A randomised controlled trial in genetically at-risk individuals to determine the efficacy of early laser treatment in preventing glaucomatous vision loss

Primary open angle glaucoma (POAG) is the commonest cause of irreversible vision loss. In the early stages of POAG before visual field loss has occurred, definitive diagnosis can be difficult. This has led to a large number of referrals (glaucoma suspects) requiring regular monitoring. There is a major gap in knowledge relating to how to identify individuals destined to become blind from glaucoma, and how they may be safely treated earlier in the course of disease. Once vision loss has been observed, selective laser trabeculoplasty (SLT) has been shown to be a safe and effective primary intervention for POAG.

We recently developed a glaucoma polygenic risk score (PRS), which effectively stratifies risk in glaucoma suspects and patients with early disease for development and progression of disease respectively, as well as treatment intensity. Prospective evaluation of Australian glaucoma suspects by our group over the past 8 years has determined that our glaucoma PRS, combined with clinical risk factors, is highly predictive of future vision loss. In addition, the burden of glaucoma suspects requiring regular monitoring according to current guidelines is unsustainable, so new monitoring and treatment strategies are required.
In this trial, 500 high-risk glaucoma suspects will be enrolled after completing comprehensive risk stratification, with at least 400 randomised to receive either SLT or sham SLT. All participants will be followed 6 months for two years, with a primary endpoint of conversion to glaucomatous visual field loss or unacceptably elevated intraocular pressure, either of which would necessitate intervention as part of standard clinical care.

The insights gained from this trial will have immediate translational implications for policy development and the rational deployment of an evidence-based glaucoma suspect monitoring and treatment program both in Australia and Internationally. Healthcare savings will accrue by prevention of glaucoma related morbidity.