The document is a detailed overview of uveitis, including its classification, causes, diagnostic approaches, and management strategies. It discusses the various types of uveitis based on etiology, anatomy, and clinical features, along with signs to identify and differentiate them. Additionally, it outlines complications associated with uveitis and emphasizes the need for systemic investigations, specifically highlighting the importance of syphilis testing in patients with uveitis.

1. Uveitis
Dr Yong Meng Hsien
Lecturer & Ophthalmologist, UKM & HCTM
yongmenghsien@ppukm.ukm.edu.my
Last edited: Feb 2022

2. The Basic

3. Approach
• History
• Examination
(ophthalmic + targeted
systemic)
– Functional tests
– Ophthalmic imaging
• Investigation
– Lab
– Ophthalmic imaging
– Associate imaging
Aim: Diagnosis + Cause + Complication
• Diagnosis (Provisional)
• Diagnosis (DDx, emergency,
life or vision-threatening)
• Cause (infectious)
• Cause (non-infectious)
• Complication (happened)
• Complication (to prevent)

4. Classification
• Etiology: Noninfectious (autoimmune) and infectious
• Anatomy: AU/IU/PU/Pan
• Clinical: onset, duration, and course
• Adult vs child
• Laterality
• Severity
• Type of inflammation- granulomatous
• Distribution (retina/choroid): focal, multifocal, diffuse
• Association: systemic dz, hypertensive (high IOP)

5. Terminology
• Anatomy & laterality: UL/BL → AU/IU/PU/panU
– IU: 15% of all uveitis/20% of paediatric uveitis
– Recurrent AU > idiopathic/HLA B 27
– CAU: <common <red but >BL >systemic >granulomatous
>pigmented KP/Cx
• Course (6wk/3mth): acute/chronic, recurrent/relapse,
remission
• Granulomatous/not
– related to the disease stage, the amount of antigen at presentation, or the
patient’s state of immunocompromise
– Non-granulomatous: lymphocytic and plasma cell infiltrate; KPs > diffuse &
fine
– Granulomatous: epithelioid and giant cells; KPs > large, clumped, or greasy
appearance, gravitational/Arlt
• Discrete granulomas  sarcoidosis and tuberculosis
• Diffuse  VKH/SO
• Zonal  lens-induced uveitis
– Others: TB/syphilis/fungal, leprosy, +-herpes
– Others: VKH/SO/sarcoidosis/MS/masquerade, phacoantigenic
– Others: orbital: histiocytosis X/juvenile xanthogranuloma

7. History
Age, gender, race
Fever/constitutional
Trauma & surgery
Contact/travel
Immuno status
STD/high risk behaviour
Animal/pets
Skin/ulcer
Joint
Respi, GI, GU

8. AU/IU- causes
• Idiopathic 50%
• Ocular
– Trauma
– HSV
– FHI/PossnerS
– Lens related
– Keratitis/scleritis
• Systemic
– HLA-B27 20%
– Others
• Infection
• Non-ifx
• Masquerade
• Drugs

9. PanU- causes
Inflam VS Ifx
• Sarcoidosis
• Behcet
• VKH
• SO
• TB/fungal/syphilis
• Endoph (exo/endo)
• Masquerade (lymphoma)
• Chronic idiopathic uveitis
Paeds DDX
• early onset sarcoidosis
• JIA
• familial juvenile systemic
granulomatosis (Blau
syndrome/AD)

10. PU- Retinitis vs Choroiditis
Retinitis Choroiditis
Superficial Deep
Margin indistinct Margin distinct
Abn retinal vessels Visible/normal retinal vessels
A/w adjacent vitritis No adjacent vitritis
> Virus/cat scratch/Lyme/Brucellosis > fungal/TB/syphilis
> Toxoplasmosis > Toxocariasis
> sarcoidosis/VKH/SO
WDS
Endogenous endopth
PU without vitritis!
- CMV, POHS, PORN

11. Vasculitis
• Infectious VS Non-infectious (neoplasia, inflammation, idiopathic)
• Ischaemic > common @ Eales/TB, Behcet  sarcoid/MS/SLE  rare  idiopathic
• Peripheral for IU, Peripheral occlusive for ARN
• VKH- capillary (fern-like leakage)

13. Retinal Vasculitis- Terms
• PathoG: thrombotic or obliterative
secondary to the infiltration of inflammatory
cells
• Perivascular sheathing
• Ischaemic retinal vasculitis
• Vaso-occlusive/Occlusive retinal vasculitis
• Obliterative retinal vasculitis
• Frosted branch angiitis

14. Retinal Vasculitis- Important Signs for DDX
• Eales: occlusive, active or healed patches of focal
choroiditis along the retinal veins, absence of other active
inflame/vitritis, predominant phlebitis (vein),
extensive/peripheral/diffuse ischaemia + TB workup
• Behcet: occlusive, more vitritis/panU but not
retinitis/choroiditis, vein (more) + artery, BRVO, + systemic
Behcet/ulcer
• SLE: >arteritis, multiple infarct (CWS), no uveitis/cells,
RAO, + SLE workup/antiphospholipid Ab, rarely occlusive
• Sarcoidosis: IWOS, multifocal periphlebitis, candle wax
dripping, rarely occlusive
• MS: IU & peripheral periphlebitis, rarely occlusive

15. PanU:
Sarcoidosis
Familial juvenile systemic
granulomatosis (Blau syndrome)
VKH
IU:
Sarcoidosis
Syphilis/TB
Multiple sclerosis
Uveitis @ Paeds DDx

17. AU- Signs
• Circumcorneal/limbal/cilliary injection
• Miosis
• Cornea –sensory & KPs
– Arlt triangle (gravitational) vs diffuse in FHI
– Mutton fat (granulomatous) vs fine
– Fine stellate/filamentous @FHI
– If early: endothelial dusting  new (white/smooth round)  old
(shrunken/pigmented, glassy)
• AC cell/flare/fibrin/hypopyon
– SUN grade & type  serous/purulent/fibrinous/sanguinoid
– Flare: active inflam, >Cx, grading (iris/lens details), laser flare photometry,
Tyndall effect
– Fibrin: >severe inflam, > HLA B27/leprosy
– Hypopyon: fibrin content >HLA B27 (common), <Behcet (+shifting), BL white
eye (Behcet/JIA/leukemia/lymphoma)
– Cell: worsen (steps), improve (2steps/0), remission (0 x 3mth)

18. AU- Signs
• Iris
– Nodule: Koeppe, Busacca (>granulomatous), Berlin @angle (>sarcoid >large pink)
• yellowish nodule from dilated vessels/roseolae @syphilis
• iris pearl @leprosy
• iris crystal/Russell bodies w Ig deposit @ CAU/FHI
– Atrophy: diffuse (>FHI) vs sectoral (>HSV/HVZ)
– Heterochromia @FHI, muddy
– NeoV: vs normal dilated vessels (>radial, >FHI)
– Ectopion uvea (chronic/NVI)
• PS/PAS
– Tented PAS @ sarcoid, broad based @TB
• Angle
– PAS/NVA/tumour
• IOP
– High (>herpes)/low/steroid induce
• Lens
– Lens related inflam, cataract as Cx
• Posterior segment
– Cx: CMO/ERM/ERD
– IU/PU/PanU, WDS

