The 1996 introduction of prostaglandin analogues was a revolutionary step in the management of glaucoma. Their patient-friendly nature, nighttime only dosing, few side effects and potential for as much as a 35% reduction in intraocular pressure has cemented their place as a first line agent for the management of ocular hypertension and primary open angle glaucoma.

There are currently three prostaglandin medications approved by the FDA: Xalatan (latanoprost 0.005%, Pfizer), Travatan Z (travaprost 0.004%, Alcon) and Lumigan (bimatoprost 0.01% and 0.03%, Allergan). Outside of the U.S., combination drops containing these agents are available: Duotrav (travaprost and timolol maleate, Alcon), Xalacom (latanoprost and timolol maleate, Pfizer) and Ganfort (bimatoprost and timolol maleate, Allergan).

The Drawbacks of BAK
While long proven to be safe and effective, possible side effects of prostaglandin analogues include hyperemia, eyelash growth and iris pigment darkening. For the elderly, there is a high likelihood of dry eye. In one study, 630 glaucoma patients in 10 centers were treated with glaucoma drops. Over 48% reported dry eye symptoms on the Ocular Surface Disease Index, with 27% rated as moderate to severe.¹ In particular, benzalkonium chloride (BAK)—a common quaternary ammonium detergent preservative—has been implicated as a significant factor in corneal toxicity. BAK is broken down to hydrogen peroxide, which is associated with considerable surface irritations and increased localized inflammation.²
BAK is present in bottled artificial tears; since they are commonly used for relief, a cumulative and negative cycle of irritation and inflammation often persists. To help combat toxicity, Alcon developed sofZia, an ionic buffered preservative system for Travatan Z—sofZia showed less cytotoxicity to epithelial and conjunctival cells than assays containing BAK or polyquad derivatives.³ 

Any eyedrop that aggravates an existing and symptomatic dry eye will not be used, hence glaucoma patients tend to be at risk for vision loss. Fortunately, on the horizon is a non-preserved glaucoma drop.

Eliminating Preservatives
In March 2011, Merck received an approvable letter for a New Drug Application from the FDA for Saflutan (tafluprost), its preservative-free prostaglandin analogue currently in use in Europe. In clinical studies in Europe and the U.S., over 1,200 patients have been treated with tafluprost either as monotherapy or as adjunctive therapy to timolol 0.5%. The most frequently reported treatment-related adverse event was ocular hyperemia, occurring in approximately 13% of patients and causing discontinuation in 0.4% of those patients. Other less common side effects include pruritus, irritation, pain, changes in eyelashes, dry eye, foreign body sensation, lid erythema and edema, blurred vision, increased lacrimation, blepharal pigmentation, discharge, photophobia and increased iris pigmentation. Reduction of intraocular pressure begins two to four hours after administration, with maximum effect reached 12 hours after instillation; the effect is maintained for at least 24 hours.

In a six-month study, tafluprost showed a significant IOP-lowering effect of 6mmHg to 8mmHg at different time points of the day, as compared to 7mmHg to 9mmHg with latanoprost.⁴ In a second six-month clinical study, tafluprost reduced IOP by 5mmHg to 7mmHg, as compared to 4mmHg to 6mmHg with timolol.⁴ The IOP-lowering effect of tafluprost was maintained up to 12 months.

In a six-week study, the IOP-lowering effect of tafluprost was compared with its vehicle when used with timolol. Compared to baseline values (measured after a four-week run on timolol), the additional IOP-lowering effects were 5mmHg to 6mmHg in the timolol-tafluprost group and 3mmHg to 4 mmHg in the timolol-vehicle group.⁴

Tafluprost is available in either 30 or 90 packs of 0.3ml single-dose containers. One single-dose container is sufficient for both eyes.

The field of glaucoma management continues to improve. New drugs are safer and more effective. Saflutan may prove to be a significant entry into our pharmaceutical toolbox for patients with severe ocular surface disease or preservative sensitivities.  

1. Fechtner RD, Godfrey DG, Budenz D, et al. Prevalence of ocular surface complaints in patients with glaucoma using topical intra-ocular pressure lowering medications. Cornea. 2010 Jun;29(6):618-21.
2. Epstein SP, Chen D, Asbell P. Evaluation of biomarkers of inflammation in response to benzalkonium chloride on corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009 Oct;25(5):415-24.
3. Ammar DA, Noecker RJ, Kahook MY. Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human epithelial cells. Adv Ther. 2010 Nov;27(11):837-45.
4. Saflutan. Electronic Medicines Compendium. Available at: www.medicines.org.uk/EMC/medicine/22237/SPC/SAFLUTAN+15+micrograms+ml+eye+drops,+solution,+single-dose+container (Accessed April 2011).