Basics
Description
Retinopathy of prematurity (ROP) is an abnormal pattern of retinal vascularization of preterm infants leading in some cases to permanent visual loss and blindness as well as many other eye problems.
Epidemiology
- ROP is the leading cause of blindness among children in the developed world:
- 0.2% of all infants born in the United States
- 20% of infants born <1,500 g
- 1,300 develop severe disease requiring treatment annually in the United States.
- Birth weight and ROP (incidence of ROP stage 1 or greater)
- <750 g: 90%
- 750 " <1,000 g: 78%
- 1,000 " 1,250 g: 47%
- >1,250 g: <1%
- Gestational age and ROP (incidence of any ROP stage 1 or greater with BW <1,251 g)
- ≤27 weeks: 83%
- 27 " 31 weeks: 55%
- ≥31 weeks: 29%
Risk Factors
- Gestational age
- Hyperoxia
- Hypoxia
- Acidosis
- Hypercarbia
- Apnea
- Bradycardia
- Nutritional deficiencies
- Ambient light
- Intraventricular hemorrhage
- Lower birth weight
- Lower gestational age
- Multiple gestation
- Born at another facility and transferred
Pathophysiology
- Normal retinal vascularization begins at the optic disc at about 16 weeks postmenstrual age and is typically completed at about term.
- Preterm delivery exposes the actively growing vessels to unusual conditions. These alter production of vascular endothelial growth factors. In some cases, the vascular growth stops and then resumes normally, whereas in other cases, the retinal blood vessels grow abnormally off the surface of the retina.
- The timing for development of acute ROP is related to postmenstrual age and not chronologic age or birth weight. It is rare to see any disease prior to 32 weeks postmenstrual age. Fewer than 10% of babies smaller than 1,250 g birth weight will have disease sufficiently severe to have treatment.
Diagnosis
History
- All infants with birth weight less than 1,500 g or gestational age less than 30 weeks are at risk.
- Other children with significant oxygen exposure are also referred for retinal evaluations.
- Each nursery needs a protocol to identify and document the infants needing examinations, both initial and follow-up. Reasons for exam deferral should be included in the medical record.
Alert
A common error in ROP management is failure to perform exams on the required schedule. The most vulnerable time for this lapse is during a transition to another unit or another facility or after discharge to home.
Physical Exam
- Requires a retinal examination with pupillary dilation, binocular indirect ophthalmoscopy, sterile eyelid speculum, and scleral depression
- Topical anesthesia may be used.
- Pupillary dilation is obtained using 1% phenylephrine/0.2% cyclopentolate solution (Cyclomydril) administered as a single drop to each eye, repeated in 5 " 10 minutes.
- Administer at least 30 minutes and preferably 1 hour prior to the exam.
- The dilating eye drops are associated with delay in gastric emptying.
- Careful monitoring is needed following the drop administration and the eye examination.
- Bradycardia and emesis are common following mydriatic eye drop administration and eye examination.
- The results of the examination should be recorded in a manner defined by the International Classification of Retinopathy of Prematurity. A retinal drawing is suggested:
- Zone I: posterior circular area of the retina centered on the optic disc with a radius twice the distance from disc to fovea
- Zone II: peripheral ring of retina extending from zone I to anterior edge of the nasal retina and estimated temporally
- Zone III: temporal retina beyond zone II
- Diagnostic retinal examinations and/or imaging should commence unless the infant is too unstable.
- At 31 weeks for those infants born at 26 weeks postmenstrual age or earlier
- By 4 weeks postnatal age for infants >26 " 30 weeks postmenstrual age
- Exams typically are ordered every 2 weeks.
- Additional examinations may be requested by neonatology for infants outside the consensus birth weight and postmenstrual age criteria.
- Subsequent examinations are determined by the ophthalmologist.
- Exams typically ordered every 2 weeks
- When there is prethreshold disease, weekly or even more frequent exams are conducted.
- When there is zone III disease, the exam interval may be lengthened.
- Exams continue until retinal vascularization into zone III is recorded.
- If VEGF inhibitors have been used for treatment, the exams may need to be extended substantially past term. Exams continue until retinal vascularization into zone III is recorded.
- ROP is typically symmetric, with similar exams in both eyes seen in 85% of infants.
- Eye examinations performed in the office setting may require monitoring depending on the infant 's medical status.