19. IU- Signs
• Vitreous/Pars plana
– Ant vitreous cell, haze/condensation
– grade of cell (MUST)/haze (NIH-SUN)/ball
– old (in the vitreous strands) vs new (syneretic areas),
– Snow ball = vitreous cell clump/ants egg >inf (+retinoschisis/neoV if prolonged)
– Snow banking = exudate plaque/post hypopyon > inf (a/w worse prognosis)
– Peripheral vasculitis (esp MS) +- neoV
– Pars planitis= idiopathic IU with snowball/banking
• AU (spill over)- esp paeds/MS/sarcoidosis/Lyme disease
• OD edema or neoV- esp paeds/syphilis/sarcoid
• Cx- cataract/glaucoma/OD/CMO/RD/VH

20. Uveitis SUN / NIH / MUST

21. IU
• chronic, relapsing disease of insidious onset
• > young (15-40), > BL +-asym
• 15% of all uveitis/20% of paediatric uveitis
• > white eye painless floaters with BOV
• Focus on vitreous + peripheral retina
• Pars planitis, posterior cyclitis, and hyalitis
• Common causes:
– idiopathic (2/3, = pars planitis)
– ifx (TB, syphilis, Lyme, cat scratch, Toxocara, Whipple)
– Inflam (sarcoid, MS, TINU/Blau/Sjogren, lymphoma, IBD)
• Rx- steroid
– Subtenon TA (0.5-1ml=20-40mg) q6-8wk or 2-3 inj over 8wk/IVTA/ozurdex: >UL w CMO
– Systemic pred 1mg/kg over 6wk taper: > BL/severe
• Rx others:
– Steroid sparing +-
– Cryo/scatter PRP esp for peripheral NeoV+VH
– PPV

22. AU signs- DDX
Iris heterochromia
• FHI (diffuse)
• Waardenburg
• Congenital Horner
• Melanoma/siderosis
• Drug- PGA
• Pawry-Romberg syndrome
• Incontinentia pigmenti
• + iris atrophy causes 
Congenital Iris Abn
• coloboma (CHARGE)
• aniridia (AD/WAGR)
• Ant seg dysgenesis
• Albinism
• Ectopia lentis et pupillae
• NF Lisch nodule
Iris atrophy
• iatrogenic/op
• injury to iris/trauma
• inflammation
– FHI (diffuse)
– posner-schlosmann
– HSV/HZV (sectoral)
– + iris nodule @ uveitis
• IOP
– AACG (spiral)
– ICE (pupil abn)
– PDS (transillumination @peripheral)
– PEX (transillumination @pupil margin)
• ischemia
– ectropian uvea/ant
ischemic/OIS/CCF/NVG

23. AU: recurrent + UL + non ifx+-viral/non systemic/non panU
1. Lens related (phacolytic/anaphylactic)
• Phacoanaphylactic- granulomatous/type III? immune complex hyperS (B cell/Arthus), +- bacteria/SO
related (1-24days post trauma)
2. Trauma related
3. FHI
• EpiD: young-middle age, +-related to rubella/CMV > HSV
• SSx: asymptomatic/white eye + recurrence AU + not response to steroid
• KPs: fine stellate diffuse KPs (white/non pigment) + no PS/PAS
• Iris: heterochromia/atrophy (moth eaten), +-Koeppe nodule +- abn iris vessel @angle (rubeotic-like)
bleed on surgery (Amsler’s sign), iris crystals/Russel bodies (plasma cells filled with antibodies)
• cataract >PSCC 70%, Glaucoma 20%, dust-like uveitis
4. Posner Schlossman/Glaucomatocyclitic crisis
• EpiD: young-middle age, +-related to CMV/HSV
• white eye + min KPs, but very high IOP (40-50mmHg) with corneal edema
• no PS/PAS/rarely uveitis
5. Viral AU (VAU): HSV, HZV, CMV, rubella
• Unilateral, white eye/low grade AU, recurrent
• IOP + cornea + iris
• AAU/CAU, Posner Schlossman, FHI, endothelitis
• PCR & Goldmann-Witmer coefficient analysis on the aqueous humor

24. Dragged OD- DDX
1. Proliferative vascular diseases
• Cicatricial ROP (MOST!)
• Proliferative DM retinopathy
• Sickle cell retinopathy
• Coat’s disease
2. Infectious
• Toxocariasis
3. Developmental disorders
• FEVR (Familial exudative vitreoretinopathy)
• Combined hamartoma of retina and RPE
• Incontinentia pigmenti
• Norrie’s disease

25. PPA- DDX
• Aging
• Myopia
• VKH
• POHS (triad: histo spot + no IU)
• Glaucoma (beta/alpha zone)

26. Pathognomonic (nearly)
• JIA: chronic anterior uveitis in paeds without
any symptoms  Cx band keratopathy,
cataract, or macular edema
• Behçet disease: transitory posterior segment
inflammation

27. Indicators of severe inflammation
•Impairment of visual function
•bilateral disease
•vitreous haze
•macular or optic nerve disease
•retinal vascular inflammation
•macular edema
•exudative detachment
•ocular structural complications that threaten
visual function

28. Complication: AU (severe/chronic)
• Uveitic macular edema
• OD swelling
• Cataract
• Corneal edema
• Band keratopathy
• Iris abnormalities

29. Complication- IU
• Macular edema
• Peripheral ERD/TRD
• Retinal neoV
• Cataract
• Retrolental or cyclitic membrane formation.
• Secondary CB detachment & hypotony

30. Complication- PU
• Macular edema
• Peripheral retinal vasculitis
• ERM
• Retinal or choroidal neoV
• E-T-R-RD
• RPE hypertrophy or atrophy
• Atrophy or swelling of retina/choroid/ON
• Pre-or sub-retinal fibrosis

31. VA impairment @uveitis
• CMO
• ERD/RRD
• ERM
• CNV (esp POHS, VKH, toxoplasmosis, PIC)
• Atrophy
• ON
• Glaucoma (uveitic/steroid induced)
• Cataract
• Cornea bandK

32. Uveitis- Workup

33. Uveitis- Ix
• No need if:
– AU 1st episode/UL/non granulomatous/mild-mod without hypopyon
– k/c/o systemic dz/ocular dz for uveitis
Systemic VS Ocular
• Ocular:
– OCT macula, Bscan, FAF/FFA/ICG
– Aq/Vitreous tap: gram stain/C&S & viral/TB/fungal PCR/C&S
– Biopsy: vitreous/conj/iris
• Systemic basic panel:
– FBC, ESR, Mantoux, CXR, VDRL
• Other Inflam Ix:
– Sarcoid panel: LDH/Ca/ACE/lysozyme/CT thorax
– CTD panel: CRP, RF/dsDNA/ANA (esp JIA)/ANCA (esp Wegener +
scleritis/PUK/sinusitis)
– Arthritis: sacroiliac/spine XR, HLA B27
– MRI brain: MS
– HLA: B5/51 (Behcet), A29 (Birdshot)
• Other Ifx Ix:
– Lyme/brucellosis/leptospirosis/toxo serology
– QuantiFERON (IF-gamma release assay)
– HIV
– Prepare for steroid: UFEME/LFT

