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Toxic conjunctivitis

Pedram Hamrah, MD
Reza Dana, MD, MPH, MSc
Section Editors
Bruce S Bochner, MD
Robert A Wood, MD
Deputy Editor
Elizabeth TePas, MD, MS


There are five main types of ocular allergy: seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC). Toxic conjunctivitis (also called toxic keratoconjunctivitis) is not allergic in nature, but it is frequently confused with allergic ocular disease. It implies direct damage to ocular tissues from an offending agent, usually a preservative or medication. The toxic agent can cause a papillary or follicular response in the conjunctiva with chronic use, and the conjunctiva can become chemotic, edematous, and hyperemic. Toxic conjunctivitis is reviewed here. The various forms of ocular allergy are reviewed separately. (See "Allergic conjunctivitis: Clinical manifestations and diagnosis" and "Vernal keratoconjunctivitis" and "Atopic keratoconjunctivitis" and "Giant papillary conjunctivitis".)


Toxic conjunctivitis typically occurs with protracted use of topical ocular medications [1]. The reaction may take days to years to develop. There also appears to be a dose-response effect with regard to the preservative concentration and total amount of preservative-containing medications used [2]. Thus, toxic ocular reactions are most frequently reported in patients with glaucoma, who are on lifelong therapy with multiple medications [3].

Results from a monkey model and human corneal epithelial cell culture suggest that preservatives in ophthalmic solutions are unlikely to cause significant direct toxicity to epithelium of otherwise normal cornea [4]. However, studies in rabbit models consistently demonstrate ocular surface toxicity with topical preservative-containing medications [3,5]. In one study, patients with dry eyes were at greater risk for the development of toxic papillary reactions than those without dry eyes [6].


Preservatives in eye medications, contact lens solutions, and artificial tears are the most common causes of toxic ocular reactions [7]. The most common types of preservatives include benzalkonium chloride (BAK or BAC), thimerosal, chlorobutanol, sodium perborate, and stabilized oxychloro complex (SOC). All of these can cause toxic, irritant, or hypersensitivity reactions [8]. However, in rabbit models, the newer-generation SOC is less cytotoxic than the other preservatives [1,3].

A number of findings are seen in patients treated with preserved medications compared with those using preservative-free therapies:

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Literature review current through: Nov 2017. | This topic last updated: Mar 16, 2016.
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