Adverse Effects

An adverse effect unique to this class of drugs is the darkening of the iris and periocular skin as a result of an increased number of melanosomes within the melanocytes, without melanocyte proliferation. Increased iris pigmentation is permanent, and the frequency of this effect depends on the baseline iris color. Most published data relate to latanoprost and suggest a risk of up to 33% after 5 years of use. In particular, up to 79% of persons with green-brown irides and up to 85% of persons with hazel (yellow-brown) irides may be affected, compared with 8% of persons with blue irides. There is no evidence to suggest that increased iris or periocular skin pigmentation is associated with any risk to the patient such as an increased risk of melanoma.

Other adverse effects reported in association with the use of a topical prostaglandin analogue include conjunctival hyperemia (a result of vasodilation, more common with bimatoprost and travoprost), hypertrichosis (Figs 12-1, 12-2), trichiasis, and distichiasis. These effects are reversible upon drug discontinuation.

Use of prostaglandin analogue eyedrops has also been associated with the development of prostaglandin-associated periorbitopathy (see Fig 2-12), a complex of abnormalities that includes deepening of the upper eyelid sulcus, upper eyelid ptosis, enophthalmos, inferior scleral show, and possibly a tight orbit. These abnormalities appear to be the result of periorbital fat atrophy. It is not clear whether this periorbitopathy is reversible.

Figure 12-1 Hypertrichosis following use of latanoprost (left eye).

(Courtesy of F. Jane Durcan, MD.)

Figure 12-2 The right (A) and left (B) eyes of a patient on unilateral treatment with a topical prostaglandin analogue for the left eye. Left-sided periorbital skin hyperpigmentation, hypertrichosis, deepening of the superior eyelid sulcus, and loss of periorbital fat are evident.

(Courtesy of Chandrasekharan Krishnan, MD.)

The development or exacerbation of preexisting cystoid macular edema (CME) can occur in certain predisposed eyes (ie, aphakic eyes, pseudophakic eyes with open posterior capsules, and eyes with uveitis). Reactivation of herpetic keratitis has been reported. Nongranulomatous anterior uveitis may occur as an idiosyncratic reaction in approximately 1% of patients.

• Camras CB, Alm A, Watson P, Stjernschantz J. Latanoprost, a prostaglandin analog, for glaucoma therapy. Efficacy and safety after 1 year of treatment in 198 patients. Latanoprost Study Groups. Ophthalmology. 1996;103(11):1916–1924.

• Weinreb RN, Ong T, Scassellati Sforzolini B, et al. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015;99(6):738–745.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.