Ebola Virus Disease (Ophthalmic Complications)

Key points at a glance

Key points of this disease

• Ebola virus disease (EVD) is a severe hemorrhagic fever with a fatality rate of around 50%. During the 2014 West African outbreak, over 28,000 people were infected. ¹⁾
• Up to 60% of survivors report ocular symptoms after acute infection, with the most common complication being uveitis (affecting up to one-third of survivors).
• The virus has been confirmed to persist in the aqueous humor (intraocular fluid) after recovery, making ophthalmic infection management important. ¹⁾³⁾
• Uveitis often develops 3–8 weeks after discharge, with risk factors including high viral load, acute-phase conjunctival injection, and older age.
• FDA-approved antiviral drugs (Inmazeb, Ebanga) and a vaccine (Ervebo) exist, but all target the Zaire strain. ¹⁾
• Future challenges include elucidating the mechanism of viral persistence in the eye as an immune-privileged organ and establishing effective treatments for ocular complications. ⁷⁾

1. Ebola Virus Disease (Ocular Complications)

Ebola virus disease (EVD) is a zoonotic infection caused by a negative-sense single-stranded enveloped RNA virus belonging to the genus Ebolavirus, family Filoviridae. Four species (Zaire, Sudan, Taï Forest, Bundibugyo) primarily cause disease in humans. Among the six strains (EBOV, SUDV, TAFV, BDBV, BOMV, RESTV), Zaire ebolavirus (EBOV) is considered the most severe. ¹⁾

First reported in 1976 in the former Zaire (now the Democratic Republic of the Congo), it caused 318 cases with an 88% fatality rate. ¹⁾ During the 2014 West African outbreak, over 28,000 cases and approximately 11,000 deaths occurred, with an overall average fatality rate of about 50%. The fatality rate varies significantly by strain: 57–90% for Zaire, 41–65% for Sudan, and 40% for Bundibugyo. ¹⁾ The natural reservoir is thought to be fruit bats of the family Pteropodidae, and transmission occurs through direct contact with blood or body fluids of infected animals or patients. ¹⁾

Ocular complications occur as part of Post-Ebola Virus Disease Syndrome (PEVDS) after recovery from acute infection. Up to 60% of survivors report some ocular symptoms after acute infection, with the most frequent being uveitis, affecting up to one-third of all survivors.

The table below shows the main strains of Ebola virus and their fatality rates.

Strain (abbreviation)	Estimated fatality rate	Main affected regions
Zaire (EBOV)	57–90%	DRC, Gabon
Sudan (SUDV)	41–65%	Sudan, Uganda
Bundibugyo (BDBV)	40%	Uganda

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Acute Phase (Incubation period 2–21 days, average 8–10 days)

Acute systemic symptoms include fever, headache, muscle pain, joint pain, abdominal pain, vomiting, diarrhea, and bleeding, among others. ¹⁾ The following eye symptoms are observed.

• Conjunctival injection/hyperemia: Occurs in 48–58% of cases. Severe bilateral hyperemia is considered a predictor of acute EVD infection.
• Subconjunctival hemorrhage: Develops reflecting a bleeding tendency.
• Vision loss: Unexplained vision loss can occur even in the acute phase.

Post-infection (PEVDS) Subjective Symptoms

• Vision loss: Due to uveitis or cataract. It has been reported that 39% of affected eyes had vision worse than 20/400.
• Foreign body sensation, photophobia, glare, halos: Associated with anterior and intermediate uveitis.
• Pain: Ocular pain associated with anterior uveitis.

Clinical Findings

Acute Ocular Findings

Conjunctival injection (48–58%): Bilateral injection is a predictor of acute infection.

Subconjunctival hemorrhage: A finding reflecting hemorrhagic diathesis.

Unexplained visual loss: May occur even in the acute phase.

PEVDS Ocular Complications

Uveitis (most common): Anterior, intermediate, posterior, or panuveitis. Onset 3–8 weeks after discharge. Unilateral and anterior uveitis are most common.

Cataract: Develops secondary to uveitis. Most common indication for surgical intervention.

Episcleritis and corneal stromal keratitis: May occur relatively early.

Optic neuropathy and ocular motility disorder: Findings in severe cases.

Viral Persistence in Anterior Chamber

Isolation of viable virus from aqueous humor: Not isolated from tears, only detected in aqueous humor.

RT-PCR at 19–34 months: All reported cases were negative.

In a cohort study of 112 people in Sierra Leone published in December 2024, the prevalence of uveitis was 21%, with posterior uveitis accounting for 57% and panuveitis for 29%, and 39% of affected eyes had visual acuity less than 20/400.

Q When does uveitis typically develop after Ebola virus infection?

A

It often develops 3 to 8 weeks after discharge. Unilateral anterior uveitis is the most common type, and risk factors include high viral load during the acute phase, conjunctival injection, and older age. Reports indicate that 21–33% of survivors develop uveitis. See also “5. Standard Treatment” for details.

