Skip to main content
Transactions of the American Ophthalmological Society logoLink to Transactions of the American Ophthalmological Society
. 1989;87:598–618.

Timolol treatment prevents or delays glaucomatous visual field loss in individuals with ocular hypertension: a five-year, randomized, double-masked, clinical trial.

M A Kass 1
PMCID: PMC1298559  PMID: 2562546

Abstract

A 5-year, randomized, double-masked, clinical trial was conducted to determine whether treatment with topical timolol maleate was effective in preventing or delaying the onset of glaucomatous visual field loss in subjects with ocular hypertension. Sixty-five individuals considered to be at moderate risk for developing open-angle glaucoma were recruited for the study. In each patient, one eye was chosen randomly to receive timolol twice-daily while the fellow eye received diluent (placebo). Timolol administration reduced IOP from baseline in the treated eyes over the course of the study by a mean +/- SD of 4.9 +/- 3.4 mm Hg. Timolol administration also produced a mean +/- SD contralateral reduction of IOP from baseline in the untreated fellow eyes of 2.9 +/- 3.1 mm Hg. The mean +/- SD difference in IOP between the treated and untreated eyes during the study was 2.3 +/- 2.6 mm Hg. Over the course of the study reproducible visual field loss developed in 4 timolol treated eyes and 10 placebo treated eyes (P = .039, McNemar test). Clinical progressive optic disc cupping was noted in four treated and eight untreated eyes (P = .11, McNemar test). In the 42 subjects who completed a minimum 4-year follow-up, baseline and final optic disc photographs were analyzed using a computer image analysis system to determine changes in the area of disc pallor. The mean +/- SD increase in optic disc pallor was 0.86% +/- 2.4% in the timolol treated eyes and 1.80% +/- 3.6% in the placebo treated eyes. This difference was statistically significant (P = .04, paired t-test). This study provides evidence that medical treatment prevents or delays the onset of glaucomatous visual field loss and optic disc damage in individuals with ocular hypertension. The magnitude of the protective effect of timolol was partially obscured by the contralateral reduction of IOP in the placebo treated fellow eyes.

