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Infectious uveitis dr martinez (1)


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Infectious uveitis dr martinez (1)

  1. 1. Clinical Aspects of Infectious Uveitis H. Nida en, MD, MHS Director, Uveitis and Ocular Immunology Fellowship Program National Eye Institute, National Institutes of Health Associate Clinical Professor, Dept of Ophthalmology The George Washington University Washington DC, 20037 Visionary Ophthalmology, September 18, 2011
  2. 2. Infectious uveitidesViral uveitis Hepesviridae family HIV HTLV Other (Rubella, west nile, measles, LCV)Fungal uveitis OHS, Candida, Aspergillosis, CryptococcosisProtozoal Uveitis ToxoplasmaHelminthic uveitis Toxocara, cysticercosis, DUSN, onchocerciasisBacterial uveitis Syphilis, Lyme, Tuberculosis, Bartonella, leptospirosis, nocardiosisInfectious Endophthalmitis Postoperative, posttraumatic, endogenous endophthalmitis
  3. 3. Viral Uveitis-Herpesviridae family (HSV I/II, CMV, VZV and EBV)Anterior uveitis R/o viral retinitis esp immunocompromised hostTreatment: topical steroids and cycloplegics (topical antivirals not useful except to prevent recurrence of keratitis if present) Oral antivirals in severe recurrent cases 400 bid acycl/500qd valacycl for HSV, 800bid acycl/1000qd valacycl for VZV
  4. 4. Herpesviridae family RetinitisAcute Retinal Necrosis (ARN) Described in 1971 (Urayama et al) Typically in otherwise healthy immune-competent adults , starts unilateral (2nd eye involvement in up to 36%) M=F, 5th to 7th decades VZV HSV CMV (+-EBV) Genetic predisposition: HLADQw7, Bw62, DR4 (caucasian), Aw33, B44, DRw6 (japanese) Clinical criteria (AUS): Peripheral retinal necrosis with discrete borders with circumferential spread typically full-thickness lesions that are white or cream colored Rapid progression w/out tx Occlusive vasculopathy with arteriolar involvement Prominent vitritis and AC inflammation Complications: Retinal breaks and RD (~75%), NV and VH Dx: clinical + PCR from ocular fluid
  5. 5. ARN
  6. 6. ARN treatment Treatment: Antivirals: induction + maintanance (3 mo) iv acyclovir (?PO) decreases risk of bilateral involvement Treatment with antivirals does not reduce the risk of RD intravitreal gancyclovir/foscarnet injection + steroids Vitrectomy/RD repair for complications ? Prophylactic laser barricade Prognosis: Guarded Regardless of complications visual outcome is poor
  7. 7. Herpesviridae family Retinitis-PORN Progressive outer retinal necrosis (PORN) primarily in immunocompromised individuals (in contrast to ARN) Advanced stages of HIV (CD4<50) Also described post-transplant Clinical characteristics:Differs multiple patchy areas of outer retinal whitening little or no inflammatory componentfrom spares the retinal vasculatureARN progression to confluent full thickness retinal necrosis occurs more rapidly (hence the name ““progressive””) can involve the posterior pole early more likely to progress to bilateral involvement (~70%) Virus: VZV most common (HSV also reported) Diagnosis: clinical +PCR (quantitative helps in determining tx response) Complications: RRD (75%)
  8. 8. No inflammationVessels sparedEarly post pole involvement
  9. 9. PORN-treatment Treatment: anti-HIV (HAART) + i.v antiviral + intravitreal ganciclovir+foscarnet Ganciclovir implant Immune reconstitution Surgery for complications Prognosis: Poor visual outcome despite antiviral treatment No light perception in 67% of eyes
  10. 10. CMV retinitisTypically in imunocompromised patients with HIV/AIDS CD4 counts of less than 50-100 cells/ L most common ocular opportunistic infection in patients with AIDS Less since HAART Can occur after renal transplantation or primary immune deficiencies Two classical clinical appearances to CMV retinitis: 1. Perivascular inflammation with irregular patches of necrotizing retinitis with hemorrhage 2. Granular lesion with central clearing and stippled retinal pigment epithelium. Other features: frosted branch angiitis, CME, retinitis progresses at the edge of previous retinal lesions (250 m per week)Complications: RRD (20%) IRU (20% to 90%) risk w/larger area vitritis, anterior uveitis, macular edema Believed to represent recovery of CMV-specific immunity topical, periocular,or oral steroids (reactivation!)
