1. Manfred Zierhut Centre of Ophthalmology University of Tuebingen, Germany Retinal Vasculitis

2. First Presentation – Ocular History June 2006  43 year old African man  OS: painful eye

3. First Presentation – General History  healthy

4. First Presentation – Ocular Examination OU  VA: 1.0/0.63  IOP: 18/48 mmHg  AC: 2+ cells, post. synechiae

5. First Presentation – Ocular Examination  Fundus OU:  massive vessel occlusion  neovasc. of the optic disc  small granuloma like changes

6. First Presentation – Fundus OD

7. First Presentation – FLA OD

8. First Diagnosis  Panuveitis with occlusive vasculitis of unclear origin

9. First Presentation – Investigastions  chest X-ray and CT: negativ  ACE 34 (8-21)  HIV, syphilis: negativ  thalassemia ß+ (heterocygote)  no sickle cells detectable

10. First Presentation – First Treatment  Corticosteroids syst.  Lasercoagulation  Mycophenolate mofetil  Avastin  Improvement of uveitis

11. Follow up – First Treatment  antiglaucomatous topical drugs  corticosteroids syst.  lasercoagulation

12. Follow up – After 1 -3 Months  improvement of inflammation, less the neovascularisation  corticosteroids syst. continued  lasercoagulation  mycophenolate mofetil  avastin

13. Follow up – After 1 to 9 Months July 2006 to March 2007  neovascularization of OD red.  more ischemia peripheral  more AC cells, IOP increased  systemic corticosteroids,  lasercoagulation  avastin

14. Follow Up – After 9 Months  inflammation reduced, but neovascularisation still detectable

15. Follow Up – After 12 Months June 2007  planned TNF-alpha blocking agents  Quantiferon-test: positive

16. Second Diagnosis  panuveitis with occlusive vasculitis probably of TB origin  but no other signs of TB detectable

17. Follow Up – After 13 Months July 2007  PET-CT scan

18. PET/CT-Scanner

19. 2. PET PET 1. Spiral CT CT 3. Fusion Combination of PET and CT

20. PET-Tracer: FDG (Fluor-18-Desoxyglucosis) „Trapping“  inflammation  tumor

21. PET/CT - Scan  enrichment of tracer in paratracheal lymph nodes  followed by biopsy KM-CT Fusion PET+CT SUV 2.4

22. Results of Biopsy PCR for TB: negative PCR for TB: negative biopsy: non caseating granulomas biopsy: non caseating granulomas diagnosis: Sarcoid diagnosis: Sarcoid planned therapy: TNF-alpha blocking agents planned therapy: TNF-alpha blocking agents

23. Phone call after 3 weeks positive TB - culture positive TB - culture

24. Follow Up – After 16 Months October 2007 start anti-TB treatment start anti-TB treatment

26. Follow Up – Next Months October 2007 clinically stable findings clinically stable findings regression of neovascularisations regression of neovascularisations occasionally intravitreal bleedings occasionally intravitreal bleedings occasionally mild IOP increase occasionally mild IOP increase

27. Follow Up – After 22 Months April 2008 back from Africa back from Africa massive increase of liver enzymes massive increase of liver enzymes stop of anti-TB treatment due to toxicity stop of anti-TB treatment due to toxicity

28. Last Control– After 94 Months October 2014 VA: 1.0/0.9 VA: 1.0/0.9 IOP: 18/22 mmHg IOP: 18/22 mmHg no AC cells, no neovascularisation no AC cells, no neovascularisation treatment: topical anti-IOP drugs treatment: topical anti-IOP drugs

29. Change of Paradigm  TB: Infectious disease creates the problems  but may initiate an immune response which may lead to uveitis  diagnosis: Chest-X-Ray, Mantoux  but in case of strong suggestion of TB QuantiFERON and PET-CT-Scan with biopsy and culture  problem: immune-mediated (latent?) TB  probably everywhere

30. Implications for Diagnosis  Tuberculosis:  PCR less effective as culture  specificity of quantiferon test may be higher than suggested in the literature  Sarcoidosis:  positive biopsy no proove of sarcoid !!  induced by TB?

31. Implications for TB-Treatment  infectious TB  anti TB-treatment  non-infectious (latent, immune-mediated) TB  anti-TB T-cells exist (+ Quantiferon Test)  despite massive IS: no generalisation  anti-TB with immunosuppressives

32. Ag-Presentation TB Antigen Uveitis T-Cells B-Cells Infectious TB Immune-mediated TB

33. Conclusion  TB may mimic sarcoid until the level of biopsy  infectious and immenumediated TB can induce panuveitis with retinal vasculitis  treatment consists of anti-TB-treatment and probably even immunosuppressive treatment