3. Introduction
• Uncommon multisystem disease of Autoimmune
etiology
• Chronic,bilateral,diffuse,granulamatous pan-uveitis
• Associated with Integumentary,Neurologic,Auditory
involvement
• Commonly affects darkly pigmented ethnic groups
• Uncommon among whites
• Rare among Sub-saharan africans
• Vogt-switzerland;Koyanagi & Harada-Japan
4. Incidence
• 4% in US
• 8% in Japan
• Most common cause of Non-Infectious uveitis in
Brazil & SaudiArabia
• Women more commonly affected than Men Except in
Japanese populations
• Most common in second to fouth decade of life
5. Aetio-pathogenesis
• Unknown
• Experimental evidence suggests Cell mediated
autoimmune process against Melanocytes of all organ
systems(genetically susceptible individuals)
• T helper-1 cells & upregulation of associated
cytokines(IL-2,IL-6 &INF-gamma) also plays a role
• Recenty study suggests that IL-23(differentiation of
IL-17 producing CD4 helper T lymphocytes)
responsible for development & maintanence of
autoimmune process
Contd...
6. • Sensitisation to melanocyte antigenic peptides by
cutaneous injury/viral infections-possible trigger
• Tyrosinase/Tyrosinase related protiens(75 Kda protein &
S-100 protein targets melaocytes
• Genetic predisposition :
• HLA-DR4 in Japanese population
• HLA DRB1 *0405,HLA DRB1*0410 haplotypes-stongly
associated risk
• 84% Hispanic patients from Southern California
found to have high relative risk with HLA-DR1 than HLA-DR4
7. Clinical features
• Prodromal stage:
• Flu like symptoms
Headache,nausea,fever,meningismus
dysacusia,tinnitus,orbital pain,photophobia
Hypersensitivity of skin & hair
• Focal Neurological signs:Cranial
neuropathies,Hemiparesis,Aphasia,Transverse myelitis & ganglionitis
• CSF Analysis:lymphocytic pleocytosis,Normal level of glucose>80% of
patients(may persist up to 8 wks)
• Auditory problem:75% of patients coincide with ocular disease
Central dysacusia for higher frequencies
tinnitus in 30% of patients in early course,improves with in 2-3 months
persistent deafness may remain
8. • Acute Uveitic stage:
• Sequential blurring of vision in both eyes 1-2 days after the
onset of CNS signs
• Granulamatous anterior uveitis
• Variable degree of vitritis
• Thickening of posterior choroid with elevation of peripapillary
retinal choroidal layer
• Hyperemia & edema of optic disc
• Multiple serous retinal detachments
• Focal serous RD often shallow(clover leaf pattern) coalasce to
form large bullous exudative RD-profound visual loss
• Less commonly,mutton fat KP’s,iris nodules at pupillary margin
are observed
• AC may be shallow due to forward displacement of lens-iris
diaphragm(ciliary body edema & annular choroidal detachment)
• IOP may be elevated or low secondary to ciliary body shut down
9.
10. • Convalescent stage:
• Several weeks later
• Resolution of exudative RD
• Gradual depigmentation of choroid leads to classic orange-red
discolouration(Sunset glow fundus)
• In addition,small,round discrete depigmented lesions –inferior
peripheral fundus
• Juxta papillary depigmentation may also occur
• Perilimbal vitiligo(Sugiura sign)-85% of japanese patients,not in
whites
• Integumentary changes:Vitiligo,poliosis,alopecia corresponds to
fundus depigmentation occurs in 30% of patients
• Skin & hair changes usually occur weeks – months after onset of
ocular inflamation but it may occur simultaneously
• 10-63% develops vitiligo on ethnic background
11.
12.
