How should retinopathy of prematurity be screened and treated in premature infants ≤31 weeks gestational age or ≤1500 g birth weight who have been exposed to supplemental oxygen?

Screening and Treatment of Retinopathy of Prematurity in High-Risk Premature Infants

All premature infants ≤31 weeks gestational age or ≤1500 g birth weight who have received supplemental oxygen must undergo ROP screening by an experienced pediatric ophthalmologist, with the first examination performed at 31-33 weeks postmenstrual age or 4 weeks chronological age (whichever is later), followed by serial examinations every 1-2 weeks until complete retinal vascularization or regression is confirmed. 1

Screening Initiation and Timing

When to Start Screening:

• Begin screening at the later of either 31-33 weeks postmenstrual age OR 4 weeks chronological age 1
• This timing applies to all infants ≤31 weeks gestational age or ≤1500 g birth weight, particularly those exposed to supplemental oxygen 1, 2
• A more conservative approach screens all infants <32 weeks gestation, even if medically stable without oxygen requirements 1

Who Performs the Examination:

• Only pediatric ophthalmologists experienced in evaluating premature infant retinas should perform screening 1
• General ophthalmologists are not suitable for ROP screening 1
• The examination must include evaluation of the optic disc, macula, retina, vessels, and choroid using indirect ophthalmoscopy with a condensing lens after adequate pupil dilation 1

Follow-Up Examination Schedule

Frequency Based on Disease Severity:

• Zone I or Zone II disease with active ROP: Ophthalmology visits every 1-2 weeks until resolution or treatment 1
• Regressing ROP with vessels in Zone III on two sequential exams: Extremely unlikely to progress to threshold ROP; less frequent monitoring acceptable 1
• Complete retinal vascularization: Screening can be discontinued 1

Critical Coordination Point:

• Never discharge infants with Zone I or II disease without confirmed follow-up appointments—this represents the greatest risk for preventable blindness 1
• Missing follow-up appointments can result in missed treatment opportunities and preventable vision loss 1

Treatment Indications and Modalities

When to Treat:

• Peripheral laser ablation is indicated for threshold ROP and has proven effective in reducing blindness 1
• Treatment timing is critical and depends on disease progression documented through serial examinations 1

Treatment Approach:

• Peripheral laser ablation remains the gold standard, particularly for Zone II disease 1
• Anti-VEGF therapy is emerging as an alternative but laser remains standard of care 3, 4

Oxygen Management During ROP Risk Period

Target Oxygen Saturations:

• During active ROP risk period: Maintain SpO2 90-95% to balance neurodevelopmental needs against ROP progression 5
• For infants with pre-threshold ROP: Target saturations of 96-99% do NOT increase ROP progression risk and may even decrease risk 1, 5
• Once past the age of oxygen-induced retinopathy risk: Target SpO2 ≥95% 1

Oxygen Management Principles:

• Avoid sustained hyperoxemia in infants with peripheral avascular retina 1
• Do not restrict oxygen excessively in infants with pre-threshold ROP—saturations of 96-99% are safe 1
• Continuous pulse oximetry monitoring is essential when supplemental oxygen is administered 5

Understanding ROP Pathophysiology to Guide Management

Two-Phase Disease Process:

Phase I (Vaso-obliteration):

• Premature birth interrupts normal retinal vascularization that begins at 16 weeks gestation 6
• High arterial oxygen levels slow normal vascularization during this vulnerable period 6
• Incomplete vessels are highly susceptible to injury from prolonged elevated oxygen and other physiologic stressors 7, 6

Phase II (Pathological Neovascularization):

• The avascular retina becomes metabolically demanding and produces excessive vascular growth factors 6
• This triggers abnormal compensatory blood vessel growth into the retina and vitreous cavity 6
• Marginally low arterial oxygen during this phase aggravates neovascularization 6

Special Considerations for Infants with Chronic Lung Disease

• Infants with chronic lung disease of infancy (CLDI) require screening even if between 29-37 weeks gestation 1
• These infants need careful coordination of oxygen management and ophthalmology follow-up 1
• Poor oxygen control in infants with unresolved ROP and CLDI may worsen ROP progression 1, 5

Common Pitfalls and How to Avoid Them

Screening Errors:

• Do not skip screening for infants 29-32 weeks who were "medically stable"—screen them anyway 1
• Do not allow general ophthalmologists to perform screening; only pediatric ophthalmologists with ROP experience 1

Follow-Up Failures:

• The greatest risk for preventable blindness occurs when infants with Zone I or II disease are discharged without confirmed follow-up 1
• Ensure appointments are scheduled before discharge, not left to parents to arrange 1

Oxygen Management Mistakes:

• Do not over-restrict oxygen in infants with pre-threshold ROP out of fear of progression—96-99% saturations are safe 1
• Do not allow sustained hyperoxemia in infants with incomplete retinal vascularization 1

Evidence Quality and Incidence Data

• Approximately 43% of at-risk premature infants develop some stage of ROP, with 12.5% developing severe ROP requiring treatment 8
• 98% of type 1 or 2 ROP cases occur in infants with birth weight <1251 g 8
• Birth weight, gestational age, and duration of oxygen exposure have the strongest associations with ROP development 2
• Vitamin A supplementation shows a trend toward reduced ROP incidence in very low birth weight infants, though this is not the primary indication for supplementation 7