Dengue fever ophthalmic manifestations: A review and update

Abstract

Dengue fever, the most common arbovirus disease, affects an estimated 390 million people annually. Dengue virus (DENV) is an RNA virus of the Flaviviridae family with four different serotypes. Dengue haemorrhagic fever is the deadliest form of dengue infection and is characterised by thrombocytopaenia, hypotension, and the possibility of multi-system organ failure. The mechanism hypothesised for DENV viral replication is intrinsic antibody-dependent enhancement, which refers to Fcγ receptor-mediated viral amplification. This hypothesis suggests that the internalisation of DENV through the Fcγ receptor inhibits antiviral genes by suppressing type-1 interferon-mediated antiviral responses. DENV NS1 antibodies can promote the release of various inflammatory mediators in the nuclear transcription factor pathway (NF-κB-dependent), including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-8. As a result, MCP-1 increases ICAM-1 expression and facilitates leukocyte transmigration. In addition, anti-DENV NS1 antibodies induce endothelial cell apoptosis via a nitric oxide-regulated pathway. A chain reaction involving pre-existing DENV heterotypic antibodies and innate immune cells causes dysfunction in complement system activity and contributes to the action of autoantibodies and anti-endothelial cells, resulting in endothelial cell dysfunction, bloodretinal barrier breakdown, haemorrhage, and plasma leakage. A spectrum of ocular diseases associated with DENV infection, ranging from haemorrhagic to

Ophthalmic complications during the dengue epidemic in Reunion Island in 2020: a case series and review of the literature

“…This leads to the release of interleukin-6 and interleukin-8, as well as monocyte chemoattractant protein (MCP-1). By increasing ICAM-1, MCP-1 increases the adhesion of immune system cells to endothelial cells [ 23 – 25 ]. Anti-NS1 antibodies therefore also appear to contribute to ocular inflammation and cell apoptosis via nitric oxide [ 26 ].…”

Ocular Manifestations of Flavivirus Infections

“…DF ranks as a significant arthropod-borne disease in tropical and subtropical regions, endemic in over 100 countries spanning America, Southeast Asia, the Western Pacific, Africa, and the Eastern Mediterranean [30]. The incidence of DF has surged 30-fold in recent decades, affecting an estimated 390 million people annually [5]. This has resulted in approximately 96 million symptomatic infections yearly, with two million cases of severe dengue and an annual death toll of 21,000 [31][32][33].…”

“…Most DF cases resolve spontaneously. However, a minority of patients may progress to a life-threatening condition known as dengue hemorrhagic fever (or dengue shock syndrome), characterized by thrombocytopenia, hypotension, and the potential for multi-system organ failure [5].…”

“…However, severe and potentially fatal systemic complications, such as hemorrhagic fever and neurological involvement, can occur. In addition to systemic infections that entail hemorrhages, vascular leakage, encephalitis, microcephaly, and Guillain-Barre syndrome, certain specific flaviviruses, including dengue fever (DFV), West Nile virus (WNV), yellow fever virus (YFV), Japanese Encephalitis virus (JEV), and Zika virus, have recently been linked to uveitis and other ocular manifestations [4][5][6][7][8]. There are no specific antiviral therapies for flavivirus infections and treatment is essentially symptomatic [3][4][5]7].…”

“…In addition to systemic infections that entail hemorrhages, vascular leakage, encephalitis, microcephaly, and Guillain-Barre syndrome, certain specific flaviviruses, including dengue fever (DFV), West Nile virus (WNV), yellow fever virus (YFV), Japanese Encephalitis virus (JEV), and Zika virus, have recently been linked to uveitis and other ocular manifestations [4][5][6][7][8]. There are no specific antiviral therapies for flavivirus infections and treatment is essentially symptomatic [3][4][5]7]. This manuscript aims to provide an Pathogens 2023, 12, 1457 2 of 21 overview of the ophthalmic manifestations associated with the most significant flavivirusrelated human diseases.…”