topical bimatoprost is a popular prostaglandin analog used primarily as a powerful ocular hypotensive agent for treatment of glaucoma ( approved in 2001 ) . it is also used cosmetically to induce hypertrichosis , approved by the us food and drug administration in 2008 as latisse ( allergan , inc , irvine , ca , usa ) . however , it may cause complications such as periocular skin hyperpigmentation , intraocular inflammation , and conjunctival hyperemia.1 these mainly affect superficial tissues and , to date , there has been no report on involvement of deeper periocular tissues as far as we are aware . herein , we report an unusual case of periocular muscle atrophy and weakness secondary to unilateral topical bimatoprost use . a 58-year - old chinese female was referred to the oculoplastics services of national university hospital , singapore , for right upper eyelid ptosis of 1.5 years duration and difficulty in closing her right eye . she had a history of bilateral primary angle closure diagnosed in 2003 , for which bilateral laser peripheral iridotomies were performed . she was started on topical latanoprost 0.005% once every night to the right eye , as intraocular pressure ( iop ) was suboptimal . subsequently , she underwent an uneventful right cataract extraction with intraocular lens implantation that same year . her condition remained stable until 2008 when there were progressive defects in her right visual field with increased iop . thus , she was started on topical bimatoprost 0.03% ( lumigan , allergan , inc ) once every night to her right eye . however , she reported an onset of right upper eyelid drooping 2 months after starting treatment . the ptosis did not show any diurnal variability or fatigability , and there was no diplopia . a detailed evaluation by the neuro - ophthalmology team revealed no underlying neurological cause . four months after starting treatment , the treated eye was found to have long eyelashes and ocular pigmentation . subsequently , the patient reported worsening of her right ptosis after 12 months on treatment and was keen for referral to the oculoplastics team . by the time the patient was reviewed by the oculoplastics team in 2010 measurements of the palpebral aperture ( pa ) of her right and left eye were 6 mm and 8 mm , respectively . measurements of marginal reflex distance 1 ( mrd1 ) for her right and left eyes were 0.5 mm and 2 mm , respectively . levator palpebrae function was 8 mm for the right eye and 14 mm for the left eye . lid creases measured 7 mm and 5 mm for the right and left eye , respectively . eventually , the patient underwent a surgical correction of her ptosis with levator muscle advancement in august 2011 . seven months after the operation , her pa measured 9 mm and 8 mm while mrd1 measured 4 mm and 3 mm for the right and left eye , respectively . the pre- and postoperative clinical photos of her eyelids are shown in figures 1 and 2 , respectively . preoperatively , she had clinically significant right ptosis obscuring her visual axis , and right lagophthalmos with orbicularis oculi muscle weakness . topical bimatoprost is highly efficacious and superior to many other anti - glaucoma eye drops.2,3 however , it commonly causes side effects such as ocular hyperemia , periocular and iris pigmentary changes , although these are mostly reversible with cessation of use.4 periorbital lipodystrophy resulting in periorbital hollowing , eyelid retraction , and enophthalmos from chronic use of bimatoprost has also been well - documented.58 upper eyelid sulcus deepening has been shown to occur significantly more frequently ( objectively and subjectively ) with bimatoprost use than with other prostaglandin analogs , namely latanoprost , tafluprost , and unoprostone.9 aihara et al reported an increased incidence of upper eyelid sulcus deepening in patients who were switched from latanoprost to bimatoprost , suggesting that the latter has a more potent effect on periorbital fat tissue.10 the term  prostaglandin - associated periorbitopathy  ( pap ) has been coined to describe the constellation of periorbital soft - tissue changes resulting from the use of topical prostaglandin analogs . the clinical features of pap include upper eyelid ptosis , deepening of the upper eyelid sulcus , involution of dermatochalasis , orbital fat atrophy , mild enophthalmos , flattening of lower eyelid bags , inferior scleral show , and tight orbits.11 these effects can appear after a period of several weeks to several years , and have been reported to be reversible upon cessation of use.11 most of the anatomical changes in pap are thought to be caused by orbital fat atrophy , while dehiscence of levator aponeurosis or mller muscle may account for the upper lid ptosis.11 it has been postulated that upregulation of prostaglandin f2- results in significant anti - adipogenic effect.12 prostaglandin f2- blocks adipogenesis through the activation of