Glaucoma

Glaucoma is a group of optic neuropathies in which progressive damage to the optic nerve leads to irreversible peripheral visual field loss, with characteristic thinning of the retinal nerve fibre layer, cupping of the optic disc, and field loss that typically precedes any loss of central visual acuity.^[1] The distinction that determines everything about management is whether the anterior chamber angle — the space where the iris meets the cornea, through which aqueous humor drains — is open or narrowed/closed. Open-angle glaucoma is the most common form: usually bilateral, chronic, and silent, with patients typically asymptomatic until advanced field loss has already occurred. Angle-closure glaucoma is fundamentally different: when the angle closes acutely, aqueous outflow is suddenly obstructed, intraocular pressure (IOP) rises rapidly, and the result is a painful, symptomatic, true ophthalmic emergency requiring an entirely different, urgent treatment sequence from routine open-angle management.^[2] Elevated IOP is the only modifiable risk factor for glaucoma, and every proven treatment — medical, laser, or surgical — works by lowering it.

Open-angle glaucoma

The great majority of patients with open-angle glaucoma are completely asymptomatic until the disease is advanced. There is no eye pain and no redness. Vision loss begins in the peripheral field and often goes unnoticed for years, since central visual acuity is preserved until late in the disease. When patients do report symptoms, they are subtle — difficulty with night driving, bumping into objects or furniture, or missing words at the edge of the visual field while reading. Because of this silent course, the diagnosis is made almost entirely on examination findings, not on presenting symptoms.

Angle-closure glaucoma

Angle-closure glaucoma can present acutely, or can be just as silent as open-angle disease.

Open-angle glaucoma

• Elevated intraocular pressure — the only modifiable risk factor.
• Advanced age.
• Positive family history of glaucoma.
• Myopia (nearsightedness).
• Vascular disease, including migraine, hypertension, and nocturnal hypotension.
• Type 2 diabetes mellitus.
• Blunt or penetrating ocular trauma.
• Previous intraocular surgery or intraocular inflammation.
• Corticosteroid use by any route — inhaled, intranasal, ophthalmic, topical, or systemic.
• Pseudoexfoliation syndrome.
• Pigment dispersion syndrome.
• Long-term oral contraceptive use (over 3 years) has been associated with primary open-angle glaucoma.

Angle-closure glaucoma

• Female sex.
• Advanced age.
• Hyperopia (farsightedness), associated with a structurally shallow anterior chamber and a narrow angle.
• Positive family history of angle-closure glaucoma.
• A previous acute angle-closure attack in the contralateral eye is a strong risk factor for the fellow eye.
• East Asian or Inuit ancestry, both associated with anatomically shallower anterior chambers.
• Proliferative diabetic retinopathy and central retinal vein occlusion, which can cause neovascular angle-closure glaucoma.

Medication-induced risk — a genuine medication-review point

• Systemic drugs with antimuscarinic (anticholinergic) activity — including many antidepressants, antihistamines, antispasmodics, and decongestants — can rarely precipitate acute angle-closure glaucoma in a predisposed patient, such as an older, significantly hyperopic patient with a positive family history who has not yet had a prophylactic iridotomy.
• Topiramate has been specifically associated with acute, bilateral, secondary angle-closure glaucoma, typically within the first weeks of starting the drug, through a distinct mechanism (ciliary body swelling and anterior lens-iris displacement) rather than classic pupillary block.^[3]
• Bupropion has also been associated with an increased risk of angle-closure glaucoma.^[4]
• Corticosteroid use by any route can precipitate or worsen open-angle glaucoma and is itself a reason for periodic IOP monitoring in a patient with additional risk factors.

Distinguishing the types of glaucoma on presentation

History

• Nature of any ocular disturbances — loss of peripheral vision, scotoma, halos around lights, decreased visual acuity.
• Impact on reading, daily activities, driving or night driving; falling; bumping into objects.
• Quality of any pain — deep orbital, brow, or headache.
• Associated systemic symptoms — abdominal pain, nausea and vomiting.
• Full medication history, specifically asking about corticosteroids (any route), drugs with antimuscarinic activity, topiramate, bupropion, and long-term oral contraceptive use (see Risk Factors).

Physical examination

• Eye examination — visual field by confrontation, optic disc cupping, and IOP measurement.
• Gonioscopy to examine the anterior chamber angle directly and classify open versus narrow/closed.

