Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

Abstract

Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain–Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8+T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as non-structural protein 5, are involved in the evasion of the host’s immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus’ ability to cross both the blood–brain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the host’s immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection.

Ocular manifestations of recent viral pandemics: A literature review

“…Ebola virus was detected in the aqueous humor of one patient, but evidence of viral transmission through tears or conjunctival secretions is still lacking (112). Zika and MRES viruses can be transmitted through ocular secretions, especially conjunctival secretions (89,113). Influenza A viruses can replicate in the conjunctiva of infected people, which could be its route of access to the respiratory mucosa (79).…”

“…The persistence of Zika virus RNA in tears 30 days post-infection has been documented. Thus, there is a potential risk of ocular transmission of Zika virus through contact with Zika virusinfected tears (89).…”

“…On the anterior segment in newborns, Zika causes iris coloboma, lens subluxation, cataract, glaucoma, microphthalmia, and intraocular calcifications. Anatomical abnormalities such as pupillary membrane and maldevelopment of the anterior chamber angles are all reported in Congenital Zika Syndrome (CZS) (89). In adults, nonpurulent conjunctivitis with hyperemia is the most common manifestation of acute Zika virus infection as it arises in about 63% of patients.…”

“…Optic disc hypoplasia with the double-ring sign, disc pallor, and enlarged cupto-disc ratio were also reported. In adults, papilledema, ophthalmoplegia, and ocular flutter were the main neuroophthalmic complications (89).…”

Clinical Management of Herpes Simplex Virus Keratitis

“…The recruited TBK1 and IKK phosphorylate interferon regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB), respectively. The activated IRF3 and NF-κB translocate to the nucleus where they stimulate genes required for coding interferons (type I IFN) and other cytokines [ 36 , 37 , 38 , 39 , 40 , 41 ]. Type I interferon induces an antiviral microenvironment, activates NK cells, and inhibits viral replication.…”