Skip to main content

Advertisement

Log in

Effects of antiglaucoma drugs on blood flow of optic nerve heads and related structures

  • Review
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

An association between glaucoma development or progression and compromised ocular blood flow has been postulated as a result of population-based studies and prospective cohort studies. Blood flow in the optic nerve head (ONH) is of primary importance in the pathogenesis of glaucoma. The potential to modify the blood flow in the ONH and its related structures has been reported in various agents, including topical antiglaucoma drugs and systemic drugs such as calcium channel antagonists, which are reviewed in this manuscript. Clinical implications of the improvement in ocular blood flow on the treatment of glaucomatous optic neuropathy require further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–7.

    Article  PubMed  CAS  Google Scholar 

  2. Leske MC, Connell AM, Wu SY, Nemesure B, Li X, Schachat A, et al. Incidence of open-angle glaucoma: the Barbados Eye Studies. The Barbados Eye Studies Group. Arch Ophthalmol. 2001;119:89–95.

    PubMed  CAS  Google Scholar 

  3. de Voogd S, Ikram MK, Wolfs RC, Jansonius NM, Hofman A, de Jong PT. Incidence of open-angle glaucoma in a general elderly population: the Rotterdam Study. Ophthalmology. 2005;112:1487–93.

    Article  PubMed  Google Scholar 

  4. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130:429–40.

  5. Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003;121:48–56.

    Article  PubMed  Google Scholar 

  6. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126:487–97.

  7. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126:498–505.

  8. Heijl A, Leske MC, Bengtsson B, Hyman L, Hussein M. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:1268–79.

    PubMed  Google Scholar 

  9. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–13 (discussion 829–30).

    Google Scholar 

  10. Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, Yang Z. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114:1965–72.

    Article  PubMed  Google Scholar 

  11. Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008;115:85–93.

    Article  PubMed  Google Scholar 

  12. Bonovas S, Peponis V, Filioussi K. Diabetes mellitus as a risk factor for primary open-angle glaucoma: a meta-analysis. Diabet Med. 2004;21:609–14.

    Article  PubMed  CAS  Google Scholar 

  13. Hayreh SS. The role of age and cardiovascular disease in glaucomatous optic neuropathy. Surv Ophthalmol. 1999;43(Suppl 1):S27–42.

    Article  PubMed  Google Scholar 

  14. Graham SL, Drance SM. Nocturnal hypotension: role in glaucoma progression. Surv Ophthalmol. 1999;43(Suppl 1):S10–6.

    Article  PubMed  Google Scholar 

  15. Comoglu S, Yarangumeli A, Koz OG, Elhan AH, Kural G. Glaucomatous visual field defects in patients with migraine. J Neurol. 2003;250:201–6.

    Article  PubMed  Google Scholar 

  16. Michelson G, Langhans MJ, Harazny J, Dichtl A. Visual field defect and perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 1998;236:80–5.

    Article  PubMed  CAS  Google Scholar 

  17. Findl O, Rainer G, Dallinger S, Dorner G, Polak K, Kiss B, et al. Assessment of optic disk blood flow in patients with open-angle glaucoma. Am J Ophthalmol. 2000;130:589–96.

    Article  PubMed  CAS  Google Scholar 

  18. Ciancaglini M, Carpineto P, Costagliola C, Matropasqua L. Perfusion of the optic nerve head and visual field damage in glaucomatous patients. Graefes Arch Clin Exp Ophthalmol. 2001;239:549–55.

    Article  PubMed  CAS  Google Scholar 

  19. Yaoeda K, Shirakashi M, Fukushima A, Funaki S, Funaki H, Abe H, et al. Relationship between optic nerve head microcirculation and visual field loss in glaucoma. Acta Ophthalmol Scand. 2003;81:253–9.

    Article  PubMed  Google Scholar 

  20. Nicolela MT, Walman BE, Buckley AR, Drance SM. Ocular hypertension and primary open-angle glaucoma: a comparative study of their retrobulbar blood flow velocity. J Glaucoma. 1996;5:308–10.

    Article  PubMed  CAS  Google Scholar 

  21. Duijm HF, van den Berg TJ, Greve EL. Choroidal haemodynamics in glaucoma. Br J Ophthalmol. 1997;81:735–42.

    Article  PubMed  CAS  Google Scholar 

  22. Evans DW, Harris A, Garrett M, Chung HS, Kagemann L. Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change. Br J Ophthalmol. 1999;83:809–13.

    Article  PubMed  CAS  Google Scholar 

  23. Liu CJ, Chiou HJ, Chiang SC, Chou JC, Chou YH, Liu JH. Variations in ocular hemodynamics in patients with early and late glaucoma. Acta Ophthalmol Scand. 1999;77:658–62.

    Article  PubMed  CAS  Google Scholar 

  24. Gherghel D, Orgul S, Gugleta K, Flammer J. Retrobulbar blood flow in glaucoma patients with nocturnal over-dipping in systemic blood pressure. Am J Ophthalmol. 2001;132:641–7.

    Article  PubMed  CAS  Google Scholar 

  25. Galassi F, Sodi A, Ucci F, Renieri G, Pieri B, Baccini M. Ocular hemodynamics and glaucoma prognosis: a color Doppler imaging study. Arch Ophthalmol. 2003;121:1711–5.

    Article  PubMed  Google Scholar 

  26. Leske MC, Wu SY, Nemesure B, Hennis A. Incident open-angle glaucoma and blood pressure. Arch Ophthalmol. 2002;120:954–9.

    PubMed  Google Scholar 

  27. Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol. 1995;113:216–21.

    Article  PubMed  CAS  Google Scholar 

  28. Bonomi L, Marchini G, Marraffa M, Bernardi P, Morbio R, Varotto A. Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology. 2000;107:1287–93.

    Article  PubMed  CAS  Google Scholar 

  29. Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch Ophthalmol. 2001;119:1819–26.

    Article  PubMed  CAS  Google Scholar 

  30. Mitchell P, Leung H, Wang JJ, Rochtchina E, Lee AJ, Wong TY, et al. Retinal vessel diameter and open-angle glaucoma: the Blue Mountains Eye Study. Ophthalmology. 2005;112:245–50.

    Article  PubMed  Google Scholar 

  31. Amerasinghe N, Aung T, Cheung N, Fong CW, Wang JJ, Mitchell P, et al. Evidence of retinal vascular narrowing in glaucomatous eyes in an Asian population. Invest Ophthalmol Vis Sci. 2008;49:5397–402.

    Article  PubMed  Google Scholar 

  32. Leske MC, Warheit-Roberts L, Wu SY. Open-angle glaucoma and ocular hypertension: the Long Island Glaucoma Case–control Study. Ophthalmic Epidemiol. 1996;3:85–96.

    Article  PubMed  CAS  Google Scholar 

  33. Oku H, Sugiyama T, Kojima S, Watanabe T, Azuma I. Experimental optic cup enlargement caused by endothelin-1-induced chronic optic nerve head ischemia. Surv Ophthalmol. 1999;44(Suppl 1):S74–84.

    Article  PubMed  Google Scholar 

  34. Cioffi GA, Sullivan P. The effect of chronic ischemia on the primate optic nerve. Eur J Ophthalmol. 1999;9(Suppl 1):S34–6.

    PubMed  Google Scholar 

  35. Hayreh SS. Anatomy and physiology of the optic nerve head. Trans Am Acad Ophthalmol Otolaryngol. 1974;78:OP240–54.

    PubMed  CAS  Google Scholar 

  36. Onda E, Cioffi GA, Bacon DR, Van Buskirk EM. Microvasculature of the human optic nerve. Am J Ophthalmol. 1995;120:92–102.

    PubMed  CAS  Google Scholar 

  37. Lieberman MF, Maumenee AE, Green WR. Histologic studies of the vasculature of the anterior optic nerve. Am J Ophthalmol. 1976;82:405–23.

    PubMed  CAS  Google Scholar 

  38. Anderson DR. Vascular supply to the optic nerve of primates. Am J Ophthalmol. 1970;70:341–51.

    PubMed  CAS  Google Scholar 

  39. Anderson DR, Braverman S. Reevaluation of the optic disk vasculature. Am J Ophthalmol. 1976;82:165–74.

    PubMed  CAS  Google Scholar 

  40. Cioffi GA, Granstam E, Alm A. Ocular circulation. In: Kaufman PL, Alm A, editors. Adler’s physiology of the eye. St. Louis: Mosby; 2003. p. 747–84.

