Beta-blockers for Glaucoma

The Beta-blocker class of medications has been used for over half a century. Indeed, all the way up through the turn of the millenium this class was the most commonly prescribed glaucoma medication. Timolol was the first beta-blocker to be successfully developed as an eye drop for the treatment of glaucoma (earlier versions of beta-blocker eye drops were toxic to the cornea). Within this class the most commonly prescribed beta-blocker is still timolol, which is almost always dispensed by the pharmacy as a generic medication.

Bottle cap color

Yellow (0.5%) or light blue (0.25%) 

How it works:

Works on the ciliary body to reduce production of aqueous fluid. 

How it is taken:

Traditionally the beta-blockers have been prescribed twice daily, once in the morning and once again at night. However, studies have demonstrated that once daily dosing can be just as effective as twice daily dosing^[1]. Additionally, there is mounting evidence that not only does the evening dose have little or no IOP-lowering effect, but it may also be detrimental to optic nerve perfusion^[2]. As such, I generally prescribe timolol to be used only in the morning. If timolol has to be used twice daily (as is the case with fixed-combination agents) then I recommend that the second dose be taken prior to 4pm in order to limit the potential systemic downside of a PM-dosed beta-blocker. 

How well does it work:

Quite well. Timolol is one of the most effective IOP lowering eye drops available. During the day it lowers the IOP more than any other class of medication with the exception of the prostaglandin analog class. However, is has very little effect on IOP during sleep^[3]. 

Side effects^[4]:

Local:

• Irritation/dryness of the eye
• Blurred vision (usually temporary)

Systemic:

• Systemic hypotension (low blood pressure)
• Bradycardia (low heart rate)
• Bronchospasm (worsening of asthma)
• Fatigue
• Mood change or worsening of depression
• Impotence
• Masking of symptoms of hypoglycemia (low blood sugar)^[5]
• Worsening of symptoms of myasthenia gravis^[6]

Interactions with other medications:

• In those already taking oral beta blockers adding timolol may provide a modest additional IOP lowering benefit without notably increasing systemic beta-blocker related side effects^[7]. 

How to minimize side effects:

• Should not be prescribed (or if so, with great caution) in those with:
  • Low heart rate or heart block
  • Asthma
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Congestive Heart Failure (CHF)
  • Diabetes prone to episodes of hypoglycemia (low blood sugar)
  • Myasthenia gravis
• Digital punctal occlusion^[8]
• Balled up tissue
• Eye drop applicator such as the Simply Touch (available on Amazon.com)

Fixed Combinations:

• Cosopt^® (dorzolamide + timolol)
• Combigan^® (brimonidine + timolol)

When might beta-blockers be prescribed?

Beta-blockers are what is called “first line therapy”. However, due to the systemic side effects of low blood pressure and heart rate, the prostaglandin analog class is now often the first to be prescribed to patients newly diagnosed with glaucoma.  

Cost?

Generic timolol is one of the medications available at Walmart and Target for under $10. Indeed, I’ve never seen lower pricing on timolol elsewhere. Even at more expensive pharmacies the generic version of timolol should be less than $25. If you are getting charged more than that for a 30 day supply then either your pharmacy or insurance company is ripping you off.

Branded versions can be far more expensive and (with the exception of the preservative-free timolol called Ocudose^®) are probably not worth the extra expense.

If you are prescribed a branded version of timolol (such as Ocudose^® or Betimol^®) that is not covered by your insurance, or even with insurance coverage it’s quite expensive, then I recommend you search out a good cash price through the website “GoodRx”. I frequently recommend this site to my patients and have been surprised at how much they can often save on certain classes of medications despite not using their insurance.

A note about Preservative-Free options:

Most prescription eye drops have a preservative which keeps bacteria from growing in the bottle. However, the most commonly used preservative, Benzalkonium chloride (BAK), can worsen dry eye and may even be toxic to the trabecular meshwork over time. Given that the trabecular meshwork is already not functioning well in most forms of glaucoma, I generally prefer to prescribe preservative-free versions of glaucoma eye drops when available and affordable.

Summary:

As with most available glaucoma medications, this class works by reducing the production of fluid in the eye. It does not directly affect the problem area of glaucoma which is the reduced flow through the trabecular meshwork.

That being said, timolol has a very long history of use in the treatment of glaucoma. It’s substantial lowering of IOP combined with its low cost make it a reasonable first choice of glaucoma treatment for those without significant cardiovascular or other systemic disease. As with all medications, treatment should be customized to the individual.

References:

[1] Soll DB. Evaluation of timolol in chronic open-angle glaucoma. Once a day vs twice a day. Arch Ophthalmol. 1980;98(12):2178–2181.115.

Yalon M, Urinowsky E, Rothkoff L, et al. Frequency of timolol administration. Am J Ophthalmol. 1981;92(4):526–529.116.

Letchinger SL, Frohlichstein D, Glieser DK, et al. Can the concentration of timolol or the frequency of its administration be reduced? Ophthalmology. 1993;100(8):1259–1262.

[2]  Harris A, Jonescu-Cuypers CP. The impact of glaucoma medication on parameters of ocular perfusion.
Curr Opin Ophthalmol. 2001;12(2):131–137

[3] Topper JE, Brubaker RF. Effects of timolol, epinephrine, and acetazolamide on aqueous flow during sleep. Invest Ophthalmol Vis Sci.1985;26(10):1315–1319. 

[4] McMahon CD, Shaffer RN, Hoskins HD Jr, et al. Adverse effects experienced by patients taking timolol. Am J Ophthalmol. 1979;88(4):736–738

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

[6]  Shaivitz SA. Timolol and myasthenia gravis. JAMA. 1979;242(15):1611–161

[7] Gross F, Schuman JS. Reduced ocular hypotensive effect of topical beta-blockers in glaucoma patients receiving oral beta-blockers. J Glaucoma.1992;1:174.

[8] Passo MS, Palmer EA, Van Buskirk EM. Plasma timolol in glaucoma patients. Ophthalmology. 1984;91(11):1361–1363

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