Bimatoprost in the treatment of eyelash hypotrichosis

Abstract

Eyelashes hypotrichosis is a condition indicated by an inadequate amount of eyelashes. Hypertrichosis of eyelashes, characterized by excessive eyelash growth, is a regular phenomenon associated with ophthalmic prostaglandin and prostamide analogs. Recently, the US Food and Drug Administration approved Latisse((R)) (bimatoprost 0.03% solution), identical to the ophthalmic solution for glaucoma treatment, for increasing eyelash length, thickness and darkness in patients with hypotrichosis of the eyelashes. When prostaglandin and prostamide analogs interact with the prostanoid receptors in the hair follicle, this most likely stimulates the resting follicles (telogen phase) to growing follicles (anagen phase). Prostaglandin and prostamide analogs may also prolong the anagen phase of eyelashes, leading to an increase of eyelash length. Although bimatoprost is effective in promoting increased growth of healthy eyelashes and adnexal hairs, its effectiveness in patients with eyelash alopecia areata is debatable and its protective effect is not yet studied in patients with eyelash loss secondary to radiation or chemotherapy. Bimatoprost is generally safe when applied to the base of the eyelashes at the lid margin with minimum side effects. However, other ocular or systemic side effects associated with ophthalmic prostaglandin and prostamide analogs may occur when instilled on the surface of the eye, and patients must be informed and monitored.

Full text

© 2010 Law, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.
Clinical Ophthalmology 2010:4 349–358
Clinical Ophthalmology Dovepress
submit your manuscript | www.dovepress.com
Dovepress
349
R E V I E W
open access to scientific and medical research
Open Access Full Text Article
Bimatoprost in the treatment of eyelash
hypotrichosis
Simon K Law
Jules Stein Eye Institute, University
of California, Los Angeles,
California, USA
Correspondence: Simon K Law
100 Stein Plaza #2-235, Jules Stein Eye
Institute, Los Angeles, CA 90095, USA
Tel +1 (310) 794-1477
Fax +1 (310) 206-7773
Email law@jsei.ucla.edu
Abstract: Eyelashes hypotrichosis is a condition indicated by an inadequate amount of
eyelashes. Hypertrichosis of eyelashes, characterized by excessive eyelash growth, is a regular
phenomenon associated with ophthalmic prostaglandin and prostamide analogs. Recently, the
US Food and Drug Administration approved Latisse
®
(bimatoprost 0.03% solution), identical
to the ophthalmic solution for glaucoma treatment, for increasing eyelash length, thickness and
darkness in patients with hypotrichosis of the eyelashes. When prostaglandin and prostamide
analogs interact with the prostanoid receptors in the hair follicle, this most likely stimulates
the resting follicles (telogen phase) to growing follicles (anagen phase). Prostaglandin and
prostamide analogs may also prolong the anagen phase of eyelashes, leading to an increase of
eyelash length. Although bimatoprost is effective in promoting increased growth of healthy
eyelashes and adnexal hairs, its effectiveness in patients with eyelash alopecia areata is debatable
and its protective effect is not yet studied in patients with eyelash loss secondary to radiation or
chemotherapy. Bimatoprost is generally safe when applied to the base of the eyelashes at the lid
margin with minimum side effects. However, other ocular or systemic side effects associated
with ophthalmic prostaglandin and prostamide analogs may occur when instilled on the surface
of the eye, and patients must be informed and monitored.
Keywords: bimatoprost, Latisse, prostaglandin, prostamide, eyelash, hypotrichosis
Introduction
Hypotrichosis is characterized by a less than normal amount of hair, and eyelashes
hypotrichosis is the term for an inadequate amount of eyelashes. Eyelashes provide
a natural protective barrier for the eyes from sunshine, wind, foreign bodies, and
perspiration. They perform a similar function to the whiskers on a cat or a mouse.
They are sensitive to the touch and provide a warning when an object is near the eye,
which in turn prompts the eye to close reflexively.
1
In addition to the protective purpose of the eyelash, a more contemporary goal for
eyelash length and thickness in modern humans is cosmetic attraction. Eyelashes frame
the eyes together with the eyebrows, hairline, cheekbones, nose, lips and chin to create a
facial appearance that is unique to every individual. The absence of eyelashes removes
one of the salient anatomical features associated with a normal facial appearance.
1
Long
eyelashes are also considered a sign of femininity and beauty in most if not all cultures.
Causes of eyelashes hypotrichosis are many, including hereditary, aging,
chemotherapy, other medical treatment and unknown causes. Physical trauma
involving the face, eye surgery and trichotillomania may also cause thin or absent
lash growth.
2,3
Number of times this article has been viewed
This article was published in the following Dove Press journal:
Clinical Ophthalmology
13 April 2010

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
350
Law
Since the introduction of latanoprost in 1996 as an
ocular hypotensive agent for the treatment of glaucoma,
hypertrichosis of eyelashes has been reported as a regular
phenomenon associated with ophthalmic prostaglandin and
prostamide analogs.
4,5
When compared to latanoprost in
clinical study, ophthalmic bimatoprost 0.03% was found
to have an even higher occurrence of eyelash growth.
6–9
Recently, Latisse
®
(Allergan Inc. Irvine, CA) which is
bimatoprost 0.03% solution and identical to the ophthalmic
solution for glaucoma treatment, was approved by the US
Food and Drug Administration (FDA) for increasing eyelash
length, thickness and darkness in patients with hypotrichosis
of the eyelashes. In this article, bimatoprost is reviewed
in terms of its pharmacology, efficacy, and safety in the
treatment of eyelash hypotrichosis. Although this review
primarily focuses on bimatoprost, it is necessary to discuss
the effects of other prostaglandin analogs on eyelashes,
particularly latanoprost, which has been more extensively
studied in hypertrichosis of eyelashes. Latanoprost and
bimatoprost also share many similarities both structurally
and pharmacologically.
Pharmacology
Human eyelash characteristics
Human have 90 to 160 eyelashes in the upper eyelid and 75
to 80 in the lower eyelid, with great variation of length.
10,11
The lashes typically originate from the anterior lamella of
the eyelid where they lie on the tarsal plate. They grow in
imperfect rows of 5 to 6 in the upper lid and 3 to 4 in the
lower lid in Caucasians.
12,13
An eyelash is terminal hair, which
is coarse, medullated, long and pigmented. In comparison,
vellus hair, which is often found on a woman’s face, is soft,
unmedullated, short and non-pigmented. Eyelashes have the
widest diameter of body hairs and are the most pigmented
of the terminal hairs.
14
Hair follicles have a unique cyclical behavior pattern and
the entire cycle varies in duration depending on the location
in the body. Each human eyelash lives an average of 3 to
6 months.
13,15
The growth phase (anagen) of the eyelash hair
follicle and eyelash lasts for approximately 30 days. At the end
of the eyelash growth period, a brief transition stage (catagen)
of 15 days follows, with shortening of the hair follicle.
