Risk Factors

• Prematurity, especially ≤30 weeks of gestation.

• Birth weight ≤1,500 g (3 lb, 5 oz).

• Use of supplemental oxygen, neonatal sepsis, hypoxemia, hypercarbia, failure to thrive, coexisting illness, Caucasian race, and male sex.

• Risk factors mentioned above, when present concurrently, have an additive effect on the risk for development of ROP.

Critical

Avascular peripheral retina. Demarcation line between vascular and avascular retina.

Other

Extraretinal fibrovascular proliferation, vitreous hemorrhage, retinal detachment, or leukocoria. Commonly bilateral. Association of “plus disease” in more severe cases includes engorgement and tortuosity of the vessels in the posterior pole and/or iris. Poor pupillary dilation despite mydriatic drops. In older children and adults, risk for decreased visual acuity, amblyopia, myopia, strabismus, macular dragging, lattice-like vitreoretinal degeneration, and retinal detachment.

• FEVR: Can appear similar to ROP, except FEVR is hereditary (although family members may be asymptomatic, and de novo mutations frequently occur) and more often asymmetric; asymptomatic family members often show peripheral retinal vascular abnormalities. There usually is no history of prematurity or oxygen therapy. See 8.3, Familial Exudative Vitreoretinopathy.

• Incontinentia pigmenti: X-linked dominant condition that usually occurs in girls. Often lethal in males. Characterized by skin changes including erythematous maculopapular lesions, vesicles, hypopigmented patches, and alopecia. Associated with eosinophilia. Central nervous system (CNS) and dental abnormalities also seen.

• See 8.1, Leukocoria, for additional differential diagnoses. 

Classification

Location

• Zone I: Posterior pole: Twice the disc–fovea distance, centered around the disc (poorest prognosis).

  NOTE With the nasal edge of the optic disc at one edge of the field of view with a 28D lens, the limit of zone I is at the temporal field of view.

• Zone II: From zone I to the nasal ora serrata; temporally equidistant from the disc.

  • Posterior Zone II: The first two disc diameters of Zone II beyond Zone I; noted to be a higher-risk area of Zone II.

  NOTE ROP should not be considered zone III until one is sure the nasal side is vascularized to the ora serrata.

• Zone III: The remaining temporal periphery.

Extent

• Number of clock hours (30-degree sectors) involved. Of note, the number of clock hours of neovascularization was important in older treatment criteria, but it is not used in the most updated treatment guidelines.

Severity

• Stage 1: Flat demarcation line separating the vascular posterior retina from the avascular peripheral retina (see Figure 8.2.1).

  Figure 8.2.1: Retinopathy of prematurity: Stage 1.

  

• Stage 2: Ridged demarcation line.

• Stage 3: Ridged demarcation line with fibrovascular proliferation or neovascularization extending from the ridge (see Figure 8.2.2).

  Figure 8.2.2: Retinopathy of prematurity: Stage 3.

  

• Stage 4A: Extrafoveal partial retinal detachment.

• Stage 4B: Fovea-involving partial retinal detachment.

• Stage 5: Total retinal detachment.

NOTE Overall stage is determined by the most severe manifestation; however, it is recommended to define each stage and extent.

“Plus” Disease

Posterior pole engorgement and tortuosity of veins and arteries; iris vascular engorgement, poor pupil dilatation, and vitreous haze with more advanced plus disease. If plus disease is present, a “+” is placed after the stage (e.g., stage 3+). If vascular dilatation and tortuosity are present but inadequate to diagnose plus disease, it is called “pre-plus” disease and noted after the stage (e.g., stage 3 with pre-plus disease). “Aggressive ROP,” rapidly progressing posterior ROP with extensive plus disease, formerly known as “rush” disease, may progress rapidly to stage 5 ROP without passing through the other stages. This aggressive ROP may also show hemorrhages at the junction between vascular and avascular retina (see Figure 8.2.3). 

Figure 8.2.3: Retinopathy of prematurity: Plus disease.

Type 1 ROP

Defines high-risk eyes that meet the criteria for treatment:

• Zone I, any stage with plus disease.

