Overview of ptosis

INTRODUCTION — Blepharoptosis, or ptosis of the eyelid, refers to drooping of the upper eyelid that usually results from a congenital or acquired abnormality of the muscles that elevate the eyelid. Ptosis may be the presenting sign or symptom of serious neurologic disease. Regardless of the etiology, when ptosis obstructs vision, it is disabling. The appropriate management requires recognition of the underlying cause.

ANATOMY — The facial or seventh nerve innervates the circumferential orbicularis oculi to close the upper and lower eyelids. The oculomotor or third cranial nerve innervates the levator palpebrae superioris to elevate the upper eyelid. The levator palpebrae superioris becomes a tendinous aponeurosis, which fuses with the anterior superior portion of the superior tarsal plate and possibly the pretarsal skin (figure 1). This junction of the aponeurosis to the tarsus and orbicularis oculi forms the eyelid crease [1].

An additional accessory smooth muscle, Müller's muscle, is innervated by the sympathetic nervous system. It arises from the undersurface of the levator palpebrae superioris and inserts into the superior tarsus. It contributes approximately 1 to 2 mm to the elevation of the upper eyelid (figure 1) [2]. Müller's muscle contributes to the over-elevation of the eyelid when a patient becomes excited or fearful and leads to mild ptosis with fatigue or inattention.

Landmarks — The eyelid crease is 6 to 7 mm away from the eyelid margin in adults. This crease is not appreciable in all eyelids (eg, those of individuals from Eastern Asia and/or with families from Eastern Asia) [3].The upper eyelid normally covers the top 1 mm of the cornea, and the lower eyelid typically lies at the junction of the cornea and sclera (picture 1) [4].

The palpebral fissure (PF) represents the distance between the upper and lower eyelid margins at the axis of the pupil. The normal PF measures 9 to 12 mm.

A point source of light directed at the patient creates a central pupillary light reflex. The distance from this reflex to the upper eyelid margin is called the margin reflex distance (MRD). Normally this measures 4 to 5 mm. MRD is often more helpful than PF since lower lid position may vary individually.

The PF and MRD provide an objective means of identifying ptosis and measuring its severity that may be useful in planning treatment.

CLINICAL APPROACH — The history and physical examination can identify the cause of ptosis in most patients (table 1). Additional diagnostic tests are indicated in some patients. (See 'Etiology and diagnosis' below.)

History — The historical features center on the timing and associated symptoms of the ptosis. Important information to gather includes the following:

●Has it been present from birth?

●Was this acute or slowly progressive?

●Does the degree of ptosis vary over the course of the day or with fatigue?

●Is there any associated headache or diplopia?

●Is there a history of ocular surgery, trauma (including birth trauma), or contact lens wear?

●Is there a family history of ptosis?

It may be helpful to consult family members and review old photographs to understand the duration and progression of the condition.

Examination — A number of examination features may help determine the cause of ptosis (table 1).

●Initial assessment – The examination begins with noting head posture and eyebrow position. Patients with ptosis may assume a chin-up position to look through the lowered palpebral fissure (PF). The eyebrows may be elevated in an effort to raise the lids.

Next, the eyelid position should be noted with the patient at rest with the eyebrows relaxed and the eyes in primary gaze. Anatomic landmarks (eyelid crease, PF and margin reflex distance [MRD]) should be specifically noted (see 'Landmarks' above). The PF might increase in downgaze in congenital ptosis but generally decreases in downgaze in acquired causes of ptosis.

●Unilateral versus asymmetric bilateral involvement – Hering's law of equal innervation applies to eyelid muscles, which are innervated by a single midline brainstem nucleus providing equal bilateral central output. In unilateral ptosis, excessive innervational stimulation often causes the contralateral eyelid to appear retracted (picture 2). If ptosis is bilateral but asymmetric, the less affected eyelid may appear normal. This can sometimes be detected by manual elevation of the obviously ptotic eyelid; a fall of the contralateral eyelid or "curtaining" confirms the bilaterality of the condition.

●Assess levator function – Levator function (LF) is assessed by measuring the excursion of the eyelid margin from downgaze to upgaze. Stabilizing the eyebrow to avoid overestimating the excursion of the lid margin may be accomplished by gentle fingertip pressure on the brow (picture 3). Normal LF is greater than 12 mm [4]. Horner syndrome causes ptosis by reducing activity of Müller's muscle; LF remains intact. LF is also preserved in acquired aponeurotic ptosis. Myopathic, neuropathic, congenital, and neuromuscular junction causes of ptosis show reduced LF.