    Google Scholar 

  41. Cunha-Vaz JG. The blood–retinal barriers. Doc Ophthalmol. 1976;41:287–327.

    Article  PubMed  CAS  Google Scholar 

  42. Tso MO, Shih CY, McLean IW. Is there a blood–brain barrier at the optic nerve head? Arch Ophthalmol. 1975;93:815–25.

    Article  PubMed  CAS  Google Scholar 

  43. Flage T. A defect in the blood–retina barrier in the optic nerve head region in the rabbit and the monkey. Acta Ophthalmol (Cph). 1980;58:645–51.

    Article  CAS  Google Scholar 

  44. Hofman P, Hoyng P, vanderWerf F, Vrensen GF, Schlingemann RO. Lack of blood–brain barrier properties in microvessels of the prelaminar optic nerve head. Investig Ophthalmol Vis Sci. 2001;42:895–901.

    CAS  Google Scholar 

  45. Araie M, Takase M, Sakai Y, Ishii Y, Yokoyama Y, Kitagawa M. Beta-adrenergic blockers: ocular penetration and binding to the uveal pigment. Jpn J Ophthalmol. 1982;26:248–63.

    PubMed  CAS  Google Scholar 

  46. Acheampong AA, Breau A, Shackleton M, Luo W, Lam S, Tang-Liu DD. Comparison of concentration–time profiles of levobunolol and timolol in anterior and posterior ocular tissues of albino rabbits. J Ocul Pharmacol Ther. 1995;11:489–502.

    Article  PubMed  CAS  Google Scholar 

  47. Mizuno K, Koide T, Saito N, Fujii M, Nagahara M, Tomidokoro A, et al. Topical nipradilol: effects on optic nerve head circulation in humans and periocular distribution in monkeys. Investig Ophthalmol Vis Sci. 2002;43:3243–50.

    Google Scholar 

  48. Ishii K, Matsuo H, Fukaya Y, Tanaka S, Sakaki H, Waki M, et al. Iganidipine, a new water-soluble Ca2+ antagonist: ocular and periocular penetration after instillation. Investig Ophthalmol Vis Sci. 2003;44:1169–77.

    Article  Google Scholar 

  49. Ishii K, Fukaya Y, Araie M, Tomita G. Topical administration of iganidipine, a new water-soluble Ca2+ antagonist, increases ipsilateral optic nerve head circulation in rabbits and cynomolgus monkeys. Curr Eye Res. 2004;29:67–73.

    Article  PubMed  CAS  Google Scholar 

  50. Maurice DM. Drug delivery to the posterior segment from drops. Surv Ophthalmol. 2002;47(Suppl 1):S41–52.

    Article  PubMed  Google Scholar 

  51. Mizuno K, Koide T, Shimada S, Mori J, Sawanobori K, Araie M. Route of penetration of topically instilled nipradilol into the ipsilateral posterior retina. Investig Ophthalmol Vis Sci. 2009;50:2839–47.

    Article  Google Scholar 

  52. Mizuno K, Koide T, Yoshimura M, Araie M. Neuroprotective effect and intraocular penetration of nipradilol, a beta-blocker with nitric oxide donative action. Investig Ophthalmol Vis Sci. 2001;42:688–94.

    CAS  Google Scholar 

  53. Ichikawa M, Okada Y, Asai Y, Hara H, Ishii K, Araie M. Effects of topically instilled bunazosin, an alpha1-adrenoceptor antagonist, on constrictions induced by phenylephrine and ET-1 in rabbit retinal arteries. Investig Ophthalmol Vis Sci. 2004;45:4041–8.

    Article  Google Scholar 

  54. Kronfeld PC. Eserine and pilocarpine: our 100-year-old allies. Surv Ophthalmol. 1970;14:479–85.

    PubMed  CAS  Google Scholar 

  55. Weber A. Uber Calabar und seine therapeutisch Verwendung. Graefes Arch Klin Exp Ophthalmol. 1876;22:215–75 (in German).

  56. Chiou GC, Yan HY. Effects of antiglaucoma drugs on the blood flow in rabbit eyes. Ophthalmic Res. 1986;18:265–9.

    Article  PubMed  CAS  Google Scholar 

  57. Green K, Hatchett TL. Regional ocular blood flow after chronic topical glaucoma drug treatment. Acta Ophthalmol (Cph). 1987;65:503–6.

    Article  CAS  Google Scholar 

  58. Yoshitomi T, Ishikawa H, Hayashi E. Pharmacological effects of pilocarpine on rabbit ciliary artery. Curr Eye Res. 2000;20:254–9.

    Article  PubMed  CAS  Google Scholar 

  59. Chiou GC, Chen YJ. Effects of antiglaucoma drugs on ocular blood flow in ocular hypertensive rabbits. J Ocul Pharmacol. 1993;9:13–24.

    Article  PubMed  CAS  Google Scholar 

  60. Schmetterer L, Strenn K, Findl O, Breiteneder H, Graselli U, Agneter E, et al. Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers. Clin Pharmacol Ther. 1997;61:583–95.

    Article  PubMed  CAS  Google Scholar 

  61. Shaikh MH, Mars JS. The acute effect of pilocarpine on pulsatile ocular blood flow in ocular hypertension. Eye (London). 2001;15:63–6.

    Article  CAS  Google Scholar 

  62. Mittag TW, Serle J, Schumer R, Brodie S, Stegman D, Schmidt KG, et al. Studies of the ocular pulse in primates. Surv Ophthalmol. 1994;38(Suppl):S183–90.

    Article  PubMed  Google Scholar 

  63. Van Buskirk EM, Bacon DR, Fahrenbach WH. Ciliary vasoconstriction after topical adrenergic drugs. Am J Ophthalmol. 1990;109:511–7.

    PubMed  Google Scholar 

  64. Sugiyama K, Bacon D, Cioffi G, Fahrenback W, Van Buskirk E. The effects of phenylephrine on the ciliary body, optic nerve head microvasculature in rabbits. J Glaucoma. 1992;1:156–64.

    Article  Google Scholar 

  65. Takayama J, Mishima A, Ishii K. Effects of topical phenylephrine on blood flow in the posterior segments of monkey, aged human eyes. Jpn J Ophthalmol. 2004;48:243–8.

    Article  PubMed  CAS  Google Scholar 

  66. Takayama J, Mayama C, Mishima A, Nagahara M, Tomidokoro A, Araie M. Topical phenylephrine decreases blood velocity in the optic nerve head, increases resistive index in the retinal arteries. Eye. 2009;23:827–34.

    Article  PubMed  CAS  Google Scholar 

  67. Mayama C, Ishii K, Saeki T, Ota T, Tomidokoro A, Araie M. Effects of topical phenylephrine, tafluprost on optic nerve head circulation in monkeys with unilateral experimental glaucoma. Investig Ophthalmol Vis Sci. 2010;51:4117–24.

    Article  Google Scholar 

  68. Gharagozloo NZ, Relf SJ, Brubaker RF. Aqueous flow is reduced by the alpha-adrenergic agonist, apraclonidine hydrochloride (ALO 2145). Ophthalmology. 1988;95:1217–20.

    PubMed  CAS  Google Scholar 

  69. Toris CB, Tafoya ME, Camras CB, Yablonski ME. Effects of apraclonidine on aqueous humor dynamics in human eyes. Ophthalmology. 1995;102:456–61.

    PubMed  CAS  Google Scholar 

  70. Robin AL, Pollack IP, House B, Enger C. Effects of ALO 2145 on intraocular pressure following argon laser trabeculoplasty. Arch Ophthalmol. 1987;105:646–50.

    Article  PubMed  CAS  Google Scholar 

  71. Brown RH, Stewart RH, Lynch MG, Crandall AS, Mandell AI, Wilensky JT, et al. ALO 2145 reduces the intraocular pressure elevation after anterior segment laser surgery. Ophthalmology. 1988;95:378–84.

    PubMed  CAS  Google Scholar 

  72. Kitazawa Y, Taniguchi T, Sugiyama K. Use of apraclonidine to reduce acute intraocular pressure rise following Q-switched Nd:YAG laser iridotomy. Ophthalmic Surg. 1989;20:49–52.

