The many pathogenetic mechanisms of FU have been proposed that an unknown process is responsible for abnormal destruction of uveal pigment and low-grade inflammation. Iris stromal atrophy and infiltration of the iris stroma and ciliary body with lymphocytes and plasma cells have been shown as the most characteristic pathologic features in eyes with FU (23, 24). Until now, anterior segment findings of FU have been extensively described. In our previous article, we have reported the posterior segment findings in detail and especially all eyes had vitreous involvement (13). The regarding posterior segment involvement have been explained with different theories, such as the direct spread of inflammation and a secondary response to inflammation in eyes with FU (24, 25).
The choroid has an unique anatomical structure that can easily be affected by systemic or ocular inflammatory conditions and many researchs concerning choroidal imaging methods have been reported in ocular diseases (26). Edi-OCT is the most used of these analyzes and measures the entire choroidal thickness both stromally and interstitially. CVI is a new choroidal imaging method and it provides better detailed data of the choroidal vascular status (18, 19).
The effects of acute and chronic inflammation on CT differ in uveitic disease (27–33). The measurement of CT has been increased in acute exacerbations of the disease in cases such as VKH, SO, posterior scleritis tha the choroidal layer is primarily involved (33). However, the variation of CT has been reported in uveitic disease without direct choroidal involvement (27–32).
Past studies on HLA-B27-associated uveitis cases without primary posterior segment involvement revealed an increase in CT in the acute phase of the disease and also a regression in the thickness by treatment. Increased CT observed in acute ocular inflammatory conditions including anterior uveitis and/or posterior uveitis involvement and without direct involvement of the choroidal layer, is explained by the inflammation-dependent increased choroidal blood flow or immunological mechanisms (30–32). The reduction in CT in chronic uveitic cases has been suggested to be associated with ischemic changes related to chronicity, fibrosis and decreased vascular component (33, 34).
In FU, chronic-persistent inflammation in the intermediate area and several mediators released in the environment are considered to eventually interact with the choroidal layer. The decline in CT was demonstrated in the studies on FU and CT (15–17). In a study on CT measurement from foveal and extrafoveal areas in 9 eyes with unilateral FU and the unaffected eyes, authors reported a significant diffuse choroidal thinning in eyes with FU (15). In a study by Balcı et al. the CT was reported to be significantly lower in 15 eyes with unilateral FU as compared with the 20 control eyes and the unaffected eyes of patients (16). In a study by Kardeş et al., the measurements of CT by edi-OCT in 25 eyes of patients with unilateral involvement were compared with the their healthy eyes and the CT was found to be significantly decreased in eyes with FU when compared to healthy eyes (296.47 ± 32.29 µm vs. 324.47 ± 26.73 µm; p = 0.001) along with a significant thinning in ganglion cell layer in eyes with FU (17). In these studies, thinning in the choroidal layer has been suggested to be linked to the presence of a chronic inflammation or the consideration of choroidal layer as a continuation of the uveal tissue (15–17). Our findings also revealed a reduction in CT in the submacular area in eyes with FU when compared to the unaffected eyes. There was also no difference between the eyes’ retinal thickness measurements in the macular area. This seems to indicate that persistent inflammation in FU eyes affects the choroidal layer due to its anatomical structure, whereas the retinal layers are not affected.
Vascular effects in the choroidal layer are evaluated indirectly in CVI measurements. CVI can potentially serve as a marker for disease activity and can be used to monitor remission during the follow-up of uveitic diseases. A decrease in CVI and an increase in CT were found in a study conducted on eyes with recurrent anterior uveitis in patients with VKH, in which the choroidal stroma was directly involved, and it was reported that the decrease in CVI was due to active infiltration of the choroidal stroma and compression on the vascular area due to edema (35). In an acute anterior uveitis exacerbation in HLA-B27-associated uveitic eyes without direct choroidal involvement, an increase in both choroidal thickness and CVI measurement due to choroidal vascular enlargement has been reported (32).
