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Pharmacological Therapy for Glaucoma

A Review

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Abstract

For some time the medical treatment of glaucoma has consisted of topical β-blockers, adrenergic agents, miotics and oral carbonic anhydrase inhibitors (CAIs). However, the therapeutic arsenal available for the medical treatment of glaucoma has recently extended with new classes of ocular hypotensive agents i.e. prostaglandins, local CAIs and α2-adrenergic agents. β-Blockers are still the mainstay in glaucoma treatment and are first line drugs. However, even if they are applied once daily, as with timolol in gel forming solution and levobunolol, the possible cardiopulmonary adverse effects of β-blockers remain a cause for concern.

When mono therapy with β-blockers is ineffective in reducing intraocular pressure (IOP) or is hampered by adverse effects, a change of monotherapy to prostaglandins, local CAIs, (X2-adrenergic agonists (brimonidine) or to dipivalyl epinephrine is advised.

Prostaglandins, local CAIs and (X2-adrenergic agonists, such as brimonidine, may in time become first line drugs because they reduce IOP effectively and until now systemic adverse effects have rarely been reported with these agents. The development of a pro-drug of either a local CAI or an α2-adrenergic agonist with a sustained and continuous effect on IOP level, which could be applied once a day is suggested.

Because of these new developments, miotics, i.e. pilocarpine and carbachol, are recommended as second or third line drugs. The cholinesterase inhibitors are considered third line drugs as better agents with fewer local and systemic adverse effects have become available.

Oral CAIs may be used temporarily in patients with elevated IOPs e.g. post-surgery or post-laser, or continuously in patients with glaucoma resistant to other treatment.

Combining ocular hypotensive drugs is indicated when the target pressure for an individual patient cannot be reached with monotherapy. Combination therapy of β-blockers is additive with prostaglandins, topical CAIs and miotics. Prostaglandins such as latanoprost can be combined with β-blockers, adrenergic agents, local CAIs and miotics. Combinations with brimonidine or local CAIs need further investigation.

Treatment of glaucoma with the new ocular hypotensive agents, either in monotherapy or combination therapy, may provide lower IOPs and delay or postpone the need for surgery.

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References

  1. Barany EH. Physiological and pharmacological factors influencing the resistance to aqeous outflow, transactions of the first conference on glaucoma. New York (NY): Josiah Jr Macy Foundation, 1955: 123–221

    Google Scholar 

  2. Goldmann H. L’origine de l’hypertension oculaire dans le glaucoma primitif. Ann Ocul 1951; 184: 1084–9

    Google Scholar 

  3. Bill A, Svedbergh B. Scanning electron microscopic studies of the trabecular meshwork and the canal of Schlemm: an attempt to localize the main resistance to outflow of aqueous humor in man. Acta Ophthalmol (Copenh) 1972; 5: 295–320

    Google Scholar 

  4. Grant WM. Experimantal aqueous perfusion in enucleated human eyes. Arch Ophthalmol 1963; 69: 783–801

    Article  PubMed  CAS  Google Scholar 

  5. Fatt I, Weissman B A. Physiology of the eye: an introduction to the vegetative-functions. Boston (MA): Butterworth-Heinemann, 1992: 60–76

    Google Scholar 

  6. Quigley HA, Vitale S. Models of open-angle glaucoma prevalence and incidence in the United States. Invest Ophthalmol Vis Sci 1997 Jan; 38(1): 83–91

    PubMed  CAS  Google Scholar 

  7. Thylefors B, Negrel AD. The global impact of glaucoma. Bull World Health Organ 1994; 72(3): 323–6

    PubMed  CAS  Google Scholar 

  8. Quigley HA, West SK, Munoz B, et al. Examination methods for glaucoma prevalence surveys. Arch Ophthalmol 1993 Oct; 111(10): 1409–15

    Article  PubMed  CAS  Google Scholar 

  9. Migdal C, Gregory W, Hitchings R. Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology 1994 Oct; 101(10): 1651–6

    PubMed  CAS  Google Scholar 

  10. Shiose Y Prevalence and clinical aspects of low tension glaucoma. In: Henkind P, editor. Acta 24th International Congress of Ophthalmology. Philadelphia (PA): JB Lippincott, 1983

    Google Scholar 

  11. Hollows FC, Graham PA. Intra-ocular pressure, glaucoma, and glaucoma suspects in a defined population. Br J Ophthalmol 1966 Oct; 50(10): 570–86

    Article  PubMed  CAS  Google Scholar 

  12. Arkell SM, Lightman DA, Sommer A, et al. The prevalence of glaucoma among Eskimos of northwest Alaska. Arch Ophthalmol 1987 Apr; 105(4): 482–5

    Article  PubMed  CAS  Google Scholar 

  13. Kolker AE, Becker B. Ocular hypertension vs open-angle glaucoma: a different view [editorial]. Arch Ophthalmol 1977 Apr; 95(4): 586–7

    Article  PubMed  CAS  Google Scholar 

  14. Phelps CD. Ocular hypertension: to treat or not to treat? Arch Ophthalmol 1977 Apr; 95(4): 588–9

    Article  PubMed  CAS  Google Scholar 

  15. Shaffer R. ’Glaucoma suspect’ or’ ocular hypertension’? Arch Ophthalmol 1977 Apr; 95(4): 588

    Article  PubMed  CAS  Google Scholar 

  16. Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham eye study monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973–1975. Surv Ophthalmol 1980 May; 24 Suppl.: 335–610

    Article  PubMed  CAS  Google Scholar 

  17. Kahn HA, Milton RC. Alternative definitions of open-angle glaucoma: effect on prevalence and associations in the Framingham eye study. Arch Ophthalmol 1980 Dec; 98(12): 2172–7

    Article  PubMed  CAS  Google Scholar 

  18. Shield MB. Textbook of glaucoma. Baltimore (MD): William and Wilkins, 1997: 11–13

    Google Scholar 

  19. Hoyng PF, Rasker MT. Four new drugs for glaucoma: apraclonidine, brimonidine, dorzolamide and latanoprost [in Dutch]. Ned Tijdschr Geneeskd 1998; 142(39): 2138–41

    PubMed  CAS  Google Scholar 

  20. Bill A. Effects of atropine and pilocarpine on aqueous humour dynamics in cynomolgus monkeys (Macaca iras). Exp Eye Res 1967 Apr; 6(2): 120–5

    Article  PubMed  CAS  Google Scholar 

  21. Bill A, Phillips CI. Uveoscleral drainage of aqueous humour in human eyes. Exp Eye Res 1971 Nov; 12(3): 275–81

    Article  PubMed  CAS  Google Scholar 

  22. Tracqui A, Kintz P, Ludes B, et al. Adverse events of anti-glaucoma beta-blockers: presentation of an original HPLC determination procedure. Acta Med Leg Soc 1989; 39(1): 397–400

    CAS  Google Scholar 

  23. Tripathi RC, Yang C, Tripathi B.J. Role of receptors in the trabecular meshwork of the eye as targeted to the development of antiglaucoma therapy. Drug Develop Res 1992; 27: 191–228

    Article  CAS  Google Scholar 

  24. Bill A, Hellsing K. Production and drainage of aqueous humor in the cynomolgus monkey (Macaca irus). Invest Ophthalmol 1965 Oct; 4(5): 920–6

    PubMed  CAS  Google Scholar 

  25. Schenker HI, Yablonski ME, Podos SM, et al. Fluorophotometric study of epinephrine and timolol in human subjects. Arch Ophthalmol 1981 July; 99(7): 1212–16

    Article  PubMed  CAS  Google Scholar 

  26. Toris CB, Camras CB, Yablonski ME. Effects of PhXA41, a new prostaglandin F2 alpha analog, on aqueous humor dynamics in human eyes [see comments]. Ophthalmology 1993 Sept; 100(9): 1297–1304

    PubMed  CAS  Google Scholar 

  27. Harrington DO. The pathogenesis of the glaucoma field; clinical evidence that circulatory insufficiency in the optic nerve is the primary cause of visual field loss in glaucoma. Am J Ophthalmol 1959; 47(2): 177–85

    PubMed  CAS  Google Scholar 

  28. Riva CE, Granwald JE, Sinclair SH. Laser Doppier measurement of relative blood velocity in the human optic nerve head. Invest Ophthalmol Vis Sci 1982 Feb; 22(2): 241–8

    PubMed  CAS  Google Scholar 

  29. Rojanapongpun P, Drance SM, Morrison B J. Ophthalmic artery flow velocity in glaucomatous and normal subjects. Br J Ophthalmol 1993 Jan; 77(1): 25–9

    Article  PubMed  CAS  Google Scholar 

  30. Hamard P, Hamard H, Dufaux J, et al. Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma. Br J Ophthalmol 1994 Jun; 78(6): 449–53

