Corneal toxicity: the epithelium and stroma in iatrogenic and factitious disease

Corneal toxicity is caused by chemical trauma and by iatrogenic and factitious disease, which are often overlooked, and which are reviewed here. The clinical signs of iatrogenic disease are usually nonspecific and identical to those resulting from other causes of surface disease. Factitious disease is either the result of mechanical trauma or the abuse of toxic eye drops. One epidemiological study, in a tertiary setting, identified 13% of keratoconjunctivitis cases as iatrogenic. Healing was prolonged taking 7-93 (median 28.5) days. Pathogenic mechanisms vary widely with different drugs and include subclinical scarring, pseudopemphigoid, drug-induced ocular cicatricial pemphigoid, and toxic follicular reactions. There is little readily available data either on the probability of the development of adverse reactions or for the comparison of different drugs. The assessment of the toxicity of topical drugs is currently by the Draize test in rabbits. New in vitro tests on human corneal epithelial cell cultures include ATP assays for cell viability, scanning EM of epithelial microvilli, and vital staining to assess cell membrane permeability and intracellular esterase. Despite their simplicity, these test systems can correlate well with clinical toxicity and provide a toxicity index for drug comparisons. Treatment requires drug withdrawal or substitution by non-preserved and less toxic preparations. Factitious injury is rare, difficult to diagnose, and should only be considered when all other diagnoses have been excluded. Prevention requires a high level of awareness of the potential for iatrogenic disease, particularly in the high-risk setting of chronic ocular surface disease.