Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune inflammatory disorder characterized by bilateral panuveitis frequently associated with neurologic, auditory, and integumentary manifestations.1 It accounts for 6% to 8% of all uveitis in Asia and 1% to 4% in North America.2
Bilateral stromal choroiditis with multifocal exudative retinal detachments (RDs) is the most characteristic finding in the acute phase, whereas recurrent posterior and/or anterior uveitis, choroidal depigmentation, and sunset glow fundus are hallmarks of the chronic/recurrent stages.3
Fluorescein angiography (FA) reveals pinpoint staining and larger hypofluorescent lesions in the early phase, which leak and become hyperfluorescent in the late phase, with pooling of dye in the areas of exudative RDs. Indocyanine green angiography (ICGA) can detect subtle changes in choroidal microvasculature, appearing as hypofluorescent dark spots, which have been shown to correspond to the choroidal inflammatory foci/granulomas.4
On conventional spectral-domain optical coherence tomography angiography (SD-OCTA), multiple areas of hypoperfusion in the choriocapillaris (CC) that seem to correspond to hypofluorescent spots on ICGA have been reported.5,6
Herein, we present the first report of widefield swept-source OCTA (SS-OCTA) in VKH and investigate its potential use in the acute stage as well as in the follow-up of VKH patients.
A 38-year-old Asian female with a history of upper respiratory infection 2 weeks prior presented complaining of 2 weeks of bilateral hearing loss, tinnitus, and blurry vision, worse in the last 5 days. Her best-corrected visual acuity (BCVA) was counting fingers at 6 feet in and 20/300 in her right and left eyes, respectively.
On examination, she had 3+ anterior chamber cells with 2+ flare and 1+ vitreous cells in both eyes, corneas with bilateral inferior keratic precipitates, pigment on the anterior lens capsules and normal intraocular pressures bilaterally. Funduscopy revealed slightly hyperemic discs and large multifocal serous retinal detachments in both eyes (Figure 1).
Color fundus photographs revealing slightly hyperemic discs and large multifocal serous retinal detachments bilaterally, marked by arrowheads. (A) Right eye. (B) Left eye.
Widefield SS-OCT high-definition (HD) 51-line (12 mm) (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, CA) showed extensive subretinal fluid (SRF) and subfoveal fluid in both eyes with multifocal serous retinal detachments. Subfoveal and posterior pole choroidal thickening was noted (Figures 2A and 2B).
Widefield swept-source optical coherence tomography with scanning protocol high-definition 51-line (12 mm) showing extensive subretinal fluid (SRF) with multifocal serous retinal detachments and choroidal thickening in both eyes (A: right eye, B: left eye) before treatment and minimal residual SRF and reduction in choroidal thickness in both eyes after treatment (C: right eye, D: left eye).
FA showed optic disc staining with typical pinpoint staining and larger hypofluorescent lesions in the early phase, which leak and become hyper-fluorescent in the late phase, with multi-lobulated pooling of dye in the areas of exudative RDs in both eyes (Figures 3A–3D).
Fluorescein angiography showing optic disc staining, typical pinpoint staining, and larger hypofluorescent lesions in the early phases (A: right eye, B: left eye), which become hyperfluorescent in the late phase (white arrowheads), with multi-lobulated pooling of dye in the areas of exudative retinal detachments in both eyes (yellow arrowheads) (C: right eye, D: left eye).
Widefield SS-OCTA montage 15 mm × 15 mm, Angio 12 mm × 12 mm, and Angio 6 mm × 6 mm was performed revealing vitreous cells (Figure 4A), extensive areas of multifocal exudative RDs in the retina depth-encoded images (Figure 4B), signal attenuation artifacts from the overlying SRF on the choroid layer (Figure 4C), and characteristic areas of flow void at the level of the CC (Figure 4D). The corresponding structural en face image of the choroid and cross-sectional OCT B-scans from choroidal and overlying retinal layers did not show any areas of signal loss, suggesting that the flow void areas in the CC likely represent true loss of flow7 (Figure 5). Focal hypoperfusion areas were also observed in deeper choroidal layers. No significant changes in the superficial and deep capillary plexus were identified.
Widefield swept-source optical coherence tomography angiography showing (A) 6 mm x 6 mm image of the vitreoretinal interface showing vitreous cells, (B) retina depth-encoded images with extensive areas of multifocal exudative retinal detachments (RDs), (C) choroid layer with focal hypoperfusion areas and signal attenuation artifacts form the overlying RDs with respective B-scan, and (D) choriocapillaris with characteristic areas of flow void and respective B-scan.
Corresponding structural en face image of the choroid and cross-sectional optical coherence tomography B-scans from choroidal and overlying retinal layers with no areas of signal loss, suggesting that the flow void areas in the choriocapillaris (CC) likely represent true loss of flow.