34. Syphilis Uveitis
• syphilis testing for all uveitis patients, as
syphilis can present as any form of uveitis, and
systemic infection is often undiagnosed
• treating with steroid in the presence of
untreated occult syphilis infection can be
disastrous for patient outcomes

35. Ocular fluid PCR
• HSV1&2/VZV/CMV- Aq=V
• Toxoplasmosis- Aq<V, Aq > if large
lesion/immunoC
• Panbacterial- genetic subunit 16s
• Panfungal- genetic subunit (5.8S/18S/28S)
• Genomic test for primary intraocular
lymphoma
• Goldmann-Witmer (GW) coefficient >
better than PCR for viral & toxoplasmosis

36. FFA in uveitis
• macular edema
• macular ischaemia
• retinal vasculitis
• secondary choroidal or retinal neoV
• areas of optic nerve, retinal, and choroidal
inflammation
• retinochoroidopathies, or white dot
syndromes, have characteristic appearances

40. Uveitis association
• Genetic/HLA
• Geography
• Sex
• Age
• Joint
• Skin
• Animal
• Other systemic
– GIT
– Renal
– CNS
– Lung

41. HLA uveitis
Autoimuune uveitis

42. HLA- principle
• HLA = cell surface molecule (encoded by MHC
gene in chr 6)
• Number= polymorphic form e.g. B-27
• Only support Dx
• Variation with race
• Transplant match (not necessary in cornea)
• WCC

43. HLA & EYE
• A2: JIA
• A11: Sympathetic ophthalmia
• A29: Birdshot (95%)
• B5: Behcet’s (70%)
• B7: toxoplasmosis, POHS, serpiginous/APMPPE choroidopathy
• B8: Sjögren’s syndrome, sarcoidosis
• B12: Ocular cicatricial pemphigoid
• B13: sarcoidosis (60%), psoriatic arthritis (also B17).
• B27: sero-ve spondyloarthropathies- AU (40%), AS/Reiter’s (90%), psoriatic/IBD
• B51: Behcet’s, Eales
• Bw54: Posner-Schlossman syndrome, VKH?
• DR2/DRw2: POHS, intermediate uveitis, APMPPE
• DR4: VKH, SO, OCP.
• DR2/15: pars planitis,MS

44. EYE & HLA
• Birdshot choroidopathy: White, HLA-A29, 96%
• Ankylosing spondylitis & Reiter's: White and Asians, HLA-B27, 89%
• Behçet's: Japanese, HLA-B5, 68%, some B51
• VKH/SO: HLA-DR4 & Dw53 (>Chinese), HLA-DR1 & DR4 (Hispanic) HLA DRB1 (Indian)
• POHS: White, HLA-B7-77%, HLA-DR2-81%
• Sarcoidosis: HLA B8 & B13
• Keratoconus: A9/10/12, B5/21
• PXF: A1/33, B8
• OHT progression to Glaucoma: B7/12
• AMD: A3, CW02/07
• Diabetic Retinopathy (DR) development: DR1/7
• Diabetic Retinopathy (DR) proliferation: DR4, DQ8
• Retinal vasculitis: B44
• Eales: B51, DR1/4
• IU: B8/51, DR2
• Pars Planitis: DR15/17/51
• SJS/TEN: HLA-B12, HLA-Aw33, and DRw53. HLA-B44
• HSV EM: HLA-DQw3

45. cytotoxic
Mooren’s ulcer
retinal vascylitis, scleritis,
marginal K, IK, wessely ring
VKH/SO, granuloma uveitis
Type V (Stimulating Ab)- grave’s, MG

46. Uveitis & geography
• birdshot chorioretinopathy in western
Europe,
• Behçet disease in Turkey and China
• tuberculous uveitis in India
• Histoplasmosis in Ohio/Mississippi valley
• Onchocerciasis in Africa/centra-south
America

47. SEX & UVEITIS
• Seronegative spondyloarthrpathies >M
–women respond to injury or infection with a dominant Th2 immune
response (leading to increased antibody production), whereas men
respond with a stronger Th1 response.
• Autoimmune dz >F
–Estrogen increases the response, whereas androgens suppress.
–Activity depends hormonal stage (pregnancy/menopause)
–Estrogen's effect on autoimmunity may be dose dependent with
lower levels being immune-stimulatory and higher levels immune-
inhibitory.
–Pregnancy with Increased levels of estrogen and progesterone in
pregnancy results in the suppression of Th1 responses and the
upregulation of Th2 responses.
•reduced Th1-associated autoimmune conditions like RA
•exacerbates Th2-associated autoimmune conditions like SLE.

48. Autoimmune
• In general, autoimmune diseases are
mediated by Th1, Th2, and Th17 cells.
• Th1- cell-mediated immunity, with interferon
(IFN)-[gamma] → tissue damage
• Th2- humoral-mediated immunity →
hypersensitivity through IL-4-mediated B-cell
recruitment.
• The role of Th17 cells and their production of
IL-17 ?unsure

49. Spondyloarthropathies
• = sero-ve (RF -ve) or HLA B-27 (80% no sx)
• General: young M >F
– AU: 2nd most common cause (20%), >severe than idiopathic, IU/PU 17%
– ankylosing spondylitis
• 90% H+/AU 25%/>white/sacroiliac & spine
(XR/ankylosis/bamboo)/heart block
–reactive arthritis (Reiter syndrome)
•75% H+/AU 20%/Urethritis-Conjunctivitis-Arthritis/preceded by
ifx/AGE, skin (keratoderma blenorrhagicum- palm/sole brown
abscess)/mouth ulcer
– psoriatic arthritis
•20% of psoriasis/AU 20% (>BL/chronic)/small jt +- dry eye/keratitis
– spondyloarthropathy with IBD (UC/Crohn)- AU (>BL/chronic) +-
PUK/scleritis
– undifferentiated spondyloarthropathy
• IX: RF -ve/XR spine & sacroiliac/HLA B-27
• Mx: AU Mx + systemic steroid/NSAIDS/MTX/AZT, glaucoma watch out

50. Animal & Eye
• Cat: toxoplasmosis, toxocara, cat-scratch
(Bartonellosis)
• Toxoplasmosis > raw meat/unwashed vege, adjacent
scar, -ve serology TRO
• Toxocara > geophagia
• Dog: toxocara
• Rat: leptospirosis
• Bird: cryptococcus neoformans (AIDS
related/choroiditis)
• Deer: Lyme (Borreliosis)- deer tick (Ixodes)

51. EYE + GIT
• IBD & Uveitis
– UC & Crohn
• Eye: AAU (5%), ES/S/conj, subepithelial K/dry eye, +-retinal
edema/retrobulbar ON/CNP
• UC GI: continuous ulcer/pseudopolyps/crypt abscesss/Ca
• Crohn GI: full thickness/multifocal/granulomatous/any GIT/gne
(CARD2/NOD2)
• Skin: oral aphthous ulcer, erythema nodosum, pyoderma
gangrenosum
• Systemic: AS/psoriasis/MS/hepatitis/thrombosis (a&v)
– Whipple (intestinal lipodystrophy)- Tropheryma whipplei
• Eye: any U/keratitis, neuroophthal (gaze/EOM/OD), oculomasticatory
myorhythmia (nystagmus+face+limb)
• Systemic: IBD/arthitis/CNS/CVS
• GI Malignancy & eye metastasis
• GI Infection & eye infection
• GI Infection & GBS

