Retinal Microvascular Network and Microcirculation Assessments in High Myopia

Abstract

Purpose: To investigate the changes of the retinal microvascular network and microcirculation in high myopia.

Design: A cross-sectional, matched, comparative clinical study.

Participants: Twenty eyes of 20 subjects with nonpathological high myopia (28 ± 5 years of age) with a refractive error of -6.31 ± 1.23 D (mean ± SD) and 20 eyes of 20 age- and sex-matched control subjects (30 ± 6 years of age) with a refractive error of -1.40 ± 1.00 D were recruited.

Methods: Optical coherence tomography angiography (OCTA) was used to image the retinal microvascular network, which was later quantified by fractal analysis (box counting [Dbox], representing vessel density) in both superficial and deep vascular plexuses. The Retinal Function Imager was used to image the retinal microvessel blood flow velocity (BFV). The BFV and microvascular density in the myopia group were corrected for ocular magnification using Bennett's formula.

Results: The density of both superficial and deep microvascular plexuses was significantly decreased in the myopia group in comparison to the controls (P < .05). The decrease of the microvessel density of the annular zone (0.6-2.5 mm), measured as Dbox, was 2.1% and 2.9% in the superficial and deep vascular plexuses, respectively. Microvessel density reached a plateau from 0.5 mm to 1.25 mm from the fovea in both groups, but that in the myopic group was about 3% lower than the control group. No significant differences were detected between the groups in retinal microvascular BFV in either arterioles or venules (P > .05). Microvascular densities in both superficial (r = -0.45, P = .047) and deep (r = -0.54, P = .01) vascular plexuses were negatively correlated with the axial lengths in the myopic eye. No correlations were observed between BFV and vessel density (P > .05).

Conclusions: Retinal microvascular decrease was observed in the high myopia subjects, whereas the retinal microvessel BFV remained unchanged. The retinal microvascular network alteration may be attributed to ocular elongation that occurs with the progression of myopia. The novel quantitative analyses of the retinal microvasculature may help to characterize the underlying pathophysiology of myopia and enable early detection and prevention of myopic retinopathy.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Fig. 1. Magnification correction of OCTA image

The OCTA original image with an image size of 245 × 245 pixels was resized to 1,024 × 1,024 pixels (Fig. 1 left). The resized image was then enlarged according to the scaling factor calculated using the axial length with Bennett’s magnification correction formula (Fig. 1 middle). After that, the enlarged image was trimmed to 1,024 ×1,024 pixels as the corrected image for myopic eye (Fig. 1 right). Bar = 500 µm.

Fig. 2. Image processing and partition of retinal vessel network

To remove and separate the large vessel from the microvascular network in the superficial microvascular network and the shadowgraphic artifact (Fig. 2 upper left), custom segmentation software applied a series of image processing procedures such as inverting, equalizing and the removing background noise and non-vessel structures to create a binary image (Fig. 2 middle left). From the binary image, any vessel with a diameter ≥ 25 µm was removed and the remaining microvessels were then skeletonized (Fig. 2 bottom left). The software detected the center of the foveal avascular zone (FAZ) by searching the intensity gradient from the image center to the periphery (Fig. 2 middle left). The center of the FAZ was used for quadrantal and annular partition (Fig. 2 upper and bottom right). After removing the avascular zone (diameter = 0.6 mm) centered on the fovea, the annulus from 0.6 mm to 2.5 mm in diameter was defined as the annular zone with a bandwidth of 0.95 mm (Fig. 2 bottom left). The annular zone was divided by vertical and horizontal meridians into four quadrantal zones, named superior temporal (ST), inferior temporal (IT), superior nasal (SN) and inferior nasal (IN) (Fig. 2 upper right). In addition, the annular zone was divided into 6 thin annuli with a bandwidth of ~0.16 mm (Fig. 2 bottom right). Bar = 500 µm.

Fig. 3. Retinal blood flow velocity in arterioles and venules

The retina of a myopia subject was imaged using RFI with a field of view of 20 degrees, centered on the fovea. The secondary and tertiary branches of the retinal vessels were measured. The arterioles (marked in red) and venules (marked in purple) were labeled and read with the measured blood flow velocities (Mean ± SD: mm/s). A negative value indicates blood flow away from the heart. In this case, the arteriolar flow moved toward the fovea. A positive value indicates blood flow toward the heart. In this case, the vessels are venules. Bar = 500 µm.

Fig. 4. Comparison of the retinal microvascular network of the myopia group and control group in superficial and deep vascular plexuses

Superficial (Fig. 4 upper left and right) and deep (Fig. 4 bottom left and right) vascular plexuses were obtained in a high myopic eye (Fig. 4 upper and bottom left) and a healthy control eye (Fig. 4 upper and bottom right). Fractal dimension (Dbox), representing the microvascular network, was calculated after the large vessels in the superficial vascular plexus and shadowgraphic projection artifact in the deep vascular plexus were removed. Dbox of the annulus from 0.6 to 2.5 mm in diameter is listed under each of the figures and shows decreased microvascular density in both Fig. 4 upper and bottom left of the myopic eye compared to the control eye (Fig. 4 upper and bottom right). Note: Fig. 4 bottom left and right are raw images and the shadowgraphic projection artifacts are present.

Fig. 5. Retinal microvascular density between the myopia subjects and the controls

Fractal analysis of the microvascular network was performed in each of the thin annuli and quadrants and fractal dimension (Dbox) was obtained, representing vessel density. The microvessel densities of the annuli (from 0.6 to 2.5 mm in diameter) of both superficial and deep vascular plexuses were significantly lower in the myopia group than in the control group (P < 0.01, Fig. 5 upper left and right). Analysis of quadrantal partitions showed significant decreases in all quadrants in both plexuses, with the exception of the ST quadrant (P < 0.05, Fig. 5 upper left and right). The microvessel density in the thin annuli from C2 to C6 were significantly lower in the myopia group compared to the control group (P < 0.05, Fig. 5 bottom left and right), except for C2 in the deep vascular plexus. ST: Superior temporal, IT: inferior temporal, SN: superior nasal, IN: inferior nasal.

Fig. 6. Relationship between retinal microvascular density and axial length and refraction

Microvascular density in both superficial and deep vascular plexuses was negatively correlated with AL and refractive diopters when the results of both groups were combined. When the densities were analyzed separately, microvascular densities in both superficial (r = −0.45, P = 0.047, Fig. 6 upper left) and deep (r = −0.54, P = 0.01, Fig. 6 upper right) vascular plexuses were negatively correlated with the axial lengths in the myopic eye. Interestingly, microvascular densities in the superficial vascular plexus (r = −0.52, P = 0.02, Fig. 6 bottom left) was negatively correlated to the refractive diopter in the control group. The black line in each panel denotes the regression line for combining both groups.