Medical therapy

BLOG: Adjunctive Medical Therapy for Glaucoma: The Case Against Timolol

August 30, 2021

1 minute read


Disclosures: Aref reports having been a speaker for Aerie and receiving research support from Allergan.

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We are extremely fortunate to be able to choose from a number of effective and relatively safe medical therapies when treating our patients with ocular hypertension and glaucoma.

In most cases, our initial reference agent will be one of the prostaglandin analogues (latanoprost, bimatoprost, travoprost or tafluprost). These agents are very effective, are administered once daily and have a good safety profile. But glaucoma care is usually not that easy. The majority of people treated require more than one agent for IOP control. What next?

Ahmad Aref

My next of choice, or complementary, medical treatments are usually either a topical carbonic anhydrase inhibitor (dorzolamide or brinzolamide) or a Rho kinase inhibitor (netarsudil). These agents are generally well tolerated, with virtually no risk of systemic adverse effects. Netarsudil has the advantages of once-daily administration and a mechanism of action consistent with the pathophysiology of glaucoma. From an efficacy perspective, both classes have been shown to provide IOP reduction over 24 hours.

What about timolol? Of course, the introduction of timolol in the late 1970s allowed ophthalmologists to medically control many glaucoma cases. At the time, many of these patients would otherwise have undergone trabeculectomy surgery. Since the introduction of timolol, we know more about the disadvantages of the agent in terms of efficacy and safety. Several studies have shown that the effectiveness of timolol is limited during the nocturnal period. These results may explain why patients whose daytime IOPs appear to be well controlled still experience glaucomatous progression – due to nighttime IOP spikes that are higher due to the decreasing effectiveness of their beta-blockers. Additionally, the daytime incremental efficacy of timolol is attenuated in patients on oral beta-blocker therapy for systemic conditions. A host of potential systemic adverse effects – from breathing disorders to erectile dysfunction – also limit the long-term use of these agents. Finally, timolol may have negative effects on ocular perfusion pressure. These effects may have particularly serious consequences for patients with low-tension glaucoma, who are believed to have a greater vascular component to their disease process.

The above reasons make timolol a third or fourth line agent for patients in my practice. I am sure that with new technologies such as contact lens sensors, we will learn more about the importance of 24-hour IOP control and the limitations of some of our topical medical agents in this regard.