●Assess for aponeurotic ptosis – With the patient looking downward, the physician can measure the distance from the eyelid crease to the eyelid margin (normal approximately 6.5 mm) [5]. An increased distance or redundancy of the eyelid crease suggests levator aponeurosis dehiscence or slippage [6]. This crease is not appreciable in all eyelids (eg, those of individuals from Eastern Asia and/or with families from Eastern Asia) [3].The crease is often less distinct or absent in patients with congenital ptosis.

●Assess pupil size and function – The examination should also include notation of pupil size and reactivity. When a third nerve palsy involves the pupil, it will appear larger than the contralateral pupil and react poorly to light and accommodation. By contrast, an ipsilateral, miotic pupil with normal reactivity will accompany ptosis in the setting of a Horner syndrome. The anisocoria is more evident in a darkened room.

●Assess extraocular movements – Extraocular motility and ocular alignment should be tested. Lesions of the third cranial nerve will frequently include some eye movement abnormality (see 'Third nerve palsy' below). Orbicularis weakness suggests a myopathic or neuromuscular junction cause. Myopathic disease often results in bilateral symmetric ophthalmoplegia without diplopia. Eye movements may be normal or abnormal in cases of myasthenia gravis (MG).

●Assess for neuromuscular junction disease – Evidence of levator fatigue should be sought for the diagnosis of neuromuscular junction disease. If the ptosis fluctuates throughout the examination, then evidence for fatigability of the levator muscle is present. Fatigue can also be induced by prolonged activation of the levator palpebrae muscle in sustained upgaze for at least one minute [7]. Enhancement of ptosis during prolonged upgaze or upon return to primary gaze suggests fatigability. Eyelid "curtaining" as discussed above is suggestive but not specific for myasthenia. Finally, a Cogan lid twitch, a transient overshoot of eyelid position when the patient saccades from downgaze to primary gaze position, also suggests eyelid neuromuscular junction disease. (See "Ocular myasthenia gravis", section on 'Examination for eyelid fatigue'.)

ETIOLOGY AND DIAGNOSIS — The underlying etiology of ptosis is generally apparent after history and physical examination. The major clinical features of the more common causes are presented (table 1). Additional diagnostic testing may help confirm some diagnoses. As an example, an imaging study is indicated only in patients who have a third nerve palsy or Horner syndrome.

Congenital ptosis — Congenital ptosis is most often associated with absence or reduction of striated levator palpebrae superioris muscle [8]. Müller's muscle remains relatively intact [9].

Congenital ptosis is usually unilateral (in 69 to 75 percent), neurologically isolated, and nonprogressive [10-12]. There can be a familial association, but it may be unrecognized if family members are only mildly affected [11]. Levator function (LF) varies in proportion to the degree of ptosis. Lid creases are often absent or lower than normal. Other ophthalmologic findings may include amblyopia and strabismus in 20 to 30 percent [11,13]. Approximately 5 percent of these patients cannot elevate the involved eye, presumably because the superior rectus and levator palpebrae superioris originate from a common embryologic source [14].

Rarely, a patient may have congenitally aberrant innervation of the levator muscle by the mandibular branch of the trigeminal nerve (Marcus Gunn jaw winking) causing eyelid retraction when the patient contracts the pterygoid muscle during the acts of sucking, jaw opening, or lateral jaw movement (picture 4) [15]. LF is variable or decreased, the upper eyelid crease is present, and there may be strabismus.

Congenital orbital fibrosis, an autosomal dominant condition producing fibrosis of the extraocular muscles and limited eye movements, sometimes includes associated ptosis [11] (see "Causes of vertical strabismus in children", section on 'Congenital fibrosis of the extraocular muscles'). Blepharophimosis is another dominantly inherited condition associated with severe bilateral ptosis with telecanthus, hypertelorism, and epicanthus inversus [12].

A congenital Horner syndrome produces a lighter colored iris on the affected side [11]. In the absence of clear birth trauma, any child with a Horner syndrome should be evaluated for secondary causes. (See 'Horner syndrome' below.)

Aponeurotic — In adults, the most common cause of acquired ptosis is spontaneous disinsertion or dehiscence of the levator aponeurosis, the tendon connecting the levator to the tarsal plate [16]. Clinical features include elevated or absent lid crease due to weakened attachments to the tarsus and orbicularis oculi (picture 2). LF remains intact.

In older adults, aponeurotic ptosis usually results from a naturally occurring involutional change. In younger patients, ptosis may result from contact lens wear, presumably from repetitive manipulation of the upper lid during lens insertion or removal [17,18]. This is more common with rigid or hard contact lens use.