  11. 11. 59 yo moroccan male with h/o leukemia s/pchemotherapy Patient with HIV 28 yo F with angioimmunoblastic T-cell lymphoma s/p chemo
  12. 12. 20/20= 20/2543 yo jamaican female c h/o HTLV-1 associated adult lymphoma/leukemia s/p6 cycles of EPOCH-FR recently started on EPOCH-Campath (Alemtuzumab)
  13. 13. CMV retinitis-treatment Treatment: ganciclovir, foscarnet, cidofovir (Vistide, Gilead), fomivirsen (Vitravene, Novartis), and valganciclovir (Valcyte, Roche)FDA Iv ganciclovir (5 mg/kg bid) for 2 weeks (induction) once a dayapproved (maintanance) replaced by oral valganciclovir Intravitreal injection (ganciclovir/foscarnet) Intravitreal implant (ganciclovir) 6-8 month (x4 concentration than iv ganc) HAART/Immune recovery without HAART 50% reactivation despite anti-CMV therapy Prognosis: It may take 2-6 wks for progression to halt vision loss due to macular or optic nerve involvement OR CME
  14. 14. 4.5 mg gancyclovir, releases 1.4ug/hr
  15. 15. CMV retinitis-treatment resistancePhenotypic and genotypic resistance togancyclovir can occur most often secondary to mutations in the CMV UL97 gene (viral phosphotransferase) UL54 (viral DNA polymerase) The rate of resistance has declined dramatically with HAART therapy(28% to ~9%) Can be overcome with higher doses (intravitreal injection or implant)
  16. 16. 52F HIV+ F from Ethiopia referredfor recurrent CMV retinitis OSwhile on Valganciclovir x 5 mo &HAART (CD4 135) Anterior chamber tap (aqueous) and blood CMV PCR genotypic resistance to ganciclovir in blood but not in ocular fluids
  17. 17. ToxoplasmosisInfects at least 500 million persons The disease is caused by the obligateworldwide ~50% in US intracellular protozoan Toxoplasma gondii. A survey of ophthalmologists in the US: 55% of those who responded saw 1 active ocular toxoplasmosis cases in last 2 years 93% of those who responded had seen inactive cases in the last 2 years. West: In the United Kingdom the 17.5% North East: Mid West: 29.2% estimated lifetime risk for ocular 20.5% toxoplasmosis ~ 18/100 000 South: 22.8%
  18. 18. Definitivehost Toxoplasmosis Infection Congenital: transplacental transmission to the fetus chorioretinitis, encephalitis, other birth defects (TORCHS) Acquired: Ingestion of contaminated, undercooked lamb or pork (cysts) Ingestion of oocysts from soil, milk, water or unwashed vegetables rarely contaminated blood transfusions, organ transplants etc Acute infection: a flu-like illness with lymphadenopathy, fatigue, fever and malaise (~3-7%) Recurrent infections: chorioretinitis, lymphadenitis, myocarditis, polymyositis
  19. 19. Ocular toxoplasmosisOcular disease can occur afterboth congenital and acquireddisease.Clinically: anterior uveitis,vitritis with a prominent haze(headlight in the fog) andnecrotizing chorioretinitisRecurrent disease frequently isseen as a satellite lesion.Immunodeficient patients are atrisk
  20. 20. Courtesy of Rubens Belfort, MD
  21. 21. Courtesy of Rubens Belfort, MD, MBASao Paulo, Brazil
  22. 22. Treatment and Prognosis Treatment: There are no randomized, controlled large-scale clinical trials to guide therapeutic choice of agents. Pyrimethamine, sulfadiazine are used with or without prednisone. prednisone recommended to start 24 to 48 hours after the antibiotics are started. periocular or intraocular steroid injections are not recommended Bactrim (trimethoprim/sulfamethoxazole), clindamycin Atovaquone and Azithromycin. Bactrim prophylaxis? Silveira et al: 1998-2000, 7% recurrence in bactrim group vs 24% recurrence in control group. Complications: foveal involvement, ERM, CNV, BRAO, BRVO, cataract, glaucoma and CME Prognosis; Complications may result in permanent visual loss. Most patients retain good vision
  23. 23. ToxocariasisHuman toxocariasis is a helminth zoonosis due to theinfestation of humans by ascarid larvae belonging to the genusToxocara. Toxocara canis and T. cati causative agents of human disease Seroprevalence: 2-5% in western world to 60-80% in tropical countries Adult form lives in the upper digestive tract of their definitive hosts (cats/dogs) and eggs are passed in the feces Can be passed via the placenta in dogs only, milk for cat Primarily soil transmitted Pica, poor personal hygiene, raw vegetables, raw meat, exposure to puppies and kittens