Elevated IOP alone is neither a sensitive nor a specific screening test for glaucoma — a meaningful proportion of people with glaucoma have IOP within the statistically normal range, and most people with an elevated IOP reading never go on to develop glaucoma, though their risk is increased. Systematic population screening is therefore not recommended, but a dedicated ophthalmic examination including IOP should be considered for patients with a personal history (glaucoma in the contralateral eye) or family history of glaucoma, and for patients on regular corticosteroid therapy (oral, inhaled, intranasal, or topical) who have additional risk factors.^[1]

Investigations

• Comprehensive eye examination by an ophthalmologist or optometrist.
• Automated perimetry (formal visual field testing).
• Optic disc photography.
• Central corneal thickness measurement.
• Optic disc and retinal nerve fibre layer imaging (e.g. OCT).

Setting an individualized target IOP

Target IOP is set for each patient based on the extent of existing glaucomatous damage (disc cupping, peripheral field loss), the IOP range believed to have been associated with that damage, and the burden of therapy needed to reach the desired pressure. The target is adjusted further downward if progressive optic disc or visual field damage occurs despite reaching the original target — reaching a numeric target IOP is not itself proof that treatment is adequate if the disc or field is still worsening.

• Prevent, halt, or slow progressive visual field loss.
• Preserve the structure and function of the optic nerve.
• Lower intraocular pressure to an individualized target range — the only proven, modifiable lever in every form of glaucoma.
• In acute angle-closure glaucoma specifically: rapidly eliminate pain and urgently lower IOP to prevent permanent optic nerve damage and vision loss.
• Improve or maintain quality of life and functional vision, including night driving and reading.

Correct eye drop administration technique

Topical glaucoma medications are highly concentrated to achieve adequate penetration into the eye, and a meaningful fraction of every dose drains through the nasolacrimal duct into the nose and throat, where it is absorbed directly into the systemic circulation, bypassing first-pass hepatic metabolism. This is the mechanism behind the systemic beta-blockade risk from topical timolol and betaxolol (see Red Flags and Drug Tables), and is a genuine, teachable adherence and safety point for every patient started on any topical glaucoma medication.

• Nasolacrimal occlusion: press gently on the inner corner of the eye, over the tear duct, for 2 to 5 minutes after instilling each drop, or simply close the eyelids gently for the same duration. Both meaningfully reduce systemic absorption.^[7]
• Wait at least 5 minutes between two different eye drops, to avoid washing out the first medication before it has been absorbed.
• Remove soft contact lenses before instilling drops and wait at least 15 minutes before reinserting them — the benzalkonium chloride preservative in many formulations can be absorbed by, and discolour, soft lenses.
• Blot away any excess solution that runs onto the eyelid skin, particularly with a prostaglandin analogue, to reduce the risk of periocular skin darkening.
• Do not let the dropper tip touch the eye or any other surface, to avoid contaminating the bottle and causing a serious eye infection.

Cannabis is not an appropriate glaucoma treatment

Laser and surgical escalation

Lifestyle modification has not been shown to alter the course of glaucoma, though regular aerobic exercise can modestly lower IOP in some patients — a reasonable general health recommendation, but never a substitute for IOP-lowering treatment. When medical therapy is insufficient, not tolerated, or adherence is a genuine ongoing concern, laser or surgical treatment is used to lower IOP directly.

Pregnancy

Breastfeeding

Brimonidine should not be used by a breastfeeding parent of a young infant — it is absorbed systemically and can cause apnea and CNS depression in a nursing infant, mirroring the reason it is contraindicated in young children. Timolol passes into breast milk; weigh the importance of the drug against potential infant exposure. Prostaglandin analogue data in lactation are limited; use with caution.

Pediatrics

Brimonidine is contraindicated in infants and young children (generally under 2 years of age) because of CNS depression, apnea, bradycardia, hypotension, and hypothermia risk from systemic absorption relative to body weight, and should be used with caution in older young children for the same reason. Congenital glaucoma requires urgent pediatric ophthalmology referral rather than adult-pattern management. Most other topical agents are not authorized for pediatric use in Canada due to a lack of pediatric data, not a known specific harm.

Renal and hepatic impairment

Oral carbonic anhydrase inhibitors (acetazolamide, methazolamide) are contraindicated in significant renal or hepatic impairment given the risk of drug accumulation, worsening acidosis, or precipitating hepatic coma; use topical agents preferentially in this population, since their systemic absorption and clearance burden are far lower.

Older adults

The most common population for open-angle glaucoma, and often the population where adherence to a topical drop regimen is most challenged by cost, technique (poor dexterity, difficulty aiming the bottle), or memory. Laser trabeculoplasty is a reasonable earlier option, not only a last resort, in this group. Older adults are also more likely to be on interacting systemic cardiac or respiratory medications, making the beta-blocker screening step in every glaucoma prescription review especially important.