52. Eye + Renal
• Uveitis
– Tubulointerstitial nephritis and uveitis (TINU)
• Young girl proteinuria, renal then BL AAU (80%)/CAU/panU
• 10% CKD/others resolved spontaneously or with steroid
– IgA nephropathy (Berger disease)
• Young hematuria, AAU
– CTD + renal Cx (lupus/SLE/Wegener)
– Paraneoplastic in renal CA
• Microvasculopathy/metobolic
– CKD & DR
• Renal tumour
– Eye metatstasis
– Wilms tumour & aniridia
– Phacomatoses: SWS (hemangioma), VHL (choroidal angioma & renal ca)
• Congenital
– Alport’s syndrome with lenticonus
– Senior–Loken syndrome and Bardet–Moon–Biedl syndrome (RP & renal)
– CHARGE syndrome
• Renal treament
– Alpha IF & retinopathy
• Others
– mesangiocapillary (or membranoproliferative) GN type II or dense-deposit disease (DDD) with drusen

53. Nystagmus + face + limb dyskinesia
• Oculomasticatory myorhythmia (OMM @ Whipple’s dz)
– Nystagmus: slow/smooth pendular
– Facial: contractions of the masticatory muscles, supranuclear vertical
gaze palsy
– Limbs: rhythmic movements
• Oculo-facial-skeletal myorhythmia (OFSM)
– = OMM but > rhythmic movements of the proximal and distal skeletal
muscles
• Oculopalatal myoclonus (brainstem CVA)
– Nystagmus: convergent-divergent
– Facial: palatal myoclonus
– Limbs: myoclonus

54. Drugs → Uveitis
• Pilocarpine- Iritis
• Xalatan- AU/CMO
• Rifabutin, cidofovir- AU
• Ethambutol- O neuritis (+-
Isoniazid/Streptomycin)
• Fingolimod- CMO

55. JRA/JIA
General h JIA = arthritis of at least 6wk without identifiable cause (<16yo)
h Onset peak 2yo (<16yo), F: M (5:1)
h Usually chronic, most common uveitis in paeds (50%)
h Uveitis after arthritis (95%, 90% of it within 4yr) > before (5%) arthritis
Patho - Non granulomatous
- Genetic and initiated by environmental factor +- infectious agents
Clinical 5 grp: polyA +- RF, pauciA early-late (pauci=oligo= 4or less), systemic
- CAU & AAU
- CAU> no pain/redness + non granulomatous
- Risk of AU: if +ANA/F/pauci-oligo/RF –ve, onset <6yo/within 4 yr of onset  for
frequency of eye examination 3mth-12mthly
- F> chronic/Cx/need screen VS M >acute
- Cx: band K 40%, cataract 40%, glaucoma, PS/CMO/ERM, ciliary membrane +-
amblyopia
Mx h Ix: +ANA (>AU), -RF (>AU in polyA RF-ve)
h Screen JIA no uveitis: depends on risk, 3-12mth,
h Monitor JIA +uveitis: 3m if stable, recent change of Rx gutt 1m vs systemic 2m
h Rx: AU topical 1st! Taper+monitor till 3mth  if >1drops OD KIV systemic.
h Rx > MTX (1st line)  Adalimumab/Humira and infliximab
Remark Taper: topical first  2yr stable then oral IMT (oral steroid is always bringing only)

57. • Recommendations for the screening,
monitoring, and treatment of JIA-associated
CAU and AAU

58. Pars Planitis
General h Young/teen
Patho h Idioppathic
h a/w MS
h DDX toxocariasis (severe IU)
Clinical h IU/snowball/snowbank
h Cx: band K, CMO
Mx h Local steroid (periocular)
Remark

59. Behcet
General h systemic occlusive vasculitis
h > Asian/>M/30s
h BL 80%
Patho h Unknown/Genetic (HLA B51/B5)/autoimmune/ifx
h artery & vein occlusion with Tcell/neutrophil infiltration (non granulomatous)
h Rapid symptoms resolution 1-2wk bu t frequent relapse
h Non granulomatous
Clinical h Japan diagnostic system: 4major = complete (oral/skin/genital ulcer + uveitis),
incompete/suspect/possible
h ISG: oral ulcer (=/>3x/yr) + any 2/4 (genital/skin ulcer/uveitis/pathergy +ve)
h ICBD 2011 9=/>3pt): ocular 2pt, genital 2pt, oral/skin/pathergy/vascular 1pt
h Eye (70%): PanU + retinal vasculitis/necrotizing/ischemia/atrophy
- Hypopyon: Shifting, non granulomatous AU, cold, angle +- pigment pellets
- BRAO/BRVO, glaucoma, cataract, OD atrophy
h Systemic: CNS IIH/thrombosis, GI, CVS, arthritis
Mx h ESR/CRP/CXR/MRI brain & FFA perivascular staining + fern-like leakage
(capillaries >3quad)
h steroid → IMT (AZT → CSA/infliximab/MTX)

60. Sarcoidosis
General h Multisystem non caseating granulomatous dz
h 20-50 vs early onset (<5), ethnic (>european/african), F=M
h 90% lung/50% ocular/10% of uveitic cases
Patho h Unknown/Genetic (I/II HLA DRB1)/Infection (ACCESS)
h Granuloma/Langerhans/inclusion body (Schaumann/Asteroid)
Clinical h Systemic vs ocular, definite/presumed/probable/possible
h Ocular: acute/chronic/pan-uveitis (granulomatous), tent PAS, TM nodule
OD/choroid/retina granuloma, vasculitis/candle wax dripping (irreg granuloma
along veins)
h Orbital: granuloma/infiltration (conj/eyelid/lacrimal gland/7CNP)
h Acute: Lofgren (EN), Heerfordlt syndrome (parotitis)
h variant Mikulicz syndrome (BL sym lacrimal +- salivary gland lymphocytic
infiltration)
Mx h Peripheral anergy test
h CXR (Type I-III)/CT → Ca/ACE/lysozyme/liver enzyme → HPE biospy
h Steroid/IMT/cycloplegic

