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In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model
Published on: January 21, 2018
Unfolding the Pitchfork Sign in Type 2 Choroidal Neovascularization: A Longitudinal Analysis and 3-Dimensional
Edoardo Balduzzi1,2, Giovanni Ometto3,4, Francesco Bandello1,2
1Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Purpose:
To longitudinally characterize and redefine the structural basis and clinical significance of the pitchfork sign in type 2 choroidal neovascularization (CNV) using multimodal imaging with 3-dimensional confirmation.
Design:
Retrospective observational study.
Subjects:
Thirty-nine eyes with treatment-naive type 2 CNV showing a pitchfork sign on spectral-domain OCT.
Methods:
Outer retinal changes were graded, focusing on splitting at the ellipsoid zone (EZ) and infolding of the external limiting membrane (ELM). Quantitative measures included projection number, maximal fold height, subretinal fluid (SRF) height, subretinal hyperreflective material (SHRM) height, and posttreatment pigment epithelial detachment (PED) height; correlations with best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) were assessed. Three-dimensional reconstructions of the outer retina were generated to verify the spatial configuration of folds.
Main Outcome Measures:
Structural characterization of the retinal layer involved in the pitchfork sign; quantitative morphologic parameters (projection number and maximal fold height); their correlation with exudative and anatomical features (SRF, SHRM, PED height); and association with BCVA.
Results:
The pitchfork sign occurred in idiopathic (69%), inflammatory (23%), and myopic (8%) CNV, indicating it is not disease-specific. Imaging revealed a reproducible mechanical sequence: elevation of the outer retina by type 2 CNV; cleavage at the EZ with formation of a new fluid-filled split between the EZ and ELM; centrifugal buckling and infolding from the lesion margin toward the CNV core; and, in some eyes, transient partially enclosed "mushroom-shaped" closed folds that trapped fluid. These folds ultimately collapsed into sharply angulated vertical hyperreflective lines-the pitchfork configuration. Three-dimensional reconstructions confirmed that the apparent "tines" are radially arranged outer retinal folds anchored to the neovascular complex. Quantitatively, fold number correlated with SRF height (r = 0.40, P = 0.01), SHRM height (r = 0.41, P = 0.009), and maximal fold height (r = 0.49, P = 0.002). Greater maximal fold height was associated with worse presenting BCVA (r = 0.48, P = 0.003). After anti-VEGF, all folds resolved, and the CNV regressed beneath a continuous retinal pigment epithelium, forming a fibrovascular PED whose height at follow-up correlated with baseline fold count (r = 0.35, P = 0.04).
Conclusions:
The pitchfork sign in type 2 CNV reflects transient, mechanically induced folding and splitting of the outer retina overlying subretinal neovascular tissue, rather than an inflammatory biomarker. Greater retinal deformation at presentation was associated with worse presenting vision and with a higher fibrovascular PED after treatment.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