Finally, the follicle enters a resting phase (telogen) of about
100 days, leading to the detachment of the eyelash.
10,13,16–18
The proportion of follicles in telogen is normally higher in
eyelashes than scalp hairs. One study estimated 59% to 85%
of eyelash follicles are in telogen phase, depending on whether
they are on the upper or lower lid.
18
The length of an eyelash can vary greatly, from 8 to
12 mm in the upper lid and from 6 to 8 mm in the lower lid,
and depends on the ethnicity of the individual.
10,11
Eyelash
follicle growth rate is also quite variable, with an average of
0.12 to 0.14 mm daily.
11,13
All eyelashes are characterized by
a tendency to bend from the bulb to the top of the shaft.
13
The
degree of curvature depends on ethnic origin.
11
Interestingly,
eyelashes do not turn grey with aging, or only at a very late
stage.
10
Several factors are involved with hair follicle growth
and cycling but their effects on eyelash growth are unclear.
Androgens are the principal hormones that control sexual
hair growth by receptors localized in the dermal papilla, but
eyelashes do not seem to be as sensitive.
19,20
Retinoic acid
derivatives affect the hair growth cycle in mice by increasing
the length of the anagen phase, and insulin-like growth factor-
I slows the hair cycle entry in the catagen phase. Growth
hormone, insulin, glycocorticoids, and prolactin are also
implicated, but there is no evidence to support an involvement
of these hormones in eyelash growth.
17
Prostamides metabolism
Bimatoprost is a synthetic product initially designed
pharmacologically to reduce the intraocular pressure (IOP)
for the treatment of glaucoma. It is structurally similar
to the other prostaglandin F
2α
(PGF
2α
) analogs, includ-
ing latanoprost, travoprost and unoprostone, but has an
ethyl amide instead of an isopropyl ester at the C-1 car-
bon of the alpha chain. Bimatoprost has been proposed
to be similar to a class of naturally occurring fatty acid
amides otherwise known as “prostamides” (prostaglandin
ethanolamides).
21,22
Prostamides are recently identif ied as a unique
class of compounds that are formed from anandamide
catalyzed by cyclooxygenase-2 (COX-2). Anandamide
is one of the naturally occurring mammalian endogenous
cannabis-like ligands (endocannabinoids) derived from
arachidonic acid.
The biosynthesis of anandamide consists of two steps of
enzymatic reactions: (1) formation of the membrane glyceropho-
spholipid precursor, N-arachidonoylphospharidylethanolamide
(NArPE), by the transfer of a fatty acyl chain from the sn-1
position of glycerophospholipids to the amino group of pho
sphatidylethanolamine, (2) enzymatic hydrolysis of NArPE
catalyzed by a N-acylphophatidylethanolamides selec-
tive phospholipase D (NAPE-PLD) to form anandamide.
23
After synthesis, anandamide is rapidly inactivated via a
tightly controlled series of events involving sequestration

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
351
Bimatoprost for eyelash hypotrichosis
by cells and enzymatic hydrolysis of its amide bond to
arachidonic acid and ethanolamide.
24
With the presence of an
arachidonate moiety in their chemical structure, anandamide
and another endocannabinoid, 2-arachidonoylglycerol
(2-AG) are substrates for enzymes of the arachidonate
casade including COX-2, but not COX-1.
25
Similar to the
conversion of arachidonic acids to prostaglandins by COX
and prostaglandins synthase, COX-2 converts anandamide
to the endoperoxide intermediates prostamide G
2
(PMG
2
)
and prostamide H
2
(PMH
2
), which are then converted by
specific prostaglandins synthases to the various prostamides.
26
However, unlike anandamide, prostamides do not possess
cannabimimetic and related activity, and their physiological
actions have not been fully investigated.
Synthetic prostamide analog, bimatoprost, and
prostaglandin F
2α
analogs, such as latanoprost, travoprost
and unoprostone are effective ocular hypotensive agents.
The mechanism of IOP reduction involves secretion of
metalloproteinases by ciliary smooth muscle cells and
remodeling of the extracellular matrix, the resulting
widening of intermuscular spaces, and ultimately an
increase of uveoscleral outflow of aqueous. Although
prostamides are structurally similar to prostaglandins, they
exhibit no meaningful activity at prostanoid receptors.
26
Experimental evidence suggests that prostamides may act
as endogenous ligands at their own receptors (prostamide
receptors). Nevertheless, prostamide activity has not
been demonstrated in the absence of prostanoid receptor
activity.
26
In a recent study, Liang at al identified 6 splicing
variants of prostanoid FP receptor mRNA in human ocular
tissues.
27
Immunoprecipitation analysis further confirmed
that the FP receptor is dimerized with FP receptor variant-4
(altFP4). It appears that the FP-altFP4 heterodimer maintains
responsiveness to PGF
2α
and its analogs and acquires
sensitivity to bimatoprost. It was also found that PGF
2α
and
bimatoprost has a different calcium mobilization profile.
PGF
2α
elicited a rapid increase in intracellular calcium
followed by a steady state phase. In contrast, bimatoprost
elicited an immediate increase in intracellular calcium
followed by a second phase, and the prostamide antagonist,
AGN211335, selectively and dose-dependently inhibited
the bimatoprost-initiated second phase, but did not block
the action of PGF
2α
. Novel ligand-recognition sites may
have emerged as a result of prostanoid-prostanoid receptor
hererodimerization, and FP-altFP complexes may represent
the underlying basis of bimatoprost pharmacology on IOP.
27
It remains to be proven if this receptor heterodimerization
is also responsible for the action of bimatoprost on eyelash
growth.
Hair growth induced by prostaglandins
and prostamides
Prostaglandins are probably involved in a specific and
complex network in hair growth and differentiation control.
Most of the hair cell types are endowed with prostaglandin
metabolism machinery and are able to produce PGE
2
and/or PGF
2α
; and all prostaglandin receptors are pres-
ent in hair follicle.
28–30
The epithelial part of the hair bulb
was identified by immunohistology and enzyme-linked
immunosorbent assays as the main source of prostaglandin
synthesis and interconversion.
28
Both the F series and
E series prostaglandins may have an effect on hair growth.
31
Inhibitors of prostaglandin endoperoxide synthase such
as indomathacin, ibuprofen, and aspirin were shown to
block prostaglandin synthesis and inhibit hair growth.
32,33
Minoxidil, a known hair growth agent, was reported to
activate activity of purified COX-1, suggesting a positive
role of prostaglandin in hair growth onset.
34
Latanoprost,
a PGF
2α
analog, was found to be able to promote hair
regrowth in C57/B16 mouse model.
35
PGF
2α
and PGE
2
were
reported to have hypertrichotic effects on mice.
