VKH

1. VOGT KOYANAGI HARADA
DISEASE
Dr. Gauree Gattani Krishnan
II Year DNB

2. Introduction
• Vogt-Koyanagi-Harada (VKH)
disease is a multisystemic
disorder characterized by
granulomatous panuveitis with
exudative retinal detachments
that is often associated with
neurologic and cutaneous
manifestations.

3. History
• Poliosis +ocular inflammation Vogt in 1906
• Primary posterior uveitis +exudative RDs +CSF
pleocytosis Einosuke Harada
• B/l chronic iridocyclitis + skin & hair
depigmentation  Koyanagi
• This constellation of findings was termed “uveitis
with polosis, vitiligo, alopecia and dysacusis.”
• Babel in 1932and Bruno & McPherson in 1945
suggested that these processes represent a
continuum of the same disease, thereafter
recognized as Vogt–Koyanagi–Harada syndrome

4. Epidemiology
• Asian, Middle Eastern, Hispanic, and Native
American populations.
• Several HLA associations including HLA-DR4,
HLA-DR53, and HLA-DQ4

6. • female predilection.
• Most patients are in their second to fifth decades
of life.
• children may also be affected

7. Prodromal stage
Uveitic stage
Chronic (convalescent) stage
Chronic recurrent stage
Stages

8. The prodromal stage
• May last only a few days
• Headaches, nausea,
dizziness, fever, orbital
pain, and meningismus.
• Light sensitivity and
tearing may occur 1 to 2
days following the above
symptoms.
• Rarely neurological signs
like cranial nerve palsies
and optic neuritis.
• CSF pleocytosis

9. The uveitic stage
• Presents with blurring of
vision in both eyes.
• One eye may be affected first
 followed a few days later by
the second eye.
• This uveitis consists of
▫ thickening of the posterior
choroid with elevation of the
peripapillary retinochoroidal
layer,
▫ multiple serous retinal
detachments
▫ hyperemia, and edema of the
optic nerve head.

10. Fluorescein angiogram of the acute uveitis stage shows multiple hyperfluorescent
dots at the level of retinal pigment epithelium during the mid ateriovenous phase

11. Note staining of the subretinal fluid during the late phase of the
angiogram.

12. The uveitic stage
• The inflammation
eventually becomes
diffuse, extending into
the anterior segment and
revealing the presence of
flare and cells in the
anterior chamber.
• Less commonly, mutton-fat
KPs, small nodules on the iris
surface and pupillary margin,
may be seen.
• The inflammatory infiltrate in
the ciliary body and choroid
may cause forward
displacement of the lens iris
diaphragm, leading to acute
angle-closure glaucoma or
annular choroidal detachment

13. The chronic (convalescent) stage
• Occurs several weeks after the acute uveitic stage
• Characterized by development of vitiligo,
poliosis and depigmentation of the choroid
• Perilimbal vitiligo, also known as Sugiura’s sign
may develop at this stage (Japanese paitients)

14. Bilateral upper-eyelid vitiligo

15. poliosis developed during the chronic stage of Vogt–Koyanagi–Harada disease

16. Chronic stage of Vogt–Koyanagi–Harada disease shows extensive posterior synechiae,
areas of depigmentation involving iris, and loss of pigment at the limbus
(Sugiura’s sign)

17. The chronic stage
• Choroidal depigmentation occurs a few months after
the uveitic phase. This leads to the characteristic pale
disc with a bright red-orange choroid known as
“sunset-glow fundus.”
• The juxtapapillary area may show marked
depigmentation.
• In Hispanics, the sunset-glow fundus may show foci
of RPE changes in the form of hyperpigmentation or
hypopigmentation.
• At this stage small, yellow, well-circumscribed areas
of chorioretinal atrophy may appear mainly in the
inferior midperiphery of the fundus.
• This convalescent phase may last for several months.

