The glaucoma is a chronic progressive, sight-threatening disease that requires the use of topical intraocular pressure (IOP) lowering drugs, to be administered for decades and, in many cases, for life. However, topical glaucoma drugs are associated with a significant incidence of ocular surface disease (OSD). Importantly, almost half of glaucoma patients worldwide receive more than one IOP-lowering drug, with the gradual implementation of multiple topical agents to reduce and achieve the desired target pressure.
Today, a multitude of treatment options are available, which can be administered as fixed combinations or simultaneously. However, active compounds, individually or in combination, their excipients, and in particular preservatives, interact in complex ways with the ocular surface. The management and optimisation of ocular surface health is, therefore, a major challenge in the management of glaucoma.
Glaucoma treatment and OSD: the correlation
Many studies Observational studies have shown that the prevalence of OSD related to glaucoma therapy is much higher than that found in the general population, in fact as many as 45-60% of patients using preservative eye drops are clinically affected by ocular surface disease. Long-term use of topical IOP-lowering drugs can induce ocular discomfort, tear film instability, Meibomian gland dysfunction, conjunctival inflammation, subconjunctival fibrosis, epithelial damage and allergic blepharitis. In addition, it is plausible that the ocular surface is damaged at various levels by subtle subclinical inflammation, observed in 80% of pharmacologically treated glaucoma patients, which can cause serious consequences, up to devastating diseases such as toxic pseudopemphigoid.
In addition, OSD may reduce long-term tolerance and adherence to topical therapy, due to a wide range of adverse events occurring within a few months of starting treatment.
Benzalkonium chloride (BAK) toxicity
A large number of clinical and experimental studies have documented a strong correlation between signs and symptoms of OSD with the number of glaucoma medications used and, in particular, with cumulative exposure to benzalkonium chloride (BAK). In fact, most dispensers of standard multi-use eye drops contain BAK as a preservative.
Several evidences suggest that on the ocular surface, BAK causes tear film instability, loss of calico cells, conjunctival squamous metaplasia, cell apoptosis, disruption of the corneal epithelial barrier, corneal nerve damage and potential damage to deeper ocular tissues, where it gradually accumulates. These pathological changes to the ocular surface may also be associated with subsequent conjunctival fibrosis, and thus increase the risk of filtering surgery failure, especially in those patients treated with multiple BAK drugs stored for many years.
Preservative-free drugs for the treatment of glaucoma: a possible solution
Growing data suggest, therefore, that prevention or amelioration of OSD can be achieved by eliminating BAK exposure through the use of preservative-free glaucoma eye drops (PF).
Preservative-free (PF) drugs are a viable treatment strategy in the ongoing management of glaucoma. By removing the toxicity of preservatives, PF formulations provide tangible clinical benefits. In addition, they improve tolerability and adherence, leading to a positive impact in long-term intraocular pressure (IOP) control.
For example, to date, for most patients with glaucoma or ocular hypertension, the initial topical eye drop of choice is a prostaglandin analogue (PGA), due to its superior 24-hour efficacy and satisfactory tolerability profile. Undoubtedly, prostaglandins, enzyme products of essential fatty acids, show an excellent overall safety profile, however they exhibit a number of ocular side effects, such as conjunctival hyperemia, iris hyperpigmentation, periocular skin darkening, hypertrichosis and OSD. In contrast, patients treated with PGA without conservatives have been shown to develop fewer adverse effects. The same was observed for prostaglandin/timolol combinations without preservatives.
Studies on pilocarpine, beta-blockers, CAI and brimonidine and on combinations, albeit in smaller numbers, showed similar results regarding safety and tolerability of the preservative-free versions.
Overall, therefore, the switch from preservative to PF drugs offers the relevant advantage of reducing side effects caused by the preservative agent. The improved tolerability is observed in clinical signs, as well as in improved quality of life for patients. The reduction in adverse effects also improves adherence to therapy and supports physicians in the management of their glaucoma patients.
English 
Italian