Currently, 5 prostaglandin (PG) analogues have been approved by the FDA for clinical use (Table 16-11). Latanoprost, bimatoprost, travoprost, and tafluprost are administered once daily, with nighttime dosing; unoprostone is used twice daily. Tafluprost is available preservative-free in single-use containers. Latanoprost, travoprost, tafluprost, and unoprostone are prodrugs that require hydrolyzation before becoming active compounds in the eye. Except for unoprostone, whose exact mechanism of action remains unknown, they interact with the prostaglandin FP receptor. In contrast, bimatoprost is not a prodrug, and it acts on the prostamide receptor.
Latanoprost is a prodrug of prostaglandin F2α (PGF2α); it penetrates the cornea and becomes biologically active after being hydrolyzed by corneal tissue esterase. It appears to lower IOP by enhancing uveoscleral outflow and may reduce the pressure by 6–9 mm Hg (25%–35%). In addition to once-daily dosing, other advantages of the drug are a lack of cardiopulmonary adverse effects and additivity to other antiglaucoma medications.
A unique ocular adverse effect associated with this class of drugs is the darkening of the iris and periocular skin as a result of increased numbers of melanosomes (increased melanin content, or melanogenesis) within the melanocytes. The risk of iris pigmentation correlates with baseline iris pigmentation. In 10%–20% of light-colored irides, increased pigmentation may occur in the initial 18–24 months of therapy, whereas nearly 60% of eyes that are light brown or 2-toned may experience increased pigmentation over the same period. The long-term sequelae of this adverse effect, if any, are unknown. Other adverse effects associated with topical PG analogues are conjunctival injection, hypertrichosis of the eyelashes, CME, and uveitis. CME and uveitis are more common in eyes with preexisting risk factors for either condition.
Table 16-11 Prostaglandin Analogues
Reported systemic reactions include flulike symptoms, rash, and possible uterine bleeding in postmenopausal women. Reactivation of herpetic keratitis has been reported with use of latanoprost. Topical PGs are classified as category C according to the FDA’s use-in-pregnancy ratings. Although their elimination from human plasma is rapid, PGs are known to cause contraction of the uterus. Thus, topical PGs should be used with caution in pregnant patients.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.