Emerging drugs for the treatment of glaucoma: a review of phase II & III trials

References

• Aihara M, Lu F, Kawata H, et al. Omidenepag isopropyl versus latanoprost in primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 2020;220:53–63.
   PubMed Web of Science ®Google Scholar
• Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma. JAMA. 2014;311(18):1901.
   PubMed Web of Science ®Google Scholar
• Inoue K. Managing adverse effects of glaucoma medications. Clin Ophthalmol. cited May 2014;903. DOI: 10.2147/OPTH.S44708.
   PubMedGoogle Scholar
• Shalaby WS, Shankar V, Razeghinejad R, et al. Current and new pharmacotherapeutic approaches for glaucoma. Expert Opin Pharmacother. 2020;21(16):2027–2040.
   PubMed Web of Science ®Google Scholar
• Aihara M, Lu F, Kawata H, et al. Pharmacokinetics, safety, and intraocular pressure-lowering profile of omidenepag isopropyl, a selective, nonprostaglandin, prostanoid EP2 receptor agonist, in healthy Japanese and Caucasian volunteers (phase I study). J Ocul Pharmacol Ther. 2019;35(10):542–550.
   PubMed Web of Science ®Google Scholar
• Roy Chowdhury U, Millar JC, Holman BH, et al. Effect of ATP-sensitive potassium channel openers on intraocular pressure in ocular hypertensive animal models. Invest Ophthalmol Vis Sci. 2022;63(2):15.
   PubMedGoogle Scholar
• Quigley HA. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–267.
   PubMed Web of Science ®Google Scholar
• Varma R, Lee PP, Goldberg I, et al. An assessment of the health and economic burdens of glaucoma. Am J Ophthalmol. 2011;152(4):515–522.
   PubMed Web of Science ®Google Scholar
• Li T, Lindsley K, Rouse B, et al. Comparative effectiveness of first-line medications for primary open-angle glaucoma. Ophthalmology. 2016;123(1):129–140.
   PubMed Web of Science ®Google Scholar
• Boland MV, Ervin A-M, Friedman DS, et al. Comparative effectiveness of treatments for open-angle glaucoma: a systematic review for the U.S. Preventive services task force. Ann Intern Med. 2013;158(4):271.
   PubMed Web of Science ®Google Scholar
• Tanna A. BCSC 10: glaucoma. 2021.
   Google Scholar
• Goel M. Aqueous humor dynamics: a review~!2010-03-03~!2010-06-17~!2010-09-02~! Open Ophthalmol J. 2010;4(1):52–59.
   PubMedGoogle Scholar
• Malihi M, Sit AJ. Aqueous humor dynamics and implications for clinical practice. Int Ophthalmol Clin. 2011;51(3):119–139.
   PubMedGoogle Scholar
• Toris CB, Yablonski ME, Wang Y-L, et al. Aqueous humor dynamics in the aging human eye. Am J Ophthalmol. 1999;127(4):407–412.
   PubMed Web of Science ®Google Scholar
• Johnson M, McLaren JW, Overby DR. Unconventional aqueous humor outflow: a review. Exp Eye Res. 2017;158:94–111.
   PubMed Web of Science ®Google Scholar
• Nicox Visible Science. Nicox reports positive results of secondary analyses from phase 2 trial further highlighting potential of NCX 470 in glaucoma. 2021.
   Google Scholar
• Duggan S. Omidenepag Isopropyl Ophthalmic Solution 0.002%: first Global Approval. Drugs. 2018;78(18):1925–1929.
   PubMed Web of Science ®Google Scholar
• Kirihara T, Taniguchi T, Yamamura K, et al. Pharmacologic characterization of omidenepag isopropyl, a novel selective EP2 receptor agonist, as an ocular hypotensive agent. Invest Ophthalmol Vis Sci. 2018;59(1):145.
   PubMed Web of Science ®Google Scholar
• Fuwa M, Toris CB, Fan S, et al. Effects of a novel selective EP2 receptor agonist, omidenepag isopropyl, on aqueous humor dynamics in laser-induced ocular hypertensive monkeys. J Ocul Pharmacol Ther. 2018;34(7):531–537.
   PubMed Web of Science ®Google Scholar
• Olander KW, Sato MA, Abrams MA, et al. A randomized phase 2 trial comparing omidenepag isopropyl 0.002% once and twice daily in subjects with primary open-angle glaucoma or ocular hypertension (SPECTRUM-6). J Glaucoma. 2021;30(6):473–480.
