Topical Treatment for Open Angle Glaucoma

Lois Crabtree

Glaucoma

Glaucoma refers to a group of conditions that lead to damage of the optic nerve head, typically caused by raised intra-ocular pressure. Primary open angle glaucoma is the commonest glaucoma type in the UK and affects 8% of people at 80 years old (1). In open angle glaucoma the iridocorneal angle is open but aqueous flow is diminished.  

As glaucoma progresses, it can lead to peripheral visual field loss. The mainstay of treatment initially is with eye drops with the aim of lowering intraocular pressure. Intraocular pressure is determined by the production, circulation and drainage of aqueous humour and is considered normal if between 11-21mmHg (2). If treated, glaucoma progression can be delayed and most people will not have severe visual impairment (3).  

Aqueous Humour Production and Outflow

Aqueous humour is a clear colourless fluid produced by the ciliary processes of the ciliary body. The ciliary body produces aqueous humour at a rate of 2.5 μl per minute. The conventional route for aqueous humour to drain is via the trabecular meshwork and is pressure dependent. The non-conventional route is via the uveoscleral pathway, where aqueous humour drains into the ciliary muscle, and through the sclera. Around 10-40% of aqueous drainage occurs via this route and it is pressure independent (4).   

Glaucoma Medications

Glaucoma medications primarily act by reducing the production or increasing the outflow of aqueous humour. The aim of treatment is to reduce the intraocular pressure, and this will be measured at subsequent appointments to monitor response.   

Beta Blockers

Mechanism of action: acts on the ciliary body to reduce aqueous humour production

Side effects:

Local – burning, stinging, redness.

Systemic – bronchospasm, bradycardia, syncope, depression

Contraindications: asthma, cardiovascular problems (bradycardia, heart block)

Examples include timolol (non-selective) and betaxolol (selective) 

Prostaglandin analogues

Mechanism of action: increase aqueous outflow by the uveoscleral route

Side effects: brown iris pigmentation, peri-ocular skin pigmentation, hypertrichosis of eyelashes, pain and irritation, cystoid macular oedema (rare)

Contraindications: Uveitis (can precipitate an episode)

Examples include latanoprost and travoprost (bimatoprost is a prostamide, and has a slightly different structure to prostaglandin analogues but is often included in the same group)  

Alpha-2 agonists (sympathomimetics)

Mechanism of action: alpha-2 agonists, decrease production of aqueous humour

Side effects:

Local – allergic blepharoconjunctivitis.

Systemic– lethargy, fatigue, dry mouth

Contraindications: If also taking monoamine oxidase inhibitors (MOAIs), heart block

Examples include brimonidine and apraclonidine 

Carbonic anhydrase (CA) inhibitors

Mechanism of action: reduce production of aqueous humour (reduces bicarbonate production)

Side Effects:

Local (common) – eye irritation, pain, blepharitis.

Systemic – headache, drowsiness, gastrointestinal symptoms

Contraindications: brinzolamide should not be used in severe kidney/liver dysfunction, and dorzolamide in severe kidney dysfunction

Examples include dorzolamide and brinzolamide  Of note, fixed combination preparations and preservative free drops are available.

Decreasing Production of Aqueous HumourIncreasing Outflow of Aqueous Humour
Beta blockers Prostaglandin analogues
Alpha-2 agonists
Carbonic anhydrase inhibitors

Current Guidelines

The National Institute of Clinical Excellence (NICE) have guidelines on the management of primary open angle glaucoma which are outlined below (5): 

1st line treatment        

Prostaglandin analogue or a beta blocker 

2nd line treatment (if 1st line treatment was unsuccessful or not tolerated)·        

Switch to another first line therapy·        

Use a combination of medications (E.g. beta blocker and a prostaglandin analogue)·        

Switch to a second line therapy (CA inhibitors, miotic, or alpha agonist)·        

Consider laser or surgical treatment  

Management Points to Consider

Adherence to glaucoma therapy is known to be poor amongst patients (6). Therefore, clear instructions and advice is an important aspect of glaucoma management. Below is a guide to aid discussions with patients when explaining how to use eye drops.  

1. Inform the patient to follow the specific instructions regarding dosage and timing of the eye drops you have given them

2. If using more than one eye drop, advise that they should wait 3-5 minutes between each medication

3. Advise the patient to wash their hands before using the eye drops. Shake the bottle before use, and remove the cap without touching the dropper tip

4.Explain to the patient that they can tilt their head back and look up, with one hand pull the eyelid down away from the eye. Hold the dropper tip directly over the eyelid pocket, avoid touching the bottle on their eye or eyelid. Squeeze the bottle gently and let the eye drop fall into the pocket.

5. If the patient finds this difficult you can suggest lying down, adjusting mirror positioning, or using eye drop dispensers

6. Advise the patient to close their eyes and avoid blinking. If possible, show them how to put pressure over the lacrimal sac, which should be performed for 1-2 minutes to increase ocular absorption and decrease systemic absorption.

References 

1. Prevalence | Background information | Glaucoma | CKS | NICE [Internet]. [cited 2021 Nov 22]. Available from: https://cks.nice.org.uk/topics/glaucoma/background-information/prevalence/

2. Oxford Handbook of Ophthalmology. Oxford Handbook of Ophthalmology. Oxford University Press; 2014.

3. King A, Azuara-Blanco A, Tuulonen A. Glaucoma. Vol. 346, BMJ (Online). British Medical Journal Publishing Group; 2013.

4. Lam K, Lawlor M. Anatomy of the Aqueous Outflow Drainage Pathways. In: Minimally Invasive Glaucoma Surgery. Springer, Singapore; 2021. p. 11–9.

5. NICE. Overview | Glaucoma: diagnosis and management | Guidance | NICE [Internet]. NICE Guidance. NICE; 2017 [cited 2021 Oct 29]. Available from: https://www.nice.org.uk/guidance/ng81

6. Rotchford AP, Murphy KM. Compliance with timolol treatment in glaucoma. Eye. 1998;12(2):234–6.

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