Structural and microvascular changes of the peripapillary retinal nerve fiber layer in Von Hippel-Lindau disease: an OCT and OCT angiography study

Abstract

Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic disease caused by VHL gene mutation. Retinal hemangioblastomas (RH) are vascularized tumors and represent the main ocular manifestation of the disease. Histopathologically, RH are composed of capillary vessels and stromal cells, the neoplastic population of the lesion. The origin of these stromal cells remains controversial, even if they are hypothesized to be glial cells. The aim of the present study was to investigate neuronal and microvascular changes of the peripapillary retinal nerve fiber layer, in which glial cells, neurons and capillaries (the radial peripapillary capillary plexus) interact. VHL patients with or without peripheral RH were enrolled and compared to healthy controls. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness was measured by means of optical coherence tomography (OCT). The following vascular parameters of the radial peripapillary capillary plexus were quantified using OCT angiography: Vessel Area Density,Vessel Length Fraction, Vessel Diameter Index and Fractal Dimension. One hundred and nine eyes of 61 patients, and 56 eyes of 28 controls were consecutively studied. Mean pRNFL was significantly thinner in VHL eyes without RH versus eyes with RH and controls. Mean pRNFL thickness did not differ between VHL eyes with RH and controls. All OCTA vascular parameters were reduced in VHL eyes with or without RH versus controls, with significative difference for Vessel Diameter Index. The same OCTA parameters did not significantly differ between VHL eyes with or without RH. In VHL eyes without RH, pRNFL thinning may be the consequence of impaired perfusion of the radial peripapillary capillary plexus, while the increase of pRNFL thickness in VHL eyes with RH may depend on possible activation and proliferation of the other RNFL resident cells, the glial cells.

Figure 1

Peripapillary OCT-Angiography capillary plexus in VHL eye (A) and Healthy control (B). En face OCT-Angiography of the Radial Peripapillary Capillary Plexus showed reduced vascular perfusion in a VHL eye (A) compared to a healthy control (B). Quantification of plexus perfusion, expressed through evaluation of Vessel Area Density (VAD), Vessel Length Fraction (VLF), Vessel Diameter Index (VDI), Fractal Dimension on binary image (FDbin) and Fractal Dimension on skeletonized image (FDsk) indexes, detected a significant reduction in VHL eyes of VDI parameter.