Prostaglandin Analogues for Glaucoma

Prostaglandin analogues are the most effective single topical agents for lowering intraocular pressure and are the usual first-line drugs in open-angle glaucoma and ocular hypertension. Once-daily dosing, little systemic effect and good efficacy at night make them well suited to long-term use.

Mechanism. Selective agonists at the prostanoid FP receptor in the ciliary muscle remodel the extracellular matrix, reducing resistance and increasing uveoscleral outflow. Some also increase trabecular outflow (latanoprostene bunod releases nitric oxide). Bimatoprost is a prostamide.

Pharmacokinetics. The isopropyl ester prodrugs (latanoprost, travoprost, tafluprost) are hydrolysed in the cornea to the active acid; peak effect is 8 to 12 hours after the dose, and the effect lasts 24 hours. Systemic exposure is brief, with plasma half-life of about 17 minutes.

• Latanoprost 0.005 percent: the most widely used and cheapest; store unopened bottles at 2 to 8 degrees Celsius, then at room temperature for up to 6 weeks after opening.
• Bimatoprost 0.01 or 0.03 percent: slightly greater pressure reduction; more hyperaemia and eyelash growth.
• Travoprost 0.004 percent: similar efficacy.
• Tafluprost 0.0015 percent: preservative-free single-dose units.
• Latanoprostene bunod 0.024 percent: nitric oxide donating; where available.
• Fixed combinations with timolol: one drop once daily.

Regimen. One drop in the affected eye once daily, preferably in the evening. A second daily dose reduces effect. Pressure falls by 25 to 33 percent within 2 to 4 weeks; assess response after 4 to 6 weeks. Contact lenses are removed before use and may be replaced after 15 minutes.

Selection. First choice in most patients without contraindication. Good option when once-daily dosing helps adherence. Use a different class in uveitic glaucoma, after herpetic keratitis, in cystoid macular oedema, in pregnancy where possible, and when patient objects to eyelash or iris changes. Switch to a second prostaglandin analogue if the first fails to lower pressure by 15 percent or more.

Contraindications and cautions. Hypersensitivity; active intraocular inflammation (uveitis); herpetic keratitis; aphakia and pseudophakia with a torn posterior capsule, or risk factors for macular oedema; use with care in pregnancy and avoid in breastfeeding where alternatives exist.

Local effects. Conjunctival hyperaemia (most frequent), eyelash growth, thickening and darkening; periocular and iris pigmentation (irreversible, mainly in mixed-colour irises); deepening of the upper lid sulcus and orbital fat loss with some agents; ocular itching and dry eye; cystoid macular oedema; reactivation of herpes simplex keratitis and uveitis.

Interactions. Leave a 5-minute interval between different drops; topical NSAIDs may reduce effect.

Monitoring. Pressure at 4 to 6 weeks and then every 3 to 6 months; photograph or note iris and eyelid changes; ask about macular symptoms after cataract surgery.

Special groups. Pregnancy: avoid if alternatives exist (possible effect on uterine tone). Children: used under specialist care. Region: iris colour change is mainly a concern in mixed-colour irises; refrigeration of unopened latanoprost may be hard in hot climates, so ask pharmacies about storage and store opened bottles away from heat and sunlight.