Over time and with the progression of technology, the physiological age of humans is increasing, and neurodegenerative diseases, such as ATD, are attracting increasing attention from the public. The adverse effects of these diseases on the daily lives of the elderly also interfere with the lives of many families. As ATD is a common disease in neurology, pathological changes in intracranial nerves have been identified . The accompanying reduction in the thickness of the retinal neuroepithelial layer of the eyes has gradually become a consensus sign [10–17]. However, few studies have examined parameters related to retina and choroidal blood vessels of patients with ATD; thus, this study was designed in an attempt to explore these parameters.
The most common intracranial vessel changes observed in patients with ATD include impaired self-clearance of the A beta protein, impairments in the blood-brain barrier, decreased vessel density, decreased vessel diameter, and decreased blood flow . These findings provide good insights into the potential changes in the retina and choroid, because the vessels in these structures are homologous to those in the brain. In our study, the detailed vessel distribution parameters near the macular area were precisely analysed using zoning. The blood vessel length density and blood vessel width density in different areas of the macula of patients with ATD were lower than the normal control group, except the outer ring nasal area and outer ring temporal area. The automatic regulation of the human circulation is complex, and many factors ensure a stable local blood supply when vascular density parameters change. The process of autoregulation depends on the local mitogenic response, endothelium-derived substances, local metabolic factors and the autonomic nerves . A decrease in the vascular density might not directly reflect a decrease in the retinal blood supply in patients with ATD, but we observed changes in the retinal microcirculation of patients with ATD by performing a comparative analysis, which provided support for the clinical prospect of the OCTA-assisted diagnosis of ATD.
The retinal vessel system including radial capillary network near nipples, shallow vessel plexus and three parts of the deep vessel plexus , the deep shallow vessel plexus and vessel plexus near the centre concave and macular area of avascular area, called the foveal avascular zone (FAZ) . In previous studies, the FAZ area was enlarged in patients with diabetic retinopathy and macular branch vein occlusion, according to an FFA examination. Moreover, the FAZ is extremely susceptible to changes in local blood supply, and an increase in the FAZ area is a sign of ischaemia. Thus, the blood supply of the retina can be measured by observing the changes in the FAZ area [22–23]. In our study, the FAZ area was significantly increased in patients in the ATD group compared with the normal control group. Based on this result, the blood supply of the shallow retina is affected by such diseases as ATD, showing a decreasing trend. The results of this study should be confirmed using colour Doppler imaging (CDI).
After discovering statistically significant differences between the aforementioned indicators, our research began to focus on the relevant influencing factors. Basic data were collected for all subjects, including age, IOP, axial length, CCT, MMSE score, and MoCA score. According to the univariate linear regression analysis, the surface vessel parameters, complete vessel length density and complete vessel width were negatively correlated with age and axial length, and positively correlated with the MMSE and MoCA scores. Age and axial length were the two main factors affecting the surface vessel parameters of the macular area in previous studies [24–27], and these results were consistent with univariate correlation analysis. Therefore, when we explore the effects of diseases such as ATD on retinal blood vessels, the difference in mean values must be considered when determining the effects of confounding factors. After adjusting for age and MoCA scores, the MMSE score was positively correlated with the parameters, and the axial length was negatively correlated with the parameters in the multivariate regression analysis. The MMSE score and axial length were the most significant factors affecting the surface retinal vessel parameters in the macular area. As one of the diagnostic criteria for clinical ATD, the MMSE score can be used as an index of disease progression. We concluded that the severity of ATD disease progression is significantly correlated with surface retinal vessel parameters in the macular area. In the comparative analysis of FAZ and CT, after considering the combined effects of confounding factors, the MoCA score was significantly negatively correlated with FAZ. MoCA is also one of the diagnostic criteria for ATD, and a high score also indicates an increasing severity of the disease. Therefore, we postulate that the degree of progression of ATD disease is more serious, and the distribution of the vasculature to the surface of the retina in the macular area will gradually decrease.
The Mini-Mental State Examination (MMSE) score comprehensively, accurately and quickly reflect the subject’s mental state and level of cognitive impairment. The MMSE score provides scientific evidence for a clinical psychology diagnosis, treatment and neuropsychological research. This score is widely used at home and abroad, and it is the preferred scale for dementia screens. However, the scoring system also has certain limitations. The MMSE scoring system covers fewer cognitive domains, and the two cognitive domains of orientation and language ability are assessed in a relatively large proportion of questions. The proportion of questions assessing other cognitive domains is small, and the scores for each cognitive domain differ. Memory testing is relatively straightforward and is not sensitive to screens for impairments in individual cognitive domains (such as memory and executive function). For patients with higher education levels, the scale is in the normal range because the assessment is too simple, which easily conceals the cognitive impairment of patients [28–33]. The Montreal Cognitive Assessment (MoCA) score is an assessment tool used to quickly screen for cognitive dysfunction. A screen for mild cognitive impairment (such as amnestic cognitive impairment) and suspected dementia in a single cognitive domain is more sensitive. The cognitive domain is more extensive and comprehensive, the score distribution is more reasonable. The scores for visual space and executive function are improved, the memory test is more reasonable, the number and difficulty of words are increased, and the time of delayed recall is prolonged. MoCA reflects the true state of the patient’s memory. However, the score requires patients to have a certain level of literacy and ability to cooperate, and no study with a large sample size either at home or abroad has screened for cognitive impairment using MoCA. Thus, a recognized threshold for screening for dementia and mild cognitive impairment is not available [34–37]. Although the two scoring systems have advantages and disadvantages, experts and scholars at home and abroad indicate that the MoCA score is more sensitive and accurate than the MMSE score [34–37]. In our study, after adjusting for the confounding effects of multiple factors, the MMSE score was significantly associated with the surface retinal vessel parameters in the macular area, while the MoCA score was significantly associated with the area of the fovea in the macular area. As we mentioned above, the FAZ surface is actively affected by changes in local blood supply. Therefore, is the effect on the retinal blood supply caused by changes in the FAZ area more sensitive than changes in the surface retinal blood vessel parameters? In addition, does this difference in sensitivity coincide with the difference in sensitivity between the MoCA and MMSE scores? In-depth investigations of big data will be worthwhile. In addition, the differences in statistical correlations may also provide corresponding recommendations for the current clinical diagnosis of ATD. The combination and complementation of the two scoring systems might provide a better method for AD diagnostic screening.