  24. 24. Ocular Toxocariasis Result of migration of larva to the eye ““ocular larva migrans”” Primarily in young patients Ocular toxocariasis: ~1.0% uveitis patients Most patients report a history of recent exposure to puppies Unilateral 50% - a granuloma in the peripheral retina (age: 6-40) 25% - a granuloma in the macula (age:6-14) 25% - endophthalmitis (age: 2-8) Diagnosis: Serum ELISA: NEGATIVE in up to 50% ! OR AC/Vitreous tap Peripheral blood eosinophilia (may be absent in ocular toxocara) Serum total IgE , LFTs Imaging for liver, lung, CNS involvement Complications: TRD, CME, Vitritis Vitritis 52.6%, CME 47.4%, TRD 36.8%
  25. 25. Ocular toxocariasisTreatment: Albendazole 10mg/kg PO BID x 5-14d (better tolerated and larger decrease in eosinophilia) Thiabendazole 25mg/kg PO BID x 5-14d Prednisone Ivermectin Not very effective and not recommended
  26. 26. SyphilisMay affect all ocular tissue; uveitis is most common, Bilateral in 50% of thecasesGreat masquarader Anterior, intermediate, posterior and panuveitis,retinitis, retinal vasculitis, papillitis and neuroretinitisTests for syphilis fall into four categories 1. Direct microscopy when lesions are present 2. Nontreponemal tests: VDRL, RPR Clumping of cardiolipin ( lecithin and cholesterol) False Negative in 30% False positive in SLE and other autoimmune disorders, tissue damage, liver diseases, pregnancy, other Treponema- Lyme disease, Leptospirosis 3. Treponemal tests FTA-ABS (Fluorescent Treponemal Antibody absorption test) detects antibody to T. pallidum after serum treated with nonpathogenic treponemal antigen; High sensitivity and specificity MHA-TP (Hemagglutination tests): 15% + in SLE and can be + in Lyme disease 4. Direct antigen and the bacterial DNA detection, research HIV TEST !
  27. 27. Syphylis-treatment Ocular Inflammation secondary to syphilis should be treated as neurosyphilis (AAO), Lumbar puncture Routine RPR or VDRL and FTA-ABS or MHA-TP HIV testingChao JR, Khurana RN– and Rao NA. Syphilis: reemergence of an old adversary. Ophthalmology 2006:113: 2074-2079Aldave AJ et al (2001) Current Opinion in Ophthal. 12: 433-441
  28. 28. Lyme DiseaseIt is most frequent tick-born infectious disease in certainregions of US and Europe US: Coastal North-East, North west California and Great lakes regions The causative pathogen is Borrelia burgdorferi The tick must feed for at least 36 hours for transmission of the agentThree stages of the disease Early localized infection (stage 1): erythema migrans, fever, malaise, fatigue, headache, myalgias, arthralgias, conjunctivitis Early disseminated infection (stage 2: occurring days to weeks later) neurologic, musculoskeletal or cardiovascular and uveitis Late disseminated infection (stage 3) Arthritis +-uveitis neuropathy or encephalopathyDx: clinical+ Isolation of organism from advancing marginof the erythema migrans; ELISA; IgG and IgM andWestern blot
  29. 29. 20/20 OD 20/80 OS A 27 year old male from California, an avid hiker c/o scotoma, photopsia in the left eye. Reported fever, generalized 20/20 20/20 malaise and some joint discomfort for 1mo ANA, RF, CXR, PPD and Sy serology (-), Laboratory work up was significant for After iv ceftriaxone treatment for 3 wks positive ELISA Lyme antibody titers 3.4 Western blot was positive for Lyme IgG Prophylaxis: A single dose of doxycycline 200mg orally(prevention should be emphasized) Courtesy of Narsing Rao, MD
  30. 30. OCT-tuberculous granulomas?
  31. 31. Presumed tubercular serpiginous-like choroiditis Gupta et al. Ophthalmology 2003 Serpiginous choroiditis relapsing despite corticosteroids and CSAHighly positive PPD. PCR from aqueous and vitreous in 4 samples was (+) positive for Mtb. No more relapse after anti-TB therapy. Follow-up : 3 y and without Rx
  32. 32. AIDS or other immunecomprimising diseases-particular concern Brevundimonas endogenous endophthalmitisAspergillus enendophthalmitis in CLL s/p chemococcidioidomycosis
  33. 33. When to suspect an infectious agent? 1- Clinical presentation may be helpful but non specific 2- Systemic manifestations (immune- compromise (HIV/AIDS), fever, neutropenia) 3- Steroid-resistance or -dependence 4- No evidence for a specific auto- inflammatory condition (JIA, VKH, SO, Behçet) or a malignant disease 5- Epidemic outbreak!
  34. 34. Diagnostic strategy Infectious agent Diagnostic strategy HSV, CMV, VZV PCR > GW EBV, HHV-8 PCR Toxoplasmosis GW > PCR Toxocariasis WB Tuberculosis PPD/Chestx-ray nPCR Whipple PCR Fungal Culture/PCR
  35. 35. Summary All atypical forms of uveitis deserve further investigations to exclude an infectious etiology prednisone or other uveitis treatment can cause significant worsening Early Dx remains the best way to propose a specific Rx and achieve long-term remission or healing
  36. 36. Thank you Special thanks to:Dr Chan and our clinical fellows