Glaucoma: how it causes blindness and how it is treated

Glaucoma (Papahewa) ranks as the second most cause of blindness in Kiwis over the age of 65 (Blind Low Vision New Zealand, n.d.). For any individual, blindness is debilitating (Vuletić et al., 2016). There is a significant loss of independence, where you lose the ability to drive, enjoy television and even navigate around your own household.

This post acts as background information needed for an original article I wrote, asking a bigger question: can Cannabis be used to treat glaucoma?

We will cover:

• how we see and the basics functions of the eye in relation to glaucoma,
• what glaucoma is and how it causes blindness, and
• current glaucoma treatments.

Disclaimer — this is for educational purposes only. If you have any eye issues please consult your local eye care professional.

As a note, I’ve written this for the public as well as eye care professionals. So there will be over-laboured points and potentially confusing ideas. Please feel free to skip around. I wrote this with everyone in mind. You might have noticed already, but in parenthesis, I’ve included some sources. In advance, I’d like to thank you for having to deal with this, and I hope you enjoy and become more educated/refreshed (please share this with friend and family if you did). Comment below if you have anything to add.

This is orginally posted, here.

How do our eyes work?

Pathology is disease. Disease is where we lose normal function. Before we understand the pathology of glaucoma, we need to understand how the eye functions normally.

The human eye acts as a simple camera. Light from the outside world enters the eye first through the cornea, going through many structures like the lens, until it reaches the back of the eye, or retina.

The retina contains light-detecting cells called photoreceptors. Photoreceptors transform light into electrical signals for the brain to interpret. These electrical signals travel along nerve cells called retinal ganglion cells (RGCs).

RGCs contain a very long cable-like structure called axons. Axons from all the RGCs converge at the optic nerve. The optic nerve acts as a cable connecting the eye to the brain (Zhu et al., 2012).

Simply put, glaucoma is where this cable — the optic nerve — becomes damaged. A damaged cable can no longer transfer information from the eye to the brain, resulting in blindness. This damage may or may not be related to eye pressure.

Humour giveth

Now we understand how we see and the basic definition of glaucoma. We must also understand the role of aqueous humour (AH). AH is a fluid that fills part of the eye. AH is necessary for providing nutrients to and removing waste from these internal structures. This is because these internal structures lack a blood supply.

The regulation of AH production and removal gives the eye its own pressure (To et al., 2002).

The ciliary epithelium located at the ciliary body and back surface of the iris produces AH.

The ciliary epithelium (CE) consists of two layers of cells, pigmented and non-pigmented. These cells facilitate water and nutrients from the blood to the posterior chamber, making up AH.

The pigmented CE lines the side with the blood vessels, and the non-pigmented CE lines the posterior chamber’s side (Macknight et al., 2000).

There are three mechanisms responsible for AH formation. They are:

• diffusion,
• ultrafiltration, and
• active secretion.

Diffusion and ultrafiltration require no energy. Diffusion involves the movement of solutes (dissolved molecules in water) from the blood in capillaries around the ciliary body into the posterior chamber of the eye (Goel et al., 2010).

Ultrafiltration involves the movement of water and small molecules and particles dissolved in water (limited by size and charge) thanks to an osmotic gradient (phenomena where water moves into an area of high solute concentration to low solute concentration) (Goel et al., 2010).

Finally, active secretion makes up the bulk of AH formation, about 80–90%. Energy is used to move charged particles or ions from the blood into the posterior chamber. There are two primary ion movements:

1. sodium (Na⁺) via Na⁺/K⁺-ATPase, and
2. bicarbonate (HCO⁻) by carbonic anhydrase (To et al., 2002),

Other ions and molecules that are transported include:

1. chlorine (Cl⁻), through various transporters, and
2. ascorbic acid (or vitamin C), using a sodium-dependant vitamin C transporter.

The movement of these ions results in the movement of nutrients and water from the blood to the AH. Later, we will see why this is important because these transporters become targets for drugs in glaucoma treatment (Goel et al., 2010).

Humour taketh away

With the formation of AH comes its drainage and subsequent removal. As the AH moves from the posterior to the anterior chamber, it approaches two exit ways:

• conventional, and
• unconventional.

In the conventional pathway, the AH exits the eye through the trabecular meshwork (TM) located at the angle where the back of the cornea and iris meet. Eventually, the AH will end up back into the body’s blood supply through the Schlemm’s canal, collector channels, then into the aqueous veins and episcleral veins.