    Article  PubMed  CAS  Google Scholar 

  31. Rankin SJ, Walman BE, Buckley AR, et al. Color Doppler imaging and spectral analysis of the optic nerve vasculature in glaucoma [see comments]. Am J Ophthalmol 1995 Jun; 119(6): 685–93

    PubMed  CAS  Google Scholar 

  32. Robert Y, Steiner D, Hendrickson P. Papillary circulation dynamics in glaucoma. Graefes Arch Clin Exp Ophthalmol 1989; 227(5): 436–9

    Article  PubMed  CAS  Google Scholar 

  33. Quigley HA, Addicks EM, Green WR, et al. Optic nerve damage in human glaucoma. II: the site of injury and susceptibility to damage. Arch Ophthalmol 1981 Apr; 99(4): 635–49

    Article  PubMed  CAS  Google Scholar 

  34. Quigley HA, Addicks EM, Green WR. Optic nerve damage in human glaucoma. III: quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol 1982 Jan; 100(1): 135–46

    Article  PubMed  CAS  Google Scholar 

  35. Quigley HA, Hohman RM, Addicks EM, et al. Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol 1983 May; 95(5): 673–91

    PubMed  CAS  Google Scholar 

  36. Sommer A. Intraocular pressure and glaucoma. Am J Ophthalmol 1989 Feb; 107(2): 186–188

    PubMed  CAS  Google Scholar 

  37. Vogel R, Crick RP, Newson RB, et al. Association between intraocular pressure and loss of visual field in chronic simple glaucoma [see comments]. Br J Ophthalmol 1990 Jan; 74(1): 3–6

    Article  PubMed  CAS  Google Scholar 

  38. Quigley HA, Tielsch JM, Katz J, et al. Rate of progression in open-angle glaucoma estimated from cross-sectional prevalence of visual field damage [see comments]. Am J Ophthalmol 1996 Sept; 122(3): 355–63

    PubMed  CAS  Google Scholar 

  39. O’Brien C, Schwartz B, Takamoto T, et al. Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma. Am J Ophthalmol 1991 Apr; 111(4): 491–500

    PubMed  Google Scholar 

  40. Chauhan BC, Drance SM. The relationship between intraocular pressure and visual field progression in glaucoma. Graefes Arch Clin Exp Ophthalmol 1992; 230(6): 521–6

    Article  PubMed  CAS  Google Scholar 

  41. Jampel HD. Target pressure in glaucoma therapy [review]. J Glauc 1997 Apr; 6(2): 133–8

    CAS  Google Scholar 

  42. Spaeth GL, Baez KA. Argon laser trabeculoplasty controls one third of cases of progressive, uncontrolled, open angle glaucoma for 5 years. Arch Ophthalmol 1992 Apr; 110(4): 491–4

    Article  PubMed  CAS  Google Scholar 

  43. Laser trabeculoplasty for primary open-angle glaucoma. Ophthalmology 1996 Oct; 103(10): 1706-12

  44. Buckley SA, Reeves B, Burdon M, et al. Acute angle closure glaucoma: relative failure of YAG iridotomy in affected eyes and factors influencing outcome. Br J Ophthalmol 1994 July; 78(7): 529–33

    Article  PubMed  CAS  Google Scholar 

  45. von Weber A. Die Ursache des Glaukoms. Albr Graefes Arch Ophthalmol 1877; 23: 91–4

    Google Scholar 

  46. Kaufman PL, Barany EH. Residual pilocarpine effects on outflow facility after ciliary muscle disinsertion in the synomolgus monkey. Invest Ophthalmol 1976 July; 15(7): 558–61

    PubMed  CAS  Google Scholar 

  47. Kaufman PL, Barany EH. Loss of acute pilocarpine effect on outflow facility following surgical disinsertion and retrodisplacement of the ciliary muscle from the scierai spur in the cynomolgus monkey. Invest Ophthalmol 1976 Oct; 15(10): 793–807

    PubMed  CAS  Google Scholar 

  48. Crawford K, Kaufman PL. Pilocarpine antagonizes prostaglandin F2 alpha-induced ocular hypotension in monkeys. Evidence for enhancement of Uveoscleral outflow by prostaglandin F2 alpha. Arch Ophthalmol 1987 Aug; 105(8): 1112–16

    Article  PubMed  CAS  Google Scholar 

  49. Drance SM, Nash PA. The dose response of human intraocular pressure to pilocarpine. Can J Ophthalmol 1971 Jan; 6(1): 9–13

    PubMed  CAS  Google Scholar 

  50. Harris LS, Galin MA. Dose response analysis of pilocarpine-induced ocular hypotension. Arch Ophthalmol 1970 Nov; 84(5): 605–8

    Article  PubMed  CAS  Google Scholar 

  51. Abramson DH, Coleman DJ, Forbes M, et al. Pilocarpine. Effect on the anterior chamber and lens thickness. Arch Ophthalmol 1972 Jun; 87(6): 615–20

    Article  PubMed  CAS  Google Scholar 

  52. Poinoosawmy D, Nagasubramanian S, Brown, et al. Effect of pilocarpine on visual acuity and on the dimensions of the cornea and anterior chamber. Br J Ophthalmol 1976 Oct; 60(10): 679

    Article  Google Scholar 

  53. Levene RZ. Uniocular miotic therapy. Trans Am Ac Ophthalmol Otolaryng 1975 Mar; 79(2): OP376–80

    CAS  Google Scholar 

  54. Pape LG, Forbes M. Retinal detachment and miotic therapy. Am J Ophthalmol 1978 Apr; 85(4): 558–66

    PubMed  CAS  Google Scholar 

  55. Beasley H, Fraunfelder FT. Retinal detachments and topical ocular miotics. Ophthalmology 1979 Jan; 86(1): 95–8

    PubMed  CAS  Google Scholar 

  56. O’Brien CS, Swan KD. Carbaminoylcholinechloride in the treatment of glaucoma simplex. Arch Ophthalmol 1942; 27: 253–7

    Article  Google Scholar 

  57. Reichert RW, Shields MB, Stewart WC. Intraocular pressure response to replacing pilocarpine with carbachol. Am J Ophthalmol 1988 Dec; 106(6): 747–8

    PubMed  CAS  Google Scholar 

  58. Townsend DJ, Brubaker RF. Immediate effect of epinephrine on aqueous formation in the normal human eye as measured by fluorophotometry. Invest Ophthalmol Vis Sci 1980 Mar; 19(3): 256–66

    PubMed  CAS  Google Scholar 

  59. Nagataki S, Brubaker RF. Early effect of epinephrine on aqueous formation in the normal human eye. Ophthalmology 1981 Mar; 88(3): 278–82

    PubMed  CAS  Google Scholar 

  60. Erickson-Lamy KA, Nathanson JA. Epinephrine increases facility of outflow and cyclic AMP content in the human eye in vitro. Invest Ophthalmol Vis Sci 1992 Aug; 33(9): 2672–8

    PubMed  CAS  Google Scholar 

  61. Obstbaum SA, Kolker AE, Phelps CD. Low-dose epinephrine. Arch Ophthalmol 1974 Aug; 92(2): 118–20

    Article  PubMed  CAS  Google Scholar 

  62. Garner LL, Johnstone WW, Ballintine EJ, et al. Effect of 2% levo-rotary epinephrine on the intraocular pressure of the glaucomatous eye. Arch Ophthalmol 1959; 62: 230

    Article  CAS  Google Scholar 

  63. Becker B, Pettit TH, Gay AJ. Topical epinephrine therapy of open angle glaucoma. Arch Ophthalmol 1961; 66: 219

    Article  PubMed  CAS  Google Scholar 

  64. Kronfeld PC. Dose-effect relationship as an aid in the evaluation of ocular hypotensive drugs. Invest Ophthalmol 1964; 3: 258

    PubMed  CAS  Google Scholar 

  65. van Alphen GW. The adrenergic receptors of the intraocular muscles of the human eye. Invest Ophthalmol 1976 June; 15(6): 502–5

    PubMed  Google Scholar 

  66. Kolker AE, Becker B. Epinephrine maculopathy. Arch Ophthalmol 1968 May; 79(5): 552–62

    Article  PubMed  CAS  Google Scholar 

  67. Michels RG, Maumenee AE. Cystoid macular edema associated with topically applied epinephrine in aphakic eyes. Am J Ophthalmol 1975 Sep; 80 (3 Pt 1): 379–88

    PubMed  CAS  Google Scholar 

  68. Thomas JV, Gragoudas ES, Blair NP, et al. Correlation of epinephrine use and macular edema in aphakic glaucomatous eyes. Arch Ophthalmol 1978 Apr; 96(4): 625–8