    PubMed  CAS  Google Scholar 

  73. Robin AL. Short-term effects of unilateral 1 % apraclonidine therapy. Arch Ophthalmol. 1988;106:912–5.

    Article  PubMed  CAS  Google Scholar 

  74. Serdahl CL, Galustian J, Lewis RA. The effects of apraclonidine on conjunctival oxygen tension. Arch Ophthalmol. 1989;107:1777–9.

    Article  PubMed  CAS  Google Scholar 

  75. Celiker UO, Celebi S, Celiker H, Celebi H. Effect of topical apraclonidine on flow properties of central retinal and ophthalmic arteries. Acta Ophthalmol Scand. 1996;74:151–4.

    Article  PubMed  CAS  Google Scholar 

  76. Oruc S, Sener EC. A comparative study on the effects of apraclonidine and timolol on the ophthalmic blood flow velocity waveforms. Int Ophthalmol. 1999;23:69–73.

    Article  PubMed  CAS  Google Scholar 

  77. Kim TW, Kim DM. Effects of 0.5 % apraclonidine on optic nerve head and peripapillary retinal blood flow. Br J Ophthalmol. 1997;81:1070–2.

    Article  PubMed  CAS  Google Scholar 

  78. Avunduk AM, Sari A, Akyol N, Ozturk O, Kapicioglu Z, Erdol H, et al. The one-month effects of topical betaxolol, dorzolamide and apraclonidine on ocular blood flow velocities in patients with newly diagnosed primary open-angle glaucoma. Ophthalmologica. 2001;215:361–5.

    Article  PubMed  CAS  Google Scholar 

  79. Gabelt BT, Robinson JC, Hubbard WC, Peterson CM, Debink N, Wadhwa A, et al. Apraclonidine and brimonidine effects on anterior ocular and cardiovascular physiology in normal and sympathectomized monkeys. Exp Eye Res. 1994;59:633–44.

    Article  PubMed  CAS  Google Scholar 

  80. Maus TL, Nau C, Brubaker RF. Comparison of the early effects of brimonidine and apraclonidine as topical ocular hypotensive agents. Arch Ophthalmol. 1999;117:586–91.

    Article  PubMed  CAS  Google Scholar 

  81. Schmidt KG, Klingmuller V, Gouveia SM, Osborne NN, Pillunat LE. Short posterior ciliary artery, central retinal artery, and choroidal hemodynamics in brimonidine-treated primary open-angle glaucoma patients. Am J Ophthalmol. 2003;136:1038–48.

    Article  PubMed  CAS  Google Scholar 

  82. Vetrugno M, Maino A, Cantatore F, Ruggeri G, Cardia L. Acute and chronic effects of brimonidine 0.2 % on intraocular pressure and pulsatile ocular blood flow in patients with primary open-angle glaucoma: an open-label, uncontrolled, prospective study. Clin Ther. 2001;23:1519–28.

    Article  PubMed  CAS  Google Scholar 

  83. Carlsson AM, Chauhan BC, Lee AA, LeBlanc RP. The effect of brimonidine tartrate on retinal blood flow in patients with ocular hypertension. Am J Ophthalmol. 2000;129:297–301.

    Article  PubMed  CAS  Google Scholar 

  84. Liu CJ, Ko YC, Cheng CY, Chou JC, Hsu WM, Liu JH. Effect of latanoprost 0.005 % and brimonidine tartrate 0.2 % on pulsatile ocular blood flow in normal tension glaucoma. Br J Ophthalmol. 2002;86:1236–9.

    Article  PubMed  Google Scholar 

  85. Feke GT, Hazin R, Grosskreutz CL, Pasquale LR. Effect of brimonidine on retinal blood flow autoregulation in primary open-angle glaucoma. J Ocul Pharmacol Ther. 2011;27:347–52.

    Article  PubMed  CAS  Google Scholar 

  86. Ohkubo H, Chiba S. Pharmacological analysis of vasoconstriction of isolated canine ophthalmic and ciliary arteries to alpha-adrenoceptor agonists. Exp Eye Res. 1987;45:263–70.

    Article  PubMed  CAS  Google Scholar 

  87. Sugiyama T. Effects of topically applied bunazosin hydrochloride on choroidal capillary blood flow and intraocular pressure of rabbit eye. Nihon Ganka Gakkai Zasshi. 1991;95:449–54 (in Japanese).

    Google Scholar 

  88. Sugiyama T, Oku H, Moriya S, Shimizu K, Azuma I. Evaluation of bunazosin hydrochloride with a model of ocular circulation disturbance induced by endothelin-1. Nihon Ganka Gakkai Zasshi. 1994;98:63–8 (in Japanese).

    Google Scholar 

  89. Goto W, Oku H, Okuno T, Sugiyama T, Ikeda T. Amelioration of endothelin-1-induced optic nerve head ischemia by topical bunazosin. Curr Eye Res. 2005;30:81–91.

    Article  PubMed  CAS  Google Scholar 

  90. Goto W, Oku H, Okuno T, Sugiyama T, Ikeda T. Amelioration by topical bunazosin hydrochloride of the impairment in ocular blood flow caused by nitric oxide synthase inhibition in rabbits. J Ocul Pharmacol Ther. 2003;19:63–73.

    Article  PubMed  CAS  Google Scholar 

  91. Trew DR, Wright LA, Smith SE. Ocular responses in healthy subjects to topical bunazosin 0.3 %—an alpha 1-adrenoceptor antagonist. Br J Ophthalmol. 1991;75:411–3.

    Article  PubMed  CAS  Google Scholar 

  92. Elena PP, Denis P, Kosina-Boix M, Saraux H, Lapalus P. Beta adrenergic binding sites in the human eye: an autoradiographic study. J Ocul Pharmacol. 1990;6:143–9.

    Article  PubMed  CAS  Google Scholar 

  93. Millar JC, Wilson WS, Carr RD, Humphries RG. Drug effects on intraocular pressure and vascular flow in the bovine perfused eye using radiolabelled microspheres. J Ocul Pharmacol Ther. 1995;11:11–23.

    Article  PubMed  CAS  Google Scholar 

  94. Hayashi-Morimoto R, Yoshitomi T, Ishikawa H, Hayashi E, Sato Y. Effects of beta antagonists on mechanical properties in rabbit ciliary artery. Graefes Arch Clin Exp Ophthalmol. 1999;237:661–7.

    Article  PubMed  CAS  Google Scholar 

  95. Chiou GC, Chen YJ. Effects of d- and l-isomers of timolol on retinal and choroidal blood flow in ocular hypertensive rabbit eyes. J Ocul Pharmacol. 1992;8:183–90.

    Article  PubMed  CAS  Google Scholar 

  96. Jay WM, Aziz M, Green K. Effect of topical epinephrine and timolol on ocular and optic nerve blood flow in phakic and aphakic rabbit eyes. Curr Eye Res. 1984;3:1199–202.

    Article  PubMed  CAS  Google Scholar 

  97. Tomidokoro A, Araie M, Tamaki Y, Tomita K. In vivo measurement of iridial circulation using laser speckle phenomenon. Investig Ophthalmol Vis Sci. 1998;39:364–71.

    CAS  Google Scholar 

  98. Tamaki Y, Araie M, Tomita K, Tomidokoro A. Effect of topical timolol on tissue circulation in optic nerve head. Jpn J Ophthalmol. 1997;41:297–304.

    Article  PubMed  CAS  Google Scholar 

  99. Ishii K, Araie M. Effect of topical timolol on optic nerve head circulation in the cynomolgus monkey. Jpn J Ophthalmol. 2000;44:630–3.

    Article  PubMed  CAS  Google Scholar 

  100. Haefliger IO, Lietz A, Griesser SM, Ulrich A, Schotzau A, Hendrickson P, et al. Modulation of Heidelberg Retinal Flowmeter parameter flow at the papilla of healthy subjects: effect of carbogen, oxygen, high intraocular pressure, and beta-blockers. Surv Ophthalmol. 1999;43(Suppl 1):S59–65.

    Article  PubMed  Google Scholar 

  101. Netland PA, Schwartz B, Feke GT, Takamoto T, Konno S, Goger DG. Diversity of response of optic nerve head circulation to timolol maleate in gel-forming solution. J Glaucoma. 1999;8:164–71.