The unconventional pathway involves AH exiting through the ciliary muscle and out the sclera (Goel et al., 2010).

Why is Glaucoma important?

Glaucoma is a major cause of visual impairment in the world (World Health Organization, 2017). An estimated 91,000 Kiwis may have this disease, half of which do not know they have it.

Glaucoma is a continuum (Weinreb & Khaw, 2004):

• Early stages, not being able to detect even with testing. Identifying risk factors like family history and routine monitoring become important.
• Detectable with tests but without any symptoms. This is where clinical tests are paramount in closely monitoring the disease and whether treatment should be initiated or changed.
• End-stage. Symptoms are noticeable. This is beyond repair. Vision loss is permanent, and treatment aims to save what remains.

Glaucoma needs to be caught early, and the only way is by routine eye examinations. Symptoms of vision loss only occur at the late disease stage. Treatment from this point cannot bring back lost vision. Glaucoma New Zealand recommends everyone have an eye examination by the age of 45. If all is normal, then an eye exam every five years.

What is Glaucoma?

From my experience, glaucoma’s fame comes from the ‘puff’ test or ‘pressure’ test. The discomfort of having air blown into your eyes is so memorable that it stands as the hallmark test for glaucoma. Unfortunately, it’s not that simple. The ‘pressure’ test, though important, is only one measurement used in the complex diagnosis of glaucoma.

Glaucoma is better described as a group of diseases, all of which are characterised in three ways (Thylefors & Negrej, 1994):

1. Damage to the optic nerve in the form of ‘cupping’.
2. This damage results in progressive visual field loss.
3. This damage may or may not be related to intraocular pressure (IOP).

The simplest definition I give for glaucoma is where the connection between the eye the brain becomes damaged, resulting in loss of peripheral vision.

Glaucoma is challenging to diagnose. For an individual who potentially has the disease, they sit on a spectrum (Weinreb & Khaw, 2004):

• Early stages, not being able to detect even with testing. This is where it is important to identify risk factors like family history, age and race, and be monitored more routinely.
• Detectable with tests but without any symptoms. This is where routine clinical tests are paramount in closely monitoring the disease and whether or not treatment should be initiated or changed based on its effectiveness.
• End-stage and symptoms become noticeable. Vision loss is beyond repair, and treatment aims to save what remains.

Symptoms only occur at the late stages of the disease, where treatment cannot bring back lost vision. Routine eye examinations are paramount in catching glaucoma early and monitoring those who have a family history

When determining the presence of glaucoma, we must adopt a detective’s approach. We must gather clues to determine a guilty (or innocent) verdict. We do this by performing several different tests (Glaucoma Research Foundation, 2020). These tests can include:

• our friend again, measuring eye pressure, which is called tonometry,
• analysing the state of the optic nerve by looking into the eye, also known as ophthalmoscopy (additionally, photography and taking scans using optical coherence tomography [OCT] are used the document the condition of the optic nerve, which can be used as a comparison in the future) (Boston, 2020),
• examining the peripheral vision — perimetry,
• observing the drainage mechanism of the eye using gonioscopy,
• looking at the thickness of cornea with pachymetry,

A collection of these tests’ results is combined to determine glaucoma diagnosis. Not just eye pressure alone. Additionally, most of these tests need to be repeated over multiple eye exams.

The many types of Glaucoma

Glaucoma is an umbrella term. We need to know the type of glaucoma to formulate the best treatment plan. There are different types and are classified by:

• eye pressure: high or normal,
• drainage angle: open or closed,
• and if this angle is closed, the time of presentation: acute (sudden) or chronic (long-standing),
• or if the angle is open, then eye pressure again: high or low,
• cause of glaucoma: If a cause is present, then the glaucoma is secondary to this cause; if not, then this is considered primary

Here are some examples of glaucoma (National Eye Institute, 2020):

• Normal-Tension Glaucoma (NTG) — normal eye pressure, but there is damage to the optic nerve typical of glaucoma.
• Primary Open Angle Glaucoma (POAG) — high eye pressure, open-angle, no other causes.
• Acute Angle Closure Glaucoma (AACG) — elevated eye pressure due to a closed drainage angle, severe pain, considered an ocular emergency.
• Pseudo-exfoliation Glaucoma (PEX) — elevated eye pressure, open-angle, clumps of dandruff-like protein clogging the drainage angle, a secondary open-angle glaucoma.
• Pigment Dispersion Syndrome (PDS) — elevated eye pressure, open-angle, pigment from the iris has rubbed off, accumulating at the drainage angle, a cause and thus secondary open-angle glaucoma.
• Neovascular Glaucoma — elevated eye pressure resulting from irregular blood vessels growing and blocking the eye’s drainage angle, a secondary glaucoma.

