Prostaglandin analogues: past, present, and future

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This literature review is focused on the prostaglandin topical analogues and describes peculiarities of their structure, pharmacokinetics and pharmacodynamics, results of clinical trials and meta-analyzes, as well as modern trends in the topical IOP-lowering glaucoma therapy evolution.

Yury S Astakhov

FSBEI HE “Academician I.P. Pavlov First St Petersburg State Medical University” of the Ministry of Healthcare of Russia

Author for correspondence.

Russian Federation, Saint Petersburg, Russia

MD, PhD, professor. Ophthalmology Department

Pavel A Nechiporenko

FSBEI HE “Academician I.P. Pavlov First St Petersburg State Medical University” of the Ministry of Healthcare of Russia


Russian Federation, Saint Petersburg, Russia

MD, PhD, assistant. Ophthalmology Department

  1. Национальное руководство по глаукоме: для практикующих врачей / под ред. Е.А. Егорова, Ю.С. Астахова, В.П. Еричева. – 3-е изд., испр. и доп. – М.: ГЭОТАР-Медиа, 2015. – С. 190–197. [Natsional’noe rukovodstvo po glaukome: dlya praktikuyushchikh vrachei. Ed by E.A. Egorov, Yu.S. Astakhov, V.P. Erichev. Moscow; GEOTAR-Media; 2015. P. 190-197 (In Russ.)]
  2. Alm A, Grierson I, Shields MB. Side effects associated with prostaglandin analog therapy. Surv Ophthalmol. 2008;53Suppl1: S93-S105. doi: 10.1016/j.survophthal.2008.08.004.
  3. Alm A, Schoenfelder J, McDermott J. A 5-year, multicenter, open-label, safety study of adjunctive latanoprost therapy for glaucoma. Arch Ophthalmol. 2004;122:957-965. doi: 10.1001/archopht.122.7.957.
  4. Alm A, Villumsen J, Tornquist P, et al. Intraocular pressure-reducing effect of PhXA41 in patients with increased eye pressure: a one-month study. Ophthalmology. 1993Sep;100:1312-7. doi: 10.1016/S0161-6420(93)31482-X.
  5. Alm A. Latanoprost in the treatment of glaucoma. Clinical Ophthalmology. 2014;8:1967-1985.
  6. American Academy of Ophthalmology Glaucoma Panel. Primary open-angle glaucoma suspect. San Francisco (CA): American Academy of Ophthalmology; 2010.
  7. Aptel F, Cucherat M, Denis P. Efficacy and tolerability of prostaglandin analogs: a meta-analysis of randomized controlled clinical trials. J Glaucoma. 2008;17:667-673. doi: 10.1097/IJG.0b013e3181666557.
  8. Aptel F. Preservative-free versus preserved latanoprost eye drops in patients with open-angle glaucoma or ocular hypertension. Current Medical Research and Opinion. 2016;32(8):1457-1463. doi: 10.1080/03007995.2016.1202818.
  9. Aref AA. Sustained drug delivery for glaucoma: current data and future trends. Curr Opin Ophthalmol. 2016 Oct 19. [Epub ahead of print; doi: 10.1097/ICU.0000000000000334].
  10. Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-42. doi: 10.1097/00061198-200004000-00002.
  11. Bacharach J, Dubiner HB, Levy B, et al. Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. Ophthalmology. 2015;122:302-7. doi: 10.1016/j.ophtha.2014.08.022.
  12. Bacharach J. Rho Kinase/Norepinephrine Transporter Inhibition for the Treatment of Glaucoma and Ocular Hypertension. Glaucoma Today. 2016 Mar/Apr 2;14:43-45.
  13. Bill A. Conventional and uveoscleral drainage of aqueous humour in the cynomolgus monkey (Macaca irus) at normal and high intraocular pressures. Exp Eye Res. 1966;5:45-54. doi: 10.1016/S0014-4835(66)80019-2.
  14. Bill A. Movement of albumin and dextran through the sclera. Arch Ophthalmol. 1965;74:248-252. doi: 10.1001/archopht.1965.00970040250024.
  15. Bill A. The aqueous humour drainage mechanism in the cynomolgus monkey (Macaca irus) with evidence for unconventional routes. Invest Ophthalmol Vis Sci. 1965;4:911-919.
