Background

Hair growth occurs in a cyclic phase. Each hair and follicle undergoes repeated cycles of active growth followed by periods of rest. At any given time the hair follicle can be found in one of three phases: anagen, the active growth period; catagen, the intermediate stage; and telogen, or the resting phase. The complex neural, vascular, hormonal and environmental factors that govern this cycle are too complex for the intended purposes of this review. It is undeniable however that any arrest, stimulation or alteration of this delicate balance can result in poliosis, trichiasis, hypertrichosis and alopecia.

Prostaglandin analogs have become a cornerstone of glaucoma therapy. The ability of this class of glaucoma medications to alter the eyelashes has been widely reported in the literature. Increased length, thickness, pigmentation and even number have been reported. One recent report involved a case of unilateral trichiasis, or misdirected eyelashes, associated with the monocular use of topical prostaglandins.¹ Poliosis, or whitening of the eyelashes, was recently reported by a group in Australia as a bilateral side effect in seven patients undergoing treatment for primary open angle glaucoma with topical prostaglandin F2 alpha analogs.

Hypertrichosis, or increased lash length, pigmentation or thickness is a relatively common side effect of prostaglandin use. Latanoprost was shown in one study to produce hypertrichosis with a higher incidence in the female population than male.³ As alluded to earlier, this side effect did not have a particularly deleterious psychological effect on their female patients. In this study, this potentially permanent side effect showed an overall incidence rate of no more than 3 percent.

The amount of time before the onset of hypertrichosis is variable. Patient factors such as genetics, compliance and amount of solution being administered all play a role in the onset of clinically observable signs. One group found a 0 percent incidence of eyelash change at one month, 33 percent at three months and 46.2 percent at 12 months. No significant relationship between eyelash changes and iris hyperpigmentation was noted.⁴ Bimatoprost was shown to induce hypertrichosis and increased pigmentation of the vellus hairs in the malar region after two months of unilateral therapy.⁵

The mechanisms of hypertrichosis and latanoprost were studied in laboratory mice and the stump-tailed macaque. The increase in number of lashes is related to latanoprost's ability to stimulate anagen, or the growth phase, from follicles that are in the telogen or resting phase, while inducing hypertrophic changes in the involved hair follicles. The increased length of lashes is due to latanoprost's ability to prolong the anagen phase of the hair cycle.⁶

Presumably, if a patient is to continue prostaglandin therapy indefinitely, the induced hypertrichosis would be permanent. However, it has been reported that cessation of prostaglandin therapy and associated increased eyelash growth is indeed reversible.^5,7 A patient receiving unilateral latanoprost therapy underwent trabeculectomy surgery and subsequent cessation of the latanoprost. Within eight months, the abnormal eyelashes had disappeared.⁷ In patients suffering from alopecia areata, latanoprost was shown to reverse the alopecia and stimulate hair growth of the patient's eyelashes.^6,8

Alopecia areata is a disease with hair loss of the scalp or any hair-bearing surface. Hair loss can manifest itself on the scalp (alopecia totalis) or on the entire body (alopecia universalis.)⁹ It has been proposed that alopecia is autoimmune in nature and targeted at specific hair follicles. Drug-induced alopecia, more specifically related to topical glaucoma medications, has rarely been reported. A definitive link between systemic beta-blockers and alopecia has been well-documented. ^10,11

Case Report: Topical Beta-Blocker and Alopecia

A 63-year-old Caucasian male had been treated for primary open angle glaucoma for nine years, using only topical beta blockers since diagnosis. Initially Timoptic XE 0.5% (timolol maleate) was used for six years, but due to insurance reimbursement reasons, generic timolol maleate 0.5% gel-forming solution was substituted. The medication was used once daily in both eyes for two years prior to initial presentation at our office. He was not using any other systemic or topical medications. A review of systems was remarkable for a six-month history of alopecia. Psychologically the patient was emotionally distressed. He stated that he "looked to be about 90 years of age" instead of his actual age. Initially his hair loss was concentrated on the scalp with loss of lashes and eyebrows (alopecia totalis). However, over the subsequent six months, the hair loss progressed with complete scalp, facial, axial, pectoral and pubic alopecia (alopecia universalis). The patient denied any other constitutional symptoms and had recently undergone extensive laboratory testing of blood, thyroid and liver function in an effort to determine the etiology of the alopecia.  All systems testing

proved negative. Best corrected visual acuity was 20/20 OD and 20/70 OS. A trace afferent pupillary defect was noted OS. Anterior segment findings were significant for madarosis or loss of lashes OU. Intraocular pressures were 15 and 16 mm Hg respectively. The treatment plan was to discontinue the timolol in order to establish a baseline pretreatment intraocular pressure and to determine if there was a causative relationship to the alopecia. The patient returned in one month and reported a modest increase in hair growth. Within six months of cessation of the medication the patient reported full regrowth of all body and scalp hair, as well as an improved quality of life.—W.M, D.G