There are many other examples. Performing the aforementioned tests can determine what type of glaucoma a patient is suffering from. Knowing what type will affect the treatment method.

How Glaucoma does its damage

Remember, the optic nerve’s primary role is to relay sensory information from the eye to the brain. Glaucoma is when the optic nerve becomes damaged. This damage results in vision, more specifically peripheral vision loss.

How does this damage occur?

There are three proposed mechanisms, which may be independent or working in parallel (Gupta et al., 2009):

1. Mechanical theory: increased eye pressure (from some cause such as a blocked drainage angle) causes mechanical damage to the optic nerve structure called the lamina cribosa. Imagine the optic nerve is a cable. The wires running through this cable are called axons. Axons are part of the retinal ganglion cells (RGCs), responsible for relaying the information from the retina to the brain. Sense turns into perception. The axons also facilitate the flow of a signalling chemical called neurotrophin in the opposite direction, from the brain to retinal ganglion cells. These axons pass through the lamina cribosa when approaching the brain. Elevated eye pressure results in deformation of the lamina cribosa. This damaged the axons leads to restricted flow of neurotrophin. Lack of neurotrophin results in RGCs performing apoptosis (or programmed cell death). Loss of RGCs means less visual information reaches the brain. This manifests as visual field loss and change in the appearance of the optic nerve.
2. Vascular theory: Another proposed mechanism involves reduced blood flow to the vessels that nourish the optic nerve. A healthy optic nerve and retina require consistent and good blood flow or perfusion. Age results in reduced blood perfusion. In addition to this, increased sensitivity to endothelin-1 (a chemical signal that causes blood vessels to constrict — reducing blood flow), characteristic of diseases with reduced blood flow, is associated with glaucoma, along with migraines. The lack of stable and reliable blood supply results in RGC death. And hence, loss of vision.
3. Glutamate theory: Elevated levels of glutamate surrounding the retina can cause apoptosis of retinal ganglion cells. Glutamate is a neurotransmitter or a molecule that is responsible for sending signals between nerve cells. High levels of glutamate are toxic to surrounding cells, leading to cell death. This mechanism is controversial since some studies indicate no changes in glutamate levels. Also, apoptosis results in high glutamate levels; this mechanism may be in sequence with the previous two.

Other mechanisms include:

1. Nitric oxide (NO): NO freely enter cells. NO can react with cell metabolites resulting in highly oxidative molecules. Oxidative molecules or free radicles are toxic to the cells internal components. An excess of these can damage the cell and, ultimately, the cell’s death and destruction.
2. Oxidative stress: Glutathione and ascorbic acids are both present in the tissues of the eyes. They are very effective in reducing oxidative stress. When blood flow is poor, glutathione and ascorbic acid levels can drop. The eye becomes more susceptible to oxidative stress. Like with increased NO, this can result in cell death.

Treatments for Glaucoma

We have determined this patient is at risk of losing sight from glaucoma. Treatment is deemed necessary. How we treat can be split into three broad categories:

• medical or drug,
• laser treatment, and
• surgical.

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

Despite eye pressure not being a definitive sign of glaucoma, decreasing eye pressure reduces glaucomatous visual field loss (Heijl, 2002). This is even the case with normal-tension glaucoma (NTG), where there is glaucoma but normal eye pressure (CNTGSG, 1998).

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

In most cases, the first-line treatment for glaucoma is medical or drugs. If the eye pressure reduction is not at an acceptable level, other treatment options must be explored either exclusively or concurrently (Conlon et al., 2017).

Glaucoma Medical Drug Treatment

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 AH outflow 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 iris colour change (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.

Glaucoma Laser Treatment

Laser treatment is considered in addition to or when medication does not acceptably reduce eye pressure. Often, laser treatment is performed by an ophthalmologist 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 method of prevention 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).