mitogen - activated protein kinase , resulting in the inhibitory phosphorylation of peroxisome proliferator - activated receptor - gamma , a nuclear hormone receptor central to adipocyte differentiation.13,14 topical prostaglandin analogs have been shown to downregulate the expression of peroxisome proliferator - activated receptor - gamma and inhibit the accumulation of intracytoplasmic lipid droplets.15 the reversal of fat atrophy upon cessation of use may be due to removal of this inhibition , allowing adipogenesis to recommence . imaging of orbits ( computed tomography and magnetic resonance imaging ) has ruled out orbital pathology in the fellow eye ( resulting in pseudo - enophthalmos ) and other disease processes such as cicatrizing changes.5,6 periorbital changes may be underestimated , as they may be subtle or attributed to age - related volume depletion . bilateral topical use of prostaglandin analog eye drops in glaucoma may lead to equivocal changes in both eyes , which may be less obvious and thus under - reported . however , in asians , who tend to have greater upper eyelid fullness , unilateral periorbital fat atrophy may result in more obvious disfigurement.16 to date , as far as we are aware , there has been no report of topical bimatoprost use resulting in periorbital muscle atrophy . in figure 1 , it can also be seen that the patient had deepening of her upper eyelid sulcus and dermatochalasis involution . clinical eyelid measurements clearly showed reduced function of the right upper eyelid , suggesting that the effects of topical bimatoprost may not be limited to periorbital fat . reduced levator function and ptosis may be masked by the more common eyelid retraction and deepening of the upper eyelid sulcus . peplinski and albiani smith postulated that mller muscle ( smooth muscle ) may be directly affected by prostaglandin - mediated pathways , but whether there is a similar effect on levator muscle ( striated muscle ) remains unknown.17 other reasons for the induced right ptosis might have been stretching of the eyelid due to initiation of glaucoma - drop usage , disruption of the whitnall s suspensory ligament from the relative enophthalmos , or the patient s previous cataract surgery , even though there was no fixing of patient s superior rectus during the surgery . further studies are warranted . in this case , the patient was advised to stop topical bimatoprost and right ptosis correction surgery was performed successfully . in figure 2 , it can be seen that the upper eyelid sulcus deepening was much reduced , with a marked improvement in the dermatochalasis involution after the surgery . it may be worthwhile to note that topical bimatoprost used cosmetically can also cause unwanted side effects such as conjunctival hyperemia and iop reduction.18 therefore , while considered generally safe when applied superficially to the base of eyelashes , ocular side effects can still occur with risk of instillation onto the eye surface . herein , we report an unusual and previously unreported case of upper eyelid ptosis secondary to levator muscle atrophy as a result of the chronic unilateral use of topical bimatoprost . clinicians and patients should be aware of this , as it may compromise visual field and be potentially disfiguring , especially when used monocularly . patients using latisse should similarly be warned , since the cosmetic and ophthalmic preparations are identical . although this side effect may not be completely reversible with discontinuation of medication , this case shows that it may be successfully corrected with surgical intervention
topical bimatoprost is a common and popular prostaglandin analog used as an ocular hypotensive agent in the treatment of glaucoma . 
 side effects include ocular hyperaemia , ocular pruritus , and periocular and iris pigmentary changes . 
 perioribital lipodystrophy is another well - documented outcome associated with chronic use of topical bimatoprost , which results in periorbital hallowing , upper eyelid sulcus deepening , eyelid retraction and enophthalmos . 
 we report an unusual case of periocular muscle atrophy and weakness from unilateral topical bimatoprost use . 
 our patient had primary angle closure and experienced a right upper eyelid ptosis 2 months after she started to use topical bimatoprost in that eye . 
 clinical measurements of her eyelids clearly showed reduction in the function of her right levator muscle , suggesting that effects of topical bimatoprost may not be limited to periorbital fat . 
 she was advised to stop topical bimatoprost and right ptosis correction surgery with levator muscle advancement was performed successfully . 
 ophthalmologists and patients should be aware of this potential rare side effect of topical bimatoprost , as it may be potentially disfiguring , especially with monocular use . 
 however , its exact mechanism of action needs to be clarified further .