West Nile Retinopathy

Key Points at a Glance

Key Points of This Disease

• West Nile retinopathy is a multifocal chorioretinitis caused by West Nile virus (WNV) infection.
• WNV is a flavivirus primarily transmitted by the bite of Culex mosquitoes.
• Approximately 80% of ocular complications are asymptomatic multifocal chorioretinitis.
• Chorioretinal lesions show a characteristic pattern of linear or scattered distribution.
• Serological tests (IgM antibody and neutralizing antibody) are necessary to confirm WNV infection.
• There is no established treatment; supportive care is the mainstay for systemic infection.
• In most cases, ocular disease is self-limiting and vision returns to baseline.

1. What is West Nile Retinopathy?

West Nile Retinopathy is a type of multifocal chorioretinitis caused by West Nile Virus (WNV) infection. WNV was first isolated in 1937 in the West Nile region of Uganda. In the United States, it was first identified in New York in 1999.

WNV is a single-stranded RNA flavivirus belonging to the Japanese encephalitis virus serogroup. It is a zoonotic disease, with wild birds serving as reservoir hosts. Horses and humans act as dead-end hosts.

80% of WNV infections in humans are subclinical. The remaining 20% present as a febrile illness. Approximately 1% of all infections result in West Nile neuroinvasive disease, manifesting as meningoencephalitis or acute flaccid paralysis.

Among ocular symptoms, asymptomatic multifocal chorioretinitis is the most common (about 80% of all ocular complications). Other ocular complications include anterior uveitis, retinal vasculitis, optic neuritis, subconjunctival hemorrhage, abducens nerve palsy, and nystagmus ¹².

Q How common is West Nile retinopathy?

A

Ocular complications are classified as rare complications among all WNV infections, but the most frequent ocular complication is multifocal chorioretinitis (asymptomatic in about 80%). Ocular involvement occurs via hematogenous spread (through the choroid) or neural spread from the central nervous system.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Subjective symptoms occur when there is active infection or when lesions involve the macula. However, about 80% of cases are asymptomatic.

When symptomatic, the following symptoms appear.

• Decreased vision: Caused by macular chorioretinal lesions or secondary complications.
• Floaters: Reflects inflammatory involvement of the vitreous body.
• Visual field defects: Occur depending on the distribution of lesions.
• Conjunctival injection: Associated with active ocular inflammation.
• Diplopia: Occurs when abducens nerve palsy (sixth cranial nerve palsy) is present.

Persistent visual impairment is caused by the following conditions:

• Chorioretinal scar at the fovea
• Choroidal neovascularization
• Vitreous hemorrhage
• Tractional retinal detachment
• Ischemic maculopathy
• Optic atrophy
• Retrogeniculate damage

In particular, cases complicated by occlusive retinal vasculitis have been reported to have a high frequency of permanent visual impairment in patients with diabetes and in the elderly ³⁴.

Clinical Findings

WNV lesions of the chorioretina are characteristically observed as linearly arranged or scattered chorioretinal lesions ⁵.

Active Lesions

Shape: Round, deep, with a creamy (milky white) appearance.

Distribution: Linear arrangement or scattered. A linear pattern along the nerve fiber layer suggests neural spread.

Inactive Lesions

Appearance: Atrophic, with a targetoid appearance accompanied by some pigmentation.

Course: Remains as chorioretinal scars after resolution of active inflammation.

Slit lamp examination is used to evaluate the morphology of active and inactive lesions.

Q Do all people infected with WNV develop eye symptoms?

A

Not necessarily. About 80% of ocular complications are asymptomatic multifocal chorioretinitis, and fundus lesions are often discovered without the patient reporting eye symptoms. Typically, they are found only after ophthalmologic examination following a diagnosis of WNV infection.

3. Causes and Risk Factors

WNV is transmitted by the bite of mosquitoes of the Culex genus, especially Culex pipiens. The virus enters the human body when an infected mosquito bites.