   PubMedGoogle Scholar
• Inoue K, Shiokawa M, Katakura S, et al. Periocular Adverse Reactions to Omidenepag Isopropyl. Am J Ophthalmol. 2022;237:114–121.
   PubMedGoogle Scholar
• Jayanetti V, Sandhu S, Lusthaus JA. The latest drugs in development that reduce intraocular pressure in ocular hypertension and glaucoma. J Exp Pharmacol. 2020;12:539–548.
   PubMedGoogle Scholar
• Wirta DL, Kuwayama Y, Lu F, et al. Phase 2b, randomized, 3-month, dose-finding study of sepetaprost in patients with primary open-angle glaucoma or ocular hypertension: the ANGEL study. J Ocul Pharmacol Ther. 2022 February 15;38(3):240–251. cited February 15, 2022.
   PubMedGoogle Scholar
• Brigell M, Withers B, Buch A, et al. Tie2 activation via VE-PTP inhibition with razuprotafib as an adjunct to latanoprost in patients with open angle glaucoma or ocular hypertension. Transl Vis Sci Technol. 2022;11(1):7.
   PubMedGoogle Scholar
• Li G, Nottebaum AF, Brigell M, et al. A small molecule inhibitor of VE-PTP activates Tie2 in Schlemm’s Canal increasing outflow facility and reducing intraocular pressure. Invest Ophthalmol Vis Sci. 2020;61(14):12.
   Web of Science ®Google Scholar
• Impagnatiello F, Toris CB, Batugo M, et al. Intraocular pressure–lowering activity of NCX 470, a novel nitric oxide–donating bimatoprost in preclinical models. Invest Ophthalmol Vis Sci. 2015;56(11):6558.
   PubMed Web of Science ®Google Scholar
• Nicox Visible Science. Nicox’s NCX 470 demonstrates significant intraocular pressure lowering in dolomites phase 2 glaucoma trial. Available from: globenewswire.com.
   Google Scholar
• Helzner J. Nicox begins second phase 3 trial of NCX 470. Available from: glaucomaphysician.net.
   Google Scholar
• Martínez T, González MV, Roehl I, et al. In vitro and in vivo efficacy of SYL040012, a novel siRNA compound for treatment of glaucoma. Mol Ther. 2014;22(1):81–91.
   PubMed Web of Science ®Google Scholar
• Moreno-Montañés J, Sádaba B, Ruz V, et al. Phase I clinical trial of SYL040012, a small interfering RNA targeting β-adrenergic receptor 2, for lowering intraocular pressure. Mol Ther. 2014;22(1):226–232.
   PubMed Web of Science ®Google Scholar
• Sylentis. Sylentis announces top-line results from phase II study SYLTAG for RNAi drug bamosiran (SYL040012) in glaucoma. Available from: https://www.sylentis.com.
   Google Scholar
• Qlaris. Qlaris bio enrolls first patient in phase 1/2 Studies of QLS-101, an investigational therapy designed to lower episcleral venous pressure (EVP) in patients with glaucoma. Available from: businesswire.com.
   Google Scholar
• Roy Chowdhury U, Viker KB, Stoltz KL, et al. Analogs of the ATP-sensitive potassium (K ATP) channel opener cromakalim with in vivo ocular hypotensive activity. J Med Chem. 2016;59(13):6221–6231.
   PubMedGoogle Scholar
• Roy Chowdhury U, Dosa PI, Fautsch MP. ATP sensitive potassium channel openers: a new class of ocular hypotensive agents. Exp Eye Res. 2017;158:85–93.
   PubMed Web of Science ®Google Scholar
• Roy Chowdhury U, Bahler CK, Holman BH, et al. Ocular hypotensive effects of the ATP-sensitive potassium channel opener cromakalim in human and murine experimental model systems. PLoS One. 2015;10(11):e0141783.
   PubMedGoogle Scholar
• Tran E, Sanvicente C, Hark LA, et al. Educational intervention to adopt selective laser trabeculoplasty as first-line glaucoma treatment: randomized controlled trial: educational intervention on selective laser trabeculoplasty. Eur J Ophthalmol. 2022;32(3):1538–1546.
