Macular Perfusion Impairment in Von Hippel-Lindau Disease Suggests a Generalized Retinal Vessel Alteration.

Elisabetta Pilotto,Alfonso Massimiliano Ferrara,Edoardo Midena,Elisabetta Beatrice Nacci,Gilda De Mojà,Stefania Zovato

doi:10.3390/jcm9082677

Abstract

Background: To evaluate macular perfusion in patients with Von Hippel–Lindau (VHL) disease. Methods: VHL patients with or without peripheral retinal hemangioblastomas (RHs) were consecutively enrolled. A group of healthy subjects served as controls. Macular perfusion was analyzed by means of OCT angiography (OCTA) in the superficial vascular plexus (SVP), and in the intermediate (ICP) and deep retinal capillary (DCP) plexuses. The following OCTA parameters were measured: Vessel Area Density (VAD), Vessel Length Fraction (VLF), Vessel Diameter Index (VDI) and Fractal Dimension (FD). Results: Sixty-three VHL patients (113 eyes) and 28 healthy controls (56 eyes) were enrolled. All OCTA quantitative parameters were reduced in VHL patients vs. controls, reaching statistical significance for VAD of the SVP (0.348 ± 0.07 vs. 0.369 ± 0.06, p = 0.0368) and VDI of all plexuses (p < 0.03 for all). No significant differences were detected between eyes without or with peripheral RHs. Conclusions: Macular perfusion is reduced in VHL patients demonstrating retinal vessel changes that are independent of the presence of peripheral RHs. VHL gene mutations disrupt the hypoxia-induced (HIF)/vascular endothelium growth factors (VEGF) pathway and the Notch signaling, both essential for the normal retinal vasculogenesis and angiogenesis. Therefore, an anomalous generalized retinal vascular development may be hypothesized in VHL disease.

Highlights

Von Hippel–Lindau (VHL) disease (OMIM 193300) is an autosomal dominant heritable cancer syndrome with an incidence of 1 in 36,000 live births per year, caused by the oncosuppressor VHL gene mutation
Macular perfusion impairment was detected in patients with VHL disease and no retinal hemangioblastomas (RHs) at the posterior pole using Optical coherence tomography (OCT) angiography (OCTA)
The main vascular changes were detectable at the superficial vascular plexus (SVP) level, where the vascular area density (VAD) and the vessel diameter index (VDI) were significantly reduced, depicting a vascular bed characterized by retinal vessels lower in number and thinner in diameter compared to healthy controls

Summary

Introduction

Von Hippel–Lindau (VHL) disease (OMIM 193300) is an autosomal dominant heritable cancer syndrome with an incidence of 1 in 36,000 live births per year, caused by the oncosuppressor VHL gene mutation. Macular perfusion was analyzed by means of OCT angiography (OCTA) in the superficial vascular plexus (SVP), and in the intermediate (ICP) and deep retinal capillary (DCP) plexuses. All OCTA quantitative parameters were reduced in VHL patients vs controls, reaching statistical significance for VAD of the SVP (0.348 ± 0.07 vs 0.369 ± 0.06, p = 0.0368) and VDI of all plexuses (p < 0.03 for all). No significant differences were detected between eyes without or with peripheral RHs. Conclusions: Macular perfusion is reduced in VHL patients demonstrating retinal vessel changes that are independent of the presence of peripheral RHs. VHL gene mutations disrupt the hypoxia-induced (HIF)/vascular endothelium growth factors (VEGF) pathway and the Notch signaling, both essential for the normal retinal vasculogenesis and angiogenesis. An anomalous generalized retinal vascular development may be hypothesized in VHL disease

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