Clinicopathologic Correlation of Anti–Vascular Endothelial Growth Factor–Treated Type 3 Neovascularization in Age-Related Macular Degeneration

Academic Article


  • Purpose: To correlate histologic results with previously recorded multimodal imaging results from a patient with type 3 neovascularization secondary to age-related macular degeneration (AMD). Design: Case study, clinical imaging, laboratory imaging, and eye-tracked clinicopathologic correlation. Participant: An 86-year-old white woman with type 3 neovascularization secondary to AMD treated with 6 intravitreal injections of bevacizumab. Methods: Multimodal retinal imaging at each clinic visit was correlated with ex vivo and high-resolution histologic images of the preserved donor eye. Clinical imaging included serial near-infrared reflectance and eye-tracked spectral-domain OCT. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding to clinical OCT signatures. Main Outcome Measures: Histologic correlates for clinical OCT signatures were sought, including reflectivity of the vascular complex, intraretinal hyperreflective foci and intraretinal cellularity, analysis of the topography of pathologic features, and evaluation of the sub–retinal pigment epithelium (RPE) plus basal lamina (BL) space. Results: Clinical imaging showed a deep neovascular lesion in close relationship with a mixed serous and drusenoid pigment epithelium detachment (PED), characteristic of type 3 neovascularization. Antiangiogenic therapy achieved a complete resolution of exudation. The PED progressively flattened with each treatment, leaving a persistent triangular hyperreflectivity in the outer retina. This persistent deep lesion histologically correlated with a vascular complex implanted into sub-RPE basal laminar deposit. No connection between the choriocapillaris and the sub-RPE plus BL space was observed. Both RPE-derived and lipid-filled cells were correlated with clinical intraretinal hyperreflective foci. The sub-RPE plus BL space contained macrophages, lymphocytes, Müller cell processes, and subducted RPE. Conclusions: Clinicopathologic correlation of type 3 neovascularization showed vascular elements of retinal origin accompanied by collagenous material and Müller cell processes implanting into thick sub-RPE basal laminar deposit, which may simulate the appearance of chorioretinal anastomosis. Surrounding RPE-derived and lipid-filled cells thought to be microglia correlated with clinical intraretinal hyperreflective foci.
  • Published In

  • Ophthalmology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Li M; Dolz-Marco R; Messinger JD; Wang L; Feist RM; Girkin CA; Gattoussi S; Ferrara D; Curcio CA; Freund KB
  • Start Page

  • 276
  • End Page

  • 287
  • Volume

  • 125
  • Issue

  • 2