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BACKGROUND Many women desire prominent eyelashes. In December 2008, bimatoprost ophthalmic
solution 0.03% was approved for the treatment of hypotrichosis of the eyelashes in the United States.
OBJECTIVE To review eyelash physiology and the proposed mechanisms by which the topical prostamide product bimatoprost enhances eyelash growth.
METHODS AND MATERIALS Clinical and preclinical studies pertaining to the efficacy, safety, and
mechanisms of action of bimatoprost are presented.
RESULTS Treatment with bimatoprost increases the percentage of eyelash follicles in anagen at any
one time. This probably accounts for its ability to lengthen lashes. Bimatoprost-induced stimulation of
melanogenesis appears to result in darker lashes and, at the same time, appears to increase the size of
the dermal papilla and hair bulb, affecting lash thickness and fullness. Such effects, largely demonstrated in animal studies, are consistent with the results of a recent Food and Drug Administration phase
III clinical trial. The favorable safety profile of bimatoprost in human subjects is probably secondary to
the limited exposure of ocular tissues resulting from topical application at the base of the upper lashes.
CONCLUSION By influencing the eyelash hair cycle and follicles, bimatoprost ophthalmic solution
0.03% is a safe and effective means of enhancing eyelash growth.
Dr. Cohen has served as a consultant and clinical trial participant for Allergan, Inc.
he eyes have long been recognized as an important facet of physical beauty.1,2 Male and
female observers have associated enhanced appearance of the eyes of women with significantly greater
attractiveness.3 Beautiful eyes are also associated
with social advantages.1 Long and thick or full eyelashes are a symbol of beauty and femininity in many
cultures, whereas the loss of eyelashes has been associated with a loss of attractiveness and psychosocial distress.46 Women often consider longer,
thicker, fuller eyelashes to be desirable, and greater
growth of ones eyelashes has been described as
having a positive psychological effect.7,8 For thousands of years, women have employed techniques to
enhance the prominence of their eyelashes.9
AboutSkin Dermatology and DermSurgery, Englewood and Lone Tree, Colorado; yDepartment of Dermatology,
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nisms of action by which the prostamide bimatoprost enhances the growth of eyelashes. We will
review preclinical and clinical data regarding the
safety of bimatoprost and its effects on eyelash
growth.
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Figure 2. Eyelash hair cycle representation.19,20,22 Copyright 1999 Massachusetts Medical Society. All rights reserved.
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Scalp
Hair
Upper Eyelashes
48 years
68 years
515%
512 months
12 months
50%
Yes
0.300.40
No
0.15
B100,000
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reverse.10 Unlike their effects on scalp hairs, androgens have no effect on eyelash growth.24
The differences between scalp hair and eyelashes
have important implications for the development
and use of hair growth drugs on these hairs. The
characteristics of the eyelash growth cycle suggest
that treatments that initiate or prolong anagen may
have more immediate, visible effects on eyelashes
than on the nonbalding scalp.
BimatoprostFEyelash Growth in
Glaucoma Trials
Bimatoprost is a synthetic prostamide F2a analog.29
The prostamides and their structural analogs are
structurally, pharmacologically, and functionally
distinct from prostaglandins and prostaglandin
analogs (Figure 3).2931 Bimatoprost ophthalmic
solution 0.03% (Lumigan, Allergan, Inc., Irvine,
CA) was approved in 2001 for the reduction of high
intraocular pressure (IOP) in patients with openangle glaucoma or ocular hypertension.32 It is considered the most efficacious antiglaucoma drug
available,29 and its safety and effectiveness as an
IOP-lowering agent has been established in clinical
trials lasting up to 4 years.33,34
Bimatoprost exerts its effects by stimulating the
prostamide receptor, which is pharmacologically
distinct from F prostanoid (FP) receptors.29,34 Although the existence of the prostamide receptor, an
entity distinct from the FP receptor, has been established via multiple lines of evidence,29,3436 it has
been hypothesized that FP and prostamide receptors
may be messenger ribonucleic acidsplicing variants
of the same gene.29 Although prostaglandin receptors involved in the development and regrowth of the
hair follicle have been identified throughout the hair
follicle, particularly in the dermal papilla outer root
sheath,37,38 it is unknown whether bimatoprost
exerts effects on receptors in these locations. The
ability of bimatoprost to affect eyelash growth and
appearance was first detected in clinical trials of the
drug as an ocular antihypertensive agent. In these
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HO
C2H5
CON
H
HO
OH
Bimatoprost
HO
C2H4OH
CON
H
HO
OH
Prostamide F2
HO
COOH+
HO
OH
Prostamide F2 Acid
Figure 3. Structures of bimatoprost, prostamide F2a, and
prostaglandin F2a acid.31
BimatoprostFMechanism of Action
A series of recent animal (mouse) studies have
revealed that treatment with bimatoprost results in
multiple changes to the hair cycle of eyelashes
(Figure 4) (unpublished data). A 2-week course of
bimatoprost resulted in a greater proportion of follicles in the anagen phase of the hair cycle. A concomitant decrease in the percentage of follicles in
telogen was observed, suggesting that bimatoprost
stimulated the transition from telogen to anagen and
that bimatoprost treatment was associated with
prolonged duration of anagen. Such changes in the
length of anagen probably manifest as observable
increases in eyelash length associated with treatment.
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Figure 5. Percentage of subjects with at least a 1-grade improvement in Global Eyelash Assessment score from baseline.47
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use of mascara.
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Conclusions
With many women wishing to improve the appearance of their eyelashes, bimatoprost ophthalmic solution 0.03% provides a new, safe, and effective
option for growing natural eyelashes, making them
longer, thicker or fuller, and darker. The ability of
bimatoprost to enhance eyelash growth emerged as a
serendipitous side effect when the drug was instilled as an eyedrop to treat glaucoma. Animal
models suggest that bimatoprost stimulates follicles
to remain in the anagen phase longer while shortening the telogen phase of the hair cycle. This
supports the hypothesis that bimatoprost increases
the percentage of eyelashes in anagen and the duration of anagen to result in longer lashes. Bimatoprost
also stimulates melanogenesis and enlarges the
diameter of the hair shaft, accounting for greater
darkness and thickness or fullness of eyelashes,
respectively.
The aesthetic effects of bimatoprost were established in a large controlled clinical trial that demonstrated that the topical application of bimatoprost
0.03% to the upper eyelid is associated with significant growth of a subjects own natural eyelashes
and results in longer, thicker or fuller, and darker
eyelashes within 4 months of treatment. Subjects in
the bimatoprost group also reported significantly
greater increases in satisfaction than those in the
vehicle group. The trial enrolled healthy adults, and
therefore, the ability of bimatoprost to stimulate
growth of eyelashes in cases of trauma or alopecia or
in patients with other relevant medical conditions
has not been fully studied. Future research should
evaluate the effects of bimatoprost on these subgroups.
The safety of bimatoprost for the reduction of IOP
has been well established in clinical trials up to 4
years in length, as well as extended clinical experience totaling an estimated 9 million patient-years of
exposure.33 Topical administration of bimatoprost
0.03% results in lower exposure to the drug than
ocular administration, potentially explaining the low
incidence of side effects with the cutaneous
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Editorial assistance was provided by Health Learning Systems, a part of CommonHealth, Parsippany,
NJ.
References
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