Kia ora e hoa ma,

Can cannabis be used as a legitimate treatment for glaucoma?

Before we answer this question so far, we are covering the basics:

• how the eye works, and

• how glaucoma causes vision loss.

In this newsletter, we will learn about common glaucoma treatments.

First, we must determine if there is risk of losing sight from glaucoma. If that's the cases, we commence treatment. Glaucoma treatment is split into three broad categories:

• medical or drug,

• laser treatment, and

• surgical.

Before we dive into each treatment category, we need to understand the aim of treatment.

Aim of Treatment

The goal is to reduce eye pressure. This is done by either reducing production or increasing drainage of aqueous humour (AH) using drugs, laser, and/or surgery.

Despite eye pressure not being a definitive sign of glaucoma, decreasing eye pressure reduces further glaucomatous visual field loss (Heijl, 2002). This is true even when the eye pressure is normal (e.g. in normal-tension glaucoma or NTG) (CNTGSG, 1998).

The aim is for a 30% reduction in eye pressure (CNTGSG, 1998), but this will depend on age, stage of disease, and glaucoma type. Maintaining reduced pressure will be required for the lifetime of the patient.

In most cases, the first-line treatment for glaucoma is medical or drugs. If reduced eye pressure is not met to an acceptable standard, other treatment options are explored either exclusively or concurrently (Conlon et al., 2017).

Medical/Drugs

Most medical drugs to treat glaucoma come in the form of eye drops (come exceptions include DIAMOX, which is an oral tablet). In New Zealand, optometrists who are Board approved can prescribe glaucoma medication (Optometrists and Dispensing Optician Board, n.d.).

There are five main classes of drugs used to treat glaucoma. They include (in parenthesis is an example of a brand name, followed by the name of the drug):

• Prostaglandin analogues (e.g. XALATAN®, latanoprost),

• Beta-blockers (e.g. Arrow-Timolol, timolol),

• Alpha-agonists (e.g. IOPIDINE®, apraclonidine),

• Carbonic anhydrase inhibitors (e.g. DIAMOX, acetazolamide)

• Muscarinic agnoists (e.g. ISOPTO® CARPINE, pilocarpine)

Prostaglandin analogues act on increasing outflow of AH through the non-conventional pathway (uveoscleral pathway). A few mechanisms exist. One involves activation of matrix metalloproteinases, special enzymes that clear the space between cells allowing for more drainage — like clearing the leaves from a drain (Toris et al., 2008). Increased outflow leads to reduced eye pressure. Interesting prostaglandins' side effects include increased lash length growth and change in iris colour (Holló, 2006).

Beta-blockers, as the name suggests, block beta-adrenergic receptors. These receptors exist at the ciliary processes, where AH is produced. Blocking these receptors using drugs reduces AH production, reducing eye pressure (Trope & Clark, 1982). Side effects of beta-blockers can conflict with heart medication and aggravate underlying asthma symptoms. A careful history of the patient's underlying health conditions is paramount (Hoscheit, 2003).

Alpha-agonists activate alpha-adrenergic receptors (more specifically alpha-2). Like beta-adrenergic receptors, they also exist in the ciliary processes. Alpha-agonists, when activated, reduce AH production. Additionally, they are also able to increase outflow. Both reduce eye pressure in a two-pronged approach. Some alpha-agonists can also prevent self-programmed death of retinal ganglion cells — the messengers between the eyes and the brain. This is another way to treat glaucoma that doesn't only involve lowering eye pressure. Alpha agonists are notorious for causing eye irritation through allergy (Arthur & Cantor, 2011).

Carbonic anhydrase inhibitors (CAIs) act on carbonic anhydrase. Recall how carbonic anhydrase is responsible for the active transport of bicarbonate (HCO⁻), which results in water entering the eye and production of AH. CAIs halt this transport of bicarbonate, reducing the production of AH and reducing eye pressure. CAIs come in both eye drop formulation (dorzolamide) and oral tablet (acetazolamide), the latter being more effective but also with more side effects (Portellos et al., 1998). Side effects can range from fatigue, weight loss, loss of libido, and even kidney stones. Generally, CAIs are not used as a first-line drug (Epstein & Grant, 1977).

Muscarinic antagonists (MAs) activate the ciliary muscle of the eye. This causes the drainage mechanism, trabecular meshwork (TM), to open more. When the TM opens, this resulting in increased AH outflow and reducing eye pressure. MAs' side effects include blurred vision and reduced night vision thanks to pupil constriction (Gil et al., 2001).