• Zone I, stage 3 without plus disease.

• Zone II, stage 2 or 3 with plus disease.

Type II ROP

Defines less severely advanced eyes that should be monitored closely for progression to type 1 disease:

• Zone I, stage 1 and 2 without plus disease.

• Zone II, stage 3 without plus disease.

Screening Recommendations

• Birth weight ≤1,500 g.

• Gestational age ≤30 weeks.

• Selected infants with birth weight >1,500 g or gestational age ≥31 weeks with unstable clinical course thought to be at high risk.

• Timing of first eye examination is based on postmenstrual (gestational age at birth plus chronologic age) and postnatal (chronologic since birth) age. The first eye examination should start at 31 to 32 weeks postmenstrual age or 4 weeks postnatal age, whichever is later.

NOTE The American Academy of Pediatrics provides updated guidelines for ROP screening in premature infants. For the latest recommendations, please see their most recent policy statement available at aap.org.

1. Dilated retinal examination with scleral depression at 31 to 32 weeks after date of mother’s last menstrual period or 4 weeks after birth, whichever is later.

2. Can dilate with any two-agent combination from the following: phenylephrine, 1%; tropicamide, 1%; cyclopentolate, 0.2% to 0.5%. A fixed combined drop of phenylephrine 1% and cyclopentolate 0.2% is available. Consider repeating the drops in 30 to 45 minutes if the pupil is not dilated.

• Therapeutic goal is ablation of avascular peripheral retina with near-confluent spots. Laser photocoagulation is preferred over cryotherapy. Treatment should be instituted within 48 to 72 hours (See Figure 8.2.4). Intravitreal anti-VEGF agents (0.625 mg in 0.025 mL of solution of bevacizumab is the typical dosing) is another treatment modality, particularly for aggressive ROP cases in Zone I or posterior Zone II. The long-term effects and potential risks of these medications in preterm infants are yet to be determined, and late ROP reactivation can occur with intravitreal anti-VEGF treatment. Long-term follow-up is critical and prophylactic laser photocoagulation for persistent avascular peripheral retina is considered in some cases.

  Figure 8.2.4: Retinopathy of prematurity after laser treatment.

  

• Type 1 ROP needs treatment. 

• Type 2 ROP should be followed closely.

• For acute stages 4 and 5: Surgical repair of retinal detachment by vitrectomy.

• A single ocular examination is sufficient only if it unequivocally shows full retinal vascularization in both eyes.

• One week or less: immature vascularization, zone I, no ROP; immature retina localized to boundary of zones I and II; zone I, stage 1 or 2; zone II, stage 3; or any concern for aggressive ROP.

• One to 2 weeks: immature vascularization localized to posterior zone II; or zone II, stage 2; or zone I, regressing ROP.

• Two weeks: immature vascularization localized to zone II, no ROP; zone II, stage 1; or zone II, regressing ROP.

• Two to 3 weeks: zone III, stage 1 or 2; or zone III, regressing ROP.

1. Children who have had ROP have a higher incidence of myopia, strabismus, amblyopia, macular dragging, cataracts, glaucoma, and retinal detachment. An untreated fully vascularized fundus needs examination at age 6 months to rule out these complications.

   NOTE Because of the possibility of late retinal detachments and other ocular complications, ROP patients should be followed at yearly intervals for life.

2. Acute-phase ROP screening can be discontinued when any of the following signs is present, indicating that the risk of visual loss from ROP is minimal or passed:

   • Zone III retinal vascularization attained without previous zone I or II ROP. If there is doubt about the zone or if the postmenstrual age is <35 weeks, confirmatory examinations may be warranted.

   • Postmenstrual age of 50 weeks and no ROP disease equivalent to or worse than zone I, any stage or zone II, stage 3.

   • Full retinal vascularization in close proximity to the ora serrata (for cases treated with anti-VEGF therapy).

   • If treated with anti-VEGF, follow-up should be extended due to risk of ROP recurring after 65 to 70 weeks postmenstrual age, if retinal vascularization remains incomplete. Consider prophylactic laser to undeveloped avascular retina if unable to assure follow-up examinations.