GLAUCOMA MEDICATION

The preservatives contained in some glaucoma eye drops have side effects which can reduce the quality of life over the short term and the efficacy of treatment over the long term, said Frances Meier-Gibbons MD, Rapperswill, Switzerland. “The adverse effects of preservative agents lead to reduced compliance and therefore to higher costs. There are alternatives to preserved eye drops and many patients would benefit from using them,” she said at a Glaucoma Day session of the XXXI Congress of the ESCRS in Amsterdam.

Almost all topical IOP-lowering eye drops contain preservative agents to reduce the risk of microbial contamination. Benzalkonium chloride (BAK) is the most widely used preservative agent. It is a cationic surfactant that leads to cell lysis. The concentration of BAK in glaucoma eye drops typically ranges from 0.004 per cent to 0.02 per cent. However, BAK is unreliable as a means of maintaining the sterility of eye drops, she said. In fact, one study showed that up to 34.8 per cent of eye drop bottles with the preservative are contaminated after two weeks of use. (Tasli et al, ent Eur J Public Health. 2001;9(3):162-4.)

Furthermore, IOP-lowering drugs that contain BAK have been linked to adverse reactions and ocular surface disease. The typical side effects of preservative agents, especially BAK, include allergic reactions such as photophobia, stinging and burning, which occur in up to 11 per cent of patients. Other side effects include dry eye sensations that increase with increasing number of BAK containing drugs. “BAK has a direct toxic effect on the ocular surface. It decreases tear film stability. It causes inflammatory cell infiltration, it induces epithelial abnormalities and it leads to inflammation in the eye that can be found even in the posterior part of the eye,” Dr Meier- Gibbons said. Dr Meier-Gibbons noted that a very important side effect in the long term of eye drops containing preservatives is a reduction in the success rate of glaucoma operations.

Ocular surface disease

Ocular surface disease frequently occurs in patients using glaucoma medications, she noted. In a study involving 630 glaucoma patients receiving topical medications, 14 per cent had severe ocular surface disease and a further 14 per cent had moderate ocular surface disease and 21 per cent had mild ocular surface disease, comprising together 49 per cent of the glaucoma patients (Fechtner et al, Cornea 2010. 29(6):618-621). “Ocular surface disease is a multifactorial disease with intrinsic and extrinsic factors. It involves tear-film disturbances and dryness and ocular surface changes with ocular discomfort, reduction of the visual acuity and a reduction of the quality of life,” Dr Meier- Gibbons said.

A study published recently showed that the risk factors for developing ocular surface disease include the number of medications used, the prolonged use of preserved drugs and the total BAK exposure (Rossi et al, Eur J Ophthalmol. 2013 May-Jun;23(3):296-302).

She added that after inadequate IOP reduction, the occurrence of side effects is the second most important reason glaucoma patients change their medication. Treatment becomes more expensive when patients have to change from one agent to another. A review of 500 patients treated at a centre in The Netherlands showed that cost of treating a patient rose from $347 (€256) when patients had no adjustments in their medication to $1,765 (€1,304) when patients required three or more adjustments to their medication. Outpatient visits to the ophthalmologist and medication contributed most to total costs. (Oostenbrink et al, 2001, J Glauc ; 10: 184-191.)

Preservative-free eye drops

Preservative-free single-use IOP-lowering eye drop preparations are now commercially available. Studies involving patients who change to BAK-free treatment have shown that there is a reduction in ocular surface disease and improvement of quality-oflife. (Uusitalo et al Acta Ophthalmolgica. 2010;88:329-36 . Katz et al, Clin Ophthalmol. 2010; 4: 1253–1261.) “The European Glaucoma Society supports the utilisation of preservative-free ophthalmic agents for chronic glaucoma treatment because they recognise the problems the preservatives can cause for the ocular surface,” Dr Meier-Gibbons said.

Glaucoma patients who are most likely to benefit from preservative-free medication are those with a known allergy to the preservative, those with severe dry eye and children. Additional indications for preservative-free eye drops are patients who have a long life expectancy, ocular surface disease or who are at a high risk for surgical intervention.

“I would probably not change a patient to preservative-free drops if they were 80 years old and doing well on their current drops and were not likely to require surgery. However, I would change a patient below the age of 60 to a preservative-free regimen and would also do so in patients taking two or more drugs and also those showing signs of ocular surface disease,” Dr Meier- Gibbons added.