Viral infections and pathogenesis of glaucoma: a comprehensive review

Abstract

SUMMARY 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.

SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure

“…With recent clinical findings, it is becoming increasingly clear that SARS-CoV-2 infection has broad implications in ocular disease sequelae [4,5,15]. The ocular mucosal milieu has been identified as the most susceptible region that can be affected by transmissible microorganisms, including viral and bacterial pathogens such as herpes simplex virus-1, influenza, Zika, and Staphylococcus aureus [16,28,[47][48][49][50][51]. Previous studies have shown the presence of SARS-CoV-2 RNA and proteins in various ocular tissues and fluids, including conjunctiva, limbus, tears, and aqueous humor, indicating that the eye could be a potential site of infection and transmission [21,25,38].…”

“…SARS-CoV-2 has demonstrated ocular tissue tropism with pervasive ocular manifestations, including conjunctivitis, keratoconjunctivitis, episcleritis, hyperemia, chemosis, epiphora, dry eye or foreign body sensation, eye redness, tearing, itching, ocular pain, cotton wool spots, hyperreflective lesions at the level of ganglion cell and inner plexiform layers, retinal artery and vein occlusion, retinal hemorrhage, vascular sheathing, macular neuroretinopathy, optic nerve infarction, optic nerve edema, optic neuropathies, cerebral vein thrombosis, uveitis, and glaucoma [2,[6][7][8][9][10][11][12][13][14][15]. Recently, we reviewed the ocular complications caused by many conventional and emerging viruses, including SARS-CoV-2, which is considered relatively uncommon due to underreporting or improper diagnosis [16]. Early during the pandemic, studies on SARS-CoV-2 were primarily focused on respiratory manifestations of the virus with little or no knowledge of its ocular disease sequelae; however, more recent data have supported a much higher incidence of ocular comorbidities.…”

Update on Diagnosis and Treatment of Uveitic Glaucoma

“…Identifying the cause of uveitis is crucial, as in cases of infectious etiology, where treating the underlying infection will expedite resolution of the disease. This is best exemplified in herpetic or toxoplasmic uveitis, where antiviral and antiparasitic medication produce an immediate improvement to the clinical signs and symptoms [ 33 , 34 ]. It has been shown that IOP in CMV-positive PSS is more difficult to control than in CMV-negative cases.…”