Retinal vessels are the only blood vessels in human body that can be directly observed and measured. They are small blood vessels that are similar in structure and physiological function to the terminal blood vessels of important organs such as the heart, brain, and kidney. Therefore, the change in the diameters of retinal vessels can reflect the physiological and pathological changes in other organs, tissues, and their blood vessels to a certain extent, so their lesions have an important auxiliary role in the diagnosis of other systemic diseases.
In some early studies, it was found that DR development widened the retinal veins. However, due to technical limitations, it was difficult to quantitatively assess the specificity of such changes. This finding has not been listed as an observation indicator for DR at home or abroad, and only the relatively easily observed venous beading can be used as one of the markers for venous abnormalities and non-proliferative DR. In this study, it was found that the RVOD and RVLD of retinal veins in DR patients were larger than those in the NDR group; that WLR, WT, and WCSA in DR patients were much larger than those in non-DR patients; and that they were all linearly correlated with DR stage. The more severe the DR, the larger the diameters of the retinal vein and the thicker the vessel wall. However, there was no correlation between the duration of diabetes and retinal vessel diameter. This conclusion is consistent with the knowledge that the vein diameters of DR patients are widened8. After the occurrence of DR, if the retinal vein diameter is enlarged, this may predict the progression of DR. Clinically, it is generally accepted that patients with a long duration of diabetes and poorly controlled fasting blood glucose are more likely to develop DR and experience DR progression, reflecting the inseparable relationships between the diameter of retinal veins, fasting blood glucose level, and diabetes duration. It is certain that in patients with T2DM, changes in retinal vascular diameter, especially venous diameter, are a warning sign for the occurrence and progression of microvascular complications in T2DM, and changes in venous diameter are the earliest microcirculatory abnormalities in patients with T2DM.
Although the likelihood of concurrent DR and severe progression increase with a longer diabetes duration, the diabetes duration is not completely equivalent to that of DR, and our multivariate linear regression analysis also excluded the correlation between diabetes duration and DR. This study also provides more detailed and practical reference indices of WT and WCSA. Because the impact of vessel pulsation on the vessel wall is less than the impact of vessel pulsation on vessel diameter, the measures such as WT and WCSA have higher reproducibility and higher research value. Some studies suggest that inflammatory response leads to venous distension and increases WT9, further increasing WCSA, which is consistent with the results of this study. Moreover, retinal blood circulation disorders in diabetic patients often damage the function of vascular endothelial cells, raise the expression of nitric oxide in endothelial cells, mediate retinal flash stimulation through nitric oxide10,11, and thus participate in the regulatory process of vasodilatation. Some research also suggests that hyperglycaemia can cause retinal hypoxia and lactate accumulation, and venous dilation is a compensatory mechanism to increase blood supply to the retina12. Due to the limitations of the present experiments, the sensitivity of WT, RVOD, and RVLD and the timing of their changes could not be compared, though they should be in the future.
In this experiment, the RAOD, RALD, WT, and WCSA of retinal arteries in DR patients were significantly greater than those in non-DR patients. Moreover, RALD and WT were linearly correlated with DR stage. Cheung et al.13 found that retinal arteries widened with increasing blood glucose and glycosylated haemoglobin and the progression of DR. Islam et al.14 suggested that retinal artery diameter was not associated with the progression of DR, which was inconsistent with the above findings. However, some researchers have found that the retinal artery of DR patients became narrower8. Therefore, the correlations between diabetes and retinal artery remain controversial. This is perhaps due to the different races of the studied populations, the individual-level differences, and different sample sizes in different studies.
In patients with T2DM, fasting blood glucose level is a factor influencing the retinal vein diameter. When the fasting blood glucose level increases, the retinal vein diameter shows a tendency to dilate; however, the fasting blood glucose level does not affect the retinal artery diameter. This may be related to the structure and plasticity of the retinal artery and vein as well as the sensitivity of measurement methods. Clinically, retinal vein dilation is more likely to be observed when fasting blood glucose is elevated. In patients with T2DM, blood pressure influences the retinal artery diameter, and the retinal artery diameter tends to narrow with increasing blood pressure. Some researchers have given antihypertensive treatment to diabetic patients with hypertension to control their blood pressure to a good level and have found that the diameter of the retinal artery will gradually increase after treatment. The above conclusions suggest a strong correlation between retinal artery diameter and blood pressure.
In clinical practice, retinal artery stenosis is generally considered an early indicator of vascular damage due to age, hypertension, and other cardiovascular diseases, and structural changes to the retinal artery can provide an early warning about the health or disease of microvessels. In other words, if retinal arteriolar stenosis occurs in patients with T2DM, it may indicate high blood pressure, progression of diabetes, or vascular damage, suggesting the possibility of damage caused by complications such as DR and diabetic nephropathy15,16. Strict blood pressure control can significantly reduce the macrovascular and microvascular complications in patients with T2DM. Moreover, it is easier to control the blood pressure stably than to control the blood glucose stably, and it is more effective to prevent and treat chronic complications of T2DM by controlling blood pressure than by controlling blood glucose. The conclusions drawn by current studies on the changes in retinal artery diameter in diabetic patients are still controversial, and a larger sample size and further investigation are needed. However, we provide some new arterial parameters, such as WT and WCSA, in this study, and the inter-group differences between these measures were significant. These data have important research value and expand the ways in which the relationship between DR and retinal vessel diameters can be studied.
Wong et al.17 showed that in patients with T2DM, long-term stimulation to the vascular wall by factors such as hyperglycaemia, lactate accumulation, insulin resistance, and haemodynamic changes caused vascular wall remodelling. According to whether WCSA is enlarged or not, the remodelling can be divided into inward eutrophic remodelling and inward hypertrophic remodelling18–21. In vitro experiments by Endemann et al.22 showed that eutrophic remodelling is a common form of structural change in resistance vessels in patients with essential hypertension, while hypertrophic remodelling is common in hypertensive patients with diabetes. In this study, the experimental results obtained through non-invasive SD-OCT on humans are consistent with the results of those in vitro experiments.
This study has several limitations. First, because the retinal vessels are close to the surface of the retina, it is difficult to distinguish the upper wall of the blood vessel from the tissue, resulting in a larger outer diameter of the blood vessel and a thicker vessel wall(Fig. 3). Second, the FWHM method can reduce the measurement error. However, it is not fully automated; there is a possibility of error, and the steps are too cumbersome and inefficient.