Ptosis may develop after ocular surgery when an eyelid speculum is used. Six percent of cataract surgeries have postoperative ptosis as a complication [19,20]. Older patients with already weakened aponeurosis are believed to be at higher risk, but postoperative ptosis is a well-documented phenomenon in young patients as well; 10 percent of patients with an average age of 34 years developed ptosis after radial keratotomy in one reported series [21]. Trauma and chronic lid rubbing are other causes of aponeurotic ptosis [22].

Mechanical — Mechanical ptosis can occur as a result of excess weight on the upper lid (picture 5). Causes include infections, inflammation, and eyelid tumors (dermoid cyst, metastatic neuroblastoma, chalazion, rhabdomyosarcoma, neurofibroma, hemangioma, others) [11] (see "Eyelid lesions"). Mechanical ptosis can easily be diagnosed from examination and history.

Neurologic — Neurologic disease affecting the muscle, neuromuscular junction, cranial nerve, and the brainstem may lead to ptosis.

Third nerve palsy — The inferior division of the oculomotor nerve (CN3) innervates the ipsilateral inferior rectus, medial rectus, and inferior oblique. It also carries the efferent pupillary fibers from the Edinger-Westphal nucleus. The superior division innervates the superior rectus and levator palpebrae superioris. The brainstem subnucleus of the levator is unpaired, and a lesion there produces bilateral ptosis. Peripheral third nerve lesions are much more common.

A complete third nerve palsy is easily recognizable with profound ptosis, significant ophthalmoplegia, and diplopia. Because profound ptosis may occlude vision, the patient may not have diplopia and may be unaware of pupillary involvement. LF is decreased or absent. If involved, the pupil may be mid-dilated and poorly reactive, and the anisocoria will be more prominent in bright light. Partial oculomotor weakness may show only mild ptosis, and eye movement abnormalities can be subtle (picture 6).

Dysfunction of the third cranial nerve (oculomotor nerve) can result from lesions anywhere along its path between the oculomotor nucleus in the midbrain and the extraocular muscles within the orbit. Causes range in severity from those that are immediately life-threatening to those that are benign and self-limited. This topic is discussed separately. (See "Third cranial nerve (oculomotor nerve) palsy in adults" and "Third cranial nerve (oculomotor nerve) palsy in children".)

Horner syndrome — The clinical triad of Horner syndrome (ipsilateral ptosis, miosis, and anhidrosis) is produced from a disruption in the three-neuron oculosympathetic chain (picture 7). Anhidrosis may be absent or unnoticed, but miosis is invariable. The anisocoria appears more prominent in dim light with delayed dilation of the ipsilateral pupil. Since Müller's muscle is affected instead of the levator superioris, the ptosis is mild, usually 1 to 2 mm. The ipsilateral lower lid can also be slightly higher, further narrowing the palpebral fissure (PF); this can give the appearance of the eye being sunken in (ie, pseudoenophthalmos). Other acute features of sympathetic disruption include ipsilateral conjunctival injection, nasal stuffiness, and increased near point of accommodation [23].

Topical administration of 10 percent cocaine eyedrops can confirm the diagnosis of Horner syndrome. The normal pupil dilates more than the Horner pupil, increasing the degree of anisocoria. Alternatively, instillation of 0.5 percent apraclonidine will dilate the Horner pupil and raise the Horner eyelid in many cases. Horner syndrome is discussed separately. (See "Horner syndrome".)

Neuromuscular junction disorders — Neuromuscular junction disorders, which often produce ptosis, include myasthenia gravis (MG) and botulism. Ptosis and diplopia may occur in the Lambert-Eaton myasthenic syndrome (LEMS), but they are rarely prominent or presenting symptoms [24]. LEMS is not typically considered in the differential diagnosis of ptosis.

Myasthenia gravis — MG is an autoimmune disorder directed at the postganglionic acetylcholine receptors in the neuromuscular junction of skeletal muscles. The hallmark of MG is the variability and fatigability of both signs and symptoms. The initial presentation may occur as isolated ocular findings in approximately 50 percent of cases. Unilateral or bilateral ptosis can develop with or without diplopia and ocular motor deficits. Fatigability, Cogan lid twitch, orbicularis oculi weakness, and curtaining (see 'Examination' above) are frequently seen but are neither requirements nor pathognomonic findings of myasthenia. LF is often abnormal [25]. Resting with eyes closed for several minutes or placing an ice pack on the ptotic eyelid for one minute may result in transient improvement of ptosis secondary to MG. The diagnosis and management of ocular MG are discussed separately. (See "Ocular myasthenia gravis".)