   PubMedGoogle Scholar
• Musch DC, Gillespie BW, Lichter PR, et al. Visual field progression in the collaborative initial glaucoma treatment study. Ophthalmology. 2009;116(2):200–207.e1.
   PubMed Web of Science ®Google Scholar
• Lichter P. Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943–1953.
   PubMed Web of Science ®Google Scholar
• Gupta D, Musch DC, Niziol LM, et al. Refusal of trabeculectomy for the fellow eye in collaborative initial glaucoma treatment study (CIGTS) participants. Am J Ophthalmol. 2016;166:1–7.
   PubMedGoogle Scholar
• Jampel HD, Musch DC, Gillespie BW, et al. Perioperative complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS). Am J Ophthalmol. 2005;140(1):16–22.
   PubMed Web of Science ®Google Scholar
• Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019;393(10180):1505–1516.
   PubMed Web of Science ®Google Scholar
• Toris CB, Gabelt BT, Kaufman PL. Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction. Surv Ophthalmol. 2008;53(6):S107–S120.
   PubMedGoogle Scholar
• Crowston JG, Aihara M, Lindsey JD, et al. Effect of latanoprost on outflow facility in the mouse. Invest Ophthalmol Vis Sci. 2004;45(7):2240.
   PubMedGoogle Scholar
• Richter M, Krauss AH-P, Woodward DF, et al. Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide. Invest Ophthalmol Vis Sci. 2003;44(10):4419.
   PubMed Web of Science ®Google Scholar
• Lin L, Zhao YJ, Chew PTK, et al. Comparative efficacy and tolerability of topical prostaglandin analogues for primary open-angle glaucoma and ocular hypertension. Ann Pharmacother. 2014;48(12):1585–1593.
   PubMed Web of Science ®Google Scholar
• Johnstone MA, Albert DM. Prostaglandin-induced hair growth. Surv Ophthalmol. 2002;47:S185–S202.
   PubMed Web of Science ®Google Scholar
• Wistrand PJ, Stjernschantz J, Olsson K. The incidence and time-course of latanoprost-induced iridial pigmentation as a function of eye color. Surv Ophthalmol. 1997;41:S129–S138.
   PubMed Web of Science ®Google Scholar
• Filippopoulos T, Paula JS, Torun N, et al. Periorbital changes associated with topical bimatoprost. Ophthalmic Plast Reconstr Surg. 2008;24(4):302–307.
   PubMed Web of Science ®Google Scholar
• Ida Y, Hikage F, Umetsu A, et al. Omidenepag, a non-prostanoid EP2 receptor agonist, induces enlargement of the 3D organoid of 3T3-L1 cells. Sci Rep. 2020;10(1):16018.
   PubMedGoogle Scholar
• Oogi S, Nakakura S, Terao E, et al. One-year follow-up study of changes in prostaglandin-associated periorbital syndrome after switch from conventional prostaglandin F2alfa to omidenepag isopropyl. Cureus. [Published online 2020 Aug 27]. DOI:10.7759/cureus.10064
   Google Scholar
• Wendel C, Zakrzewski H, Carleton B, et al. Association of postoperative topical prostaglandin analog or beta-blocker use and incidence of pseudophakic cystoid macular edema. J Glaucoma. 2018;27(5):402–406.
   PubMed Web of Science ®Google Scholar
• Holló G, Aung T, Cantor LB, et al. Cystoid macular edema related to cataract surgery and topical prostaglandin analogs: mechanism, diagnosis, and management. Surv Ophthalmol. 2020;65(5):496–512.
   PubMed Web of Science ®Google Scholar
• Sears ML. Regulation of aqueous flow by the adenylate cyclase receptor complex in the ciliary epithelium. Am J Ophthalmol. 1985;100(1):194–198.
   PubMedGoogle Scholar
• Neufeld AH, Bartels SP, Liu JHK. Laboratory and clinical studies on the mechanism of action of timolol. Surv Ophthalmol. 1983;28:286–290.
   PubMedGoogle Scholar
• Allen RC, Hertzmark E, Walker AM, et al. A double-masked comparison of betaxolol vs timolol in the treatment of open-angle glaucoma. Am J Ophthalmol. 1986;101(5):535–541.
   PubMed Web of Science ®Google Scholar
• Leske MC, Heijl A, Hyman L, et al. Early manifest glaucoma trial. Ophthalmology. 1999;106(11):2144–2153.
