Primary open-angle glaucoma (POAG) is the most common form of glaucoma in North America, affecting approximately 3 million between ages 40-80 in the U.S. The main goal of glaucoma treatment is reducing internal eye pressure, or intraocular pressure (IOP). This is usually done with topical treatments that contain prostaglandin analogues (PGAs), alpha agonists, beta blockers, carbonic anhydrase inhibitors (CAIs), or parasympathomimetic agents.

PGAs—most commonly latanoprost, bimatoprost, and travoprost—are considered to be the safest and most effective. They’re also convenient, due to their once-daily application. No direct comparisons have been done between the competing leading therapies, however. 

To fill this knowledge gap, a research team from the University of Montreal conducted a network meta-analysis comparing the effectiveness of the most often used therapies, while also comparing the newly-developed PGA Vyzulta, or latanoprostene bunod (LBN), to the leading PGAs in treating open-angle glaucoma (OAG).*

What they did

A systematic literature review was conducted involving 106 randomized control trials (RCTs) gleaned from the Medline, Embase, and PubMed databases. 

The trials had to:

• Have been published between January 1, 2014, and March 19, 2020
• Result in IOP reduction after three months for at least two different treatments
• Involve a minimum of 10 participants in each arm of the trial
• Follow up with participants for at least 28 days after randomization 

The model ranked each treatment by:

• Relative effect (probability of being more effective)
• Surface under the cumulative ranking curve (SUCRA), which is a number from 0-100% (0% represents the least effective treatment while 100% represents the most effective)

The 106 studies compared 16 interventions. A total of 138 direct comparisons were performed based on 93 two-armed trials, 11 three-armed trials, and two (2) four-armed trials. 

What they found

Results of the analysis revealed that, after three months, all active drugs demonstrated an improved reduction of IOP when compared with a placebo, with LBN showing the second greatest reduction after bimatoprost 0.03%. Unoprostone showed the least reduction compared with a placebo.

In comparison with other medications, LBN performed better than:

• PGAs: Unoprostone, Latanoprost, and Tafluprost 
• Beta blockers: Apraclonidine, Betaxolol, Brimonidine, Brinzolamide, Carteolol, Dorzolamide, and Timolol  

Calculated relative effects suggested that LBN has a 51% likelihood of being one of the two best treatments and a 70% likelihood of being one of the three best treatments, but the results were not statistically significant.

SUCRA results showed the following percentages: 

• Bimatoprost 0.03% (94%)
• LBN (88%) 
• Bimatoprost 0.01% (87%)
• Tafluprost (78%)
• Travoprost (73%) 
• Levobunolol (72%) 
• Latanoprost (68%) 
• Timolol (48%) 
• Brimonidine (47%) 
• Carteolol (38%) 
• Apraclonidine (30%) 
• Dorzolamide (23%)
• Brinzolamide (22%)
• Betaxolol (22%)
• Unoprostone (11%)  
• Placebo (0%)

What it means

LBN may be a promising option for treating glaucoma patients. The findings indicated that LBN was more effective than several PGAs and most beta-blockers in lowering IOP. The study did not include visual field outcomes, which would have provided more meaningful clinical data. 

Many factors, besides medication effectiveness ratings, should be considered when choosing a glaucoma treatment, such as:

• Patient’s medical history and preference
• Risk factors 
• Likelihood of compliance

Despite the lack of significant relative effect, when compared with the most widely used PGAs, LBN was statistically: 

• More efficient than latanoprost and tafluprost
• Similar to bimatoprost 0.01%
• Slightly less efficient than bimatoprost 0.03% 

*Harasymowycz, P., Royer, C., Xianying Cui, A., Barbeau, M., et al. (2021, Feb. 24). Short-Term Efficacy of Latanoprostene Bunod for the Treatment of Open-Angle Glaucoma and Ocular Hypertension: A Systematic Literature Review and a Network Meta-Analysis. British Journal of Ophthalmology.  https://bjo.bmj.com/content/early/2021/02/04/bjophthalmol-2020-317262 

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