Diabetic retinopathy (DR) is one of the most detrimentallong-term diabetes complications that damage fundus retinal microvasculature complications in DM patients (1). Although mild DR complications can be cured by proper management of the diabetic condition, DR induced gradual deterioration of vision is a common risk factor for permanent blindness in DM patients (2–5). Non-proliferative DR (NPDR) is characterized by asymptomatic microvascular changes or minute leaks in the retina, which ultimately develops into proliferative DR (PDR) or diabetic macular edema (DME) with the gradual progression of DM (6, 7). Therefore, early diagnosis of DR and precise estimation of the retinal damage already caused by DM are critical for the prevention of aging-independent retinal damage and complete blindness (5, 8).

The ultra-wide-angle imaging of the swept-source optical coherence tomography angiography (SS-OCTA) has multiple advantages like faster scanning speed, higher signal intensity, and deeper penetration depth. This technique is also used to detect early phases of retinal microvascular damages in DM patients, It did not lead to obvious visual impairment (9–11). Since SS-OCTA operates at 1,050 nm wavelength light sources, so it is less susceptible to energy attenuation in the fundus and offers better penetrance capacity. And they are very important factors for accurate diagnosis and clinical researches of DR. Studies have shown that SS-OCTA provides consistent results with OCTA in the diagnosis of DR (12). Moreover, compared with the spectral-domain optical coherence tomography angiography (SD-OCTA), SS-OCTA has a larger inspection scope, higher frequency, and faster scanning speed. Thus, SS-OCTA can more accurate and real-time monitor the peripheral retinal VD lesions of DR patients (13–15).

SS-OCTA can also present clearer choroidal images, automatically detect and analyze choroidal thickness, reduce manual measurement errors, and improve the efficiency of choroidal observation and diagnosis. With increasing scan depth, the possibility of signal attenuation will be further reduced, which is suitable for imaging larger fields and distinct observation of the vitreous body, retina, choroid, and sclera for detailed study of the fundus in DM patients (16). Such unique advantages of SS-OCTA method have immense clinical significance for early diagnostic confirmation of lesion extent in DME.

In this study, the SS-OCTA technique was applied to observe and quantitatively analyze the retinal and choroidal microvascular parameters like VD, capillary network, and morphological alterations and compare the foveal avascular zone (FAZ) in different macular regions between healthy subjects and patients with NPDR or PDR. Therefore, this study would provide critical diagnostic guidelines for DM patients with different degrees of retinal damage.

Previous study has shown that patients with T2DM are more likely to have enlarged FAZ compared to their age-matched non-diabetic control subjects (20). In diabetic patients eyes, DR can lead to progressive macular ischemic changes. Under this circumstance, the advent of SS-OCTA technology provides a unique opportunity to non-invasively study macular perfusion and several other pathological parameters in the diabetic eye (20–22). Our patho-clinical observations confirmed gradually increasing FAZ and RT, while the significant overall decrease in VD in all areas of central fovea and PD as the DR pathology moved forward from NPDR to PDR stage (6, 23, 24). The rapid development of SS-OCTA technology provided an accurate, fast, and reproducible method for detecting fundus VD modulations in DR patients.

Compared with OCTA, the SS-OCTA provides superior angiogram montages covering larger areas with distinct retinal capillaries to the mid-periphery (25, 26). It is beyond the scope of the traditional seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) standard. Therefore, SS-OCTA analysis yields high-content information for disease diagnosis. By employing SS-OCTA technique, we found significant differences annular area of choroidal blood perfusion, large and medium vessel indices, and choroidal thickness between the healthy control group and PDR or NPDR group. It suggested that the retinal imaging of SS-OCTA may reveal crucial findings facilitating DR diagnosis and understand the patho-mechanisms of NPDR to PDR progression.

Furthermore, we observed that both NPDR and PDR patients exhibited considerable ischemic alterations in the macular regions, in addition to the decreased retinal VD and PD around the central fovea. This observation indicated that the change of retinal ischemic area in DR patients might not be limited on the macular area. This is similar to previous studies (27). Additionally, CVI and CVV are novel quantitative parameters for choroidal choroidal vascular health markers, suggesting severe choroidal injury in PDR. Similar to previous reports (28, 29), there were no significant differences in CVI and CVV of fovea between the control subjects and NPDR group. However, this were contradictory about the correlation between CVI or CVV in the control subjects and PDR group, possibly because we did not distinguish whether the patients also had DME (30). Although the algorithm of SS-OCTA for detecting choroidal vascular correlation index still needs to be refined, SS-OCTA makes it possible for us to evaluate choroidal quantification, which will provide advantages for the diagnosis and treatment of choroidal vascular diseases in different DR patients.

Notably, the difference in the ischemic damage of macular area between the DR patients and control subjects was found to be directly associated with the area measured in the annular region with the fovea at the center. While, based on these findings, it was obvious that there would be a significant difference in macular lesion area between NPDR and PDR patients. On the other hand, a comparatively larger lesion area might be helpful in providing a more accurate diagnosis in the case of PDR than in NPDR. Subsequently, we identified differential damage intensities in peripheral retinal perfusion rates between the PDR and NPDR patients, as well as with the healthy control group, which might provide a new paradigm shift in our understanding of the mechanism of the progression of DR. Together, these findings demonstrated the potential benefits of SS-OCTA evaluation for diagnostic stratification between different stages of retinal injury.

Although SS-OCTA devices provide the possibility of wide-field imaging, there are still some limitations. For example the artifacts caused by the eye movement or blinking, the segmentation errors, and so on. And the leakage could not be detected by SS-OCTA. Additionally, a controlled prospective study with larger sample size was needed to further study.

In summary, identification of the differences in retinal VD and RT between NPDR and PDR patients could indicate possible mechanistic of DR progression. SS-OCTA examination has promising benefits in the early diagnosis of DR pathology as well as in the differentiation between various stages of disease progression.

The original contributionspresented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

The Human Research was approved by the Institutional Ethics Committee of Shandongeye hospital (Approval No. 2019S001) on November 11, 2019. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

TiL, QZ, and WLdesigned and conducted clinical examinations, wrote, and revised the manuscript. GS, WW, MF, XX, and ToL prepared the figures and tables and interpreted the results. All authors contributed to the revision steps and approved the final version of the manuscript for submission.

This studywas supported by a grant from the Natural Key Research and Development Project (2016YFC1305500), Bethune Langmu Young Scholars Research Fund (BJ-LM2021007J).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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