   PubMed Web of Science ®Google Scholar
• Liu JHK, Kripke DF, Weinreb RN. Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure. Am J Ophthalmol. 2004;138(3):389–395.
   PubMed Web of Science ®Google Scholar
• Nau CB, Malihi M, McLaren JW, et al. Circadian variation of aqueous humor dynamics in older healthy adults. Invest Ophthalmol Vis Sci. 2013;54(12):7623–7629.
   PubMedGoogle Scholar
• Brubaker RF. Flow of aqueous humor in humans [The Friedenwald Lecture]. Invest Ophthalmol Vis Sci. 1991;32(13):3145–3166.
   PubMed Web of Science ®Google Scholar
• Kazemi A, McLaren JW, Trese MGJ, et al. Effect of timolol on aqueous humor outflow facility in healthy human eyes. Am J Ophthalmol. 2019;202:126–132.
   PubMedGoogle Scholar
• Kolli A, Toris CB, Reed DM, et al. The effects of topical timolol and latanoprost on calculated ocular perfusion pressure in nonglaucomatous volunteers. J Ocul Pharmacol Ther. 2021;37(10):565–574.
   PubMedGoogle Scholar
• Buckley MM-T, Goa KL, Clissold SP. Ocular Betaxolol. Drugs. 1990;40(1):75–90.
   PubMed Web of Science ®Google Scholar
• Maus TL. Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow in humans. Arch Ophthalmol. 1997;115(1):45.
   PubMedGoogle Scholar
• van der Valk R, Webers CAB, Schouten JSAG, et al. Intraocular pressure–lowering effects of all commonly used glaucoma drugs. Ophthalmology. 2005;112(7):1177–1185.
   PubMed Web of Science ®Google Scholar
• Schmickl CN, Owens RL, Orr JE, et al. Side effects of acetazolamide: a systematic review and meta-analysis assessing overall risk and dose dependence. BMJ Open Respir Res. 2020;7(1):e000557.
   PubMed Web of Science ®Google Scholar
• Ebied AM, Gracey S. Acetazolamide-induced sickle cell crisis. Ann Pharmacother. 2018;52(10):1047–1048.
   PubMed Web of Science ®Google Scholar
• Storgaard L, Tran TL, Freiberg JC, et al. Glaucoma clinical research: trends in treatment strategies and drug development. Front Med. 2021;8. DOI: 10.3389/fmed.2021.733080
   Google Scholar
• Greenfield DS, Liebmann JM, Ritch R. Brimonidine: a new alpha2-adrenoreceptor agonist for glaucoma treatment. J Glaucoma. 1997;6(4):250–258. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9264305
   PubMedGoogle Scholar
• Potter DE, Crosson CE, HEATH AR, et al. Alpha 2 and DA 2 agonists as antiglaucoma agents: comparative pharmacology and clinical potential. J Ocul Pharmacol Ther. 1990;6(3):251–257.
   Google Scholar
• Schuman JS. A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension. Arch Ophthalmol. 1997;115(7):847.
   PubMed Web of Science ®Google Scholar
• Liu JHK, Medeiros FA, Slight JR, et al. Diurnal and nocturnal effects of brimonidine monotherapy on intraocular pressure. Ophthalmology. 2010;117(11):2075–2079.
   PubMed Web of Science ®Google Scholar
• Bowman RJC, Cope J, Nischal KK. Ocular and systemic side effects of brimonidine 0.2% eye drops (Alphagan®) in children. Eye. 2004;18(1):24–26.
   PubMed Web of Science ®Google Scholar
• Tanna AP, Johnson M. Rho kinase inhibitors as a novel treatment for glaucoma and ocular hypertension. Ophthalmology. 2018;125(11):1741–1756.
   PubMed Web of Science ®Google Scholar
• Kazemi A, McLaren JW, Kopczynski CC, et al. The effects of netarsudil ophthalmic solution on aqueous humor dynamics in a randomized study in humans. J Ocul Pharmacol Ther. 2018;34(5):380–386.
   PubMed Web of Science ®Google Scholar
• Sit AJ, Gupta D, Kazemi A, et al. Netarsudil improves trabecular outflow facility in patients with primary open angle glaucoma or ocular hypertension: a phase 2 study. Am J Ophthalmol. 2021;226:262–269.
   PubMedGoogle Scholar
• Singh IP, Fechtner RD, Myers JS, et al. Pooled efficacy and safety profile of netarsudil ophthalmic solution 0.02% in patients with open-angle glaucoma or ocular hypertension. J Glaucoma. 2020;29(10):878–884.
