Preservative-Free Prostaglandin Analogs and Prostaglandin/Timolol Fixed Combinations in the Treatment of Glaucoma: Efficacy, Safety and Potential Advantages

Abstract

Glaucoma therapy-related ocular surface disease (OSD) is a serious pathology with a broad spectrum of insidious clinical presentations and complex pathogenesis that undermines long-term glaucoma care. Preservatives, especially benzalkonium chloride (BAK), contained in topical intraocular pressure-lowering medications frequently cause or aggravate OSD in glaucoma. Management of these patients is challenging, and to date often empirical due to the scarcity of controlled long-term clinical trials. Most of the available data are extracted from case series and retrospective analysis. Preservative-free prostaglandins and prostaglandin/timolol fixed combinations are novel options developed to remove the harmful impact of preservatives, especially BAK, upon ocular tissues. Based on what is currently known on the value of preservative-free antiglaucoma therapies it is tempting to speculate how these new therapies may affect the future medical management of all glaucoma patients. This article provides a comprehensive and critical review of the current literature on preservative-free prostaglandins and preservative-free prostaglandin/timolol fixed combinations.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: The VISIONARY Study

“…Topical IOP-lowering medication remains the mainstay of glaucoma therapy [1][2][3][4][5]. Strong IOP-lowering efficacy, a simplified instillation regimen, and good topical and systemic tolerance are all essential for optimal treatment outcomes and long-term adherence with topical glaucoma medications [6,7]. When monotherapies do not reach the target IOP, combination therapy is necessary [6].…”

“…Prostaglandin analogue (PGA) and beta-receptor blocker (typically timolol 0.5%) combination therapies are among the most extensively used medications in glaucoma care [6,8]. Fixed-dose combination (FC) formulations are frequently used in preference to the administration of the corresponding concomitant medications, since they simplify the treatment regimen and reduce the number of daily instillations as well as the total amount of preservatives applied to the eye [1,6,7,[9][10][11].…”

“…Preservative-free (PF) topical glaucoma therapy has become increasingly used in the management of glaucoma worldwide [7,[10][11][12][13][14][15][16][17][18]. Preservatives, and in particular benzalkonium chloride (BAK), the most commonly used preservative, have been shown to induce and seriously worsen ocular surface disease (OSD) [7,[19][20][21][22][23][24]. Preservative-induced OSD is a major problem in the long-term topical treatment of glaucoma, affecting 45-60% of chronically treated glaucomatous eyes [7,25,26].…”

Real-life experience of using brinzolamide/brimonidine fixed drop combination in a tertiary glaucoma centre

“…In the long run, many glaucoma patients require more than one active intraocular pressure (IOP)-lowering molecule to reach the target IOP and prevent glaucomatous progression, and a considerable subset of the patients requires complex medication comprising more than two active IOP-lowering molecules [1][2][3][4]. Use of topical fixed dose combinations (FCs) reduces the number of daily eye drop instillations and therefore supports adherence [1,5,6]. However, in almost all IOP-lowering FCs, one of the active ingredients is a beta receptor blocker (timolol), which makes it impossible to combine the timolol-containing FCs.…”

Mitochondrial Dysfunctions May Be One of the Major Causative Factors Underlying Detrimental Effects of Benzalkonium Chloride

“…Many in vivo and in vitro studies have been developed to alleviate [29,36,[75][76][77][78][79][80], to predict or even reverse [21] the toxic effects of BAC, to replace it for other less toxic preservatives [7,26,32,[81][82][83][84][85][86][87][88][89], or to remove BAC from formulations before the use [90].…”