Complete blood count, antinuclear antibodies, syphilis serology, angiotensin converting enzyme, lysozyme, QuantiFERON-TB Gold (Qiagen, Hilden, Germany), and chest X-ray were all normal. Lumbar puncture was not performed. Our patient was diagnosed to have VKH disease and subsequent treatment with intravenous methylprednisolone and oral prednisone was initiated.
At 5 weeks' follow-up, BCVA was 20/32 and 20/25 in her right and left eyes, respectively. Anterior chamber cells and flare had completely resolved, and trace vitreous cells were present in both eyes. Fundus examination revealed discs with sharp margins, RPE mottling, resolution of SRF, and bilaterally attached retinas with resolved serous detachments in the periphery. Widefield SS-OCTA showed resolution of subfoveal fluid, minimal residual SRF, trace vitreous cells, choroid with no signal attenuation artifacts form the overlying SRF, and a decrease in size and number of CC flow void areas (Figure 6).
Widefield swept-source optical coherence tomography angiography comparison before treatment (A, B, C) versus after treatment showing trace vitreous cells in the vitreoretinal interface (D), decrease in size and number of choriocapillaris flow void areas (E), and choroid with decreased focal hypoperfusion areas and no signal attenuation artifacts (F).
With the advent of OCTA, noninvasive, highly detailed, depth-encoded visualization of retinal and choroidal microvasculature became available, allowing for separate assessment of the CC perfusion.8
To the best of our knowledge, this is the first report of widefield SS-OCTA in VKH, and only the second using SS-OCTA, in general. In the present case of VKH, wide field SS-OCTA demonstrated characteristic areas of flow void at the level of CC in the acute phase that did decrease in size with treatment.
Compared to SD-OCTA, SS-OCTA enables detection of less strong signal from the CC due to greater penetration through the RPE, higher energy scans and less sensitivity to roll-off in the standard vitreoretinal scanning protocol used in the clinical practice.9,10,11 Thus, flow void in the CC observed by SS-OCTA is more likely to correspond to true loss of flow more so than low signal eliminated due to thresholding. Absence of signal loss on the corresponding choroidal structural en face image and cross-sectional OCT B-scans further suggests that the areas of flow void in the CC likely represented true loss of flow more so than artifacts. Besides, widefield SS-OCTA also allowed for visualization of vitreous inflammation in the acute phase.
Our findings build upon previous reports suggesting that the pathogenesis of VKH is linked to choroidal circulatory disturbances and increased choroidal thickness.12 Histopathologic studies have shown that although VKH disease primarily affects the choroidal stroma, localized ischemic changes in the CC may also be found, especially in recurrent cases13 In a recent study of a Chinese VKH cohort, a negative correlation between vascular density of the CC layer and BCVA was established, linking structural and flow changes with visual impairment in patients with VKH.14 Hence, evaluation of the CC layer as well as the deeper choroidal layers via OCTA might offer further understanding of the pathophysiology in VKH disease and allow for a better monitoring of disease activity.
Thus far, ICGA remains the gold standard to evaluate choroidal pathologies, including VKH.15 Even though ICGA is a very sensitive imaging modality in detecting subclinical inflammatory changes in the CC and choroidal stromal vessels in early stages or after systemic therapy,4,16 it remains an invasive procedure with the risk of potentially serious dye-related adverse effects,17 making it not ideal for repeated follow-up testing to monitor disease activity.
To date, few data have been published on the OCTA features of VKH. A single case of VKH using narrow field (3 mm × 3 mm) SS-OCTA was recently published describing subfoveal choroidal thickening and dark patchy areas at the level of CC corresponding to ischemia.18 The few reports on VKH with SD-OCTA describe multiple foci of CC flow void being well correlated with ICGA hypofluorescent areas.5,6,19,20 Wintergerst et al. reported marked areas of focal hypoperfusion in deeper choroidal layers than the CC (Sattler's layer).19
Of interest, reappearance of areas of CC hypoperfusion on OCTA without any detectable changes on ICGA prior to clinical recurrence has been described5 suggesting OCTA-detected CC changes may be either more sensitive or may precede changes in ICGA in some cases of VKH.
A gradual resolution in the CC flow void areas on OCTA has been found to be well-correlated with the decrease in the subfoveal choroidal thickness on enhanced-depth imaging OCT (EDI-OCT) and the resolution of SRF.5 Cases where OCTA changes in CC were identifiable, whereas no significant findings on EDI-OCT have been described.5
In light of the above, OCTA might be even more sensitive in disease persistence than the current gold-standard imaging techniques upon which the revised criteria for VKH are based.1 Therefore, OCTA may greatly supplement EDI-OCT and reduce the need for dye-related modalities such as ICGA or FA in routine follow-up of VKH patients in clinical practice.
Widefield SS-OCTA enables detection of vitreous inflammation, identification of the changes at the level of CC in the acute phase of VKH, and may be a novel valuable tool not only to diagnose, but also to noninvasively monitor disease progression, persistence, resolution, recurrence, and guide therapy in VKH disease in the future.
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