13. • Chronic recurrent stage:
• Repeated bouts of granulamatous anterior uveitis
• Development of KP’s,posterior synechiae,iris
nodules,iris depigmentation,stromal atropy
• Posterior segment recurrences associated with
vitritis,papillitis,multifocal choroiditis,exudative RD
• Anterior segment recurrence coincides with sub-clinical
choroidal inflammation requires systemic
therapy
• Sequelae of chronic inflammation leads to
PSCC,glaucoma,CNV,sub retinal fibrosis
14. Histo-pathology
• Acute uveitic stage:
• Diffuse ,non-necrotising granulamatous inflammation
• consists of lymphocytes,macrophages admixed with
epitheloid and multi-nucleated giant cells with involvement
of chorio-capillaries
• Proteinaceous fluid exudates are observed in sub-retinal
space between detached neuro-sensory retina and RPE
• Peripapillary choroid –most common site of granulamatous
inflammation,ciliary body & iris may also affected
• Focal aggregates of epitheloid histiocytes admixed with
RPE(Dalen Fuchs nodules) appear between Bruch’s
membrane & RPE
15. • Convalescent stage:
• Non-granulamatous inflammation
• Infiltration of lymphocytes,few plasma cells,absence
of epitheloid histiocytes
• Number of choroidal melanocytes decrease with loss
of melanin pigment(Sunset glow fundus)
• Appeareance of numerous small atrophic depigmented
lesion in peripheral retina corresponds to focal loss
of RPE cells with chorio-retinal adhesion
16. • Chronic recurrent stage:
• Granulamatous choroiditis
• Damage to chorio-capillaries
• Clinically and pathologically similar to SO but there
are different trigerring events & mode of
sensitisation
17.
18. Diagnosis
• usually clinical
• Characterised by Exudative RD in acute stage,Sunset glow fundus in
chronic recurrent stage
• CBC,Mantoux test,TPHA-To rule out infectious cause
• FFA,ICG Angiography,OCT,USG,Lumbar puncture helps in
confirming diagnisis
• FFA:
• Acute uveitic stage:numerous hyperfluorescent foci at level of RPE
in early stage followed by pooling of dye in sub-retinal space in
areas of Neurosensory dtachment
• Majority shows disc leakage,CME & retinal vascular leakage are
uncommon
• Convalescent & Chronic recurrent stage:
• Focal RPE loss and atrophy produce multiple hyperfluorescent
window defects without progressive staining
19.
20. • ICG Angiography:
• highlights choroidal pathology
• Shows delay in choriocapillaries & choroidal vessel
perfusion
• Early choroidal vessel stromal hyperfluorescence &
leakage
• Disc hyperfluorescence
• Multiple hypofluorescent spots throughout the
fundus indicates foci of lymphocytic infiltration
• Hyperfluorescent pinpoint changes with in areas of
exudative RD
• Hypofluorescent spots-sensitive marker and follow up
of sub clinical choroidal inflammation(when
fundoscopic & FFA findings are unremarkable)
21. • USG:
• Helpful in diagnosis in presence of media opacity
• Shows diffuse,low to medium reflective thickening of
posterior choroid ,most prominent in peripapillary
area with extension to equatorial region
• Exudative RD
• Vitreous opacification
• Posterior thickening of sclera
22. • OCT:
• helps in diagnosis & monitoring of
• Serous macular detachment
• CME
• CNVM
• Lumbar puncture:
• Done in atypical cases who presented early with
neurological signs
• Shows lymphocytic pleocytosis
25. Immunomodulator therapy(IMT)
• Methotrexate:15mg once a week plus
• Folic acid 5mg once daily for six days
• Liver toxicity
• Mycophenolate mofetil:500mg twice daily
• 1500mg max/day(1000+500mg)
• Azathioprine:50mg thrice/twice daily-renal toxicity
• Cyclosporine:2-3mg/kg body weight
• renal toxicity
• Cyclophosphamide:50mg thrice daily orally
• hematuria
• Inv:CBC,LFT,RFT,Blood sugar,blood pressure
26. Prognosis
• Good with prompt and agressive therapy
• In addition to cataract and
glaucoma,subretinal fibrosis and choroidal
neovascular membrances may occur
28. Introduction
• Chronic, relapsing, occlusive systemic vasculitis
• Etiology unknown
• Affects both anterior & posterior segment
• Adamantiades & Behcet
• Most common-Northern hemisphere in countries of
eastern mediterranean & on eastern rim of Asia(old
silk route)
29. Prevalance
• 80-300 cases per one lakh in Turkey
• 8-10 cases per one lakh in Japan
• 0.4 cases per one lakh in US
• Complete type of BD- Men
• Incomplete type of BD- equally affected
• Typical age of onset- 25-30 years of age
• Can occur in 10-15 years of age
• Mostly sporadic
• Familal cases are also reported
30. • Pathogenesis:
• Unknown
• Environmental factors-potential cause (not proved)
• No infectious agents-reproduced from lesions
• Clinically & experimentally unlike other autoimmune diseases
• HLA association:
• HLA B12-Mucocutaneous lesions
• HLA B27-arthritis
• HLA B51-Ocular lesions
• Not reproducible in all patients
• Little diagnostic value
• Histology:
• Early lesions-delayed type of hypersensitivity
• Late lesions:immune-complex type reaction
32. Systemic manifestations(Non-ocular)
• Aphthous Ulcer:
• Most frequent finding in BD
• Discrete,round or oval,white ulcerations with red
rim(size 2 to 15 mm)
• Recurrent mucosal ulcers-discomfort & pain
• Lips,gums,palate,tongue,uvula,posterior pharynx)
• Recur every 5-10 days or every month
• Lasts from 7-10 days,heal without much scarring
33.
