Vogt-Koyanagi-Harada (VKH) disease is a granulomatous immune-mediated inflammatory disease that is more common in Asian, Hispanic, and Middle Eastern ethnicities.1 VKH disease is classified into an acute stage with mostly bilateral posterior uveitis associated with neurological findings, such as meningismus, tinnitus, and cerebrospinal fluid pleocytosis, and a chronic stage with recurrent posterior, as well as anterior inflammation and ocular and integumentary depigmentations.2 Multiple areas of pinpoint leakage are often present on fluorescein angiography (FA), which are commonly associated with exudative retinal detachments.1 Using high-resolution optical coherence tomography angiography (OCTA) in VKH disease, multiple transient large areas of flow void in the choriocapillaris corresponding to hypofluorescent spots on indocyanine green angiography (ICGA) have been reported.3,4 To date, it is unclear whether choroidal vessels below the choriocapillaris are involved and how this involvement might present on OCTA.
Here, we report the case of a 19-year-old Middle Eastern male who presented with a 6-day history of blurred vision accompanied by head, neck, and eye pain. Best-corrected visual acuity (BCVA) was 6/60 in the right eye and 6/24 in the left eye. On funduscopy, multiple areas of exudative retinal detachments were visible (Figure 1A). OCT revealed subretinal septa and heterogeneous subretinal material (Figures 1B and 1C). Multiple hyper- and hypofluorescent spots were apparent on FA and ICGA, respectively, in the early phase (Figures 1D and 1F). Pooling of dye in areas of exudative retinal detachments and optic disc leakage were present in the late phase of FA (Figures 1E and 1G). A spinal tap was performed and a cerebral fluid pleocytosis of 424 leukocytes/μL was evident. Based on the current diagnostic criteria, acute incomplete VKH disease was diagnosed.2 Intravenous therapy with 400 mg prednisolone was initiated, which was increased to 1,000 mg when BCVA decreased to hand movement and 6/60, respectively, after 2 days. Spectral-domain OCTA (AngioPlex; Carl Zeiss Meditec, Jena, Germany) was performed at that point, which revealed significant choroidal hypoperfusion at the level of Sattler's layer (Figures 2A and 2F), which was identified as previously described.5 After 3 days of high-dose corticosteroid treatment, BCVA improved to 6/15 and 6/9.5 and overall choroidal perfusion improved on OCTA (Figures 2B and 2G). Choroidal hypoperfused spots on OCTA correlated well with hypofluorescent areas on ICGA in an overlay projection (shown for the right eye in Figures 2K–2N). Steroids were reduced to 70 mg by mouth and 2 weeks after, baseline BCVA improved to 6/7.5 bilaterally. Choroidal perfusion on OCTA had further improved but still showed significant defects and additionally some new flow voids (Figures 2C and 2H). From that time point on, prednisolone was tapered in 5-day steps to 40 mg, 30 mg, 20 mg, and 10 mg and then discontinued. Four weeks after, baseline BCVA was 6/6 bilaterally and choroidal hypoperfusion on OCTA had resolved (Figures 2D and 2I) and stayed stable at 6 weeks after baseline (Figures 2E and 2J). To verify truly decreased perfusion on OCTA, all OCTA images were compared to structural en face analysis and OCT B-scans from choroidal and overlying retinal layers to exclude general loss of signal. All OCTA B-scans were manually reviewed for segmentation errors and corrected where necessary.
Baseline examination at presentation. Multicolor fundus photography of the right and left eyes (A) demonstrating multiple areas of subretinal fluid; optical coherence tomography scan with corresponding B-scan position in infrared image of the left (B) and right (C) eyes showing exudative retinal detachments with subretinal septa; (D and F) early phase fluorescein angiography (left side, respectively) revealing multiple hyperfluorescent and indocyanine angiography (right side, respectively) multiple hypofluorescent spots; (E and G) late phase fluorescein angiography (left side, respectively) showing pooling of dye in areas of exudative retinal detachments and optic disc leakage.
En face visualization of the central 3 mm × 3 mm Sattler's layer on optical coherence tomography angiography (OCTA) of the right (A–E) and left (F–J) eyes for different points of time and overlay montage of OCTA with fluorescein angiography (K) and indocyanine green angiography (ICGA) (L–N). The OCTA Sattler's layer slab was generated with decorrelation tail removal and ranges from 64 μm to 115 μm below the retinal pigment epithelium. (A–J) OCTA Sattler's layer slab from the right and left eye from different time points as specified on the left. Multiple areas of subthreshold perfusion were present at baseline and resolved over time. OCTA slabs were compared with structural OCT in order to exclude general loss of signal. (K) Central fluorescein angiography with overlay of OCTA retinal layer slab. (L–M) Central ICGA with overlay of OCTA Sattler's layer slab, exemplary areas of hypoperfusion indicated by red circles; (L) only ICGA, (M) semitransparent, (N) full overlay.
