Department of Ophthalmology, Stanford University School of … · 2016. 12. 13. · Uveitis Emmett...

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10 μm

Mosquito-Borne Uveitis

Emmett T. Cunningham, Jr, MD, PhD, MPHDepartment of Ophthalmology, California Pacific Medical CenterDepartment of Ophthalmology, Stanford University School of MedicineFrancis I. Proctor Foundation, UCSF School of MedicineWest Coast Retina Medical Group

UCSF December Course- 2016San Francisco, CA

Mosquito Proboscis

www.gettyimages.comMosquitos … Aedes aegypti

Aedes albopictus

Global Distribution of Aedes albopictus

Global Distribution of Aedes aegypti

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Global Distribution of Aedes albopictus

Global Distribution of Aedes aegypti

Tropics: 36% of the Earth’s LandmassOne-Third of the Earth’s Population

Tropics: 36% of the Earth’s LandmassOne-Third of the Earth’s Population

http://education.nationalgeographic.org/encyclopedia/tropics/

23.5 o N – Tropic of Cancer

23.5 o S – Tropic of Capriocorn

Equator

Global Air Travel

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Heavily Interconnected • Malaria – 450,000 Deaths/year• Measles• Mumps• Rubella• Filariasis• Pork tapeworm• Hepatitis C

• 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 Zikaviruses)

• Pestivirus• Hepacivirus (hepatitis C viruses)

The Flaviviridae Family

http://www.utmb.edu/discoveringdenguedrugs-together/Diseases/Flaviviridae%20Family.asp

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West Nile VirusWest Nile Virus• Flavivirus genus• Flaviviridae family• Positive-sense, single stranded RNA virus • ~ 12Kb.

WNVLifecycle

US Outbreak1999

Identified in Uganda

1937

Israeli Outbreak1957

West Nile Virus

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Global Distribution of West Nile Virus

Courtesy Mr. Nicholas Jones, Uveitis, 2nd Edition, 2013

1999 2000

2001 2002

http://www.cdc.gov/westnile/resources/pdfs/wnvguidelines.pdf

West Nile Virus – USA, 1999-2012CDC ArboNET

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622166

41569868

25263086

42693630

1356720

1019712

56742469

22051566

0 2000 4000 6000 8000 100001999200020012002200320042005200620072008200920102011201220132014

2015 YTDCases of WNV Reported to the CDC by Year

< 1 / 100,000 / year

Index Cases, NYC

Average Annual Incidence of WNV Human Neuroinvasive Disease

by Decile, 1999 – 2012, USA CDC ArboNET

More Common in Elderly

Number of Cases of WNV Human Neuroinvasive Disease

by week, 1999 – 2012, USA CDC ArboNET

More Common in Summer / Fall

http://diseasemaps.usgs.gov/mapviewer/West Nile Virus

Human - 1566

Mosquito

2015 To DateCases reported to CDC ArboNET

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Systemic Disease• 2 – 14 day incubation• 80% asymptomatic• 15% symptomatic, WN Fever – self limited, ~ 1 week

• Fever• Headache• Myalgia• Arthralgia• Malaise• Nausea• Vomiting• Skin Rash• Pharyngitis

• 5% WN Encephalitis – Severe headache, meningismus, confusion, stupor/coma, tremors, convulsions, paralysis, death – typically older or debilitated (diabetes).

AsymptomaticSymptomaticEncephalitis

80% 15%5%

Retina 2003; 23(1):97-99Arch Ophthalmol 2003; 121:205-207

Ocular Disease• AC inflammation• Vitreous inflammation• Retinal vasculitis• Retinitis• Choroiditis (ICGA)• Multifocal chorioretinitis

curvilinear pattern

Courtesy Prof. Moncef Khairallah

Early LesionsDeep, Yellow-White


Multifocal ChorioretinitisOften Curvilinear Pattern

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Ophthalmol 2003; 110:1732-1736

http://www.westcoastretina.com/WestCoastRetina/Feb-2014.html Courtesy West Coast Retina

West Nile Virus Chorioretinitis

Courtesy K. Bailey Freund

West Nile Virus Chorioretinitis

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FA

ICGA

Multifocal ChorioretinitisOften Curvilinear Pattern

More on ICGA

West Nile Virus LesionsNerve Fiber Layer Distribution?

Spurious . . .?


Multifocal Chorioretinitis

Often Curvilinear Pattern

FA

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00:56.19 05:45.9620/20

Courtesy Dr. Steve Bennett

Retina. 2006 Mar;26(3):365-7.

Courtesy Prof. Rathinam Sivakumar

Neuroretinitis – RetinitisVascular Occlusion

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Dengue Virus

Dengue• Flavivirus genus• Flaviviridae family• Positive-sense, single stranded RNA virus • ~ 11Kb.