    Article  PubMed  CAS  Google Scholar 

  69. Corwin ME, Spencer WH. Conjunctival melanin depositions: a side effect of topical epinephrine therapy. Arch Ophthalmol 1963; 69: 73

    Article  Google Scholar 

  70. Cashwell LF, Shield MB, Reed JW. Adrenochrome pigmentation. Arch Ophthalmol 1977 Mar; 95(3): 514–15

    Article  PubMed  CAS  Google Scholar 

  71. Green WR, Kaufer GJ, Dubroff S. Black cornea: a complication of topical use of epinephrine. Ophthalmologica 1967; 154(2): 88–95

    Article  PubMed  CAS  Google Scholar 

  72. Madge GE, Geeraets WJ, Guerry D. Black cornea secondary to topical epinephrine. Am J Ophthalmol 1971 Jan; 71(1 Suppl. 5) 402–5

    PubMed  CAS  Google Scholar 

  73. Kaback MB, Podos SM, Harbin TSJ, et al. The effects of dipivalyl epinephrine on the eye. Am J Ophthalmol 1976 June; 81(6): 768–72

    PubMed  CAS  Google Scholar 

  74. Mandell AI, Stentz F, Kitabchi AE. Dipivalyl epinephrine: a new pro-drug in the treatment of glaucoma. Ophthalmology 1978 Mar; 85(3): 268–75

    PubMed  CAS  Google Scholar 

  75. Kass MA, Mandell AI, Goldberg I, et al. Dipivefrin and epinephrine treatment of elevated intraocular pressure: a comparative study. Arch Ophthalmol 1979 Oct; 97(10): 1865–6

    Article  PubMed  CAS  Google Scholar 

  76. Krieglstein GK, Leydhecker W. The dose-response relationships of dipivalyl epinephrine in open-angle glaucoma. Albr Graefes Arch Ophthalmol 1978 Feb; 205(3): 141–6

    Article  CAS  Google Scholar 

  77. Bill A, Heilmann K. Ocular effects of clonidine in cats and monkeys (Macaca irus). Exp Eye Res 1975 Nov; 21(5): 481–8

    Article  PubMed  CAS  Google Scholar 

  78. Krieglstein GK, Gramer E. The response of ophthalmic arterial pressure to topically applied clonidine. Albr Graefes Arch Ophthalmol 1978 Jul; 207(1): 1–5

    Article  CAS  Google Scholar 

  79. Harrison R, Kaufmann CS. Clonidine: effects of a topically administered solution on intraocular pressure and blood pressure in open-angle glaucoma. Arch Ophthalmol 1977 Aug; 95(8): 1368–73

    Article  PubMed  CAS  Google Scholar 

  80. Heilmann K. Studies on the effect of Catapresan on the intraocular pressure. 3 [in German]. Klin Monatsbl Augenheilkd 1972 Oct; 161(4): 425–30

    PubMed  CAS  Google Scholar 

  81. Thumm HW, Jahnke R. Der einfluss vom clonidin auf den augeninnendruck und die pupillenweite. In: Merte HJ, K Heilmann, editors. Clonidin in der Augenheilkunde. Stuttgaat: Ferdinand Enke Verlag, 1974

    Google Scholar 

  82. Gharagozloo NZ, Relf SJ, Brubaker RF. Aqueous flow is reduced by the alpha-adrenergic agonist, apraclonidine hydrochloride (ALO 2145). Ophthalmology 1988 Sep; 95(9): 1217–20

    PubMed  CAS  Google Scholar 

  83. Lee DA, Topper JE, Brubaker RF. Effect of clonidine on aqueous humor flow in normal human eyes. Exp Eye Res 1984 Mar; 38(3): 239–46

    Article  PubMed  CAS  Google Scholar 

  84. Toris CB, Tafoya ME, Camras CB, et al. Effects of apraclonidine on aqueous humor dynamics in human eyes. Ophthalmology 1995 Mar; 102(3): 456–61

    PubMed  CAS  Google Scholar 

  85. Robin AL. Short-term effects of unilateral 1% apraclonidine therapy. Arch Ophthalmol 1988 Jul; 106(7): 912–15

    Article  PubMed  CAS  Google Scholar 

  86. Abrams DA, Robin AL, Pollack IP, et al. The safety and efficacy of topical 1% ALO 2145 (p-aminoclonidine hydrochloride) in normal volunteers. Arch Ophthalmol 1987 Sept; 105(9): 1205–7

    Article  PubMed  CAS  Google Scholar 

  87. Stewart WC, Laibovitz R, Horwitz B, et al. A 90-day study of the efficacy and side effects of 0.25% and 0.5% apraclonidine vs 0.5% timolol. Apraclonidine Primary Therapy Study Group. Arch Ophthalmol 1996 Aug; 114(8): 938–42

    Article  PubMed  CAS  Google Scholar 

  88. Koskela T, Brubaker RF. Apraclonidine and timolol: combined effects in previously untreated normal subjects. Arch Ophthalmol 1991 Jun; 109(6): 804–6

    Article  PubMed  CAS  Google Scholar 

  89. Nagasubramanian S, Hitchings RA, Demailly P, et al. Comparison of apraclonidine and timolol in chronic open-angle glaucoma. A three-month study. Ophthalmology 1993 Sep; 100(9): 1318–23

    CAS  Google Scholar 

  90. Krupin T, Stank T, Feitl ME. Apraclonidine pretreatment decreases the acute intraocular pressure rise after laser trabeculoplasty or iridotomy. J Glauc 1992; 1: 79

    Article  Google Scholar 

  91. Holmwood PC, Chase RD, Krupin T, et al. Apraclonidine and argon laser trabeculoplasty [see comments]. Am J Ophthalmol 1992 Jul; 114(1): 19–22

    PubMed  CAS  Google Scholar 

  92. Araie M, Ishi K. Effects of apraclonidine on intraocular pressure and blood-aqueous barrier permeability after phacoemulsification and intraocular lens implantation. Am J Ophthalmol 1993 Jul; 116(1): 67–71

    PubMed  CAS  Google Scholar 

  93. Robin AL. Effect of topical apraclonidine on the frequency of intraocular pressure elevations after combined extracapsular cataract extraction and trabeculectomy. Ophthalmology 1993 May; 100(5): 628–33

    PubMed  CAS  Google Scholar 

  94. Silverstone DE, Brint SF, Olander KW, et al. Prophylactic use of apraclonidine for intraocular pressure increase after Nd: YAG capsulotomies [see comments]. Am J Ophthalmol 1992 Apr; 113(4): 401–5

    PubMed  CAS  Google Scholar 

  95. Butler P, Mannschreck M, Lin S, et al. Clinical experience with the long-term use of 1 % apraclonidine: incidence of allergic reactions. Arch Ophthalmol 1995 Mar; 113(3): 293–6

    Article  PubMed  CAS  Google Scholar 

  96. Stewart WC, Laibovitz R, Horwitz B, et al. A 90-day study of the efficacy and side effects of 0.25% and 0.5% apraclonidine vs 0.5% timolol (Apraclonidine Primary Therapy Study Group). Arch Ophthalmol 1996 Aug; 114(8): 938–42

    Article  PubMed  CAS  Google Scholar 

  97. Stewart WC, Ritch R, Shin DH, et al. The efficacy of apraclonidine as an adjunct to timolol therapy (Apraclonidine Adjunctive Therapy Study Group) [published errata appear in Arch Ophthalmol 1995 Sep; 113(9): 1112 and 1995 Nov; 113(11): 1465. Arch Ophthalmol 1995 Mar; 113(3): 287–92

    Article  PubMed  CAS  Google Scholar 

  98. Wilkerson M, Lewis RA, Shields MB. Follicular conjunctivitis associated with apraclonidine. Am J Ophthalmol 1991 Jan; 111(1): 105–6

    PubMed  CAS  Google Scholar 

  99. Jampel HD, Robin AL, Quigley HA, et al. Apraclonidine: a one-week dose-response study. Arch Ophthalmol 1988 Aug; 106(8): 1069–73

    Article  PubMed  CAS  Google Scholar 

  100. Coleman AL, Robin AL, Pollack IP, et al. Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine. Arch Ophthalmol 1990 Sep; 108(9): 1264–7

    Article  PubMed  CAS  Google Scholar 

  101. Burke J, Schwartz M. Preclinical evaluation of brimonidine. Surv Ophthalmol 1996 Nov; 41 Suppl. 1: S9–18

    Article  PubMed  Google Scholar 

  102. Toris CB, Gleason ML, Camras CB, et al. Effects of brimonidine on aqueous humor dynamics in human eyes. Arch Ophthalmol 1995 Dec; 113(12): 1514–17