There is no direct choroidal involvement in FU. However, decrease in CT was reported in both the aforementioned studies (15–17) as well as in the current study. In our study, the submacular CVI measurements revealed a significant decrease in eyes with FU compared to healthy eyes.
In addition, a significant decrease was observed in the submacular area in the evaluation of LA and luminal-stromal area ratio. This reveals that the continuous chronic inflammation in FU causes inflammation-mediated thinning in the vascular area of the choroid, even if it is not a uveitic disease directly involving the choroidal structures. This thinning in CVI and LA measurements has emerged as an evidence of affected choroidal layer. In the literature review, in a study in which submacular CVI was measured, it was found that the submacular CVI measurement of 39 unilateral FU eyes was lower than the other healthy eyes and the control group (24 eyes) (36).
The choroid layer has a very different anatomical structure from the retinal layer. The choroidal circulation is a high-flow system with a structure allowing the transfer of metabolites and mediators in the choroid and surrounding tissues. Therefore, as shown in the aforementioned studies in anterior uveitic eyes and also in our study, it is easily affected by inflammatory processes even those not directly affecting itself. These results show us clearly that this involvement in the choroidal layer is secondary to inflammation rather than uveal tissue continuity or direct involvement.
FU causes significant thinning in the iris stroma layer and ciliary body (23, 24). However, no change in the SA measurements in the choroidal layer found in our study may be another explanation for the choroid not being affected directly. Also, the reduction in the thickness of the choroidal layer in our study occurs as a result of the decrease in the LA. LA involvement is thought to be due to changes in the vascular system resulting from chronic inflammation.
Another region evaluated in our study is the peripapillary area. The peripapillary area has a unique importance in terms of both anatomical and functional structure. The blood supply to the surface nerve fiber layer and prelaminar part of the optic nerve head is provided by the peripapillary choroidal vessels (37). The analysis of peripapillary choroidal vascularity may be helpful in evaluating optic nerve head blood flow. Glaucoma and ocular hypertension have been reported as common complications of FU in several reports (38, 39). It is known that FU has an increased risk of glaucoma for reasons abnormal angle vessels, obstruction of trabecular meshwork by inflammatory cells, disruption of uveal and juxtacanalicular structures, trabecular meshwork fibrosis and steroid-induced ocular hypertension (22, 40). Therefore vascular support of peripapillary area should be well evaluated in these eyes. In a study conducted with optic coherence tomography angiography, it was found that radial peripapillary capillary vessel density was lower in 34 unilateral FU eyes without glaucomatous signs compared to other healthy eyes and control eyes (37 eyes), and chronic inflammation in FU has led to impaired blood flow at the optic nerve head (39).. Our study is the first investigation evaluating the choroidal vascular changes in the peripapillary region in eyes with FU. In the peripapillary CVI evaluation, a decrease was detected in all quadrants compared to the healthy eye, but the decrease in superior and inferior were significant. In addition, the decrease in LA in all quadrants in the peripapillary area is remarkable and the decrease in the superior area was found to be statistically significant. This shows us that peripapillary choroidal blood flow is impaired in these eyes without glaucoma, and the sensitivity of these eyes to glaucoma may be even more pronounced. The observation of changes and involvement of CVI and LA detected in the macular area also in the peripapillary area demonstrates the likelihood of effects via similar mechanisms. In addition, the correlation between the decrease in submacular CVI and the peripapillary sup-inf CVI demonstrates that the parallel and prominent involvement of several areas of the choroid layer anatomically. Albeit not statistically significant, peripapillary CT findings in our study indicate thinning in all quadrants compared to healthy eyes. This may indicate the likelihood of being affected secondary to chronic inflammation as in the submacular CT.
The only disadvantage of our study is the lack of data on duration of uveitis history in patients. Since the eyes with FU are usually asymptomatic, it is difficult to determine this course precisely.
As a result, a structurally and functionally healthy choroidal vasculature plays an essential role in the normal function of the macula and peripapillary region. In eyes with FU, especially the changes in the peripapillary area are remarkable as these eyes are prone to glaucoma. The examination of choroidal vascular changes offers a novel explanation to the pathological involvement of choroid in FU.