3. Causes and Risk Factors

EBOV is an enveloped negative-sense RNA virus with a genome of approximately 19 kb and 7 genes. ¹⁾⁵⁾ Fruit bats are considered the natural reservoir, and transmission occurs through direct contact with blood or body fluids of infected animals or humans. ¹⁾

Risk factors for ocular complications (PEVDS) are as follows:

• High viral load during the acute phase: Associated with viral entry into the aqueous humor.
• Conjunctival injection during the acute phase: A predictor of uveitis development.
• Older age: Associated with increased risk of ocular complications in survivors.
• Persistence of virus in body fluids: Virus may persist in semen and aqueous humor after recovery. ¹⁾³⁾

Infection Prevention and Precautions for Healthcare Workers

• Ebola virus is primarily transmitted through direct contact with blood, body fluids, or secretions. Aerosol transmission does not usually occur.
• Since viable virus may persist in the aqueous humor of survivors, appropriate personal protective equipment (PPE) should be used during ophthalmic procedures.
• Virus detection in tears has not been reported, so the risk during routine eye examinations is considered low.

4. Diagnosis and Testing Methods

Diagnosis in the acute phase

Definitive diagnosis of acute EVD is only possible in BSL-4 research facilities. ¹⁾

Test method	Timing	Notes
RT-PCR (NAT)	Early after onset	WHO recommended. A negative result within 48 hours of exposure cannot rule out infection. 1)
IgM/IgG serology	After acute phase	Becomes positive days to weeks after infection
Virus isolation	Acute phase	Only possible in BSL-4 facilities

Note that a negative result within 48 hours of exposure cannot rule out infection. ¹⁾

Ophthalmic Diagnosis After Infection (PEVDS)

Multimodal imaging is used for ophthalmic diagnosis after infection.

• Slit-lamp microscopy: Evaluate findings of anterior uveitis (keratic precipitates, flare, anterior chamber cells).
• Fundus photography and fluorescein angiography: Evaluate posterior uveitis and chorioretinitis.
• OCT (optical coherence tomography): Evaluate retinal lesions. Abnormalities in the outer retinal layers have been reported as characteristic findings.
• Characteristics of retinal lesions: Predominantly non-pigmented lesions. Accompanied by “Dark without pressure (DWP).” Peripapillary lesions tend to follow the horizontal raphe and avoid the fovea.

Differential Diagnosis

• Acute phase: Differentiation from chikungunya fever, dengue fever, typhoid fever, Zika virus infection, and malaria is necessary.
• Post-infectious uveitis: Differentiate from HSV, cytomegalovirus, EBV, West Nile virus, dengue, Zika, POHS (presumed ocular histoplasmosis), sarcoidosis, syphilis, tuberculosis, and toxoplasmosis.

Q What are the imaging findings of retinal lesions caused by Ebola virus?

A

Retinal lesions are characteristically non-pigmented and accompanied by “Dark without pressure (DWP).” Peripapillary lesions tend to follow the horizontal raphe and avoid the fovea. OCT shows abnormalities in the outer retinal layers. Multimodal imaging is useful for diagnosis.

5. Standard Treatment

Systemic Treatment in the Acute Phase

The mainstay of acute EVD management is supportive care (fluid and electrolyte management, symptomatic treatment). Two antiviral drugs approved by the FDA in October 2020 are available. ¹⁾

• Inmazeb (atoltivimab/maftivimab/odesivimab-ebgn): A combination of three monoclonal antibodies.
• Ebanga (ansuvimab-zykl, mAb114): Single monoclonal antibody.

The PALM trial reported 28-day mortality of 34% in the mAb114 group, 35% in the REGN-EB3 (precursor of Inmazeb) group, compared to 50% with the former standard drug ZMapp and 53% with remdesivir. ⁷⁾⁸⁾

Acute Systemic Treatment

Supportive care: Fluid and electrolyte correction and symptomatic treatment are fundamental.

Inmazeb: FDA approved (October 2020). Combination of three monoclonal antibodies. Targets Zaire strain.

Ebanga (mAb114): FDA approved (October 2020). Single monoclonal antibody. Targets Zaire strain.

Treatment of Uveitis

Steroid eye drops: 4 times daily to every hour (depending on severity). Combine with cycloplegics.

Oral prednisone: Consider systemic steroids for severe cases.

Intravitreal steroid injection: An option for refractory cases.

Immunomodulatory drugs: Their role is currently unknown.

Cataract Surgery

Most common surgical intervention: Performed for uveitis-related cataract.

Preoperative evaluation: Consider the risk of residual virus in the aqueous humor. RT-PCR at 19–34 months was negative in all reported cases.

Postoperative management: High risk of complications due to prior uveitis, requiring careful management.

Precautions for Ophthalmic Treatment of Ebola Survivors

• Because viable virus may persist in the aqueous humor, appropriate infection control protocols must be followed during intraocular surgery.
• In EVD-endemic areas (e.g., DRC), access to ophthalmic care is limited, and treatment delays can worsen visual prognosis. ³⁾
• Cataract surgery in survivors with a history of uveitis carries a higher risk of postoperative inflammation and complications than usual.