Recheck IOP about 4 weeks after starting or changing any topical therapy, since the full pressure-lowering effect takes time to stabilize — this is a hard rule for beta-blockers specifically, but is good practice for every class. At scheduled follow-up, reassess automated visual fields and optic disc appearance (photography or imaging) for progression, not just the IOP number in isolation, since a numeric target can be met while the disc or field is still worsening. Adjust the individualized target IOP downward whenever progression continues despite reaching the prior target. After an acute angle-closure attack, recheck IOP within the first hour of emergency treatment and periodically thereafter, and examine the fellow eye — it carries a meaningfully increased risk of a future attack of its own and should be evaluated for prophylactic laser iridotomy. At every refill, re-screen for new systemic disease (asthma, COPD, bradycardia, heart block) or a newly started interacting drug that would change the safety of an existing topical beta-blocker.

1. Confirm adherence and correct technique — right eye(s), right frequency, adequate spacing between different drops, and punctal occlusion — before assuming the drug itself has failed.
2. If IOP remains above target on monotherapy, add a second agent from a different class rather than simply increasing the dose of the first; switch within class only if the issue is intolerance rather than inadequate effect.
3. Prefer a fixed-combination product over separate bottles when two or more classes are needed long-term, to support adherence.
4. Reassess for a medication-induced or secondary cause of treatment-resistant elevated IOP — a new corticosteroid prescription (any route), or a new systemic anticholinergic, topiramate, or bupropion exposure.
5. If maximally tolerated medical therapy still fails to reach target IOP or halt progression, escalate to laser trabeculoplasty.
6. If laser trabeculoplasty is insufficient or not appropriate, escalate to incisional surgery — a filtration procedure or a drainage device.
7. For acute angle-closure not responding to combined topical and systemic emergency therapy within about an hour, add IV mannitol and proceed urgently to laser iridotomy or iridoplasty, or surgical iridectomy, without further delay.

• Assuming a normal IOP reading rules out glaucoma — a meaningful proportion of people with glaucoma have IOP within the statistically normal range.
• Mistaking acute angle-closure glaucoma for conjunctivitis, migraine, or gastroenteritis — missing the red flags delays truly emergency care.
• Giving pilocarpine as the very first drug in acute angle-closure — at very high IOP the iris sphincter is ischemic and will not respond; other agents must lower IOP first.
• Prescribing or refilling a topical beta-blocker without asking about asthma, COPD, or bradycardia/heart block — a genuinely serious systemic-absorption risk pharmacists are positioned to catch.
• Not counselling on punctal occlusion or eyelid closure — a simple technique that meaningfully reduces systemic absorption and side effects for every topical glaucoma medication, especially beta-blockers.
• Missing a medication-review opportunity — not flagging a new systemic anticholinergic, topiramate, or bupropion prescription in a patient with known narrow angles or significant hyperopia.
• Assuming more frequent dosing of a prostaglandin analogue improves control — more than once daily actually reduces the pressure-lowering effect.
• Combining two prostaglandin analogues, or two topical beta-blockers, together — no added benefit, only added cost and side effects.
• Recommending cannabis for IOP control — short duration of action and psychotropic effects make it an inappropriate glaucoma treatment.
• Failing to arrange examination and prophylactic laser iridotomy for the fellow eye after an acute angle-closure attack in one eye.

How to use this table: doses are adult doses for ophthalmic solutions unless stated otherwise, and require patient-specific confirmation. Select any drug name to open its complete Pharmasist Drug Database page. All topical agents reach the systemic circulation to some degree through nasolacrimal drainage — punctal occlusion after every drop meaningfully reduces this (see Non-Pharmacologic Treatment).

Prostaglandin analogues, ophthalmic

First-line therapy for most patients with open-angle glaucoma given effectiveness, once-daily dosing, and a favourable systemic safety profile. ^[1]

Beta-blockers, ophthalmic

Reduce IOP by decreasing aqueous humor production. A meaningful fraction of every dose is absorbed systemically — screen for asthma, COPD, and cardiac conduction disease before every prescription and refill.

Alpha-2 adrenergic agonists, ophthalmic

Carbonic anhydrase inhibitors, ophthalmic

Lower systemic exposure than an oral carbonic anhydrase inhibitor; useful add-on or alternative for a beta-blocker-intolerant patient.

Cholinergic agonist, ophthalmic

Fixed-combination products, ophthalmic

More convenient and may improve adherence for patients who need more than one agent class to reach target IOP; also reduce cumulative preservative exposure and washout from sequential dosing. ^[6]

Carbonic anhydrase inhibitors, oral

Systemic agents reserved for the acute angle-closure emergency sequence and for short-term or adjunctive use in chronic disease, given a substantial rate of systemic intolerance with prolonged therapy.

Osmotic (hyperosmotic) agent — emergency use only

Rho-kinase inhibitors (e.g. netarsudil) are a newer topical class used in some other countries but are not currently marketed in Canada, so no Canadian dosing is given here.