Glaucoma, one of the leading causes of blindness, is most often treated with medications in the form of eyedrops. If you are involved in treating glaucoma patients, it is important to know how often they are used, how they work, common side effects, and whether a generic is available. Also, it is good to be able to instruct patients on how to properly administer eyedrops (spacing different drops a few minutes, punctal occlusion to reduce systemic absorption and therefore systemic side effects), how to store the drops (some should be refrigerated), and whether the drops have to be shaken before use.

To make things easier to remember, think of glaucoma medications in terms of the class of medication.

Prostaglandin analogs (PGAs)

PGAs (teal bottle cap) are by far the most commonly used. Xalatan (latanoprost, Pfizer [generic available]), Lumigan (bimatoprost, Allergan [generic available]), and Travatan Z (travoprost, Alcon [generic available]) have been on the market the longest. Zioptan (tafluprost, Akorn [no generic]) is newer and the only preservative-free PGA. Vyzulta (latanoprostene bunod, Bausch + Lomb [no generic]) is the newest option. It is unique because it splits into two active drugs as soon as it is absorbed into the eye: latanoprost and nitric oxide. Nitric oxide causes cell relaxation in the trabecular meshwork, thereby increasing aqueous outflow. Therefore, Vyzulta can have a greater IOP-lowering effect, according to a 2015 British Journal of Ophthalmology article by Weinreb et al.

PGAs are used once daily, usually at bedtime. They improve the outflow of aqueous. Side effects include redness and irritation, stinging, iris color change, darkening of eyelid skin, eyelash growth, droopy eyelids, and sunken eyes. There are no systemic side effects.

Rho kinase inhibitors

Rho kinase inhibitors (white bottle cap) are the newest glaucoma medications, available since 2018. So far there is only one: Rhopressa (netarsudil, Aerie Pharmaceuticals [no generic available]). It has a triple mechanism of action: it both increases the drainage and decreases the production of aqueous while also decreasing the episcleral venous pressure, all of which help lower IOP. It is also a once-daily medication, usually at bedtime. Because there is no generic and no other alternative in this class of medication, it can be expensive and less affordable for some patients. Side effects include redness (sometimes very impressive), stinging, corneal whorl-like deposits, and tiny conjunctival hemorrhages.

 Beta-blockers

Beta-blockers (yellow bottle cap) have been around for decades and are prescribed frequently. The most common one is timolol and is available as a generic, either 0.25% or 0.5%. Brand names including Timoptic and Timoptic-XE (Bausch + Lomb), Istalol (Bausch + Lomb), and Betimol (Akorn). Some timolol formulations are “gel-forming” and are designed to have a longer lasting effect; others are regular solution-type drops. Timoptic Ocudose (Bausch + Lomb) is a preservative-free timolol option.

Other beta-blockers are used less frequently. They include Betagan (levobunolol, Allergan), OptiPranolol (metipranolol, Bausch + Lomb) and Ocupress (carteolol, Bausch + Lomb).

Beta-blockers reduce IOP by decreasing aqueous production. They are prescribed either once or twice daily. Beta-blockers are generally well-tolerated in terms of ocular side effects but can have serious systemic side effects, such as low blood pressure, reduced heart rate, fatigue, shortness of breath (they can make asthma symptoms worse), and even reduced libido and depression. In diabetics, they can mask symptoms of hypoglycemia, or low blood sugar.

Another important drug in this group, Betoptic (betaxolol, Alcon) is a “cardioselective” beta-blocker. It has fewer side effects and therefore can be used (with caution) in patients who have asthma. Unlike the others, it has a light blue bottle cap.

Carbonic anhydrase inhibitors (CAIs)

CAIs (orange bottle cap) reduce IOP by causing decreased aqueous production. There are two drops in this category: Trusopt (dorzolamide, Merck [generic available]) and Azopt (brinzolamide, Alcon [no generic]). Azopt is a suspension and has to be shaken before use to be effective.

CAIs need to be used three times a day; however, they are often prescribed to be used twice a day. Side effects of CAIs are stinging, burning, eye discomfort, blurred vision, and changes in taste sensation.

Oral CAIs also are available and are more commonly used in emergency situations. Options include Diamox (acetazolamide, Alembic [generic available]) and Neptazane (methazolamide, Perrigo [generic available]). These have more severe side effects including tingling in hands and feet, fatigue, nausea, vomiting, frequent urination, and even heart arrhythmias due to electrolyte imbalance.

Alpha-agonists

Alpha-agonists (purple bottle cap) work to both decrease production of aqueous and increase drainage. Alphagan-P 0.1% or 0.15% (brimonidine, Allergan [generic available as either 0.15% or 0.2%]) needs to be used three times a day. Alphagan-P has a purite preservative that breaks down into natural tear components and may be better tolerated in people who have allergic reactions to the more common BAK preservative in the generic version.

Iopidine (apraclonidine, Alcon [generic available]) is another alpha-agonist but is rarely prescribed because it doesn’t work well long term. It is often used prior to procedures in the office (e.g. laser procedures) to prevent post-procedure IOP spikes. Side effects are burning or stinging, redness, fatigue, headache, insomnia, depression, anxiety, drowsiness, dry mouth and nose, and relatively high likelihood of allergic reaction.

 Miotics

Miotics (green bottle cap) improve aqueous outflow. Pilocarpine (several brand names) is the oldest glaucoma medication. Among the other options is carbachol (several brand names). These are rarely used due to a relatively low potency, short duration of action and a slew of side effects (dim vision, brow ache, redness, irritation, myopia, cataracts, increased inflammation, retinal detachment, nausea, vomiting, diarrhea, sweating, breathing problems, slow heart rate, and increased urination). Miotics also constrict the pupil and can be used for that usually during surgery.

Combination glaucoma drops

Combination drops (blue, light green, or white bottle caps) offer more IOP lowering with less exposure to preservatives and potential financial savings compared to using individual component medications. They include: Cosopt (dorzolamide-timolol, Akron [generic available]) and Combigan (brimonidine-timolol, Allergan [no generic]), both of which are twice-daily medications and have blue bottle caps. Cosopt PF (Akorn) is a preservative-free option.

Simbrinza (brimonidine-brinzolamide, Alcon [no generic]) was developed specifically as the only combination glaucoma drop without the beta-blocker timolol. It has to be shaken before use and it needs to be used three times a day, which makes it more difficult to use. It has a light green bottle cap.

Rocklatan (netarsudil-latanoprost, Aerie Pharmaceuticals [no generic]) the newest combination drop, is used once daily. It has a white bottle cap.

Compounding pharmacies, such as Ocular Science and Imprimis, have developed combination eyedrops that contain multiple glaucoma medications in the same bottle. Ocular Science has three compounded glaucoma drops (brand name Omni), including one that contains four different classes of medication. Imprimis has seven different offerings (brand name Simple Drops), all of which are preservative-free. The idea is to improve compliance, possibly reduce cost, and reduce exposure to preservatives. Compounded medications are not FDA approved but are manufactured in FDA-regulated facilities.

Conclusion

By understanding the basics of glaucoma medications, you can help patients in their fight against this potentially blinding disease. Although it may seem like a lot of facts to memorize, if you pay attention to what medications patients are using and how and keep in mind the few different categories of medications (and their associated cap colors), it should become easy to remember over time. OP