    Article  PubMed  CAS  Google Scholar 

  102. Fuchsjager-Mayrl G, Wally B, Rainer G, Buehl W, Aggermann T, Kolodjaschna J, et al. Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension. Br J Ophthalmol. 2005;89:1293–7.

    Article  PubMed  CAS  Google Scholar 

  103. Tamaki Y, Araie M, Tomita K, Nagahara M, Tomidokoro A. Effect of topical beta-blockers on tissue blood flow in the human optic nerve head. Curr Eye Res. 1997;16:1102–10.

    Article  PubMed  CAS  Google Scholar 

  104. Grunwald JE. Effect of timolol maleate on the retinal circulation of human eyes with ocular hypertension. Investig Ophthalmol Vis Sci. 1990;31:521–6.

    CAS  Google Scholar 

  105. Yoshida A, Ogasawara H, Fujio N, Konno S, Ishiko S, Kitaya N, et al. Comparison of short- and long-term effects of betaxolol and timolol on human retinal circulation. Eye (London). 1998;12(Pt 5):848–53.

    Article  Google Scholar 

  106. Nicolela MT, Buckley AR, Walman BE, Drance SM. A comparative study of the effects of timolol and latanoprost on blood flow velocity of the retrobulbar vessels. Am J Ophthalmol. 1996;122:784–9.

    PubMed  CAS  Google Scholar 

  107. Altan-Yaycioglu R, Turker G, Akdol S, Acunas G, Izgi B. The effects of beta-blockers on ocular blood flow in patients with primary open angle glaucoma: a color Doppler imaging study. Eur J Ophthalmol. 2001;11:37–46.

    PubMed  CAS  Google Scholar 

  108. Bergstrand IC, Heijl A, Wollmer P, Hansen F, Harris A. Timolol increased retrobulbar flow velocities in untreated glaucoma eyes but not in ocular hypertension. Acta Ophthalmol Scand. 2001;79:455–61.

    Article  PubMed  CAS  Google Scholar 

  109. Lubeck P, Orgul S, Gugleta K, Gherghel D, Gekkieva M, Flammer J. Effect of timolol on anterior optic nerve blood flow in patients with primary open-angle glaucoma as assessed by the Heidelberg retina flowmeter. J Glaucoma. 2001;10:13–7.

    Article  PubMed  CAS  Google Scholar 

  110. Evans DW, Harris A, Cantor LB. Primary open-angle glaucoma patients characterized by ocular vasospasm demonstrate a different ocular vascular response to timolol versus betaxolol. J Ocul Pharmacol Ther. 1999;15:479–87.

    Article  PubMed  CAS  Google Scholar 

  111. Galassi F, Sodi A, Renieri G, Ucci F, Pieri B, Harris A, et al. Effects of timolol and dorzolamide on retrobulbar hemodynamics in patients with newly diagnosed primary open-angle glaucoma. Ophthalmologica. 2002;216:123–8.

    Article  PubMed  CAS  Google Scholar 

  112. Harris A, Spaeth GL, Sergott RC, Katz LJ, Cantor LB, Martin BJ. Retrobulbar arterial hemodynamic effects of betaxolol and timolol in normal-tension glaucoma. Am J Ophthalmol. 1995;120:168–75.

    PubMed  CAS  Google Scholar 

  113. Trew DR, Smith SE. Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma. Br J Ophthalmol. 1991;75:71–5.

    Article  PubMed  CAS  Google Scholar 

  114. Claridge KG, Smith SE. Diurnal variation in pulsatile ocular blood flow in normal and glaucomatous eyes. Surv Ophthalmol. 1994;38(Suppl):S198–205.

    Article  PubMed  Google Scholar 

  115. Morsman CD, Bosem ME, Lusky M, Weinreb RN. The effect of topical beta-adrenoceptor blocking agents on pulsatile ocular blood flow. Eye (London). 1995;9(Pt 3):344–7.

    Article  Google Scholar 

  116. Man in ’t Veld AJ, Schalekamp MA. How intrinsic sympathomimetic activity modulates the haemodynamic responses to beta-adrenoceptor antagonists. A clue to the nature of their antihypertensive mechanism. Br J Clin Pharmacol. 1982;13:245S–57S.

    Google Scholar 

  117. Janczewski P, Boulanger C, Iqbal A, Vanhoutte PM. Endothelium-dependent effects of carteolol. J Pharmacol Exp Ther. 1988;247:590–5.

    PubMed  CAS  Google Scholar 

  118. Tomidokoro A, Tamaki Y, Araie M, Tomita K, Muta K. Effect of topical carteolol on iridial circulation in pigmented rabbit eyes. Jpn J Ophthalmol. 1998;42:180–5.

    Article  PubMed  CAS  Google Scholar 

  119. Tamaki Y, Araie M, Tomita K, Tomidokoro A. Effect of topical carteolol on tissue circulation in the optic nerve head. Jpn J Ophthalmol. 1998;42:27–32.

    Article  PubMed  CAS  Google Scholar 

  120. Sugiyama T, Azuma I, Araie M, Fujisawa S, Urashima H, Nagasawa M. Effect of continuous intravenous infusion of carteolol chloride on tissue blood flow in rabbit optic nerve head. Jpn J Ophthalmol. 1999;43:490–4.

    Article  PubMed  CAS  Google Scholar 

  121. Grunwald JE, Delehanty J. Effect of topical carteolol on the normal human retinal circulation. Investig Ophthalmol Vis Sci. 1992;33:1853–6.

    CAS  Google Scholar 

  122. Tamaki Y, Araie M, Tomita K, Tomidokoro A, Nagahara M. Effects of topical adrenergic agents on tissue circulation in rabbit and human optic nerve head evaluated with laser speckle tissue circulation analyzer. Surv Ophthalmol. 1997;42(Suppl 1):S52–63.

    Article  PubMed  Google Scholar 

  123. Mizuki K, Yamazaki Y. Effect of carteolol hydrochloride on ocular blood flow dynamics in normal human eyes. Jpn J Ophthalmol. 2000;44:570.

    Article  PubMed  Google Scholar 

  124. Vuori ML, Ali-Melkkila T, Kaila T, Iisalo E, Saari KM. Beta 1- and beta 2-antagonist activity of topically applied betaxolol and timolol in the systemic circulation. Acta Ophthalmol (Cph). 1993;71:682–5.

    Article  CAS  Google Scholar 

  125. Hoste AM, Sys SU. The relaxant action of betaxolol on isolated bovine retinal microarteries. Curr Eye Res. 1994;13:483–7.

    Article  PubMed  CAS  Google Scholar 

  126. Orgul S, Mansberger S, Bacon DR, Van Buskirk EM, Cioffi GA. Optic nerve vasomotor effects of topical beta-adrenergic antagonists in rabbits. Am J Ophthalmol. 1995;120:441–7.

    PubMed  CAS  Google Scholar 

  127. Sato T, Muto T, Ishibashi Y, Roy S. Short-term effect of beta-adrenoreceptor blocking agents on ocular blood flow. Curr Eye Res. 2001;23:298–306.

    Article  PubMed  Google Scholar 

  128. Araie M, Muta K. Effect of long-term topical betaxolol on tissue circulation in the iris and optic nerve head. Exp Eye Res. 1997;64:167–72.

    Article  PubMed  CAS  Google Scholar 

  129. Kim JH, Kim DM, Park WC. Effect of betaxolol on impaired choroidal blood flow after intravitreal injection of endothelin-1 in albino rabbits. J Ocul Pharmacol Ther. 2002;18:203–9.

    Article  PubMed  CAS  Google Scholar 

  130. Tamaki Y, Araie M, Tomita K, Nagahara M. Effect of topical betaxolol on tissue circulation in the human optic nerve head. J Ocul Pharmacol Ther. 1999;15:313–21.

    Article  PubMed  CAS  Google Scholar 

  131. Gupta A, Chen HC, Rassam SM, Kohner EM. Effect of betaxolol on the retinal circulation in eyes with ocular hypertension: a pilot study. Eye (London). 1994;8(Pt 6):668–71.

    Article  Google Scholar 

  132. Erkin EF, Tarhan S, Kayikcioglu OR, Deveci H, Guler C, Goktan C. Effects of betaxolol and latanoprost on ocular blood flow and visual fields in patients with primary open-angle glaucoma. Eur J Ophthalmol. 2004;14:211–9.

