OCTA is a noninvasive procedure and can be depth-segmented to afford 3D volumetric scans. By using motion contrast to acquire images, the vasculature of the retina and choroid can be visualised to display structural and blood flow information and is used as an imaging method for evaluating various retinal diseases. Thus far, no study has evaluated the detailed characteristics of retinal vasculature in smoking patients with early and intermediate dry AMD through an imaging approach. The introduction of OCTA has permitted the imaging of the retinal layer vasculature without injecting a dye.
In this cross-sectional control study, we investigate retinal vessel features and other retina-related indices in patients affected by early and intermediate dry AMD by using OCTA. Overall, we found that retinal vessels and retina-related indices are altered in these patients. The whole, foveal and parafoveal vessel densities of SCP and the whole and parafoveal vessel densities of DCP in patients with early and intermediate dry AMD are all significantly lower than those in normal controls. This difference also occurs in the dry AMD and control nonsmoking subgroups, and the sensitivity of SCP vessel density is higher than that of DCP vessel density. This finding may be because OCTA focuses on the superficial retina to avoid the influence of attenuation and artifacts of vitreous opacity or other AMD pathologically related signals and the shadow effect of deep-layer vessel density in the retina[14,15]. We speculate that the loss of retinal vessels in patients with early and intermediate dry AMD may stimulate the ischaemia mechanism of retina. The loss of retinal cells can be caused by this mechanism, which may indicate that the changes in retinal vessels play a certain role in the dry AMD pathogenesis. In a previous study, the change in the vessel density of SCP has been well tested by OCTA[16,17]. Mastropasqua et al. found a significant reduction in superficial and deep retinal vessel densities in patients with AMD compared with those in healthy controls. Our results are consistent with those in previous studies. We also found that the value of foveal vessel density of SCP in the dry AMD smoking group is significantly higher than that in the dry AMD nonsmoking group. Moreover, although no significant difference is observed in the other indices of SCP and DCP, an increasing trend is found in the AMD smoking group compared with that in the AMD nonsmoking group. At present, no relevant literature is available to explain this phenomenon. We speculate that this finding may be due to a compensatory increase in retinal blood supply with early and intermediate dry AMD long-term smokers. Chronic smoking and dry AMD can cause the loss of choroidal capillaries and ischaemia, which may lead to the compensatory increase in retinal blood. In the normal control group, the SCP blood density of the smoking subgroup also has an increasing trend compared with that of the nonsmoking subgroup, but no statistical difference is observed. However, for patients with AMD, the compensatory effects are more pronounced in the smoking subgroup than in the nonsmoking subgroup. To a certain extent, the mechanism of the compensatory increase in blood flow caused by smoking has weakened the difference in blood flow changes in dry AMD smokers with control smokers. However, this finding is only our conjecture, and we need to combine the analysis of a large number of clinical samples and the histopathological study of retina and choroid for verification.
FAZ shows as a clear round or oval nonvascular signal area in OCTA and is often used as a quantitative analysis index to measure macular ischaemia, which is related to retinal function damage. In this study, we found no significant change in FAZ in normal control group and dry AMD group and their subgroups. Many authors revealed no significant difference in FAZ and shape in between the early and intermediate dry AMD and control groups[19,20]. The results of our study are consistent with those of previous studies, suggesting that the perfusion of central vessels in the fovea may not play a role in the pathogenesis of dry AMD. This finding is different from the results of FAZ in retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, the severity of which is related to the enlargement of FAZ. In addition, we found that the value of FD in the normal nonsmoking group is significantly higher than that in the dry AMD nonsmoking group. In the current research, articles about the relationship between FD and dry AMD remain lacking.
Smoking is a major and changeable risk factor for AMD, which poses a serious threat to the normal function of human vascular system. Long-term smoking can cause irreversible damage to blood vessels by increasing the flow resistance of terminal blood vessels and reducing blood flow. Mechanisms include direct toxic effects on the endothelial cells of ocular blood vessels, damage of the vascular structure and destruction of vascular function[22–24]. The components in cigarette smoke have a direct toxic effect on the endothelium, and nicotine may cause structural damage in vitro and in vivo[22,25]. Previous studies found that smoking is not associated with macular perfusion. However, in different OCTA algorithms, different boundaries are used for interlayer segmentation, which may lead to differences in related detection indices. Therefore, the differences between OCTA systems and measurement methods must be considered when comparing different research literature. At the same time, the parafoveal vessel density of DCP in the smoking group is significantly lower compared with that in the control group. This result is consistent with that of a previous study, suggesting that smoking may cause a local ischaemic microenvironment, which may be a risk factor for the development of choroidal neovascularisation in smokers. Given the multiple properties, including the distance from the large arterioles, the complex vascular structure and the high metabolic activity, DCP is susceptible to oxidative damage and poor perfusion caused by smoking. Our study also showed that the pack–year history is negatively correlated with the parafoveal vessel density of DCP. We can infer that with prolonged smoking, the vessel density of DCP decreases. This finding explains that the chronic effects of smoking damage microvessels continuously, highlighting the importance of quitting smoking for health.
In accordance with our results, the inner and full-layer FRT of dry AMD group are thinner than that of the normal group. The reason may be the decrease in the retinal vessel density of patients with dry AMD and the ischaemia mechanism in the retina, leading to decreased intraretinal cells. Rogala et al.  showed inner retinal layer thinning in patients with dry AMD. Our results are consistent with those of previous studies. At the same time, the inner FRT is positively correlated with the foveal vessel density of SCP, and the outer FRT is positively correlated with the foveal vessel density of DCP. Therefore, we speculate that dry AMD may lead to changes in the structure and blood flow of the retina first and that the microvascular insult and thinning of retinal structure are mutual cause and effect. The alteration in retinal structural and microvascular properties may further elucidate the progress of dry AMD. Next, we can refine the staging and observe the sequence of changes in the retinal structure and blood flow as dry AMD progresses. The combination of these two indicators can be used to provide reference clinical indicators for the research pathogenesis on dry AMD. According to previous data, an evident correlation between smoking and FRT is not observed[10,32,33]. In the present study, we found no correlation between pack–year history and FRT and no significant change in FRT in groups of smoking and nonsmoking. These findings are consistent with those in previous data. However, relevant research to further prove the relationship between FRT and dry AMD remains lacking.
In the next step, we can further study the effect of smoking on the retina of late AMD and analyse the relationship between the progress of dry AMD and the detection index of the retina. Remarkable differences in the gender of the included researchers are observed because the gender distribution of smoking groups is uneven, which is an irreconcilable contradiction. Thus, we should expand the sample size of each group to improve the study. Furthermore, large studies that investigate the chronic effects of smoking on retinal microcirculation in the macula may help explain the role of smoking as a risk factor on systemic vascular diseases.