Medical management of glaucoma

Summary

The mainstay of medical management for glaucoma comprises different varieties of topical drops. In this article we discuss the main drugs used and important side effects.

Prostaglandin Derivatives

MoA: Increasing uveoscleral aqueous outflow

Indication: Prostaglandin analogues have one of the best IOP-lowering effects, and are often preferred to beta-blockers as they have fewer side effects

Examples: Latanoprost, Travoprost, Bimatoprost, Tafluprost. All topical.

Ocular side effects:

• Conjunctival hyperaemia

• Eyelash thickening, lengthening and hyperpigmentation

• Iris hyperpigmentation

• Increased risk of cystoid macular oedema post cataract surgery

Systemic side effects:

• Mild - include headache, malaise, myalgia, skin rash

Latanoprost has the best side effect profile and is often the first line agent. The other, newer examples may have greater IOP-lowering effect, however.

💡 Did you know: The iris hyperpigmentation which may occur as a side effect of prostaglandin analogue use is due to an increase in pigmented granules within the superficial stroma, and has nothing to do with melanocyte count?

Beta-blockers

MoA: Decreasing aqueous production (action on the ciliary epithelium)

Cautions: Should not be applied at bedtime. They exacerbate hypotension during sleep, reducing optic disc perfusion which can precipitate visual field deterioration. Systemic side effects are common, especially if also taking oral beta blockers

Indication: Safer than prostaglandin derivatives in cases of ocular inflammation and cystoid macular oedema or if history of herpes simplex keratitis

Examples: Timolol. Betaxolol, Levobunolol, Carteolol, Metipranolol. All topical. Carteolol exhibits intrinsic sympathomimetic actiity and is also more selective on the eye than systemically - hence may have a lower side effect profile

Ocular Side Effects:

• Mild - include allergy and punctate keratitis

Systemic Side Effects:

• Bronchospasm

• Heart block, bradycardia, hypotension

• Sleep disorders, reduced exercise tolerance, hallucinations, depression, decreased libido

💡 Did you know: 2% of patients without asthma will develop airway disease within 12 months of starting a beta blocker, due to the bronchospasm effect?

Alpha-2 agonists

MoA: Decreasing aqueous production (action on the ciliary epithelium) and increases uveoscleral aqueous outflow

Indications: Apraclonidine is mainly used to prevent/treat sudden rise in IOP following laser surgery to the anterior segment

Examples: Brimonidine, Apraclonidine, all topical

Side effects: Allergic conjunctivitis with Brimonidine

Carbonic anhydrase inhibitors

MoA: inhibit aqueous secretion

Cautions: This class of drugs are chemically related to sulfonamide antibiotics and are therefore relatively contraindicated in sulfonamide allergy

Topical

Indications:

Examples: Dorzolamide, Brinzolomide

Side Effects: Stinging and transient bitter taste - particularly with Dorzolamide

Systemic

Indication: Generally used in short term treatment in acute glaucoma - systemic side effects prevent longterm use

Examples: Acetazolamide, Dichlorphenamide, Methazolamide

Ocular side effects: choroidal effusion post cataract surgery

Systemic side effects: paraesthesia, hypokalaemia, malaise, Steven-Johnson’s syndrome, dose related bone marrow suppression, idiosyncratic aplastic anaemia (rare)

Miotics

MoA: Cholinergic agonists - open the angle by causing contraction of sphincter pupillae, pulling peripheral iris away from the trabecular meshwork. Contraction of ciliary muscle also increases trabecular outflow.

Indication: Angle closure glaucoma

Examples: Pilocarpine, carbachol, all topical

Ocular side effects: Miosis, brow ache, myopic shift, worsening of cataract symptoms

Systemic side effects: Confusion, bradycardia, bronchospasm, GI symptoms (cholinergic SEs!)

Osmotic agents

MoA: Allow water to be drawn out from the vitreous to the blood through an osmotic gradient

Caution: Patients with cardiac or renal disease due to increased extracellular volume

Indication: For short term reduction in IOP resistant to other treatment, or in exceptionally high IOP prior to surgery. Not useful in cases of inflammatory glaucoma however, where blood-aqueous barrier is often breached

Examples: Mannitol (IV), glycerol (oral), isosorbide (oral)

Side effects: Cardiovascular overload due to extracellular volume, urinary retention, headache, backache, nausea and confusion

Combined preparations

These have the added benefit of lots of drugs and are better for patient compliance. Examples include:

• Cosopt®: timolol and dorzolamide, administered twice daily.

• Xalacom®: timolol and latanoprost once daily.

• TimPilo®: timolol and pilocarpine twice daily.

• Combigan®: timolol and brimonidine twice daily.

References

1. Bowling, Brad. Kanski’s Clinical Ophthalmology: A Systematic Approach . 2016. Open WorldCat , http://public.ebookcentral.proquest.com/choice/publicfullrecord.aspx?p=2029294.