VKH disease is considered as a non-necrotizing diffuse granulomatous inflammatory disease of the uvea with epithelioid cells and surrounding lymphocytes forming granulomas, which are thought to correspond to hypofluorescent spots on ICGA.1 Based on this the monitoring of VKH disease by ICGA has been established and has proven to be one of the most useful tests for evaluation of treatment efficacy.1
With the advent of OCTA, highly detailed visualization of retinal and choroidal perfusion has become available. Furthermore, OCTA also allows for a stratification of different retinal and choroidal layers, which is not possible with fluorescein angiography and ICGA. So far, OCTA has only been utilized to examine choriocapillaris perfusion in VKH disease.3,4 However, the choriocapillaris is usually spared during the early stages of disease, potentially due to the immunosuppressive effect of the retinal pigment epithelial cells.1 Hence, evaluation of deeper choroidal layers might aid further understanding of the pathophysiology in VKH disease and allow for a better monitoring of disease activity. Therefore, assessment of deeper layers than the choriocapillaris on OCTA, like the Sattler's layer, is warranted.
Furthermore, enhanced depth OCT imaging suggests a significant reduction in the number of choroidal vessels in VKH disease in the acute and convalescent stages.6 However, as the study by Li et al. was based on OCT, only a structural evaluation was possible. As OCTA also allows for a functional evaluation (ie, evaluation of perfusion), it might be promising for further investigation of this finding.
In this case, marked areas of focal hypoperfusion in Sattler's layer in addition to previously described choriocapillary hypoperfusion3,4 were present on OCTA during the acute stage of VKH disease. They corresponded well with hypofluorescent areas on ICGA and, therefore, might represent choroidal granulomas. These hypoperfused spots in Sattler's layer on OCTA resolved during a time period of 4 weeks, and perfusion stayed stable until 6 weeks. This case report showed that VKH disease-specific alterations of choroidal perfusion are present in Sattler's layer on OCTA, hence also deeper layers than the choriocapillaris should be taken into account when assessing choroidal diseases like VKH on OCTA.
These preliminary results indicate that evaluation of deeper choroidal layers may further aid disease monitoring and prediction of prognosis in choroidal diseases like VKH. Involvement of the choriocapillaris and deeper choroidal layers may be a sign of greater inflammation and hence impact prognosis. It has been shown that ICGA can be used to detect subclinical choroidal inflammation, which cannot be recognized clinically.1 This raises the question whether this subclinical disease activity can also be detected with OCTA.
- Du L, Kijlstra A, Yang P. Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment. Prog Retin Eye Res. 2016;52:84–111. doi:10.1016/j.preteyeres.2016.02.002 [CrossRef]
- Read RW, Holland GN, Rao NA, et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: Report of an international committee on nomenclature. Am J Ophthalmol. 2001;131(5):647–652. doi:10.1016/S0002-9394(01)00925-4 [CrossRef]
- Aggarwal K, Agarwal A, Mahajan S, et al. (2016) The role of optical coherence tomography angiography in the diagnosis and management of acute Vogt-Koyanagi-Harada disease. Ocul Immunol Inflamm. 2018;26(1):142–153 doi:10.1080/09273948.2016.1195001 [CrossRef]
- Aggarwal K, Agarwal A, Deokar A, et al. Distinguishing features of acute Vogt-Koyanagi-Harada disease and acute central serous chorioretinopathy on optical coherence tomography angiography and en face optical coherence tomography imaging. J Ophthalmic Inflamm Infect. 2017;7(1):3. doi:10.1186/s12348-016-0122-z [CrossRef]
- Chen FK, Viljoen RD, Bukowska DM. Classification of image artefacts in optical coherence tomography angiography of the choroid in macular diseases. Clin Exp Ophthalmol. 2016;44(5):388–399. doi:10.1111/ceo.12683 [CrossRef]
- Li M, Liu Q, Luo Y, et al. Enhanced depth SD-OCT images reveal characteristic choroidal changes in patients with Vogt-Koyanagi-Harada disease. Ophthalmic Surg Lasers Imaging Retina. 2016;47(11):1004–1012. doi:10.3928/23258160-20161031-04 [CrossRef]