columbia contributions

Eyelash Hypertrichosis in a Patient Treated With Topical Latanoprost Bruce E. Strober, MD, PhD, New York, New York Seth Potash, MD, New York, New York Marc E. Grossman, MD, New York, New York

We describe a female patient with a history of pri- dal color believed to be secondary to increased mary open-angle glaucoma who, following treatment melanin production in the melanocytes of the iris with topical latanoprost, a synthetic prostaglandin stroma.4 We report the case of a patient who displayed

F2 analog, developed hypertrichosis of the eye- eyelash hypertrichosis a more recently recognized side lashes. Hypertrichosis, a recently described side effect of latanoprost therapy. The occurrence of effect of latanoprost—together with iridal pigmenta- increased local eyelash growth and pigmentation in tion—represents a potentially permanent cosmetic patients treated with latanoprost is a novel and side effect associated with the use of this highly unexpected side effect of PGF2. effective intraocular pressure–lowering agent. The molecular mechanism underlying latanoprost- Case Report induced hypertrichosis is unknown. A 72-year-old white female with an 8-year history of primary open-angle glaucoma developed progressive

Latanoprost is a topically applied prostaglandin F2 visual field loss and glaucomatous optic nerve cup- (PGF2) analog recently shown to be highly effective ping with uncontrollable IOP, despite maximally in the management of chronic open-angle glaucoma.1 tolerated medical therapy and previous argon laser Latanoprost reduces intraocular pressure (IOP) by trabeculoplasty in both eyes. The patient underwent increasing uveoscleral outflow. Unlike the action of trabeculectomy in the left eye in July 1996, which re- traditional ocular hypotensive agents such as timolol, sulted in such significant improvement in IOP that latanoprost does not affect the production of aqueous topical therapy in that eye was discontinued. humor.2 The advantages of latanoprost include not Though the patient’s right optic nerve showed ev- only its highly effective ocular hypotensive effect, idence of only minimal glaucomatous damage, the IOP which is superior to that of timolol,1 but also its very in that eye was elevated to an unacceptable level, de- favorable side effect profile. More important—and in spite a regimen of levobunolol 0.5%, pilocarpine 4%, contrast to timolol—topical latanoprost lacks any de- and dorzolamide 2%. Latanoprost 0.002% was added tectable systemic side effects because of both its lower to her therapeutic regimen with modest improve- once-per-day dosing and very short pharmocologic ment. Within a few months, the patient noted that half-life in the circulation (<20 minutes).3 Initial the eyelashes of both eyelids had become longer, phase III studies on latanoprost revealed local ocular thicker, and more numerous. side effects, such as superficial punctate keratopathy, Further elevation of the IOP in her right eye over conjunctival hyperemia, and iridal color change (also the next few months necessitated a trabeculectomy. called prostaglandin-induced iridal pigmentation [PIIP]).1 However, the hypertrichosis persisted even after all PIIP occurs in 11% to 23% of patients using la- topical glaucoma therapy was discontinued. In addi- tanoprost and represents a permanent alteration in iri- tion, the patient reported new vellus hair growth on her right earlobe. Dr. Strober is from the Department of Medicine, New York University School of Medicine, New York. Dr. Potash is from the Comment Department of Opthalmology, White Plains Hospital Center, New Since latanoprost’s approval as a standard ocular York. Dr. Grossman is from the Department of Dermatology, hypotensive agent, hypertrichosis and increased pig- College of Physicians and Surgeons, Columbia Presbyterian Medical Center, New York, New York. mentation of the eyelashes have been noted in a series Reprints: Marc E. Grossman, MD, 12 Greenridge Ave, Suite 403, of patients with glaucoma who were treated with top- White Plains, NY 10605. ical latanoprost. These patients exhibited an increased

