Viral infections and pathogenesis of glaucoma: a comprehensive review

Abstract

Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.

Keywords: CMV; Ebola; HSV; SARS-CoV-2; VZV; Zika; dengue; glaucoma; ocular infections; optic neuritis; uveitis; virus.

FIG 1

A schematic depicting the role of viruses in the pathogenesis of glaucoma. Many oculotropic viruses (e.g., HSV, VZV, CMV, EBV, CHIKV, RUBV, EBOV, DENV, WNV, HBV, HCV, ZIKV, and SARS-CoV-2) cause immune cell-mediated ocular inflammation, called uveitis, that results into elevated IOP. This virus-induced IOP often leads to the development of glaucomatous pathology resulting in vision loss. Image created with BioRender.com.