Full text

PDF
598

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armaly M. F., Krueger D. E., Maunder L., Becker B., Hetherington J., Jr, Kolker A. E., Levene R. Z., Maumenee A. E., Pollack I. P., Shaffer R. N. Biostatistical analysis of the collaborative glaucoma study. I. Summary report of the risk factors for glaucomatous visual-field defects. Arch Ophthalmol. 1980 Dec;98(12):2163–2171. doi: 10.1001/archopht.1980.01020041015002. [DOI] [PubMed] [Google Scholar]
  2. Armaly M. F. Ocular pressure and visual fields. A ten-year follow-up study. Arch Ophthalmol. 1969 Jan;81(1):25–40. doi: 10.1001/archopht.1969.00990010027005. [DOI] [PubMed] [Google Scholar]
  3. Becker B., Morton W. R. Topical epinephrine in glaucoma suspects. Am J Ophthalmol. 1966 Aug;62(2):272–277. doi: 10.1016/0002-9394(66)91483-8. [DOI] [PubMed] [Google Scholar]
  4. Bengtsson B. Manifest glaucoma in the aged I: occurrence nine years after a population survey. Acta Ophthalmol (Copenh) 1981 Jun;59(3):321–331. doi: 10.1111/j.1755-3768.1981.tb02996.x. [DOI] [PubMed] [Google Scholar]
  5. Chauhan B. C., Drance S. M., Douglas G. R. The effect of long-term intraocular pressure reduction on the differential light sensitivity in glaucoma suspects. Invest Ophthalmol Vis Sci. 1988 Oct;29(10):1478–1485. [PubMed] [Google Scholar]
  6. Chiou G. C., Yan H. Y. Effects of antiglaucoma drugs on the blood flow in rabbit eyes. Ophthalmic Res. 1986;18(5):265–269. doi: 10.1159/000265445. [DOI] [PubMed] [Google Scholar]
  7. Chisholm I. A., Stead S., Tan L., Melenchuk J. W. Prognostic indicators in ocular hypertension. Can J Ophthalmol. 1980 Jan;15(1):4–8. [PubMed] [Google Scholar]
  8. Daubs J. G., Crick R. P. Effect of refractive error on the risk of ocular hypertension and open angle glaucoma. Trans Ophthalmol Soc U K. 1981;101(1):121–126. [PubMed] [Google Scholar]
  9. David R., Livingston D. G., Luntz M. H. Ocular hypertension--a long-term follow-up of treated and untreated patients. Br J Ophthalmol. 1977 Nov;61(11):668–674. doi: 10.1136/bjo.61.11.668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. David R., Livingston D., Luntz M. H. Ocular hypertension: a comparative follow-up of black and white patients. Br J Ophthalmol. 1978 Oct;62(10):676–678. doi: 10.1136/bjo.62.10.676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Drance S. M., Schulzer M., Douglas G. R., Sweeney V. P. Use of discriminant analysis. II. Identification of persons with glaucomatous visual field defects. Arch Ophthalmol. 1978 Sep;96(9):1571–1573. doi: 10.1001/archopht.1978.03910060205003. [DOI] [PubMed] [Google Scholar]
  12. Drance S. M., Schulzer M., Thomas B., Douglas G. R. Multivariate analysis in glaucoma. Use of discriminant analysis in predicting glaucomatous visual field damage. Arch Ophthalmol. 1981 Jun;99(6):1019–1022. doi: 10.1001/archopht.1981.03930011019007. [DOI] [PubMed] [Google Scholar]
  13. Eddy D. M., Sanders L. E., Eddy J. F. The value of screening for glaucoma with tonometry. Surv Ophthalmol. 1983 Nov-Dec;28(3):194–205. doi: 10.1016/0039-6257(83)90097-8. [DOI] [PubMed] [Google Scholar]
  14. Graham P. A. The definition of pre-glaucoma. A prospective study. Trans Ophthalmol Soc U K. 1969;88:153–165. [PubMed] [Google Scholar]
  15. Grunwald J. E. Effect of topical timolol on the human retinal circulation. Invest Ophthalmol Vis Sci. 1986 Dec;27(12):1713–1719. [PubMed] [Google Scholar]
  16. Hart W. M., Jr, Yablonski M., Kass M. A., Becker B. Multivariate analysis of the risk of glaucomatous visual field loss. Arch Ophthalmol. 1979 Aug;97(8):1455–1458. doi: 10.1001/archopht.1979.01020020117005. [DOI] [PubMed] [Google Scholar]
  17. Hiller R., Sperduto R. D., Krueger D. E. Race, iris pigmentation, and intraocular pressure. Am J Epidemiol. 1982 May;115(5):674–683. doi: 10.1093/oxfordjournals.aje.a113350. [DOI] [PubMed] [Google Scholar]
  18. Høvding G., Aasved H. Prognostic factors in the development of manifest open angle glaucoma. A long-term follow-up study of hypertensive and normotensive eyes. Acta Ophthalmol (Copenh) 1986 Dec;64(6):601–608. doi: 10.1111/j.1755-3768.1986.tb00675.x. [DOI] [PubMed] [Google Scholar]
  19. Kitazawa Y., Horie T., Aoki S., Suzuki M., Nishioka K. Untreated ocular hypertension. A long-term prospective study. Arch Ophthalmol. 1977 Jul;95(7):1180–1184. doi: 10.1001/archopht.1977.04450070078004. [DOI] [PubMed] [Google Scholar]
  20. Kitazawa Y. Prophylactic therapy of ocular hypertension. A prospective study. Trans Ophthalmol Soc N Z. 1981;33:30–32. [PubMed] [Google Scholar]
  21. Kwitko G. M., Shin D. H., Ahn B. H., Hong Y. J. Bilateral effects of long-term monocular timolol therapy. Am J Ophthalmol. 1987 Dec 15;104(6):591–594. doi: 10.1016/0002-9394(87)90169-3. [DOI] [PubMed] [Google Scholar]
  22. Leske M. C., Rosenthal J. Epidemiologic aspects of open-angle glaucoma. Am J Epidemiol. 1979 Mar;109(3):250–272. doi: 10.1093/oxfordjournals.aje.a112680. [DOI] [PubMed] [Google Scholar]
  23. Linnér E. Ocular hypertension. I. The clinical course during ten years without therapy. Aqueous humour dynamics. Acta Ophthalmol (Copenh) 1976 Dec;54(6):707–720. doi: 10.1111/j.1755-3768.1976.tb01790.x. [DOI] [PubMed] [Google Scholar]
