Unveiling the Hidden Risks of ROP: How Isolated Retinal Neovascularization Signals Severe Disease Progression in Premature Infants

  • Overview of Isolated Retinal Neovascularization (IRNV):

    • IRNV, previously termed “popcorn” lesions, is a common finding in stage 2 and 3 retinopathy of prematurity (ROP), visualized as neovascular tufts posterior to the ridge.

    • Pathophysiology: Driven by low birth weight (BW), low gestational age (GA), and high/fluctuating oxygen exposure, leading to abnormal retinal neovascularization.

 

  • Epidemiology and Risk Factors:

    • IRNV Demographics: Occurs in higher-risk infants with lower BW (660.1 vs. 916.8 g, P=0.001) and lower GA (24.9 vs. 26.1 weeks, P=0.01).

    • Zone I Predominance: IRNV strongly associated with Zone I ROP (63.4% vs. 15.8%, P<0.001), indicating more posterior, severe disease.

 

  • Imaging and Diagnosis:

    • Ultrawidefield OCT (UWF-OCT):

      • Captures >140° en face scans, providing high-contrast visualization of IRNV compared to traditional fundus photography.

      • Identifies IRNV morphologies: isolated tufts, coalescent NV separate from the ridge, or confluent NV merging with the stage 3 ridge.

    • IRNV Detection: Found in 37% (22/60) of infants with stage 2 or worse ROP in a single-center study.

  • Clinical Significance:

    • Disease Progression:

      • IRNV as a Risk Factor: Independently associated with progression to stage 3 (68.2% vs. 13.2%, P<0.001) and treatment-requiring ROP (54.5% vs. 15.8%, P=0.002), even when controlling for GA, BW, and Zone I disease.

      • IRNV often precedes stage 3 by ~2.5 weeks (range 0–8 weeks), appearing at a mean postmenstrual age of 35 weeks.

    • Vascular Severity Score (VSS):

      • Eyes with IRNV have higher peak VSS (5.61 vs. 3.73, P<0.001) and elevated VSS throughout the disease course, particularly at postmenstrual ages 34–37 weeks (4.02 vs. 3.03, P=0.01).

 

  • Morphological and Longitudinal Features:

    • IRNV Location: Predominantly temporal (100%), with nasal involvement in 22.7% and all-quadrant involvement in treatment-requiring cases.

    • Recurrence Post-Treatment: IRNV can redevelop after initial regression following intravitreal bevacizumab, requiring subsequent laser for persistent avascular retina.

    • 3D OCT Evaluation: UWF-OCT provides volumetric analysis of IRNV, potentially serving as a biomarker for disease burden.

  • Treatment Implications:

    • Anti-VEGF and Laser:

      • Of 18 infants requiring treatment, 8 received intravitreal bevacizumab followed by laser for persistent avascular retina.

      • IRNV presence increases likelihood of needing intervention, highlighting its prognostic value.

    • Monitoring: Eyes with IRNV require closer follow-up due to higher risk of progression and reactivation.

  • Future Directions:

    • OCT-Based Classification: IRNV’s association with severe ROP suggests potential for integration into future ICROP classifications.

    • Research Needs: Longitudinal studies to clarify IRNV’s role in ROP regression vs. progression and its response to therapies.

Citation

Burt SS, Woodward M, Ni S, et al. Isolated Retinal Neovascularization in Retinopathy of Prematurity: Clinical Associations and Prognostic Implications. Ophthalmology Retina. 2024;8(10):1021-1028. doi:10.1016/j.oret.2024.04.026