Washout Duration of Prostaglandin Analogues: A Systematic Review and Meta-analysis

Abstract

Topic Prostaglandin analogues (PGAs) are first-line medical therapy for primary open angle glaucoma (POAG) and ocular hypertension (OHT). Intraocular pressure (IOP) lowering effects in full responders are known to be 25–33% for this class; however, partial responders and nonresponders do exist. In clinical trials or prospective series, discontinuation and washout of PGAs is necessary to evaluate true change in IOP from novel surgeries and medical therapies. Clinical Relevance To identify all relevant papers with pertinent data on washout of PGAs and quantify the duration and long-term effect of reported PGA washout periods in glaucoma and OHT patients. Methods A systematic review and meta-analysis was conducted to investigate the long-term effects on IOP after discontinuation of topical PGAs POAG and OHT patients. The main search was conducted in MEDLINE/PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, and BIOSIS Previews and conference proceedings. Results 1055 papers were identified, 548 were independently screened by two physicians., and 56 papers were analyzed for washout durations. The mean washout was found to be 4.56 weeks (±1.25), with the mode and median being 5 weeks. Five studies were analyzed as randomized control trials in which latanoprost was discontinued for 4 weeks prior to restarting another intraocular pressure-lowering drug. Meta-analysis revealed a 4-week discontinuation of latanoprost, on average, subjects returned to their baseline IOP. Conclusion A significant IOP-lowering effect of latanoprost was not observed beyond 4 weeks, suggesting this may be an appropriate washout period for latanoprost. We could not identify appropriate washout periods for either travoprost or bimatoprost, although a majority of articles had 4-week washout durations for the two drugs. Despite the widespread use of this class of medication, there is a paucity of literature on the effects of PGA washout in patients that are treatment naïve to other topical medications.

Epidemiological Characteristics of Inpatients Undergoing Surgery for Glaucoma at Tianjin Eye Hospital from 2013 to 2017

“…One reason may be the insidious onset of POAG, and the other may be the popularity of prostaglandin derivatives, which have long-lasting efficacy and safety [ 16 ]. It has been proven that prostaglandin derivatives can effectively reduce IOP by 25∼33% [ 17 ].…”

Topical Medication Therapy for Glaucoma and Ocular Hypertension

“…Prostaglandins (PGs) are potent biologically active metabolites of the arachidonic acid that modulate many biological responses in various tissues including the eye ( Matsou and Anastasopoulos, 2018 ). PGAs represent the first-line medical therapy to cure POAG and OHT, since they target different PG receptors to reduce IOP ( Diaconita et al, 2018 ; Angeli and Supuran, 2019 ) ( Table 1 ).…”

“…Prostaglandin F2 (PGF2) analogs bind to PG receptors and promote muscle relaxation and extracellular matrix remodeling in the ciliary muscle and TM, thus increasing AH outflow in both the conventional and unconventional pathways ( Matsou and Anastasopoulos, 2018 ; Jayanetti et al, 2020 ). PGF2 analogs reduce IOP by 25–33% ( Diaconita et al, 2018 ), they are widely available on the market in most countries ( Matsou and Anastasopoulos, 2018 ), and include latanoprost (Xalatan ® ), bimatoprost (Lumigan ® ), travoprost (Travatan Z ® ), and tafluprost (Tapros ® ) ( Matsou and Anastasopoulos, 2018 ).…”

Matrix Metalloproteinases and Glaucoma Treatment

“…In fact, a washout period of 4 weeks for PGAs has typically been used in clinical trials in glaucoma, and there is evidence of lingering effects of the PGAs in some patients beyond 4 weeks. 99 We hypothesize that the continued IOP-lowering effect seen in some patients for several weeks after topical PGA washout reflects the time required for reversal of the PGA-induced MMP-mediated remodeling of outflow tissues. Because the effects of PGAs on MMP expression are concentration dependent, we reasoned that it might be possible to achieve more extensive tissue remodeling, and a longer remnant effect on IOP, if a higher drug concentration was achieved in the outflow tissues.…”