34. • Skin lesions:
• Erythema Nodosum:
• painful,recurrent lesion
• noted over external surfaces-tibia & also over face,neck &
buttock
• Disappear with minimal scarring
• Acne vulgaris:
• Folliculitis like skin lesion
• Face & upper thorax
• 40% patients exhibit cutaneous pathergy(development of
sterile pustule at the site of venipuncture or injection)
• Not pathognomonic of BD
• Genital ulcers:
• Appearance similar to aphthous ulcer
• Male-scrotum/penis
• Female-vulva/vaginal mucosa
36. • Neurological:10%
• Most serious of all
• 10%patients with neuro BD have ocular disease
• 30%patients with ocular BD have neurological
involvement
• Affects motor system
• Widespread vasculitis-headache
• Stroke,palsies,acute confusional state-25%patient
• Cranial nerve palsies,papillitis,visual field
defects,papilloedema (thrombosis of superior sagital
sinus/other venous sinuses)
• Mortality rate-10%
• Men>women
37. Ocular manifestations
• 70% patients with BD
• Men>women
• 80% bilateral
• Non granulamatous,panuveitis with necrotising obliterative vasculitis
• Recurrent,relapsing condition cause permanent,irreversible ocular
damage
• Severe vision loss-25% patients
• Anterior uveitis:
• Transient hypopyon:25%
• shift with patient’s head position
• disperse with head shaking
• may not visible unless viewed by Gonioscopy
• can resolve spontaneously without treatment
• explosive onset(within hours)
38.
39. • Posterior segment:
• Most common form of uveitis seen in children & adults with BD
• obliterative necrotising retinal vasculitis,both arteries & veins
• BRVO,Isolated BRAO,Combined,vascular sheating with vitritis
with CME
• Retinal ischemia-NV,NVI,NVG
• Repeated episodes-vessels become white & necrotic
• Acute vasculitis may be associated with multifocal areas of
chalky white retinitis
• Ischemic vasculitis with retinitis mimic acute retinal necrosis
syndrome/necrotising herpetic/retinitis
• ONH-25%
• Vasculitis affectin arterioles of optic nerve leads to progressive
optic neuropathy
44. FFA
• Marked dilatation & occlusion of retinal
capillaries with perivascular staining
• Evidence of retinal ischemia
• Leaking of fluorescein in to macula
• CME
• Retinal neovascularisation may leak
46. Treatment
• Aim:not only to treat but to control acute inflammation
• To prevent/decrease number of relapses with IMT
• systemic corticosteroids
• Azathioprine-preserving visual acuity,control oral,genital
lesions,arthritis
• The European league against rheumatism panel:
• Azathioprine with corticosteroids(first line)
• Cyclosporine/Infliximab(second line)
• Tacrolimus-less toxic(substitute)
• Colchicine-mucocutaneous disease
• Mycophenolate mofetil:also successful
• Chlorambucil-effective at lower doses
• Cyclophaspamide-alternative to chlorambucil
• INF alpha-2a-highly effective in BD
