Alternatives for reducing preservative loads must be considered when assessing the ocular surface of patients being treated in the long-term with IOP-lowering medications
As a chronic disease, glaucoma requires long-term, lifetime treatment, often with multiple ophthalmic medications. These medications can cause local side effects as a result of active ingredients or other components, especially preservatives. It is, therefore, essential to monitor the impact of glaucoma therapy on the ocular surface.
The prevalence of ocular surface disease (OSD) is high in glaucoma patients.1 A number of factors - including increased age and medications typically taken by seniors, such as antihypertensives, antidepressants and antihistamines - can cause dry eye symptoms and OSD. Additionally, repeated exposure to certain preservatives used in glaucoma medications can exacerbate this condition.
In a study of 630 glaucoma or ocular hypertension patients on topical IOP-lowering medications, nearly half had OSD index scores reflecting at least mild OSD symptoms; more than a quarter were classified as having moderate or severe OSD.2
Although benzalkonium chloride (BAK) does a remarkable job of keeping multidose eye drops sterile, animal experiments and clinical studies have shown that BAK can have dose-dependent toxic effects, compromising tear film stability and causing irritation to the cornea and conjunctiva. These ocular side effects may cause symptoms such as stinging, burning and dryness.1,4
In addition, preservatives can affect the goblet cells by reducing their number and production of the protective mucin layer.8 Other effects of excessive preservative use include conjunctival epithelium inflammation and subconjunctival fibrosis.1
The side effects associated with long-term use of preserved anti-glaucoma medications can also adversely impact patient compliance with therapy and the likelihood of successful treatment.9
Can therapy be modified?
The incidence of dry eye and OSD in glaucoma patients have been shown to increase with the dose and duration of glaucoma medications containing preservatives.1,10,11 Researchers of a cross-sectional study of glaucoma patients used a multivariate logistic regression model and found that each additional BAK-containing eye drop was associated with two times higher odds of demonstrating lissamine green staining.10
Patients who have already been diagnosed with dry eye have a tear film and ocular surface that in some respects is compromised when compared with that of the non-dry eye patient. If they are using BAK-preserved artificial tears, they may be introducing more preservatives to a frail tear film.
Even patients without a dry eye diagnosis who are at increased risk due to environmental factors, such as frequent computer use, may experience ocular surface problems once preserved glaucoma medications are introduced. Some researchers have even postulated that the prevalence of dry eye in the ageing population may actually be increasing because of long-term use of multiple glaucoma medications.1
Some patients have direct allergic reactions to preservatives, especially those whose eyes have been hypersensitized by repeated and long-term use of preserved eye drops.4
In attempts to minimize preservative loads to the ocular surface, combination medications have been used to deliver the effectiveness of two medications in the convenience of a single bottle. In addition to being convenient, they can reduce preservative loads to the ocular surface significantly.
Dorzolamide hydrochloride-timolol maleate ophthalmic solution (Cosopt, Merck & Co.) and brimonidine tartrate 0.2%/timolol maleate ophthalmic solution 0.5% (Combigan, Allergan) are both examples of combination agents that are commonly used.