Analysis of the Responsiveness of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in the Treatment of OAG/OHT Patients
Release time：2021-10-18 10:40:00
Aim. Within the clinical setting, some patients have been identified as lacking in response to PGAs. This meta-analysis study aimed to evaluate the responsiveness of latanoprost, travoprost, bimatoprost, and tafluprost in OAG/OHT patients, latanoprost nonresponders (LNRs), and the IOP-reducing efficacy and safety. Methods. A literature search was conducted on PubMed, Embase, and the Cochrane Controlled Trials Register. The primary clinical endpoint was the number of responders at the end of the study. The secondary clinical endpoint was the IOP reduction at the endpoint from baseline. Safety evaluation included five common adverse events: conjunctival hyperemia, hypertrichosis, ocular burning, ocular itching, and foreign-body sensation. Results. Eleven articles containing ten RCTs were included in this meta-analysis study. The results highlighted that, in the OAG/OHT population, there was no statistically significant difference in the responsiveness of the four PGAs. Bimatoprost had a better IOP-reducing efficacy than latanoprost. There was no significant difference in the IOP-reducing efficacy of travoprost, latanoprost, and tafluprost. In LNRs, the responsiveness of bimatoprost, travoprost, and latanoprost did not show statistical differences. Bimatoprost reduced IOP with a greater extent than latanoprost and travoprost in LNRs, while there was no significant difference in the IOP-reducing efficacy of travoprost and latanoprost. No serious adverse events occurred with the treatment of the four PGAs. The prevalence of conjunctival hyperemia due to bimatoprost or tafluprost was significantly higher than that of latanoprost. Other adverse events had no significant difference between the four drugs. Conclusion. The existing studies cannot prove that latanoprost, travoprost, bimatoprost, and tafluprost have different responsiveness in OAG/OHT patients. Switching to bimatoprost or travoprost cannot achieve a significant improvement in responsiveness in LNRs. Bimatoprost has a better IOP-reducing efficacy than latanoprost and travoprost. No serious adverse events occurred during treatment with any medication we studied.
Glaucoma is the most common irreversible blindness-inducing disease on a global scale, characterized by a chronic and progressive optic neuropathy and visual field loss . Intraocular pressure (IOP) is the main risk factor for optic nerve damage, and regulation of IOP is the only clinically proven treatment that can delay disease progression . Previous research has demonstrated that lowering of the IOP by 1 mmHg can reduce the risk of glaucomatous progression by approximately 10% . Topical use of ocular hypotensive agents is typically the first therapeutic option in glaucoma. Since the 1990s, prostaglandin F2α analogues (PGAs) have gradually replaced β-blockers as the first-choice therapy due to their high clinical efficacy to reduce IOP, minimal side effects, and once-daily dosage regimens, consequently facilitating patient compliance [4, 5].
PGAs mainly decrease IOP by increasing outflow facility through an IOP-independent uveoscleral pathway. Some studies have revealed that they can also affect the IOP-dependent conventional trabecular meshwork (TM) outflow pathway [5, 6]. Among the PGAs used in the clinic, latanoprost and travoprost are ester prodrug analogs of prostaglandin F2α (PGF2α). Though usually classified as prostaglandin analogues, bimatoprost is an amide prodrug of 17-phenyl-PGF2α (similar to PGF2α) [1, 7]. Tafluprost is a unique PGF2α analog. The major modification of tafluprost is the substitution of the C-15 hydrogen and hydroxyl group with two fluorine atoms . PGAs can bind to prostaglandin receptors EP and FP in the ciliary muscle, induce ciliary muscle relaxation, and increase uveoscleral outflow facility. These drugs also increase cell contractility of the TM as well as decrease endothelial cell contractility within Schlemm’s canal, mediating aqueous humor outflow through the conventional pathway . PGAs can degrade the extracellular matrix (ECM), which results in ECM turnover in the uvea and TM and ultimately reduces outflow resistance .
PGAs have been proven effective in decreasing IOP and are widely used in the treatment of glaucoma. However, after PGA therapies, some patients do not demonstrate a significant reduction in IOP,or fail to achieve the target IOP. Such patients are usually defined as nonresponders. Although there is no clear definition, nonresponders typically refer to patients with an IOP reduction of <15% from baseline after treatment . It was reported that, in American and European populations, 12–41% of patients with glaucoma demonstrated low response to latanoprost, and such patients are defined as latanoprost nonresponders (LNRs). In Singapore, these data are approximately 5.4% . Martínez and colleagues  reported that approximately 11% of Hispanics are LNRs. It was reported that the efficacy of latanoprost is significantly undermined in elderly patients and in European and American populations . However, other studies revealed that age and baseline IOP are not factors affecting patient responsiveness to PGAs [14, 15]. Several studies demonstrated that replacing latanoprost with bimatoprost or travoprost can further decrease IOP in LNRs [16–18]. This can be due to varying PGA not acting on the same receptor . Some researchers postulated that bimatoprost interacts with a unique receptor that is unassociated with other PGA receptors. However, this “undefined receptor” has not yet been cloned [1, 10].
This meta-analysis aimed to evaluate the responsiveness of latanoprost (0.005 mg/mL), travoprost (0.004 mg/mL), bimatoprost (0.03 mg/mL), and tafluprost (0.0015 mg/mL) eye-drop-based therapies in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and whether substituting latanoprost with other PGAs can further reduce the IOP in LNRs. This study also evaluated the IOP-reducing efficacy and safety of the four PGAs in patients with OAG or OHT.