This detailed research investigated retinal microvasculature evaluated by OCTA in eyes affected by AU. We noninvasively evaluated FAZ and VD in patients with AU during the attack using OCTA and compared the results to normal eyes. This is the first study to investigate the retinal vascularity alterations determined by OCTA on acute AU only. Our results show that there was a transient increase in VD of DCP during the AU attack, especially in the foveal sector of DCP, and the area of deep FAZ transiently decreased during the attack.
Regardless of the anatomic location in uveitis, the underlying intraocular inflammation can lead to microvascular changes in the macula [6, 17–19]. This is postulated to be a result of the discharge of inflammatory mediators that break the inner and outer blood-retinal barrier [5, 19, 20]. This breakdown which can cause microvascular alterations, occurs even in AU, probably due to the spread of inflammatory mediators from the anterior to the posterior segment [5, 9]. FA can be used to detect microvascular alterations. Chi et al. detected cystoid macular edema with peripheral vascular leakage in eyes with AU using FA . During FA, early-phase frames are requisite in identifying microvascular changes and in the scanning of the capillaries before dye leakage . It is hard to capture improved images, primarily because of the limited duration of the early scans, light scattering, and early dye leakage . Furthermore, FA has a poor resolution of the DCP, it is invasive and it entails a risk of anaphylaxis .
OCTA is a non-contact imaging tool that provides a depth-resolved view of both the retinal and the choroidal microvasculature. It compares sequential scans and detects motion contrast via analyzing blood cells movement over time . It is repeatable and ensures almost histological resolution for analysis of VD . It allows for both qualitative and quantitative assessment of the vessels and facilitates the measurement of FAZ [26, 27]. OCTA ensures high-resolution scans of both the SCP and DCP and visualization of microvascular alterations, that are not detected via FA . OCTA provides important clues about the DCP that may be selectively affected in inflammation . Assessment of the changes in DCP may give additional information concerning the effects of inflammation in uveitis . However, it may not detect blood flow < 0.3 mm/s and > 2 mm/s . It cannot show leakage, which may be advantageous in some cases as it provides microvascular morphological detail in all segments . It provides a static image and is more prone to artifacts [15, 27]. Even though blood cells are the sole moving element in the retina, some non-vascular factors can also cause a signal .
Khairallah et al. compared FA and OCTA in Behcet’s uveitis and found that FAZ sizes in both the SCP and DCP were larger in uveitic eyes . They declared that OCTA allowed better visualization of perifoveal vascular changes than FA in Behcet’s uveitis . It was reported that deep foveal and parafoveal VDs in OCTA images were significantly lower in Behcet’s uveitis . Tian et al. detected more frequent changes in choriocapillaris and DCP than in the SCP in intermediate uveitis via OCTA .
Kim et al. measured the retinal microvasculature in anterior and posterior uveitis using OCTA, by randomly dividing patients into 3 groups . They applied different processing and segmentation settings to each group and found that there were significantly lower VD in SCP and DCP of uveitic eyes than those of healthy eyes . They showed that there were no differences in any parameter based on anatomic classification of uveitis . Nevertheless, there were 7 and 8 eyes with AU was in groups 1 and 2, respectively, and there were not any eyes with AU in group 3 . In addition, they did not exclude patients with diabetes . Detection of lower VD in DCP may be the result of mechanical displacement by the macular edema or due to weakening of the DCP signal by the macular edema.
In our study, the exclusion of eyes with macular edema prevented a decrease in signal quality and mechanical displacement effects. The mean VD in DCP was significantly higher in eyes with AU during the attack than after recovery in our study (p = 0.04). In the control group, the mean VD in DCP was significantly lower than in the eyes with AU during the attack, especially in the foveal sector of DCP (p = 0.048 for DCP, p = 0.001 for the foveal sector of DCP). After recovery, VD in each segment including DCP were similar between the uveitis and the control group (p > 0.05). We hypothesize that inflammatory mediators may disturb the blood-retinal barrier and thus increase blood flow, VD, and permeability. Nevertheless, we presume that these changes caused by inflammatory mediators may be temporary. Although the mean VD in DCP in the control and uveitis groups did not change significantly after recovery, surprisingly, there was a significant increase in VD in the foveal sector of DCP (p = 0.03). Prospective studies are necessary to explain this result.
It was postulated that eyes with AU had larger superficial and deep FAZ compared to healthy controls in the presence of macular edema and they could not be differentiated from healthy controls in the absence of macular edema . However, there were only 6 eyes without macular edema and 5 eyes with macular edema in the AU group in the same study . We found that deep FAZ was diminished significantly (p = 0.001) in the eyes with AU during the attack. None of our cases had macular edema. Deep FAZ area was significantly lower in eyes with AU attack compared to the control group (p = 0.003) whereas superficial FAZ changes during the AU attack were not significant. Deep FAZ was similar between the control and the uveitis group after recovery (p > 0.05), so we can hypothesize that the decrease in deep FAZ was not permanent.
Basarir et al. evaluated HLA-B27 positive AU and found that the CMTs of both affected and unaffected eyes had no differences . Unlike this, the CMT was significantly reduced in uveitic eyes after recovery in our study (p = 0.005). The relationship between VD, FAZ and retinal thickness has been reported [33–35]. Yu et al. found that retinal thickness was positively correlated with VD and negatively correlated with the FAZ area . It was noted that at the level of SCP and DCP, VD was correlated with the macular thickness [33, 35] and there was a negative correlation between foveal thickness and superficial FAZ area in normal eyes . Our results are consistent with those in the literature. We found a negative correlation of superficial and deep FAZ with CMT and CFT, and there was a correlation between VD of SCP and DCP and retinal thickness.
Despite the inclusion of a higher number of eyes than in previous studies, our study has limitations: All patients were from the same center, which limits the generalizability of the results. We evaluated all AU cases as a whole and did not group patients based on etiology. Instead of making repeated measurements at regular intervals during the recovery period, measurements were taken in the period after complete recovery. Therefore, the correlation between the degree of anterior chamber inflammation (aqueous flare and/or cell) and OCTA parameters could not be evaluated.
In conclusion, we showed significant changes in the affected eye during AU attacks when compared to unaffected eyes, which mostly resolved when inactivity was achieved. We detected a reduction in the FAZ and an increase in the VD of the DCP of the retina during active AU, and these findings were reversible. According to our results, AU may affect the macular microvasculature, which is usually temporary, especially in the DCP. OCTA provides a detailed image of the macular microvasculature, making it possible to detect these microvascular changes. Further prospective trials with larger sample sizes could provide an idea about the effects of the disease in the posterior segment and perhaps treatment monitoring and prognosis.