Systemic Reviews of Glaucoma Interventions Have Poor Reliability

Self-instillation of eye drops in patients with glaucoma eyes. An elderly man with glaucoma.
Investigators say much of what is published should not be used to develop or alter clinical practice guidelines for patients with glaucoma.

Most systemic reviews of glaucoma interventions present unreliable data that should not be used to develop or alter clinical practice guidelines, according to a publication in Ophthalmology Glaucoma. The research was overseen by a global team of 16 researchers who evaluated more than 5 years’ worth of systematic reviews of glaucoma interventions. 

Clinical practice guidelines are designed to support decision-making, improve outcomes, optimize resource utilization, and reduce clinical practice variation. To develop guidelines, researchers identify the relevant questions on the topic, synthesize the best evidence in systematic reviews (ideally from high-quality randomized controlled trials), and provide clinically relevant recommendations.

Using a database maintained by the Cochrane Eyes and Vision United States Satellite, the team assessed the body of evidence on recommended clinical interventions to treat glaucoma and then created a list of potentially reliable reviews that can be used to update glaucoma practice guidelines. They examined all glaucoma-related Cochrane systematic reviews published before August 7, 2019, and all non-Cochrane systematic reviews published between January 1, 2014, and August 7, 2019.

They identified 129 systematic reviews that met the criteria for evaluation. Of these, only 49 (38%) were deemed reliable. In its review, the team found that open-angle glaucoma was the subject of the most reviews, with medical management (17/49) and intraocular pressure (IOP; 43/49) being the most common interventions and outcomes studied. Most reviews found a high degree of uncertainty in the evidence, which makes recommending an intervention difficult, according to researchers.

The researchers did identify reviews with high-certainty evidence about several topics, including:

  • Reducing IOP helps prevent glaucoma and its progression.
  • Prostaglandin analogs are the most effective medical treatment for lowering IOP.
  • Laser trabeculoplasty is as effective as medical treatment as a first-line therapy for controlling IOP.
  • The use of IOP-lowering medications peri- or postoperatively with laser treatment reduces the risk for postoperative IOP spikes.
  • Conventional surgery (ie, trabeculectomy) is more efficacious than medications in reducing IOP.
  • Antimetabolites and beta-radiation improve IOP control after trabeculectomy.

Conversely, the team found weak evidence regarding the effectiveness of minimally invasive glaucoma surgeries. They also report no evidence from systematic reviews to support neuroprotection, nutritional supplementation, or alternative therapies for managing glaucoma. Additionally, behavioral and educational interventions to improve adherence to glaucoma medication did not prove effective, according to the report.

“Our findings demonstrate the need for improved quality and cohesion in future research, both primary and secondary, on interventions for glaucoma conditions,” according to the study’s researchers. 

Researchers noted some limitations of their study, including the characteristics of the reviews that were included. Classification of reliability focused solely on five criteria applied to the systematic review report. They didn’t assess the strength of the evidence any further than it was assessed in each review. Interpreting and drawing conclusions from uncertain evidence is complex and subjective. As such, the investigators recommend extreme caution when interpreting the quoted “conclusions” of the included reviews. Lastly, even with the team’s decision to include only reviews published within the last 5 years, it is possible that a reliable systematic review may not be updated.


Qureshi R, Azuara-Blanco A, Michelessi M, et al. What do we really know about the effectiveness of glaucoma interventions?: an overview of systematic reviews. Ophthalmol Glaucoma. Published online February 9, 2021. doi:10.1016/j.ogla.2021.01.007