In their 2018 CMAJ article, Kisilevsky and DeAngelis illustrated the occurrence of ocular vasculopathy in association with the administration of a topical eye decongestant. 1 The pathogenesis and clinical manifestations that they reported essentially parallel the complications of use of α-adrenergic agents in other conditions such as rhinitis medicamentosa and dermatitis medicamentosa.2,3 However, such rebound vascular effects may also be influenced by cofactors such as benzalkonium chloride, which may be present as preservatives in these pharmacologic solutions.4 Preservatives in most topical ocular products may cause direct toxicity or local allergic reactions in some patients. Either of these adverse effects could be associated subsequently with an actual or presumed vasculopathy.
Benzalkonium chloride is one of the most common and potentially toxic preservatives in topical eye solutions.5 Concentrations of this chemical vary from 0.005% to 0.02% in many targeted therapeutic ocular solutions (e.g., combined with active agents for glaucoma) or in putatively soothing or hydrating solutions more popularly referred to as “natural tears.”6 This agent can disrupt surface corneal epithelium, alter surface tear film formation and lead to surface structure necrosis.6,7 Such toxicity is dependent on dose and time accrual.6–8 In animal models, aganglionosis of the esophagus or bowel can be achieved by brief local exposures to benzalkonium chloride with similar or slightly higher concentrations (0.02% to 0.5%).9,10
Other non–benzalkonium chloride, nonmedicinal constituents may also pose problems. Borate as a preservative may cause local reactions in some patients, and castor oil (used as a lipid absorption enhancer) may induce allergic reactions.11 Foreign compounds presented to the ocular surface have the potential to stimulate the induction of local allergic immunoglobulin E–mediated or type IV hypersensitivity reactions.12
Although the design of preservative-free eye solutions aims to eliminate any such direct toxicity or local allergy, most common ocular preparations continue to use antimicrobial preservatives to promote product longevity or allow for multi-use. In the interim, physicians should be wary of the potential for nonmedicinal components of ocular solutions to cause disease.
Footnotes
Competing interests: None declared.