Diagnostic Tests & Interpretation
Imaging
- Wide-field digital camera with images of posterior pole, as well as superior, inferior, nasal, and temporal retinas, allows documentation and review of the findings as well as consultation.
- The images are reviewed either in real-time or using store-forward technology for evidence of referral-warranted ROP, at which time indirect ophthalmoscopy must be performed to determine if the patient has reached the treatment threshold or be monitored.
- Some facilities are using telemedicine as a substitute, rather than a supplement, for a clinical exam.
- Skilled nursery personnel are needed to handle the camera and obtain useful images.
- Plan for image review and urgent treatment referral when needed.
Diagnostic Procedures/Other
- Ophthalmic ultrasonography
- If difficult to obtain adequate indirect ophthalmoscopy, B-mode ultrasound of the eye can be useful to determine progression of ROP to retinal detachment and to monitor the detachment.
Differential Diagnosis
- Norrie disease
- Incontinentia pigmenti
- Familial exudative vitreoretinopathy
- Trauma
- Stickler syndrome
- Cyanotic congenital heart disease in rare cases
- Idiopathic
Treatment
Surgery/Other Procedures
- Each nursery needs a policy in place for where and how treatment is to be performed.
- Treatment should be performed within 48 hours if at all possible.
- Treatment is recommended when a particular stage of disease called type 1 occurs. Type 1 is ROP in zone I or II with PLUS characteristics (dilation and tortuosity of retinal arteries and veins), any stage in zone I, and stage 2 or 3 in zone II. Ideally, the treatment is completed within 48 hours, depending on the stability of the infant.
- Standard care treatment of ROP is ablation (destruction) of the peripheral nonvascularized retina using a laser incorporated into a binocular indirect ophthalmoscope.
- Requires airway management, topical eye drop anesthesia, and either sedation or general anesthesia
- 25% have unfavorable visual outcomes at 6 years.
- 9% have unfavorable structural outcomes at 6 years.
- 83% of treatments performed in infants ≤27 weeks ' gestation
- Cryotherapy of the peripheral retina that has not been vascularized (anterior) has been shown to be effective compared to observation.
- Used less frequently today because of pain, tissue damage, and difficulty treating more posterior disease
- Improves the chance of favorable structural outcomes at age 15 years from 48 to 70%
- Vitreoretinal surgery including vitrectomy is performed after retinal ablation or intravitreal injection has failed and the infant has progressed to stage 4 or 5 ROP (retinal detachment).
- Rarely associated with visual outcome of 20/200 or better (16%)
- Retinal reattachment in about 30%
Medication
- Oxygen restriction: Restriction of oxygen to 85 " 89% saturation measured by pulse oximetry has been associated with a reduction in the risk of severe ROP but was associated with an increased mortality rate.
- Oxygen supplementation: In the Stop-ROP trial, supplemental oxygen for infants with prethreshold disease appeared to reduce the rate of progression but was associated with increased risk for pulmonary disease.
- Vascular endothelial growth factor (VEGF) inhibitors (e.g., bevacizumab)
- Intravitreal injection of a small dose of one of these drugs is currently of great interest.
- In a clinical trial, a single dose of bevacizumab was more effective than laser ablation for zone I disease.
Ongoing Care
Follow-up Recommendations
- Infants with treated ROP and more severe stages of ROP without treatment typically require lifelong ophthalmologic monitoring.
- Substantially increased risk for the development of multiple eye conditions
- Retinal detachment
- Strabismus
- Amblyopia
- Myopia
- Glaucoma
- Optic nerve atrophy
- Cerebral visual impairment
- Infants with prethreshold ROP have moderately increased risk of the ophthalmic conditions mentioned above. Referral managed with typical practice.
- A history of treatment for ROP is correlated with a high risk of disability on motor, communication " social, self-care, and continence scales on the Wee-FIM (Functional Independence Measure for Children).