Q Is there any special risk for cataract surgery in Ebola survivors?

A

Due to a history of uveitis, the risk of postoperative complications is higher than usual. There is also a risk of viral persistence in the aqueous humor, but reports at 19–34 months showed all cases were RT-PCR negative. Adherence to appropriate infection control protocols during surgery is recommended.

6. Pathophysiology and Detailed Pathogenesis

Viral Cell Entry Mechanism

EBOV enters through mucous membranes or abraded skin. After the envelope glycoprotein (GP) binds to the host cell surface, the virus is internalized by macropinocytosis. Within endosomes, cathepsin L/B cleaves the GP1 domain, which then binds to the intracellular NPC1 (Niemann-Pick C1) receptor, triggering membrane fusion. ⁵⁾

Initial infection targets are macrophages and dendritic cells (antigen-presenting cells), which mediate systemic viral dissemination. Viral immune evasion mechanisms include VP24 inhibiting MAPK and NF-κB signaling, and VP35 inhibiting dsRNA recognition and IFN expression. ⁵⁾

Ocular Entry and Immune Privilege

The eye is one of the “immune-privileged organs” (along with the brain and reproductive organs) where the virus can persist after acute infection. ⁷⁾ During acute EVD, EBOV is thought to enter ocular tissues, evade immune surveillance, and persist in the aqueous humor. While virus has not been isolated from tears, viable virus has been isolated from the aqueous humor, suggesting that the unique immune-privileged environment of the eye contributes to viral persistence. ⁷⁾

It has been shown that EBOV enters and persists in immune-privileged tissues including the eye during acute EVD, with viable virus isolated from the aqueous humor but not from tears. ⁷⁾

Q Why does Ebola virus persist in the eye?

A

The eye, along with the brain and reproductive organs, is called an “immune-privileged organ,” an environment with limited immune surveillance. During acute EVD, the virus is thought to enter the anterior chamber and persist by escaping the immune response. Viable virus has been isolated from the aqueous humor but not from tears. ⁷⁾

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7. Latest Research and Future Prospects (Investigational Reports)

For patients: Please read this

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

Vaccines

• Ervebo (rVSV-ZEBOV): Approved by the FDA in December 2019. For individuals aged 18 and older. Single intramuscular dose. Targets only the Zaire strain. ¹⁾ Administered over 250,000 times during the 2018–2020 outbreak in the DRC. ³⁾
• Zabdeno/Mvabea (two-dose vaccine): Two doses administered 8 weeks apart. For individuals aged 1 year and older. ¹⁾

Research on Antiviral Drugs and Neutralizing Antibodies

The broadly neutralizing antibody MBP134AF has shown efficacy against three strains (EBOV, SUDV, BDBV), and research is ongoing. Whether anti-EBOV treatments are effective against viral persistence in immune-privileged organs such as the eye remains unclear at this time. ⁷⁾

Small Molecule Entry Inhibitors

Research is progressing on small molecule compounds that inhibit viral entry via the NPC1 receptor. ⁵⁾

• Toremifene: Inhibits cell entry in vitro with EC50 = 0.162 μM.
• Berbamine hydrochloride: Achieved 100% survival in a mouse model.
• Remdesivir: In vitro EC50 = 0.06 μM against EBOV. However, clinical efficacy in the PALM trial was limited (lethality rate 53%). ⁵⁾⁸⁾

Q Are there vaccines or treatments for Ebola virus?

A

Vaccines include Ervebo (FDA approved December 2019, single dose) and Zabdeno/Mvabea (two doses, for individuals aged 1 year and older). As treatments, Inmazeb and Ebanga were FDA approved in October 2020, but both target the Zaire strain. ¹⁾ No effective treatments currently exist for other strains (such as the Sudan strain).

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8. References

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2. Rwagasore E, Nsekuye O, ElKhatib Z, et al. Lessons learned from Sudan Ebola Virus Disease (SUDV) preparedness in Rwanda. J Epidemiol Glob Health. 2023;13:528-538.
3. Ahmad B, Sagide M, Ntamwinja S, et al. National burden of Ebola virus disease in Democratic Republic of the Congo. Ann Med Surg. 2024;86:4579-4585.
4. Drogy M, Glezer C, Engel E, et al. Systematic review and meta-analysis of female reproductive health following Ebola virus disease. Am J Trop Med Hyg. 2025;112:663-673.
5. Durante D, Murugesh V, Kalanquin T, et al. Small molecule drug discovery for Ebola virus disease. RSC Med Chem. 2025;16:4571-4598.
6. Nash RK, Bhatia S, Morgenstern C, et al. Ebola Virus Disease mathematical models and epidemiological parameters. Lancet Infect Dis. 2024;24:e762-e773.
7. O’Donnell KL, Marzi A. Immunotherapeutics for Ebola Virus Disease: hope on the horizon. Biologics. 2021;15:79-86.
8. Gao Y, Zhao Y, Guyatt G, et al. Effects of therapies for Ebola virus disease: a systematic review and network meta-analysis. Lancet Microbe. 2022;3(9):e683-e692.