The emphasis of treatment for glaucoma has been the reduction of intraocular pressure (IOP) to a safer level, which, in turn, theoretically will prevent further visual loss. It has been assumed that lowering IOP by medical means has no adverse effect, which could negate the beneficial effect of IOP reduction. However, several reports have raised the possibility that some may adversely affect visual function.1,2 In several studies betaxolol and timolol were compared with respect to their effect on IOP reduction and perimetric findings.3–5 Although timolol lowered IOP more effectively, betaxolol was more effective in preserving the visual field.
These findings suggest that IOP reduction is not the only parameter that demands attention. In this study, we attempted to evaluate various topical antiglaucoma medications in a normal population in terms of their short term effect on visual function; only minimal effects on IOP reduction were expected since this study population did not have glaucoma.
Methods
Five prospective, randomised, masked studies of levobunolol, dipivefrin, apraclonidine, betaxolol, and dorzolamide, respectively, were conducted over 5 years. In each study, 20 normal volunteers had baseline testing, including measurement of visual acuity (VA), IOP, visual field (VF) with the Humphrey computerised perimeter (HCP) program 24-2, and pupil size. One eye was randomly assigned to treatment and given a test dose of either a glaucoma medication or a placebo. VF testing was repeated in 1 hour. The same eye was later given the opposite drop (the drug if a placebo was used, a placebo if the drug was used) and a third set of visual field studies was done. Paired t test and signed rank test were used in the statistical analysis.
All subjects had normal ocular examinations, with best corrected visual acuity of 20/30 or better. The mean baseline IOP was 13.3 mm Hg right eye and 13.5 mm Hg left eye (range 10–18 mm Hg). When levobunolol was administered, there was a mean deviation of −2.9 dB compared with −1.9 dB for the placebo (p<0.05) (Table 1). There were no significant differences in terms of other global values (short term fluctuation, pattern standard deviation, and corrected pattern standard deviation), visual acuity, and pupil size.
Table 1.
Effects of topical glaucoma medications on automated perimetry
| MD (dB) | C/W placebo | |
| Dipivefrin | −0.86 | −1.05 |
| Apraclonidine | −0.36 | −0.44 |
| Levobunolol | −2.90 | −1.90* |
| Betaxolol | −1.23 | −0.79 |
| Dorzolamide | +0.16 | +0.12 |
* p<0.05.
Thus, in a normal population, a single dose of several topical glaucoma medications had little or no effect on perimetry. The possible mild suppression of retinal sensitivity with levobunolol is of unknown clinical significance.
Comment
Flammer and Drance tested several drugs topically, all of which reduced retinal sensitivity on threshold perimetry in contrast with oral acetazolamide, which improved perimetry results in 75 patients with elevated IOP or in the very early stages of chronic open angle glaucoma.6 Paterson found that acute IOP reduction increased retinal sensitivity.7 Martin-Boglind and coworkers showed that the influence of topical glaucoma medications (epinephrine, timolol, betaxolol, pilocarpine) on the high pass resolution threshold was negligible in normal subjects.8 Edgar and coworkers found no significant change with dipivefrin in normal subjects.9 In our studies, only levobunolol caused a mild generalised decrease in visual function compared to controls on visual field testing of normal subjects. Short term fluctuation was not altered and there was no relative focal defect when levobunolol was compared with placebo. Since these were controlled trials, the placebo effect was not a factor. Vasoactivity, direct effect on neuronal elements, corneal epithelial alteration, and refractive change of current glaucoma drugs should be also considered. The mechanism by which various topical glaucoma medications affect retinal sensitivity remains unclear. The effect may be due to changes in blood flow to the posterior segment of eye. Further study is needed.
References
- 1.Holmin C, Thorburn W, Krakau CET. Treatment versus no treatment in chronic open angle glaucoma. Acta Ophthalmol 1988;66:170–3. [DOI] [PubMed] [Google Scholar]
- 2.Chauhan BC, Drance SM, Douglas GR. The effect of long-term intraocular pressure reduction on the differential light sensitivity in glaucoma suspects. Invest Ophthalmol Vis Sci 1988;29:1478–85. [PubMed] [Google Scholar]
- 3.Messmer C, Flammer J, Stumpfig D. Influence of betaxolol and timolol on the visual fields of patients with glaucoma. Am J Ophthalmol 1991;112:678–81. [DOI] [PubMed] [Google Scholar]
- 4.Collignon-Brach J. Longterm effect of topical beta-blockers on intraocular pressure and visual field sensitivity in ocular hypertension and chronic open-angle glaucoma. Surv Ophthalmol 1994;38(Suppl):S149–55. [DOI] [PubMed] [Google Scholar]
- 5.Vainio-Jylha E, Vuori ML. The favorable effect of topical betaxolol and timolol on glaucomatous visual fields: a 2-year follow-up study. Graefes Arch Clin Exp Ophthalmol 1999;237:100–4. [DOI] [PubMed] [Google Scholar]
- 6.Flammer J, Drance SM. The effect of a number of glaucoma medications on the differential light threhold. In: Greve EL, Heijl A, ed. Fifth international visual field symposium, Sacramento 1982. The Hague: Dr W Junk, 1983:153–6.
- 7.Paterson G. Effect of intravenous acetazolamide on relative arcuate scotomas and visual field in glaucoma simplex. Proc Roy Soc Med 1970;63:865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Martin-Boglind LM, Graves A, Wanger P. The effect of topical antiglaucoma drugs on the results of high-pass resolution perimetry. Am J Ophthalmol 1991;111:711–14. [DOI] [PubMed] [Google Scholar]
- 9.Edgar DF, Crabb DP, Rudnicka AR, et al. Effects of dipivefrin and pilocarpine on pupil diameter, automated perimetry and log MAR acuity. Graefes Arch Clin Exp Ophthalmol 1999;237:117–24. [DOI] [PubMed] [Google Scholar]