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Kisilevsky and DeAngelis illustrate the occurrence of ocular vasculopathy in association with the administration of a topical eye decongestant.1 The pathogenesis and clinical manifestations essentially parallel the complications of α-adrenergic agent use in other diseases such as rhinitis medicamentosa and dermatitis medicamentosa.2,3 It may very well be, however, that any such rebound vascular effects are also influenced by co-factors such as benzalkonium chloride (BAK) which may be present as preservatives in these pharmacological solutions.4 The general medical community is unlikely to consider that preservatives in almost any topical ocular product may cause direct toxicity or local allergic reactions in some patients. Either of the latter could be associated subsequently with an actual or presumed vasculopathy.
BAK 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 BAK can disrupt surface corneal epithelium, alter surface tear film formation, and lead to surface structure necrosis.6,7 Such toxicity is dose-dependent and time-accrued.6-8 In animal models, aganglionosis of esophagus or bowel can be achieved by brief local exposures to BAK with similar or slightly higher concentrations (0.02% to 0.5%).9,10
Other non-BAK, non-medicinal constituents may also pose problems. Borate as a preservative may cause local reactions for some, and castor oil (used as a lipid absorption enhancer) may induce allergy reactions.11 Foreign compounds presented to the ocular surface have the potential to stimulate the induction of local allergic IgE-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 anti-microbial preservatives in order to promote product longevity or allow for multi-use. In the interim, physicians should be wary of the potential for non-medicinal components of ocular solutions to cause disease.
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