36
PGF
2α
and prostaglandin F receptor analogs were able to induce
telogen to anagen transition. Similar effects were found on
stump-tailed macaque.
37
Although prostaglandin metabolism machinery and
prostaglandin receptors are present in hair follicle, the
mechanisms by which prostaglandins and prostamides
trigger eyelash growth are not clear. So far, this area of
research is limited to prostaglandin analogs, or specifically,
latanoprost. It is suggested that hypertrichosis following
administration of prostaglandin analogs is probably a result
of the induction of the anagen phase in telogen phase follicles
of eyelashes.
15
Prostaglandin analogs may also prolong
the anagen phase of eyelashes, leading to an increase of
eyelash length.
38
The increased anagen duration has been
hypothesized to be determined at the initiation of the anagen
phase and is probably controlled by the dermal papilla.
39
In
a study to determine the minimum interval of latanoprost
exposure necessary to cause hypertrichosis of eyelashes,
brief exposure to latanoprost (22 days) was associated
with hypertrichosis similar to those following sustained
exposure. The effect persisted to some degree throughout
the duration of a follow-up interval of 14 months.
15
The
author suggested that a program is initiated to trigger the
anagen phase of the hair cycle in the follicles of eyelashes

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
352
Law
and that this program is able to proceed in the absence of
an ongoing stimulus.
15
Efcacy
Hair growth associated with
prostaglandin and prostamide analogs
Increase of hair growth is regularly associated with ophthalmic
application of different prostaglandin and prostamide analogs
in patients of different ethnicities and age groups. In a series
of 317 patients, Demitsu et al reported latanoprost-induced
hypertrichosis in 77% of patients.
40
In Japanese patients
receiving ophthalmic latanoprost treatment for its ocular
hypotensive effect, increased vellus hair of the lid was
noted in 37.6% and hypertrichosis of eyelashes was noted
in 50.5% of patients.
41
In a study to compare the eyelash
lengthening effect of latanoprost in adults and children
with glaucoma, Elgin et al found that the mean difference
in eyelash lengths at baseline and the sixth month was
0.67 ± 0.09 mm in adults and 0.75 ± 0.25 mm in children.
42
After taking travoprost 0.004% for 12 months, changes in
eyelashes, including increased length, thickness, density, and
color, were reported in 57% of patients.
43
Eyelash growth has
been reported in 12.6% to 35.7% of patients during clinical
trials of bimatoprost 0.03%.
6,44,45
In a 3-month bimatoprost versus latanoprost trial, eyelash
growth was more common in the bimatoprost group (13%
bimatoprost vs. 4% latanoprost).
6
Hypertrichosis appears
to occur earlier during bimatoprost treatment as compared
to latanoprost. This may be because of the possibility
that bimatoprost, unlike latanoprost, does not need to be
converted into an active metabolite in order to extend potent
pharmacological activity. Another possible explanation is that
bimatoprost sensitivity may be conferred by interacting with
FP-altFP heterodimer receptor instead, and the additional
secondary calcium signaling pathway elicited by bimatoprost
may translate into a stronger response of hair growth.
Bimatoprost seems to be able to increase the length of the
eyelash more than latanoprost. In an unpublished randomized
vehicle-controlled, multicenter, clinical trial, 278 patients
were assigned to apply either one drop of bimatoprost
(n = 137) or vehicle only (n = 141) to the upper eyelid margin
at the base of the eyelashes once nightly for 16 weeks.
46
Eyelash prominence, measured primarily by length but also
by thickness and darkness, was rated using a 4-point Global
Eyelash Assessment scale developed by the manufacturer. An
increase in the scale occurred in 78% (1 grade) and 32.8%
(2 grades) on bimatoprost compared to 18% and 1.4% in the
vehicle group, respectively. In the bimatoprost group, eyelash
length increased an average of 1.4 mm (25%) compared to
0.1 mm (2%) in the vehicle group after 16 weeks of treat-
ment.
46
In a prospective study assessing the effect of eyelash
growth in the ipsilateral eyelids of patients treated with
unilateral ophthalmic latanoprost for glaucoma, Johnstone
documented an average increase of 19.5% in eyelash length
with mean treatment duration of 20 weeks.
4
The FDA has approved bimatoprost in a 0.03% solution
for increasing eyelash length, thickness and darkness in
patients with hypotrichosis of the eyelashes. For eyelash
enhancement, one drop of bimatoprost 0.03% solution is
placed on a single-use applicator and applied to the upper
eyelid margin along the roots of the eyelashes once nightly;
a new applicator should be used for each eye.
Characteristics of eyelashes
in the presence of prostaglandin
and prostamide analogs
Hypertrichosis is a regular seen side effect in eyes treated
with ophthalmic prostaglandin and prostamide analogs. In
a prospective study of 43 patients who were unilaterally
treated with latanoprost, researchers identified a number
of characteristics of eyelashes treated with latanoprost.
4
After treatment, eyelashes increased in length, thickness,
and pigmentation. The number of eyelashes also increased
in preexisting lash rows and in areas of transition between
the terminal lashes along the lash line and the vellus hairs
of the skin. These hairs had a more robust appearance, were
longer, thicker, and more heavily pigmented, and arose at a
more acute angle from the skin than in the control eye. The
vellus and intermediate hairs had transformed into terminal
hairs, and produced the appearance of new rows of terminal
eyelashes in the lid margin. The changes in the appearance
of the eyelashes were not limited to the lashes along the
lid margin, but also affected the hairs in the medical and
lateral canthal areas.
4
It is reasonable to expect that all these
changes may be more prominent and obvious in bimatoprost
treatment. The clinically observable eyelashes hypertrichosis
resolved following discontinuation of latanoprost or
bimatoprost.
4,46
Even brief exposure to an ophthalmic prostaglandin analog
appears to be associated with eyelash change. Johnstone
reported that a very brief exposure to latanoprost could
produce a similar effect of eyelash growth as compared
to chronic exposure.
15
However, the hypertrichosis had a
marked irregular pattern of lash curling. The author postulated

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
353
Bimatoprost for eyelash hypotrichosis
that the differences in appearance of eyelashes and pattern
of eyelash growth between brief exposure and sustained
exposure to prostaglandin analogs may be secondary to a
lack of uniform penetration into the hair follicle leading to
asymmetric development of the follicle and inner root sheath.
Some patients were also found to have persistent trichomegaly
up to 14 months following a brief exposure to latanoprost.
15
It
is uncertain if similar characteristics of eyelash growth after
brief exposure may happen to bimatoprost applied to upper
eyelid margin along the roots of the eyelashes.
The hypertrichosis of eyelashes associated with
prostaglandin and prostamide analogs usually occurs together
with darkening of the eyelashes. However, some patients
developed bilateral poliosis after using different ophthalmic
prostaglandin F
2α
analogs for treating primary open angle
glaucoma.