Glaucoma Surgery

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

A sight-threatening condition, Glaucoma can significantly change an individual’s life. The disease involves damage to the connection between the eye and the brain. This connection we call the optic nerve.

Glaucoma is difficult to diagnose. The test for eye pressure alone is not sufficient. Tests for the condition of the optic nerve, visual field, and corneal thickness are required and combined to determine a diagnosis for glaucoma.

There are a variety of glaucoma types. This is important to investigate because this will determine treatment. Treatment is defined into three broad categories: drug, laser, and surgical.

The next stage is to explore Cannabis and its possibility of use as a glaucoma treatment. Please share this post with anyone who will find this useful. If you have any questions, please comment below or get in touch. Please subscribe to my FREE weekly newsletter if you want to keep up to date with any new blog posts.

References

Arthur, S., & Cantor, L. B. (2011). Update on the role of alpha-agonists in glaucoma management. Experimental Eye Research, 93(3), 271–283. https://doi.org/10.1016/j.exer.2011.04.002

Blind Low Vision New Zealand. (n.d.). Blindness and Low Vision in New Zealand — Latest statistics. Blind Low Vision NZ. Retrieved March 7, 2021, from https://blindlowvision.org.nz/information/statistics-and-research/

Collaborative Normal-Tension Glaucoma Study Group (CNTGSG). (1998). Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. American Journal of Ophthalmology, 126(4), 487–497. https://doi.org/10.1016/s0002-9394(98)00223-2

Conlon, R., Saheb, H., & Ahmed, I. I. K. (2017). Glaucoma treatment trends: a review. Canadian Journal of Ophthalmology, 52(1), 114–124. https://doi.org/10.1016/j.jcjo.2016.07.013

De Leo, D., Hickey, P. A., Meneghel, G., & Cantor, C. H. (1999). Blindness, Fear of Sight Loss, and Suicide. Psychosomatics, 40(4), 339–344. https://doi.org/10.1016/S0033-3182(99)71229-6

DeBry, P. W. (2002). Incidence of Late-Onset Bleb-Related Complications Following Trabeculectomy With Mitomycin. Archives of Ophthalmology, 120(3), 297. https://doi.org/10.1001/archopht.120.3.297

Epstein, D. L., & Grant, W. M. (1977). Carbonic Anhydrase Inhibitor Side Effects. Archives of Ophthalmology, 95(8), 1378. https://doi.org/10.1001/archopht.1977.04450080088009

Gil, D., Spalding, T., Kharlamb, A., Skjaerbaek, N., Uldam, A., Trotter, C., Li, D., WoldeMussie, E., Wheeler, L., & Brann, M. (2001). Exploring the potential for subtype-selective muscarinic agonists in glaucoma. Life Sciences, 68(22), 2601–2604. https://doi.org/10.1016/S0024-3205(01)01058-X

Glaucoma Research Foundation. (2020, January 9). Five Common Glaucoma Tests. Glaucoma Research Foundation. https://www.glaucoma.org/glaucoma/diagnostic-tests.php

Goel, M., Picciani, R. G., Lee, R. K., & Bhattacharya, S. K. (2010). Aqueous Humor Dynamics: A Review. The Open Ophthalmology Journal, 4(1), 52–59. https://doi.org/10.2174/1874364101004010052

Gupta, S., Agarwal, P., Saxena, R., Agrawal, S., & Agarwal, R. (2009). Current concepts in the pathophysiology of glaucoma. Indian Journal of Ophthalmology, 57(4), 257. https://doi.org/10.4103/0301-4738.53049

Heijl, A. (2002). Reduction of Intraocular Pressure and Glaucoma Progression. Archives of Ophthalmology, 120(10), 1268. https://doi.org/10.1001/archopht.120.10.1268

Holló, G. (2006). The side effects of the prostaglandin analogues. Expert Opinion on Drug Safety, 6(1), 45–52. https://doi.org/10.1517/14740338.6.1.45

Hoscheit, A. M. (2003, July 22). Interactions with Glaucoma Meds. Www.reviewofoptometry.com. https://www.reviewofoptometry.com/article/interactions-with-glaucoma-meds

