Category:Glaucoma medications

A glaucoma medication is an intraocular-pressure-lowering medicine used in the management of glaucoma, the optic-nerve disease in which a characteristic excavation of the optic disc and a corresponding loss of peripheral vision occur over years in association with a level of intraocular pressure that the optic nerve of a given patient cannot tolerate. The category includes the five established pharmacological classes (prostaglandin analogues, topical beta-blockers, topical alpha-2 agonists, topical and oral carbonic anhydrase inhibitors, and the cholinergic miotics) and the newer Rho-associated kinase (ROCK) inhibitors and selective adenosine-A1 agonists.

The disease was named in classical antiquity. Hippocrates used the word glaukos (γλαυκός, bluish-grey) for the discoloured iris of advanced cases. The connection between optic-disc cupping, visual-field loss, and elevated intraocular pressure was made by the German ophthalmologist Albrecht von Graefe in Berlin in 1857, who also performed the first iridectomy as a treatment.^[1] Surgical management dominated the field until the late nineteenth century, when the discovery of pharmacological alternatives began.

The first effective medical treatment was a plant alkaloid. The English physician Thomas Fraser of Edinburgh reported in 1862 that an extract of the Calabar bean Physostigma venenosum, used as an ordeal poison in West Africa, produced miosis when dropped into the eye; the alkaloid responsible, physostigmine (eserine), was isolated by Jobst and Hesse in 1864. Physostigmine and the related cholinergic alkaloid pilocarpine (from the South American plant Pilocarpus jaborandi, isolated by Hardy in 1875) were applied as miotic drops in glaucoma; both lower intraocular pressure by contracting the ciliary muscle and pulling open the trabecular meshwork, improving aqueous outflow. The miotics were the mainstay of medical glaucoma therapy for ninety years, although their pupillary constriction, dim-vision side effect, and induction of cataract progressively narrowed their use.

The first systemic glaucoma medicine was a sulfonamide. Acetazolamide was developed by Roblin and Clapp at Lederle in 1953 as a carbonic anhydrase inhibitor; its diuretic effect was noted first, but Bernard Becker in 1954 showed that it also reduced aqueous-humour production by the ciliary epithelium and lowered intraocular pressure substantially.^[2] Systemic carbonic anhydrase inhibitors continue to be used acutely for the management of acute angle-closure glaucoma and chronically in advanced cases not controlled by topical agents; the topical analogues dorzolamide (Merck, 1995) and brinzolamide (Alcon, 1998) provide the local effect without the systemic side effects of paraesthesia, metallic taste, and renal-stone formation.

The 1970s brought the first selective topical adrenergic medicine. Timolol, a non-selective beta-blocker originally developed by Merck as a systemic antihypertensive, was reformulated as 0.25% and 0.5% ophthalmic drops and approved for glaucoma in 1978; topical timolol reduces aqueous-humour production by acting on beta-2 receptors of the ciliary epithelium and lowers intraocular pressure by 25 to 30 percent.^[3] Timolol remained the standard first-line medical therapy for the next twenty years, until the prostaglandin era; its systemic absorption from the conjunctival sac, however, is sufficient to produce bradycardia, bronchospasm, and depressed mood in susceptible patients, and the medicine has retreated to second-line use. The selective alpha-2 agonist apraclonidine (1987) and the more selective and better-tolerated brimonidine (Allergan, 1996) lower intraocular pressure both by reducing aqueous secretion and by enhancing uveoscleral outflow.

The transformative class of contemporary glaucoma medicine was the prostaglandin analogue. The Hungarian-American pharmacologist László Bitó at Columbia, working in the 1970s on the effects of prostaglandins on intraocular pressure, observed paradoxically that low concentrations of certain prostaglandin F2α analogues lowered, rather than raised, the pressure by markedly enhancing the uveoscleral pathway of aqueous outflow.^[4] Bito's collaboration with Pharmacia produced latanoprost (Xalatan, 1996), the first prostaglandin analogue glaucoma medicine; bimatoprost (Lumigan, Allergan, 2001), travoprost (Alcon, 2001), and tafluprost followed. The class lowers intraocular pressure by 28 to 32 percent on once-daily evening dosing, has minimal systemic effect, and has displaced beta-blockers as the standard first-line medical therapy. The principal cosmetic side effects, progressive darkening of the iris (in genetically heterochromic eyes), darkening and lengthening of the eyelashes (an effect that bimatoprost is separately marketed under the trade name Latisse for cosmetic use), and periorbital fat atrophy with deepening of the upper lid sulcus, are recognised and are accepted in exchange for the IOP benefit.

The most recent pharmacological additions act on the trabecular meshwork directly. The Rho-associated kinase inhibitor netarsudil (Aerie, 2017) lowers IOP by relaxing actomyosin contractility in the trabecular meshwork and Schlemm's canal, increasing trabecular outflow. The selective adenosine-A1 receptor agonist trabodenoson and the fixed-combination drops (netarsudil-latanoprost, brimonidine-timolol, dorzolamide-timolol, latanoprost-netarsudil) round out the contemporary pharmacopoeia. Selective laser trabeculoplasty has emerged in parallel as a first-line procedural alternative to chronic eye drops, and the LiGHT trial in 2019 found that primary SLT produced equivalent IOP control with a higher quality-of-life score than primary medical therapy. The medicine-versus-laser-versus-incisional-surgery decision is now a genuine three-way choice rather than a sequential escalation.

By mechanism:

• Prostaglandin analogues (enhanced uveoscleral outflow): latanoprost, bimatoprost, travoprost, tafluprost
• Topical beta-blockers (reduced aqueous production): timolol, betaxolol (β1-selective, less bronchospasm risk), levobunolol, carteolol
• Topical alpha-2 agonists (reduced aqueous production, enhanced uveoscleral outflow): brimonidine, apraclonidine
• Topical carbonic anhydrase inhibitors (reduced aqueous production): dorzolamide, brinzolamide
• Oral carbonic anhydrase inhibitors (advanced or acute cases): acetazolamide, methazolamide
• Cholinergic miotics (improved trabecular outflow, ciliary-muscle contraction): pilocarpine, carbachol; the indirect-acting echothiophate (largely obsolete)
• Rho-associated kinase inhibitors: netarsudil
• Hyperosmotic agents (emergency IOP reduction in acute angle closure): intravenous mannitol, oral glycerol
• Fixed combinations: dorzolamide-timolol, brimonidine-timolol, brinzolamide-brimonidine, netarsudil-latanoprost, bimatoprost-timolol

The boundary of this category is "medicine prescribed in the management of glaucoma." The category overlaps almost completely with the ocular hypotensive agents category, which is organised by the same medicines but emphasises mechanism (IOP lowering) over indication (glaucoma). The two categories are kept as parallel listings for the convenience of readers approaching from each direction. The medicines used in the surgical management of glaucoma (intraoperative mitomycin-C, antiproliferative 5-fluorouracil) are not glaucoma medications in the conventional sense and are listed under their oncologic or surgical categories. The neuroprotective and neurotrophic agents in trial for non-IOP-mediated optic-nerve preservation in glaucoma (citicoline, brimonidine in some neuroprotection trials, intravitreal nerve-growth factor) are not yet established in standard care and are not collected here. Ophthalmologic medicines used for conditions other than glaucoma (the ophthalmic antibiotics, antifungals, mydriatics, cycloplegics, the ophthalmic antihistamines, the intravitreal anti-VEGF agents for macular degeneration) belong to those respective categories.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.