47
Eyelash regrowth in alopecia areata
There are case reports of the successful use of prostaglandin
analogs including latanoprost and bimatoprost in the treatment
of eyelash alopecia areata.
48–51
In an 11-year-old patient who
had alopecia areata with bilateral loss of eyelashes, Mehta et al
reported a successful regrowth of the eyelashes after cutaneous
treatment with latanoprost.
51
Minimal lash growth was noted
on all four lids 4 weeks after application of latanoprost once
daily, and pronounced lash growth was noted in 8 weeks.
Treatment was then altered to once a week and the number of
eyelashes was maintained over the next 6 months.
51
However, lack of efficacy of topical latanoprost and
bimatoprost ophthalmic solutions in promoting eyelash growth
in patients with alopecia areata has also been reported.
52
In a
16-week, randomized, investigator masked, controlled study,
11 patients with alopecia areata and greater than 50% bilateral
eyelash loss were randomized to receive an application of
either latanoprost or bimatoprost to the upper and lower eyelid
margins of one eye only. No appreciable eyelash regrowth was
noted on clinical assessment of eyelid margins or on review
of digital photographs after 16 weeks. Authors questioned
whether ocular instillation of prostaglandin analogs used in
glaucoma treatment may be more effective in stimulating
eyelash growth.
52
In patients without eyelashes, it may be
difficult to keep the cutaneously applied medication on the
lid margin for adequate penetration into the hair follicles. It is
also possible that irreparable damage to the follicle stem cells
in some patients may have led to irreversible hair loss.
In another prospective study of similar design with
bimatoprost 0.03% solution instilled on the eye, 7 patients
(11 patients enrolled, 7 completed the study) with eyelash
alopecia areata with greater than 50% bilateral eyelash
loss received bimatoprost solution once daily to one eye,
while the untreated eye served as the control.
49
Bimatorpost
was found to be ineffective in promoting eyelash growth
in 5 patients with 95% or greater eyelash loss caused by
alopecia areata. However, in 2 patients with 30% and 40%
eyelashes present at baseline, some bilateral eyelash growth
was noted.
49
Another prostaglandin analog, travoprost, has
also been studied in eyelash alopecia areata. Growth of
eyelashes was observed in only 1 out of 3 patients, whereas all
three developed increased pigmentation of the eyelid skin.
53
It seems that prostaglandin or prostamide analogs are only
effective in promoting eyelash regrowth in patients with a
mild form of eyelash alopecia areata.
Eyelashes regrowth in other
causes of hypotrichiasis
Prostaglandin analogs, not prostamide, have been studied
in animal model of hair injury associated with radiation
therapy and chemotherapy. Prostaglandin E
2
(PGE
2
) analog
was shown to have a significant degree of protection against
radiation-induced or doxorubicin-induced alopecia in
mice.
54–56
This protective effect has yet to be studied in human
undergoing radiation therapy or chemotherapy.
Safety
Side effects of ophthalmic prostaglandin
and prostamide analogs
Prostaglandin and prostamide analogs have been associated
with similar systemic and local side effects when administered
topically on the surface of the eye as an ocular hypotensive
agent for glaucoma. When bimatoprost is applied to
the eyelashes and lid margins in very close proximity to the
surface of the eye to promote growth of the eyelash, potential
side effects may occur if the medication is administered
inappropriately on the surface of the eye.
Ophthalmic use of prostaglandin analogs and bimatoprost
is known to be associated with increase iris pigmentation.
Iris darkening may be due to increase of melanin granule
size secondary to an induced heightened melanogenesis.
57,58
Older patients may have more iris color change when topical
prostaglandin is used.
59
Patients with hazel irises that have
mixed coloring are at higher risk of iris darkening, whereas
homogenous blue or brown irises have relatively little
likelihood of getting induced iris darkening.
60
Conjunctival hyperemia is associated with ophthal-
mic prostaglandin analogs and bimatoprost. It is the most

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
354
Law
common adverse event associated with bimatoprost 0.03%
as ophthalmic therapy for glaucoma, which occurred in 42%
to 46% of patients.
6,44,45
Approximately 1% to 4% of patients
discontinued treatment with bimatoprost 0.03% because of
conjunctival hyperemia.
44,45
Comparing with latanoprost,
bimatoprost has significantly more conjunctival hyperemia
and increased eyelash growth reported, but headaches were
more commonly reported with latanoprost.
6–8,61,62
Increase of pigmentation of the periocular skin is seen
with ophthalmic prostaglandin analogs or bimatoprost
therapy. The increase of pigmentation is caused by
increased melanogenesis without melanocyte proliferation
or inflammation.
63
This side effect occurs more frequently
with bimatoprost than latanoprost. Wiping the lid was found
to help decrease the hyperpigmentation when a topical drop
is used.
64
Patients are advised to blot off any solution that
drips from the treated area.
Deepening of the eyelid sulcus, periorbital fat atrophy,
and relative enophthalmos have been reported with
ophthalmic travoprost and bimatoprost used in treatment of
glaucoma.
65–68
In some patients the disparity of periorbital
appearance between the treated eye and the fellow eye
returned to normal after discontinuation of the ophthalmic
prostaglandin analogs or prostamide for a relatively long
interval.
66,68
The exact mechanism is uncertain, but fatty
degeneration and reduced collagen fibers in the levator
complex caused by the prostaglandin or prostamide analogs
have been proposed as a possible mechanism.
66,68
Anterior uveitis has been reported in patients using
ophthalmic prostaglandin or prostamide analogs.
69,70
Anterior
uveitis has been observed in approximately 1% of patients
receiving latanoprost, which resolves with corticosteroid
therapy.
71
Association of latanoprost and uveitis has been
confirmed with a dechallenge and rechallenge method in
two studies.
72,73
Because of the similar efficacy and safety
profile between prostaglandin analogs and bimatoprost,
use of these agents is generally avoided in eyes with active
inflammation.
The association of herpetic simplex viral infection
and prostaglandin analogs and bimatoprost has been
documented.
74,75
Herpes simplex keratitis has been reported
to develop after initiation of latanoprost therapy with
dechallenge and rechallenge method.
76
In another case report,
2 patients developed HSV dermatitis of the periocular skin
after using latanoprost.
77
Latanoprost has been shown to
worsen acute herpetic keratitis in the rabbit eye (New Zealand
white (NZW) rabbit) and increase the risk of recurrences
in latently infected animals.
78
However, in the Induced
Reactivation and Spontaneous Shedding HSV-1/NZW rabbit
latency models, latanoprost was not found to promote ocular
shedding of HSV-1.
79
Use of any topical prostaglandin and
prostamide analogs in patients with a history of ocular
herpetic viral infection should be avoided.
Patients with active or at risk of ocular inflammation or
infection should avoid using bimatoprost to promote eyelash
growth.