   PubMed Web of Science ®Google Scholar
• Kahook MY, Serle JB, Mah FS, et al. Long-term safety and ocular hypotensive efficacy evaluation of netarsudil ophthalmic solution: rho kinase elevated IOP treatment trial (ROCKET-2). Am J Ophthalmol. 2019;200:130–137.
   PubMed Web of Science ®Google Scholar
• Snell S. On eserine and pilocarpine in glaucoma, and eserine in ocular neuralgia. BMJ. 1882;1(1118):811–812.
   PubMedGoogle Scholar
• Croft MA, Oyen MJ, Gange SJ, et al. Aging effects on accommodation and outflow facility responses to pilocarpine in humans. Arch Ophthalmol. 1996;114(5):586–592.
   PubMedGoogle Scholar
• Zimmerman TJ, Wheeler TM. Side effects and ways to avoid them. Ophthalmology. 1982;89(1):76–80.
   PubMedGoogle Scholar
• Ammar DA, Noecker RJ, Kahook MY. Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human ocular epithelial cells. Adv Ther. 2010;27(11):837–845.
   PubMed Web of Science ®Google Scholar
• Baudouin C, Denoyer A, Desbenoit N, et al. In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2012;110:40–63.
   PubMedGoogle Scholar
• Tham Y-C, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040. Ophthalmology. 2014;121(11):2081–2090.
   PubMed Web of Science ®Google Scholar
• Charters L. Novel devices, drugs driving expansion in glaucoma market. Ophthalmol Times. 2022 Feb;47(2).
   Google Scholar
• Reports MI. Glaucoma treatment market - Growth, trends, COVID-19 impact, and forecasts (2022 – 2027). 2021.
   Google Scholar
• Delveinsight. Glaucoma - Market insight, epidemiology and market forecast - 2032. 2022.
   Google Scholar
• Brubaker RF. Targeting outflow facility in glaucoma management. Surv Ophthalmol. 2003;48(Suppl 1):S17–20.
   PubMed Web of Science ®Google Scholar
• Nakamura N, Honjo M, Yamagishi R, et al. Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction. Sci Rep. 2021;11(1):16257.
   PubMedGoogle Scholar
• Aihara M, Lu F, Kawata H, et al. Twelve-month efficacy and safety of omidenepag isopropyl, a selective EP2 agonist, in open-angle glaucoma and ocular hypertension: the RENGE study. Jpn J Ophthalmol. 2021;65(6):810–819.
   PubMedGoogle Scholar
• Impagnatiello F, Bastia E, Almirante N, et al. Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma. Br J Pharmacol. 2019;176(8):1079–1089.
   PubMed Web of Science ®Google Scholar
• Sit AJ, McLaren JW. Measurement of episcleral venous pressure. Exp Eye Res. 2011;93(3):291–298.
   PubMed Web of Science ®Google Scholar
• Steel C, Sookdeo HK, Htoo T, et al. Ocular tissue conversion and activity profile of QLS-101, a novel topical IOP-lowering therapeutic. Invest Ophthalmol Vis Sci Ophthalmol Vis Sci. 2021;62:2755.
   Google Scholar
• Roy Chowdhury U, Rinkoski TA, Bahler CK, et al. Effect of cromakalim prodrug 1 (CKLP1) on aqueous humor dynamics and feasibility of combination therapy with existing ocular hypotensive agents. Invest Ophthalmol Vis Sci. 2017;58(13):5731.
   PubMedGoogle Scholar
• Schachar RA, Raber S, Courtney R, et al. A phase 2, randomized, dose-response trial of taprenepag isopropyl (PF-04217329) versus latanoprost 0.005% in open-angle glaucoma and ocular hypertension. Curr Eye Res. 2011;36(9):809–817.
   PubMed Web of Science ®Google Scholar
• Schachar RA, Raber S, Thomas KV, et al. Subclinical increased anterior stromal reflectivity with topical taprenepag isopropyl. Cornea. 2013;32(3):306–312.
   PubMedGoogle Scholar
• Santen Pharmaceutical. Santen and ube announces launch of glaucoma and ocular hypertension treatment EYBELIS ophthalmic solution 0.002% in South Korea. 2021.
