In this study, we utilized OCTA to analyze the macular microvasculature and further explore the morphological changes of FAZ. We found that several FAZ parameters were larger in highly myopic eyes than in non-highly myopic eyes, and that the differences were even more pronounced in the deep FAZ layer. Moreover, the acircularity and circularity indexes of the FAZ were significantly correlated with FAZ enlargement in highly myopic eyes, whereas no significant relationships were found between these parameters in the non-highly myopic group. To our knowledge, this was the first report to determine FAZ deformation in high myopia.
Several reports have investigated the FAZ in myopic eyes.5, 14–16,21,22 Sung et al. reported lower peripapillary vessel density and larger superficial and deep FAZ areas in highly myopic eyes, as elucidated using OCTA.5 He et al. also demonstrated that reduced radial peripapillary capillary, deep parafoveal vessel density, and enlarged FAZ area occurred in high myopia.14 Similarly, Cheng et al. showed that increased FAZ area and decreased vessel density in the superficial and deep layers were correlated with axial elongation.15 All these studies reported that FAZ enlargement was accompanied by a reduction of retinal vessel density in the macular region, indicating that the size of the FAZ indirectly reflects variations in retinal perfusion. Although we did not measure vessel density in the present study, our results are in accordance with those of the previous reports.
The mechanism of FAZ enlargement in myopic eyes remains unclear, although some hypotheses have been offered. First, retinal vascular trunk dragging during myopia progression may decrease retinal blood flow and further result in variation in the FAZ size. Two previous studies reported that the FAZ areas were significantly associated with optic nerve head tilt, which occurs during axial elongation.5,14 Second, in eyes with axial elongation, overall macular thinning may cause reduced oxygen consumption, resulting in decreased retinal blood flow and increased FAZ area.23,24 In the current study, the FAZ areas in highly myopic eyes were significantly larger than those in non-highly myopic eyes, and the difference was more significant in the deep FAZ layers, suggesting that the deep capillary plexus is more susceptible to myopia-related changes, possible because the arterial blood supply differs between the superficial and deep capillary plexuses. The oxygen and nutrition demand of the superficial retina is met by the central retinal artery, while that of the deep retina is met by the choroidal vascular system.25 Since choroidal thinning is more prominent in highly myopic eyes,26 FAZ enlargement might be more pronounced in the deep retinal layer.
Numerous studies have researched FAZ deformation, but none have explored the morphological changes in the FAZ in high myopia. In the present study, we speculated that either or both of the following mechanisms influence FAZ morphology: First, the retinal vascular trunk in the ONH was dragged, resulting in irregular reduction in macular blood perfusion, with consequent FAZ deformation and enlargement during axial elongation. Second, despite individual variations, the FAZ morphology in non-highly myopic eyes may be relatively circular in most cases. Moreover, as the retinal vascular trunk was dragged nasally in highly myopic eyes, the macular microvasculature may have been distorted towards the ONH, leading to FAZ deformation. One prospective observational study on progressive myopia indicated that the retinal vasculature at the posterior pole was unchanged, and that only the central vascular trunk in the lamina cribrosa was dragged nasally.27 However, that study did not measure the retinal vasculature of the macular region using OCTA; from a macroscopic point of view, it demonstrated that the posterior polar blood vessels did not change, but it did not analyze the macular microvasculature. As such, the results were insufficient to explain the lack of variation in the FAZ capillaries. Therefore, depending on geometrical change in the FAZ, it may be possible to confirm myopia severity and macular perfusion status. Future longitudinal study should verify this.
Of note, we found that the FAZ areas were not significantly associated with the acircularity or circularity index in non-highly myopic eyes. However, they were positively correlated with acircularity index and negatively correlated with circularity index in highly myopic eyes, suggesting that the FAZ area becomes larger and more acircular as myopia progresses. Variations in the FAZ acircularity/circularity indexes and FAZ size may have multiple clinical significances. Kwon et al. showed that a decreased FAZ circularity index was significantly associated with central visual field defect, and that the FAZ size was significantly associated with the severity of central visual field defect in glaucomatous eyes.28 Choi et al. reported that decreased FAZ circularity index may represent a disruption of the parafoveal capillary network in patients with glaucoma.29 Kim et al. also showed that decreased FAZ circularity is a good indicator of vascular dropout, and that it is associated with disease progression in vascular maculopathy.30 Another study found a significant difference in acircularity index between controls and non-proliferative DR. This result could inform objective staging of the disease.13 Before the disease has progressed significantly, the retinal microvascular system in myopic eyes has already suffered structural damage, and discernible microvascular changes are visible in the FAZ. Given that FAZ acircularity is associated with visual field defects and macular vascular dropout, our results might explain the reason for the high prevalence of central scotoma in myopic glaucoma.
Recently, Krawitz et al. reported that, unlike other indicators such as area, perimeter, and length, the acircularity index can quantify FAZ geometry without the need for axial length measurements to correct for retinal magnification.13 It follows that the acircularity index (including circularity index) could serve as indicators to predict pathological myopic changes in advance. Long-term monitoring of FAZ evolution using the acircularity and circularity indexes may be necessary to substantiate the clinical value of these metrics, which are not influenced by ocular magnification correction.
The limitations of the current study were as follows: The study was retrospective, and to evaluate the specific influence of axial myopia, we set further criteria, which resulted in a small sample size. A prospective big data study is needed to improve data accuracy. Furthermore, we did not measure the retinal thickness in detail. One previous study demonstrated that early foveal microcirculatory alterations in diabetic eyes were related to macular ganglion cell/inner plexiform layer thickness, regardless of the presence of DR.30 Intraretinal thickness may therefore be related to FAZ deformation in myopic eyes. Future studies should investigate this relationship further to deepen the current understanding of myopia progression.
In conclusion, we observed FAZ enlargement in highly myopic eyes, especially in the deep retinal layer. This enlargement accompanied changes in the acircularity and circularity indexes of the FAZ in highly myopic eyes. Further research should address whether these findings are associated with future disease development in highly myopic eyes.