Global Distribution of Dengue Virus

Courtesy Mr. Nicholas Jones, Uveitis, 2nd Edition, 201350-100M New Cases per Year

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10969

1552

6169

8253

551

33

642

243

554

772

654

364

0 2000 4000 6000 8000 10000 12000

2010

2011

2012

2013

2014

2015 YTD

Cases of Dengue Reported to the CDC by Year

Imported Locally Aquired

< 1 / 100,000 / yearMostly Florida and Texas

http://diseasemaps.usgs.gov/mapviewer/Dengue

Locally Acquired33 Cases

Imported364


Systemic Disease• 2 – 14 day incubation• Asymptomatic• Non-specific febrile illness• Classic Dengue fever

• High Fever• Severe Headache• Myalgia• Arthralgia• Malaise• Nausea• Vomiting• Maculopapular Skin Rash

• 10% - Dengue Hemorrhagic Fever Shock Syndrome

https://viraldiseasesd.wikispaces.com/Dengue+Fever

https://microbewiki.kenyon.edu/index.php/Dengue_transmission

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Ocular Disease75% BilateralMay be Serotype Specific• Subconjunctival hemorrhage• AC inflammation• Vitreous inflammation• Retinal hemorrhage• Retinal vasculitis• Retinal vascular occlusion• Retinitis• Deep retinal spots / foveolitis• RPE mottling• Serous retinal detachment• Choroiditis (ICGA)

HemorrhageYellow-White Lesions

Dengue VirusSubconjunctival HemorrhagePlatelet Counts < 50,000/ul

https://openi.nlm.nih.gov/detailedresult.php?img=2566568_1757-1626-1-204-1&req=4

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Courtesy Dr. Stephen Teoh

Dengue VirusActive Lesions



FAFA



ICGAICGA



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“Foveolitis” Courtesy Dr. Stephen Teoh Courtesy Dr. Padmamalini Mahendradas

Dengue Virus Infection20/40

CF


Courtesy Prof. Khalid Tabbara

Dengue VirusInactive Lesions

Courtesy Prof. Khalid Tabbara

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Courtesy Dr. Srinivasan Sanjay

Dengue Virus+ 9 Months, Inactive

Courtesy Dr. Srinivasan Sanjay

Dengue VirusActive Lesions – Retinitis / Intraretinal Hemorrhage

Courtesy Prof. Chee Soon Phaik

Dengue VirusActive Lesions – Retinitis / Intraretinal Hemorrhage


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Dengue VirusActive Lesions – Vasculitis


Dengue VirusActive Lesions – Vasculitis


Dengue VirusActive Lesions – Foveolitis


Chikungunya• Alphavirus genus• Togaviridae family. • Positive-sense, single stranded RNA virus • ~ 12Kb.

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Described in 1953, East AfricaTanzaniaMozambique

In “Makonde,” Chikungunya means “to walk bent over.”

A reference to the stooped posture of many sufferers.

Chikungunya

Global Distribution of Chikungunya

Courtesy Mr. Nicholas Jones, Uveitis, 2nd Edition, 2013

http://diseasemaps.usgs.gov/mapviewer/Chickunugnya

Locally Acquired152

Imported538


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https://www.sciencenews.org/article/chikungunya-move June 2, 2015 https://www.sciencenews.org/article/chikungunya-move June 2, 2015

Systemic Disease• 2 – 14 day incubation• Acute

• Fever• Headache• Low back pain• Severe joint pain• Myalgia• Malaise• Nausea• Vomiting

• Severe – multi-organ failure, CNS involvement, death

In “Makonde,” Chikungunya means “to walk bent over.”

Ocular Disease• AC inflammation +/- high IOP• Vitreous inflammation• Retinal hemorrhage• Retinal vasculitis• Retinal vascular occlusion• Retinitis• Neuroretinitis• Serous retinal detachment• Choroiditis (ICGA)

Courtesy Dr. Padmamalini Mahendradas

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Am J Ophthalmol 2007; 144:552-556

Common• AC / Vitreous cell• Neuritis• Retinitis +/- SRD

Courtesy Prof. Richard Rosen

20/30 20/50Chikungunya Fever

Courtesy Prof. Richard Rosen

20/30 20/50

1:11 2:16

Chikungunya Fever

Courtesy Prof. Richard Rosen20/20 20/20

+ Two MonthsOral CST, Topical CST, Topical Cyloplegic / Mydriatic

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Courtesy Prof. Rathinam Sivakumar

Chikungunya Fever

Courtesy Dr. Padmamalini Mahendradas

4 WEEKS 16 WEEKS

20/30

20/4020/20

20/20

Presentation

Courtesy Dr. Annie Mathai and Dr. Nidhi Relhan

Chikungunya Fever

Am J Ophthalmol 2007; 144:552-556

Vision at Last Visit Variable

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Zika Virus

Zika Virus• Flavivirus genus• Flaviviridae family• Positive-sense, single stranded RNA virus • ~ 12Kb.

