12/2/2016 UCSF December Course- 2016 San Francisco, CA Mosquito-Borne Uveitis Emmett T. Cunningham, Jr, MD, PhD, MPH Mosquito Department of Ophthalmology, Proboscis California Pacific Medical Center Department of Ophthalmology, Stanford University School of Medicine Francis I. Proctor Foundation, Mosquitos … Aedes aegypti UCSF School of Medicine 10 μm West Coast Retina Medical Group www.gettyimages.com Global Distribution of Aedes albopictus Aedes albopictus Global Distribution of Aedes aegypti 1
12/2/2016 Global Distribution of Aedes albopictus Global Distribution of Aedes aegypti Tropics: Tropics: 36% of the Earth’s Landmass 36% of the Earth’s Landmass Global Air Travel One-Third of the Earth’s Population One-Third of the Earth’s Population 23.5 o N – Tropic of Cancer Equator 23.5 o S – Tropic of Capriocorn http://education.nationalgeographic.org/encyclopedia/tropics/ 2
12/2/2016 • Malaria – 450,000 Deaths/year Heavily Interconnected • Measles • Mumps • Rubella • Filariasis • Pork tapeworm • Hepatitis C The Flaviviridae Family • Enveloped viruses • Icosahedral structures • A positive sense, single-strand RNA genome (~ 12kb) • Transcribed as a single polyprotein • More than 100 different members • Subdivided into: • Flavivirus (including Yellow fever, Japanese Encephalitis, West Nile, dengue, and Zika viruses) • Pestivirus • Hepacivirus (hepatitis C viruses) http://www.utmb.edu/discoveringdenguedrugs-together/Diseases/Flaviviridae%20Family.asp 3
12/2/2016 West Nile Virus West Nile Virus • Flavivirus genus • Flaviviridae family • Positive-sense, single stranded RNA virus • ~ 12Kb. West Nile Virus US Outbreak WNV 1999 Israeli Outbreak 1957 Lifecycle Identified in Uganda 1937 4
12/2/2016 1999 2000 Global Distribution of West Nile Virus 2001 2002 Courtesy Mr. Nicholas Jones, Uveitis, 2 nd Edition, 2013 West Nile Virus – USA, 1999-2012 CDC ArboNET http://www.cdc.gov/westnile/resources/pdfs/wnvguidelines.pdf 5
12/2/2016 Average Annual Incidence of WNV Cases of WNV Reported to the CDC by Year Human Neuroinvasive Disease 2015 YTD 1566 by Decile, 1999 – 2012, USA CDC ArboNET 2014 2205 2013 2469 2012 5674 2011 712 2010 1019 2009 720 < 1 / 100,000 / year More Common in Elderly 2008 1356 2007 3630 2006 4269 2005 3086 2004 2526 2003 9868 2002 4156 2001 66 2000 Index Cases, NYC 21 1999 62 0 2000 4000 6000 8000 10000 Number of Cases of WNV 2015 To Date Cases reported to CDC ArboNET Human Neuroinvasive Disease by week, 1999 – 2012, USA CDC ArboNET Human - 1566 More Common in Summer / Fall Mosquito http://diseasemaps.usgs.gov/mapviewer/ West Nile Virus 6
12/2/2016 Systemic Disease • 2 – 14 day incubation Retina 2003; 23(1):97-99 Arch Ophthalmol 2003; 121:205-207 • 80% asymptomatic • 15% symptomatic, WN Fever – self limited, ~ 1 week • Fever • Headache • Myalgia • Arthralgia 15% 80% Asymptomatic • Malaise 5% Symptomatic • Nausea • Vomiting Encephalitis • Skin Rash • Pharyngitis • 5% WN Encephalitis – Severe headache, meningismus, confusion, stupor/coma, tremors, convulsions, paralysis, death – typically older or debilitated (diabetes). Ocular Disease Early Lesions Multifocal Chorioretinitis Deep, Yellow-White • AC inflammation Often Curvilinear Pattern • Vitreous inflammation • Retinal vasculitis • Retinitis • Choroiditis (ICGA) • Multifocal chorioretinitis curvilinear pattern Courtesy Prof. Moncef Khairallah Courtesy Prof. Moncef Khairallah 7
12/2/2016 Ophthalmol 2003; 110:1732-1736 West Nile Virus Chorioretinitis West Nile Virus Chorioretinitis Courtesy K. Bailey Freund http://www.westcoastretina.com/WestCoastRetina/Feb-2014.html Courtesy West Coast Retina 8
12/2/2016 West Nile Virus Lesions Nerve Fiber Layer Distribution? FA Multifocal Chorioretinitis Often Curvilinear Pattern More on ICGA Spurious . . .? Courtesy Prof. Moncef Khairallah ICGA FA Multifocal Chorioretinitis Often Curvilinear Pattern Courtesy Prof. Moncef Khairallah 9
12/2/2016 20/20 00:56.19 05:45.96 Courtesy Dr. Steve Bennett Neuroretinitis – Retinitis Vascular Occlusion Retina. 2006 Mar;26(3):365-7. Courtesy Prof. Rathinam Sivakumar 10
12/2/2016 Dengue • Flavivirus genus • Flaviviridae family • Positive-sense, single stranded RNA virus Dengue Virus • ~ 11Kb. Global Distribution of Dengue Virus 50-100M New Cases per Year Courtesy Mr. Nicholas Jones, Uveitis, 2 nd Edition, 2013 11
