Glaucoma is the leading cause of visual loss.
This lecture will cover the medical management of glaucoma/grøn stær, which is the most common therapy for intraocular pressure reduction. Visual loss from glaucoma is irreversible, and the goal of treatment is to prevent loss of vision. Reducing intraocular pressure is the only known way to cheat glaucoma. And this may be achieved with medication, laser surgery. Results from several landmark studies including the ocular hypertension treatment study, the early manifest glaucoma trial, and collaborative normal tension glaucoma study show that a lower IOP reduces the risk of developing glaucoma and slow the risk of disease progression. Not too long ago, elevated interocular pressure and glaucoma are synonymous, where any elevation of IOP was considered glaucoma.
However, it became recognized that an elevation of IOP was not a component of the definition of glaucoma, and has been classified as a risk factor, rather than a clinical feature of glaucoma. The glaucoma community then realized that not glaucomas are alike. And, despite low IOPs, some patients continue to have progressive optic nerve damage. The concept of target IOP was conceived, which highlighted that treatment should, therefore, be individualized. This refers to a range of IOP where the upper limit is unlikely to result in further damage to the optic nerve. This is not a fixed number, for the rest of the patients follow up, and needs to be reassessed and changed as dictated by IOP fluctuations, nerve changes, and visual field progression. Risk factor should also be taken into accounts, such as how advanced the glaucoma is at present, the severity of damage, and the patient’s life expectancy. Today, we will go through a brief overview of the different medication classes that we use to treat glaucoma. Beta-blockers were first introduced in 1978 in the form of Timolol maleate. Other beta-blockers were later introduced, including Betaxolol, which is cardioselective and blocks beta-1 adrenergic receptors.
Beta-blockers work by reducing aqueous production. Typically, the drugs are well tolerated, but the larger concern was the systemic absorption and potential side effects. These are well described, and these include precipitation of asthma attacks through bronchoconstriction, masking of hypoglycemia, fatigue, and bradycardia. They have been found to be less effective in patients taking systemic beta-blockers. However, they appear safe, as lots of patients, with no contraindications, avoid them. One main advantage of this drug class is the availability of Timolol as a generic and is, therefore, cost-effective. The use of beta antagonist has declined with the introduction of prostaglandin analogs. Prostaglandin analogs work by increasing uveoscleral outflow and allow 25% to 30% reduction in IOP. Tachyphylaxis and systemic side effects are rare. And local side effects are well tolerated. Hyperaemia is most common, and other effects include iris darkening through the increase of melanin, precipitation of anterior uveitis and cystoid macular edema.
Eyelash growth is also common, but fortunately, it’s only a cosmetic concern. These agents have become the primary agent for therapy, as they are more efficacious with fewer side effects and have a more friendly once a day dosing schedule. Adrenergic agonists inhibit aqueous production and aqueous enzyme outflow. They allow for 20% to 30% reduction in the IOP. Several known side effects of Apraclonidine, the first drug in this class, include the development of allergic follicular conjunctivitis and tachyphylaxis. The alpha-adrenergic agonists of choice are now Brimonidine, which still carries some of the side effects to some extent. They have a short duration of action, requiring them to be used on a three times a day dosing when used singly, which is where they have been delegated as a secondary role as the drug of choice.
Adrenergic agonists are safe, but they should not be used in children younger than six years of age, as it can cause central nervous system suppression. Cholinergic agonists cause ciliary muscle spasm, leading to improved flow through the trabecular meshwork. Pilocarpine is most commonly used, though it has decreased in popularity due to its four times a day dosing schedule and common local side effects, which include brow ache, blurred vision, and a myopic shift. Carbonic anhydrase inhibitors reduce aqueous production and allow a 15% to 20% drop in IOP. This was initially available as an oral preparation and was known to induce systemic side effects. Commonly, a metallic taste in the mouth, depression, and importantly, kidney stones and aplastic anemia. Topical preparations dramatically reduce systemic side effects, though local irritation is common, and especially pronounced with Dorzolamide.
These drugs are from the sulfur family, and therefore, contraindicated in patients with sulfur allergies. Hyperosmotic agents reduce IOP by causing a reduction in various volume, by creating an osmotic gradient between the vitreous and intravascular fluid. They may be administered orally or intravenously, and are more valuable in situations of acute intra-ocular pressure elevations. In angle-closure ancillary block glaucomas, hyperosmotic agents work through reducing IOP and deepening of the anterior chamber, the reduced vitreous volume. These medications should not be given chronically to treat glaucoma, due to potentially serious systemic side effects of electrolyte imbalance and kidney failure. When monotherapy fails, combination therapy is effective in further lowering IOP. Fixed-dose combinations, in addition to further IOP, lowering, keep treatment regimes simple, and therefore, help with patient compliance. A majority of combination preparations include timolol, though more recently, a new FDA approved Sumbrinza, does not have the beta-blocker component, which eliminates the associated cardiovascular or Padmini adverse effects. Glaucoma medications are ever evolving with increased efficacy. Prostaglandins are currently the primary agent of choice, though the arsenal of medical therapy is ever increasing.
Potential side effects can be avoided by calibrating the patient’s profile to the appropriate medication. Thank you for listening.
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