    PubMed  CAS  Google Scholar 

  133. Di Carlo FJ, Leinweber FJ, Szpiech JM, Davidson IW. Metabolism of l-bunolol. Clin Pharmacol Ther. 1977;22:858–63.

    PubMed  Google Scholar 

  134. Dong Y, Ishikawa H, Wu Y, Yoshitomi T. Vasodilatory mechanism of levobunolol on vascular smooth muscle cells. Exp Eye Res. 2007;84:1039–46.

    Article  PubMed  CAS  Google Scholar 

  135. Leung M, Grunwald JE. Short-term effects of topical levobunolol on the human retinal circulation. Eye (London). 1997;11(Pt 3):371–6.

    Article  Google Scholar 

  136. Bloom AH, Grunwald JE, DuPont JC. Effect of one week of levobunolol HCl 0.5 % on the human retinal circulation. Curr Eye Res. 1997;16:191–6.

    Article  PubMed  CAS  Google Scholar 

  137. Bosem ME, Lusky M, Weinreb RN. Short-term effects of levobunolol on ocular pulsatile flow. Am J Ophthalmol. 1992;114:280–6.

    PubMed  CAS  Google Scholar 

  138. Kanno M, Araie M, Koibuchi H, Masuda K. Effects of topical nipradilol, a beta blocking agent with alpha blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans. Br J Ophthalmol. 2000;84:293–9.

    Article  PubMed  CAS  Google Scholar 

  139. Sugiyama T, Kida T, Mizuno K, Kojima S, Ikeda T. Involvement of nitric oxide in the ocular hypotensive action of nipradilol. Curr Eye Res. 2001;23:346–51.

    Article  PubMed  CAS  Google Scholar 

  140. Araki H, Itoh M, Nishi K. Effects of nipradilol on the microvascular tone of rat mesentery: comparison with other beta-blockers and vasodilators. Arch Int Pharmacodyn Ther. 1992;318:47–54.

    PubMed  CAS  Google Scholar 

  141. Yoshitomi T, Yamaji K, Ishikawa H, Ohnishi Y. Vasodilatory effects of nipradilol, an alpha- and beta-adrenergic blocker with nitric oxide releasing action, in rabbit ciliary artery. Exp Eye Res. 2002;75:669–76.

    Article  PubMed  CAS  Google Scholar 

  142. Kanno M, Araie M, Tomita K, Sawanobori K. Effects of topical nipradilol, a beta-blocking agent with alpha-blocking and nitroglycerin-like activities, on aqueous humor dynamics and fundus circulation. Investig Ophthalmol Vis Sci. 1998;39:736–43.

    CAS  Google Scholar 

  143. Kida T, Sugiyama T, Harino S, Kitanishi K, Ikeda T. The effect of nipradilol, an alpha-beta blocker, on retinal blood flow in healthy volunteers. Curr Eye Res. 2001;23:128–32.

    Article  PubMed  CAS  Google Scholar 

  144. Nakanishi M, Sugiyama T, Nakajima M, Ikeda T. Changes in orbital hemodynamics induced by nipradilol in healthy volunteers. J Ocul Pharmacol Ther. 2004;20:25–33.

    Article  PubMed  CAS  Google Scholar 

  145. Ziai N, Dolan JW, Kacere RD, Brubaker RF. The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human eyes. Arch Ophthalmol. 1993;111:1351–8.

    Article  PubMed  CAS  Google Scholar 

  146. Toris CB, Camras CB, Yablonski ME. Effects of PhXA41, a new prostaglandin F2 alpha analog, on aqueous humor dynamics in human eyes. Ophthalmology. 1993;100:1297–304.

    PubMed  CAS  Google Scholar 

  147. Alm A, Villumsen J, Tornquist P, Mandahl A, Airaksinen J, Tuulonen A, et al. Intraocular pressure-reducing effect of PhXA41 in patients with increased eye pressure. A one-month study. Ophthalmology 1993;100:1312–6 (discussion 6–7).

    Google Scholar 

  148. Ishikawa H, Yoshitomi T, Mashimo K, Nakanishi M, Shimizu K. Pharmacological effects of latanoprost, prostaglandin E2, and F2alpha on isolated rabbit ciliary artery. Graefes Arch Clin Exp Ophthalmol. 2002;240:120–5.

    Article  PubMed  CAS  Google Scholar 

  149. Ishii K, Tomidokoro A, Nagahara M, Tamaki Y, Kanno M, Fukaya Y, et al. Effects of topical latanoprost on optic nerve head circulation in rabbits, monkeys, and humans. Investig Ophthalmol Vis Sci. 2001;42:2957–63.

    CAS  Google Scholar 

  150. Ohashi M, Mayama C, Ishi K, Araie M. Local effect of topical FP-receptor agonists on retinal vessels of the ipsilateral posterior retina in normal rabbit eyes. Clin Exp Ophthalmol. 2008;36:767–74.

    Article  Google Scholar 

  151. Ohashi M, Mayama C, Ishii K, Araie M. Effects of topical travoprost and unoprostone on optic nerve head circulation in normal rabbits. Curr Eye Res. 2007;32:743–9.

    Article  PubMed  CAS  Google Scholar 

  152. Seong GJ, Lee HK, Hong YJ. Effects of 0.005 % latanoprost on optic nerve head and peripapillary retinal blood flow. Ophthalmologica. 1999;213:355–9.

    Article  PubMed  CAS  Google Scholar 

  153. Gherghel D, Hosking SL, Cunliffe IA, Armstrong RA. First-line therapy with latanoprost 0.005 % results in improved ocular circulation in newly diagnosed primary open-angle glaucoma patients: a prospective, 6-month, open-label study. Eye (London) 2008;22:363–9.

    Google Scholar 

  154. Tamaki Y, Nagahara M, Araie M, Tomita K, Sandoh S, Tomidokoro A. Topical latanoprost and optic nerve head and retinal circulation in humans. J Ocul Pharmacol Ther. 2001;17:403–11.

    Article  PubMed  CAS  Google Scholar 

  155. Harris A, Migliardi R, Rechtman E, Cole CN, Yee AB, Garzozi HJ. Comparative analysis of the effects of dorzolamide and latanoprost on ocular hemodynamics in normal tension glaucoma patients. Eur J Ophthalmol. 2003;13:24–31.

    PubMed  CAS  Google Scholar 

  156. Zeitz O, Matthiessen ET, Reuss J, Wiermann A, Wagenfeld L, Galambos P, et al. Effects of glaucoma drugs on ocular hemodynamics in normal tension glaucoma: a randomized trial comparing bimatoprost and latanoprost with dorzolamide [ISRCTN18873428]. BMC Ophthalmol. 2005;5:6.

    Article  PubMed  CAS  Google Scholar 

  157. Inan UU, Ermis SS, Yucel A, Ozturk F. The effects of latanoprost and brimonidine on blood flow velocity of the retrobulbar vessels: a 3-month clinical trial. Acta Ophthalmol Scand. 2003;81:155–60.

    Article  PubMed  CAS  Google Scholar 

  158. Sponsel WE, Mensah J, Kiel JW, Remky A, Trigo Y, Baca W, et al. Effects of latanoprost and timolol-XE on hydrodynamics in the normal eye. Am J Ophthalmol. 2000;130:151–9.

    Article  PubMed  CAS  Google Scholar 

  159. Geyer O, Man O, Weintraub M, Silver DM. Acute effect of latanoprost on pulsatile ocular blood flow in normal eyes. Am J Ophthalmol. 2001;131:198–202.

    Article  PubMed  CAS  Google Scholar 

  160. Sponsel WE, Paris G, Trigo Y, Pena M, Weber A, Sanford K, et al. Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy. Am J Ophthalmol. 2002;133:11–8.

    Article  PubMed  CAS  Google Scholar 

  161. Vetrugno M, Cantatore F, Gigante G, Cardia L. Latanoprost 0.005 % in POAG: effects on IOP and ocular blood flow. Acta Ophthalmol Scand Suppl. 1998;227:40–1.

    PubMed  Google Scholar 

  162. McKibbin M, Menage MJ. The effect of once-daily latanoprost on intraocular pressure and pulsatile ocular blood flow in normal tension glaucoma. Eye (London). 1999;13(Pt 1):31–4.

