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Glaucoma and ocular hypertension can effectively be treated topically with IOP-lowering drops.
Preservatives are often used to maintain the sterility of ophthalmic medications, the most common of which is benzalkonium chloride (BAK), with concentrations ranging from 0.004% to 0.025%. However, BAK is associated with a host of adverse side effects that can ultimately result in negative clinical outcomes.
"BAK is notorious for causing irritation in the treated eye, characterized as burning, stinging, foreign body sensation, as well as more serious complications such as conjunctivitis, corneal abrasions, and dry eye," said Christophe Baudouin, MD, PhD, professor, Department of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris. "Patients using eye drops without such irritation-causing preservatives would likely fare better, particularly in a long-term therapy setting."
"Even at low concentrations, BAK is toxic to ocular tissues and can cause unwanted side effects in the treated eye," he said. "Topical ophthalmic solutions free of preservatives can help patients adhere to treatment regimens and improve clinical outcomes."
Dry eye is a common adverse side effect seen in patients who use topical ophthalmic medications that contain preservatives such as BAK. The symptoms of dry eye are typically characterized by inadequate quantity of tears, impairment of the protective tear film, and ocular surface damage leading to local symptoms of dryness, irritation, photophobia, fatigue, and loss of visual acuity.
Disruptive effect on tear film
BAK has been shown to have a disruptive effect on the tear film by exerting a detergent effect on its lipid layer. This reduces the stability of the tear film, causing it to evaporate more rapidly, resulting in increased ocular dryness. This impaired protective layer will further predispose the eye to inflammation and conjunctival metaplasia. According to Dr. Baudouin, preservatives also have destructive effects on the mucous-secreting cells, reducing the number of goblet cells and production of the protective mucous layer, further predisposing the patient to symptoms of dry eye.
Other negative effects of preservatives include inflammation of the conjunctival epithelium and development of subconjunctival fibrosis. This can sometimes culminate in toxic pseudopemphigoid, a severe sight-threatening disease, which can be more commonly seen in patients who receive anti-glaucoma treatment including preservatives compared with patients who do not receive topical therapy.
"The toxic effects of preservatives are initially sub-clinical but compounded by chronic and repeated exposure that occurs with long-term glaucoma management," Dr. Baudouin said. "The long-term cumulative application of preservative-containing anti-glaucoma medications to the ocular surface is associated with the signs and symptoms of ocular discomfort and can often lead to premature cessation of therapy."
Topical medication is the first-line therapy in patients suffering from open angle glaucoma or ocular hypertension. Topical ophthalmic treatments are generally well-tolerated by patients in the short term, however, Dr. Baudouin said treatment compliance becomes a real issue in the long term because of the commonly seen adverse side effects, most often due to the preservatives in the medications.
"Patients who experience adverse side effects from anti-glaucoma medications not only can have a decreased quality of life but are less likely to comply with their treatment program," he said. "Non-compliance with medication regimens and premature discontinuation of drop therapy can result in detrimental long-term implications for a patient's visual health."
According to Dr. Baudouin, switching from preserved to preservative-free glaucoma medications or at least reducing the number of preserved medications can have a positive impact on the functional aspects of the eye structure as well as reduce the clinical symptoms experienced by the patient. He said that preservative-free anti-glaucoma medications can achieve the same IOP-lowering effect as those medications containing preservatives. Preservative-free medications would be particularly useful in those patients who have a hypersensitivity to preservatives or concomitant dry eye or ocular surface disease.
"Glaucoma is a progressive disease and it is not uncommon that patients are prescribed multiple concomitant anti-glaucoma treatments," Dr. Baudouin concluded. "The more these patients can tolerate their topical therapeutic regimens, i.e., experience minimal adverse side effects, the better chance they will have in complying with therapy, and avoiding topical preparations containing preservative agents can be the key."