  16. Bill A, Barany EH. Gross facility, facility of conventional routes, and pseudofacility of aqueous humor outflow in the cynomolgus monkey. Arch Ophthalmol. 1966;75(5):665-673. doi: 10.1001/archopht.1966.00970050667017.
  17. Bill A, Phillips CI. Uveoscleral drainage of aqueous humour in human eyes. Exp Eye Res. 1971;12(3):275-281. doi: 10.1016/0014-4835(71)90149-7.
  18. Boland MV, Ervin AM, 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;158:271-9. doi: 10.7326/0003-4819-158-4-201302190-00008.
  19. Cheng JW, Cai JP, Li Y, et al. A meta-analysis of topical prostaglandin analogs in the treatment of chronic angle-closure glaucoma. J Glaucoma. 2009;18:652-7. doi: 10.1097/IJG.0b013e31819c49d4.
  20. Cheng JW, Wei RL. Meta-analysis of 13 randomized controlled trials comparing bimatoprost with latanoprost in patients with elevated intraocular pressure. Clin Ther. 2008;30:622-632. doi: 10.1016/j.clinthera.2008.04.006.
  21. Chuman H, Chuman T, Nao-i N, Sawada A. The effect of L-arginine on intraocular pressure in the human eye. Curr Eye Res. 2000;20(6):511-516. doi: 10.1076/0271-3683(200006)2061-YFT511.
  22. Connor AJ, Fraser SG. Glaucoma prescribing trends in England 2000 to 2012. Eye (Lond). 2014;28:863-9. doi: 10.1038/eye.2014.114.
  23. Cucherat M, Stalmans I, Rouland JF. Relative efficacy and safety of preservative-free latanoprost (T2345) for the treatment of open-angle glaucoma and ocular hypertension: an adjusted indirect comparison meta-analysis of randomized clinical trials. J Glaucoma. 2014;23:e69-e75. doi: 10.1097/IJG.0b013e3182a075e6.
  24. Daka Q, Trkulja V. Efficacy and tolerability of mono-compound topical treatments for reduction of intraocular pressure in patients with primary open angle glaucoma or ocular hypertension: an overview of reviews. Croat Med J. 2014;55(5):468-480. doi: 10.3325/cmj.2014.55.468.
  25. Dams I, et al. Therapeutic uses of prostaglandin F2 analogues in ocular disease and novel synthetic strategies. Prostaglandins & Other Lipid Mediat. 2013Jul-Aug;104-105:109-21. doi: 10.1016/j.prostaglandins.2013.01.001.
  26. Denis P, Lafuma A, Khoshnood B, et al. A meta-analysis of topical prostaglandin analogues intraocular pressure lowering in glaucoma therapy. Curr Med Res Opin. 2007;23:601-8. doi: 10.1185/030079907X178720.
  27. Dhillon J. Rhokinase Inhibitors-A Novel Potential Treatment Modality in Glaucoma. Delhi J Ophthalmol. 2016;26;272-4. doi: 10.7869/djo.189.
  28. European Glaucoma Society. Terminology and guidelines for glaucoma. Ссылка активна на 3.12.2016.
  29. Eyawo O, Nachega J, Lefebvre P, et al. Efficacy and safety of prostaglandin analogues in patients with predominantly primary open-angle glaucoma or ocular hypertension: a meta-analysis. Clin Ophthalmol. 2009;3:447-456.
  30. Fuma S, Shimazawa M, Imamura T, et al. Neuroprotective Effect of Ocular Hypotensive Drugs: Latanoprost/Timolol in Combination Are More Effective than Each as Monotherapy in RGC-5. Biol Pharm Bull. 2016;39(2):192-8. doi: 10.1248/bpb.b15-00584.
  31. Funke S, Beck S, Lorenz K, et al., Analysis of the effects of preservative-free tafluprost on the tear proteome. Am J Transl Res. 2016;8(10):4025-4039.
  32. Gandolfi S, Simmons ST, Sturm R, et al. Three-month comparison of bimatoprost and latanoprost in patients with glaucoma and ocular hypertension. Adv Ther. 2001;18:110-121. doi: 10.1007/BF02850299.
  33. Garcia GA, Ngai P, Mosaed S, Lin KY. Critical evaluation of latanoprostene bunod in the treatment of glaucoma. Clin Ophthalmol. 2016Oct18;10:2035-2050. doi: 10.2147/OPTH.S103985.
  34. Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015Apr4;385(9975):1295-304. doi: 10.1016/S0140-6736(14)62111-5.
  35. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:1268-79. doi: 10.1001/archopht.120.10.1268.
