Eye (2021) 35:2468–2481 https://doi.org/10.1038/s41433-021-01547-5 REVIEW ARTICLE A review of acquired blepharoptosis: prevalence, diagnosis, and current treatment options 1 2 3 4 Jason Bacharach ● Wendy W. Lee ● Andrew R. Harrison ● Thomas F. Freddo Received: 11 February 2021 / Revised: 15 March 2021 / Accepted: 7 April 2021 / Published online: 29 April 2021 © The Author(s) 2021. This article is published with open access Abstract Blepharoptosis (ptosis) is among the most common disorders of the upper eyelid encountered in both optometric and ophthalmic practice. The unilateral or bilateral drooping of the upper eyelid that characterises ptosis can affect appearance and impair visual function, both of which can negatively impact quality of life. While there are several known forms of congenital ptosis, acquired ptosis (appearing later in life, due to a variety of causes) is the predominant form of the condition. This review summarises the prevalence, causes, identification, differential diagnosis, and treatment of acquired ptosis. Particular attention is paid to the differential diagnosis of acquired ptosis and emerging treatment options, including surgical and pharmacologic approaches. 1234567890();,: 1234567890();,: Literature search notes either congenital (present at or shortly following birth) or acquired (appearing later in life). Ptosis is broadly recog- Literature cited in this review was identified via a broad nised as being among the most common disorders of the search of the PUBMED online database for English-lan- eyelid encountered in the clinic, however data from large guage, peer-reviewed publications including search terms population-based studies are limited. Estimates of ptosis such as “ptosis,”“epidemiology,”“etiology,”“eyelid,” prevalence are largely based on data from region-specific “surgical,”“pharmacologic,”“Müller’s muscle,”“adrener- studies, which report rates between 4.7 and 13.5% in adult gic,”“visual field,” and “quality of life.” Relevant primary populations and support the widespread nature of the con- and review articles were reviewed and cited when providing dition [1–3]. Furthermore, these studies consistently reveal unique primary data or a current summary of fundamental that, within adult populations, the incidence of ptosis concepts. Also included, when relevant, were primary or increases with age (Table 1 and Acquired ptosis risk fac- review articles not identified via PUBMED, but cited in tors). Reports of ptosis incidence in surgical populations are publications retrieved via this literature search. consistent with those in broader patient populations. In a study evaluating a cohort of 623 patients referred for sur- gery in an oculoplastics department in Singapore, ptosis Acquired ptosis overview, prevalence, and was the most common condition, occurring in 11.7% of impacts patients [4]. Drooping of the upper eyelid due to ptosis can lead to the Blepharoptosis, more commonly known as “ptosis,” is an condition’s characteristic ‘sleepy’ appearance, as well as abnormal drooping of the upper eyelid with the eye in asymmetry, in both unilateral and bilateral cases [5, 6]. primary gaze. This drooping can affect one or both eyes, Studies reveal that this can have important impacts on and based on time of appearance, it is broadly classified as patient well-being, including reduced independence and * Jason Bacharach 3 Department of Ophthalmology and Visual Neurosciences, [email protected] Department of Otolaryngology, University of Minnesota, Minneapolis, MN, USA 1 North Bay Eye Associates, Petaluma, CA, USA 4 Massachusetts College of Pharmacy and Health Sciences, 2 Bascom Palmer Eye Institute, University of Miami Miller School Worcester, MA, USA of Medicine, Miami, FL, USA A review of acquired blepharoptosis: prevalence, diagnosis, and current treatment options 2469 Table 1 Studies reporting on the prevalence of ptosis in the general adult population. Study Location Subjects evaluated Ptosis prevalence Other associated factors Over- By sex By age Eye(s) affected all Forman et al. 1995 United Kingdom N = 400 adults ≥50 11.5% • M: 9.0% • 50–59 years old: 2.4% • 57% of cases bilateral • n/a [1] years old (166 • F: 13.2% • 60–69 years old: 8.9% M; 234 F) • 70–79 years old: 12.5% • ≥80 years old: 42.9% Hashemi et al. Iran N = 4737 adults 4.7% • M: 4.0% • 45–49 years old: 3.1% • 27.7% of cases bilateral • Hypertension, diabetes 2016 [2] 44-69 years old • F: 5.2% • 50–54 years old: 3.7% (1946 M; 2791 F) • 55–59 years old: 4.7% • 60–64 years old: 7.1% • 65–69 years old: 5.8% Kim et al. 2017 [3] South Korea N = 17,286 adults 13.5% • 50.1% of patients with • 40–49 years old: 5.4% • Not specified • Hypertension. diabetes, higher BMI, ≥40 years old ptosis were F • 50–59 years old: 11.6% history of CV disease, hyperopia, (48.8% M; • 60–69 years old: 19.8% strabismus, cataract 51.2% F) • ≥70 years old: 32.8% BMI body mass index, CV cardiovascular. increased appearance-related anxiety and depression [ altering ophthalmic conditions, suchlevels as previously strabismus reported [ in patients withthan other typical appearance- norms inrelated