Bimatoprost ophthalmic solution 0.03% is the only FDA-approved product to safely and effectively enhance the growth of a patient’s own eyelashes. Bimatoprost is a synthetic prostamide, or prostaglandin ethanolamide, analog approved in 2001 for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension (Lumigan package insert, Allergan, Inc., 2006). In one clinical trial, when administered as an eye drop for the treatment of glaucoma, eyelash growth was noted in 42.6% of patients treated with bimatoprost once daily for a year [21]. Although such growth was recorded as an adverse event, the potential aesthetic benefits of eyelash growth were recognized and led to the development and testing of bimatoprost as a product designed to increase eyelash prominence. When prescribed to enhance eyelash prominence, bimatoprost is accompanied by sterile, single-use-per-eye applicators and should be applied once daily to the skin of the upper eyelid margin at the base of the eyelashes (Latisse package insert, Allergan, Inc., 2008).
The safety and efficacy of once-daily bimatoprost 0.03% solution in increasing overall eyelash prominence following dermal administration to the upper-eyelid margins was evaluated in a recent multicenter, double-blinded, randomized, vehicle-controlled, parallel study of 278 adult patients [22]. Starting at 8 weeks of treatment, bimatoprost was associated with significantly greater increases in overall eyelash prominence than vehicle as measured by at least a one-grade increase on the four-grade Global Eyelash Assessment (GEA) scale. These changes were sustained throughout the remainder of the treatment period (16 weeks) and, at week 16, 78.1% of subjects treated with bimatoprost exhibited at least a one-grade increase from baseline in GEA score compared with 18.4% of patients treated with vehicle (P < 0.0001) (Fig. 2). Improvements in GEA scores continued to favor bimatoprost 4 weeks after discontinuation of treatment (i.e., the post-treatment visit at week 20). In the same study, efficacy was assessed by digital image analysis of superior-view eyelash photographs taken with standardized equipment and after uniform subject preparation at all visits. As assessed by such analysis, at week 16 bimatoprost treatment was associated with a mean 25% increase in eyelash length vs. 2% for vehicle, a mean 106% increase in eyelash thickness vs. 12% for vehicle, and a mean 18% increase in eyelash darkening vs. 3% for vehicle (Fig. 3). Subjects treated with bimatoprost for eyelash growth also reported feeling significantly more satisfied with their eyelashes, more confident in their looks, more attractive, more professional, and more satisfied with their daily routine than those subjects receiving vehicle as assessed by patient-reported outcome questionnaires.
Although the mechanism by which bimatoprost enhances eyelash growth has not been fully elucidated, it is believed to increase the percentage of lash follicles in and the duration of anagen (Fig. 1b) (Latisse package insert, Allergan, Inc., 2008). Bimatoprost also appears capable of stimulating melanogenesis [23], which likely explains the changes in the pigmentation of eyelashes observed with use. The duration of the effect of bimatoprost on eyelashes is not fully known and has not been evaluated beyond 4 weeks post-treatment. Furthermore, the ability of bimatoprost to affect the growth of eyelashes in patients with systemic diseases or eyelash loss has not been evaluated.
The safety of bimatoprost, applied either dermally or as an eye drop, has been demonstrated in numerous trials [21, 24]. When applied as an eye drop (i.e., for the treatment of ocular hypertension), bimatoprost was generally well tolerated with long-term use for up to 4 years [24]. Other than eyelash growth, the most common adverse events reported when bimatoprost is instilled into the eye include conjunctival hyperemia, eye pruritus, eye dryness, a burning sensation in the eye, eyelid pigmentation, foreign body sensation, eye pain, and visual disturbance [21, 24; Lumigan package insert, Allergan, Inc., 2006]. Although rare, bimatoprost when applied as an eye drop has also been associated with increases in iris pigmentation, which are generally thought to be permanent [25]; Lumigan package insert, Allergan, Inc., 2006]. While iris pigmentation was not seen in the controlled clinical studies with dermal application for eyelash growth, there have been a small number of post-marketing reports of iris pigmentation following use of bimatoprost for eyelash growth (data on file, Allergan Medical Affairs, June 2010). Post-marketing reports are often incomplete and difficult to evaluate on an individual basis. However, to date there have been no identified trends of risk factors reported in these small numbers of cases. Patients should be advised of the small potential for increased brown iris pigmentation which is likely to be permanent. Infection following application is also a possibility and should be limited by following the package insert instructions for application with daily single-dose applicators for each eye, which are provided with each package.
Although clinical experience regarding the safety of bimatoprost 0.03% applied dermally is limited, available data suggest that the safety profile may be even more favorable than that described above for intraocular administration. In the pivotal trial, the most common adverse events associated with bimatoprost use were eye pruritus, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and erythema of the eyelid, all occurring in fewer than 4% of patients (Latisse package insert, Allergan, Inc., 2008). Conjunctival hyperemia was the only specific event reported at a significantly higher rate by subjects receiving bimatoprost (3.6%) than those receiving vehicle (0%) (P = 0.03) [22]. For comparison, in a 3-month trial of once-daily bimatoprost treatment for glaucoma or ocular hypertension (i.e., the drug was instilled as an eye drop), the incidence of treatment-related conjunctival hyperemia and eye pruritus was approximately 46 and 9%, respectively [26]. Furthermore, dermal application of bimatoprost was not associated with iridal pigmentation or clinically meaningful changes in intraocular pressure [22; Latisse package insert, Allergan, Inc., 2008]. Differences in safety profiles of bimatoprost by route of administration may be partially explained in that a single application of bimatoprost 0.03% to the upper-eyelid margin using the provided applicator delivers approximately 5% of the dose delivered for the treatment of glaucoma (Allergan, Inc., unpublished data). Moreover, when applied to the upper-eyelid margin, subsequent absorption of the active drug into ocular tissues is expected to be minimal due to the barrier function of the skin and the small surface area to which the dose is applied.
The ability of prostaglandin analogs to increase eyelash growth does not appear limited to bimatoprost. Published reports describe latanoprost and travoprost, both prostaglandin analogs used to treat ocular hypertension, as being associated with eyelash changes, including increases in length and darkness [3, 5, 13, 27–29]. Studies evaluating the clinical efficacy of bimatoprost versus latanoprost for the treatment of ocular hypertension suggest that the side effect of increased eyelash growth is more common with bimatoprost [28]. However, these results are not necessarily comparable to those when these drugs are applied to the upper-eyelid margin, which have not been evaluated in any head-to-head studies. In addition, studies in which increased eyelash growth is recorded as an adverse event typically fail to quantify the changes using objective measures.
While other prostaglandin analogs appear capable of influencing eyelash growth, these products are not FDA-approved for the treatment of hypotrichosis. Their efficacy when applied to the upper-eyelid margins has not been fully studied in clinical trials. Moreover, the safety of these drugs when applied dermally has not been fully evaluated.