Rift Valley fever (RVF) is a zoonotic disease caused by the Rift Valley fever virus, a single-stranded negative-sense RNA arbovirus with a tripartite genome. It is classified under the genus Phlebovirus, family Bunyaviridae.
Systemic symptoms include headache, retro-orbital pain, myalgia, and arthralgia. Severe disease occurs in less than 2% of cases but can lead to serious complications such as encephalitis, hepatitis, hemorrhagic fever, and visual impairment.
Ocular symptoms occur in a subset of RVF patients, with reported frequency varying by outbreak size and detection methods. In a large outbreak in southwestern Saudi Arabia, visual symptoms appeared 4–15 days after systemic symptom onset, and posterior segment lesions, primarily macular and paramacular retinitis, were frequently observed 2).
Since the 1950s, outbreaks of Rift Valley fever have been reported in East African and Southern African countries. It spread to West Africa in the 1980s and to Yemen and Saudi Arabia through livestock trade in the 2000s. In the 21st century, outbreaks have occurred in Kenya, Somalia, Egypt, Madagascar, Tanzania, South Africa, Namibia, Niger, Uganda, and Mauritania.
The endemic transmission cycle is maintained by mosquitoes of the Aedes genus. During El Niño-Southern Oscillation (ENSO) events, mosquito breeding sites increase, leading to an epizootic transmission cycle. Secondary vectors include Anopheles, Culex, and Mansonia species.
Human infection occurs through the following two routes:
Rarely, vertical transmission has also been reported.
There have been no reports of occurrence in Japan. The main endemic areas are Africa and the Middle East. This disease is considered in the differential diagnosis when a patient with a history of travel to endemic areas presents with uveitis of unknown cause.
After the onset of Rift Valley fever, the period until the appearance of unilateral or bilateral visual symptoms is generally 4 to 15 days 2).
Acute hemorrhagic conjunctivitis may also present as an anterior segment symptom.
Posterior Segment Findings
Macular and perimacular retinitis: The most characteristic and frequent ocular lesion. It is observed as a well-defined lesion, sometimes accompanied by surrounding milky-white lesions and retinal hemorrhages 1,2).
Retinal vasculitis: Primarily phlebitis; arteritis is less common. Sheathing of blood vessels is observed.
Vitritis: Vitreous cells and vitreous opacities occur.
Optic disc edema or pallor: Observed in severe cases.
Anterior Segment Findings
Anterior uveitis: Transient inflammation with non-granulomatous keratic precipitates (+1 to +3 cells) and anterior chamber flare.
Panuveitis: Inflammation extending from the anterior to the posterior segment.
Acute hemorrhagic conjunctivitis: May appear as a finding limited to the anterior segment.
Fluorescein angiography (FA) reveals the following findings.
Rift Valley fever virus is an arbovirus transmitted by mosquitoes of the genus Aedes. Risk factors include the following:
During El Niño-Southern Oscillation events, mosquito breeding sites increase, raising the risk of outbreaks.
The WHO-recommended confirmatory diagnostic methods for Rift Valley fever are as follows:
| Test Method | Target | Notes |
|---|---|---|
| RT-PCR | Viral RNA | Plasma/serum as specimen |
| ELISA | IgM/IgG antibodies | Combined with molecular testing |
| Antigen detection | Rift Valley fever virus antigen | ELISA + molecular testing |
Because the period of viremia is transient, RT-PCR alone may miss the diagnosis. Additional serological testing is necessary. The broad overlap of symptoms with other hemorrhagic fevers and the lack of point-of-care diagnostic tools pose diagnostic challenges.
Ophthalmologically, slit-lamp microscopy and fundus examination with indirect ophthalmoscopy are fundamental. For the evaluation of anterior uveitis, assessment of anterior chamber cell count and flare is important. Fluorescein angiography (FA) is useful for evaluating the extent and activity of retinitis and vasculitis.
The following infectious diseases are considered in the differential diagnosis for ocular findings of Rift Valley fever.
In differential diagnosis, travel history to endemic areas, contact with animals, and mosquito exposure history are important clues.
Ocular findings appear 4 to 20 days after the onset of systemic symptoms of Rift Valley fever. Visual symptoms are typically noticed after an average of 5 to 14 days. In patients who report visual symptoms after infection in an endemic area, Rift Valley fever retinitis should be considered.
There are no FDA-approved treatments for Rift Valley fever. Management is primarily supportive care.
To reduce the risk of hemorrhagic complications, the following medications should be avoided:
Ribavirin has not been proven effective in vivo and is currently not recommended due to an increased risk of neurological complications.
No specific therapeutic agent exists. For ocular symptoms, symptomatic treatment with artificial tears and topical steroid eye drops is performed. Active ocular lesions usually resolve spontaneously within 10 to 12 weeks, but subsequent scar formation determines visual prognosis.
The mechanism of ocular complications in Rift Valley fever virus infection remains largely unclear. Both immune-mediated reactions and direct viral toxicity may be involved.
The following findings have been reported on postmortem examination:
However, the presence of the virus in ocular tissues has not been proven.
In a study using subcutaneously infected Sprague-Dawley rats, live virus was isolated from the retina, ciliary body, choroid, and optic nerve 4). This result indicates that Rift Valley fever virus has tropism for the posterior segment of the eye. Increased inflammatory cytokines and leukocyte counts in ocular tissues were also confirmed 4).
No conclusion has been reached at this time. While the virus has not been demonstrated in ocular tissues at autopsy, live virus has been isolated from the posterior segment in animal models 4). Both direct viral toxicity and immune-mediated reactions may be involved.
Rift Valley fever virus has limited antigenic diversity and is listed by the WHO as a priority pathogen with high epidemic potential. Nevertheless, no licensed vaccine for humans currently exists. Vaccine development is a central issue in prevention strategies.
Active ocular lesions (retinitis, retinal hemorrhage, vitreous reaction) usually resolve spontaneously within 10 to 12 weeks2). Anterior uveitis resolves within 2 to 3 weeks without treatment. An outbreak report from Rwanda described characteristic infrared imaging findings and suggested that the oral corticosteroid group may have had greater visual improvement, but caution is needed in interpretation as it was a non-randomized study3).
However, scar formation is the most common complication. The causes of poor visual outcomes can be broadly divided into the following three categories.
After scar formation, central visual impairment may persist. In particular, macular and paramacular scars, vascular occlusion, and post-infectious optic atrophy are the main causes of poor visual outcomes2).
