of Prematurity. Moderate extraretinal fibrovascular proliferation.
Retinopathy of Prematurity. Severe extraretinal fibrovascular proliferation.
Retinopathy of Prematurity. A comparison between attached and detached retina.
Retinopathy of Prematurity. Retinopathy of prematurity (ROP) threshold, according to the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Cooperative Group.
Retinopathy of Prematurity. Treatment guidelines, according to the Early Treatment for Retinopathy of Prematurity (ET-ROP) study.
Retinopathy of Prematurity. Laser photocoagulation. RPE = retinal pigment epithelium.
Retinopathy of Prematurity. Cryotherapy probe application.

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Author

Siva Subramanian, MD, FAAP Emeritus Chief of Neonatal-Perinatal Medicine, Medstar Georgetown University Hospital; Professor Emeritus of Pediatrics and Obstetrics, Senior Ethicist, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center

Siva Subramanian, MD, FAAP is a member of the following medical societies: American Pediatric Society, American Association for the Advancement of Science, American College of Nutrition, American Pediatric Society, American Society for Parenteral and Enteral Nutrition, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Melissa D Kern, MD Owner and Ophthalmologist in Pediatric and Adolescent Ophthalmology and Adult Strabismus, Arlington-Loudon Pediatric Ophthalmology; Chief of Surgery (Ophthalmology), Virginia Hospital Center

Melissa D Kern, MD is a member of the following medical societies: Northern Virginia Academy of Ophthalmology

Disclosure: Nothing to disclose.

William F Deegan, III, MD Associate Clinical Professor of Ophthalmology, Georgetown University School of Medicine; Attending Surgeon, Spectrum Retina and Ocular Oncology, Virginia Hospital Center Health System

William F Deegan, III, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, Massachusetts Medical Society, Washington Academy of Eye Physicians and Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Arun K Pramanik, MD, MBBS Professor of Pediatrics, Louisiana State University Health Sciences Center

Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Santina A Zanelli, MD Associate Professor, Department of Pediatrics, Division of Neonatology, University of Virginia Health System

Santina A Zanelli, MD is a member of the following medical societies: American Academy of Pediatrics, American Epilepsy Society, Society for Neuroscience, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American Association for Physician Leadership, American Heart Association, American College of Nutrition

Disclosure: Nothing to disclose.

Monisha Bahri, MBBS, MD Attending Physician, Department of Neonatalogy, Washington Hospital Center

Monisha Bahri, MBBS, MD is a member of the following medical societies: American Academy of Pediatrics, Medical Council of India, Indian Academy of Pediatrics

Disclosure: Nothing to disclose.

Gonzalo (Vike) Vicente, MD, FAAP Consulting Ophthalmologist, Eye Doctors of Washington

Gonzalo (Vike) Vicente, MD, FAAP is a member of the following medical societies: American Academy of Ophthalmology, American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus, American Medical Association

Disclosure: Nothing to disclose.

Retinopathy of Prematurity Workup

Approach Considerations

Other Tests

Ophthalmologic evaluation in retinopathy of prematurity (ROP)

Staging

Zones of disease

Types

Procedures

Gestational Age at Birth (wk)	Chronologic Age (wk)	Postmenstrual Age (wk)
22^*	9	31
23^*	8	31
24	7	31
25	6	31
26	5	31
27	4	31
28	4	32
29	4	33
30	4	34
31 (if necessary)	4	35
32 (if necessary)	4	36

Retinopathy of Prematurity Workup

Approach Considerations

Other Tests

Ophthalmologic evaluation in retinopathy of prematurity (ROP)

Staging

Zones of disease

Types

Procedures

References

Tables

Contributor Information and Disclosures

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