Since software that automatically divides and measures the choroidal thickness using OCT instruments is not available, most research projects still require the observer to manually draw the inner and outer lines of the choroid and use manual callipers to complete all measurements, which inevitably introduces certain measurement errors. All measurements in this study were performed using a self-designed image measurement software to minimize measurement errors. In our study, the mean choroidal thickness in the macular area of the ATD group was less than the normal group, and the mean difference was statistically significant. After correction, univariate and multivariate regression analyses revealed a positive correlation between the MoCA score and the choroidal thickness in the macular area. The choroidal membrane accounts for 80–90% of the total blood flow to the eye and plays important roles in providing nutrition to outer layer of the retina and maintaining the structure and function of the retina. Amyloid deposits in the choroid, particularly in the choriocapillaris, have been reported in a histopathological study of a patient with primary systemic amyloidosis by Ts’o and Bettman . On the other hand, Roybal et al.  retrospectively analysed 4 patients with amyloid-induced chorioretinopathy and reported a thicker hyporeflective choriocapillaris band in the OCT images that was caused by the accumulation of amyloid deposits. Because amyloid deposits are typical pathological manifestations of ATD, researchers have speculated that the degree of progression of ATD is more serious, and the altered blood flow to the outer layer of the retina will increase. The decrease in the choroid thickness may be related to choroid atrophy secondary to amyloid angiopathy. According to several independent studies, patients with ATD present with different types of visual dysfunction, such as decreased colour vision sensitivity and contrast sensitivity defects [40–43]. Both the choroidal circulation and retinal circulation are involved in meeting the metabolic requirements of photoreceptors for oxygen . The retina requires a continuous supply of oxygen. If the intraocular pressure suddenly increases to the average level of systemic arterial pressure, the retinal vessel circulation is interrupted. Vision disappears only in 4–9 seconds [45–46]. In addition, scintillation stimulation increases the retinal vessel diameter and retinal blood flow [47–51]. Under physiological conditions, the retinal blood flow supply is closely related to the normal execution of its function. In our study, a new and convenient RETeval system was used to record flash electroretinograms, and the amplitude (peak to trough distance) was used as a primary reference to evaluate the response of cones, rods and Müller cells. The retinal response to flash stimuli decreased in patients with ATD. This result is consistent with our hypothesis about the obstruction of choroid blood flow. Although the research in this area is not extensive, our findings provide a potential insight into the relationship between blood supply and visual function of patients with ATD, but further studies are needed in the future.
This research also has some limitations. First, the analysis of vessel parameters was limited to the inner boundary membrane layer and the inner plexus layer; we were unable to obtain the deeper retinal vessel parameters due to the limitations of the analysis software. Second, as a non-invasive technique for measuring choroidal thickness, EDI-OCT has excellent repeatability. However, it only reflects a static structure rather than dynamic changes in blood flow and does not accurately describe the haemodynamic characteristics of the choroid. Therefore, some important information may be lost. Third, some researchers have shown dynamic changes in the choroidal thickness in 24 h [52–54]. Although the imaging data collected from subjects in our study were mainly recorded in the afternoon (14:00–17:00), errors were not able to be completely excluded. Moreover, we manually measured the choroidal thickness at several sites and thus were unable to completely exclude measurement error and local choroidal changes. These limitations are supported by technological innovations that automatically delineate choroidal regions and measure thickness, and we anticipate that more studies of this topic supported by new technologies will be published in the future. Fourth, the data of flash ERGs varied substantially. Conditions permitting, a larger number of subjects will effectively improve the reliability of the data.
In contrast to the traditional ATD diagnostic approach assessing changes in brain and neural function, we examined the changes in the microcirculation of the retina and fundus of patient with ATD, a degenerative disease, using OCTA in the present study. Our selected subjects tended to be patients with early- and middle-stage ATD, and the changes in the microcirculation observed using OCTA may be auxiliary diagnostic criteria for ATD. Using non-interventional methods, ATD screening was conducted at the early stage to achieve the early prevention and administer clinical interventions for ATD. On the other hand, a study assessing the long-term follow-up of patients with ATD using OCTA also has potential for development and may provide a more convenient and intuitive conclusion regarding the effect of treatments on ATD. OCTA has strong prospects for the clinical diagnosis and follow-up of ATD.