ROP (Retinopathy of prematurity) Updates

Lecture done Dr. Dr. Alaa Khamees, commentary Prof. Khalil alsalem

ROP ( Retinopathy of prematurity) is a vaso-proliferative retinopathy of incompletely vascularized preterm retina driven by disordered oxygen regulation, inflammation, and VEGF signaling. The International Classification of ROP, Third Edition (ICROP3), refined descriptions of zones (including posterior zone II), stages, plus disease, and—crucially—post-treatment “reactivation/regression” patterns relevant in the anti-VEGF era.

Risk factors FOR ROP

Principal risks are low gestational age and birth weight, with additive effects from prolonged supplemental oxygen/ventilation, sepsis/NEC, poor postnatal weight gain, transfusions, and systemic inflammation. Morbidity-based screening pathways (for very sick infants who do not meet GA/BW thresholds) are now embedded in several national guidelines to avoid misses in late-preterm but unwell neonates.

Pathophysiology (two-phase model).

Phase 1 (vaso-attenuation): relative hyperoxia and reduced IGF-1 after preterm birth suppress physiologic retinal angiogenesis. Phase 2 (vaso-proliferation): as the avascular retina becomes hypoxic, VEGF surges, driving pathologic neovascularization and plus disease; anti-VEGF therapy alters regression patterns and can permit further physiologic peripheral vascularization, but introduces the possibility of late reactivation. ICROP3 explicitly codifies these post-treatment courses for standardized reporting.

Recent research highlights in ROP

Randomized data have matured beyond BEAT-ROP. BEAT-ROP (bevacizumab vs laser in stage 3+ zone I/II) showed lower recurrence in zone I with bevacizumab and continued peripheral vascularization, but the trial was underpowered for systemic safety.
RAINBOW compared ranibizumab (0.1/0.2 mg) with laser in very-low-birth-weight infants; two-year outcomes suggest comparable structural outcomes with less high myopia after 0.2 mg ranibizumab and without detected adverse effects on non-ocular development, although extended monitoring remains prudent. Subsequent analyses and reviews through 2023–2024 support ranibizumab 0.2 mg as an effective option and note its regulatory approvals in multiple regions.
Emerging practice surveys indicate a global increase in anti-VEGF use, particularly for zone I/AP-ROP, with variability in dosing, retreatment intervals, and surveillance protocols—underscoring the need for center-specific pathways.

Screening & treatment guidelines (practical points).

Screening.

Core criteria remain GA and BW thresholds with earlier first exams for the most immature infants; national policies increasingly add morbidity-based “sick infant” triggers and endorse wide-field imaging as an adjunct. Coordination with neonatology to ensure continuity across transfers is emphasized.

Staging/terminology.

Use ICROP3 nomenclature for zone (including posterior zone II), stage, plus/pre-plus, and document regression vs reactivation after therapy.

Treatment selection.

Laser photocoagulation remains standard for type 1 ROP outside the posterior pole; it avoids systemic VEGF suppression but ablates peripheral retina and is associated with higher rates of high myopia. ScienceDirect

Anti-VEGF (ranibizumab 0.2 mg; bevacizumab off-label) is favored for zone I and aggressive/posterior disease to preserve the macula/periphery and facilitate physiologic vascularization. However, it requires prolonged surveillance (months) for late reactivation and careful consideration of systemic exposure. Shared decision-making with NICU teams and families is essential. ScienceDirect+1

Follow-up. After anti-VEGF, schedule extended, frequent exams until vascularization reaches zone III and remains stable; document any reactivation precisely per ICROP3. PubMed

Prognosis and complications.
With timely screening and treatment, structural outcomes are favorable for most infants; nonetheless, lifetime ocular sequelae are common. High myopia, astigmatism, anisometropia/amblyopia, strabismus, and late retinal detachment warrant long-term pediatric ophthalmic follow-up. Risk of detachment persists into adolescence/adulthood, particularly after severe Retinopathy of prematurity. Some series suggest less high myopia after ranibizumab vs laser, but refractive outcomes vary by zone/stage and treatment timing. AAO+1

Key takeaways for treating ROP patients

Apply ICROP3 uniformly and document post-treatment status.

Use morbidity-based screening triggers to capture at-risk late-preterm, critically ill infants.

Select laser vs anti-VEGF by zone and disease biology; if using anti-VEGF, commit to extended surveillance for reactivation.

Build a lifelong follow-up plan targeting refractive error, amblyopia, strabismus, glaucoma, and late tractional events.

Selected references: ICROP3 (Ophthalmology, 2021–2022); BEAT-ROP (NEJM, 2011); RAINBOW 2-year outcomes (EClinicalMedicine/Lancet group, 2021; updates 2024); updated UK screening guideline (2024) reflecting morbidity-based criteria and imaging adjuncts.