Uganda1947 - Monkeys

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How Zika Spread – 70-year Migration

Africa Southeast Asia Pacific Islands Americas

1947

20072016

1970s

New England Journal of Medicine; January 13, 2016 DOI: 10.1056/NEJMp1600297

Systemic Disease

• 1 in 5 symptomatic• 2 to 10 day incubation• Non-specific febrile illness• Fever• Arthralgias• Maculopapular Skin Rash

https://en.wikipedia.org/wiki/Zika_virus#/media/File:Zika.Virus.Rash.Arm.2014.jpg

Maculopapular Rash

http://www.memeornah.com/trending/zika-virus-rash/887/

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Testing

• Serum PCR within 7 days• Thereafter serum PRNT

(Plaque ReductionNeutralization Technique) assay.

• Antibody crossreactivitywith Dengue, WNV, etc

http://www.medscape.com/viewarticle/862671

Areas Susceptible to Spread of Zikahttp://www.nytimes.com/interactive/2016/02/06/science/air-travel-from-countries-affected-by-zika.html

Risk of Local Zika Transmission: Year Round Seasonal

http://www.nytimes.com/interactive/2016/02/06/science/air-travel-from-countries-affected-by-zika.html

US – Brazil Travel Routes

Zika Risk

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Zika Risk

Maculopapular RashConjunctivitis

www.eurosurveillance.com

Child with Microcephaly, Recife, Brazilhttp://www.who.int/emergencies/zika-virus/situation-report-26-02-2016.pdf

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“Severe Macular Neuroretinal Atrophy”

Courtesy Dr. Camila Ventura of the Altino Ventura Foundation in Recife, Brazil

25%10%15%10%10%75%25%40%15%15%

10 Microcephalic Infants

• 40% Exopharia• 20% Esophoria• 10% Horizontal Nystagmus

• 65% RPE Alterations• 25% Optic Disc Hypoplasia• 15% RPE Atrophy• 15% Optic Disc Pallor


RPE AlterationsAtophic Lesion


RPE AlterationsAtrophic Lesions

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RPE AlterationsAtrophic Lesions

http://www.nature.com/eye/journal/v19/n5/images/6701857f15.jpg

Optic Disc Hypoplasia - Signs1) Small disc

(Disc-foveal distance > 3 DD)2) “Double-ring sign”3) +/- Vascular tortuosity

JAMA Ophthalmol. 2016 Aug 1;134(8):912-918.

40 Infants with MicrocephalyZika + Mothers (64% symptomatic)

37 eyes (46%) of 22 patients (55%) with findings

Increased Frequency• First Trimester Exposure• Smaller Cephalic Perimeter

• RPE Mottling (28%)• Optic Disc Hypoplasia (18%)• Increased cip/Disc (11%)• RPE Atrophy (8%)• Optic Disc Pallor (8%)

RPE Alterations

RPE Atrophy

TortuosityVaso-

Obliteration

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39-year-old Male Physician• Known Zika Infection• Blurred vision one week later• 20/40 OU• IOP 40 mmHg OD; 28 mmHg OS• 1+ AC reaction OU• Cleared with topical CST and cycloplegic/mydriatic

N Engl J Med. 2016 Jul 28;375(4):394-396.

40s-year-old man• Rash and Conjunctivitis x 2 days• Serum PCR, IgM, PRNT +; AC PCR + Zika• 20/20 OD; 20/40 OS• IOP normal• Tr + AC reaction OD; 2+ OS• Cleared with topical CST and cycloplegic/mydriatic

Courtesy Dr. João M. Furtado, MD

Ophthalmology 2016; Jul 27. pii: S0161-6420(16)30507-3. doi: 10.1016/j.ophtha.2016.06.039. [Epub ahead of print]

64-year-old manerythematous rash / arthritis

for 10 days aftermission work in Haiti

Courtesy Dr. Will Parke

February, 201620/20


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February, 20163/200 for 3 days

IOP Normal

“Ring of Gray Perifoveal Coloration in Roughly a ‘Bull’s-Eye’ shape”Courtesy Dr. Will Parke

February, 20163/200 for 3 days

RPE Alterations


00:28.36


02:33.14


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April, 201620/20


20/20


3/200Presentation

+ 2 Months

Unilateral Acute Idiopathic Maculopathy (+Coxsackie)

Courtesy Dr. J. Michael Jumper, West Coast Retina

RPE Alterations

Ocular Disease• Conjunctivitis• AC inflammation (+/-hypertensive)• RPE Alterations / Atrophy• Optic Disc Hypoplasia (Neonates)• UAIM-like outer retinal inflammation

AnteriorUveitis

Conjunctivitis

UAIM

Adults

NeonatesRPE

Alterations

RPE Atrophy Disc Hypoplasia

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Zika Ophthalmic Images Courtesy of

Camila V. Ventura, MDRacife, Brazil

Rubens Belfort, Jr, MDSão Paulo, Brazil

Darius Moshfeghi, MDStanford, CA, USA

João M. Furtado, MDSão Paulo, Brazil

D. Wilkin (Will) Parke, III, MDMinneapolis, MN, USA

[email protected]

West Coast Retina, San Francisco, CA

Department of Ophthalmology, Stanford University School of … · 2016. 12. 13. · Uveitis Emmett...

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