Ocular Manifestations of Flavivirus Infections

Abstract

Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections and epidemics on a global scale. They represent a major cause of systemic morbidity and death and are expanding worldwide. Among this group, dengue fever, the West Nile virus, yellow fever, Japanese Encephalitis, and, recently, the Zika virus have been linked to a spectrum of ocular manifestations. These manifestations encompass subconjunctival hemorrhages and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatments of flavivirus infections are currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for the yellow fever virus, dengue virus, and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic manifestations of the foremost flavivirus-associated human diseases.

Keywords: Japanese encephalitis virus; Kyasanur forest disease virus; West Nile virus; Zika virus; dengue fever virus; eye; flavivirus; yellow fever.

Figure 1

Schematic representation of a flavivirus viral particle (A) and genome (B). Adapted from https://viralzone.expasy.org/24 (accessed on 1 January 2011) with authorization [12].

Figure 2

Fluorescein angiogram of the right eye of a 33-year-old woman presenting with sudden loss of vision 1 week after the onset of dengue hemorrhagic fever showing dengue maculopathy, manifesting as severe retinal vasculitis with prominent vascular leakage (Courtesy of Pr Soon Phaik Chee).

Figure 3

(A) Red-free fundus photograph of the left eye of a patient with dengue fever shows a subretinal round, yellowish lesion at the fovea (white arrow). (B) Optical coherence tomography through the lesion demonstrates conical foveal elevation (yellow arrow) with focal outer neurosensory retinal pigment epithelium thickening (Courtesy of Pr Soon Phaik Chee).

Figure 4

Color fundus photographs (A) and fluorescein angiograms (B) of the left eye of a diabetic patient with WNV infection show inactive multifocal chorioretinitis with typical linear clustering and the ‘target-like appearance’ of chorioretinal lesions (white arrowheads) with central hypofluorescence and peripheral hyperfluorescence (yellow arrowheads). Note the presence of associated moderate to severe non-proliferative diabetic retinopathy.

Figure 5

Fundus photograph of the left eye of a newborn with congenital Zika virus syndrome shows macular, well-delineated atrophic lesions (Courtesy of Pr Rubens Belfort).