The current study demonstrated that ICGA findings suggestive of disease-related choroidal inflammation was observed in a considerable proportion of patients with long-standing VKH disease whose treatment was tapered according to clinical and FA evaluation. Disease-related choroidal inflammation on ICGA was highly prevalent even among patients under systemic treatment as well as among those with no clinically detectable disease activity, thus confirming previous studies in European and Asian population and reinforcing the usefulness of ICGA to assist monitoring disease activity to better tailor treatment strategies.
Bouchenaki and Herbort described ICGA findings suggestive of choroidal involvement in acute VKH disease, which were less evident in the chronically evolving disease, and proposed ICGA as a useful tool to monitor the effect of steroid therapy [7
]. Subtle ICGA findings in patients with VKH disease were subsequently shown to represent otherwise unnoticeable posterior segment disease-related activity [4
]. These findings were described in the context of VKH disease during anterior segment relapses in the chronic phase and in patients tapering treatment in the convalescent phase of the disease. In both scenarios, intensification of immunosuppressive treatment resolved both, clinically apparent as well as the underlying disease process. Kawaguchi et al. coined the term partially treated VKH disease to describe patients in the convalescent phase whose treatment was intense enough to abolish anterior segment activity while leaving signs of choroidal involvement on ICGA, and who experienced progressive fundus depigmentation (sunset-glow fundus) [4
]. In the current study, roughly three quarters of the eyes with long-standing VKH disease presented ICGA findings suggestive of disease-related choroidal inflammation regardless of the presence of activity on clinical examination. In fact, 70.0% of eyes demonstrated disease-related choroidal inflammation on ICGA without clinical evidence of disease activity, thus suggesting the presence of subclinical choroidal inflammation. Considering treatment regimen by the time of disease diagnosis, the majority of the patients included in this study had received early high-dose treatment. However, they were not systematically monitored with ICGA during the systemic treatment course, and clinical appraisal and fluorescein angiography were the only parameters used to taper treatment. Coupled with previous reports of better outcomes in more intensely treated patients, these observations provide additional evidence to support the possible role of ICGA in the adjustment of therapy at this stage of VKH disease [4
]. The importance of ICGA guided management of VKH disease to meaningfully assess choroidal inflammation has been recently reinforced by Bouchenaki and Herbort [3
]. These authors proposed that zero tolerance to subclinical choroidal inflammation could avoid irremediable evolution towards sunset glow fundus [3
In the current study, fuzzy vessels and late diffuse hyperfluorescence were the most frequently findings observed on ICGA, thus suggesting some alteration in choroidal vessels’ permeability and choriocapillaris involvement [6
]. Dark dots were considered only if they became isofluorescent (or mildly hyperfluorescent) in late-phase frames [6
], and were the least observed ICGA finding in the current study. These observations are in line with previous histopathologic studies in patients with VKH and chronic disease in which a diffuse, non-granulomatous choroiditis accompanied by choriocapillaris involvement was described [1
]. Additional findings identifiable on angiographic studies that have been correlated to serious ocular manifestations and/or severe choroidal inflammation at the acute uveitic stage of VKH disease [18
], such as the presence of choroidal folds as reported by Wu et al. [18
], were not identified in the current study.
Disease-related choroidal inflammation on ICGA was apparently more easily observed among those patients with milder fundus changes than in those with more severe fundus changes in the current study (Figure ; Additional file 1
: Table S3) [22
]. It is possible that some eyes with fundus-based severe disease could also present subclinical choroidal inflammation that remains undetected on ICGA due to a combination of factors, such as the limited ability to identify ICGA signs of choroidal inflammation in a severely altered fundus with destruction and scarring of a considerable proportion of the choroidal stroma [6
]. Naturally, the identification of the ICGA findings indicative of choroidal inflammation in patients with mild fundus changes seems an easier task. It should be noted that this study has limitations due to the relatively small number of patients and its cross-sectional design. In addition, the misinterpretation of the ICGA findings should always be considered in studies of this nature. Future studies, combining ICGA with other fundus imaging modalities such as fundus autofluorescence and enhanced depth imaging optical coherence tomography may facilitate our understanding of the choroidal involvement in patients with VKH disease [24
], independent of the severity of disease associated fundus alterations.
Figure 2 Color fundus photography (photomontage) from patients with Vogt-Koyanagi-Harada and long-standing disease. Mild (A) and severe disease (B) according to fundus-based disease severity grading (as per standardized analytic framework for ocular fundus alterations (more ...)