Vogt-Koyanagi-Harada Syndrome
Prof. dr. Ph. Kestelyn
© 2008 Universitair Ziekenhuis Gent
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VKH Disease
• Multisystem disease
• Chronic, bilateral, granulomatous panuveitis associated
with central nervous system, auditory and
integumentary manifestations
Moorthy et al: Surv Ophthalmol 1995; 39:265 (review)
Read et al: Am J Ophthalmol 2001;131:647
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VKH (Vogt-Koyanagi-Harada Syndrome)
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Systemic disorder
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eyes/ears
 meninges
 skin
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VKH (Vogt-Koyanagi-Harada Syndrome)
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First description: 12th century Mohammad-al-Ghafiqi
Vogt: 1906 one case
Koyanagi: 1923 six cases
Harada: 1926 posterior uveitis and pleocytosis of CSF
 Vogt-Koyanagi-Harada or VKH
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VKH (Vogt-Koyanagi-Harada Syndrome)
Epidemiology
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more prevalent in darker skinned ethnic groups
common
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in Japan
in people from Mediterranean origin
in American Indians/Africans
in Indians
2nd to 4th decade
approx. 15% < 16 in Turkey and Saudi Arabia
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VKH (Vogt-Koyanagi-Harada Syndrome)
Clinical course
4 phases
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prodromal
acute uveitic
convalescent or chronic
chronic recurrent
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VKH (Vogt-Koyanagi-Harada Syndrome)
Systemic Findings
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Prodromal stage
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headache, orbital pain
 neck stiffness
 neurologic symptoms
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lumbar puncture: pleocytosis in 80% (lymphocytes ↑,
monocytes ↑, normal glucose)
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VKH (Vogt-Koyanagi-Harada Syndrome)
Auditory Findings
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concurrent with ocular findings
hearing loss for higher frequencies
dysacousia
tinnitus
objective signs > subjective symptoms
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 audiology
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VKH (Vogt-Koyanagi-Harada Syndrome)
Skin lesions
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sensitivity to touch of hair and skin (active phase)
vitiligo/poliosis (convalescent phase)
alopecia
seen in ¾ of patients
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VKH (Vogt-Koyanagi-Harada Syndrome)
Ocular Findings
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bilateral disease
granulomatous panuveitis
AS involvement
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often nongranulomatous in acute phase
 iris nodules and mutton fat KP’s in chronic or recurrent
disease
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shallowing of the AC + IOP ↑
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inflammatory swelling of ciliary body
pupillary block
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surgical iridectomy mandatory
formation of AS  chronic glaucoma
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VKH (Vogt-Koyanagi-Harada Syndrome)
Ocular Findings
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perilimbal vitiligo (Sugiura’s sign)
poliosis ( loss of lashes and regrowth of depigmented white
lashes)
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VKH (Vogt-Koyanagi-Harada Syndrome)
Ocular Findings (posterior)
Acute phase
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swelling of the optic nerve
important vitreous reaction
exsudative retinal detachment
yellow-white retinal lesions in the
periphery (Dalen-Fuchs nodules?)