    Article  PubMed  CAS  Google Scholar 

  103. Wen R, Cheng T, Li Y, et al. Alpha 2-adrenergic agonists induce basic fibroblast growth factor expression in photoreceptors in vivo and ameliorate light damage. J Neurosci 1996 Oct; 16(19): 5986–92

    PubMed  CAS  Google Scholar 

  104. Walters TR. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies. Surv Ophthalmol 1996 Nov; 41 Suppl. 1: S19–26

    Article  PubMed  Google Scholar 

  105. Derick RJ, Robin AL, Walters TR, et al. Brimonidine tartrate: a one-month dose response study [published erratum appears in Ophthalmology 1997 Mar; 104(3): 346]. Ophthalmology 1997 Jan; 104(1): 131-6

    Google Scholar 

  106. Schuman JS. Clinical experience with brimonidine 0.2% and timolol 0.5% in glaucoma and ocular hypertension. Surv Ophthalmol 1996 Nov; 41 Suppl. 1: S27–37

    Article  PubMed  Google Scholar 

  107. Schuman JS, Horwitz B, Choplin NT, et al. A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension: a controlled, randomized, multicenter clinical trial (Chronic Brimonidine Study Group). Arch Ophthalmol 1997 Jul; 115(7): 847–52

    Article  PubMed  CAS  Google Scholar 

  108. Serie JB. A comparison of the safety and efficacy of twice daily brimonidine 0.2% versus betaxolol 0.25% in subjects with elevated intraocular pressure: the Brimonidine Study Group III. Surv Ophthalmol 1996 Nov; 41 Suppl. 1: S39–47

    Google Scholar 

  109. LeBlanc RP. Twelve month result of an ongoing randomized trial comparing brimonidine tartraat 0.2% and timolol 0.5% given twice daily in patients with glaucoma or ocular hypertension. Ophthalmology 1998 Oct; 105(10): 1960–7

    Article  PubMed  CAS  Google Scholar 

  110. Phillips CI, Howitt G, Rowlands DJ. Propranolol as ocular hypotensive agent. Br J Ophthalmol 1967 Apr; 51(4): 222–6

    Article  PubMed  CAS  Google Scholar 

  111. Coakes RL, Brubaker RF. The mechanism of timolol in lowering intraocular pressure in the normal eye. Arch Ophthalmol 1978 Nov; 96(11): 2045–8

    Article  PubMed  CAS  Google Scholar 

  112. Zimmerman TJ, Harbin R, Pett M, et al. Timolol and facility of outflow. Invest Ophthalmol Vis Sci 1977 Jul; 16(7): 623–4

    PubMed  CAS  Google Scholar 

  113. Sonntag JR, Brindley GO, Shields MB. Effect of timolol therapy on outflow facility. Invest Ophthalmol Vis Sci 1978 Mar; 17(3): 293–6

    PubMed  CAS  Google Scholar 

  114. Topper JE, Brubaker RF. Effects of timolol, epinephrine, and acetazolamide on aqueous flow during sleep. Invest Ophthalmol Vis Sci 1985 Oct; 26(10): 1315–19

    PubMed  CAS  Google Scholar 

  115. Zimmerman TJ, Kaufman HE. Timolol: a beta-adrenergic blocking agent for the treatment of glaucoma. Arch Ophthalmol 1977 Apr; 95(4): 601–4

    Article  PubMed  CAS  Google Scholar 

  116. Zimmerman TJ, Kaufman HE. Timolol, dose response and duration of action. Arch Ophthalmol 1977 Apr; 95(4): 605–7

    Article  PubMed  CAS  Google Scholar 

  117. Zimmerman TJ, Canale P. Timolol: further observations. Ophthalmology 1979 Jan; 86(1): 166–9

    PubMed  CAS  Google Scholar 

  118. Ritch R, Hargett NA, Podos SM. The effect of 1.5% timolol maleate on intraocular pressure. Acta Ophthalmol 1978 Feb; 56(1): 6–10

    CAS  Google Scholar 

  119. Boger WP, Steinert RF, Thomas JV. Timolol in the therapy of ‘ocular hypertension’. Surv Ophthalmol 1980 Nov; 25(3): 195–202

    Article  PubMed  Google Scholar 

  120. Boger WP, Puliafito CA, Steinert RF, et al. Long-term experience with timolol ophthalmic solution in patients with open-angle glaucoma. Ophthalmology 1978 Mar; 85(3): 259–67

    PubMed  Google Scholar 

  121. Radius RL, Diamond GR, Pollack IP, et al. Timolol: a new drug for management of chronic simple glaucoma. Arch Ophthalmol 1978 Jun; 96(6): 1003–8

    Article  PubMed  CAS  Google Scholar 

  122. Obstbaum SA, Galin MA, Katz IM. Trimolol: effect on intraocular pressure in chronic open-angle glaucoma. Ann Ophthalmol 1978 Oct; 10(10): 1347–51

    PubMed  CAS  Google Scholar 

  123. Lin LL, Galin MA, Obstbaum SA, et al. Longterm timolol therapy. Surv Ophthalmol 1979 May; 23(6): 377–80

    Article  PubMed  CAS  Google Scholar 

  124. Wilson RP, Kanal N, Spaeth GL. Timolol: its effectiveness in different types of glaucoma. Ophthalmology 1979 Jan; 86(1): 43–50

    PubMed  CAS  Google Scholar 

  125. Boger WP. Timolol: short term ‘escape’ and long term ‘drift’ [editorial]. Ann Ophthalmol 1979 Aug; 11(8): 1239–42

    PubMed  Google Scholar 

  126. Steinert RF, Thomas JV, Boger WP. Long-term drift and continued efficacy after multiyear timolol therapy. Arch Ophthalmol 1981 Jan; 99(1): 100–3

    Article  PubMed  CAS  Google Scholar 

  127. Bischoff P. Experiences with timolol in treatment of glaucoma. Klin Monatsbl Augenheilkd 1978 Aug; 173(2): 202–207

    PubMed  CAS  Google Scholar 

  128. Oksala A, Salminen L. Tachyphylaxis in timolol therapy for chronic glaucoma. Klin Monatsbl Augenheilkd 1980 Oct; 177(4): 451–4

    Article  PubMed  CAS  Google Scholar 

  129. Mills KB. Blind randomised non-crossover long-term trial comparing topical timolol 0.25% with timolol 0.5% in the treatment of simple chronic glaucoma. Br J Ophthalmol 1983 Apr; 67(4): 216–19

    Article  PubMed  CAS  Google Scholar 

  130. Katz IM, Berger ET. Effects of iris pigmentation on response of ocular pressure to timolol. Surv Ophthalmol 1979 May; 23(6): 395–8

    Article  PubMed  CAS  Google Scholar 

  131. Salminen L, Imre G, Huupponen R. The effect of ocular pigmentation on intraocular pressure response to timolol. Acta Ophthalmologica 1985; 173 Suppl.: 15–18

    PubMed  CAS  Google Scholar 

  132. McMahon CD, Shaffer RN, Hoskins HDJ, et al. Adverse effects experienced by patients taking timolol. Am J Ophthalmol 1979 Oct; 88(4): 736–8

    PubMed  CAS  Google Scholar 

  133. Van Buskirk EM. Adverse reactions from timolol administration. Ophthalmology 1980 May; 87(5): 447–50

    PubMed  Google Scholar 

  134. Bonomi L, Zavarise G, Noya E, et al. Effects of timolol maleate on tear flow in human eyes. Albr Graefes Arch Ophthalmol 1980; 213(1): 19–22

    Article  CAS  Google Scholar 

  135. Coakes RL, Mackie IA, Seal DV Effects of long-term treatment with timolol on lacrimal gland function. Br J Ophthalmol 1981 Sep; 65(9): 603–5

    Article  PubMed  CAS  Google Scholar 

  136. Fraunfelder FT. Interim report: national registry of possible drug-induced ocular side effects. Ophthalmology 1980 Feb; 87(2): 87–90

    PubMed  CAS  Google Scholar 

  137. Nelson WL, Fraunfelder FT, Sills JM, et al. Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution, 1978–1985. Am J Ophthalmol 1986 Nov; 102(5): 606–11

    PubMed  CAS  Google Scholar 

  138. Diggory P, Cassels-Brown A, Vail A, et al. Avoiding unsuspected respiratory side-effects of topical timolol with cardio-selective or sympathomimetic agents [published erratum appears in Lancet 1995 Jul; 346(8970): 322]. Lancet 1995 Jun; 345(8965): 1604–6

