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Vogt Koyanagi Harada Disease

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VKH

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Vogt Koyanagi Harada Disease

  1. 1. VOGT KOYANAGI HARADA DISEASE Dr. Gauree Gattani Krishnan II Year DNB
  2. 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. 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. 4. Epidemiology • Asian, Middle Eastern, Hispanic, and Native American populations. • Several HLA associations including HLA-DR4, HLA-DR53, and HLA-DQ4
  5. 5. • female predilection. • Most patients are in their second to fifth decades of life. • children may also be affected
  6. 6. Prodromal stage Uveitic stage Chronic (convalescent) stage Chronic recurrent stage Stages
  7. 7. 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
  8. 8. 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.
  9. 9. Fluorescein angiogram of the acute uveitis stage shows multiple hyperfluorescent dots at the level of retinal pigment epithelium during the mid ateriovenous phase
  10. 10. Note staining of the subretinal fluid during the late phase of the angiogram.
  11. 11. 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
  12. 12. 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)
  13. 13. Bilateral upper-eyelid vitiligo
  14. 14. poliosis developed during the chronic stage of Vogt–Koyanagi–Harada disease
  15. 15. 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)
  16. 16. 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.
  17. 17. Chronic stage of Vogt–Koyanagi–Harada disease revealing sunset-glow fundus in an Asian patient
  18. 18. Chronic stage of Vogt–Koyanagi–Harada disease revealing sunset-glow fundus in an in a Hispanic woman
  19. 19. Chronic stage of Vogt–Koyanagi–Harada disease revealing oval nonpigmented and pigmented retinal pigment epithelium atrophic lesions
  20. 20. 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.
  21. 21. Note the iris nodule at the pupillary margin in a Hispanic male with chronic recurrent-stage Vogt–Koyanagi–Harada disease.
  22. 22. Chronic recurrent stage of Vogt–Koyanagi–Harada disease showing multiple small nodules in the iris and extensive posterior synechiae.
  23. 23. 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
  24. 24. A 28-year-old Hispanic female developed submacular choroidal neovascular membrane and hemorrhage during the chronic recurrent stage
  25. 25. fluorescein angiogram shows typical neovascular membrane
  26. 26. 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
  27. 27. • 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.
  28. 28. 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
  29. 29. 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
  30. 30. • 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
  31. 31. 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
  32. 32. 3. Integumentary finding • (not preceding onset of central nervous system or ocular disease) a) Alopecia, or b) Poliosis, or c) Vitiligo
  33. 33. 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.
  34. 34. 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
  35. 35. • 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.
  36. 36. 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
  37. 37. 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
  38. 38. Chronic recurrent stage of Vogt– Koyanagi–Harada disease shows choroidal inflammation, retinal pigment epithelium proliferation, and degeneration of overlying retina
  39. 39. • 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
  40. 40. 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)
  41. 41. 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.
  42. 42. • Early anteriovenous phase of fluorescein angiogram exhibiting multiple hyperfluorescent dots at the retinal pigment epithelium level.
  43. 43. Late phase of the angiogram shows increased fluorescence of the dots and staining of subretinal fluid. Note disc staining.
  44. 44. 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
  45. 45. 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
  46. 46. 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.
  47. 47. Hypofluorescent dark dots in ICG
  48. 48. 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.
  49. 49. 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.
  50. 50. 4) Primary intraocular lymphoma, 5) Uveal lymphoid infiltration, 6) Acute posterior multifocal placuoid pigment epitheliopathy (APMPPE), and 7) Sarcoidosis.
  51. 51. 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
  52. 52. • 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.
  53. 53. • 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
  54. 54. Others • Patients with inflammatory cell infiltration in the anterior chamber require topical corticosteroids and cycloplegics to reduce ciliary spasm and prevent posterior synechiae formation
  55. 55. 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
  56. 56. Complications The complications of chronic recurrent VKH include • Cataract • Glaucoma • Choroidal neovascularization • Subretinal fibrosis • Optic atrophy
  57. 57. The fundus showing subretinal fibrosis in a patient with chronic recurrent stage of Vogt–Koyanagi–Harada disease.

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