The incubation period is usually 2 to 15 days.

Major risk factors are listed below.

• Residence or travel in endemic areas: Endemic areas include parts of Africa, Europe, the Middle East, West Asia, Australia, and North America (from Canada to Venezuela). In the United States, 5,674 cases and 286 deaths were reported to the CDC in 2012.
• Older age (50 years or older): Higher risk of neuroinvasive disease and severe complications.
• Immunocompromised state: Includes cancer, diabetes, hypertension, kidney disease, and solid organ transplantation.
• Exposure to mosquitoes in summer: Outbreaks are most common in summer.
• Lack of protective measures: Risk increases when protective clothing or insect repellent is not used.

Other transmission routes besides mosquitoes include blood transfusion, organ transplantation, laboratory exposure, and vertical transmission during pregnancy.

Prevention and Daily Care

• In endemic areas, wear long sleeves and long pants, and use insect repellent containing DEET on exposed skin.
• Eliminate standing water sources such as puddles and containers that can breed mosquitoes.
• When receiving blood transfusions or organ transplants, ensure that the medical facility uses screened products.
• If diagnosed with WNV infection, it is recommended to have an eye examination to check the fundus.

4. Diagnosis and Testing Methods

Clinical Diagnosis

Since 80% of ocular WNV infections are asymptomatic, a high index of clinical suspicion is necessary. Actively suspect WNV infection in patients with the following history:

• Recent mosquito exposure history.
• History of travel to endemic areas
• History of blood transfusion or organ transplantation
• Preceding systemic symptoms such as fever, headache, myalgia, and maculopapular rash

To diagnose West Nile retinopathy in a patient not infected with WNV, serological confirmation of WNV infection itself is a prerequisite.

Ophthalmic Examination

The characteristics of each examination are shown below.

Examination	Characteristics
Fluorescein angiography (FA)	Active: early hypofluorescence → late staining. Inactive: central hypofluorescence + peripheral hyperfluorescence
Indocyanine green angiography (ICGA)	Can detect more lesions than FA
Autofluorescence (AF)	Highlights old scars more clearly than FA or fundus photography
OCT angiography (OCTA)	Noninvasively evaluates capillary nonperfusion areas in occlusive vasculitis3

Blood and Clinical Laboratory Tests

Serological testing for WNV IgM and neutralizing antibodies in blood or cerebrospinal fluid is the basis for diagnosis.

• IgM antibody: Indicates active infection. May not become positive within the first 8 days after infection.
• IgG antibody alone positive: Only indicates past flavivirus infection and does not imply active infection.
• Plaque reduction neutralization test (PRNT): Used as a confirmatory test.
• Immunofluorescence assay (IFA) and nucleic acid amplification test (NAT): Adjunctive diagnostic tools.

Nucleic acid tests such as the Procleix® WNV Assay are used for pre-transfusion screening.

Differential Diagnosis

Many diseases present with symptoms similar to WNV.

• Central nervous system symptoms: Herpes simplex virus-1 encephalitis, enterovirus, Japanese encephalitis, EB virus infection, HHV-6, legionellosis, Rocky Mountain spotted fever
• Ophthalmic differential diagnosis: Syphilitic chorioretinitis, toxoplasmic chorioretinitis, sarcoidosis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), birdshot chorioretinopathy

5. Standard Treatment

Currently, there is no established specific treatment for WNV infection.

Management of Systemic Infection

For systemic infection, supportive treatment is the mainstay.

• Mild cases: Outpatient observation. Symptomatic treatment for fever, headache, myalgia, etc.
• Severe cases: Hospitalization may be required for intravenous fluids, respiratory management, etc.

Ophthalmic Management

Specific ocular treatment is generally unnecessary, and in most cases, ocular disease follows a self-limited course.

• Choroidal neovascularization (CNV): If secondary CNV occurs, anti-VEGF therapy may be considered.
• For complications such as vitreous hemorrhage, tractional retinal detachment, and ischemic maculopathy, ophthalmic interventions should be considered according to each condition.