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Case report
female, 22 years old
Ethiopian (in Belgium since 20 months)
bilateral loss VA (RE 1 month, LE 1 week),
photophobia, orbital pain
general history : unremarkable
ocular history : unremarkable
no medication
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Ophthalmological examination
VA:
OD: CF 2m, no Parinaud 10
OS: CF 3m, no Parinaud 10
SLE:
OD: flare, cells +(+), fine precipitates
OS: flare, cells +
IOP:
OU: 14 mmHg
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Fundoscopy:
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VKH (Vogt-Koyanagi-Harada Syndrome)
Ocular Findings (posterior)
convalescent or chronic phase
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neovascularisation of retina/optic
nerve
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recurrent vitreous hemorrhages
often intraretinal NV of the macula
reactive proliferation of the RPE:
scars, RPE clumping
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VKH (Vogt-Koyanagi-Harada Syndrome)
Ocular Findings (late)
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“sunset glow” fundus = depigmentation of the posterior pole
(RPE + choroid)
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VKH (Vogt-Koyanagi-Harada Syndrome)
Ocular Findings (late)
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Subretinal / fibrosis / RPE alterations / disciform scars
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VKH (Vogt-Koyanagi-Harada Syndrome)
Ocular Findings (late)
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subretinal/fibrosis/disciform scars/RPE alterations
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VKH (Vogt-Koyanagi-Harada Syndrome)
Natural history
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isolated posterior disease (Harada)
isolated ocular forms (probable VKH)
clinical course
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severe ocular inflammation  depigmentation 
quiescence
anterior + posterior inflammation  depigmentation 
recurrent anterior disease
chronic ongoing inflammation
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VKH
Diagnosis
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clinical findings
FA/ICG
ultrasound
lumbar puncture
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VKH (Vogt-Koyanagi-Harada Syndrome)
FA in VKH
Acute phase:
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numerous punctate hyperfluorescent dots RPE level
staining of subretinal fluid
optic nerve leakage
Convalescent phase:
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window defects, CNV, subretinal fibrosis
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Fluo-angiography:
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VKH (Vogt-Koyanagi-Harada Syndrome)
ICG findings in VKH
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early choroidal stromal vessel hyperfluorescence
hypofluorescent dark dots
fuzzy vessels (vasculitis)
disc hyperfluorescence
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Ultrasound:
thickening of the posterior choroid
serous retinal detachment
no T- sign
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VKH (Vogt-Koyanagi-Harada Syndrome)
Pathogenesis
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antigen driven immune response
antigen = human melanocyte?
T-cell mediated specific killing against P-36 melanoma cell
line (Maezawa et al)
sequence of tyrosinase family proteins induces proliferation
of lymphocyte in VKH patients
injection of tyrosinase + gp 100 injection in Lewis rats
produces animal model of VKH(Sugita et al)
identification of several T-cell lines against tyrosinase and
tyrosinase related protein (Gocho et al)
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VKH (Vogt-Koyanagi-Harada Syndrome)
Pathogenesis
• certain racial groups.
• immunogenetic predisposition.
• strong association with HLA-DR4 and HLA-DRw53 with
the most significant risk allele being HLA-DRB1*0405.
• causative pathogenic antigen binds with HLA-DRB1*0405
molecule which presents the antigen to T cells to activate
them.
© 2008 Universitair Ziekenhuis Gent
Fang and Wang: Curr Eye Res 2008;33:517 (review).
Read et al: Curr Opin Ophthalmol 2000;11:437 (review).
Yamaki et al: Int Ophthalmol Clin 2002;42:13 (review).
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VKH (Vogt-Koyanagi-Harada Syndrome)
Pathology
• granulomatous panuveitis.
• lymphocytes, epitheloid cells, few plasma cells, multinucleated
giant cells.
• epitheloid cells and giant cells contain melanin pigment.
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VKH (Vogt-Koyanagi-Harada Syndrome)
Treatment
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systemic corticosteroids
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intravenous pulse therapy
 oral treatment (2 mg/kg/day)
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no difference pulse ↔ high dose oral (Read et al)
better little outcome high dose steroids > low dose
(Miyanaga et al)
duration ~ inflammatory activity
slow taper over 1 year period
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topical treatment for anterior uveitis
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VKH (Vogt-Koyanagi-Harada Syndrome)
Treatment
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slow taper over 1 year period or ~ inflammatory activity
consider adding cyclosporine to reduce side effects of high
dose steroids
mofetil mycofenolate ?
adalimumab (Humira)?
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VKH Prognosis
• visual prognosis is generally favorable.
• 87.5% achieved V.A. of ≥20/40.
• high-dose systemic corticosteroids for >9 months with
slow tapering significantly improves the prognosis and
decreases risk of recurrence.
• age older than 18 years is significantly associated with the
development of complications.
• visual prognosis is generally favorable in children.
Al-Kharashi, Abu El-Asrar: Int Ophthalmol 2007;27:201
Abu El-Asrar et al: Eye 2008;22:1124
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Thank you !
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