   Google Scholar
• Santen Pharmaceutical. Santen and ube announces U.S. FDA acceptance of new drug application for STN10117 (DE-117) (JAN: omidenepag isopropyl) as a treatment for patients with glaucoma and ocular hypertension. 2021.
   Google Scholar
• Shiratori N, Nishio Y, Takeda A, et al. Twenty-Four-hour intraocular pressure control with omidenepag isopropyl 0.002% in patients with glaucoma and ocular hypertension. Clin Ophthalmol. 2021;15:3997–4003.
   PubMed Web of Science ®Google Scholar
• Inoue K, Inoue J, Kunimatsu-Sanuki S, et al. Short-term efficacy and safety of omidenepag isopropyl in patients with normal-tension glaucoma. Clin Ophthalmol. 2020;14:2943–2949.
   PubMed Web of Science ®Google Scholar
• Iwamura R, Tanaka M, Okanari E, et al. Identification of a selective, non-prostanoid EP2 receptor agonist for the treatment of glaucoma: omidenepag and its prodrug omidenepag isopropyl. J Med Chem. 2018;61(15):6869–6891.
   PubMedGoogle Scholar
• Esaki Y, Katsuta O, Kamio H, et al. The Antiglaucoma Agent and EP2 Receptor Agonist Omidenepag Does Not Affect Eyelash Growth in Mice. J Ocul Pharmacol Ther. 2020;36(7):529–533.
   PubMed Web of Science ®Google Scholar
• Yamagishi-Kimura R, Honjo M, Aihara M. The roles played by FP/EP3 receptors during pressure-lowering in mouse eyes mediated by a dual FP/EP3 receptor agonist. Invest Ophthalmol Vis Sci. 2022;63(2):24.
   PubMedGoogle Scholar
• Santen Pharmaceutical. US ophthalmic pipeline and clinical trials. Available from: Santenusa.com.
   Google Scholar
• Pharmaceuticals A. No title. Available from: globenewswire.com.
   Google Scholar
• Gonzalez V, Moreno-Montañés J, Oll M, et al. Results of phase IIB SYLTAG clinical trial with bamosiran in patients with glaucoma. Invest Ophthalmol Vis Sci. 2016;57(12):3023.
   Google Scholar
• Roy Chowdhury U, Kudgus RA, Holman BH, et al. Pharmacological profile and ocular hypotensive effects of cromakalim prodrug 1, a novel ATP-sensitive potassium channel opener, in normotensive dogs and nonhuman primates. J Ocul Pharmacol Ther. 2021;37(5):251–260.
   PubMedGoogle Scholar
• Lyons LJ, Wu KY, Baratz KH, et al. Honeycomb epithelial edema associated with rho kinase inhibition: a case series and review of the literature. Cornea. 2022;41(2):243–248. DOI:10.1097/ICO.0000000000002694.
   PubMedGoogle Scholar
• Roy Chowdhury U, Kudgus RA, Rinkoski TA, et al. Pharmacological and pharmacokinetic profile of the novel ocular hypotensive prodrug CKLP1 in Dutch-belted pigmented rabbits. PLoS One. 2020;15(4):e0231841.
   PubMed Web of Science ®Google Scholar
• Yanochko GM, Affolter T, Eighmy JJ, et al. Investigation of ocular events associated with taprenepag isopropyl, a topical EP2 agonist in development for treatment of glaucoma. J Ocul Pharmacol Ther. 2014;30(5):429–439.
   PubMed Web of Science ®Google Scholar
• Weinreb RN, Ong T, Scassellati Sforzolini B, et al. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015;99(6):738–745.
   PubMed Web of Science ®Google Scholar
• Harris A, Ward CL, Rowe-Rendleman CL, et al.Ocular Hypotensive Effect of ONO-9054, an EP3/FP Receptor Agonist: Results of a Randomized, Placebo-controlled, Dose Escalation Study. J Glaucoma. 2016;25(10):e826-e833. DOI: 10.1097/IJG.0000000000000449
   Google Scholar
• Walters TR, Kothe AC, Boyer JL, et al.A Randomized, Controlled Comparison of NCX 470 (0.021%, 0.042%, and 0.065%) and Latanoprost 0.005% in Patients With Open-angle Glaucoma or Ocular Hypertension: The Dolomites Study. J Glaucoma. 2022;31(6):382-391. DOI: 10.1097/IJG.0000000000002030
   Google Scholar