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Selecting the right topical glaucoma therapy is important

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Ophthalmology Times Europe, Ophthalmology Times Europe November 2022, Volume 18, Issue 09

Studies reveal the advantages of numerous new glaucoma treatments that offer a wider range of options for individual patients.

Reviewed by Dr Janet B. Serle.

Physicians who treat glaucoma have several classes of effective topical treatments from which to choose, including branded drugs, generic drugs and compounded medications, and the optimal choice for an individual patient may not always be obvious. Dr Janet B. Serle, professor emeritus of ophthalmology at the Icahn School of Medicine at Mount Sinai, New York, New York, United States, walked physicians through advantages and disadvantages of the various treatments.

New medications to enhance aqueous outflow

Glaucoma causes changes in the ocular anterior segment that affect the trabecular outflow pathway. Physicians have access to new medications with mechanisms of action that directly affect the trabecular cells and outflow tissues to improve aqueous outflow.

The newest additions to the ocular hypotensive armamentarium are netarsudil (Rhopressa, Aerie Pharmaceuticals), latanoprostene bunod (Vyzulta, Bausch + Lomb), and a fixed-dose combination of netarsudil and latanoprost (Rocklatan, Aerie Pharmaceuticals), all of which enhance the ability of the trabecular meshwork to function properly.

Dr Serle described a recent clinical trial that demonstrated that netarsudil enhances outflow facility and decreases episcleral venous pressure in patients with glaucoma, improving outflow through both the proximal and distal portions of the outflow pathway.1 Phase 3 clinical trials have clearly demonstrated the efficacy of netarsudil and the fixed-dose combination as single therapies.2,3 Real-world studies provide information in a broader patient population, and in patients taking other medications to treat glaucoma.

Dr Serle reported on two real-world studies conducted with netarsudil. The first, of 340 eyes of 233 patients, demonstrated additional intraocular pressure (IOP) reductions of 15% following addition of netarsudil. The IOP reductions were similar in eyes treated with more-than- and fewer-than-three medications.4

The second—a multicentre, open-label, Phase 4 study5—included 242 of 261 patients enrolled. When netarsudil was added to a multi-drug regimen, substantially more patients achieved lower target IOPs than before netarsudil was added. Additional IOP reductions of 4.3–4.5 mm Hg occurred when netarsudil was added to regimens of patients taking one or more topical medications, Dr Serle reported.

Latanoprostene bunod has been shown to enhance the outflow through the trabecular meshwork in ex vivo studies. In a retrospective real-world study, latanoprostene bunod achieved additional decreases in IOP of 2.0–2.5 mm Hg when the drug replaced a prostaglandin analogue.6 Additional IOP reductions of over 3 mm Hg were observed in more than 50% of patients followed for almost 6 months.

Compounded medications

Compounded medications are not approved by the US Food and Drug Administration but are compounded at facilities regulated by the agency. The concerns about these medications include their safety and sterility, whether they have similar efficacy to branded and generic medications, the out-of-pocket cost and the different dosing regimens of drugs that are compounded together.

Dr Serle identified two studies of compounded products in the literature.One study7 compared a dual fixed-dose combination drug with a triple fixed-dose combination (i.e., brimonidine 0.2%/timolol 0.5% versus bimatoprost 0.01%/brimonidine 0.25%/timolol 0.5%). Both drugs were dosed twice daily.

The patients who received the triple combination had greater IOP reductions at 12 weeks. However, Dr Serle believes that this did not confirm the benefits of the triple combination product because the comparison may have been unequal; the triple combination contained a prostaglandin.

A second study compared a fixed-dose combination of two drugs compared with a fixed-dose combination of three drugs:8 respectively, bimatoprost 0.01%/timolol 0.5% dosed once daily and dorzolamide/brimonidine 0.15%/timolol 0.5% dosed twice daily. Both combinations were effective, with slightly greater reductions in IOP in the combination containing bimatoprost. Dr Serle considered that the message from this study is that for a patient who is intolerant of a prostaglandin analogue, a triple combination may have sufficient efficacy in some patients compared with a dual combination.

Generic and brand medications

Physicians probably prescribe more generics than branded medications due to the lower cost and greater availability of the former. The disadvantages of the generics are that the bottle designs and dropper sizes can differ, based upon the generic manufacturer, making patient adjustment difficult; in addition, bioequivalence and not therapeutic equivalence is required for generic drug approval.

Dr Serle concluded that many excellent ocular hypotensive therapies are available. She advised ophthalmologists to continue to use those that have proven to be efficacious over the years and to incorporate newer options into treatment plans, because certain patients may benefit from the newer agents.

Janet B. Serle, MD
P: (001) 516-731-4800
This article is adapted from Dr Serle’s presentation at the American Society of Cataract and Refractive Surgery’s 2022 annual meeting in Washington, DC, United States. She has no financial interest in this subject matter.
References
1. Sit AJ, Gupta D, Kazemi A, et al. Netarsudil improves trabecular outflow facility in patients with primary open angle glaucoma or ocular hypertension: a phase 2 study. Am J Ophthalmol. 2021;226:262-269.
2. Serle JB, Katz LJ, McLaurin E, et al; ROCKET-1 and ROCKET-2 Study Groups. Two phase 3 clinical trials comparing the safety and efficacy of netarsudil to timolol in patients with elevated intraocular pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). Am J Ophthalmol. 2018;186:116-127.
3. Asrani S, Robin AL, Serle JB, et al; MERCURY-1 Study Group. Netarsudil/latanoprost fixed-dose combination for elevated intraocular pressure: three-month data from a randomized phase 3 trial. Am J Ophthalmol. 2019;207:248-257.
4. Shiuey EJ, Mehran NA, Ustaoglu M, et al. The effectiveness and safety profile of netarsudil 0.02% in glaucoma treatment: real-world 6-month outcomes. Graefes Arch Clin Exp Ophthalmol. 2022;260:967-974.
5. Zaman F, Gieser SC, Schwartz GF, et al. A multicenter, open-label study of netarsudil for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension in a real-world setting. Curr Med Res Opin. 2021;37:1011-1020.
6. Radell JE, Sharma HK, Auyeung KL, et al. Two-year experience with latanoprostene bunod in clinical practice. J Glaucoma. 2021;30:776-780.
7. Belfort R Jr, Paula JS, Lopes Silva MJ, et al. Fixed-combination bimatoprost/brimonidine/timolol in glaucoma: a randomized, masked, controlled, phase III study conducted in Brazil. Clin Ther. 2020;42:263-275.
8. Garcia-Lopez A, Paczka JA, Jimenez-Roman J, et al. Efficacy and tolerability of fixed-combination bimatoprost/timolol versus fixed-combination dorzolamide/brimonidine/timolol in patients with primary open-angle glaucoma or ocular hypertension: a multicenter, prospective, crossover study. BMC Ophthalmol. 2014;14:161.

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