The main purpose of this study is to compare the difference of ONH between SHM and PM, so as to find the measurable indicators of morphological and microcirculatory parameters related to ONH. At present, the clinical definition of PM is not clear. Therefore, it is necessary to discover the unique features of PM from the existing examination equipment.
1 The relative position of ONH
Previous study have shown that axial myopia mainly depends the posterior eyeball enlargement, and the closer the posterior pole the more obvious[6]. To assess the extent of expansion of the posterior eyeball, We measured the DFD and angle α. DFD is a description of the relative position of ONH and fovea, and we found that DFD in the PM group was longger than the SHM group. In a prospective study[7], it was found that DFD increased from (4.98±0.3) mm to (6.11±0.5) mm in adolescents with an increasing AL. As a characteristic indicator of the posterior polar morphological changes of HM, angle α is an important reference for the nasal displacement of ONH. We found that the angle α of SHM (122.85±22.34) bigger than PM(113.77±17.39). Compared with the SHM, the distance between ONH and fovea of PM was further widened, and the upper and below retinal vessels were pulled to cause the reduction of vascular clamp. In a prospective observation study, Lee[8] found that with axial elongation of myopia, the central vascular trunk of retina were dragged nasally, believing that nasally passive traction of the lamina cribiosa was the main reason. Changes in DFD and angle α can be explained by the expansion of the posterior eyeball in myopia, and the closer the posterior pole the more obvious. Therefore, it is once again proved that the posterior eyeball enlargement and the peripapillary tissue pulling displacement are progressive aggravation in PM.
2 The shape and size of ONH
Normal ONH is round or oval with an average diameter of 1.5mm. ONH is the access of the optic nerve and retinal vessels in eye, consisting of nerves, vessels and bindweb. The changes of ONH are often manifested as tilt and PPA in HM. Results show that there is no significant difference between the area and SD of ONH in SHM group and PM group, while LD and tilt index of ONH are significantly different, and the ratio of tilt increased in PM. On the one hand, the ONH becomes more non-round and more flat in HM. On the other hand, the serious tilt and distorted deformation have an adverse impact on the optic nerve and resulting in vision decline[9]. This indicates that the identifiable or quantitative parameters should be obtained from the tilt and deformation of ONH.
3 The size and type of peripapillary atrophy(PPA)
PPA is attributed to photoreceptor reduction, RPE and choroid capillary loss, bruch membrane displacement or defects. As a characteristic change of myopia, the expansion of PPA indicates the progression of myopia. During 20 years prospective studies on fundus in children with HM, Yokoi[10] found that 87% of adults with PM had diffuse choroid retinal atrophy in childhood, suggesting that adult patients with PM already showed a fundus appearance different from the fundus appearance in children with simple myopia. Meanwhile, the sign of peripapillary diffuse chorioretinal atrophy in childhood may be an indicator or biomarker for more advanced myopic chorioretinal atrophy in later life. Our results show that the PPA area and radian of the PM group were significantly greater than the SHM. However, the actual area size cannot be calculated due to image analysis using image J software. So we introduce the ratio of PPA area / ONH area (PPA/ONH) to estimate the size of the PPA. The PPA/ONH of the PM group was 1.24 ± 0.17, significantly greater than 0.52 ± 0.04 in the SHM group. It indicates that when the PPA area is bigger than the ONH area, we need to carefully examine and find evidence of PM.
4 The thickness of the peripapillary tissue
ONH is seamless connected to the RNFL, choroid, and sclera, and which play a key role in morphology changes. PRNFL mainly shows changes in thickness and distribution in HM. Our results show that the average thickness of PRNFL in PM group is lower than that of SHM group, especially inferior and superior; However, the temporoinferior PRNFL of PM group is slightly higher than that of SHM group. Analogously, while studying the changes in displacement and morphology of ONH, Tan[11] found that the angle between the superior and inferior temporal RNFL bundles decreased by 3.3°for every 1mm increasing of AL. A reasonable explanation is that the retina pulls along with the ONH to the nasal side in axial myopia, and the inferior and superior RNFL move closer toward the temporal side. Clinically, there is often a shift of the peak RNFL position to the temporal side, which leads to relative thickening in temporal.