61. International Workshop on Ocular Sarcoidosis (IWOS)
• 7signs:
– (1) mutton-fat keratic precipitates (KPs)/small granulomatous KPs and/or iris nodules
(Koeppe/Busacca),
– (2) trabecular meshwork (TM) nodules and/or tent-shaped peripheral anterior synechiae (PAS),
– (3) vitreous opacities displaying snowballs/strings of pearls,
– (4) multiple chorioretinal peripheral lesions (active and/or atrophic),
– (5) nodular and/or segmental peri-phlebitis (± candlewax drippings) and/or retinal macroaneurism in
an inflamed eye,
– 6) optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule, and
– (7) bilaterality
• 5labs Ix:
– (1) negative tuberculin skin test in a BCG-vaccinated patient or in a patient having had a positive
tuberculin skin test previously,
– (2) elevated serum angiotensin converting enzyme (ACE) levels and/or elevated serum lysozyme,
– (3) chest x-ray revealing bilateral hilar lymphadenopathy (BHL),
– (4) abnormal liver enzyme tests, and
– (5) chest CT scan in patients with a negative chest x-ray result.
• Four levels of certainty for the diagnosis of ocular sarcoidosis (diagnostic criteria) were
recommended in patients in whom other possible causes of uveitis had been excluded:
– (1) biopsy-supported diagnosis with a compatible uveitis was labeled as definite ocular sarcoidosis;
– (2) if biopsy was not done but chest x-ray was positive showing BHL associated with a compatible
uveitis, the condition was labeled as presumed ocular sarcoidosis;
– (3) if biopsy was not done and the chest x-ray did not show BHL but there were 3 of the above
intraocular signs and 2 positive laboratory tests, the condition was labeled as probable ocular
sarcoidosis; and
– (4) if lung biopsy was done and the result was negative but at least 4 of the above signs and 2
positive laboratory investigations were present, the condition was labeled as possible ocular
sarcoidosis

62. SO
General h BL diffuse granulomatous panU with prior ocular trauma/op
h rare/2% of uveitic cases
Patho h Unknown/Genetic (HLA DR/DQ 4/W53/B)
h exposed uvea → conj lymphatic → spleen (autoAb) & LN (cell mediated ) →
autoAb vs uveatogenic tissue (retinal/choroid)
Clinical h onset: >5/7, 80% <3mth>, 90% <1yr>, the rest anytime
h BL PanU: >PU/choroid granuloma, Dalen Fuchs (btw RPE-bruch/mid
equatorial/epithelioid + pigment) + AU (granulomatous) + Cx  sunset glow
h +- systemic features (like VKH)
h NO retinal/chorio-capillary involvement
h + ext to sclera/OD/macula/vessels
h FFA: Dalen Fuch (hypo then hyper), leak/pool (SRF/RPE/chorioV >VKH), ICG
(hypo choroidal lesion)
Mx h Enucleation within 2wk injury
h Steroid (slow taper 6/12) + IMT

63. VKH & SO- The Similarity
• Bilateral, young-old age
• Diffuse granulomatous inflammation
• Non necrotizing
• Autoimmune
• Genetic predisposition (HLA DR4/53/DQ4)
• Systemic features (CNS/Ear/Skin)- VKH > SO
• CNS: menigismus, CSF pleocytosis
• Ear: tinnitus/dysarcusis
• Derm: poliosis/vitiligo/alopecia + Sugiura sign (perilimbal vitiligo)
• S&Sx of granulomatous PanU
• Dallen Fuchs nodules
• Choroiditis
• Exudative RD & subretinal fluid – VKH > SO
• Sunset glow/PPA
• Treatment with immunosuppressor/steroid

64. VKH VS SO
VKH SO
Pathogenesis
Against melanocyte Uveitogenic vs antibody
Genetic predisposition > autoimmune Autoimmune > genetic predisposition
Risk factors
Associated with systemic dz Assocaiated with eye trauma/surgery
Asian/Black/Dark pigmented No preference
Pathological changes
4 stages: prodrome/acute
uveitic/convalescent/chronic recurrent
No stages
Choriocapillaries involvement
(FFA starry night/fern-like cap leak)
uncommon

65. Choroidal Inflammation

66. DDX- Choroiditis
White Dot Syndromes
– Acute Posterior Multifocal
Placoid Pigment Epitheliopathy
(APMPPE)
– Serpiginous Choroiditis
– Multiple Evanescent White Dot
Syndrome (MEWDS)
– Birdshot retinochoroidopathy
-- Multifocal Choroiditis (MFC)
and Panuveitis Syndrome
(MCP) & Punctate Inner
Choroidopathy (PIC)
– Acute Zonal Occult Outer
Retinopathy (AZOOR)
Infectious
– Tuberculosis
– Syphilis
– Ocular Histoplasmosis
Syndrome
-Fungal
-Endophthalmitis
Non-Infectious (systemic inflam)
– Vogt-Koyanagi-Harada
syndrome (VKH)
– Sympathetic Ophthalmia
– Masquerade syndromes (i.e.
lymphoma)
– Sarcoidosis
--Pars Planitis
– Posterior Scleritis

67. WDS- General
• Choroidal inflam involved choriocap (hypoperfusion)/outer retina/RPE
• Idiopathic +- autoimmune/ifx
• DDx: TB/syphilis/POHS/ifx, sarcoidosis/VKH/SO/CTD, choroidal mets/lymphoma
• EpiD:
– Young female myopic: MEWDS/MFC-PIC-MCP/AZOOR/AMN, birdshot (older)
– M=F & young to middle-age: APMPPE/serpiginous
• SympT: acute BOV/scotoma 
– UL: MEWDS
– BL: APMPPE/Serpiginous
– UL BL: birdshot/AZOOR
– Viral prodrome: APMPPE/MEWDS/AZOOR
– Self limited: APMPPE/MEWDS, PIC/AMN/AIM/ARPE
– Progress/recur: Serpiginous/Birdshot/MCP/AZOOR (Cx: CNV/CMO/atrophy/ERM)
• Signs: choroiditis + min AU/vitritis (no systemic inflam/ifx)
– Placoid/serpiginous (size 1-2DD): APMPPE (post pole)/serpiginous (periOD)/Birdshot (smaller
fleck/periOD)
– Dots : MEWDS (wheath cluster), Birdshot (periOD), MFC (curvilinear), AZOOR (zonal)
• Ix- OCT: elevation@outer retina/disruption of outer hyperR band/IS-OS+-CMO/CNV
• Ix- FFA: early hypo (block)  late hyper (leak/stain) +- window defect (atrophy)
• Ix: ICG: persistent hypo (lesion > than clinically)
• Ix: FAF: hyper if sick, hypo if dead RPE
• Ix: EOG abn (RPE), ERG initially normal  a-wave abn
• Mx: observe  steroid

68. APMPPE
General h M=F + young to middle-aged
h +-HLA B7/DR2
SSx h Acute BL (pre-URTI)  resolved <wks> +-persistent/relentless
h Multifocal/cream colour placoid size 1-2DD @post pole
Mx h Observe (good recovery) > steroid
Remark ● a/w cerebral vascullitis, headache, hearing loss, tinnitus
Serpiginous
General h M=F + young to middle-aged
h HLA B7
SSx - Acute BL  recurrent  BOV/scotoma persistent
- PeriOD  centripedal serpiginous (pseudopodial/map-like)  scar +
new
Mx Steroid/IMT/CNV Rx
Remark Guarded prognosis

69. Birdshot
General h White Caucasian + >F + middle-aged (30-70)
h HLA A29 (95%)- normal white population 7%
Clinical h Acute UL to BL  progressive/relapsing x years  persistent BOV/scotoma
h Criteria x 3 (BL symmetrical + Birdshot flecks/mild vitritis/CMO + HLA A29)
h Choroiditis- periOD >inf/post pole (oval cream colour/size ¼- 1 ½ DD), no
pigment
h Atrophic scar- punched out clear margin
h Cx: vasculitis/OD edema-atrophy/CNV/CMO/RP-like (with minimal pigment)
Mx - Steroid +- 2nd line
Remark ERG negative pattern (normal a but reduce b)
Guarded if untreated