Prognosis
- If ROP treatment was required, visual outcomes reported at 15 years:
- 25% with 20/20 " 20/40
- 50% with 20/20 " 20/200
- 33% with less than 20/200
Additional Reading
- Early Treatment for Retinopathy of Prematurity Cooperative Group, Good WV, Hardy RJ, et al. Final visual acuity results in the Early Treatment for Retinopathy of Prematurity study. Arch Ophthalmol. 2010;128(6):663 " 671. [View Abstract]
- Fierson WM, et al. Policy statement: screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013;131(1):189 " 195. [View Abstract]
- International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123(7):991 " 999. [View Abstract]
- Mintz-Hittner HA, Kennedy KA, Chuang AZ, et al. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603 " 615. [View Abstract]
- Palmer EA, Hardy RJ, Dobson V, et al. 15-year outcomes following threshold retinopathy of prematurity: final results from the multicenter trial of cryotherapy for retinopathy of prematurity. Arch Ophthalmol. 2005;123(3):311 " 318. [View Abstract]
- The natural ocular outcome of premature birth and retinopathy. Status at 1 year. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1994;112(7):903 " 912. [View Abstract]
Codes
ICD09
- 362.20 Retinopathy of prematurity, unspecified
- 362.22 Retinopathy of prematurity, stage 0
- 362.23 Retinopathy of prematurity, stage 1
- 362.24 Retinopathy of prematurity, stage 2
- 362.25 Retinopathy of prematurity, stage 3
- 362.26 Retinopathy of prematurity, stage 4
- 362.27 Retinopathy of prematurity, stage 5
ICD10
- H35.109 Retinopathy of prematurity, unspecified, unspecified eye
- H35.119 Retinopathy of prematurity, stage 0 unspecified eye
- H35.129 Retinopathy of prematurity, stage 1 unspecified eye
- H35.139 Retinopathy of prematurity, stage 2, unspecified eye
- H35.142 Retinopathy of prematurity, stage 3, left eye
- H35.121 Retinopathy of prematurity, stage 1, right eye
- H35.103 Retinopathy of prematurity, unspecified, bilateral
- H35.113 Retinopathy of prematurity, stage 0, bilateral
- H35.133 Retinopathy of prematurity, stage 2, bilateral
- H35.122 Retinopathy of prematurity, stage 1, left eye
- H35.162 Retinopathy of prematurity, stage 5, left eye
- H35.151 Retinopathy of prematurity, stage 4, right eye
- H35.102 Retinopathy of prematurity, unspecified, left eye
- H35.131 Retinopathy of prematurity, stage 2, right eye
- H35.149 Retinopathy of prematurity, stage 3, unspecified eye
- H35.152 Retinopathy of prematurity, stage 4, left eye
- H35.141 Retinopathy of prematurity, stage 3, right eye
- H35.169 Retinopathy of prematurity, stage 5, unspecified eye
- H35.101 Retinopathy of prematurity, unspecified, right eye
- H35.132 Retinopathy of prematurity, stage 2, left eye
- H35.159 Retinopathy of prematurity, stage 4, unspecified eye
- H35.143 Retinopathy of prematurity, stage 3, bilateral
- H35.112 Retinopathy of prematurity, stage 0, left eye
- H35.163 Retinopathy of prematurity, stage 5, bilateral
- H35.153 Retinopathy of prematurity, stage 4, bilateral
- H35.161 Retinopathy of prematurity, stage 5, right eye
- H35.111 Retinopathy of prematurity, stage 0, right eye
- H35.123 Retinopathy of prematurity, stage 1, bilateral
SNOMED
- 415297005 Retinopathy of prematurity (disorder)
- 124111000119102 Retinopathy of prematurity stage 0 (finding)
- 408847006 Retinopathy of prematurity stage 1 - demarcation line (disorder)
- 408848001 Retinopathy of prematurity stage 2 - intraretinal ridge (disorder)
- 408851008 Retinopathy of prematurity stage 5 - total retinal detachment
- 408850009 Retinopathy of prematurity stage 4 - subtotal retinal detachment
- 408849009 Retinopathy of prematurity stage 3 - ridge with extraretinal fibrovascular proliferation (disorder)
FAQ
- Q: Does intrauterine growth retardation (IUGR) affect the chance for development of ROP?
- A: The chance for development of ROP in an infant with IUGR is more related to the postmenstrual birth age rather than the birth weight. However, in as much as the IUGR infant is sick, that could increase the risk over infants of similar postmenstrual age at birth.
- Q: When should a missed exam be made up?
- A: In most cases, it is safe to wait a week unless there has been recent evidence of stage 2 or worse disease in which case the exam should be completed as soon as the infant is stable for the dilated exam.
- Q: Does acute ROP ever need to be retreated?
- A: Following ablative therapy, about 10% of eyes will need additional treatment to untreated areas of the retina if the PLUS disease has not begun to diminish. This typically occurs about 10 " 14 days. The rate for retreatment after VEGF inhibitor therapy is not yet well established.