    Article  PubMed  CAS  Google Scholar 

  139. Sadiq SA, Fielding K, Vernon SA. The effect of timolol drops on respiratory function. Eye 1998; 12 (Pt 3a): 386–9

    Article  PubMed  Google Scholar 

  140. Shaivitz SA. Timolol and myasthenia gravis. JAMA 1979 Oct; 242(15): 1611–12

    Article  PubMed  CAS  Google Scholar 

  141. Coppeto JR. Timolol-associated myasthenia gravis. Am J Ophthalmol 1984 Aug; 98(2): 244–5

    PubMed  CAS  Google Scholar 

  142. Velde TM, Kaiser FE. Ophthalmic timolol treatment causing altered hypoglycemic response in a diabetic patient. Arch Intern Med 1983 Aug; 143(8): 1627

    Article  PubMed  CAS  Google Scholar 

  143. Zimmerman TJ, Sharir M, Nardin GF, et al. Therapeutic index of pilocarpine, carbachol, and timolol with nasolacrimal occlusion. Am J Ophthalmol 1992 Jul; 114(1): 1–7

    PubMed  CAS  Google Scholar 

  144. Reiss GR, Brubaker RF. The mechanism of betaxolol, a new ocular hypotensive agent. Ophthalmology 1983 Nov; 90(11): 1369–72

    PubMed  CAS  Google Scholar 

  145. Caldwell DR, Salisbury CR, Guzek JP. Effects of topical betaxolol in ocular hypertensive patients. Arch Ophthalmol 1984 Apr; 102(4): 539–40

    Article  PubMed  CAS  Google Scholar 

  146. Feghali JG, Kaufman PL. Decreased intraocular pressure in the hypertensive human eye with betaxolol, a beta 1-adrenergic antagonist. Am J Ophthalmol 1985 Dec; 100(6): 777–82

    PubMed  CAS  Google Scholar 

  147. Stewart RH, Kimbrough RL, Ward RL. Betaxolol vs timolol: a six-month double-blind comparison. Arch Ophthalmol 1986 Jan; 104(1): 46–8

    Article  PubMed  CAS  Google Scholar 

  148. Radius RL. Use of betaxolol in the reduction of elevated intraocular pressure. Arch Ophthalmol 1983 Jun; 101(6): 898–900

    Article  PubMed  CAS  Google Scholar 

  149. Collignon-Brach J. Long-term effect of ophthalmic beta-adrenoceptor antagonists on intraocular pressure and retinal sensitivity in primary open-angle glaucoma. Curr Eye Res 1992 Jan; 11(1): 1–3

    Article  PubMed  CAS  Google Scholar 

  150. Messmer C, Flammer J, Stumpfig D. Influence of betaxolol and timolol on the visual fields of patients with glaucoma. Am J Ophthalmol 1991 Dec; 112(6): 678–81

    PubMed  CAS  Google Scholar 

  151. Kaiser HJ, Hammer J, Messmer C. Thirty month visual field follow up of glaucoma patients treated with beta blockers. J Glauc 1992; 1: 153

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  153. Hoste AM. Ca2+ channel blocking activity of propranolol and betaxolol in isolated bovine retinal microartery. J Cardiovasc Pharmacol 1998; 32(3): 390–6

    Article  PubMed  CAS  Google Scholar 

  154. Schoene RB, Abuan T, Ward RL, et al. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol 1984 Jan; 97(1): 86–92

    PubMed  CAS  Google Scholar 

  155. Dunn TL, Gerber MJ, Shen AS, et al. The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects. Am Rev Respir Dis 1986 Feb; 133(2): 264–8

    PubMed  CAS  Google Scholar 

  156. Harris LS, Greenstein SH, Bloom AF. Respiratory difficulties with betaxolol. Am J Ophthalmol 1986 Aug; 102(2): 274–5

    Article  PubMed  CAS  Google Scholar 

  157. Roholt PC. Betaxolol and restrictive airway disease: case report. Arch Ophthalmol 1987 Sep; 105(9): 1172

    Article  PubMed  CAS  Google Scholar 

  158. Nelson WL, Kuritsky JN. Early postmarketing surveillance of betaxolol hydrochloride, Sept 1985–Sept 1986. Am J Ophthalmol 1987 Apr; 103(4): 592

    PubMed  CAS  Google Scholar 

  159. Ball S. Congestive heart failure from betaxolol: case report. Arch Ophthalmol 1987 Mar; 105(3): 320

    Article  PubMed  CAS  Google Scholar 

  160. Le Jeunne C, Munera Y, Hugues FC. Systemic effects of three beta-blocker eyedrops: comparison in healthy volunteers of beta 1- and beta 2-adrenoreceptor inhibition. Clin Pharmacol Ther 1990 May; 47(5): 578–83

    Article  PubMed  CAS  Google Scholar 

  161. Vuori ML, Ali-Melkkila T, Kaila T, et al. Beta 1- and beta 2-antagonist activity of topically applied betaxolol and timolol in the systemic circulation. Acta Ophthalmol 1993 Oct; 71(5): 682–5

    CAS  Google Scholar 

  162. Orlando RG. Clinical depression associated with betaxolol. Am J Ophthalmol 1986 Aug; 102(2): 275

    Article  PubMed  CAS  Google Scholar 

  163. Lynch MG, Whitson JT, Brown RH, et al. Topical beta-blocker therapy and central nervous system side effects: a preliminary study comparing betaxolol and timolol. Arch Ophthalmol 1988 Jul; 106(7): 908–11

    Article  PubMed  CAS  Google Scholar 

  164. Cinotti A, Cinotti D, Grant W, et al. Levobunolol vs timolol for open-angle glaucoma and ocular hypertension. Am J Ophthalmol 1985 Jan; 99(1): 11–17

    PubMed  CAS  Google Scholar 

  165. Berson FG, Cohen HB, Foerster RJ, et al. Levobunolol compared with timolol for the long-term control of elevated intraocular pressure. Arch Ophthalmol 1985 Mar; 103(3): 379–82

    Article  PubMed  CAS  Google Scholar 

  166. Boozman FW, Carriker R, Foerster R, et al. Long-term evaluation of 0.25% levobunolol and timolol for therapy for elevated intraocular pressure. Arch Ophthalmol 1988 May; 106(5): 614–18

    Article  PubMed  Google Scholar 

  167. The Levobunolol Study Group. Levobunolol: abeta-adrenoceptor antagonist effective in the long-term treatment of glaucoma [appended]. Ophthalmology 1985 Sep; 92(9): 1271–6

    Google Scholar 

  168. Geyer O, Lazar M, Novack GD, et al. Levobunolol compared with timolol: a four-year study. Br J Ophthalmol 1988 Dec; 72(12): 892–6

    Article  PubMed  CAS  Google Scholar 

  169. The Levobunolol Study Group. Levobunolol: a four-year study of efficacy and safety in glaucoma treatment. Ophthalmology 1989 May; 96(5): 642–5

    Google Scholar 

  170. Silverstone D, Zimmerman T, Choplin N, et al. Evaluation of once-daily levobunolol 0.25% and timolol 0.25% therapy for increased intraocular pressure. Am J Ophthalmol 1991 Jul; 112(1): 56–60

    PubMed  CAS  Google Scholar 

  171. Wandel T, Fishman D, Novack GD, et al. Ocular hypotensive efficacy of 0.25% levobunolol instilled once daily. Ophthalmology 1988 Feb; 95(2): 252–5

    PubMed  CAS  Google Scholar 

  172. Derick RJ, Robin AL, Tielsch J, et al. Once-daily versus twice-daily levobunolol (0.5%) therapy: acrossover study. Ophthalmology 1992 Mar; 99(3): 424–9

    PubMed  CAS  Google Scholar 

  173. Frishman WH, Covey S. Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism [review]. J Clin Pharmacol 1990 May; 30(5): 412–21

    PubMed  CAS  Google Scholar 

  174. Hirota A, Mishima H, Kiuchi Y, et al. Effect of topical 8-hydroxy carteolol on intraocular pressure and melanin granules [in Japanese]. Acta Soc Ophthalmol Jpn 1991 Aug; 95(8): 752–7

    CAS  Google Scholar 

  175. Coulangeon LM, Sole M, Menerath JM, et al. Aqueous humor flow measured by fluorophotometry. A comparative study of the effect of various beta-blocker eyedrops in patients with ocular hypertension [in French]. Ophtalmologie 1990 Mar; 4(2): 156–61

    PubMed  CAS  Google Scholar 

  176. Scoville B, Mueller B, White BG, et al. A double-masked comparison of carteolol and timolol in ocular hypertension. Am J Ophthalmol 1988 Feb; 105(2): 150–4

    PubMed  CAS  Google Scholar 

  177. Stewart WC, Shields MB, Allen RC, et al. A 3-month comparison of 1% and 2% carteolol and 0.5% timolol in open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol 1991; 229(3): 258–61

