Reappraisal of the management of Vogt-Koyanagi-Harada disease: sunset glow fundus is no more a fatality

Abstract

Purpose: Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. Aim of the study was to gather a body of evidence from the literature and from experts that systemic corticosteroid combined with non-steroidal immunosuppressive therapy should become the standard of care in initial-onset VKH disease.

Methods: Literature was reviewed and leading experts in VKH were consulted in different parts of the world in order to put forward a consensus attitude in the management of initial-onset VKH disease.

Results: There was a substantial body of evidence in the literature that early aggressive and sustained corticosteroid and non-steroidal immunosuppressive therapy in initial-onset VKH disease allows to achieve full control of choroidal inflammation, eliminating any subclinical choroidal inflammation, and substantially reduces recurrences with improvement of anatomical and functional outcomes. This was in agreement with experts' opinion and practice. ICGA was the method of choice to monitor disease evolution.

Conclusion: Since the choroidal space is easily accessible to systemic therapy and because inflammation in VKH disease is exclusively originating from the choroidal stroma, early and sustained treatment right at the onset of the disease process with dual corticosteroid and non-steroidal immunosuppressive therapy can result in full "healing" in many cases preventing sunset glow fundus which results from depigmentation from chronic uncontrolled inflammation.

Keywords: Granulomatous uveitis; Immunosuppressive therapy; Indocyanine green angiography; Stromal choroiditis, autoimmune disease; Vogt–Koyanagi–Harada disease.

Conflict of interest statement

Conflict of interest

None of the authors have a financial nor a proprietary interest in the subject matter or materials discussed in this manuscript.

Informed consent

For this type of study formal consent is not required.

Research involving animal and human rights

All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Figures

Fig. 1

During the prodromal stage of the disease, subclinical choroidal inflammation is silently developing in the choroidal stroma as shown on cartoon (top left). This subclinical choroidal involvement can only be detected by ICGA, possibly by choroidal OCT. On the fundus pictures shown on top right, the right fundus is discoloured yellow due to massive choroidal infiltration. The right fundus looks normal and this patient was diagnosed as “unilateral” VKH disease. FA shows no lesions (six bottom left frames) but ICGA (six bottom right frames) clearly shows numerous hypofluorescent dark dots (HDDs) indicating choroidal granulomas in the apparently uninvolved eye

Fig. 2

Acute exudative initial-onset VKH disease. Peripapillary and retinal exudative detachments seen on fundoscopy (top left) and FA (bottom left). Extrachoroidal structures are involved when choroidal disease spills over to neighbouring structures (cartoon, top right). Optical coherence tomography (OCT) shows clearly the detachment of the neurosensory retina (middle figure on the right). Moderate granulomatous anterior uveitis accompanying posterior involvement. (bottom right)

Fig. 3

Sensitivity and global panfundal information given by ICGA. Case of VKH disease responsive to initial highly dosed corticosteroids with peripheral recurrence under mycophenolic acid (Myfortic ®) and cyclosporine (CsA) characterized by numerous HDDs (top pictures). After introduction of infliximab complete resolution of choroiditis within 5 weeks (bottom pictures), establishing infliximab as the therapy to which this patient was responsive. Posterior pole involvement was minimal and choroidal OCT did not reflect spectacular improvement of choroiditis

Fig. 4

Indocyanine green angiographic signs. ICGA is the only technique to analyse choroidal inflammatory signs including early stromal hyperfluorescent vessels (top left), hypofluorescent dark dots (HDD) indicating choroidal granuloma (top right), fuzzy indistinct choroidal vessels (top 2 frames of bottom left quartett). After 3 days of intravenous 1000 mg daily methylprednisolone the normal pattern of vessels is again recognizable (bottom 2 frames of bottom left quartett). Bottom right quartett of frames shows diffuse late hyperfluorescence and hyperfluorescent inflamed disc

Fig. 5

A ICGA is more reactive than EDI-OCT for close, visit by visit follow-up. Patient with initial onset VKH disease having responded to initial high-dose IV and then oral corticosteroids, together with mycophenolic acid Myfortic® and cyclosporine (CsA)with reduction of ICGA score from 31/40 to 6/40 (a), using an established dual FA/ICGA scoring system [61, 62]. Under Myfortic® and CsA, ICGA score increased again to 17/40 (b), not reflected in EDI-OCT that shows slight decrease of choroidal thickness (c, d). B Indocyanine green angiography is more reactive than EDI-OCT for precise follow-up of VKH disease (same patient as in Fig. 3) Patient with VKH disease under Myfortic® and CsA to which choroiditis is not responding with an ICGA score of 20.5/40 (a). After 6 months, it was decided to add Remicade® (Infliximab, an anti-TNF-blocker, 5mg/kg per infusion). 5 weeks later (3 infusions), HDDs completely disappeared with a decrease of ICGA score from 20.5 ± 4.9 to 1 (p < 0.03) (b), while choroidal thickness showed a slight non-significant difference, 507 ± 66 versus 460 ± 18 μm (p = 0.31) (c, d)

Fig. 5

A ICGA is more reactive than EDI-OCT for close, visit by visit follow-up. Patient with initial onset VKH disease having responded to initial high-dose IV and then oral corticosteroids, together with mycophenolic acid Myfortic® and cyclosporine (CsA)with reduction of ICGA score from 31/40 to 6/40 (a), using an established dual FA/ICGA scoring system [61, 62]. Under Myfortic® and CsA, ICGA score increased again to 17/40 (b), not reflected in EDI-OCT that shows slight decrease of choroidal thickness (c, d). B Indocyanine green angiography is more reactive than EDI-OCT for precise follow-up of VKH disease (same patient as in Fig. 3) Patient with VKH disease under Myfortic® and CsA to which choroiditis is not responding with an ICGA score of 20.5/40 (a). After 6 months, it was decided to add Remicade® (Infliximab, an anti-TNF-blocker, 5mg/kg per infusion). 5 weeks later (3 infusions), HDDs completely disappeared with a decrease of ICGA score from 20.5 ± 4.9 to 1 (p < 0.03) (b), while choroidal thickness showed a slight non-significant difference, 507 ± 66 versus 460 ± 18 μm (p = 0.31) (c, d)

Fig. 6

Signs found in chronically evolving disease. Chronic granulomatous uveitis with old pigmented KPs (top left), Koeppe nodules, iris infiltration and Busacca nodules (top right). Mid-periphery hypopigmented lesions are shown on the middle left picture and sunset-glow-fundus on the right middle picture. Mottled irregular, disturbed RPE in the posterior pole and high-water marks indicating limit of reattached serous retinal detachment as well as disc hyperfluorescence seen on the FA frame (bottom left). Only ICGA can show that disease is still active as evidenced by the numerous dark dots (bottom right)