Allergic Reaction to Topical Eyedrops
Purpose of Review: To examine recently published papers dealing with drug-induced allergic reactions. As allergy is only one possible mechanism, this review was extended to all reports or studies describing allergic, inflammatory or toxic effects related to eyedrops since 2004.
Recent Findings: These studies were first classified into clinical reports or surveys, experimental works and biological studies showing drug-induced effects on the ocular surface or eyelids. Studies aimed at determining the role of preservatives or comparing preservative-free and preserved eyedrops were further analysed separately.
Summary: Reports on allergic or toxic reactions of eyedrops are published repeatedly. The reports raising the most important issues are those concerning antiglaucoma drugs. They consistently describe inflammatory reactions at the conjunctival level, with strong evidence that preservative is a major source of toxicity for the ocular surface.

There is now a large amount of evidence from experimental and clinical studies that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort upon instillation, tear film instability, conjunctival inflammation, subconjunctival fibrosis, conjunctival epithelium apoptosis, corneal surface impairment, and a potential risk of the failure of further glaucoma surgery. Subclinical inflammation has also been described, with significant infiltration of the conjunctival epithelium and substantia propria by inflammatory cells in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e. allergic, toxic or inflammatory, as well as the respective roles of the active compound and the preservative in inducing toxic or pro-inflammatory effects of ophthalmic solutions is still being debated. The most frequently used preservative, benzalkonium chloride, has widely demonstrated its toxic effects in laboratory, experimental and clinical studies. As a quaternary ammonium, this compound is much more than an excipient, and has been shown to cause directly or has shown some evidence of causing tear film instability, the loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, severe loss of endothelial cells if accidentally introduced in the anterior chamber, and even blood-aqueous barrier disruption in the early phase of pseudophakia, leading to the new concept of pseudophakic preservative maculopathy.

During the past year several papers were published dealing with eyedrop toxicity or allergy, most of them confirming the large role, even though not exclusive, of preservatives in inducing adverse events on the ocular surface. Some reports were focused on allergic manifestations, others were aimed at investigating ocular surface inflammation with more sophisticated tools and techniques, in relation to eyedrops and their preservatives. This review is divided into three parts: (1) clinical reports on drug-induced ocular manifestations; (2) biological studies; and (3) comparative studies aimed at determining the role of the preservative.