Common to many is the great fear of losing sight (De Leo et al., 1999). So why do patients not take their drops? (Park et al., 2012) The side effects of these drugs are understandably undesirable. The main challenge is getting patients to understand that these drops won't make anything better; it stops vision from getting worse! Constant review and patient education are important.

Laser

Laser treatment is considered in addition to or when medication does not acceptedly reduce eye pressure. Often, laser treatment is performed by an opthalmologist who specialises in glaucoma.

There are many different laser treatments. This is different from the well-known 'LASIK', which is used to correct eye focus. A collection of laser treatments concerning glaucoma include:

• Selective laser trabeculoplasty

• Peripheral iridotomy

• Endoscopic cyclophotocoagulation

Selective laser trabeculoplasty (SLT) is commonly used to treat open-angle type glaucoma like primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEX). This involves using a special laser called a Nd:YAG laser. This is aimed at one of the eye's drainage mechanisms — the trabecular meshwork (TM). Termed selective, this form of treatment does not cause collateral damage to the surrounding tissue like its predecessor, argon laser trabeculoplasty. SLT stimulates migration of the body's immune cells, macrophages and monocytes to the TM. These cells clear and promote healthy growth of the TM, resulting in improved drainage and reduced eye pressure (Latina & Tumbocon, 2012).

Peripheral iridotomy (PI) is used to reduce the chance of developing acute angle-closure type glaucoma. This involves the same laser as in SLT, instead aimed at the edge of the iris furthest from the pupil (or peripheral iris). PI is used prophylactically (this means a prevention method even when there is no disease) to prevent pupil block (Nolan et al., 2000). To understand how this works, we need to understand what is pupil block. This is where the edge of the pupil adheres to the lens (posterior synechiae). Trapped AH increases pressure behind the iris, causing it to bow forward. This closes the drainage angle, leading to increased eye pressure (Mapstone, 1968). PI provides an alternative route for AH to travel from the posterior chamber to the anterior chamber and out through the TM, preventing the iris from bowing forward and closing the angle. However, cataract surgery (which involves exchanging the eye's natural lens) appears to be a more superior option to PI in treating angle-closure (Radhakrishnan et al., 2018).

Endoscopic Cyclophotocoagulation (ECP) is more invasive compared to the previously mentioned laser treatments. A small cut is made at the cornea's edge, and the diode laser and other components (e.g. camera) is inserted through this cut into the eye. The laser is directed at the cells that produce AH, essentially stopping their function. This results in reduced production of AH, reducing eye pressure. ECP is used when most treatment options have been exhausted (Pastor et al., 2001).

Surgical

Surgical methods are performed if medication or laser do not reach desired outcomes (Conlon et al., 2017). These types of surgeries include:

• Trebeculectomy

• Microinvasive glaucoma surgery

Trabeculectomy involves the surgeon creating an alternative pathway for AH to travel. Though this is considered the gold standard of treatment, there is a considerable infection risk — the pressure of drops too low causing the eyeball to collapse, and cataract (clouding of the eye's lens) (Moster, 2013; DeBry, 2002).

Microinvasive glaucoma surgery (MIGS) — also termed minimally invasive glaucoma surgeries, the authors of Conlon et al., 2016 felt micro was more appropriate — involves tiny tubular devices (e.g. iStent, Hydrus) to increase the outflow of AH. MIGS aims to provide an adequate drop in eye pressure with minimal surgical trauma, safety and allowing for good patient recovery. MIGS is performed a bit earlier in the treatment journey, after medication and before highly invasive surgery. Often this procedure coupled together with cataract surgery (Conlon et al. 2016).

Conclusion

Before understanding if cannabis can be used as a legitimate form of glaucoma treatment, we need first to understand how the eye works, what glaucoma is, and how it is treated.

Treatment aims to reduce eye pressure. This can be done by either reducing the production or increasing the drainage of AH.

In this edition, we have learnt the glaucoma treatments. They are in three categories: medical, laser and surgical.

Normally, medical treatment is the first line of action, followed by laser and surgery. The former has fewer complications compared to the latter, which involves more ongoing care.

Next, we will explore what we have all been waiting for: to see if cannabis is an effective form of glaucoma treatment.

Did you find this useful? If you did, please forward this on to family and friends so they can find it useful too.

Thanks for reading, and all the best for the week ahead.

Ngā mihi nui,

Shivan :)

References

(Provided in a blog post later on)

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