OCTA is a new imaging technology that provides noninvasive fundus angiography, which works without contrast medium and avoids allergies and various contraindications. OCTA relies on the intrinsic motion of the fundus vasculature network to separate stationary structures to identify the blood flow. OCTA can also provide a 3D partition by comparing 2D images taken by indocyanine green angiography and fluorescein fundus angiography , which avoids artifacts and limitations such as a limited measurement time window and discomfort during inspection. OCTA is reliable, noninvasive, efficient, high quality and safe for fundus vascular imaging [16, 17]. Fundus perfusion depends on the orbital blood supply, and patients with TAO show orbital perfusion changes caused by pathological changes in orbital tissues. A previous study found certain hemodynamic changes in the ocular vasculature under Doppler imaging, and the condition in the ocular vasculature improved after orbital decompression . Although color Doppler imaging has been widely used in vessel inspection, after certain ocular vasculature changes were detected, fundus perfusion changes can hardly be observed by Doppler imaging. Therefore, OCTA would be a perfect choice for further inspection to evaluate the status in fundus vessels.
In our present study, significant thinner RNFL thickness accompanied by higher IOP level was observed in active TAO patients, and the most affect RNFL quadrants were temporal and inferior quadrants. Active TAO patients often suffer from secondary compressive IOP rise, thus leading to RNFL defects [18, 19]. Localized RNFL thinning might be related to the position of compression. Earlier detection of RNFL thinning would suggest the presence of optic neuropathy, indicating its use in the evaluation of this disease profile.
Significant greater CT was observed in active and inactive TAO eyes as compared to the normal eyes. Çalışkan et al.  found the subfoveal CT in active TAO patients was significantly greater than those with inactive TAO or healthy individuals, even after adjusting for age, axial length and IOP. Similar results were observed in another study conducted by Özkan et al. . Besides, Yu et al.  also identified increased CT in TAO patients at different locations in the macular region. The possible explanation for the choroidal variations might be the venous obstruction and congestion, caused by reduce orbital venous drainage, which was the result of increased retrobulbar pressure [20, 22].
OCTA has been widely used to analyze the detailed characterization of the retinal and choroidal vasculature in the macular and peripapillary regions [23–25]. Due to the limitations of the analysis software, only superficial vascular plexus in the macular region could be quantitatively analyzed in our study. The FAZ area is a capillary-free area in the central macula that serves as the most sensitive part of the retina. In our study, the FAZ area was significantly enlarged in active TAO patients. But we didn’t detect disintegrity of the vascular arcades surrounding the FAZ area. Previous studies reported that the enlargement of FAZ area more objectively supported the findings of capillary nonperfusion [26, 27]. As we known, the superficial vascular plexus is responsible for the metabolic demand of the parafoveal ganglion cell layer. Our findings suggest a complex vascular impairment, with ischaemic damage to the full-thickness neuroretinal layer.
The macular vessel density and perfusion density of the superficial layer were quantitatively evaluated in TAO patients. Inactive TAO patients had significantly higher macular vessel density than that in active TAO and controls. With regard to perfusion density, the pairwise comparison results were not completely consistent. Collectively, the data analysis revealed that inactive TAO patients seemed to have greater perfusion density. However, Ye at al.  reported that active TAO patients presented with an increased retinal microvascular density. This incongruity may be due to the study design and the study population. Their study only enrolled active TAO subjects and analyzed the macular macrovascular and microvascular densities separately.
These changes might be correlated with variations in orbital blood flow. Doppler imaging of orbital vessels revealed that the resistance index (RI) in the ophthalmic artery (OA) was decreased inactive TAO patients, but systolic velocity remained unchanged, suggesting increased blood flow in OA in inactive TAO patients. The RI in the central retinal artery (CRA) was increased, and the velocity and RI in superior ophthalmic vein (SOV) showed no difference compared with that in the control group . The increased blood supply in the ocular vasculature may partly explain the increased vessel density. Walasik-Szemplińska D et al.  found that RI in OA decreased in active TAO. Velocity and RI were increased in CRA, while increased RI and decreased velocity were detected in SOV, indicating circulatory disorder in the ocular vasculature. Reverse flow was also observed in SOV, indicating severe stasis in SOV, which usually correlated with enlarged extraocular muscles. The SOV was considered to play important roles in the inflammatory stage in TAO, and recent studies have demonstrated blood flow reduction in the SOV during active TAO, indicating orbital circulation disorder was resulted from a total effect of increasing venous pressure and high RI, which was caused by elevated intraorbital pressure. Autoimmune inflammation in orbital tissues, including interstitial tissues, orbital fat and extraocular muscles, was the main cause of the high intraorbital pressure . Moreover, Onaran et al.  observed a reduction in SOV flow among patients after orbital decompression along with the disappearance of the reverse flow. Therefore, we proposed that vascular physiological changes and elevated intraorbital pressure caused by the direct effect of autoimmune inflammation on ocular vessel and orbital tissues lead to variations in fundus blood flow in active TAO, along with effects on RNFL thickness, CT, FAZ, vessel density and perfusion density, as observed in our study.
In the ROC analysis, OCT-derived RNFL thickness and choroidal thickness showed apparent diagnostic ability in TAO, which were consistent with previous studies [9, 18]. The FAZ area, vascular density and perfusion density also exhibited a significant discriminatory power to distinguish between TAO patients and controls. We hypothesize that these parameters may have the predictive value in the diagnosis of TAO. In addition, non-invasive measurements of these parameters are easily accepted by the patients. Clearly, these parameters were poor markers, further investigations are needed to substantiate these findings in a much larger cohort.
As a preliminary study, our present findings have several limitations. First, this was a cross-sectional study without follow-up data, which prevented us to correlate the vascular changes with the disease progression. Second, the morphology of the superficial retinal vessels is not equal to the hemodynamic changes, which may limit our understanding of the pathogenesis. Third, analysis of the retinal vessel parameters was limited to the superficial layer due to the limitation of analysis software, further investigations of deep retinal vessels should be performed to better demonstrating the retinal vessel variations. Fourth, the small sample size due to the rigorous selection standards might also limit the interpretation of the results. Nevertheless, our results indicated retinal and choroidal variations in TAO patients, further researches are highlighted to supplement and extend these preliminary results.