Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions

Figures & data

Table 1 Overview of Subtypes of Group B and D HAdV with Sites of Infection

Group	HAdV Subtypes	Site of Infection
Group B HAdV	3, 7, 11, 14, 16, 21, 34, 35, 50, 55, 66, 68, and 76–79	Conjunctiva, urinary tract, respiratory tract, and gastrointestinal tract
Group D HAdV	8, 9, 10, 13, 15, 17, 19, 20, 22–30, 32, 33, 36–39, 42–47, 51, 53, 54, 56, 58–60, 63–65, 67, 69–75, 80–88, and 90–103	Cornea, urinary tract, respiratory tract, gastrointestinal tract, and conjunctiva

Note: Data from these publications.^11,12

Figure 1 Set up for in-office povidone-iodine irrigation. From left to right: nitrile gloves, topical anesthetic, topical NSAID, betadine, 5% solution, saline solution, and folded paper towel for saline rinse.

Figure 2 Presentation of an inflamed inferior palpebral conjunctiva with pseudomembrane (black arrow) in a patient with adenoviral keratoconjunctivitis.

Note: Copyright ©2018. Dove Medical Press. Reproduced from Chigbu DI, Labib BA. Pathogenesis and management of adenoviral keratoconjunctivitis. Infect Drug Resist. 2018;11:981–993.²

Table 2 Efficacy and Adverse Effects of Antiviral and Anti-Inflammatory Agents

Treatment/Management	Efficacy	Adverse Effects
PVI irrigation	Off-label use for EKC; reduces risk of disease transmission	Dry eye symptoms, corneal epithelial damage/toxicity with repeated use. ^Citation104
Cidofovir	Antiviral activity against HAdV5 exhibited in animal models. ^Citation105 Cidofovir 1% lowered the frequency of severe corneal opacities in patients with adenoviral keratoconjunctivitis.^Citation64,Citation106	Narrow therapeutic index when used topically; high doses for greater than one week associated with rare cases of lacrimal canalicular blockade in rabbit models.^Citation107
Ganciclovir	3% ganciclovir reduced HAdV 5 replication and pathogenesis in animal models.^Citation108 Ganciclovir is efficacious against HAdV types that cause EKC.^Citation46 Ganciclovir ophthalmic gel treatment prevents complications in adenoviral ocular infection. ^Citation109	Transient blur following instillation, eye irritation, punctate keratitis, conjunctival hyperemia.^Citation108
Brincidofovir	Brincidofovir has antiviral activity against adenoviruses. ^Citation55, ^Citation105, ^Citation110^–^Citation113	Mild gastrointestinal tract upset, asymptomatic and elevated levels of serum transaminases^Citation114 diarrhea, acute graft versus host disease, abdominal pain, nausea/vomiting, decreased appetite, peripheral edema, hyperglycemia, hypokalemia, rash, fatigue, fever.^Citation115
Topical corticosteroids	Relief of EKC symptoms and Persistent adenoviral SEIs.^Citation2,Citation63	Glaucoma and cataracts.^Citation116
Topical cyclosporine	Effective against persistent adenoviral SEIs.^Citation66,Citation69,Citation117^–^Citation119	Transient or long-lasting burning sensation;^Citation120 ocular pain/irritation, redness; eyelid swelling in Steven Johnsons patients.^Citation121
Topical tacrolimus	Superior to dexamethasone in reducing symptomology and SEIs^Citation70 as well as a safe and effective treatment of adenoviral SEIs.^Citation87,Citation122,Citation123	Transient burning sensation.^Citation124

Table 3 Challenges and Solutions in the Management of Adenoviral Keratoconjunctivitis

Challenges	Potential Solutions
High likelihood of transmission and epidemic spread/burden	Health education in infected individuals and effective disinfection/prevention protocols
Persistent HAdV secretion in the tears	Further research regarding the development of a prophylactic antiviral agent
Reactivation of persistent latent HAdV in the host	Prevention of spread, treatment of immunocompromised individuals
Group D HAdV can cause oculogenital infection	Appropriate testing for HAdV subtype from urethra and conjunctiva in men
Duration of symptoms and transmission of EKC	Antivirals: ganciclovir, cidofovir, PVI irrigation
Poor bioavailability and high toxicity of cidofovir	Lipid-linked derivative brincidofovir and potential development of ophthalmic formulation
Development and/or persistence of SEIs	Topical corticosteroid therapy
Side effects of long-term corticosteroid use (ie, elevated IOP and cataract formation)	Immunotherapy such as topical cyclosporine or tacrolimus
Corticosteroids prolonging viral shedding	Combination PVI/dexamethasone ophthalmic solution
Conjunctival or corneal scarring	Pseudomembrane removal, PTK

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