    Article  PubMed  CAS  Google Scholar 

  178. Tsuchisaka H, Kin K, Matsumoto S, et al. Multi institutional evaluation of timolol and carteolol for glaucomas. Ganka Rinsho Iho 1991; 85: 1136–40

    Google Scholar 

  179. Horie T, Takahashi O, Shirato S, et al. Comparison of ocular hypotensive effects of topical timolol and carteolol. Jpn J Clin Pharmacol 1982; 36: 1065–70

    Google Scholar 

  180. Mills KB, Raines M, Joyce P. A single blind, stratified, randomised, non crossover trial comparing carteolol 1% with timolol 0.25% in the long term management of glaucoma. Br J Clin Prac 1987; 41 Suppl. 51: 10–12

    Google Scholar 

  181. Schnarr KD. Comparative multicenter study of carteolol eyedrops with other beta blockers in 768 patients under normal conditions. Klin Monatsbl Augenheilkd 1988 Feb; 192(2): 167–72

    Article  PubMed  CAS  Google Scholar 

  182. Flury H, Tournoux A, Martenet AC. Tolerance and pharmacologic effectiveness of antiglaucoma eyedrops. Klin Monatsbl Augenheilkd 1986 Jun; 188(6): 573–5

    Article  PubMed  CAS  Google Scholar 

  183. van Brummelen P. The relevance of intrinsic sympathomimetic activity for beta-blocker-induced changes in plasma lipids. J Cardiovasc Pharmacol 1983; 5 Suppl. 1: S51–5

    Article  PubMed  Google Scholar 

  184. Freedman SF, Freedman NJ, Shields MB, et al. Effects of ocular carteolol and timolol on plasma high-density lipoprotein cholesterol level. Am J Ophthalmol 1993 Nov; 116(5): 600–11

    PubMed  CAS  Google Scholar 

  185. Battershill PE, Sorkin EM. Ocular metipranolol: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in glaucoma and ocular hypertension. Drugs 1988 Nov; 36(5): 601–15

    Article  PubMed  CAS  Google Scholar 

  186. Dausch D, Brewitt H, Edelhoff R. Metipranolol eyedrops: clinical suitability in the treatment of chronic open angle glaucoma. In: Merte HJ, editor. Metipranolol. Wien: Springer-Verlag, 1983

    Google Scholar 

  187. Serie JB, Lustgarten JS, Podos SM. A clinical trial of metipranolol, a noncardioselective beta-adrenergic antagonist, in ocular hypertension. Am J Ophthalmol 1991 Sept; 112(3): 302–7

    Google Scholar 

  188. Merte HJ, Stryz JR, Mertz M. Comparative studies of initial pressure reduction using 0.3% metipranolol and 0.25% timolol in eyes with wide-angle glaucoma. Klin Monatsbl Augenheilkd 1983 Apr; 182(4): 286–9

    Article  PubMed  CAS  Google Scholar 

  189. Schmitz-Valckenberg P, Jonas J, Brambring DF. Reductions in pressure with metipranolol 0.1%. ZPrakt Augenhkd 1984; 5: 171–5

    Google Scholar 

  190. Muller O, Knobel HR. Effectiveness and tolerance of metipranolol: results of a multi-center long-term study in Switzerland. Klin Monatsbl Augenheilkd 1986 Jan; 188(1): 62–3

    Article  PubMed  CAS  Google Scholar 

  191. Ecoffet M, Demailly P. Mid-term results of a double-blind study comparing metipranolol to timolol in the treatment of primary open-angle glaucoma. J Fr Ophtalmol 1987; 10(6–7): 451–4

    PubMed  CAS  Google Scholar 

  192. Bleckmann H, Pham Duy T, Grajewski O. Therapeutic efficacy of metipranolol eyedrops 0.3% versus timolol eyedrops 0.25%: a double blind cross over study. In: Merte HJ, editor. Metipranolol. Wien: Springer-Verlag, 1983

    Google Scholar 

  193. Kruse W. Metipranolol in glaucoma therapy. Der Augenartz 1983; 3: 168–72

    Google Scholar 

  194. Denffer H. Efficacy and tolerance of metipranolol: results of a multi center long term study. In: Merte HJ, editor. Metipranolol. Wien: Springer-Verlag, 1983

    Google Scholar 

  195. Krieglstein GK, Novack GD, Voepel E, et al. Levobunolol and metipranolol: comparative ocular hypotensive efficacy, safety, and comfort. Br J Ophthalmol 1987 Apr; 71(4): 250–3

    Article  PubMed  CAS  Google Scholar 

  196. Akingbehin T, Villada JR. Metipranolol-associated granulomatous anterior uveitis. Br J Ophthalmol 1991 Sep; 75(9): 519–23

    Article  PubMed  CAS  Google Scholar 

  197. Schultz JS, Hoenig JA, Charles H. Possible bilateral anterior uveitis secondary to metipranolol (optipranolol) therapy. Arch Ophthalmol 1993 Dec; 111(12): 1606–7

    Article  PubMed  CAS  Google Scholar 

  198. Melles RB, Wong IG. Metipranolol-associated granulomatous iritis. Am J Ophthalmol 1994 Dec; 118(6): 712–15

    PubMed  CAS  Google Scholar 

  199. Akingbehin T, Villada JR, Walley T. Metipranolol-induced adverse reactions: I. The rechallenge study. Eye 1992; 6 (Pt 3): 277–9

    Article  PubMed  Google Scholar 

  200. Burvenich H. Metipranolol associated granulomatous anterior uveitis: not so uncommon as thought. Bull Soc Belg Opthalmol 1995; 257: 63–6

    CAS  Google Scholar 

  201. Watanabe TM, Hodes BL. Bilateral anterior uveitis associated withabrandof metipranolol. Arch Ophthalmol 1997 Mar; 115(3): 421–2

    Article  PubMed  CAS  Google Scholar 

  202. Patel NP, Patel KH, Moster MR, et al. Metipranolol-associated nongranulomatous anterior uveitis. Am J Ophthalmol 1997; 123(6): 843–4

    PubMed  CAS  Google Scholar 

  203. Friedland BR, Maren TH. Pharmacology of the eye. Berlin: Springer-Verlag, 1984

    Google Scholar 

  204. Wistrand PJ, Schenholm M, Lonnerholm G. Carbonic anhydrase isoenzymes CA I and CA II in the human eye. Invest Ophthalmol Vis Sci 1986 Mar; 27(3): 419–28

    PubMed  CAS  Google Scholar 

  205. Friedland BR, Mallonee J, Anderson DR. Short-term dose response characteristics of acetazolamide in man. Arch Ophthalmol 1977 Oct; 95(10): 1809–12

    Article  PubMed  CAS  Google Scholar 

  206. Becker B. Decrease in intraocular pressure in man by acarbonic anhydrase inhibitor (Diamox). Am J Ophthalmol 1954; 37: 13–17

    PubMed  CAS  Google Scholar 

  207. Dailey RA, Brubaker RF, Bourne WM. The effects of timolol maleate and acetazolamide on the rate of aqueous formation in normal human subjects. Am J Ophthalmol 1982 Feb; 93(2): 232–7

    PubMed  CAS  Google Scholar 

  208. Grant WM, Trotter RR. Diamox (acetazolamide): in the treatment of glaucoma. Arch Ophthalmol 1954; 51: 735–9

    Article  CAS  Google Scholar 

  209. Dahlen K, Epstein DL, Grant WM, et al. A repeated dose-response study of methazolamide in glaucoma. Arch Ophthalmol 1978 Dec; 96(12): 2214–18

    Article  PubMed  CAS  Google Scholar 

  210. Fraunfelder FT, Meyer SM, Bagby Jr GC, et al. Hematologic reactions to carbonic anhydrase inhibitors. Am J Ophthalmol 1985 July; 100(1): 79–81

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  212. Sugrue MF, Mallorga P, Schwam H, et al. A comparison of L-671,152 and MK-927, two topically effective ocular hypotensive carbonic anhydrase inhibitors, in experimental animals. Curr Eye Res 1990 Jun; 9(6): 607–15

    Article  PubMed  CAS  Google Scholar 

  213. Strahlman E, Tipping R, Vogel R. A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol (International Dorzolamide Study Group). Arch Ophthalmol 1995 Aug; 113(8): 1009–16

    Article  PubMed  CAS  Google Scholar 

  214. Maus TL, Larsson LI, McLaren JW, et al. Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow in humans. Arch Ophthalmol 1997 Jan; 115(1): 45–9

    Article  PubMed  CAS  Google Scholar 

  215. Chrisp P, Sorkin EM. Ocular carteolol: a review of its pharmacological properties, and therapeutic use in glaucoma and ocular hypertension [published erratum appears in Drugs Aging 1994 Jan; 4(1): 62]. Drugs Aging 1992 Jan; 2(1): 58-77

