Omidenepag isopropyl
Omidenepag isopropyl (a prodrug of the biologically active metabolite omidenepag) is a relatively selective prostaglandin EP2 receptor agonist with a novel mechanism of action. It reduces elevated intra-ocular pressure (IOP) by increasing aqueous humour drainage through the trabecular and uveoscleral outflow pathways. Clinical efficacy has been confirmed in several studies.[88]Kuo HT, Yeh CY, Hsu AY, et al. Clinical efficacy of omidenepag isopropyl for primary open-angle glaucoma, normal tension glaucoma, or ocular hypertension: a meta-analysis. J Ocul Pharmacol Ther. 2023 Aug 9.
https://www.liebertpub.com/doi/10.1089/jop.2023.0058
http://www.ncbi.nlm.nih.gov/pubmed/37579061?tool=bestpractice.com
Approval has been granted in the US for the reduction of elevated or increased IOP in patients with open-angle glaucoma or ocular hypertension. Notable adverse effects include conjunctival hyperaemia, corneal thickening, macular oedema/cystoid macular oedema and ocular inflammation.[89]Bae BJ, Kang EM, Lee SY. Cystoid macular edema associated with omidenepag isopropyl in a phakic eye with an implantable collamer lens: a case report. BMC Ophthalmol. 2023 Jul 26;23(1):334.
https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-023-03091-0
http://www.ncbi.nlm.nih.gov/pubmed/37495978?tool=bestpractice.com
It should be used with caution in patients with aphakic or pseudophakic eyes.[90]Matsuo M, Matsuoka Y, Tanito M. Efficacy and patient tolerability of omidenepag isopropyl in the treatment of glaucoma and ocular hypertension. Clin Ophthalmol. 2022;16:1261-79.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9058248
http://www.ncbi.nlm.nih.gov/pubmed/35510270?tool=bestpractice.com
Ripasudil
Ripasudil is a rho kinase inhibitor. Efficacy of ripasudil has been demonstrated in combination with timolol or latanoprost.[61]Clement Freiberg J, von Spreckelsen A, Kolko M, et al. Rho kinase inhibitor for primary open-angle glaucoma and ocular hypertension. Cochrane Database Syst Rev. 2022 Jun 10;6(6):CD013817.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9185806
http://www.ncbi.nlm.nih.gov/pubmed/35686679?tool=bestpractice.com
[62]Nana Wandji B, Bacq N, Ehongo A. Efficacy and safety of rho kinase inhibitors vs. beta-blockers in primary open-angle glaucoma: a systematic review with meta-analysis. J Clin Med. 2024 Mar 18;13(6):1747.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10971175
http://www.ncbi.nlm.nih.gov/pubmed/38541970?tool=bestpractice.com
Ripasudil plus timolol significantly reduced IOP compared with timolol monotherapy; combination therapy was associated with increased ocular adverse effects.[61]Clement Freiberg J, von Spreckelsen A, Kolko M, et al. Rho kinase inhibitor for primary open-angle glaucoma and ocular hypertension. Cochrane Database Syst Rev. 2022 Jun 10;6(6):CD013817.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9185806
http://www.ncbi.nlm.nih.gov/pubmed/35686679?tool=bestpractice.com
[62]Nana Wandji B, Bacq N, Ehongo A. Efficacy and safety of rho kinase inhibitors vs. beta-blockers in primary open-angle glaucoma: a systematic review with meta-analysis. J Clin Med. 2024 Mar 18;13(6):1747.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10971175
http://www.ncbi.nlm.nih.gov/pubmed/38541970?tool=bestpractice.com
No study has compared the efficacy of ripasudil monotherapy with that of beta-blocker monotherapy.[62]Nana Wandji B, Bacq N, Ehongo A. Efficacy and safety of rho kinase inhibitors vs. beta-blockers in primary open-angle glaucoma: a systematic review with meta-analysis. J Clin Med. 2024 Mar 18;13(6):1747.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10971175
http://www.ncbi.nlm.nih.gov/pubmed/38541970?tool=bestpractice.com
Ripasudil is not currently available in the US or Europe.
