In this study, we found RPC density decreased with increasing AL, which was in accordance with findings of previous studies [9, 10]. It was speculated that the excessive elongation of eyeball could cause thinning of retina, which might lead to decrease in blood circulation [11, 12]. Nevertheless, the mechanism underlying the reduced blood flow in eyes with HM still required further investigation. In most previous studies, only wRPC density was evaluated, so we examined RPC in more detail in this study. Notably, our results showed all RPC density decreased when emmetropia progressed towards low-to-moderate myopia, except iRPC density increased. We speculated the tension on the posterior pole of eyeball increased as its axial elongation, which would affect more significantly in peripapillary area than in center of optic disc [13]. Besides, there might be potential compensatory mechanism to improve blood supply inside optic disc to maintain normal function, which required further research to study specific mechanism underlying the increasing iRPC density in HM eyes. However, Yaprak et al. did not detect decrease of iRPC density in HM group, while they did not observe any correlation between AL and iRPC. They thought the stabilization of iRPC density might be related to only non-pathological HM included in their study [8]. We speculated differences of their results from ours might be attributed mainly to insufficient sample size, for 188 subjects in our research and 75 subjects in Yaprak’s research. Few studies have reported OCTA iRPC density results, so further studies with larger sample size were necessary. iRPC density, the only vessel density indicator changed in LM or MM compared to EM in our study, maintained significantly increasing trend in whole progression of myopia degree. Therefore, we speculated increase of iRPC density might indicate patients more likely to develop into HM in the future, and its increase could be used as key monitoring indicator of myopia progression. Additionally, our results found RPC density of NS, NI, IN quadrants remarkably reduced when LM or MM developed further to HM. Previous studies also showed the vessel loss in nasal quadrant was most serious in HM than LM group [14]. We suggested that RPC density in nasal quadrant might be more susceptible to myopic-related structural changes than in other quadrants, so its decline could be used as important monitoring indicator of myopia progression. In current study, we adopted AL rather than dioptric values to measure the degree of myopia, because dioptric values could be affected by crystalline lens status and it was known that axial elongation is related to the mechanism of myopic optic disc change [15]. Liu et al. also showed that AL was more strongly associated with myopic retinal change than refractive error [16].

We found a negative correlation between AL and RNFLT in most quadrants, which accorded well with some previous studies [17,18,19]. This could be due to the elongation of globe leading to mechanical stretching and thinning of scleral and retina, although it was yet to be ascertained whether the RNFLT was decreased at the histologic level. Additionally, we found RNFLT decreased in temporal quadrant, but increased in temporal quadrant as AL increasing, which suggested redistribution of RNFL might occur in the development of myopia. Sung Ganekal et al. also reported RNFLT thinning was seen in all quadrants except in temporal quadrants [5]. Kim et al. demonstrated that retina was dragged toward the temporal horizon as AL increasing. In this progress, RNFL layers are compressed against the bundles originating from the opposite hemisphere at the horizontal raphe, and this would result in thickening of RNFLT in the temporal quadrant. In contrast, the nasal retina would become thinner as it is stretched [17]. However, there were some quadrantal differences of RNFLT in different studies. Leung et al. found RNFLT significantly thicker in HM group, especially in the 12, 1, and 7 o’ clock sectors [18]. Instead, in the study of Seo et al., the RNFLT of the 1, 2, 5, 6, and 12 o’ clock sectors were significantly thinner in HM group than in LM group. At the same time, they found HM group showed significantly thicker RNFLT than LM group at the 8, 9, and 10 o’clock sectors [14]. We speculated that these differences might be attributed mainly to the OCT imaging equipment used. Seo used a Cirrus HD-OCT device with software version 6.0, whereas Leung used Stratus OCT version 3 that obtained 12 RNFLT values from each scan. Besides, regional ethnic differences or insufficient sample size should be considered as well. Additionally, the default was that each quadrant is a whole, so statistic data may also cancel each other if the results of the internal parts were contradictory.

Of note, when emmetropia progressed towards low-to-moderate myopia and high myopia, RPC density changed earlier, and its range of changing quadrants was larger than RNFLT. Therefore, we speculated that the susceptibility of RPC density was higher than RNFLT, which might be new observational indexes in the diagnosis of myopia. Nevertheless, the confusion whether this retinal response preceded or followed the vascular compromise was still controversial. Our study shares the limitations associated with cross-sectional studies, which cannot confirm causation, so further longitudinal studies and specific mechanisms research are required for additional investigation. In addition, we found RPC density positively correlated with RNFLT, which was in accordance with the findings of previous studies [20,21,22]. Sung et al. speculated that RNFL thinning might affect regional oxygen demand or the need of vascular supply in peripapillary region, and thereby triggered the retinal vascular adjustment via autoregulatory mechanisms [15]. Similarly, it was possible that an increase of RNFLT could lead to increase in oxygen and nutrient demands, thereby increasing retinal perfusion [23]. However, we thought this conclusion might be doubtful, for the changed quadrants of RNFLT and RPC density not synchronizing. Sung et al. speculated that morphologic changes of optic disc caused additional mechanical strain to microvasculature at the peripapillary region and resulted in deep peripapillary microvascular remodeling [15]. Additionally, Jonas et al. reported that the excessive elongation of eyeball caused stretching and thinning especially in the posterior pole, which might result in both enlargement of optic disc and thinning of RNFL [24]. Therefore, we should recognize that in addition to considering the effect of AL on the OCT RPC measurements in myopic adults, disc area should also be considered for analysis [14]. Besides, we found pRNFLT positively correlated with disc area. It has been postulated that eyes with larger optic disc area may retain more retinal nerve fiber axons [15, 25]. Alternatively, the larger the optic disc area, the shorter the distance between machine scanning circle and disc margin, which might result in the overestimation of RNFLT [26].

Moreover, as the integrity of RNFL is a recognized surrogate for glaucomatous change [18], we think impact of both HM and glaucoma on RNFLT should be comprehensively considered when using RNFLT to evaluate the progression of optic neuropathy in HM patients with glaucoma. On the one hand, the increased risk of development of glaucomatous change may be related to the already reduced RNFLT in myopic eyes. On the other hand, the reduced RNFLT in myopia may itself represent a risk factor for development of glaucoma.