This prospective study showed improved ocular surface tolerance and similar efficacy with a preservative-free version of latanoprost (T2345) compared with benzalkonium chloride (BAK)-preserved latanoprost (BPL; Xalatan) in patients with ocular hypertension (OHT) or primary open angle glaucoma (POAG).
This new formulation was developed in order to avoid the undesirable effects of BAK, such as conjunctival hyperemia, decreased tear turnover, reduced tear film break-up time, inflammatory cell infiltration of the cornea, and toxic effects to the ocular surface. T2345 is the first preservative-free formulation of latanoprost to demonstrate noninferiority compared with BPL in reducing IOP.
This was a phase III, noninferiority, multicenter and investigator-masked study. It included 402 patients with POAG or OHT already managed by BPL monotherapy for at least nine months. After a wash-out period, they were randomized to receive T2345 or BPL (one drop into the affected eye(s)) once daily for 84 days.
Mean IOP reduction was 8.6 ± 2.6 mmHg (36 percent) on T2345 and 9.0 ± 2.4 mmHg (38 percent) on BPL, confirming noninferiority of T2345 to BPL. Noninferiority of T2345 was observed from day 15 onward.
The most frequent ocular adverse event, drug intolerance, was reported in one patient on T2345 versus four patients on BPL. Moderate to severe conjunctival hyperemia was less frequent on T2345 than on BPL at day 42 (20.2 vs. 30.6 percent; P = 0.003) and day 84 (21.4 vs. 29.1 percent; P = 0.02). Upon instillation, the global subjective ocular symptom score was significantly lower on T2345 than BPL on day 42 (0.15 vs. 0.41; P = 0.001) and day 84 (0.18 vs. 0.46; P = 0.001).
The study's findings do not indicate that the IOP-lowering efficacy of latanoprost is dependent upon the presence of BAK. The relatively high BAK concentration (0.02%) in preserved latanoprost has been justified by the popular assumption that BAK is necessary for latanoprost solubilization, and that BAK acts as a protective and stabilizing agent for PGA.
The formulation of T2345 eye drops has been developed based on specific polymeric agents that allow stabilization of latanoprost in the absence of BAK and at room temperature, and facilitate ocular penetration of PGA. The authors say that the study's safety results suggest a better local tolerance of T2345 compared with BPL, with less conjunctival hyperemia and fewer subjective symptoms upon instillation (especially burning/stinging and pruritus). These observations may be explained by the absence of the preservative BAK in the T2345 formulation.
They conclude that the ocular surface side effects of preserved anti-glaucoma medications should not be neglected as they may deeply impact patients' quality of life, compliance and later surgical outcome.