Specic safety concerns of bimatoprost
used in treating hypotrichiasis
The most common local side effects reported by subjects in the
clinical trial using bimatoprost as treatment of hypotrichosis
were essentially consistent with those experienced by patients
using bimatoprost as a treatment in glaucoma. The most
common side effects in the clinical trial were eye pruritus,
conjunctival hyperemia, eye irritation, dry eye symptoms,
and erythema and hyperpigmentation of the eyelids.
46
Although increase of the length, thickness and darkness of
eyelashes are desirable effects of bimatoprost in treatment of
hypotrichosis, excessive growth and thickness of the eyelashes
has been reported after using the ophthalmic solution of
bimatoprost 0.03% once daily after 1 to 3 months.
80–82
Patients were reported to have increased hair growth in the
malar regions and external canthal area, excessive growth
of eyelashes and eyebrows, and eyelid hyperpigmentation.
In one patient, whose eyelash and eyebrow growth returned
to normal within 2 months of stopping the ophthalmic
bimatoprost treatment, the medication was restarted with
instruction to thoroughly clean the ophthalmic solution
drippings from her eyes. Nevertheless, after one month of
reinstating the treatment, excessive growth and thickness of
the eyelashes and eyebrow was again observed along with
malar hypertrichosis and eyelid hyperpigmentation.
81
In
addition, lash ptosis and trichiasis secondary to misdirected
eyelash growth have also been reported in association with
latanoprost and travoprost use.
83,84
Ophthalmic bimatoprost 0.03% has been reported to
cause changes in the pigmentation of tissues, including
pigmentation of the periocular skin. Bimatoprost-induced
periocular hyperpigmentation appears between 3 to 6 months,
with hyperpigmentation resolving between 3 to 12 months
upon discontinuation of the drug.
85,86
Increased iris pigmentation has been cited as a side
effect of ophthalmic bimatoprost when used in glaucoma
treatment. However, iris pigmentation changes were not
noted in the clinical trial of bimatoprost used for promoting
eyelash growth. This is probably because the drug was

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
355
Bimatoprost for eyelash hypotrichosis
applied at the lid margin and the root of the eyelashes and
intraocular penetration was therefore minimized.
46
Since
iris pigmentation change, associated with use of ophthalmic
prostaglandin analog, can be permanent, patients who desire
to use bimatoprost to promote eyelash growth must be
informed of this possible side effect.
As mentioned above, there are patients reported to develop
poliosis together with hypertrichosis when
ophthalmic
prostaglandin analog is used in treating glaucoma. Chen
et al reported a series of 7 patients, aged 59 to 78, who
developed poliosis after prostaglandin analogs were used;
including 4 patients on latanoprost, 2 patients on bimatoprost,
and 1 patient on travaprost. Poliosis was noted as earlier as
6 weeks after starting treatment.
47
The affected lashes were
typically interspersed with normally pigmented lashes. The
authors observed on several occasions that the white lashes
were new, implying that the side effect may result from
failure of pigmentation in newly stimulated eyelash growth
or a stimulated growth of previously inconspicuous white
lashes.
47
A possible explanation proposed by the authors is
that during the anagen phase of the hair follicle cell cycle,
genetically predetermined differences in follicular response
results in some dermal papillae secreting mitogens, whereas
others synthesize inhibitory factors and result in varying
response of hair follicles to prostaglandin analogs.
15,47
The commercially available bimatoprost products (both
Latisse
®
and Lumigan
®
[also marketed by Allergan Inc.])
contain benzalkonium chloride as preservative. Ocular
exposure to benzalkonium chloride may have a cytotoxic
effect on human cornea in some patients, and clinically
present as erosion of epithelium, irritation, foreign body
sensation, and other dry eye symptoms.
87
Cystoid macular edema has been reported when
ophthalmic bimatoprost was used in high-risk patients
(aphakia, pseudophakia with ruptured posterior capsule
during surgery, history of uveitis, or retinal inflammatory
or vascular disease). Cystoid macular edema developed in a
patient with glaucoma therapy switched from latanoprost to
bimatoprost 9 months after cataract surgery.
88
Systemic side effects of bimatoprost
Systemic adverse events reported after treatment with
bimatoprost 0.03% have included symptoms of common cold
and upper respiratory tract infection, headaches, abnormal
liver function tests, asthenia and hirsutism. Bimatoprost
0.03% did not have any clinically significant effect on heart
rate or blood pressure in patients with glaucoma or ocular
hypertension in clinical trials.
45,89,90
Since bimatoprost is similar in structure and outcome with
the other topical prostaglandin analogs, it is important to be
aware of the side effects reported with the other prostaglandin
analogs. There is a case report of abdominal cramps
associated with travoprost confirmed by dechallenge and
rechallenge procedures.
91
Other systemic events, each with
an incidence of 1 or 2%, included chest pain/angina, muscle/
joint/back pain and rash/allergic skin reaction. Angina,
arterial hypertension, and tachycardia have been anecdotally
reported following latanoprost use.
92,93
In a randomized study,
headache was more frequent in patients receiving latanoprost
than in those receiving bimatoprost although this difference
did not reach statistical significance.
6
Patients with no prior
history of migraine and/or headache have reported migraine
after receiving latanoprost treatment.
62
Bimatoprost is classified as a category C drug according to
the use-in-pregnancy ratings of the FDA. Category C denotes
that animal reproduction studies have shown an adverse effect
on the fetus, with no adequate and well-controlled studies in
humans. Potential benefits of the drug, however, may warrant
its use in pregnant women despite potential risks. Experience
of ophthalmic prostaglandin analogs and prostamide use
during human pregnancy is limited. In an observation study
of 10 pregnant women exposed to latanoprost during the
first trimester, 9 women delivered normal fetuses with
no malformations. One pregnancy was complicated by
miscarriage, which occurred 2 weeks after treatment was
ended in a 46-year-old woman, primi-gravida, who had
increased reproductive risk related to her advanced age.
94
Conclusion
Latisse
®
is identical to Lumigan
®
with bimatoprost 0.03%
as the active ingredient. Lumigan
®
is marketed for reduction
of elevated IOP in patients with glaucoma, while Latisse
®
is approved for increasing eyelash length, thickness and
darkness in patients with hypotrichosis of the eyelashes. For
eyelash enhancement, 1 drop of bimatoprost 0.03% solution
is placed on a single-use applicator and applied to the upper
eyelid margin along the roots of the eyelashes once nightly;
a new applicator should be used for each eye.
Bimatoprost is a synthetic prostaglandin analog. But unlike
the prostaglandin F
2α
analogs such as latanoprost, travoprost
and unoprostone, bimatoprost has an ethyl amide rather than
an isopropyl ester at the C-1 carbon of the alpha chain, and
can be classified as a prostamide. Prostaglandin or prostamide
analogs are potent agents in the reduction of elevated IOP and
hypertrichosis was found to be a regular side effect. This once
perceived side effect is now a desirable outcome for patients

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
356
Law
who prefer to have longer, thicker, and darker eyelashes.
