In early diabetes patients, before retinal damage, the microvessels have changed. Local hyperglycemia will activate vascular smooth muscle cells and perimural cells. Even when blood sugar returns to a stable state, there will still be apoptosis of pericytes, swelling of the basement membrane, proliferation of vascular endothelial cells, and neuronal damage, also called metabolic memory [4]. Therefore, it is particularly important to identify early retinal abnormalities in patients with diabetes.
The retinas of diabetes patients will have abnormal color vision and contrast sensitivity before pathological changes occur [5–6]. Kim et al. [7] found that the thinning of ganglion cells and inner plexiform layer cells in the macular region of patients with diabetes retinopathy preceded the occurrence of microvascular injury by optical coherence tomography scanning, which confirmed that there was a certain relationship between neurodegenerative changes and microvascular structural abnormalities in the early stage. This study elaborates the relationship between the two from the perspective of the retinal function of diabetes patients.
Due to the increase of retinal blood flow in diabetes patients and the heterogeneity of its distribution [8–10], some studies [11] have concluded that the amplitude of mf ERG’s first and second order responses increase. On the contrary, other studies [12] have suggested that the amplitude of early diabetes patients is lower than that of those without diabetes. The present study showed that the P1 wave amplitude density of the first ring to the fifth ring was lower than that of the control group, but there was no statistical difference, which is consistent with a previous study [6]. This may be because the blood glucose control of the enrolled patients in this study was relatively stable and maintained at a normal level for a long duration; its amplitude density was close to that of healthy people. More importantly, when there is no obvious retinopathy at the early stage, mf ERG can only selectively reflect the defects of the inner retinal function, while the amplitude density is a total response of all retinal cells and cannot specifically reflect the functional changes of cells in a certain area.
In this study, we found that the implicit time delay of the P1 and N1 waves in some areas of the retina in the experimental group was significantly different from that in the control group. This may be due to the occlusion of the capillary network in the early stage, which led to ischemia, hypoxia, and an undetectable non-perfusion area [13]. Nevertheless, there were still no instances of apparently retinopathy, such as microaneurysms and hard exudates.
In addition, we also found that the temporal region was more sensitive to hyperglycemic injury than the nasal region, which may be because the temporal retinal vessels have poor expansion reserve capacity under the conditions of ischemia and hypoxia and thus are more intolerant to hypoxia [14–16]. Another reason may be that more cone cells and ganglion cells are distributed in the nasal and macular regions [16], while mf ERG simply records the functions of bipolar cells and the inner segments of photoreceptors.
We observed that the decrease of amplitude density was not proportional to the delay of implicit time; Jonsson also reached this conclusion [17]. This may be related to the fact that the multifocal electroretinogram focuses on reflecting the function of the local retina, while the abnormality of a certain ring parameter cannot reflect the defect of the entire retinal function. Therefore, this paper innovatively proposes a method for analyzing the two separated rings together in order to reflect the retinal function abnormality of diabetes patients who ignore retinopathy at an early stage. The composite ROC curve showed higher specificity and sensitivity in the diagnosis of retinal abnormalities in early diabetes patients, and its area under the curve was larger than that of a single ring. Among them, the area under the compound curve of the first ring and third ring was the largest, revealing that the abnormality of the posterior pole retinal function was the main source of the whole retinal function defect when there was no visible retinal damage at an early stage.
In general, the function of the retina has been abnormal for a significant period before diabetes patients have visual retinopathy. For diabetes retinopathy, age-related macular degeneration and other major cumulative local retinal (posterior pole) diseases, multifocal electroretinogram can effectively identify early abnormalities. Ischemia and hypoxia, local blood flow remodeling, and local metabolic changes may be the main reasons for the delay of implicit time in early diabetes patients. This study confirmed that when multifocal electroretinogram is implicit, this parameter can more sensitively reflect the abnormality of retinal function and can be used to evaluate the retinal function of early diabetes patients without visible retinopathy.