The choroid, as a vascular tissue, lies between scleral and retina. Compared with normal people, both in anatomy and OCT, choroid is shown to be significantly atrophy and thinning in HM[12]. Moreover, our study further demonstrated that the choroid of PM(93.82±29.96μm) was thinner compared with SHM(108.75±30.70μm). Subregional measurements show that nasal and superior PCT were thicker than the inferior and temporal PCT, where the temporal side was the thinnest. This heterogeneity of altered choroid may be an intrinsic reason why myopia-associated fundus lesions often occurring on the temporal side of ONH[13]. Choroid not only support outer retinal nutrition, but also release multiple vascular factors to regulate scleral growth. Studies have found that a compensatory increase in retinal vessel oxygen saturation was observed in moderate myopia, which may be related to insufficient choroid blood supply to the outer retina and increased oxygen consumption. But this compensatory effect disappears immediately when HM occurs, making the retina more prone to pathological changes. Meanwhile, Liu[14] found that the choroid is involved in the transmission of biological signals from retina to sclera, and is involved in the regulation of scleral remodeling and staphyloma. Therefore, more attention should be paid to choroid to assess the progression of PM.
As the outermost layer of the eyeball, the sclera plays an important role in stabilizing intraocular pressure, protecting intraocular structure and maintaining normal morphology. The morphology and structure of the sclera is constantly changing, and its biochemical and biomechanical properties change with AL, including phenotype of the scleral fibroblasts and composition of the extracellular matrix[15]. Whether the posterior scleral bound is detected by SS-OCT is closely related to the choroidal thickness and the bruch membrane atrophy, so the full sclera appearance reflects the pathologic status of eyeball. Ohno-Matsui used the SS-OCT to find that 57% of the eyes can show the whole scleral structure, and the Tenon's capsule and orbital fat tissue can also be shown in some eyes[16]. In this study, the rate of full-peripapillary sclera appearance in whole subjects reached 51.3%, and the rate in PM(63.6%) was significantly higher than that in SHM(46.4%). This also means that prescleral tissue atrophy was much higher in the PM than SHM. However, no comparable parameters were obtained by scleral thickness, and may suggest that PST isn't a reliable indicator of PM.
In conclusion, we speculate that choroidal changes may precede the RNFL and sclera, by affecting the blood supply of the two tissues, stimulate myopia toward HM, and ultimately result in PM. These initial insights may provide clues and basis for further investigation of histology in HM.
5 The microcirculation of the ONH
In this study, the PVD was lower in the PM group compared with the SHM. Similarly, a study showed that HM with less peripapillary retinal blood flow index and vessel density(VD) compared to the emmetropia, suggesting decreased peripapillary microcirculation perfusion[17]. We also found that the PVD in PM was lower in each direction than in SHM, and the VD in the temporal direction was higher than that in the nasal direction in both group. This result may suggest that blood flow may be preferentially perfused in the bow-shaped nerve fiber region to meet the energy metabolic needs of RNFL. Just as no significant VD reduction was found in the macula of HM. Such a relative retention of retinal blood flow perfusion in the vital area can ensure the normal visual function. At the same time, we found that the PCT in the nasal direction was thicker than that in the temporal direction, quite opposite to the results of retinal blood perfusion. The reason may be due to the anatomical characteristics of the ONH, and the complex blood circulation, witch mainly provided by the retinal circulation and choroidal circulation. Meanwhile, the Zinn-Haller provided the main blood supply to the lamina cribiosa of ONH, and Ishida[18] found that the distance between the Zinn-Haller and the boundary of ONH increased significantly with AL. On the one hand, the Zinn-Haller may play a key role in maintaining blood perfusion stabilization in the ONH; On the other hand, the progressive tilt and rotation of ONH are often accompanied by abnormal and slow choroidal circulation and terminal artery occlusion in HM, It is easy to occur circulation disorder in ONH. However, the mechanism of reduced retinal and choroidal perfusion is unclear. It is often believed that hyperexpansion causes the retina and choroidal thinning in HM, and these thinning tissues may reduce oxygen demand and thus blood perfusion[19].
We acknowledge a number of limitations associated with our study. This is a retrospective study and hence longitudinal data were not available, thus, it may not reflect the true representative of the population. Furthermore, as the requirements of SS-OCT scan quality, most patients with PM were excluded from the study, and selection bias inevitably occurs. Last, the magnification effect of images may affect the results of OCT measurements (e. g., vessel density and area), but the current formula for amplification correction is not uniform, and remeasurement is separated from the OCT measure system, which may bring new deviations. However, the range of 4.5×4.5mm scans used in this study is small enough that the effect of the amplification effect is not significant.