  36. Holmin C, Thorburn W, Krakau CE. Treatment versus no treatment in chronic open angle glaucoma. Acta Ophthalmol Copenh. 1988;66:170-73. doi: 10.1111/j.1755-3768.1988.tb04006.x.
  37. Holmstrom S, Buchholz P, Walt J, et al. Analytic review of bimatoprost, latanoprost and travoprost in primary open angle glaucoma. Curr Med Res Opin. 2005;21:1875-83. doi: 10.1185/030079905X65600.
  38. Honrubia F, Garcia-Sánchez J, Polo V, et al. Conjunctival hyperaemia with the use of latanoprost versus other prostaglandin analogues in patients with ocular hypertension or glaucoma: a meta-analysis of randomised clinical trials. Br J Ophthalmol. 2009;93:316-321. doi: 10.1136/bjo.2007.135111.
  39. Hotehama Y, Mishima HK, Kitazawa Y, et al. Ocular hypotensive effect of phXA41 in patients with ocular hypertension or primary open-angle glaucoma. Jpn J Ophthalmol. 1993;37(3):270-4.
  40. Hughes E, Spry P, Diamond J. 24-hour monitoring of intraocular pressure in glaucoma management: a retrospective review. J Glaucoma. 2003;12:232-6. doi: 10.1097/00061198-200306000-00009.
  41. Kara C, Şen EM, Elgin KU, et al. Does the intraocular pressure-lowering effect of prostaglandin analogues continue over the long term? Int Ophthalmol. 2016Aug 9. [Epub ahead of print; doi: 10.1007/s10792-016-0315-3].
  42. Konstas AGP, et al. 24-h Efficacy of Glaucoma Treatment Options. Adv Ther. 2016;33:481-517. doi: 10.1007/s12325-016-0302-0.
  43. Konstas AG, Katsimbris JM, Lallos N, et al. Latanoprost 0.005% versus bimatoprost 0.03% in primary open-angle glaucoma patients. Ophthalmology. 2005;112:262-266. doi: 10.1016/j.ophtha.2004.08.022.
  44. Konstas AG, Mantziris DA, Cate EA, Stewart WC. Effect of timolol on the diurnal intraocular pressure in exfoliation and primary open-angle glaucoma. Arch Ophthalmol. 1997;115:975-9. doi: 10.1001/archopht.1997.01100160145002.
  45. Konstas AG, Mantziris DA, Stewart WC. Diurnal intraocular pressure in untreated exfoliation and primary open-angle glaucoma. Arch Ophthalmol. 1997;115:182-5. doi: 10.1001/archopht.1997.01100150184006.
  46. Kotikoski H, Alajuuma P, Moilanen E, et al. Comparison of nitric oxide donors in lowering intraocular pressure in rabbits: role of cyclic GMP. J Ocul Pharmacol Ther. 2002;18(1):11-23. doi: 10.1089/108076802317233171.
  47. Lee AJ, McCluskey P. Clinical utility and differential effects of prostaglandin analogs in the management of raised intraocular pressure and ocular hypertension. Clin Ophthalmol. 2010Jul 30;4:741-764.
  48. Lewis RA, Levy B, Ramirez N, et al. Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomised, controlled study in patients with open-angle glaucoma or ocular hypertension. Br J Ophthalmol. 2016;100:339-44. doi: 10.1136/bjophthalmol-2015-306778.
  49. Li N, Chen XM, Zhou Y, et al. Travoprost compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension: meta-analysis of randomized controlled trials. Clin Exp Ophthalmol. 2006;34:755-64. doi: 10.1111/j.1442-9071.2006.01237.x.
  50. Li T, et al. Comparative Effectiveness of First-Line Medications for Primary Open-Angle Glaucoma: A Systematic Review and Network Meta-analysis. Ophthalmology. 2016Jan;123(1):129-40. doi: 10.1016/j.ophtha.2015.09.005.
  51. Lin L, Zhao YJ, Chew PTK, et al. Comparative efficacy and tolerability of topical prostaglandin analogues for primary open-angle glaucoma and ocular hypertension. Annals of Pharmacotherapy. 2014;1-9. doi: 10.1177/1060028014548569.
  52. Nagasubramanian S, Sheth GP, Hitchings RA, et al. Intraocular pressure-reducing effect of PhXA41 in ocular hypertension: comparison of dose regimens. Ophthalmology. 1993Sep;100:1305-11. doi: 10.1016/S0161-6420(13)31817-X.
  53. Narayanaswamy A, et al. A randomized, crossover, open label pilot study to evaluate the efficacy and safety of Xalatan® in comparison with generic Latanoprost (Latoprost) in subjects with primary open angle glaucoma or ocular hypertension. Indian J Ophthalmol. 2007;55:127-31. doi: 10.4103/0301-4738.30707.