    Article  Google Scholar 

  163. Georgopoulos GT, Diestelhorst M, Fisher R, Ruokonen P, Krieglstein GK. The short-term effect of latanoprost on intraocular pressure and pulsatile ocular blood flow. Acta Ophthalmol Scand. 2002;80:54–8.

    Article  PubMed  CAS  Google Scholar 

  164. Sponsel WE, Paris G, Trigo Y, Pena M. Comparative effects of latanoprost (Xalatan) and unoprostone (Rescula) in patients with open-angle glaucoma and suspected glaucoma. Am J Ophthalmol. 2002;134:552–9.

    Article  PubMed  CAS  Google Scholar 

  165. Sakurai M, Araie M, Oshika T, Mori M, Masuda K, Ueno R, et al. Effects of topical application of UF-021, a novel prostaglandin derivative, on aqueous humor dynamics in normal human eyes. Jpn J Ophthalmol. 1991;35:156–65.

    PubMed  CAS  Google Scholar 

  166. Azuma I, Masuda K, Kitazawa Y, Takase M, Yamamura H. Double-masked comparative study of UF-021 and timolol ophthalmic solutions in patients with primary open-angle glaucoma or ocular hypertension. Jpn J Ophthalmol. 1993;37:514–25.

    PubMed  CAS  Google Scholar 

  167. Hayashi E, Yoshitomi T, Ishikawa H, Hayashi R, Shimizu K. Effects of isopropyl unoprostone on rabbit ciliary artery. Jpn J Ophthalmol. 2000;44:214–20.

    Article  PubMed  CAS  Google Scholar 

  168. Yu DY, Su EN, Cringle SJ, Schoch C, Percicot CP, Lambrou GN. Comparison of the vasoactive effects of the docosanoid unoprostone and selected prostanoids on isolated perfused retinal arterioles. Investig Ophthalmol Vis Sci. 2001;42:1499–504.

    CAS  Google Scholar 

  169. Sugiyama T, Azuma I. Effect of UF-021 on optic nerve head circulation in rabbits. Jpn J Ophthalmol. 1995;39:124–9.

    PubMed  CAS  Google Scholar 

  170. Kimura I, Shinoda K, Tanino T, Ohtake Y, Mashima Y. Effect of topical unoprostone isopropyl on optic nerve head circulation in controls and in normal-tension glaucoma patients. Jpn J Ophthalmol. 2005;49:287–93.

    Article  PubMed  CAS  Google Scholar 

  171. Beano F, Orgul S, Stumpfig D, Gugleta K, Flammer J. An evaluation of the effect of unoprostone isopropyl 0.15 % on ocular hemodynamics in normal-tension glaucoma patients. Graefes Arch Clin Exp Ophthalmol. 2001;239:81–6.

    Article  PubMed  CAS  Google Scholar 

  172. Tamaki Y, Araie M, Tomita K, Nagahara M, Sandoh S, Tomidokoro A. Effect of topical unoprostone on circulation of human optic nerve head and retina. J Ocul Pharmacol Ther. 2001;17:517–27.

    Article  PubMed  CAS  Google Scholar 

  173. Makimoto Y, Sugiyama T, Kojima S, Azuma I. Long-term effect of topically applied isopropyl unoprostone on microcirculation in the human ocular fundus. Jpn J Ophthalmol. 2002;46:31–5.

    Article  PubMed  CAS  Google Scholar 

  174. Polska E, Doelemeyer A, Luksch A, Ehrlich P, Kaehler N, Percicot CL, et al. Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl. Arch Ophthalmol. 2002;120:348–52.

    Article  PubMed  CAS  Google Scholar 

  175. Sugiyama T, Mashima Y, Yoshioka Y, Oku H, Ikeda T. Effect of unoprostone on topographic and blood flow changes in the ischemic optic nerve head of rabbits. Arch Ophthalmol. 2009;127:454–9.

    Article  PubMed  Google Scholar 

  176. Brubaker RF, Schoff EO, Nau CB, Carpenter SP, Chen K, Vandenburgh AM. Effects of AGN 192024, a new ocular hypotensive agent, on aqueous dynamics. Am J Ophthalmol. 2001;131:19–24.

    Article  PubMed  CAS  Google Scholar 

  177. Brandt JD, VanDenburgh AM, Chen K, Whitcup SM. Comparison of once- or twice-daily bimatoprost with twice-daily timolol in patients with elevated IOP: a 3-month clinical trial. Ophthalmology 2001;108:1023–31 (discussion 32).

    Google Scholar 

  178. Goldberg I, Cunha-Vaz J, Jakobsen JE, Nordmann JP, Trost E, Sullivan EK. Comparison of topical travoprost eye drops given once daily and timolol 0.5 % given twice daily in patients with open-angle glaucoma or ocular hypertension. J Glaucoma. 2001;10:414–22.

    Article  PubMed  CAS  Google Scholar 

  179. Netland PA, Landry T, Sullivan EK, Andrew R, Silver L, Weiner A, et al. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001;132:472–84.

    Article  PubMed  CAS  Google Scholar 

  180. Takagi Y, Nakajima T, Shimazaki A, Kageyama M, Matsugi T, Matsumura Y, et al. Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug. Exp Eye Res. 2004;78:767–76.

    Article  PubMed  CAS  Google Scholar 

  181. Sutton A, Gilvarry A, Ropo A. A comparative, placebo-controlled study of prostanoid fluoroprostaglandin-receptor agonists tafluprost and latanoprost in healthy males. J Ocul Pharmacol Ther Off J Assoc Ocul Pharmacol Ther. 2007;23:359–65.

    Article  CAS  Google Scholar 

  182. Aihara M. Clinical appraisal of tafluprost in the reduction of elevated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. Clin Ophthalmol. 2010;4:163–70.

    Article  PubMed  Google Scholar 

  183. Allemann R, Flammer J, Haefliger IO. Vasoactive properties of bimatoprost in isolated porcine ciliary arteries. Klin Monbl Augenheilkd. 2003;220:161–4.

    Article  PubMed  Google Scholar 

  184. Allemann R, Flammer J, Haefliger IO. Absence of vasoactive properties of travoprost in isolated porcine ciliary arteries. Klin Monbl Augenheilkd. 2003;220:152–5.

    Article  PubMed  Google Scholar 

  185. Inan UU, Ermis SS, Orman A, Onrat E, Yucel A, Ozturk F, et al. The comparative cardiovascular, pulmonary, ocular blood flow, and ocular hypotensive effects of topical travoprost, bimatoprost, brimonidine, and betaxolol. J Ocul Pharmacol Ther. 2004;20:293–310.

    Article  PubMed  CAS  Google Scholar 

  186. Akarsu C, Yilmaz S, Taner P, Ergin A. Effect of bimatoprost on ocular circulation in patients with open-angle glaucoma or ocular hypertension. Graefes Arch Clin Exp Ophthalmol. 2004;242:814–8.

    Article  PubMed  Google Scholar 

  187. Chen MJ, Cheng CY, Chen YC, Chou CK, Hsu WM. Effects of bimatoprost 0.03 % on ocular hemodynamics in normal tension glaucoma. J Ocul Pharmacol Ther. 2006;22:188–93.

    Article  PubMed  CAS  Google Scholar 

  188. Izumi N, Nagaoka T, Sato E, Mori F, Takahashi A, Sogawa K, et al. Short-term effects of topical tafluprost on retinal blood flow in cats. J Ocul Pharmacol Ther Off J Assoc Ocul Pharmacol Ther. 2008;24:521–6.

    Article  CAS  Google Scholar 

  189. Akaishi T, Kurashima H, Odani-Kawabata N, Ishida N, Nakamura M. Effects of repeated administrations of tafluprost, latanoprost, and travoprost on optic nerve head blood flow in conscious normal rabbits. J Ocul Pharmacol Ther. 2010;26:181–6.

    Article  PubMed  CAS  Google Scholar 

  190. Kurashima H, Watabe H, Sato N, Abe S, Ishida N, Yoshitomi T. Effects of prostaglandin F(2alpha) analogues on endothelin-1-induced impairment of rabbit ocular blood flow: comparison among tafluprost, travoprost, and latanoprost. Exp Eye Res. 2010;91:853–9.