Prevention

Primary prevention of infection is the cornerstone of WNV infection control. Wearing protective clothing, using insect repellent, and controlling mosquito larvae are proven measures. A WNV vaccine is currently under development, and clinical trials have not been completed.

Treatment Considerations

• No antiviral drugs for WNV infection have been established to date.
• Most chorioretinal lesions are self-limited, but macular lesions and secondary complications (CNV, vitreous hemorrhage, etc.) may result in visual impairment.
• When West Nile neuroinvasive disease (meningoencephalitis) is present, collaboration with neurology and infectious disease departments is essential.

Q Can West Nile retinopathy be cured?

A

In the majority of cases, ocular disease is self-limited and vision returns to baseline. However, complications such as foveal chorioretinal scarring, choroidal neovascularization, and optic atrophy may result in permanent visual impairment.

6. Pathophysiology and Detailed Pathogenesis

The exact molecular pathophysiology of WNV infection is under investigation, but the following mechanisms are supported.

WNV enters cells through interaction with Toll-like receptor 3 (TLR3). WNV infection triggers a TLR3-induced inflammatory response that may weaken the blood-brain barrier. This allows the virus to enter the brain and cause more severe neuropathology.

As a member of the Flaviviridae family, WNV is a single-stranded RNA virus that uses host cell proteins to produce progeny virus particles.

Two routes of ocular involvement are hypothesized.

• Hematogenous spread: During the viremic phase, the virus reaches the choroid and causes inflammation of the retinal pigment epithelium and outer retina through choroidal small vessels.
• Neural spread: Propagation from the central nervous system to the retinal nerve fiber layer. The pattern of linear scarring along the distribution of the nerve fiber layer suggests this route.

In addition, individuals with homozygous mutations in the CCR5 (chemokine receptor 5) gene, while protected against HIV infection, may be predisposed to developing neurological symptoms of WNV.

7. Latest Research and Future Perspectives (Research-stage Reports)

For patients: Please read this

The following content is currently in the research stage or under clinical trials, and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Vaccine Development

Human WNV vaccines are still in development and clinical trials. WNV vaccines for horses have been approved in some countries, but research continues for human application.

Antiviral Drug Research

Ribavirin, interferon, and intravenous immunoglobulin (IVIG) have been used in in vitro or animal model studies, but their efficacy in humans has not been established.

Long-term Prognosis Studies of Ocular Complications

Long-term outcome data on WNV ocular complications such as choroidal neovascularization and optic atrophy are limited. Further investigation is needed regarding the application and efficacy of anti-VEGF therapy.

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8. References

Footnotes

1. Rousseau A, Haigh O, Ksiaa I, Khairallah M, Labetoulle M. Ocular Manifestations of West Nile Virus. Vaccines (Basel). 2020;8(4):641. PMID: 33147758. ↩

2. Ruiz-Lozano RE, Zafar S, Berkenstock MK, Liberman P. Ocular manifestations of West Nile virus infection: A case report and systematic review of the literature. Eur J Ophthalmol. 2025;35(3):844-855. PMID: 39659186. ↩

3. Khairallah M, Kahloun R, Gargouri S, et al. Swept-Source Optical Coherence Tomography Angiography in West Nile Virus Chorioretinitis and Associated Occlusive Retinal Vasculitis. Ophthalmic Surg Lasers Imaging Retina. 2017;48(8):672-675. PMID: 28810044. ↩ ↩²

4. Chan CK, Limstrom SA, Tarasewicz DG, Lin SG. Ocular features of west nile virus infection in North America: a study of 14 eyes. Ophthalmology. 2006;113(9):1539-1546. PMID: 16860390. ↩

5. Khairallah M, Ben Yahia S, Ladjimi A, et al. Chorioretinal involvement in patients with West Nile virus infection. Ophthalmology. 2004;111(11):2065-2070. PMID: 15522373. ↩