Latina, M. A., & Tumbocon, J. A. (2012). Selective Laser Trabeculoplasty. In World Clinics in Opthalmology — Innovations in Primary Open Angle Glaucoma (pp. 1–10). Jaypee — Highlights Medical Publishers, Inc. https://www.google.co.nz/books/edition/World_Clinics_in_Ophthalmology_Innovatio/sHWXXKD-KloC?hl=en&gbpv=1&dq=selective+laser+trabeculectomy+latina+park&pg=PA1&printsec=frontcover

Macknight, A. D., McLaughlin, C. W., Peart, D., Purves, R. D., Carre, D. A., & Civan, M. M. (2000). Formation Of The Aqueous Humor. Clinical and Experimental Pharmacology and Physiology, 27(1–2), 100–106. https://doi.org/10.1046/j.1440-1681.2000.03208.x

Mapstone, R. (1968). Mechanics of pupil block. British Journal of Ophthalmology, 52(1), 19–25. https://doi.org/10.1136/bjo.52.1.19

Moster, M. R. (2013, May 9). Trabeculectomy Postop: Staying on Track. Www.reviewofophthalmology.com. https://www.reviewofophthalmology.com/article/trabeculectomy-postop-staying-on-track-42261

National Eye Institute. (2020, December 22). Types of Glaucoma | National Eye Institute. National Eye Institute. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/glaucoma/types-glaucoma

Nolan, W. P., Foster, P. J., Devereux, J. G., Uranchimeg, D., Johnson, G. J., & Baasanhu, J. (2000). YAG laser iridotomy treatment for primary angle closure in east Asian eyes. British Journal of Ophthalmology, 84(11), 1255–1259. https://doi.org/10.1136/bjo.84.11.1255

Optometrists and Dispensing Optician Board. (n.d.). Glaucoma prescribing. ODOB. Retrieved March 24, 2021, from https://www.odob.health.nz/i-am-registered/therapeutic-prescribing/glaucoma-prescribing/

Park, M. H., Kang, K.-D., & Moon, J. (2012). Noncompliance with glaucoma medication in Korean patients: a multicenter qualitative study. Japanese Journal of Ophthalmology, 57(1), 47–56. https://doi.org/10.1007/s10384-012-0188-6

Pastor, S., Singh, K., Lee, D. A., Juzych, M. S., Lin, S. C., Netland, P. A., & Nguyen, N. T. A. (2001). Cyclophotocoagulation A report by the american academy of ophthalmology. Ophthalmology, 108(11), 2130–2138. https://doi.org/10.1016/s0161-6420(01)00889-2

Radhakrishnan, S., Chen, P. P., Junk, A. K., Nouri-Mahdavi, K., & Chen, T. C. (2018). Laser Peripheral Iridotomy in Primary Angle Closure. Ophthalmology, 125(7), 1110–1120. https://doi.org/10.1016/j.ophtha.2018.01.015

Thylefors, B., & Negrej, A.-D. (1994). The global impact of glaucoma. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2486713/pdf/bullwho00414-0005.pdf

To, C., Kong, C., Chan, C., Shahidullah, M., & Do, C. (2002). The mechanism of aqueous humour formation. Clinical and Experimental Optometry, 85(6), 335–349. https://doi.org/10.1111/j.1444-0938.2002.tb02384.x

Toris, C. B., Gabelt, B. T., & Kaufman, P. L. (2008). Update on the Mechanism of Action of Topical Prostaglandins for Intraocular Pressure Reduction. Survey of Ophthalmology, 53(6), S107–S120. https://doi.org/10.1016/j.survophthal.2008.08.010

Trope, G. E., & Clark, B. (1982). Beta adrenergic receptors in pigmented ciliary processes. The British Journal of Ophthalmology, 66(12), 788–792. https://doi.org/10.1136/bjo.66.12.788

Vuletić, G., Šarlija, T., & Benjak, T. (2016). Quality of life in blind and partially sighted people. Journal of Applied Health Sciences, 2(2), 101–112. https://doi.org/10.24141/2/2/3

Weinreb, R. N., & Khaw, P. T. (2004). Primary open-angle glaucoma. The Lancet, 363(9422), 1711–1720. https://doi.org/10.1016/s0140-6736(04)16257-0

World Health Organization. (2017, December 8). Global data on visual impairment. World Health Organization. https://doi.org//entity/blindness/publications/globaldata/en/index.html

Zhu, J., Zhang, E., & Del Rio-Tsonis, K. (2012). Eye Anatomy. ELS. https://doi.org/10.1002/9780470015902.a0000108.pub2