70. MEWDS
General h Young +F+myopia + UNILATERAL!!
SSx - Acute UL (pre-URTI)  self limiting
- White dots (wheath cluster)/transient flecks @ post pole
Mx - Observe > steroid
MFC/MCP/PIC
General h Young+F+myopia
Clinical h Acute BL  PIC self limit VS MCP progress/Cx
h Dots- discrete cluster/100-300um @ post pole/periOD  Schlaegel lines
(curvilinear pattern)
h Late → punched out/atrophic scar, CNV (25-50%), CMO (rare)
Mx -steroid > observe/Rx Cx (CNV/CMO)
AZOOR
General h Young+F+myopia
Clinical h Acute UL to BL  progress  persistent BOV/scotoma
h Dots- OD/post pole zonal lesion  Late → atrophy/RP-like
Mx -steroid > observe

71. Others WDS
Young F & UL > BL & self limiting + pre URTI
1. Acute macular neuroretinopathy
– brown-red/wedge-tear drop-pedal shape
lesion/tips point center
2. Acute idiopathic maculopathy
– M=F & sudden severe central LOV
– ERD/RPE disturbance/Bull’s eye
3. Acute idiopathic blind spot enlargement
– OD neuritis (RAPD) + blind spot enlarge + pigment
4. Acute RPE epitheliitis (Krill dz)
– hyperP lesions + yellow hypoP halo @post pole (FFA reverse)

73. Uveitis- Treatment

74. Uveitis- Mx
• Mx: etiology + laterality + anatomy + symptomatic relief
• Ifx → Antibiotic
• Non ifx → UL (local Rx), BL (systemic Rx) steroid/IMT
• AU- topical
• IU- regional (periocular or intravitreal) or oral (steroid+-IMT)
• PU/PanU- oral (steroid+-IMT)
• ✘ steroid- FHI (not resolved) > APMPPE, MEWDS, pars planitis
(self resolved)
• PS++  topical cycloplegic/subconj Mydricaine (or pledget x
5min, commercial No.2 for adult, No.1 for paeds)
• Fibrin++  intracameral rTPA 12.5-2.5 ug/0.1ml
• Oral NSAIDs  scleritis or IU
• Uveitis with NVD/NVE
– FFA for CFO
• no CFO → treat inflam/ifx → NeoV regress
• yes CFO → + PRP +- antiVEGF?
– NeoV at IU/peripheral → CryoT

75. Non Infectious Uveitis- Mx
• Steroid local & regional
– Topical (AU)
• New: difluprednate 0.05% (Durezol) > effective/bioavailability/penetration than pred forte
– Subconj dexa 4mg/0.1ml
– Orbital floor/post. subtenon triamcinolone 40mg/1ml (effect peak 4wk max 3mth,
can give q2-4wk total 4-6times >IU/PU)
– IVT triamcinolone 4mg/0.1ml (2mth effect)
– Dexamethasone implant
• Ozurdex (injectable, 4-6mth effect)
– Fluocinolone acetonide implant
• Retisert (surgically implant, 2-3yr effect)
• Iluvien (injectable, 2-3 yr effect)
• Steroid systemic
– oral 0.5-2mg/kg/day (immuno suppress/anti-inflam dose)
– Ind: IU/PU/PanU, bilateral, chronic, visual threatening, failed above
• Systemic steroid sparing/second line agent (CAU)
– When to start? unable to taper down to safe dose (7.5mg) with relapse, frequent
relapse, steroid Cx
– AZT, CSA, MTX, Mycophenolate MMF, tacrolimus
– Biologic: IF-beta (in MS-related IU), anti-TNF infliximab, rituximab

76. Vasculitis- Mx
• Underlying causes
• Non infectious: steroid & steroid sparing
IMT
• Retinal photocoagulation
– FFA based for ischaemic/capillary non
perfusion area
• +- antiVEGF
– Not primary treatment +- >occlusion
– For persistent/recurrent NV after retinal laser

78. ImmunoModulator (IMT)
• Stimulant (IF/IL)
• Immunosuppressant
– Corticosteroid
– Antimetabolite (AZT/MTX/MPM)
– T cell/calcineurin inhibitor (CSA/Tacro-Siro-limus)
– Alkylating agents (cyclophosphamide/chlorambucil)
– Biologic (TNF-a AG, IL-1/IL-6 AG, IFN-a, IVIg)

80. MUST
• Multicenter Uveitis Steroid Treatment trial
• Up to 7 yr follow up
• Adequate immunosuppression to taper
prednisone to 7.5mg/day or less, together with
IMT VS long-lasting regional corticosteroid
therapy (fluocinolone acetonide implant)
– systemic adverse effects were no greater, except
for a greater use of antibiotics for infections
– superior visual outcomes because chorioretinal
damage @uveitis relapse before re-implant of the
regional therapy  saw-tooth decline

81. SITE
• Systemic Immunosuppressive Therapy for Eye
Diseases
• 9250 patients with ocular inflammation with up to
30 years of follow-up
• Risk of cancer for IMT
• TNF inhibitors: increased total and cancer mortality
• Alkylating: non-statistical significant increase risk of
cancer
• Antimetabolites or calcineurin inhibitors: no
significant risk

82. Prednisolone
• Initiation
– 1 mg/kg/day up to a maximum of 60 mg/day
– range 0.5-2mg/kg/day
– >60 mg/day = increased risk of ischemic necrosis of bone
– IVMP 1g x 3d: if need immediate control, followed by oral steroid +-
IMT, avoid rapid IV (<30min) arrhythmia/MI/ifx
• Taper
– After 2 to 4 weeks
– of control/resolve/improve
– Target dose is =/<7.5mg/day
– Still increased risk of CVD
• 5 mg/day x 22yr
• 7.5 mg/day x 15yr

83. Prednisolone
• Flare/Exacerbation
– TRO ifx/non adherence/DDx/rapid taper with rebound
– If tapering  resume a higher dosage for another
month or until the disease is quiet  taper back to just
above the threshold at which the disease reactivated
– Taper slower/longer if =/<7.5mg OD <3mth still
– IMT if >7.5mg OD >3mth already
• Stop with remission
– hypothalamic–pituitary axis may not return for 6 to 12
months after tapering for chronic cases  adrenal crisis

84. Prednisolone- AE/Monitor/Supplement
• Short-term: ifx, BP, DXT
• Long-term: immune, bone, cushing, psychosis
• Eye: IOP, cataract, ifx
• Metabolic: HPT, fluid retention, DM, hyperlipidemia, atherosclerosis
• Cushingoid (moon facies, weight gain, fat redistribution, and increased acne)
• Immune: Infection
• Bone Skin: Osteoporosis, easy bruising, and poor wound healing, delay growth <15yo
• Psy: Anxiety, sleeplessness, mood changes
• Monitor
– BP and blood glucose q3mth
– Bone BMD yearly
– Lipid profile yearly
• Supplement
– 1500mg Ca, 800 IU Vit D daily (esp 1st 6-mth- greatest bone loss)
– If BMD=osteoporosis  antiresorptive e.g. calcitonin/alendronate
– H2 blockers for patients taking prednisone is unnecessary ?PPI

85. IMT- IndiC
Therapeutic needs, Uveitis type, Severity
• Steroid-sparing:
– prolonged steroid >3mth & >7.5mg/day
– SE, intolerate
– Poor response
– worsens on high-dose
– no response after 2-4wk
– better but not quiet after 4 wk of high dose
– relapse despite 7.5mg OD
• Initial Rx in:-
– Poor natural history
– OCP with ocular involvement
– Behcet with posterior segment involvement
– SO/VKH, serpiginous choroiditis, Birdshot
– Systemic protection
– necrotizing scleritis & PUK with systemic vasculitis
– Severe advanced inflammatory damage
– Reserved as 2nd line:
– SE & cancer risk
– bladder cancer (cyclophosphamide), leukemia, lymphoma, non melanoma skin
cancer (AZT & CSA for postTx case) and, possibly, overall cancer.

86. IMT- How to choose
• Availability/cost  AE vs efficacy
• Antimetabolite
– MMF & AZT- most effective
– AZT vs MMF – least & best tolerable
– MTX- best for paeds, worst for fetus
– MTX- not for hepatitis or alcoholic
• T cell inhibitors
– CSA- less effective vs antimetabolite
– > combination therapy w antimetabolite
– Not for CKD
• Alkylating
– most potent & potentially remission-inducing
– BUT most SE/cancer risk, IV pulse or oral daily

87. IMT- Pre & Starting
• baseline vital organ function (liver/kidney/BM)
• screen for active/latent infectious diseases
• TRO pregnancy & chance
• history of malignancy & testing for TB & HIV
before biologic therapy
• Administration
– bridging with steroid (wk-mth)- high dose if active/relapse,
same dose if stable
– Taper of steroid after 4-8wk
– monitoring blood tests (1wk-2wk-4wk-2mth-3mth)
– DDX inadequate suppression/ifx due to over suppression
– Other systemic features of ifx VS inflam
– Lymphocyte count 0.8-1.2 = adequate

88. IMT- Increase, Combine & Taper
• Step up dose
– Dose escalation: low dose  increments every 4-6weeks  optimal
dose
– Rapid incrementation: low dose  2wk to assess tolerability 
max/optimal dose (esp for MTX & MMF)
• Combination
– Antimetabolite + CSA
– Alkylating usually solo
– Antimetabolite + biologic
• Taper/off IMT/2nd line
– Usually after off the oral prednisolone
– Usually >3yr use & >2yr stable/control for non-alkylating
– Usually >3yr use & >1yr stable/control for alkylating
– Taper slowly with long duration each of step (3-6mth)

89. IMT- No response
• TRO:
– treatment nonadherence
– infections (syphilis, TB, vira)
– masquerade syndromes incl lymphoma
• Dose step-up, combine, switch

90. IMT in Pregnancy
• CI in pregnancy: cyclophosphamide, chlorambucil
and methotrexate.
• Esp MTX (category X)
– even in a male patient who may impregnate someone
– Evan also CI for BF
– use two forms of birth control.
– at least three months after it is stopped.
– But very good for paed uveitis/JIA
– Use topical/regional medication if possible
– Pregnancy = progresterone more = more anti-
inflammatory  but post partum flare

91. IMT- Paeds
• MTX
• +- CSA
• Growth
• should not receive live virus vaccine (MMR vaccine, varicella-
zoster virus vaccine, oral polio vaccine, BCG) while on therapy for 3
months after stopping therapy or > 20 mg prednisone daily
• If possible, varicella-zoster vaccine should be given before the
start of therapy.
• systemic viral diseases, they should receive a yearly influenza
vaccine, and if susceptible, varicella-zoster virus immune globulin
upon close exposure to chickenpox.
• If CD4 <200 cells per ml, consider P. carinii prophylaxis.

93. Azathioprine (Imuran)
• Purine (A&G) analogue
• MOA: activated to 6-mercaptopurine (6-MP) by thiopurine
S-methyltransferase (TPMT, enzyme activity = Rx response)
→ false coding → - DNA replication/RNA transcription
• Dose: start 50 mg/day x 1wk → most effective at
2mg/kg/day (aim)  3-4mg/kg/day (unusual)
• IndiC:
– Ocular: Behçet disease (1st)/VKH/SO, IU, necrotizing scleritis,
Wegener
• SE:
– GI (25%), BMS/pancytopenia, hepatotoxic (2%) → FBC/LFT!!
– Use lower dose if +allopurinol
– LFT q12 weeks. When toxicity occurs (> 1.5 times upper
limit of normal), the dose should be decreased by 25 to 50
mg per day, and LFT 2 weeks. If > 5x upper limit 
discontinued

94. Methotrexate
• Preferably 1st choice for paeds uveitis & sarcoidosis
• Folic acid analogue
• MOA: - dihydrofolate reductase (DHFR) → - thymidylate/purine
synthesis → - DNA/RNA/AA & adenosine release (anti-inflammation)
• IndiC:
– Systemic CTD esp RA, sarcoidosis
– Ocular esp JIA & paeds uveitis (1st line!), scleritis
– Lymphoma
• Dose
– Weekly dose: 2.5mg-7.5mg weekly, 10mg (Start) → 15mg (aim)  25mg
(max) (need 6wk for effect  6/12 to peak effect)
– + folinic acid/folate 1mg OD (except on day of MTX)
– IVT 400ug for refractory uveitis/uveitic CME
• SE
– GI (10%), BMS, hepatotoxic (15%), teratogenic → FBC/LFT/no pregnant/no
hepatitis/no alcohol, or need to stop >3/12 before pregnant!, double
contraceptive

95. Mycophenolate Mofetil/MMF (CellCept)
• Preferably 1st choice for adult uveitis
• Active: MPA (mycophenolic acid)
• MoA: -inosine monophosphate dehydrogenase → -
purine synthesis/DNA replication
• IndiC:
– chronic uveitis @adult/paeds esp Wegener
• Dose:
– 250mg BD  500mg BD (start) 1g BD (aim)  1.5g BD
(unusual)
– fast to peak effect (4mth)
• SE:
– relatively safe- >GI/esp diarrhea, less BM suppress, reduce
contraception effect, 1st trimester risk, renal toxic

96. Cyclosporin
• Preferably as add-on after antimetabolite
• Fungal Baeuveria
• MOA: - T cell signal → - transcription of IL/cytokines
• Indication:
– systemic: CTD (RA/SLE), nephrotic syndrome
– ocular: VKC/AKC/rosacea/blepharitis, uveitis/graft vs host,
dry eye, Behcet (2nd)
• Dose
– RA: start 1mg/kg BD (50-100mg/day) → step up q4wk →
max 2mg/kg BD  2.5mg/kg BD (unusual)
– Excrete biliary
• SE: HPT, renal/neuro-toxic, gingival hyperplasia →
BP/RP/LFT/FBC!! +Mg/lipid profile

97. Tacrolimus & Sirolimus
• Fungal Streptomyces
• Tacro= calcineurin inhibitor (-T/-IL)
– Dose: 0.05–0.15 mg/kg/day
– Vs CSA: lower dose/more potent/less SE (still
need FBC/RP)
• Siro= non-calcineurin inhibitor (-T/-AB & B
cell)