18. Chronic stage of Vogt–Koyanagi–Harada disease revealing
sunset-glow fundus in an Asian patient

19. Chronic stage of Vogt–Koyanagi–Harada disease revealing
sunset-glow fundus in an in a Hispanic woman

20. Chronic stage of Vogt–Koyanagi–Harada disease revealing oval
nonpigmented and pigmented retinal pigment epithelium atrophic lesions

21. The chronic recurrent stage
• The chronic recurrent stage consists of a smoldering
panuveitis with acute episodic exacerbations of
granulomatous anterior uveitis.
• Recurrent posterior uveitis with exudative retinal
detachment is uncommon.
• The anterior uveitis may be resistant to local and
systemic corticosteroid therapy.
• Iris nodules may be seen during this phase These
appear as round, whitish, well circumscribed
nodules on a background of atrophic iris stroma.

22. Note the iris nodule at the pupillary margin in a Hispanic male with chronic
recurrent-stage Vogt–Koyanagi–Harada disease.

23. Chronic recurrent stage of Vogt–Koyanagi–Harada disease showing multiple
small nodules in the iris and extensive posterior synechiae.

24. The chronic recurrent stage
• The most visually debilitating complication of the
chronic inflammation during this stage appears to
be the development of subretinal neovascular
membranes.
• Other features may include:
▫ Posterior subcapsular cataract
▫ glaucoma, (angle-closure or open-angle),
▫ posterior synechiae
• Linear pigmentary changes similar to those seen in
the ocular histoplasmosis syndrome and
arteriovenous anastomosis may be seen in
occasional patients

25. A 28-year-old Hispanic female developed submacular choroidal neovascular
membrane and hemorrhage during the chronic recurrent stage

26. fluorescein angiogram shows typical
neovascular membrane

27. Diagnostic criteria (American Uveitis
Society (AUS) 1978 ):
• Because of the variation in clinical presentations of VKH, the
AUS recommended the following
• (1) the absence of any history of ocular trauma or surgery; and
• (2) the presence of at least 3 of the 4 signs:
a) b/l chronic iridocyclitis
b) posterior uveitis, including exudative retinal
detachment, forme fruste of exudative retinal
detachment, disc hyperemia or edema and “sunset-glow”
fundus;
c) neurologic signs of tinnitus, neck stiffness, cranial nerve,
or central nervous system disorders, or cerebrospinal
fluid pleocytosis;
d) cutaneous findings of alopecia, poliosis, or vitiligo

28. • The authors concluded that AUS criteria for
diagnosis of VKH may not be adequate.
• Taking into account the multisystem nature of
VKH and allowing for the different ocular
findings present in the early and late stages of
the disease, the First International Workshop on
VKH proposed revised diagnostic criteria to
include clinical manifestations at various stages
of disease.

30. VKH Disease
Complete
VKH disease
Bilateral ocular involvement
Neurological/ auditory
findings
Integumentary finding
Incomplete
VKH Disease
Bilateral ocular involvement
Neurological/ auditory findings
OR
Integumentary finding
Probable VKH
Disease
Bilateral
ocular
involvement

31. A. Complete VKH disease
▫ 1. Bilateral ocular involvement (a or b must be met,
depending on the stage of disease when the patient is
examined)
 a. Early manifestations of disease
 (1) There must be evidence of a diffuse choroiditis (with or
without anterior uveitis, vitreous inflammatory reaction, or optic
disc hyperemia), which may manifest as one of the following:
▫ (a) Focal areas of subretinal fluid, or
▫ (b) Bullous serous retinal detachments
 (2) With equivocal fundus findings, both of the following must be
present as well:
▫ (a) Focal areas of delay in choroidal perfusion, multifocal areas of
pinpoint leakage, large placoid areas of hyperfluorescence, pooling
within subretinal fluid, and optic-nerve staining (listed in order of
sequential appearance) by fluorescein angiography, and
▫ (b) Diffuse choroidal thickening, without evidence of posterior
scleritis by ultrasonography

32. • b. Late manifestations of disease
▫ (1) History suggestive of prior presence of findings
from 1a, and either both (2) and (3) below, or
multiple signs from (3):
▫ (2) Ocular depigmentation (either of the following
manifestations is sufficient):
 (a) Sunset-glow fundus, or
 (b) Sugiura’s sign
▫ (3) Other ocular signs:
 (a) Nummular chorioretinal depigmented scars, or
 (b) Retinal pigment epithelium clumping and/or
migration, or
 (c) Recurrent or chronic anterior uveitis

33. 2. Neurological/auditory findings
(may have resolved by time of examination)
a) Meningismus (malaise, fever, headache,
nausea, abdominal pain, stiffness of the neck
and back, or a combination of these factors;
headache alone is not sufficient to meet the
definition of meningismus, however), or
b) Tinnitus, or
c) CSF pleocytosis

34. 3. Integumentary finding
• (not preceding onset of central nervous system
or ocular disease)
a) Alopecia, or
b) Poliosis, or
c) Vitiligo

35. B. Incomplete VKH disease
• (point 1 and either 2 or 3 must be present)
1. Bilateral ocular involvement as defined for
complete VKH disease
2. Neurologic/auditory findings as defined for
complete VKH disease above, or
3. Integumentary findings as defined for
complete VKH disease above.