Neuroprotective agents
One Cochrane review that assessed the effectiveness of neuroprotective agents in slowing the progression of open-angle glaucoma found no evidence that they prevent retinal ganglion cell death, and therefore preserve vision, in open-angle glaucoma patients.[91]Sena DF, Lindsley K. Neuroprotection for treatment of glaucoma in adults. Cochrane Database Syst Rev. 2017 Jan 25;(1):CD006539.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006539.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/28122126?tool=bestpractice.com
Further clinical research in the form of randomised controlled trials with long-term follow-up is needed to determine efficacy.[91]Sena DF, Lindsley K. Neuroprotection for treatment of glaucoma in adults. Cochrane Database Syst Rev. 2017 Jan 25;(1):CD006539.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006539.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/28122126?tool=bestpractice.com
[92]Khatib TZ, Martin KR. Neuroprotection in glaucoma: towards clinical trials and precision medicine. Curr Eye Res. 2020 Mar;45(3):327-38.
http://www.ncbi.nlm.nih.gov/pubmed/31475591?tool=bestpractice.com
New drug delivery systems
Several drug delivery systems are available, or being developed, to address patient adherence and the adverse effects associated with glaucoma medical therapy. These include punctal plugs, rings placed in the fornix, drug-eluting contact lenses, subconjunctival injections/devices, intracameral delivery systems (e.g., bimatoprost and travoprost intracameral implants [approved in the US]), and drug-eluting intra-ocular devices.[93]Perera SA, Ting DS, Nongpiur ME, et al. Feasibility study of sustained-release travoprost punctum plug for intraocular pressure reduction in an Asian population. Clin Ophthalmol. 2016 Apr 26;10:757-64.
https://www.dovepress.com/feasibility-study-of-sustained-release-travoprost-punctum-plug-for-int-peer-reviewed-fulltext-article-OPTH
http://www.ncbi.nlm.nih.gov/pubmed/27175058?tool=bestpractice.com
[94]Brandt JD, DuBiner HB, Benza R, et al. Long-term safety and efficacy of a sustained-release bimatoprost ocular ring. Ophthalmology. 2017 Oct;124(10):1565-6.
https://www.aaojournal.org/article/S0161-6420(17)30388-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/28528010?tool=bestpractice.com
[95]Gote V, Sikder S, Sicotte J, et al. Ocular drug delivery: present innovations and future challenges. J Pharmacol Exp Ther. 2019 Sep;370(3):602-24.
https://jpet.aspetjournals.org/content/370/3/602
http://www.ncbi.nlm.nih.gov/pubmed/31072813?tool=bestpractice.com
[96]Wong TT, Novack GD, Natarajan JV, et al. Nanomedicine for glaucoma: sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops. Drug Deliv Transl Res. 2014 Aug;4(4):303-9.
http://www.ncbi.nlm.nih.gov/pubmed/25787063?tool=bestpractice.com
[97]Gutiérrez-Hernández JC, Caffey S, Abdallah W, et al. One-year feasibility study of Replenish MicroPump for intravitreal drug delivery: a pilot study. Transl Vis Sci Technol. 2014 July;3(4):1.
https://tvst.arvojournals.org/article.aspx?articleid=2120943
http://www.ncbi.nlm.nih.gov/pubmed/25774328?tool=bestpractice.com
[98]Craven ER, Walters T, Christie WC, et al. 24-month phase I/II clinical trial of bimatoprost sustained-release implant (Bimatoprost SR) in glaucoma patients. Drugs. 2020 Feb;80(2):167-79.
https://link.springer.com/article/10.1007/s40265-019-01248-0
http://www.ncbi.nlm.nih.gov/pubmed/31884564?tool=bestpractice.com
[99]Dick HB, Schultz T, Gerste RD. Miniaturization in glaucoma monitoring and treatment: a review of new technologies that require a minimal surgical approach. Ophthalmol Ther. 2019 Mar;8(1):19-30.
https://link.springer.com/article/10.1007/s40123-019-0161-2
http://www.ncbi.nlm.nih.gov/pubmed/30725339?tool=bestpractice.com
[100]Berdahl JP, Sarkisian SR Jr, Ang RE, et al. Efficacy and safety of the travoprost intraocular implant in reducing topical IOP - lowering medication burden in patients with open-angle glaucoma or ocular hypertension. Drugs. 2024 Jan;84(1):83-97.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10789685
http://www.ncbi.nlm.nih.gov/pubmed/38060092?tool=bestpractice.com
[101]Sarkisian SR, Ang RE, Lee AM, et al. Travoprost intracameral implant for open-angle glaucoma or ocular hypertension: 12-month results of a randomized, double-masked trial. Ophthalmol Ther. 2024 Apr;13(4):995-1014.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10912401
http://www.ncbi.nlm.nih.gov/pubmed/38345710?tool=bestpractice.com