2
Clinical trial of bimatoprost for eyelash growth conducted by
the manufacturer and other clinical trials using bimatoprost as
a glaucoma therapy have shown that it is an effective agent
in promoting eyelash growth. Bimatoprost most likely works
by interacting with the prostaglandin receptors in the hair
follicle and stimulating the resting follicles (telogen phase)
to growing follicles (anagen phase). Although bimatoprost is
effective in promoting increased growth of healthy eyelashes
and adnexal hairs, its effectiveness in patients with eyelash
alopecia areata is debatable and its protective effect is not yet
studied in patients with eyelash loss secondary to radiation or
chemotherapy. Apparently, an intact hair follicle is necessary
for exogenous prostaglandin analogs to be effective in the
promotion of hair growth.
Bimatoprost is generally safe when applied to the base
of the eyelash at the lid margin with minimum side effects
including ocular or lid irritation, conjunctiva hyperemia and
hyperpigmentaton of the lid. Other ocular or systemic side
effects associated with ophthalmic bimatoprost and other
prostaglandin analogs when instilled on the surface of the eye
should be monitored, and patients must be informed.
Based on the general desire of longer, thicker, and darker
eyelashes as a sign of femininity and beauty in most cultures,
and the high volume of mascara sales, Latisse
®
is expected
to be a popular alternative for those seeking to augment their
lash appearance.
Disclosure
The author has received honoraria from Allergan Inc.
References
1. International society of hair restoration surgery. Eyelash
transplantation: Who, Why and How. http://www.ishrs.org/articles/
eyelash-transplantation. htm Accessed Nov 30, 2009.
2. Woodson SA. Latisse: empirical discovery yields treatment for sparse
eyelashes. Nurs Womens Health. 2009;13:243–248.
3. Pucci N, Novembre E, Lombardi E, et al. Long eyelashes in a case
series of 93 children with vernal keratoconjunctivitis. Pediatrics.
2005;115:1542–1555.
4. Johnstone MA. Hypertrichosis and increased pigmentation of eyelashes
and adjacent hair in the region of the ipsilateral eyelids of patients
treated with unilateral topical latanoprost. Am J Ophthalmol. 1997;124:
544–547.
5. Wand M. Latanoprost and hyperpigmentation of eyelashes. Arch
Ophthalmol. 1997;115:1206–1208.
6. Gandolfi S, Simmons ST, Sturm R, et al. Three-month comparison
of bimatoprost and latanoprost in patients with glaucoma and ocular
hypertension. Adv Ther. 2001;18:110–121.
7. Noecker RS, Dirks MS, Choplin NT, et al; Bimatoprost/Latanoprost
Study Group. A six-month randomized clinical trial comparing the
intraocular pressure-lowering efficacy of bimatoprost and lantanoprost
in patients with ocular hypertension or glaucoma. Am J Ophthalmol.
2003;135:55–63.
8. Parrish RK, Palmberg P, Sheu WP; XLT Study Group. A comparison
of lantaoprost, bimatoprost, and travaprost in patients with elevated
intraocular pressure: a 12-week, randomized, masked-evaluator
multicenter study. Am J Ophthalmol. 2003;135:688–703.
9. Konstas AG, Katsimbris JM, Lallos N, et al. Latanoprost 0.005%
versus bimatoprost 0.03% in primary open-angle glaucoma patients.
Ophthalmology. 2005;112:262–266.
10. Liotet S, Riera M, Nguyen H. Les cils. Physiologie, structure,
pathologie. Arch Ophthalmol. 1977;37:697–708.
11. Na JI, Kwon OS, Kim BK, et al. Ethnic characteristics of eyelashes:
a comparative analysis in Asian and Caucasian females. Br J Dermatol.
2006;155:1170–1176.
12. Montagna W, Ford DM, Histology and cytochemistry of human skin.
3. The eyelid. Arch Dermatol. 1969;100:328–335.
13. Thibaut S, De Becker E, Calsey L, et al. Human eyelash characterization.
Br J Dermatol. 2009 Sep 1. [Epub ahead of print].
14. Bartosová L. Biology of hair growth. Curr Probl Dermatol.
1984;12:1–58.
15. Johnstone MA, Albert DM. Prostaglandin-induced hair growth. Surv
Ophthalmol. 2002;47(Suppl 1):S185–S202.
16. Katz M, Wheeler KE, Radowsky M, Gordon W. Assessment of rate
of hair growth using a simple trichometer. Med Biol Eng Comput.
1979;17:333–336.
17. Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit
development. Endocr Rev. 2000;21:363–392.
18. Elder MJ. Anatomy and physiology of eyelash follicles: relevance to lash
ablation procedures. Ophthal Plast Reconstu Surg. 1997;13:21–25.
19. Bläuer M, Vaalasti A, Pauli SL, Ylikomi T, Joensuu T, Tuohimaa P.
Location of androgen receptor in human skin. J Invest Dermatol.
1991;97:264–268.
20. Randall VA, Hibberts NA, Thornton MJ, et al. The hair follicle:
a paradoxical androgen target organ. Horm Res. 2000;54:243–250.
21. Woodward DF, Krauss AH, Chen J, et al. The pharmacology of bimatoprost
(Lumigan). Surv Ophthalmol. 2001;45 Suppl 4:S337–S345.
22. Woodward DF, Krauss AH, Chen J, et al. Pharmacological
characterization of a novel antiglaucoma agent, Bimatoprost (AGN
192024). J Pharmacol Exp Ther. 2003;305:772–785.
23. Bisogno T. Endogenous cannabinoids: structure and metabolism.
J Neuroendocrinol. 2008;20 Suppl 1:1–9.
24. Alpini G, Demorrow S. Changes in the endocannabinoid system may
give insight into new and effective treatments for cancer. Vitam Horm.
2009;81:469–485.
25. Di Marzo V. Endocannabinoids: synthesis and degradation. Rev Physiol
Biochem Pharmacol. 2006;160:1–24.
26. Woodward DF, Liang Y, Krauss AH. Prostamides (prostaglandin-
ethanolamides) and their pharmacology. Br J Pharmacol. 2008;153:
410–419.
27. Liang Y, Woodward DF, Guzman VM, et al. Identification and
pharmacological characterization of the prostaglandin FP receptor and FP
receptor variant complexes. Br J Pharmacol. 2008;154:1079–1093.
28. Colombe L, Vindios A, Michelet JF, Bernard BA. Prostaglandin
metabolism in human hair follicle. Exp Dermatol. 2007;16:762–769.
29. Colombe L, Michelet JF, Bernard BA. Prostanoid receptors in anagen
human hair follicles. Exp Dermatol. 2008;17:63–72.
30. Torii E, Segi E, Sugimoto Y, et al. Expression of prostaglandin E92
receptor subtypes in mouse hair follicles. Biochem Biophys Res Comm.
