Anterior Segment Findings
Subconjunctival hemorrhage: Most common finding in the acute phase
Episcleritis: Inflammatory reaction
Anterior uveitis: Observed in the acute phase and up to 5 months after remission. Can occur even in asymptomatic cases
Dengue Virus-Related Ocular Disease
Key Points at a Glance
Section titled “Key Points at a Glance”1. What is dengue virus-associated ocular disease?
Section titled “1. What is dengue virus-associated ocular disease?”Dengue virus is a positive-sense single-stranded RNA virus of the family Flaviviridae, with at least four serotypes. It is transmitted by the bite of an infected Aedes aegypti or Ae. albopictus mosquito.
Approximately 400 million people are infected with dengue virus each year, 100 million develop symptoms, and 22,000 die. It occurs in over 100 countries and is widely distributed across Asia, Latin America, the Caribbean, Africa, and the Middle East.
Infection with one serotype provides immunity only to that serotype. Reinfection with a different serotype is possible, and secondary infection increases the risk of progression to dengue hemorrhagic fever.
:::tip Precautions before traveling to endemic areas The best way to prevent dengue virus infection is to avoid mosquito bites. In endemic areas, use insect repellent day and night, wear long sleeves, and use mosquito nets. Dengvaxia® is approved in the United States for individuals aged 9–16 with confirmed prior dengue infection, but vaccination without prior infection may increase the risk of severe disease. :::
2. Main symptoms and clinical findings
Section titled “2. Main symptoms and clinical findings”Systemic symptoms
Section titled “Systemic symptoms”The systemic symptoms of dengue fever (acute phase 2–7 days) are as follows.
- High fever, headache, retro-orbital pain
- Joint pain, muscle pain (also called “breakbone fever”)
- Rash, nausea, vomiting
- Severe cases (about 5%): shock, bleeding tendency, multi-organ failure
The average fatality rate is 2.5%.
Subjective Ocular Symptoms
Section titled “Subjective Ocular Symptoms”- Ocular hyperemia and photophobia
- Decreased visual acuity and scotoma
- Floaters
- Retro-orbital pain
Clinical Ocular Findings
Section titled “Clinical Ocular Findings”Ocular complications of dengue fever are diverse, ranging from the anterior segment to the posterior segment.
Posterior Segment Findings
Dengue maculopathy: retinal hemorrhage, soft exudates, macular edema
Serous retinal detachment: a serious complication causing vision loss
Choroidal effusion: may be accompanied by low intraocular pressure
Vasculitis/vascular occlusion: risk factors for poor visual prognosis
Neuroretinitis/optic neuritis: rare, but dengue virus can cause optic neuritis and retinochoroiditis
OCT classification of dengue maculopathy
Section titled “OCT classification of dengue maculopathy”The Eye Institute Dengue-Related Ocular Complications Working Group reported the following three types based on OCT findings.
| Type | OCT Findings | Notes |
|---|---|---|
| Type 1 | Diffuse retinal thickening | Mildest |
| Type 2 | Cystoid macular edema | Moderate vision loss |
| Type 3 | Foveolitis | Destruction of outer retinal layers. Requires time for vision recovery |
Agarwal et al. reported foveolitis (destruction of the outer retinal layers) in 75% of eyes in a retrospective study of 16 patients (32 eyes). OCT angiography showed flow voids in the superficial and deep capillary plexuses, suggesting both inflammatory and ischemic mechanisms.
Q
When does anterior uveitis occur in dengue fever?
A
Anterior uveitis has been reported to occur not only during the acute febrile phase but also up to 5 months after disease resolution. It can occur even in asymptomatic patients, so ophthalmologic evaluation is necessary if ocular symptoms develop after dengue infection.
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”Viral Replication Mechanism
Section titled “Viral Replication Mechanism”Dengue virus performs viral translation and replication in the endoplasmic reticulum (ER) of host cells. During infection, the ER is reorganized and expanded, and the virus modifies the unfolded protein response (UPR) to create an environment favorable for its replication. It also enhances replication by inducing autophagy and regulating lipid metabolism.
Risk Factors for Ocular Complications
Section titled “Risk Factors for Ocular Complications”- History of residence or travel to endemic areas
- Progression to dengue hemorrhagic fever (severe form): The more severe the thrombocytopenia, the higher the risk of hemorrhagic ocular complications
- Secondary infection (reinfection with a different serotype)
4. Diagnosis and Testing Methods
Section titled “4. Diagnosis and Testing Methods”Systemic Diagnosis
Section titled “Systemic Diagnosis”The following are used for definitive diagnosis of dengue fever:
- Serological tests: ELISA or hemagglutination inhibition test
- Viral antigen (NS1) detection: Useful in the acute phase (1–5 days after fever onset)
- PCR method: Direct detection of viral RNA
- Virus isolation: Cell culture
Ophthalmic Evaluation
Section titled “Ophthalmic Evaluation”Confirm the following findings.
- Measurement of best-corrected visual acuity
- Intraocular pressure measurement
- Slit-lamp examination (anterior chamber cells/flare, KPs, corneal findings)
- Dilated fundus examination (macula, optic nerve, peripheral retina, vitreous)
- OCT: Important for classification and follow-up of maculopathy
- Fluorescein angiography (FA): Evaluation of vasculitis and vascular occlusion
Differential Diagnosis
Section titled “Differential Diagnosis”The following similar tropical infections should be differentiated.