36. C. Probable VKH disease
• 1. Bilateral ocular involvement as defined for
complete VKH disease above.
*In all cases there should not be a history of penetrating
ocular injury or surgery preceding the initial onset of
uveitis and no clinical or laboratory evidence suggestive of
other ocular disease criteria.
Modified from 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; 131:647–652.5

38. • VKH is a non necrotizing diffuse granulomatous
inflammation involving the uvea.
• The peripapillary choroid is the predominant
site for the granulomatous inflammatory
infiltration; and a similar but less prominent
inflammation is noted in the equatorial and
anterior choroid.

39. Acute uveitic stage of
Vogt–Koyanagi–Harada
disease shows
serous detachment of
the retina, preservation
of choriocapillaris from
inflammatory cell
infiltration, and
thickening of choroid
from granulomatous
inflammatory cell
infiltration

40. Convalescent stage of
Vogt–Koyanagi–Harada
disease,
exhibiting loss of
choroidal melanocytes
and infiltration of
lymphocytes
and plasma cells in the
choroid. Note relatively
intact retinal pigment
epithelium and
neurosensory retina

41. Chronic recurrent
stage of Vogt–
Koyanagi–Harada
disease
shows choroidal
inflammation, retinal
pigment epithelium
proliferation, and
degeneration of
overlying retina

43. • Although the exact cause for the inflammation
directed at the melanocytes remains unknown,
current evidence suggests that it involves an
autoimmune process driven by T lymphocytes
against an as yet unidentified antigen(s) associated
with melanocytes.
• The mechanism that triggers the autoimmune
process is unknown, but sensitizations to
melanocyte antigenic peptides by cutaneous injury
or viral infection have been proposed as possible
factors in some cases.
• The antigenic peptides may include tyrosinase or
tyrosinase-related proteins, an unidentified 75-kDa
protein and S-100 protein.
• either HLA-DR1 or HLA-DR4 was found in 84% of
patients withVKH disease

44. Lab Investigations
• Mainly a clinical diagnosis when patient
presents with ocular and extraocular
manifestations.
• When the disease presents without extraocular
changes
▫ fluorescein angiography
▫ lumbar puncture
▫ Ultrasonography
▫ indocyanine green (ICG) angiography and
▫ optical coherence tomography (OCT)

45. FFA
• Acute stage:
▫ numerous punctate hyperfluorescent dots at the level
of RPE.
▫ These dots enlarge and stain the surrounding
subretinal fluid.
• Late phase :
▫ multiple serous retinal detachments with pooling of
dye in the subretinal space.
▫ Over 70% of patients show disc leakage
• Chronic and Recurrent stages:
▫ “moth-eaten” appearance, with multiple
hyperfluorescent RPE window defects without
progressive staining.

46. • Early anteriovenous phase of fluorescein angiogram exhibiting multiple hyperfluorescent dots at
the retinal pigment epithelium level.

47. Late phase of the angiogram shows increased fluorescence of the dots and staining
of subretinal fluid. Note disc staining.