2002;290:696–700.
31. Rosenigk HH Jr. New topical agents for hair growth. Clin Dermatol.
1988;6:119–121.
32. Meyer HC. Alopecia associated with ibuprofen. JAMA. 1979:
242:142.
33. Pillans PI, Woods DJ. Drug-associated alopecia. Int J Dermatol.
1995;34:149–158.
34. Michelet JF, Commo S, Billoni N, Mahe YF, Bernard BA. Activation
of ytoprotective prostaglandin synthase-1 by minoxidil as a possible
explanation for its hair growth-stimulating effect. J Invest Dermatol.
1997;108:205–209.

Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
357
Bimatoprost for eyelash hypotrichosis
35. Stjernschantz JW. From PGF (2alpha)-isopropyl ester to lantaoprost:
a review of the development of xalatan: the Proctor Lecture. Invest
Ophthalmol Vis Sci. 2001;42:1134–1145.
36. Sasaki S, Hozumi Y, Kondo S. Influence of prostaglandin F2α and its
analogues on hair regrowth and follicular melanogenesis in a murine
model. Exp Dermatol. 2005;14:323–328.
37. Uno H, Zimbric ML, Albert DM, Stjernschantz J. Effect of latanoprost
on hair growth in the bald scalp of the stump-tailed macaque: a pilot
study. Acta Derm Venereol. 2002;82:7–12.
38. Burnett JW, Harvey VM. Circumscribed palmar or plantar
hypokeratosis: report of two additional cases. J Am Acad Dermatol.
2004;51:843–844.
39. Paus R, Cotsarelis G. The biology of hair follicles. N Engl J Med.
1999;341:491–497.
40. Demitsu T, Manabe M, Harima N, Sugiyama T, Yoneda K,
Yamada N. Hypertrichosis induced by lantanoprost. J Am Acad
Dermatol. 2001;44:721–723.
41. Inouye K, Wakakura M, Inoue J, Matsuo H, Hara T, Tomita G. Adverse
reaction after use of latanoprost in Japanese glaucoma patients. Nippon
Ganka Gakkai Zasshi. 2006;110:581–587.
42. Elgin U, Batman A, Becker N, Iihan B. The comparison of eyelash
lengthening effect of latanoprost therapy in adults and children. Eur J
Ophthalmol. 2006;16:247–250.
43. Netland PA, Landry T, Sullivan EK, et al. Travoprost compared with
latanoprost and timolol in patients with open angle glaucoma or ocular
hypertension. Am J Ophthalmol. 2001;132:472–484.
44. Sherwood M, Brandt J; Bimatoprost Study Groups 1 and 2.
Six-month comparison of bimatoprost once-daily and twice-daily
with timolol twice-daily in patients with elevated intraocular pressure.
Surv Ophthalmol. 2001;45 Suppl 4:S361–S368.
45. Brandt JD, VanDenburgh AM, Chen K, et al. Bimatoprost Study Group.
Comparison of once- or twice-daily bimatoprost with twice-daily timolol
in patients with elevated IOP: a 3-month clinical trial. Ophthalmology.
2001;108:1023–1031.
46. Food and Drug Administration, Division of Anti-infective and
Ophthalmology Products Advisory Committee. Briefing infor-
mation: bimatoprost ophthalmic solution for the treatment of
hypotrichosis of the eyelashes. http://www.fda.gov/ohrms/dockets/
ac/08/briefing/2008-4397b1-03-FDA.pdf. Accessed Nov 30, 2009.
47. Chen CS, Wells J, Craig JE. Topical prostaglandin F2 analog induced
poliosis. Am J Ophthalmol. 2004;137:965–966.
48. Zaheri S. Hughes B. Successful use of bimatoprost in the treatment
of alopecia of the eyelashes. Clin Exp Dermatol. 2009 Nov 19. [Epub
ahead of print].
49. Ochoa BE, Sah D, Wang G, Stamper R, Price VH. Instilled bimatoprost
ophthalmic solution in patients with eyelash alopecia areata. J Am Acad
Dermatol. 2009;61:530–532.
50. Mansberger SL, Cioffi GA. Eyelash formation secondary to latanoprost
treatment in a patient with alopecia. Arch Ophthalmol. 2000;118:
718–719.
51. Mehta JS, Raman J, Gupta N, Thoung D. Cutaneous latanoprost in the
treatment of alopecia areata. Eye. 2003;17:444–446.
52. Roseborough I, Lee H, Chwalek J, Stamper RL, Price VH. J Am Acad
Dermatol. 2009;60:705–706.
53. Feletti F, Vincenzi C, Pazzaglia M, Tosti A. Periocular pigmentation
associated with use of travoprost for the treatment of alopecia areata
of the eyelashes. J Eur Acad Dermatol Venereol. 2007;21:421–423.
54. Geng L, Hanson WR, Malkinson FD. Topical or systemic 16, 16 dm
prostaglandin E2 or WR-2721 (WR-1065) protects mice from alopecia
after fractionated irradiation. Int J Radiat Biol. 1992;61:533–537.
55. Hanson wR, Pelka AE, Nelson AK, Malkinson FD. Subcutaneous or
topical administration of 16, 16 dimethyl prostaglandin E2 protects
from radiation-induced alopecia in mice. Int J Radiat Oncol Biol Phys.
1992;23:333–337.
56. Malkinson FD, Geng L, Hanson WR. Prostaglandins protect against
murine hair injury produced by ionizing radiation or doxorubicin.
J Invest Dermatol. 1993;101:135S–137S.
57. Cracknell KP, Grierson I, Hogg P, Appleton P, Pfeiffer N.
Latanoprost-induced iris darkening: a morphometric study of human
peripheral iridectomies. Exp Eye Res. 2003;77:721–730.
58. Cracknell KP, Farnell DJ, Grierson I. Monte Carlo simulation of
latanoprost induced iris darkening. Comput Methods Programs Biomed.
2007;87:93–103.
59. Arranz-Marquez E, Teus MA. Effect of age on the development of
a latanoprost-induced increase in iris pigmentation. Ophthalmology.
2007;114:1255–1258.
60. Wistrand PJ, Stjernschantz J, Olsson K. The incidence and time-course
of latanoprost-induced iridial pigmentation as a function of eye color.
Surv Ophthalmol. 1997;41(Suppl 2):S129–S138.
61. Stewart WC, Kolker AE, Stewart JA, et al. Conjunctival hyperemia in
healthy subjects after short-term dosing with latanoprost, bimatoprost,
and travoprost. Am J Ophthalmol. 2003;135:314–320.
62. Weston BC. Migraine headache associated with latanoprost. Arch
Ophthalmol. 2001;119:300–301.
63. Kapur R, Osmanovic S, Toyran S, Edward DP. Bimatoprost-induced
periocular skin hyperpigmentation: histopathological study. Arch
Ophthalmol. 2005;123:1541–1546.
