The avascular zone and neuronal remodeling of the fovea in Parkinson disease

Abstract

Inner foveal thinning and intracellular alpha-synuclein were demonstrated in the retina in Parkinson disease. While pathognomonic alpha-synuclein is associated with embryonic dopaminergic (DA) neurons, postmortem studies in the nervous system and retina show prominent effect also in non-DA neurons. We evaluated foveal capillaries and foveal thickness in 23 Parkinson disease subjects and 13 healthy controls using retinal fluorescein angiography and optical coherence tomography. The size of the foveal avascular zone inversely correlates with foveal thinning. Foveal thinning highly correlates with motor impairment and also disease duration. Quantifying capillary and neuronal remodeling could serve as biological markers.

Figure 1

OCT and fluorescein angiography. (A) Retinal thickness measured by RTtvue includes foveal thickness, considered as the central area with 1 mm diameter, and parafoveal thickness, considered as the cocentered annular area with 3 mm diameter. The IPT/IFT ratio was calculated by dividing the average inner parafoveal thickness with the average inner foveal thickness. This normalized ratio quantifies foveal pit depth. (B) FAZ area measurements based on angiography images of the retina acquired by Heidelberg OCT-angiograph. The image contrast was adjusted by the image J software to enhance the FAZ. The border of FAZ was delineated and the area within the FAZ was calculated using the software (scale, 200 μm); (C) PDACN area was measured by delineating the area within the tip of radial capillaries and then subtracting the cocentered FAZ area. (D) Radial capillaries (arrows) were counted within the central foveal area with 3 mm diameter (area within black circle). (E) Macular fractal dimensions (FD) analysis using a peak phase angiographic image of the macula. The binary image of the skeletonized macular vasculature was produced using ImageJ software, and the Standard Box-Counting method (scale, 200 μm). F, fovea; S, superior; T, temporal; N, nasal; I, inferior; OCAT, optical coherence tomography; IFT, inner foveal thickness; IPT, Inner parafoveal thickness; FAZ, foveal avascular zone; PDACN, Perifoveolar diffuse annular capillary network.

Figure 2

(A) The negative correlation of the IPT/IFT ratio with UPDRS motor score and disease duration. Notice that subjects with higher UPRDS motor score and longer disease duration have lower IPT/IFT ratio. (B) The correlation between the FAZ area and the PDACN area. A smaller FAZ area correlates with smaller PDACN area in PD. (C) The correlation between FAZ area and IPT/IFT ratio in PD and HC subjects. Notice the decreased IPT/IFT ratio in PD subjects with smaller FAZ area. Most HC have higher thickness ratio and larger FAZ. The regression line demonstrates the correlation between thickness ratio and FAZ area, separately in PD and controls. OCAT, optical coherence tomography; IFT, inner foveal thickness; IPT, Inner parafoveal thickness; FAZ, foveal avascular zone; PDACN, Perifoveolar diffuse annular capillary network.

Figure 3

(A) Area of Perifoveolar thickness attenuation in PD patients (After Spund et al.5). (B) Fluorescein angiography image of the retina showing the distribution of dopaminergic neurons represented by X in the FAZ, according to topography of DA neurons in the FAZ, after Savy et al. (C) FAZ in PD; (D) Healthy control; and a (E) DM subject. Note the smaller FAZ surrounded by richer Perifoveolar annular capillary network in PD compared to HC and DM. F, FAZ; OD, optic disc; S, superior; T, Temporal; PD, Parkinson disease; FAZ, foveal avascular zone; DM, diabetes mellitus; DA, dopaminergic; HC, healthy controls.