    Google Scholar 

  216. Kaminski S, Hommer A, Koyuncu D, et al. Influence of dorzolamide on corneal thickness, endothelial cell count and corneal sensibility. Acta Ophthalmol Scand 1998 Feb; 76(1): 78–9

    Article  PubMed  CAS  Google Scholar 

  217. Lass JH, Khosrof SA, Laurence JK, et al. A double-masked, randomized, 1-year study comparing the corneal effects of dorzolamide, timolol, and betaxolol (Dorzolamide Corneal Effects Study Group). Arch Ophthalmol 1998 Aug; 116(8): 1003–10

    PubMed  CAS  Google Scholar 

  218. Egan CA, Hodge DO, McLaren JW, et al. Effect of dorzolamide on corneal endothelial function in normal human eyes. Invest Ophthalmol Vis Sci 1998 Jan; 39(1): 23–9

    PubMed  CAS  Google Scholar 

  219. Konowal A, Morrison JC, Brown SVL, et al. Irreversible corneal decompensation in patients treated with topical dorzolamide. Am J Ophthalmol 1999 Apr; 127(4): 403–6

    Article  PubMed  CAS  Google Scholar 

  220. Silver LH. Clinical efficacy and safety of brinzolamide (Azopt), a new topical carbonic anhydrase inhibitor for primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol 1998 Sep; 126(3): 400–8

    Article  PubMed  CAS  Google Scholar 

  221. Camras CB, Bito LZ, Eakins KE. Reduction of intraocular pressure by prostaglandins applied topically to the eyes of conscious rabbits. Invest Ophthalmol Vis Sci 1977 Dec; 16(12): 1125–34

    PubMed  CAS  Google Scholar 

  222. Hoyng PF, de Jong N. Iloprost, a stable prostacyclin analog, reduces intraocular pressure. Invest Ophthalmol Vis Sci 1987 Mar; 28(3): 470–6

    PubMed  CAS  Google Scholar 

  223. Groeneboer MC, Hoyng PF, Kuizenga A. Prostaglandin F2 alpha isopropyl ester versus iloprost phenacyl ester in rabbit and beagle eyes. Curr Eye Res 1989 Feb; 8(2): 131–8

    Article  PubMed  CAS  Google Scholar 

  224. Camras CB, Schumer RA, Marsk A, et al. Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension. Arch Ophthalmol 1992 Dec; 110(12): 1733–8

    Article  PubMed  CAS  Google Scholar 

  225. Alm A, Villumsen J. PhXA34, a new potent ocular hypotensive drug: a study on dose-response relationship and on aqueous humor dynamics in healthy volunteers [see comments]. Arch Ophthalmol 1991 Nov; 109(11): 1564–8

    Article  PubMed  CAS  Google Scholar 

  226. Alm A, Villumsen J, Tornquist P, et al. Intraocular pressure-reducing effect of PhXA41 in patients with increased eye pressure: a one-month study [see comments]. Ophthalmology 1993 Sep; 100(9): 1312–16

    PubMed  CAS  Google Scholar 

  227. Hotehama Y, Mishima HK. Clinical efficacy of PhXA34 and PhXA41, two novel prostaglandin F2 alpha-isopropyl ester analogues for glaucoma treatment. Jpn J Ophthalmol 1993; 37(3): 259–69

    PubMed  CAS  Google Scholar 

  228. Nagasubramanian S, Sheth GP, Hitchings RA, et al. Intraocular pressure-reducing effect of PhXA41 in ocular hypertension: comparison of dose regimens. Ophthalmology 1993 Sep; 100(9): 1305–11

    PubMed  CAS  Google Scholar 

  229. Racz P, Ruzsonyi MR, Nagy ZT, et al. Maintained intraocular pressure reduction with once-a-day application of a new prostaglandin F2 alpha analogue (PhXA41): an in-hospital, placebo-controlled study. Arch Ophthalmol 1993 May; 111(5): 657–61

    Article  PubMed  CAS  Google Scholar 

  230. Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning: a comparison with timolol (Scandinavian Latanoprost Study Group). Ophthalmology 1995 Dec; 102(12): 1743–52

    PubMed  CAS  Google Scholar 

  231. Mishima HK, Kiuchi Y, Takamatsu M, et al. Circadian intraocular pressure management with latanoprost: diurnal and nocturnal intraocular pressure reduction and increased uveoscleral outflow [review]. Surv Ophthalmol 1997 Feb; 41 Suppl. 2: S139–44

    Article  PubMed  Google Scholar 

  232. Camras CB. Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma: a six-month masked, multicenter trial in the United States (The United States Latanoprost Study Group). Ophthalmology 1996 Jan; 103(1): 138–47

    PubMed  CAS  Google Scholar 

  233. Watson P, Stjernschantz J. A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension (The Latanoprost Study Group). Ophthalmology 1996 Jan; 103(1): 126–37

    PubMed  CAS  Google Scholar 

  234. Mishima HK, Masuda K, Kitazawa Y, et al. A comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension: a 12-week study. Arch Ophthalmol 1996 Aug; 114(8): 929–32

    Article  PubMed  CAS  Google Scholar 

  235. Camras CB, Alm A, Watson P, et al. Latanoprost, a prostaglandin analog, for glaucoma therapy: efficacy and safety after 1 year of treatment in 198 patients (Latanoprost Study Groups). Ophthalmology 1996 Nov; 103(11): 1916–24

    PubMed  CAS  Google Scholar 

  236. Rulo AH, Greve EL, Geijssen HC, et al. Reduction of intraocular pressure with treatment of latanoprost once daily in patients with normal-pressure glaucoma [see comments]. Ophthalmology 1996 Aug; 103(8): 1276–82

    PubMed  CAS  Google Scholar 

  237. Fechtner RD, Khouri AS, Zimmerman TJ, et al. Anterior uveitis associated with latanoprost. Am J Ophthalmol 1998 July; 126(1): 37–41

    Article  PubMed  CAS  Google Scholar 

  238. Hoyng PF, Rulo AH, Grève EL, et al. Fluorescein angiographic evaluation of the effect of latanoprost treatment on blood-retinal barrier integrity: a review of studies conducted on pseudophakic glaucoma patients and on phakic and aphakic monkeys. Surv Ophthalmol 1997 Feb; 41 Suppl. 2: S83–8

    Article  PubMed  Google Scholar 

  239. Warwar RE, Bullock JD, Ballal D. Cystoid macular edema and anterior uveitis associated with latanoprost use: experience and incidence in a retrospective review of 94 patients. Ophthalmology 1998 Feb; 105(2): 263–8

    Article  PubMed  CAS  Google Scholar 

  240. Moroi SE, Gottfredsdottir MS, Schteingart MT, et al. Cystoid macular edema associated with latanoprost therapy in a case series of patients with glaucoma and ocular hypertension. Ophthalmology 1999 May; 106(5): 1024–9

    Article  PubMed  CAS  Google Scholar 

  241. Camras CB. CME and anterior uveitis with latanoprost use. Ophthalmology 1998 Nov; 105(11): 1978–81

    Article  PubMed  CAS  Google Scholar 

  242. Thorne JE, Maguire AM, Lanciano R. CME and anterior uveitis with latanoprost use. Ophthalmology 1998 Nov; 105(11): 1981–3

    Article  PubMed  CAS  Google Scholar 

  243. Ayyala RS, Cruz DA, Margo CE, et al. Cystoid macular edema associated with latanoprost in aphakic and pseudophakic eyes. Am J Ophthalmol 1998 Oct; 126(4): 602–4

    Article  PubMed  CAS  Google Scholar 

  244. Callanan D, Fellman RL, Savage JA. Latanoprost-associated cystoid macular edema. Am J Ophthalmol 1998 Jul; 126(1): 134–5

    Article  PubMed  CAS  Google Scholar 

  245. Selen G, Stjernschantz J, Resul B. Prostaglandin-induced iridial pigmentation in primates. Surv Ophthalmol 1997 Feb; 41 Suppl. 2: S125–8

    Article  PubMed  Google Scholar 

  246. 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 Feb; 41 Suppl. 2: S129–38

    Article  PubMed  Google Scholar 

  247. Johnstone MA. Hypertrichosis and increased pigmentation of eyelashes and adjacent hair in the region of the ipsilateral eyelids of patients treated with unilateral topical latanoprost. Am J Ophthalmol 1997 Oct; 124(4): 544–7

    PubMed  CAS  Google Scholar 

  248. Wand M. Latanoprost and hyperpigmentation of eyelashes [letter]. Arch Ophthalmol 1997 Sep; 115(9): 1206–8

    Article  PubMed  CAS  Google Scholar 

  249. Watson PG. Latanoprost: two years’ experience of its use in the United Kingdom (Latanoprost Study Group). Ophthalmology 1998 Jan; 105(1): 82–7

