Peds Ophtho Case 4: Diagnosis & Conclusions

Diagnosis: Retinopathy of Prematurity (ROP)

Retinopathy of prematurity (ROP) is a potentially blinding disease that arises due to abnormal blood vessel growth in premature infants. About 16,000 infants in the U.S. are diagnosed with ROP annually and about 10% of them develop severe disease requiring urgent treatment.

Pathophysiology

Beginning at 14-16 weeks gestation, retinal blood vessels begin growing from the back of the eye towards the edges of the developing retina. These vessels achieve full growth near 37 weeks gestation. In premature infants, vessel growth may be incomplete, depriving the retinal periphery of oxygen and nutrients. As a result, abnormal vessel proliferation can develop, resulting in ROP.

Screening

Most infants with ROP have mild self-limiting cases and can achieve normal visual development. However, patients with severe ROP are at high risk for retinal detachment and vision loss if they are not promptly screened and treated. The American Academy of Pediatrics recommends ROP screening for all infants who are gestational age <30 weeks or who weigh ≤1500 grams. They also recommend screening if the infant has risk factors for ROP. Besides early gestational age and low birth weight, other risk factors include anemia, blood transfusions, respiratory distress, poor health, and receipt of high levels of oxygen. To screen for ROP, the ophthalmologist performs a dilated fundus exam with binocular indirect ophthalmoscopy on the patient. Because dilating drops can be absorbed systemically, infants may be at risk for adverse side effects such as bradycardia and apnea. Thus, these patients require monitoring during dilation and after examination. A lower percentage of dilating eye drops should be used in pediatric populations when available (i.e. Cyclomydril (cyclopentolate 0.02% / phenylephrine 1%)). As ROP can develop at any time and can rapidly progress, routine screening should be done until there is evidence of complete vessel growth in both eyes.

Table 1

StageExam Findings
Stage 0Underdeveloped retina. No clear distinction between the vascular and avascular retina.
Stage IMildly abnormal blood vessel growth. Distinct two-dimensional line between vascular and avascular retina. Can resolve on its own with no treatment. Normal vision can be achieved.
Stage IIModerate abnormal blood vessel growth. Wavy elevated three-dimensional line (raised ridge) between vascular and avascular retina. Can resolve on its own with no treatment. Normal vision can be achieved.
Stage IIISeverely abnormal blood vessel growth and pattern. Vessels may grow toward the center of the eye. Vessels may become dilated and tortuous (plus disease).
 
Stage III and higher are at high risk of visual impairment or blindness without intervention.
Stage IVPartial retinal detachment
Stage VComplete retinal detachment
Stage 3 (Image Courtesy of Robin Ginsburg, MD)
Stage 4 (Image courtesy of Robin Ginsburg, MD)

Treatment

ROP is classified by stage (Table 1), zone (Figure 1) and vessel appearance. When the vessels become dilated and tortuous, they are considered to have plus disease.  In general, all patients with plus disease or with ≥stage 3 ROP should be treated urgently. Findings from the Early Treatment for Retinopathy of Prematurity (ETROP) trial have shown that early intervention (i.e. within 72 hours of diagnosis) can help prevent severe vision loss. First-line treatments for ROP are laser therapy and anti-vascular endothelial growth factor (anti-VEGF) injections. All patients following treatment should be closely monitored for disease resolution as recurrence or treatment failure can occur

Figure 1 (Image courtesy of Robin Ginsburg, MD)

Follow up 

Long-term visual impairment is greatest in patients with ≥Stage III ROP and in posterior disease, especially among those who are not treated promptly, have disease recurrence or are non-responsive to treatment. These patients are also more likely to develop motor, cognitive, and hearing impairments.

Research has shown that patients with ROP (even those requiring no treatment), are at significantly greater risk for developing other eye complications later in life, including strabismus, myopia, cataracts, and amblyopia and retinal detachment. The American Academy of Pediatrics recommends follow-up examination with ophthalmology at least four to six months following NICU discharge for any patient with ROP.

References and Additional Resources:

  1. “Retinopathy of Prematurity.” American Association of Pediatric Ophthalmology and Strabismus. April 2020.  
  2. “Retinopathy of Prematurity.” National Eye Institute. July 2019.
  3. 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.
  4. Fierson WM; American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening Examination of Premature Infants for Retinopathy of Prematurity. Pediatrics. 2018;142(6):e20183061.
  5. Heidar K, Miller AM, Stevenson E, Epley D, Pihblad M et al. Retinopathy of Prematurity. Hartnett ME, Kumar P (Eds). American Academy of Ophthalmology: EyeWiki. May 2021.
  6. Stahl A, Lepore D, Fielder A, Fleck B, Reynolds JD, Chiang MF, Li J, Liew M, Maier R, Zhu Q, Marlow N. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet. 2019;394(10208):1551-1559.

Case 4 Index

Peds Ophtho Case 4 Index
Peds Ophtho Case 4: Introduction
Peds Ophtho Case 4: Additional History & Physical Exam
Peds Ophtho Case 4: DILATED FUNDUS EXAM
Peds Ophtho Case 4: Case Continued…