the general distress, population anxiety, and(CARVAL) similar and scale). to depression Patients that reportedappearance were levels (the of higher Centre appearance- of for Negative Appearance Evaluation (FNE) Research Scale),ditions Valence and related self-evaluation to of the perceivedand opinions Depression of Scale others (the(DAS (HADS)), Fear 24)), fearful anxiety orappearance-related and worrying distress depression (the con- Derriford (the Appearancequestionnaires Hospital Scale Anxiety addressing psychosocialsurgery factors, were including assessedIn a study prior in the to United Kingdom, surgery adults referred using for ptosis validated analysis also identi reduction in independenceHRQoL (greater was dif found to be, at least in part, due to the males [ with female patientsrespect reporting to DAS higher 24, mean HADS, scores FNE, than and CARVAL scores, a result of ptosis can lead to de fi sures [ decreases in health-related quality of life (HRQoL) mea- on visual ti described in detail the section titled Acquired ptosis iden- with mild unilateral visual sures, decreases in HRQoL wereciated also evident with in participants the greatest negative effect on HRQoL mea- While bilateral moderate/severe visual Institute VisualShort-Form Function Health Questionnaire Survey (SF-12) (NEI-VFQ-25). and the National Eye visual Field Test (LPFT)) revealed thatdating a 84 novel of static 85 perimetry ptoticmore test eyes recent (the had Leicester a studies Peripheral in patients with ptosis, a study vali- worsened in the moderate ptosis condition [ mild cases [ of all test points along the superior hemi even mild ptosis was associatedmild with or signi moderate(HVF) ptosis Test) using in eyelid subjectsusing at weights static baseline found and that perimetry after induction testing of (Humphrey Visual Field visual than 5200 subjects underwentlives. ophthalmic In examination the and Los Angeles Latino Eye Study (LALES), more assess HRQoL correlated with worse scores on two validated tools to greater visual fi eld, detectable via visual cation and differential diagnosis. From a functional perspective, obstruction of the pupil as The effect of ptosis goes beyond diminished performance fi 7 fi 8 ], indicating meaningful impacts on patients eld testing. Data from this population revealed that eld de ]. fi 9 eld tests. Visual – 11 fi fi — cit [ eld loss, measured using the HVF Test, ]. An evaluation of the superior visual the Medical Outcomes Study 12-item fi 10 ed signi ]. Visual fi fi eld testing and evident even in fi eld loss [ fi cant gender differences with eld loss is associated with fi fi cits in the superior visual eld testing methods are 7 fi fi ]. The reduction in eld loss was asso- fi culty driving and eld, and that this fi cant depression 11 ]. Among 8 ’ ]. The 7 daily fi , eld 8 ]. 2470 J. Bacharach et al. performing regular tasks) that arises due to visual field expression of the α1D, α2C, and β2 subtypes in patients with deficits [7]. Studies also show that improvements in sub- ptosis [18, 19]. In contrast to Müller’s muscle, the jective and objective visual performance following inter- levator predominantly expresses the β1-adrenergic receptor vention are associated with improved HRQoL-related subtype, with only trace expression of the α1, α2, and β2 measures [12, 13]. In a study of 50 patients who underwent subtypes [17]. ptosis surgery, patients showed significant improvement The frontalis muscle, which inserts at the level of the versus pre-surgery assessment, with respect to a range of eyebrows, is innervated by the facial nerve (cranial nerve vision-related activities and symptoms, including the ability VII) and its contraction raises the brow, with no direct effect to perform fine manual work, hang or reach objects above on upper eyelid elevation. In patients with ptosis, however, eye level, watch television, and read [12]. Similarly, in a compensatory raising of the brow via the frontalis study of 100 patients with unilateral or bilateral ptosis that muscle can indirectly provide slight elevation of the eyelid used the same questionnaire, improvement in the as well [15]. superior visual field following surgery was associated with a Broadly, ptosis is classified based on time of onset. greater functional index, and patients had significant Congenital ptosis (present at birth) typically has a unilateral improvement with respect to activities including performing presentation and is most often a result of developmental their occupation, playing sports, and walking without myopathy of the levator muscle that affects the levator’s assistance [13]. ability to contract and raise the upper eyelid [20–22]. Neurogenic forms of congenital ptosis can be caused by cranial nerve III abnormalities or insufficient sympathetic The upper eyelid and causes of acquired innervation of Müller’s muscle. Furthermore, several cra- ptosis niofacial syndromes or cranial dysinnervation disorders can also underlie congenital ptosis, including Marcus Gunn jaw- Elevation of the upper eyelid is largely provided by two winking syndrome or blepharophimosis [22, 23].