  24. Linnér E., Strömberg U. The course of untreated ocular hypertension. A tonographic study. Acta Ophthalmol (Copenh) 1964;42(4):836–848. doi: 10.1111/j.1755-3768.1964.tb01735.x. [DOI] [PubMed] [Google Scholar]
  25. Lundberg L., Wettrell K., Linnér E. Ocular hypertension. A prospective twenty-year follow-up study. Acta Ophthalmol (Copenh) 1987 Dec;65(6):705–708. doi: 10.1111/j.1755-3768.1987.tb07067.x. [DOI] [PubMed] [Google Scholar]
  26. Martin M. J., Sommer A., Gold E. B., Diamond E. L. Race and primary open-angle glaucoma. Am J Ophthalmol. 1985 Apr 15;99(4):383–387. doi: 10.1016/0002-9394(85)90001-7. [DOI] [PubMed] [Google Scholar]
  27. Nagin P., Schwartz B. Detection of increased pallor over time. Computerized image analysis in untreated ocular hypertension. Ophthalmology. 1985 Feb;92(2):252–261. doi: 10.1016/s0161-6420(85)34056-3. [DOI] [PubMed] [Google Scholar]
  28. Nagin P., Schwartz B., Nanba K. The reproducibility of computerized boundary analysis for measuring optic disc pallor in the normal optic disc. Ophthalmology. 1985 Feb;92(2):243–251. doi: 10.1016/s0161-6420(85)34057-5. [DOI] [PubMed] [Google Scholar]
  29. Norskov K. Routine tonometry in ophthalmic practice. II. Five-year follow-up. Acta Ophthalmol (Copenh) 1970;48(5):873–895. doi: 10.1111/j.1755-3768.1970.tb08208.x. [DOI] [PubMed] [Google Scholar]
  30. Odberg T., Riise D. Early diagnosis of glaucoma. II. The value of the initial examination in ocular hypertension. Acta Ophthalmol (Copenh) 1987 Feb;65(1):58–62. doi: 10.1111/j.1755-3768.1987.tb08492.x. [DOI] [PubMed] [Google Scholar]
  31. Perkins E. S., Phelps C. D. Open angle glaucoma, ocular hypertension, low-tension glaucoma, and refraction. Arch Ophthalmol. 1982 Sep;100(9):1464–1467. doi: 10.1001/archopht.1982.01030040442015. [DOI] [PubMed] [Google Scholar]
  32. Perkins E. S. The Bedford glaucoma survey. I. Long-term follow-up of borderline cases. Br J Ophthalmol. 1973 Mar;57(3):179–185. doi: 10.1136/bjo.57.3.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Podgor M. J., Leske M. C., Ederer F. Incidence estimates for lens changes, macular changes, open-angle glaucoma and diabetic retinopathy. Am J Epidemiol. 1983 Aug;118(2):206–212. doi: 10.1093/oxfordjournals.aje.a113628. [DOI] [PubMed] [Google Scholar]
  34. Podos S. M., Becker B., Morton W. R. High myopia and primary open-angle glaucoma. Am J Ophthalmol. 1966 Dec;62(6):1038–1043. [PubMed] [Google Scholar]
  35. Quigley H. A., Addicks E. M., Green W. R., Maumenee A. E. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol. 1981 Apr;99(4):635–649. doi: 10.1001/archopht.1981.03930010635009. [DOI] [PubMed] [Google Scholar]
  36. Radius R. L., Diamond G. R., Pollack I. P., Langham M. E. Timolol. A new drug for management of chronic simple glaucoma. Arch Ophthalmol. 1978 Jun;96(6):1003–1008. doi: 10.1001/archopht.1978.03910050527005. [DOI] [PubMed] [Google Scholar]
  37. Schappert-Kimmijser J. A five-year follow-up of subjects with intra-ocular pressure of 22-30 mm Hg without anomalies of optic nerve and visual field typical for glaucoma at first investigation. Ophthalmologica. 1971;162(4):289–295. doi: 10.1159/000306295. [DOI] [PubMed] [Google Scholar]
  38. Shin D. H., Kolker A. E., Kass M. A., Kaback M. B., Becker B. Long-term epinephrine therapy of ocular hypertension. Arch Ophthalmol. 1976 Dec;94(12):2059–2060. doi: 10.1001/archopht.1976.03910040719002. [DOI] [PubMed] [Google Scholar]
  39. Sørensen P. N., Nielsen N. V., Nørskov K. Ocular hypertension. A 15-year follow-up. Acta Ophthalmol (Copenh) 1978 Jun;56(3):363–372. doi: 10.1111/j.1755-3768.1978.tb05689.x. [DOI] [PubMed] [Google Scholar]
  40. Walker W. M. Ocular hypertension. Follow-up of 109 cases from 1963 to 1974. Trans Ophthalmol Soc U K. 1974 Jul;94(2):525–534. [PubMed] [Google Scholar]
  41. Wilensky J. T., Gandhi N., Pan T. Racial influences in open-angle glaucoma. Ann Ophthalmol. 1978 Oct;10(10):1398–1402. [PubMed] [Google Scholar]
  42. Wilensky J. T., Podos S. M., Becker B. Prognostic indicators in ocular hypertension. Arch Ophthalmol. 1974 Mar;91(3):200–202. doi: 10.1001/archopht.1974.03900060208010. [DOI] [PubMed] [Google Scholar]
  43. Wilson M. R., Hertzmark E., Walker A. M., Childs-Shaw K., Epstein D. L. A case-control study of risk factors in open angle glaucoma. Arch Ophthalmol. 1987 Aug;105(8):1066–1071. doi: 10.1001/archopht.1987.01060080068030. [DOI] [PubMed] [Google Scholar]
  44. Wilson R. P., Kanal N., Spaeth G. L. Timolol: its effectiveness in different types of glaucoma. Ophthalmology. 1979 Jan;86(1):43–50. doi: 10.1016/s0161-6420(79)35535-x. [DOI] [PubMed] [Google Scholar]
  45. Wilson R., Richardson T. M., Hertzmark E., Grant W. M. Race as a risk factor for progressive glaucomatous damage. Ann Ophthalmol. 1985 Oct;17(10):653–659. [PubMed] [Google Scholar]
  46. Zimmerman T. J., Kaufman H. E. Timolol. A beta-adrenergic blocking agent for the treatment of glaucoma. Arch Ophthalmol. 1977 Apr;95(4):601–604. doi: 10.1001/archopht.1977.04450040067008. [DOI] [PubMed] [Google Scholar]

Articles from Transactions of the American Ophthalmological Society are provided here courtesy of American Ophthalmological Society

RESOURCES