  54. Nathanson JA. Nitrovasodilators as a new class of ocular hypotensive agents. J Pharmacol Exp Ther. 1992;260(3):956-965.
  55. Noecker RS, Dirks MS, Choplin NT, et al. A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost inpatients with ocular hypertension or glaucoma. Am J Ophthalmol. 2003;135:55-63. doi: 10.1016/S0002-9394(02)01827-5.
  56. Oh DJ, Martin JL, Williams AJ, et al. Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2006;47:3887-3895. doi: 10.1167/iovs.06-0036.
  57. Orme M, Collins S, Dakin H, et al. Mixed treatment comparison and meta-regression of the efficacy and safety of prostaglandin analogues and comparators for primary open-angle glaucoma and ocular hypertension. Curr Med Res Opin. 2010;26:511-528. doi: 10.1185/03007990903498786.
  58. Orzalesi N, Rossetti L, Invernizzi T, et al. Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension. Invest Ophthalmol Vis Sci. 2000;41:2566-73.
  59. Parrish RK, Palmberg P, Sheu WP, XLT Study Group. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, masked-evaluator multicenter study. Am J Ophthalmol. 2003;135:688-703. doi: 10.1016/S0002-9394(03)00098-9.
  60. Patel SS, Spencer CM. Latanoprost: A Review of its Pharmacological Properties, Clinical Efficacy and Tolerability in the Management of Primary Open-Angle Glaucoma and Ocular Hypertension. Drugs & Aging. 1996Nov;9(5):363-378. doi: 10.2165/00002512-199609050-00007.
  61. Racz P. Ruzsonyi MR, Nagy ZT, et al. Maintained intraocular pressure reduction with once-a-day application of a new prostaglandin F2α analogue (PhXA41). An in-hospital, placebo-controlled study. Arch Ophthalmol. 1993May;III:657-61. doi: 10.1001/archopht.1993.01090050091036.
  62. Richter M, Krauss AH, Woodward DF, Lutjen-Drecoll E. 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;44:4419-26. doi: 10.1167/iovs.02-1281.
  63. Rockville MD. Agency for Healthcare Research and Quality (US); 2012 (Comparative Effectiveness Reviews, No. 60.) Доступно по: Ссылка активна на 7.08.2014.
  64. Sanford M. Preservative-Free Latanoprost Eye Drops in Patients with Primary Open-Angle Glaucoma/Ocular Hypertension. Clin Drug Investig. 2014;34:521-528. doi: 10.1007/s40261-014-0203-4.
  65. Schmier JK, Lau EC, Covert DW. Two-year treatment patterns and costs in glaucoma patients initiating treatment with prostaglandin analogs. Clin Ophthalmol. 2010;4:1137-43. doi: 10.2147/OPTH.S13884.
  66. Schuman JS, Erickson K, Nathanson JA. Nitrovasodilator effects on intraocular pressure and out ow facility in monkeys. Exp Eye Res. 1994;58(1):99-105. doi: 10.1006/exer.1994.1199.
  67. Stamer WD, Lei Y, Boussommier-Calleja A, et al. eNOS, a pressure-dependent regulator of intraocular pressure. Invest Ophthalmol Vis Sci. 2011;52(13):9438-9444. doi: 10.1167/iovs.11-7839.
  68. Stewart WC, Kolker AE, Stewart JA, et al. Conjunctival hyperemia in healthy subjects after short-term dosing with latanoprost, bimatoprost, and travoprost. Am J Ophthalmol. 2003;135:314-320. doi: 10.1016/S0002-9394(02)01980-3.
  69. Stewart WC, Konstas AG, Nelson LA, Kruft B. Meta-analysis of 24-hour intraocular pressure studies evaluating the efficacy of glaucoma medicines. Ophthalmology. 2008;115:1117-22(e1).
  70. Stjernschantz J, Alm A. Latanoprost as a new horizon in the medical management of glaucoma. Curr Opin Ophthalmol. 1996Apr;7(2):11-17. doi: 10.1097/00055735-199604000-00003.
  71. Stjernschantz J, Resul B. Phenyl substituted prostaglandin analogs for glaucoma treatment. Drugs Future. 1992;17:691-704. doi: 10.1358/dof.1992.017.08.187766.
  72. Stjernschantz J, Selén G, Sjöquist B, et al. Preclinical pharmacology of latanoprost, a phenyl-substituted PGF2α analogue. Adv Prostaglandin Thromboxane Leukotriene Res. 1995;23:513-8.
