Key messages

• Although the use of cannabinoids for glaucoma could decrease intraocular pressure, it would be transient and associated with frequent adverse effects.
• The benefit/risk balance is probably not favorable.

What is the evidence.
See evidence matrix  in Epistemonikos later

We found five systematic reviews [1],[2],[3],[4],[5] including three primary studies overall [6],[7],[8], all of which correspond to randomized controlled trials.

What types of patients were included*

All trials included adult patients with glaucoma [6],[7],[8], with average age over 50 years. Only one trial specified the type of glaucoma (primary open-angle glaucoma) [8]. Two trials [7],[8], included patients with intraocular hypertension.

What types of interventions were included*

One trial [8] used sublingual cannabinoid spray (Sativex®) at doses of 5, 20 and 40 mg. Another trial [6] used smoked marijuana with 2% tetrahydrocannabinol (THC), while the last trial [7] used marijuana in 0.01%, 0.05%, and 0.1% eye drops.All trials compared against placebo or standard treatment.

What types of outcomes
were measured

The different systematic reviews identified [1],[2],[3],[4],[5] grouped the outcomes as follows:

• Decrease in intraocular pressure, measured immediately after cannabinoid administration.
• Adverse effects.

Two trials [7],[8] analyzed the duration of the intraocular pressure decrease, while in the other trial this variable was not reported [6].

To whom this evidence does and does not apply

• The evidence presented in this summary comes from patients with primary open-angle glaucoma and patients with intraocular hypertension. However, in the absence of direct evidence it is reasonable to extrapolate to other forms of glaucoma with elevated intraocular pressure.
• It is not applicable to patients with normal tension glaucoma. On the other hand, it is questionable to apply it to patients with congenital glaucoma, since although the majority of patients present elevated intraocular pressure, the pathophysiology of the increase is different.

• The outcomes selected for the summary of findings table are those considered critical for decision-making in this clinical situation, according to the opinion of the authors of this article. In general, they coincide with those presented in the systematic reviews identified.
• It is important to emphasize that patient's preferences are more concerned about the visual implications of the disease and the prevention of blindness. However, there is evidence that the decrease in intraocular pressure maintained over time delays the progression of this disease, including the deterioration of the visual field [9].
• On the other hand, the decrease in intraocular pressure is a relevant element in clinical practice for follow-up and thus determine the success of the treatment or the need of new interventions.
• Although information on adverse effects is scarce in the evaluated trials, these are frequent in other conditions [4], so something similar should be expected in glaucoma.

• It is not possible to make an adequate balance between benefits and risks due to the existing uncertainty about the benefits. However, it is unlikely that the observed effect, being transient, will translate into a clinically relevant benefit. On the other hand, the intervention has frequent adverse effects, so the benefit/risk balance is probably not favorable.

• Commercial formulations of cannabinoids generally have a high cost. Since there is no certainty about a possible benefit, it is not possible to make an adequate cost/benefit balance.

• Most patients and doctors should lean against the use of this intervention based on the evidence presented in this summary.
• In addition, nowadays there are proven therapies for the control of glaucoma, with good results both in the short and long term.
• Some patients who place a greater value on an uncertain benefit may decide to use it, especially considering the preconceived ideas they may have about it.

Differences between this summary and other sources

• The key messages of this summary are concordant with the conclusions of the systematic reviews identified.
• This summary also coincides with the statement of the Canadian Ophthalmological Society [10] and the American Ophthalmological Society [11], who do not recommend the use of cannabinoids for the treatment of glaucoma, since although it produces a decrease in intraocular pressure, it is transient and is associated with frequent adverse effects.

• The likelihood that future evidence changes the conclusions of this summary with respect to the benefits of cannabinoids in glaucoma is high due to the existing uncertainty. It is unlikely that the conclusions about adverse effects change.
• We did not identify any ongoing trial evaluating this question in the International Clinical Trials Registry Platform of the World Health Organization.