Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity

Graefes Arch Clin Exp Ophthalmol. 2019 Apr;257(4):677-688. doi: 10.1007/s00417-019-04274-6. Epub 2019 Feb 21.


Background: The application of three-dimensional (3D) visualization techniques to evaluate the earliest visible onset of abnormal retinal vascular development in preterm infants with retinopathy of prematurity (ROP), using bedside non-contact optical coherence tomography (OCT) imaging to characterize morphology and sequential structural changes of abnormal extraretinal neovascularization.

Methods: Thirty-one preterm infants undergoing routine ROP screening with written informed consent for research imaging were enrolled in this prospective observational study. We imaged the macula and temporal periphery of preterm infants using a handheld OCT system (Envisu 2300 or handheld swept-source research system). The scans obtained were segmented and, using enhanced ray casting, were converted to 3D volumes to which color filter was applied.

Results: Using colorized 3D visualization, we defined extraretinal neovascular structures as buds, bridging networks, and placoid lesions. We could longitudinally follow progression and regression of extraretinal neovascularization in stage 3 ROP after treatment in one infant over 12 weeks and document the appearance of early buds, and formation of florid neovascularization. From stages 2 to 3 ROP, we observed progression from sessile buds to a complex plaque that corresponded to stage 3 ROP on clinical examination. We demonstrated regression of neovascular complexes to small pre-retinal tufts after treatment with anti-VEGF.

Conclusions: The extension of OCT processing to include surface flattening and colorization that further improved structural analysis rendered better understanding of extraretinal tissue. Our ability to image similar areas in the same infant over multiple visits enabled us to study the evolution of these structural components and follow pathological vascular events longitudinally in development and regression after treatment. These methods can be applied to further study which are likely contribute to our understanding of the pathophysiology of neovascularization in ROP.

Keywords: 3D; OCT; Optical coherence tomography; ROP; Retinopathy of prematurity; Visualization.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Bevacizumab / therapeutic use
  • Gestational Age
  • Humans
  • Imaging, Three-Dimensional
  • Infant
  • Infant, Premature
  • Intravitreal Injections
  • Prospective Studies
  • Retinal Neovascularization / diagnostic imaging*
  • Retinal Neovascularization / drug therapy
  • Retinal Vessels / diagnostic imaging*
  • Retinopathy of Prematurity / diagnostic imaging*
  • Retinopathy of Prematurity / drug therapy
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors


  • Angiogenesis Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab