W smith uveitis compressed 5.22.11 (1)

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UVEITIS AND OCULAR IMMUNOLOGY by Wendy Smith MD
COPE ID 31562-SD
Lecture Series 12th Visionary Ophthalmology

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W smith uveitis compressed 5.22.11 (1)

  1. 1. Uveitis W E N D Y   M   S M I T H ,   M D S E N I O R   S T A F F   F E L L O W ,  U V E I T I S   A N D   O C U L A R   I M M U N O L O G Y N A T I O N A L   E Y E   I N S T I T U T E N A T I O N A L   I N S T I T U T E S   O F   H E A L T H
  2. 2. Uveitis: Definition a generic term for intraocular inflammation. does not indicate site of inflammation does not indicate the cause: autoi mmune or infectious
  3. 3. How  Common  is  Uveitis?10-­15%  of  severe  visual  handicap  in  the  U.S.3rd leading  cause  of  blindness  in  the  worldU.S.  Incidence  52.4/100,000U.S.  Prevalence  115.3/100,000 2,400,0003  times  higher  than  previous  estimate Prevalence  higher  in  women  (1:1.4) Common  in  older  patientsGritz  and  Wong.  Ophthalmology  2004Worldwide  prevalence  ~2.4  million~5-­10%  of  cases  in  children  <16  yrs 322,000 151,200Mean  age  of  onset  is  37.2  yearsRange  20-­50  years U.S. Incidence U.S. Prevalence Worldwide
  4. 4. IUSG  Classification  of  UveitisAnterior  uveitis iris  and  pars  plicata  (CB)Intermediate  uveitis pars  plana  and  vitreousPosterior  uveitis retina  +  choroidPanuveitis
  5. 5. SUN  Grading  system  for  AC  cell  and  flareCells  per  high-­power  field  in  1x1  mm  slit  beam 0  =  <  1  cell/hpf 0.5+  =  1  -­ 5  cells 1+  =  6  -­ 15 2+  =  16  -­ 25 3+  =  26  -­ 50 4+  =  >  50Flare 0  =  none 1+  =  faint 2+  =  moderate,   (iris/lens  details  clear) 3+  =  marked (iris/lens  hazy) 4+  =  intense  (fibrin  or  plastic  aqueous)
  6. 6. National  Eye  Institute  Grading  System  for  Vitreous  Cell (No  SUN  Working  Group  Consensus) Number  of  Cells* Description Grade 0-­1 clear 0 2-­20 few  opacities trace 21-­50 scattered  opacities 1+ 51-­100 moderate  opacities 2+ 101-­250 many  opacities 3+ >250 dense  opacities 4+ *cells  are  counted  using  a  Hruby,  90  or  78  diopter  lens
  7. 7. National  Eye  Institute  Grading  System  for  Vitreous  Haze   (adopted  by  SUN  Working  Group) 0  =  Clear 0.5+/trace  =  Trace 1+  =  Few  opacities, mild  blurring 2+  =  Significant blurring  but  still visible 3+  =  Optic  nerve visible,   no  vessels  seen 4+  =  Dense  opacity obscures  optic nerve  head
  8. 8. Developing  a  Differential  Diagnosis Is  the  disease  acute  or  chronic? Where  is  the  inflammation  located  in  the  eye? Unilateral  or  bilateral? Granulomatous  or  non-­granulomatous? What  are  the  demographics  of  the  patient? Associated  symptoms? Associated  signs  on  physical  exam? How  did  the  disease  respond  to  previous  therapy?
  9. 9. Anterior  Uveitis:  ~60%  of  all  uveitisIdiopathicHLA-­B27  associated Inflammatory  bowel   Sarcoidosis disease Syphilis Ankylosing  spondylitis Glaucomatocyclitic  crisis Masquerade  syndromes Psoriatic  arthritisJIA  (Juvenile  Idiopathic  Arthritis)  associated
  10. 10. Anterior  uveitisprevalence:  81/100,000  (Gritz et  al)
  11. 11. Differential  Diagnosis  of  Stellate  Keratic  Precipitates: Fuchs  heterochromia  (rubella,  herpes,  toxoplasmosis) Viral Toxoplasmosis
  12. 12. Differential  Diagnosis  of  hypopyon: HLA-­B27  associatedLow  back  pain,  ethnicity,  GI  symptoms,  ulcers,  joints
  13. 13. JIA-­associated  uveitis <16yo,>6mo  disease Pauci-­articular:  25% Type  1=Ana+  young  girls Type  2=Older  boys  B27+ Poly-­articular:  ~15% Systemic  onset:  1-­5%Most  at  risk:ANA+,  RF-­,  pauciarticular  girlsUveitis  develops  within  5-­7  yrsNo  correlation  betw  joint  and  eyeFrequently  asymptomaticUveitis  before  joint  disease  poor  pxBK/PS/cataract/ON  hyperemia/CME  common
  14. 14. Anterior  UveitisComplications Treatment Posterior  synechiae Topical  corticosteroids Cataract   Cycloplegics Inflammation-­related Glaucoma  gtts Steroid-­induced NSAIDs  (gtt or  PO) Secondary  glaucoma Steroid  response Periocular  steroids Angle  closure Cystoid  macular  edema Systemic  steroids Band  keratopathy Systemic   more  common  in  children immunosuppression
  15. 15. Intermediate  Uveitis:  ~15%  of  all  uveitisMost  common  causes: Sarcoidosis Pars  planitis  syndrome  (idiopathic) Multiple  sclerosis Masquerade  Syndromes Infection   Toxoplasma,  Lyme,  Toxocara,  Syphilis,  TB
  16. 16. Intermediate  UveitisVitritis  +/-­ periphlebitisSnowballs,  snowbanking                (more  severe  disease  process)Pars  planitis:  PP  exudates            (HLA-­DR15) ~15%  of  patients  with  pars   planitis  will  develop  MSCME  is  the  main  vision  threatening  complication
  17. 17. Posterior  &  Panuveitis:  10-­15%  of  all  uveitisFocal  choroiditis/retinitis:   Multifocal  Retinitis: Toxocariasis Syphilis Herpes  simplex  virus,  CMV Tuberculosis Sarcoidosis Nocardiosis Masquerade  syndromes Masquerade  syndrome Candidiasis MeningococcusMultifocal  Choroiditis: SO PANuveitis: VKH Syphilis Sarcoidosis Sarcoidosis Serpiginous VKH Birdshot disease   Sympathetic  Ophthalmia Histoplasmosis/TB Infectious  endophthalmitis Masquerade  syndrome
  18. 18. Posterior  (Pan)  UveitisInflammation  involving  retina/choroid Optic  nerve: ON  Edema,  papillitis,  granuloma FA  features hot? Retinal  vasculature: Staining,  leakage,  capillary  dropout Involves  mainly  veins  vs  arteries Peripheral  vs  central Chorioretinal  lesions: Dalen-­fuchs  nodules Size,  age  of  lesion  (old  atrophic  vs  new  elevated  with  substance  to  it)
  19. 19. SarcoidosisSarcoidosis  is  a  multisystem  granulomatous  disorder   lungs  (90-­95%),  lymph  nodes,  skin,  eyes,  CNS Typically  affects  young  adults  More  commonly  seen  in  African  Americans  and  Caucasians  of  Northern  European  descent In  US  8-­10x  more  common  in  AA   AA:  35  to  82/100,000  Caucasians:  8  to  11/100,000Etiology  unknown  but  believed  to  be  immune  mediated:   genetic  predisposition  (familial  aggregation,  monozygotic  twins,  HLAB8,   HLADRB1)  and  environmental  factors  (environmental  allergens  and   infectious  agents)  have  been  suggested.Ocular  disease  most  common  extra-­pulmonary  presentation Uveitis  occurs  in  25-­50%  of  pts 20-­50  yrs,  typically  bilateral  (98%)
  20. 20. Sarcoidosis:    Dalen-­
  21. 21. Slit-like third ventricle Transependymal CSF flow Diagnosis:  Biopsy-­Proven  Neurosarcoidosis30  yo  AAM:  Referred  for  endogenous  candida  endophthalmitisAlso  has  recent  onset  of  headache,  mood  changes,  gait  abnormalities Enlarged lateral ventricles
  22. 22. Diagnostic vitrectomy: Nests of macrophages & giant cells Small and reactive lymphocytes Further work-up: hilar LAD on CT and PET scan Diagnosis: Presumed Ocular Sarcoidosis75  yo  WF  with  recent  onset  blurry  visionCarried  dx  of  SLE  for  >20  yrsCBC:  slightly  elevated  WBCNeg  or  wnl:  Lyme,  RPR,  FTA ABS,  PPD  HLA  B27  neg,  UA  &  Chem  20  wnl
  23. 23. Modified  Japanese  Criteria: Major  criteria  (skin,  oral,  genital,  eye) Minor  criteria  (arthritis,  GI,  epididymitis,  neuropsychiatric   etc)Classification Complete  (4  major),  Incomplete  (3  major  OR  ocular   disease+1  major),  Suspect  (2  major  nonocular),                       Possible  (1  major)International  Study  Group  for  BD recurrent  oral  ulcers  is  a  must  (+2  other  criteria)
  24. 24. retinitis
  25. 25. VKH:  Common  in  pigmented  ethnic  groupsBilateral  panuveitisVitiligo,  alopecia,  poliosis,  (10-­60%)Dysacusia,  tinnitus  (75%  auditory  problems)Meningitis  (80%  have  CSF  lymphocytic  pleocytosis)ON  edema  &  hyperemia,  Serous  RDDalen-­Fuchs  nodulesSunset-­glow  fundusSigiura  sign  (perilimbal  vitiligo)HLA  DR4  (esp  Japanese),  DR1
  26. 26. 24  yo Latino  male  with  VKH: Sudden  onset  blurred  vision Headache Tinnitus  &  hearing  lossOne  month  after  presentation Ten  months  after  presentation
  27. 27. End-­stage  VKH  with  diffuse  RPE  loss  and  subretinal  fibrosis
  28. 28. Retinal  VasculitisSystemic  Lupus  Erythematosus Retinopathy  is  an  important  marker  of  systemic  activity  esp  CNS  vasculitis-­75%Polyarteritis  Nodosa  (PAN) Untreated:  90%  mortalityWegener  granulomatosis   Necrotizing  granulomatosis  of  upper  &  lower  resp  tract  -­esp  paranasal  sinuses Glomerulonephritis  (85%),  peripheral  neuropathy   Untreated:  80%  mortality
  29. 29. HIV+  not  on  HAART52  yo  M RPR+  1:2048,  Syphilis  IgG+Acute  onset  of  blurred  vision  &  photophobia  OSNon-­granulomatous  anterior  uveitis  OS  >  ODVitritis  OS  >  OD Syphilis-­related  panuveitisBRAO  and  retinitis  OD Responded  to  IV  Penicillin  x  4  wks
  30. 30. Serpiginous  choroidopathy Relationship  w/TB? Treated  with  immunosuppressives HLA-­B07 >30% VA  <20/200
  31. 31. APMPPE:  Acute  posterior  multifocal  placoid  pigment  epitheliopathy Bitten  by  a  lab  animal Preceding  flu-­like  symptoms Early  hypo,  late  hyper  on  FA (White  Dot  Syndromes) Hypofluorescent  spots  on  ICG CNS  vasculitis Benign  course 20%  Visual  Sequelae
  32. 32. Posterior/Panuveitis  complicationsCataract Choroidal  Epiretinal  membrane neovascularizationSecondary  glaucoma Retinal  ischemiaHypotony Retinal   neovascularizationChronic  cystoid  macular  edema Optic  nerve  atrophySubretinal  fibrosisAtrophy  of  retina/RPE Retinal  detachment Phthisis  bulbi
  33. 33. Work-­up CBC  with  diff,Chem  20,  UA,  ESR,  CRP TB  (PPD+anergy  panel)+Chest  X-­ray Syphilis  (both  RPR  and  Sy  IgM,  IgG) HIV Additional: ACE,  lysozyme,  Ca     sarcoidosis UA-­>  TINU,  Wegener,  SLE ANA,  anti-­DNA,  RF,  anti-­CCP,  ENA  panel connective  tissue  disordersDespite  a  million  dollar  work-­up-­>   ANCAs  (c-­ANCA=PR3;;  p-­ANCA=MPO)   Wegener,  PAN Hypercoagulability  panel  (ACA,  LAC,  Factor  V  Leiden  mut)   occlusive  vasculitis40%  still  idiopathic High  Resolution  Chest  CT   TB,  sarcoidosis PFT/pulm  consult   sarcoidosis Hearing  test VKH,  sarcoidosis LP MS,  VKH,  PIOL/CNSL HLA  panel   Birdshot,  HLA-­B27,  Behçet,  MS,  sarcoid Sinus  CT   W Lumbosacral  XR/MRI HLAB27  associated  uveitides Colonoscopy   IBD,  Behçet,  malignancy  work-­up Anterior  chamber  and/or  vitreous  tap  for  PCR,  cultures,  cytokines
  34. 34. Treatment:Corticosteroids  have  been  the  mainstay  since  1970s Neutrophils Inhibit neutrophil migration neutrophil adherence to vascular endothelium bactericidal activity of neutrophils Local effects on the endothelium Mononuclea r phagocytes Chemotaxis Clearance of antibody coated particles Production of Il-1 and TNF L ymphocytes Redistribution of T lymphocytes(CD4 > CD8) Inhibit T lymphocyte activation proliferation and lymphokine production Inhibit Ig production by B cells (high dose)
  35. 35. Immunosuppressive  TherapyAntimetabolites: Methotrexate  (anti-­folate),  Azathioprine  (purine  inhibitor),   Mycophenolate  Mofetil  (pu)  (Cellcept),  Leflunomide  (pyrim  inh)T-­cell  Inhibitors: Cyclosporine,  Tacrolimus  (cacineurin),  Sirolimus(mtor)Alkylating  agents: Cyclophosphamide,  ChlorambucilBiologics: Anti-­TNF(  *infliximab,  etanercept,  adalimumab,  golimumab,   certolizumab) Anti-­IL2R  (*daclizumab,  basiliximab) Anti-­IL1  (anakinra) Anti-­B  cell  (*Rituximab,  Ocralizumab)million  dollar  treatment   ?effect  on  outcome
  36. 36. SummaryDiagnosis:  what,  where,  when,  whoDifferential:  use  to  guide  testing   rule  out  etiologies  that  must  be  treated  before   immunosuppression  (infections!)corticosteroid  treatments  (Please  refer!) If  not  responding  to  treatment,  consider  another  diagnosisGoals:  Prevent  complications,  minimize  side  effects  of  treatment,  PRESERVE  VISION
  37. 37. Thank  you!

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