    Article  PubMed  CAS  Google Scholar 

  250. Hedner J, Svedmyr N, Lunde H, et al. The lack of respiratory effects of the ocular hypotensive drug latanoprost in patients with moderate-steroid treated asthma. Surv Ophthalmol 1997 Feb; 41 Suppl. 2: S111–15

    Article  PubMed  Google Scholar 

  251. Taniguchi T, Haque MS, Sugiyama K, et al. Ocular hypotensive mechanism of topical isopropyl unoprostone, a novel prostaglandin metabolite-related drug, in rabbits. J Ocul Pharmacol Ther 1996; 12(4): 489–98

    Article  PubMed  CAS  Google Scholar 

  252. Sakurai M, Araie M, Oshika T, et al. Effects of topical application of UF-021, a novel prostaglandin derivative, on aqueous humor dynamics in normal human eyes [published erratum appears in Jpn J Ophthalmol 1992; 36(4): 491]. Jpn J Ophthalmol 1991; 35(2): 156–65

    PubMed  CAS  Google Scholar 

  253. Sakurai M, Araie M, Oshika T, et al. Effects of topical application of UF-021, a novel prostaglandin-related compound, on aqueous humor dynamics in rabbit. Jpn J Ophthalmol 1993; 37(3): 252–8

    PubMed  CAS  Google Scholar 

  254. Azuma I, Masuda K, Kitazawa Y, et al. 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(4): 514–25

    PubMed  CAS  Google Scholar 

  255. Motulsky HJ, Cunningham EM, DeBlasi A, et al. Desensitization and redistribution of beta-adrenergic receptors on human mononuclear leukocytes. Am J Physiol 1986 May; 250 (5 Pt 1): E583–90

    PubMed  CAS  Google Scholar 

  256. Kass MA. Efficacy of combining timolol with other anti-glaucoma medications. Surv Ophthalmol 1983 Dec; 28 Suppl.: 274–9

    Article  PubMed  Google Scholar 

  257. Keates EU. Evaluation of timolol maleate combination therapy in chronic open-angle glaucoma. Am J Ophthalmol 1979 Sep; 88 (3 Pt 2): 565–71

    PubMed  CAS  Google Scholar 

  258. Airaksinen PJ, Valkonen R, Stenborg T, et al. A double-masked study of timolol and pilocarpine combined. Am J Ophthalmol 1987 Dec; 104(6): 587–90

    PubMed  CAS  Google Scholar 

  259. Maclure GM, Vogel R, Sturm A, et al. Effect on the 24-hour diurnal curve of intraocular pressure of a fixed ratio combination of timolol 0.5% and pilocarpine 2% in patients with COAG not controlled on timolol 0.5%. Br J Ophthalmol 1989 Oct; 73(10): 827–31

    Article  PubMed  CAS  Google Scholar 

  260. Scharrer A, Ober M. Metipranolol 0.1% and pilocarpine 2% as a fixed combination compared to each substance alone in the treatment of glaucoma: a controlled, randomized clinical study comparing the intraindividual effects and tolerance. Klin Monatsbl Augenheilkd 1986 Dec; 189(6): 450–5

    Article  PubMed  CAS  Google Scholar 

  261. Tsoy EA, Meekins BB, Shields MB. Comparison of two treatment schedules for combined timolol and dipivefrin therapy. Am J Ophthalmol 1986 Sep; 102(3): 320–4

    PubMed  CAS  Google Scholar 

  262. Alexander DW, Berson FG, Epstein DL. A clinical trial of timolol and epinephrine in the treatment of primary open-angle glaucoma. Ophthalmology 1988 Feb; 95(2): 247–51

    PubMed  CAS  Google Scholar 

  263. Drance SM, Douglas GR, Wijsman KJ, et al. Adrenergic and adrenolytic effects on intraocular pressure. Graefes Arch Clin Exp Ophthalmol 1991; 229(1): 50–1

    Article  PubMed  CAS  Google Scholar 

  264. Allen RC, Robin AL, Long D, et al. A combination of levobunolol and dipivefrin for the treatment of glaucoma. Arch Ophthalmol 1988 Jul; 106(7): 904–7

    Article  PubMed  CAS  Google Scholar 

  265. Weinreb RN, Ritch R, Kushner FH. Effect of adding betaxolol to dipivefrin therapy. Am J Ophthalmol 1986 Feb; 101(2): 196–8

    PubMed  CAS  Google Scholar 

  266. Allen RC, Epstein DL. Additive effect of betaxolol and epinephrine in primary open angle glaucoma. Arch Ophthalmol 1986 Aug; 104(8): 1178–84

    Article  PubMed  CAS  Google Scholar 

  267. Berson FG, Epstein DL. Separate and combined effects of timolol maleate and acetazolamide in open-angle glaucoma. Am J Ophthalmol 1981 Dec; 92(6): 788–91

    PubMed  CAS  Google Scholar 

  268. Kass MA, Korey M, Gordon M, et al. Timolol and acetazolamide. A study of concurrent administration. Arch Ophthalmol 1982 Jun; 100(6): 941–2

    Article  PubMed  CAS  Google Scholar 

  269. Strohmaier K, Snyder E, Dubiner H, et al. The efficacy and safety of the dorzolamide-timolol combination versus the concomitant administration of its components. Ophthalmology 1998 Oct; 105(10): 1936–44

    Article  PubMed  CAS  Google Scholar 

  270. Boyle JE, Ghosh K, Gieser DK, et al. A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide. Ophthalmology 1998 Oct; 105(10): 1945–51

    Article  PubMed  CAS  Google Scholar 

  271. Clineschmidt CM, Williams RD, Snyder E, et al. Arandomized trial in aptients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide. Ophthalmology 1998 Oct; 105(10): 1952–9

    Article  PubMed  CAS  Google Scholar 

  272. Adamsons I, Clineschmidt C, Polis A, et al. The efficacy and safety of dorzolamide as adjunctive therapy to timolol maleate gellan solution in patients with elevated intraocular pressure. J Glauc 1998 Aug; 7(4): 253–60

    CAS  Google Scholar 

  273. Villumsen J, Aim A. The effect of adding prostaglandin F2 alpha-isopropy lester to timolol in patients with open angle glaucoma. Arch Ophthalmol 1990 Aug; 108(8): 1102–5

    Article  PubMed  CAS  Google Scholar 

  274. Lee PY, Shao H, Camras CB, et al. Additivity of prostaglandin F2 alpha-1-isopropyl ester to timolol in glaucoma patients. Ophthalmology 1991 Jul; 98(7): 1079–82

    PubMed  CAS  Google Scholar 

  275. Rulo AH, Greve EL, Hoyng PF. Additive ocular hypotensive effect of latanoprost and acetazolamide: a short-term study in patients with elevated intraocular pressure. Ophthalmology 1997 Sep; 104(9): 1503–7

    PubMed  CAS  Google Scholar 

  276. Alm A, Widengard I, Kjellgren D, et al. Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol [see comments]. Br J Ophthalmol 1995 Jan; 79(1): 12–16

    Article  PubMed  CAS  Google Scholar 

  277. Hoyng PF, Rulo A, Greve E, et al. The additive intraocular pressure-lowering effect of latanoprost in combined therapy with other ocular hypotensive agents [review]. Surv Ophthalmol 1997 Feb; 41 Suppl. 2: S93–8

    Article  PubMed  Google Scholar 

  278. Kimal AM, Topalkara A, Guler C. Additive effect of latanoprost and dorzolamide in patients with elevated intraocular pressure. Int Ophthalmol 1998; 22(1): 37–42

    Article  Google Scholar 

  279. Widengard I, Maepea O, Aim A. Effects of latanoprost and dipifevrin, alone or combined, on intraocular pressure and on blood-aqueous barrier permeability. Br J Ophthalmol 1998 Apr; 82(4): 404–6

    Article  PubMed  CAS  Google Scholar 

  280. Fristrom B, Nilsson SE. Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine: a study on patients with elevated intraocular pressure. Arch Ophthalmol 1993 May; 111(5): 662–5

    Article  PubMed  CAS  Google Scholar 

  281. Villumsen J, Alm A. Effect of the prostaglandin F2alpha analogue PhXA41 in eyes treated with pilocarpine and timolol. Invest Ophthalmol Vis Sci 1992; 33 Suppl.: 1248

    Google Scholar 

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Hoyng, P.F.J., van Beek, L.M. Pharmacological Therapy for Glaucoma. Drugs 59, 411–434 (2000). https://doi.org/10.2165/00003495-200059030-00003

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