48. Lumbar Puncture
• Rarely done
• 80% of patients with VKH disease had CSF
pleocytosis, consisting mostly of lymphocytes.
• The pleocytosis was present in
▫ 80% of patients within 1 week and in
▫ 97% of patients within 3 weeks of the onset of
uveitis.
▫ transient and resolves within 8 weeks

49. Ultrasonography
• diffuse, low-to-medium reflective thickening of the
posterior choroid
▫ The choroidal thickening is most prominent in the
peripapillary area and generally extends to the equatorial
region, becoming progressively thinner away from the optic
nerve.
• serous RD located in the posterior pole or inferiorly
• vitreous opacities
• posterior thickening of the sclera.
• UBM examination during the uveitis stage may reveal
▫ shallow anterior-chamber
▫ ciliochoroidal detachment and
▫ thickened ciliary body

50. ICG
• Uveitic stage
▫ delay in choriocapillaris and larger choroidal vessel
perfusion.
▫ Multiple hypofluorescent spots are noted throughout
the fundus and hyperfluorescent pinpoint changes are
observed in areas of exudative retinal detachment.
• Chronic recurrent stage
▫ Multiple hypofluorescent spots are present;
• Recently OCT has been used to monitor resolution
of serous retinal detachment in patients treated with
corticosteroids.

51. Hypofluorescent dark dots in ICG

53. 1) Sympathetic ophthalmia,
▫ Sympathetic ophthalmia can present with bilateral
panuveitis associated with retinal detachment and
meningismus.
▫ But always with a history of penetrating ocular injury
2) Uveal effusion syndrome,
▫ may clinically mimic VKH disease.
▫ Angiographically, the effusion syndrome may reveal
numerous fluorescent blotches in the subretinal space
during the serous detachment phase.
▫ The syndrome can involve both eyes, although not
simultaneously.
▫ Unlike VKH disease, the effusion syndrome lacks
intraocular inflammation.

54. 3) Posterior scleritis
• affects predominantly women
• Bilateral
• may present with pain, photophobia, and loss of vision,
and the vitreous often reveals cells.
• Exudative macular detachment and choroidal folds may
be noted.
• Usually patients with bilateral involvement have a
history of rheumatoid disease.
• Ultrasonography can help to differentiate posterior
scleritis from the VKH disease. The former reveals
flattening of the posterior aspect of the globe, thickening
of the posterior coats of the eye, retrobulbar edema, and
high internal reflectivity of the thickened sclera.

55. 4) Primary intraocular lymphoma,
5) Uveal lymphoid infiltration,
6) Acute posterior multifocal placuoid pigment
epitheliopathy (APMPPE), and
7) Sarcoidosis.

57. Steroids
• Early and aggressive use of systemic corticosteroids
followed by slow tapering over 3 to 6 months is the
treatment of choice to suppress the intraocular
inflammation and to prevent the development of
complications related to the ocular inflammation
• may prevent progression of the disease to the
chronic recurrent stage and may also reduce the
incidence and/or severity of extraocular
manifestations, including the development of
sunset-glow fundus

58. • recurrences do not respond as well to systemic
corticosteroid treatment.
• Such patients may show some initial response to
sub-Tenon’s injections of triamcinolone, but
they usually require immunosuppressive or
cytotoxic agents, such as ciclosporin,
azathioprine, cyclophosphamide, chlorambucil,
mycophenolate mofetil (Cell Cept), and FK506.

59. • Oral prednisone 100 to 200 mg initially, followed
by gradual taper over 3 to 6 months
• Pulse dose of methylprednisolone 1 g/day for 3
days, followed by gradual tapering of oral
prednisone over 3 to 6 months
Corticosteroids
• Cyclosporin 5 mg/kg per day
• FK506 0.1 to 0.15 mg/kg per
day
Immunosuppressive
agents
• Azathioprine 1 to 2.5 mg/kg per day
• Mycophenolate mofetil 1 to 3 g/day
• Cyclophosphamide 1 to 2 mg/kg per day
• Chlorambucil 0.1 mg/kg per day; dose adjusted
every 3 weeks to a maximum of 18 mg/day
Cytotoxic agents

60. Others
• Patients with inflammatory cell infiltration in
the anterior chamber require topical
corticosteroids and cycloplegics to reduce ciliary
spasm and prevent posterior synechiae
formation

61. Prognosis
• treated with initial high-dose systemic
corticosteroids followed by gradual tapering will
usually have a fair visual prognosis; nearly two-
thirds of these patients retain 6/12 or better
visual acuity.
• On average, most patients require treatment for
6 months

62. Complications
The complications of chronic recurrent VKH
include
• Cataract
• Glaucoma
• Choroidal neovascularization
• Subretinal fibrosis
• Optic atrophy

63. The fundus showing subretinal fibrosis in a patient with chronic recurrent
stage of Vogt–Koyanagi–Harada disease.