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

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

First Presentation – General History  healthy

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

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

First Presentation – Fundus OD

First Presentation – FLA OD

First Diagnosis  Panuveitis with occlusive vasculitis of unclear origin

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

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

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

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

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

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

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

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

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

PET/CT-Scanner

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

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

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

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

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

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

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

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

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

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

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?

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

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

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