    Article  PubMed  CAS  Google Scholar 

  191. Dobbs PC, Epstein DL, Anderson PJ. Identification of isoenzyme C as the principal carbonic anhydrase in human ciliary processes. Investig Ophthalmol Vis Sci. 1979;18:867–70.

    CAS  Google Scholar 

  192. Wistrand PJ, Schenholm M, Lonnerholm G. Carbonic anhydrase isoenzymes CA I and CA II in the human eye. Investig Ophthalmol Vis Sci. 1986;27:419–28.

    CAS  Google Scholar 

  193. Wistrand PJ, Garg LC. Evidence of a high-activity C type of carbonic anhydrase in human ciliary processes. Investig Ophthalmol Vis Sci. 1979;18:802–6.

    CAS  Google Scholar 

  194. Lindskog S. Structure and mechanism of carbonic anhydrase. Pharmacol Ther. 1997;74:1–20.

    Article  PubMed  CAS  Google Scholar 

  195. Wang RF, Serle JB, Podos SM, Sugrue MF. MK-507 (L-671,152), a topically active carbonic anhydrase inhibitor, reduces aqueous humor production in monkeys. Arch Ophthalmol. 1991;109:1297–9.

    Article  PubMed  CAS  Google Scholar 

  196. Sugrue MF. The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1996;12:363–76.

    Article  PubMed  CAS  Google Scholar 

  197. Maren TH, Conroy CW, Wynns GC, Levy NS. Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1997;13:23–30.

    Article  PubMed  CAS  Google Scholar 

  198. Sugrue MF. Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors. Prog Retin Eye Res. 2000;19:87–112.

    Article  PubMed  CAS  Google Scholar 

  199. Barnes GE, Li B, Dean T, Chandler ML. Increased optic nerve head blood flow after 1 week of twice daily topical brinzolamide treatment in Dutch-belted rabbits. Surv Ophthalmol. 2000;44(Suppl 2):S131–40.

    Article  PubMed  Google Scholar 

  200. Tamaki Y, Araie M, Muta K. Effect of topical dorzolamide on tissue circulation in the rabbit optic nerve head. Jpn J Ophthalmol. 1999;43:386–91.

    Article  PubMed  CAS  Google Scholar 

  201. Grunwald JE, Mathur S, DuPont J. Effects of dorzolamide hydrochloride 2 % on the retinal circulation. Acta Ophthalmol Scand. 1997;75:236–8.

    Article  PubMed  CAS  Google Scholar 

  202. Pillunat LE, Bohm AG, Koller AU, Schmidt KG, Klemm M, Richard G. Effect of topical dorzolamide on optic nerve head blood flow. Graefes Arch Clin Exp Ophthalmol. 1999;237:495–500.

    Article  PubMed  CAS  Google Scholar 

  203. Faingold D, Hudson C, Flanagan J, Guan K, Rawji M, Buys YM, et al. Assessment of retinal hemodynamics with the Canon laser blood flowmeter after a single dose of 2 % dorzolamide hydrochloride eyedrops. Can J Ophthalmol. 2004;39:506–10.

    PubMed  Google Scholar 

  204. Simsek T, Yanik B, Conkbayir I, Zilelioglu O. Comparative analysis of the effects of brimonidine and dorzolamide on ocular blood flow velocity in patients with newly diagnosed primary open-angle glaucoma. J Ocul Pharmacol Ther. 2006;22:79–85.

    Article  PubMed  CAS  Google Scholar 

  205. Harris A, Arend O, Kagemann L, Garrett M, Chung HS, Martin B. Dorzolamide, visual function and ocular hemodynamics in normal-tension glaucoma. J Ocul Pharmacol Ther. 1999;15:189–97.

    Article  PubMed  CAS  Google Scholar 

  206. Harris A, Arend O, Chung HS, Kagemann L, Cantor L, Martin B. A comparative study of betaxolol and dorzolamide effect on ocular circulation in normal-tension glaucoma patients. Ophthalmology. 2000;107:430–4.

    Article  PubMed  CAS  Google Scholar 

  207. Venkataraman ST, Hudson C, Rachmiel R, Buys YM, Markowitz SN, Fisher JA, et al. Retinal arteriolar vascular reactivity in untreated and progressive primary open-angle glaucoma. Investig Ophthalmol Vis Sci. 2010;51:2043–50.

    Article  Google Scholar 

  208. Kaup M, Plange N, Niegel M, Remky A, Arend O. Effects of brinzolamide on ocular haemodynamics in healthy volunteers. Br J Ophthalmol. 2004;88:257–62.

    Article  PubMed  CAS  Google Scholar 

  209. Iester M, Altieri M, Michelson G, Vittone P, Traverso CE, Calabria G. Retinal peripapillary blood flow before and after topical brinzolamide. Ophthalmologica. 2004;218:390–6.

    Article  PubMed  CAS  Google Scholar 

  210. Becker B. Decrease in intraocular pressure in man by a carbonic anhydrase inhibitor, diamox; a preliminary report. Am J Ophthalmol. 1954;37:13–5.

    PubMed  CAS  Google Scholar 

  211. Reber F, Gersch U, Funk RW. Blockers of carbonic anhydrase can cause increase of retinal capillary diameter, decrease of extracellular and increase of intracellular pH in rat retinal organ culture. Graefes Arch Clin Exp Ophthalmol. 2003;241:140–8.

    Article  PubMed  CAS  Google Scholar 

  212. Pedersen DB, Koch Jensen P, la Cour M, Kiilgaard JF, Eysteinsson T, Bang K, et al. Carbonic anhydrase inhibition increases retinal oxygen tension and dilates retinal vessels. Graefes Arch Clin Exp Ophthalmol. 2005;243:163–8.

    Article  PubMed  CAS  Google Scholar 

  213. Dallinger S, Bobr B, Findl O, Eichler HG, Schmetterer L. Effects of acetazolamide on choroidal blood flow. Stroke. 1998;29:997–1001.

    Article  PubMed  CAS  Google Scholar 

  214. Kiss B, Dallinger S, Findl O, Rainer G, Eichler HG, Schmetterer L. Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide. Am J Physiol. 1999;276:R1661–7.

    PubMed  CAS  Google Scholar 

  215. Kerty E, Horven I, Dahl A, Nyberg-Hansen R. Ocular and cerebral blood flow measurements in healthy subjects. A comparison of blood flow velocity and dynamic tonometry measurements before and after acetazolamide. Acta Ophthalmol (Cph). 1994;72:401–8.

    Article  CAS  Google Scholar 

  216. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med. 1999;341:1447–57.

    Article  PubMed  CAS  Google Scholar 

  217. Braunwald E. Mechanism of action of calcium-channel-blocking agents. N Engl J Med. 1982;307:1618–27.

    Article  PubMed  CAS  Google Scholar 

  218. Cohn JN. Calcium, vascular smooth muscle, and calcium entry blockers in hypertension. Ann Intern Med. 1983;98:806–9.

    PubMed  CAS  Google Scholar 

  219. Hof RP. Calcium antagonist and the peripheral circulation: differences and similarities between PY 108–068, nicardipine, verapamil and diltiazem. Br J Pharmacol. 1983;78:375–94.

    Article  PubMed  CAS  Google Scholar 

  220. Varadi G, Mori Y, Mikala G, Schwartz A. Molecular determinants of Ca2+ channel function and drug action. Trends Pharmacol Sci. 1995;16:43–9.

    Article  PubMed  CAS  Google Scholar 

  221. Payne LJ, Slagle TM, Cheeks LT, Green K. Effect of calcium channel blockers on intraocular pressure. Ophthalmic Res. 1990;22:337–41.

    Article  PubMed  CAS  Google Scholar 

  222. Segarra J, Santafe J, Garrido M, Martinez de Ibarreta MJ. The topical application of verapamil and nifedipine lowers intraocular pressure in conscious rabbits. Gen Pharmacol. 1993;24:1163–71.

    Article  PubMed  CAS  Google Scholar 

  223. Monica ML, Hesse RJ, Messerli FH. The effect of a calcium-channel blocking agent on intraocular pressure. Am J Ophthalmol. 1983;96:814.

    PubMed  CAS  Google Scholar 

  224. Abelson MB, Gilbert CM, Smith LM. Sustained reduction of intraocular pressure in humans with the calcium channel blocker verapamil. Am J Ophthalmol. 1988;105:155–9.