64. Centofanti M, Oddone F, Chimenti S, Tanga L, Citarella L, Manni G.
Prevention of dermatologic side effects of bimatoprost 0.03% topical
therapy. Am J Ophthalmol. 2006;142:1059–1060.
65. Peplinski LS, Albiani Smith K. Deepening of lid sulcus from topical
bimatoprost therapy. Optom Vis Sci. 2004;81:574–577.
66. Tappeiner C, Perren B, Iliev ME, Frueh BE, Goldblum D. Orbital
fat atrophy in glaucoma patients treated with topical bimatoprost-
can bimatoprost cause enophthalmos? Klin Monbl Augenheilkd.
2008;225:443–445.
67. Filippopoulos T, Paula JS, Torun N, Hatton MP, Pasquale LR,
Grosskreutz CL. Periorbital changes associated with topical bimatoprost.
Ophthal Plast Reconstr Surg. 2008;24:302–307.
68. Yang HK, Park KH, Kim TW, Kim DM. Deepening of eyelid superior
sulcus during topical travoprost treatment. Jpn J Ophthalmol.
2009;53:176–179.
69. Packer M, Fine IH, Hoffman RS. Bilateral nongranulomatous
anterior uveitis associated with bimatoprost. J Cataract Refract Surg.
2003;29:2242–2243.
70. Parentin F. Granulomatous anterior uveitis associated with bimatoprost:
a case report. Ocul Immunol Inflamm. 2003;11:67–71.
71. Smith SL, Pruitt CA, Sine CS, et al. Latanoprost 0.005% and anterior
segment uveitis. Acta Ophthalmol Scand. 1999;77:668–672.
72. Warwar RE, Bullock JD, Ballal D. Cystoid macular edema and anterior
uveitis associated with latanoprost use. Experience and incidence in a
retrospective review of 94 patients. Ophthalmology. 1998;105:263.
73. Fechtner RD, Khouri AS, Zimmerman TJ, et al. Anterior uveitis
associated with latanoprost. Am J Ophthalmol. 1998;126:37–41.
74. Kroll DM, Schuman JS. Reactivation of herpes simplex virus keratitis
after initiating bimatoprost treatment for glaucoma. Am J Ophthalmol.
2002;133:401–403.
75. Kothari MT, Mehta BK, Asher NS, Kothari KJ. Recurrence of bilateral
herpes simplex virus keratitis following bimatoprost use. Indian
J Ophthalmol. 2006;54:47–48.
76. Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex
keratitis. Am J Ophthalmol. 1999;127:602–604.
77. Morales J, Shihab ZM, Brown SM, et al. Herpes simplex virus dermatitis
in patients using latanoprost. Am J Ophthalmol. 2001;132:114–116.
78. Kaufman HE, Varnell ED, Thompson HW. Latanprost increases
the severity and recurrence of herpetic keratitis in the rabbit.
Am J Ophthalmol. 1999;127:531–536.
79. Gordon YJ, Yates KA, Mah FS, et al. The effects of Xalatan on the
recovery of ocular herpes simplex virus type 1 (HSV-1) in the induced
reactivation and spontaneous shedding rabbit models. J Ocul Pharmacol
Ther. 2003;19:233–245.
80. Hempstead N, Hempstead RW. Unilateral trichomegaly induced
by bimatoprost ophthalmic solution. J Drugs Dermatol. 2004;3:
571–572.

Clinical Ophthalmology
Publish your work in this journal
Submit your manuscript here: http://www.dovepress.com/clinical-ophthalmology-journal
Clinical Ophthalmology is an international, peer-reviewed journal
covering all subspecialties within ophthalmology. Key topics include:
Optometry; Visual science; Pharmacology and drug therapy in eye
diseases; Basic Sciences; Primary and Secondary eye care; Patient
Safety and Quality of Care Improvements. This journal is indexed on
PubMed Central and CAS, and is the official journal of The Society of
Clinical Ophthalmology (SCO). The manuscript management system
is completely online and includes a very quick and fair peer-review
system, which is all easy to use. Visit http://www.dovepress.com/
testimonials.php to read real quotes from published authors.
Dovepress
Clinical Ophthalmology 2010:4
Dovepress
submit your manuscript | www.dovepress.com
Dovepress
358
Law
81. Herane MI, Urbina F. Acquired trichomegaly of the eyelashes, and
hypertrichosis induced by bimatoprost. J Eur Acad Dermatol Venereol.
2004;18:644–645.
82. Hart J. Shafranov G. Hypertrichosis of vellus hairs of the malar
region after unilateral treatment with bimatoprost. Am J Ophthalmol.
2004;137:756–757.
83. Bearden W, Anderson R. Trichiasis associated with prostaglandin
analog use. Ophthal Plast Reconstr Surg. 2004;20(4):320–322.
84. Casson RJ, Selva D. Lash ptosis caused by latanoprost. Am J Ophthalmol.
2005;139:932–933.
85. Doshi M, Edward DP, Osmanovic S. Clinical course of bimatoprost-
induced periocular skin changes in Caucasians. Ophthalmology.
2006;113:1961–1967.
86. Herndon LW, Williams RD, Wand M, Asrani S. Increased periocular
pigmentation with ocular hypotensice lipid use in African Americans.
Am J Ophthalmol. 2003;135:713–715.
87. Baudouin C, Riancho L, Warnet JM, Brignole F. In vitro studies of
antiglaucomatous prostaglandin analogues: travoprost with and without
benzalkonium chloride and preserved latanoprost. Invest Ophthalmol
Vis Sci. 2007;48:4123–4128.
88. Carrillo MM, Nicolela MT. Cystoid macular edema in a low-risk patient
after switching from latanoprost to bimatoprost. Am J Ophthalmol.
2004;137:966–968.
89. Laibovitz RA, VanDenburgh AM, Felix C, et al. Comparison of the
ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy,
and safety evaluation of a novel compound for glaucoma management.
Arch Ophthalmol. 2001;119:994–1000.
90. Dubiner H, Cooke D, Dirks M, et al. Efficacy and safety of bimatoprost
in patients with elevated intraocular pressure: a 30-day comparison with
latanoprost. Surv Ophthalmol. 2001;45(Suppl 4):S353–S360.
91. Lee YC. Abdominal cramp as an adverse effect of travoprost.
Am J Ophthalmol. 2005;139:202–203.
92. Mitra M, Chang B, James T. Drug points. Exacerbation of angina
associated with latanoprost. BMJ. 2001;323:783.
93. Peak AS, Sutton BM. Systemic adverse effects associated with topically
applied latanoprost. Ann Pharmacother. 1998;32:504–505.
94. De Santis M, Lucchese A, Carducci B, et al. Latanoprost exposure in
pregnancy. Am J Ophthalmol. 2004;138:305–306.