12/2/2016 Cases of Dengue Reported to the CDC by Year 364 2015 YTD 33 < 1 / 100,000 / year 654 Mostly Florida and Texas 2014 551 772 2013 8253 554 2012 6169 243 2011 1552 642 2010 10969 0 2000 4000 6000 8000 10000 12000 Imported Locally Aquired 2015 To Date Systemic Disease Cases reported to CDC ArboNET • 2 – 14 day incubation • Asymptomatic Locally Acquired • Non-specific febrile illness 33 Cases • Classic Dengue fever • High Fever • Severe Headache • Myalgia • Arthralgia • Malaise Imported • Nausea 364 https://viraldiseasesd.wikispaces.com/Dengue+Fever • Vomiting • Maculopapular Skin Rash • 10% - Dengue Hemorrhagic Fever Shock Syndrome http://diseasemaps.usgs.gov/mapviewer/ Dengue https://microbewiki.kenyon.edu/index.php/Dengue_transmission 12
12/2/2016 Dengue Virus Ocular Disease Subconjunctival Hemorrhage 75% Bilateral Platelet Counts < 50,000/ul May be Serotype Specific • Subconjunctival hemorrhage Hemorrhage Yellow-White Lesions • AC inflammation • Vitreous inflammation • Retinal hemorrhage • Retinal vasculitis • Retinal vascular occlusion • Retinitis • Deep retinal spots / foveolitis • RPE mottling • Serous retinal detachment https://openi.nlm.nih.gov/detailedresult.php?img=2566568_1757-1626-1-204-1&req=4 • Choroiditis (ICGA) 13
12/2/2016 Dengue Virus Dengue Virus Active Lesions Active Lesions FA FA Courtesy Dr. Stephen Teoh Courtesy Dr. Stephen Teoh Dengue Virus Dengue Virus Active Lesions Active Lesions ICGA ICGA Courtesy Dr. Stephen Teoh Courtesy Dr. Stephen Teoh 14
12/2/2016 Dengue Virus Dengue Virus Infection Active Lesions 20/40 CF “Foveolitis” Courtesy Dr. Stephen Teoh Courtesy Dr. Padmamalini Mahendradas Dengue Virus Dengue Virus Inactive Lesions Active Lesions Courtesy Prof. Khalid Tabbara Courtesy Prof. Khalid Tabbara 15
12/2/2016 Dengue Virus Dengue Virus Active Lesions + 9 Months, Inactive Courtesy Dr. Srinivasan Sanjay Courtesy Dr. Srinivasan Sanjay Dengue Virus Dengue Virus Active Lesions – Retinitis / Intraretinal Hemorrhage Active Lesions – Retinitis / Intraretinal Hemorrhage Courtesy Prof. Chee Soon Phaik Courtesy Prof. Chee Soon Phaik 16
12/2/2016 Dengue Virus Dengue Virus Active Lesions – Vasculitis Active Lesions – Vasculitis Courtesy Prof. Chee Soon Phaik Courtesy Prof. Chee Soon Phaik Dengue Virus Active Lesions – Foveolitis Chikungunya • Alphavirus genus • Togaviridae family. • Positive-sense, single stranded RNA virus • ~ 12Kb. Courtesy Prof. Chee Soon Phaik 17
12/2/2016 In “Makonde,” Chikungunya Global Distribution of Chikungunya means “to walk bent over.” A reference to the stooped posture of many sufferers. Chikungunya Described in 1953, East Africa Tanzania Mozambique Courtesy Mr. Nicholas Jones, Uveitis, 2 nd Edition, 2013 2015 To Date Cases reported to CDC ArboNET Locally Acquired 152 Imported 538 http://diseasemaps.usgs.gov/mapviewer/ Chickunugnya 18
12/2/2016 https://www.sciencenews.org/article/chikungunya-move June 2, 2015 https://www.sciencenews.org/article/chikungunya-move June 2, 2015 Systemic Disease Ocular Disease In “Makonde,” Chikungunya means “to walk bent over.” • AC inflammation +/- high IOP • 2 – 14 day incubation • Vitreous inflammation • Acute • Retinal hemorrhage • Fever • Headache • Retinal vasculitis • Low back pain • Retinal vascular occlusion • Severe joint pain • Retinitis • Myalgia • Neuroretinitis • Malaise • Serous retinal detachment • Nausea • Choroiditis (ICGA) • Vomiting • Severe – multi-organ failure, CNS involvement, death Courtesy Dr. Padmamalini Mahendradas 19
12/2/2016 Chikungunya Fever 20/30 20/50 Am J Ophthalmol 2007; 144:552-556 Common • AC / Vitreous cell • Neuritis • Retinitis +/- SRD Courtesy Prof. Richard Rosen + Two Months Chikungunya Fever Oral CST, Topical CST, Topical Cyloplegic / Mydriatic 20/30 20/50 20/20 20/20 1:11 2:16 Courtesy Prof. Richard Rosen Courtesy Prof. Richard Rosen 20
12/2/2016 Chikungunya Fever Courtesy Dr. Padmamalini Mahendradas Courtesy Prof. Rathinam Sivakumar Chikungunya Fever 16 WEEKS Presentation 4 WEEKS 20/20 20/40 Am J Ophthalmol 2007; 144:552-556 20/20 20/30 Vision at Last Visit Variable Courtesy Dr. Annie Mathai and Dr. Nidhi Relhan 21
12/2/2016 Zika Virus • Flavivirus genus Zika Virus • Flaviviridae family • Positive-sense, single stranded RNA virus • ~ 12Kb. Uganda 1947 - Monkeys 22
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