    PubMed  CAS  Google Scholar 

  225. Netland PA, Feke GT, Konno S, Goger DG, Fujio N. Optic nerve head circulation after topical calcium channel blocker. J Glaucoma. 1996;5:200–6.

    Article  PubMed  CAS  Google Scholar 

  226. Erickson KA, Schroeder A, Netland PA. Verapamil increases outflow facility in the human eye. Exp Eye Res. 1995;61:565–7.

    Article  PubMed  CAS  Google Scholar 

  227. Melena J, Zalduegui A, Arcocha P, Santafe J, Segarra J. Topical verapamil lowers outflow facility in the rabbit eye. J Ocul Pharmacol Ther. 1999;15:199–205.

    Article  PubMed  CAS  Google Scholar 

  228. Tomita K, Araie M, Tamaki Y, Nagahara M, Sugiyama T. Effects of nilvadipine, a calcium antagonist, on rabbit ocular circulation and optic nerve head circulation in NTG subjects. Investig Ophthalmol Vis Sci. 1999;40:1144–51.

    CAS  Google Scholar 

  229. Luksch A, Rainer G, Koyuncu D, Ehrlich P, Maca T, Gschwandtner ME, et al. Effect of nimodipine on ocular blood flow and colour contrast sensitivity in patients with normal tension glaucoma. Br J Ophthalmol. 2005;89:21–5.

    Article  PubMed  CAS  Google Scholar 

  230. Nyborg NC, Prieto D, Benedito S, Nielsen PJ. Endothelin-1-induced contraction of bovine retinal small arteries is reversible and abolished by nitrendipine. Investig Ophthalmol Vis Sci. 1991;32(1):27–31.

    CAS  Google Scholar 

  231. Meyer P, Lang MG, Flammer J, Luscher TF. Effects of calcium channel blockers on the response to endothelin-1, bradykinin and sodium nitroprusside in porcine ciliary arteries. Exp Eye Res. 1995;60:505–10.

    Article  PubMed  CAS  Google Scholar 

  232. Lang MG, Zhu P, Meyer P, Noll G, Haefliger IO, Flammer J, et al. Amlodipine and benazeprilat differently affect the responses to endothelin-1 and bradykinin in porcine ciliary arteries: effects of a low and high dose combination. Curr Eye Res. 1997;16:208–13.

    Article  PubMed  CAS  Google Scholar 

  233. Harino S, Riva CE, Petrig BL. Intravenous nicardipine in cats increases optic nerve head but not retinal blood flow. Investig Ophthalmol Vis Sci. 1992;33:2885–90.

    CAS  Google Scholar 

  234. Tamaki Y, Araie M, Tomita K, Urashima H. Effects of pranidipine, a new calcium antagonist, on circulation in the choroid, retina and optic nerve head. Curr Eye Res. 1999;19:241–7.

    Article  PubMed  CAS  Google Scholar 

  235. Shimazawa M, Sugiyama T, Azuma I, Araie M, Iwakura Y, Watari M, et al. Effect of lomerizine, a new Ca(2+)channel blocker, on the microcirculation in the optic nerve head in conscious rabbits: a study using a laser speckle technique. Exp Eye Res. 1999;69:185–93.

    Article  PubMed  CAS  Google Scholar 

  236. Tamaki Y, Araie M, Fukaya Y, Nagahara M, Imamura A, Honda M, et al. Effects of lomerizine, a calcium channel antagonist, on retinal and optic nerve head circulation in rabbits and humans. Investig Ophthalmol Vis Sci. 2003;44:4864–71.

    Article  Google Scholar 

  237. Waki M, Sugiyama T, Watanabe N, Ogawa T, Shirahase H, Azuma I. Effect of topically applied iganidipine dihydrochloride, a novel calcium antagonist, on optic nerve head circulation in rabbits. Jpn J Ophthalmol. 2001;45:76–83.

    Article  PubMed  CAS  Google Scholar 

  238. Kitazawa Y, Shirai H, Go FJ. The effect of Ca2(+)-antagonist on visual field in low-tension glaucoma. Graefes Arch Clin Exp Ophthalmol. 1989;227:408–12.

    Article  PubMed  CAS  Google Scholar 

  239. Netland PA, Chaturvedi N, Dreyer EB. Calcium channel blockers in the management of low-tension and open-angle glaucoma. Am J Ophthalmol. 1993;115:608–13.

    PubMed  CAS  Google Scholar 

  240. Gaspar AZ, Flammer J, Hendrickson P. Influence of nifedipine on the visual fields of patients with optic-nerve-head diseases. Eur J Ophthalmol. 1994;4:24–8.

    PubMed  CAS  Google Scholar 

  241. Geyer O, Neudorfer M, Kessler A, Firsteter E, Lazar M, Almog Y. Effect of oral nifedipine on ocular blood flow in patients with low tension glaucoma. Br J Ophthalmol. 1996;80:1060–2.

    Article  PubMed  CAS  Google Scholar 

  242. Wilson RP, Chang WJ, Sergott RC, Moster MR, Schmidt CM, Bond JB, et al. A color Doppler analysis of nifedipine-induced posterior ocular blood flow changes in open-angle glaucoma. J Glaucoma. 1997;6:231–6.

    PubMed  CAS  Google Scholar 

  243. Schmidt KG, Mittag TW, Pavlovic S, Hessemer V. Influence of physical exercise and nifedipine on ocular pulse amplitude. Graefes Arch Clin Exp Ophthalmol. 1996;234:527–32.

    Article  PubMed  CAS  Google Scholar 

  244. Harris A, Evans DW, Cantor LB, Martin B. Hemodynamic and visual function effects of oral nifedipine in patients with normal-tension glaucoma. Am J Ophthalmol. 1997;124:296–302.

    PubMed  CAS  Google Scholar 

  245. Van den Kerckhoff W, Drewes L. Transfer of the Ca-antagonists nifedipine and nimodipine across the blood–brain barrier and their regional distribution in vivo. J Cereb Blood Flow Metab. 1985;5:S459–60.

    Google Scholar 

  246. Michalk F, Michelson G, Harazny J, Werner U, Daniel WG, Werner D. Single-dose nimodipine normalizes impaired retinal circulation in normal tension glaucoma. J Glaucoma. 2004;13:158–62.

    Article  PubMed  Google Scholar 

  247. Boehm AG, Breidenbach KA, Pillunat LE, Bernd AS, Mueller MF, Koeller AU. Visual function and perfusion of the optic nerve head after application of centrally acting calcium-channel blockers. Graefes Arch Clin Exp Ophthalmol. 2003;241:34–8.

    Article  PubMed  CAS  Google Scholar 

  248. Piltz JR, Bose S, Lanchoney D. The effect of nimodipine, a centrally active calcium antagonist, on visual function and mascular blood flow in patients with normal-tension glaucoma and control subjects. J Glaucoma. 1998;7:336–42.

    Article  PubMed  CAS  Google Scholar 

  249. Tomita G, Niwa Y, Shinohara H, Hayashi N, Yamamoto T, Kitazawa Y. Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma. Int Ophthalmol. 1999;23:3–10.

    Article  PubMed  CAS  Google Scholar 

  250. Yamamoto T, Niwa Y, Kawakami H, Kitazawa Y. The effect of nilvadipine, a calcium-channel blocker, on the hemodynamics of retrobulbar vessels in normal-tension glaucoma. J Glaucoma. 1998;7(5):301–5.

    Article  PubMed  CAS  Google Scholar 

  251. Netland PA, Grosskreutz CL, Feke GT, Hart LJ. Color Doppler ultrasound analysis of ocular circulation after topical calcium channel blocker. Am J Ophthalmol. 1995;119(6):694–700.

    PubMed  CAS  Google Scholar 

  252. Koseki N, Araie M, Tomidokoro A, Nagahara M, Hasegawa T, Tamaki Y, et al. A placebo-controlled 3-year study of a calcium blocker on visual field and ocular circulation in glaucoma with low-normal pressure. Ophthalmology. 2008;115:2049–57.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Makoto Araie.

About this article

Cite this article

Mayama, C., Araie, M. Effects of antiglaucoma drugs on blood flow of optic nerve heads and related structures. Jpn J Ophthalmol 57, 133–149 (2013). https://doi.org/10.1007/s10384-012-0220-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-012-0220-x

Keywords

Navigation