  73. Tajunisah I, Reddy SC, Fathilah J. Diurnal variation of intraocular pressure in suspected glaucoma patients and their outcome. Graefes Arch Clin Exp Ophthalmol. 2007;245:1851-7. doi: 10.1007/s00417-007-0681-7.
  74. Tan J, Berke S. Latanoprost-Induced Prostaglandin-Associated Periorbitopathy. Optometry and Vision Science. 2013;90(9):245-247. doi: 10.1097/OPX.0b013e31829d8dd7.
  75. Tanihara H, Inoue T, Yamamoto T, et al. for K-115 Clinical Study Group. One-year clinical evaluation of 0.4% ripasudil (K-115) in patients with open-angle glaucoma and ocular hypertension. Acta Ophthalmol. 2016;94:e26-34. doi: 10.1111/aos.12829.
  76. Tham YC, et al. Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040. A Systematic Review and Meta-Analysis. Ophthalmology. 2014:121(11);2081-90. doi: 10.1016/j.ophtha.2014.05.013.
  77. Traverso CE, Ropo A, Papadia M, Uusitalo H. A phase II study on the duration and stability of the intraocular pressure-lowering effect and tolerability of ta uprost compared with latanoprost. J Ocul Pharmacol Ther. 2010;26:97-104. doi: 10.1089/jop.2009.0066.
  78. Uusitalo H, Egorov E, Kaarniranta K, et al. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta-analysis of two Phase IIIb clinical trials. Clin Ophthalmol. 2016 Mar15;10:445-54. doi: 10.2147/OPTH.S91402.
  79. Uusitalo H, Pillunat LE, Ropo A. Phase III Study Investigators. Efficacy and safety of ta uprost 0.0015% versus latanoprost 0.005% eye drops in open-angle glaucoma and ocular hypertension: 24-month results of a randomized, double-masked phase III study. Acta Ophthalmol. 2010;88:12-19. doi: 10.1111/j.1755-3768.2010.01862.x.
  80. Van der Valk R, Webers CA, Schouten JS, et al. Intraocular pressure-lowering effects of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials. Ophthalmology. 2005;112:1177-85. doi: 10.1016/j.ophtha.2005.01.042.
  81. Voss K, Falke K, Bernsdorf A, et al. Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment. J Control Release. 2015Sep28;214:1-11. doi: 10.1016/j.jconrel.2015.06.035.
  82. Walters TR, DuBiner HB, Carpenter SP, et al. 24-Hour IOP control with once-daily bimatoprost, timolol gel-forming solution, or latanoprost: a 1-month, randomized, comparative clinical trial. Surv Ophthalmol. 2004;49 Suppl1: S26-S35. doi: 10.1016/j.survophthal.2003.12.017.
  83. Wang JW, Woodward DF, Stamer WD. Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow. Invest Ophthalmol Vis Sci. 2013;54:4782-4790,doi: 10.1167/iovs.13-12363.
  84. Wax MB, Camras CB, Fiscella RG, et al. Emerging perspectives in glaucoma: optimizing 24-hour control of intraocular pressure. Am J Ophthalmol. 2002;133(Suppl): S1-10. doi: 10.1016/S0002-9394(02)01459-9.
  85. WHO web link: Ссылка активна на 3.12.2016.
  86. Wilensky JT. Diurnal variations in intraocular pressure. Trans Am Ophthalmol Soc. 1991;89:757-90.
  87. Wilensky JT. The role of diurnal pressure measurements in the management of open angle glaucoma. Curr Opin Ophthalmol. 2004;15:90-2. doi: 10.1097/00055735-200404000-00005.
  88. Wizemann AJ, Wizemann V. Organic nitrate therapy in glaucoma. Am J Ophthalmol. 1980;90(1):106-109. doi: 10.1016/S0002-9394(14)75085-8.
  89. Yamagishi R, Aihara M, Araie M. Neuroprotective effects of prostaglandin analogues on retinal ganglion cell death independent of intraocular pressure reduction. Exp Eye Res. 2011Sep;93(3):265-70. doi: 10.1016/j.exer.2011.06.022.
  90. Yamamoto K, Sato K, Yukita M, et al. The neuroprotective effect of latanoprost acts via klotho-mediated suppression of calpain activation after optic nerve transection. J Neurochem. 2016Nov15. [Epub ahead of print; doi: 10.1111/jnc.13902].

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