98. Cyclophosphamide
• Alkylating agent
• most potent & potentially remission-inducing
• MOA: cross link/alkylate purine (>G) of DNA → cytotoxic/- rapid
proliferating/mitosis cells → - T/B cell
• IndiC:
– Systemic: CTD esp SLE/Wegener/GPA/vasculitis/RPC
– Ocular: Mooren, MMP, Behcet/VKH/SO
• Dose
– Oral OD, or pulse IV monthly (oral > effective than pulse IV)
– Oral 2mg (1-3)/kg/day (peak effect 1yr) --> dose is adjusted to achieve a
white blood count in the 3000 to 4000 cells/ml range when the
patient is not taking prednisone.
– Treatment is continued for 1 year and then tapered to determine if a
remission has been induced
• SE
– cystitis/hematuria, sterility, teratogenic, malignancy risk (leukemia/bladder
CA), BMS/leucopenia, increase IOP
– Monitor: FBC/UFEME & drink >2L H2O
– Opp ifx: +- PCP  consider bactrim prophylaxis

99. Chlorambucil
• Alkylating agent
• Dose: 0.1–0.2 mg/kg/day adjust similar to
cyclophosphamide
• “high-dose, short-term”: start at 2 mg/day 
escalated weekly until uveitis controlled or bone
marrow suppression  treatment is
discontinued; the mean maximum dose with this
approach is 20 mg/day
– Less SE/risk of cancer
• SE: BMS, sterility, teratogenic → FBC!

100. Infliximab (Remicade)
Adalimumab (Humira)
• TNF-alpha inhibitor
• IndiC:
– JIA, AS/spondyloarthropathies/HLA B-27
– idiopathic uveitis/behcet (2nd)/VKH/SO
• Administration
– Infli- IVI 5-8mg/kg @ D1/wk2/wk6 then q8wk
– Adali- subcutaneous 80mg stat  40mg weekly x1  40mg q2wk
• SE
– Malignancy  cervical CA (need yearly pap smear)
– Ifx  TB reactivation → Mantoux/CXR + for prophylaxis!
FBC/HepB/HepC/HIV screen
– Worsen MS
– New hypersensitivity/autoimmune dx  lupus, demyelinating dz, VH
– CCF, thrombosis
– less BMS

101. Others Biologic Agents
• Rituximab: B cell/CD 20 inhibitor
• Anakinra: IL-1 inhibitor
• Tocilizumab: IL-6 inhibitor
• IFN-alpha 2a/2b: antiviral, immunomodulatory,
and antiangiogenic effects
• Teprotumumab

102. Eye + Skin

103. Aphthous Ulcer (Canker Sores)
• Behçet syndrome
• CTD/autoimmune dz
• GIT dz/IBD/Malabsorption (UC/Crohn/pernicious
anemia)
• Immune defects such as HIV/AIDS
• Hematinic deficiency (iron, folic acid, vit B)
• Drugs (NSAIDs, alendronate, nicorandil,MTX, chemo)
• Recurrent aphthous stomatitis (RAS)
• Malignancy (SCC)
• Infection: viral/syphilis

104. Erythema Nodosum
• Drugs/SJS
• Ifx
– TB/Strep/Mycoplasma/Yersinia
– Hep C/EPV
• Inflam
– IBD
– Behcet
– Sarcoidosis (Lofgren syndrome)
– Lymphoma/leukemia/lupus/leprosy

105. Pyoderma gangrenosum

106. Other skin + eye
• keratoderma blenorrhagicum (brown
abscess@ palm/sole)- Reiter in HLA B-27 AU
• psoriasis- psoriatic arthritis in HLA B-27 AU
• Necrobiosis lipoidica diabeticorum (NLD)
@DM microangiopathy
• Papule-plaque, red brown-yellow, shiny
indurated border + atrophy center, +-ulcer/scar
• >pretibial, asymptomatic

107. Skin testing
Anergy
Pathergy
Mantous
Kveim

108. Pathergy
• Pathergy= immune system is overreacting to a minor injury
• Indications:
– Behçet's disease
– pyoderma gangrenosum
• Methods:
– skin prick test with sterile needle 22-18G → 24-48H
– small red bump or pustule at the site =+ve
– lesion +- resistant to healing (but subsequently healed with
steroid)
• Limitations:
– highly similar phenomenon (Koebner) @ autoimmune
dz/psoriasis/SLE
– sensitivity depends on race- Asian 50%, more in Mediterranean
– Caution may influence Mantoux test!

109. Mantoux
• intradermal injection of 2TU/0.1ml of PPD - Statens Serum
Institute (SSI) tuberculin RT23 → 48-72H
• Limitation:
– does not measure immunity to TB but the degree of
hypersensitivity to tuberculin
– no correlation between the size of induration and
likelihood of active TB but correlated with the future risk
of developing TB disease.
• Mantoux conversion
– second of two Mantoux tests increases by =/> 10mm
(newly obtained infection within that period) – DDX
boosting effect

110. Mantoux Interpretation (Malaysia/CDC)

111. Mantoux- Limitation
• False-Positive
– nontuberculosis mycobacteria (NTM)
– Previous BCG vaccination (aft 2mth)
• False-Negative
– anergy
• very young age (less than 6 months old)/very old
• Recent live-virus vaccination/viral illnesses (e.g., measles and smallpox/chickenpox
– very recent TB infection (within 8-10 weeks of exposure)
– very old TB infection (many years) → A repeat test /2-steps test/boosting
effect (1wk after) can result in a larger response (boosting can occur up to
2years)
*Incorrect method of administration/interpretation/Ag

112. Anergy
• Anergy= inability to mount a delayed-type hypersensitivity (DTH)
response to a battery of common skin test antigens → =
suppression of cell-mediated immunity.
• Methods
– Mantoux-method tests with 3x Ag (PPD + mumps/Candida/tetanus, all
0.1ml), used together and with cut-off diameters of 5 mm of induration
• Indications
– Immunosuppressed persons (HIV with PPD skin test reaction is
unknown/-ve )
• Factors limiting
– less standardization and reproducibility
– low risk for TB associated with a diagnosis of anergy
– lack of apparent benefit of preventive therapy for groups of anergic
HIV-infected persons.

113. Cause of Anergy Test Positive

114. Kveim Test
• Nickerson-Kveim or Kveim-Siltzbach test
• skin test for sarcoidosis
• Spleen tissue from a patient with known
sarcoidosis is injected into the skin of a
patient suspected to have the disease.
– +ve if non caseating granulomas are found (4–6
weeks later)
– False –ve: glucocorticoids treatment

116. Classical uveitis language
• Classical template for history taking
• Classical template for ocular examination
• Classical battery of tests/investigation
• Diagnosis with classical Terminology &
Classification
• Classical management plan
• Classical for Part 2 exam goers in Malaysia…
there are not basic
• Basic = relevant & targeted history, examination
& investigation  individualized

119. Specific term
• Geophagia
• Nyctalopia
• Myodesopsias
• Anti-citrullinated protein Ab

120. Coming
• OCT-A characteristics of active and inactive
chorioretinal lesions
• EDI-OCT structural alterations in several
uveitic diseases- VKH SO birdshot
• OCT based objective grading of intraocular
cells/inflammation.