- Chikungunya virus infection, Zika virus infection (same Aedes mosquito vector)
- Malaria, leptospirosis, rickettsial infections
- West Nile virus infection
- Ebola virus and hemorrhagic fever viruses (severe cases)
Q
If eye symptoms appear after returning from abroad, should dengue fever be suspected?
A
If eye redness, decreased vision, floaters, etc. appear within 2 weeks after travel to endemic areas (Asia, Central and South America, the Caribbean, Africa, the Middle East, etc.), dengue-related ocular complications should be included in the differential diagnosis. It is important to inform the ophthalmologist of your travel history.
5. Standard Treatment
Section titled “5. Standard Treatment”Systemic Treatment
Section titled “Systemic Treatment”There is no FDA-approved drug for dengue virus, and systemic treatment is mainly supportive care. For severe cases, rapid fluid resuscitation with crystalloids or colloids is performed.
Ophthalmic Treatment
Section titled “Ophthalmic Treatment”Treatment of ocular complications is based on symptoms and the degree of inflammation.
| Condition | Treatment |
|---|---|
| Anterior uveitis | Topical steroid eye drops + cycloplegic agents |
| Posterior segment lesions (maculopathy, serous retinal detachment) | Oral prednisone 0.5–1.0 mg/kg |
| Vasculitis | Oral steroids (under careful monitoring) |
| Serous retinal detachment | Most resolve spontaneously with conservative observation |
Observation
Section titled “Observation”- Anterior uveitis: Examination every 1–2 weeks until symptoms resolve
- Maculopathy: Regular monitoring with OCT
- Vasculitis/vascular occlusion: Regular fundus examination and fluorescein angiography
:::caution Note Dengue fever may be accompanied by thrombocytopenia; when performing ophthalmic procedures (intravitreal injection, surgery), collaboration with a hematologist may be necessary. During steroid therapy, also monitor platelet count trends. :::
6. Pathophysiology and Detailed Mechanism of Onset
Section titled “6. Pathophysiology and Detailed Mechanism of Onset”Mechanism of Ocular Complications
Section titled “Mechanism of Ocular Complications”The mechanism of dengue-related ocular complications is explained by a combination of inflammatory mechanisms and hemorrhagic/ischemic mechanisms.
Inflammatory mechanism: The virus directly invades the eye, or immune complexes and cytokines damage the blood-ocular barrier, inducing inflammation.
Hemorrhagic/ischemic mechanism: Thrombocytopenia and vascular wall damage cause subconjunctival hemorrhage, vitreous hemorrhage, and retinal hemorrhage. Agarwal et al. reported that OCT angiography revealed capillary flow voids, indicating that ischemia is also an important cause of ocular complications.
Timing of ocular complications: In a retrospective review of 13 patients, the onset of ocular symptoms coincided with the nadir of platelet count, suggesting that the depth of thrombocytopenia is associated with the development of ocular complications.
7. Latest Research and Future Perspectives
Section titled “7. Latest Research and Future Perspectives”Advances in Multimodality Imaging
Section titled “Advances in Multimodality Imaging”The introduction of OCT angiography (OCTA) has enabled detailed evaluation of capillary blood flow changes in dengue maculopathy. It has been reported that perfusion defects persist after treatment, and future research is expected to explore these as predictors of visual function recovery.
Development of Antiviral Drugs
Section titled “Development of Antiviral Drugs”Currently, there are no FDA-approved antiviral drugs for dengue virus, but compounds targeting viral factors (NS3 helicase, NS5 polymerase) and host factors are under development. Improved accuracy of acute-phase diagnostic assays is also expected to pave the way for early therapeutic intervention.
Challenges for Prognosis Improvement
Section titled “Challenges for Prognosis Improvement”- In cases with foveolitis, visual recovery is slow and may result in long-term visual impairment.
- In cases with vasculitis, 7 out of 13 patients had a final visual acuity of 6/12 to 6/60, indicating the need for aggressive treatment strategies.
- In patients with anterior uveitis, 83% of 65 eyes with various ocular symptoms such as anterior uveitis, optic neuritis, and maculopathy maintained visual acuity of 6/12 (0.5) or better at 1 year, and the prognosis is generally good.
:::danger Disclaimer This article is educational content intended to provide medical information. For diagnosis and treatment of individual patients, please consult your primary care physician or specialist. Please refrain from self-diagnosis or self-treatment based on the information in this article. :::
8. References
Section titled “8. References”- Teoh SC, Chee CK, Laude A, et al.; Eye Institute Dengue-related Ophthalmic Complications Workgroup. Optical coherence tomography patterns as predictors of visual outcome in dengue-related maculopathy. Retina. 2010;30(3):390-398.
- Agarwal A, Aggarwal K, Dogra M, et al.; OCTA Study Group. Dengue-Induced Inflammatory, Ischemic Foveolitis and Outer Maculopathy: A Swept-Source Imaging Evaluation. Ophthalmol Retina. 2019;3(2):170-177.
- Roy SK, Bhattacharjee S. Dengue virus: epidemiology, biology, and disease aetiology. Can J Microbiol. 2021;67(10):687-702. PMID: 34171205.