VOLUME 67, FEBRUARY 2001 109 EYELASH HYPERTRICHOSIS

number of eyelashes, with some individuals displaying FP receptor, and thus would represent the putative additional rows of eyelashes in both upper and lower targets of latanoprost-induced hypertrichosis and hy- eyelids of the treated eyes. Latanoprost-treated eyes perpigmentation. The mechanism by which la- displayed the new growth of lashlike hair in areas ad- tanoprost initiates increased eyelash pigmentation jacent to the region of normal eyelash distribution. may be similar to the augmented melanogenesis as- Furthermore, latanoprost therapy appeared to in- sociated with PIIP.3 crease eyelash pigmentation, length, and thickness.5 Further study of latanoprost may reveal cellular and 6 Wand reported that treatment with unilateral topi- biochemical effects of PGF2 within the eyelash hair fol- cal latanoprost 0.005% to the left eye of a 65-year- licle that closely resemble this prostanoid’s influence on old woman with open-angle glaucoma resulted in cells in culture. Additionally, chronic treatment with la- thicker, darker, and more numerous eyelashes limited tanoprost, when administered either locally or systemi- to the treated eye. Subsequent treatment of the right cally, perhaps affects the behavior of cells within the hair eye induced similar eyelash pigmentary changes over follicles found at other body sites. This effect of la- an 8-week period.6 tanoprost may provide an additional tool for further un- We report the development of hypertrichosis in an derstanding of both hair growth and pigmentation and older patient with open-angle glaucoma who received the biology of cellular proliferation and differentiation. topical latanoprost to only one eye but increased eye- lash growth bilaterally. We also observed increased REFERENCES vellus hair growth on the right earlobe. Both bilateral 1. Alm A, Camras CB, Watson PG. Phase III latanoprost stud- hypertrichosis in the setting of the unilateral treat- ies in Scandinavia, the United Kingdom and the United ment and increased hair growth on the earlobe are States. Surv Ophthalmol. 1997;41(suppl 2):S105-S110. somewhat perplexing, implying that either systemic 2. Toris CB, Yablonski ME, Camras CB, et al. Mechanism of absorption of latanoprost occurs, which induces hair the ocular hypotensive effect of latanoprost and the main- growth in other sites, or the possibility that the pa- tenance of normal blood-aqueous barrier function. Surv tient unknowingly applied the drug topically to these Ophthalmol. 1997;41(suppl 2):S69-S75. other sites. An increase in pigmentation of the eye- 3. Bito LAZ. Prostaglandins: a new approach to glaucoma lashes was not seen, but such an effect, much like PIIP, management with a new, intriguing side effect. Surv Oph- may be restricted to a minority of treated individuals. thalmol. 1997;41(suppl 2):S1-S14. The prostanoid family of molecules, including 4. Wistrand PJ, Stjenschantz J, Olsson K. The incidence and prostaglandins D2,E2, F2, and I2 and thromboxane time-course of latanoprost-induced iridial pigmentation as A2 (TXA2), functions as either autocrine or paracrine a function of eye color. Surv Ophthalmol. 1997;41(suppl factors with diverse biological activities.7 Only cells 2):S129-S138. that bear prostanoid receptors, designated DP, EP, FP, 5. Johnstone MA. Hypertrichosis and increased pigmentation IP, and TP, are responsive to a given prostanoid mol- of eyelashes and adjacent hair in the region of the ipsilat- ecule. The receptors, recently cloned and sequenced, eral eyelids of patients treated with unilateral topical la- belong to the family of G protein-coupled cell sur- tanoprost. Am J Ophthalmol. 1997;124:544-547. face receptors. Interaction between a protanoid and 6. Wand M. Latanoprost and hyperpigmentation of eyelashes. its receptor initiates an intracellular signaling re- Arch Ophthalmol. 1997;115:1206-1208. sponse, characterized by an increase in the formation 7. Campbell WB. Lipid-derived autacoids: eicosanoids and of diacylglycerol and inositol trisphosphate, with both platelet-activating factor. In: Gilman GG, Limbird LE, subsequent activation of protein kinase C and mobi- Molinoff PB, et al, eds. Goodman & Gilman’s The Pharma- lization of intracellular calcium.8 cological Basis of Therapeutics. 9th ed. New York, NY: The FP receptor to which latanoprost binds9 can McGraw-Hill; 1995:601-616. be shown by immunohistochemistry and in situ 8. Woodward DF, Regan JW, Lake S, et al. The molecular bi- hybridization to be expressed in all ocular tissues, ology and ocular distribution of prostanoid receptors. Surv including corneal epithelium, pigmented and unpig- Ophthalmol. 1997;41(suppl 2):S15-S21. mented epithelial cells, iris, retina, optic nerve, and 9. Abramovitz M, Boie Y, Nguyen T, et al. Cloning and ex- lens epithelial cells.8 Examination of the eyelash hair pression of a cDNA for the human prostanoid FP receptor. follicles reveals a population of cells that express the J Biol Chem. 1994;269:2632-2636.

110 CUTIS®