Botulinum toxin — Ptosis can be a complication of recent (<1 week) botulinum toxin therapy when used in the treatment of blepharospasm and cosmetic treatment of forehead, glabellar, and lateral canthal wrinkling. The package insert reports that 11 percent of patients treated for blepharospasm had ptosis as a complication. In this setting, ptosis generally resolves over three to four weeks.

Other — Ptosis is also a feature of infectious botulism. Unlike MG, however, it would be rare to have prominent ptosis without associated generalized weakness and autonomic signs. (See "Botulism".)

Myogenic

Mitochondrial myopathy — Disorders of mitochondrial function may involve the muscles of the eyes and eyelids producing chronic progressive external ophthalmoplegia (CPEO). Findings include bilateral progressive ptosis, orbicularis oculi weakness (failure to close the eye completely), and symmetric slowing of saccadic eye movements or impaired eye movements (picture 8). Subjective diplopia is infrequent because the ophthalmoplegia is usually symmetric. Early on, the eye movements may appear full, but the speed of the saccades may be dramatically slowed.

Patients with mitochondrial myopathies may present at any age. Kearns-Sayre syndrome begins in the first or second decade and, with ptosis and ophthalmoplegia, includes retinitis pigmentosa and heart block as cardinal features. The disorder CPEO does not include retinitis pigmentosa or heart block but has indistinguishable muscle pathology. The latter is a heterogeneous disorder with variable age at presentation, clinical severity, and inheritance patterns. Kearns-Sayre syndrome is discussed in more detail elsewhere. (See "Myopathies affecting the extraocular muscles in children".)

Serum lactate and pyruvate levels are often elevated in mitochondrial disease, but this is rarely diagnostic. Noninvasive tests suggestive of mitochondrial disorders include exercise intolerance and abnormal tissue oximetry [26,27]. Genetic testing for CPEO is commercially available. If negative, then the diagnosis requires a skeletal muscle biopsy (eg, deltoid or quadriceps). Ragged red fibers are seen with Gomori trichrome staining. In addition, tests for mitochondrial mutations, measurement of oxidative phosphorylation, and stains for cytochrome oxidase and succinate dehydrogenase can be helpful. Only a few centers perform these analyses, and many assays require fresh muscle tissue [28].

Oculopharyngeal muscular dystrophy — Oculopharyngeal muscular dystrophy (OPMD) is a rare, autosomal dominant myopathy that usually presents in middle age with asymmetric involvement of the levator palpebrae and pharyngeal muscles with prominent dysarthria and dysphagia. Progressive extraocular muscle weakness may develop subsequently. Genetic testing for this disorder is available. (See "Oculopharyngeal, distal, and congenital muscular dystrophies", section on 'Oculopharyngeal muscular dystrophy'.)

Myotonic dystrophy — Myotonic dystrophy is an autosomal dominant disorder characterized by variable ptosis and weakness of the face, jaw, and neck with mild weakness of the distal extremities. Associated abnormalities include cataracts, cardiac conduction defects, characteristic facies (long face with atrophy of temporalis and masseter), frontal balding, and variable intellectual impairment. Patients may also develop dysphagia and ophthalmoparesis in some cases. (See "Myotonic dystrophy: Etiology, clinical features, and diagnosis".)

Pseudoptosis — An eyelid may appear ptotic due to its relative position with respect to the eye, but the underlying pathology may not be in the lid itself. Causes include:

●Lack of posterior support in an enophthalmic eye may induce ptosis.

●A hypotropic eye that points downward appears to have a ptotic lid, but when the patient fixates with that eye the apparent droop disappears.

●A patient with lid retraction of one eye may give the false impression of ptosis in the contralateral eye.

●In older adult patients, redundant eyelid skin and prolapse of the orbital fat (dermatochalasis) can cause the eyelid to overhang the eyelid margin (picture 9).

●Finally, a patient can artificially induce the appearance of ptosis by lowering the ipsilateral eyebrow and raising the contralateral one (picture 10).

MANAGEMENT — The management of ptosis is not always satisfactory. When nonsurgical therapy is insufficiently effective or not an option, patients may be considered for surgery, which has incomplete success and associated risks.

Nonsurgical therapy — Myasthenia gravis (MG) responds to medical therapy, which is the treatment of choice for such patients.

Ptosis from Horner syndrome may improve temporarily with topical apraclonidine, naphazoline [29], or tetrahydrozoline [30]. While these have not been formally studied as treatment for ptosis, these can help with symptoms. The author uses apraclonidine 0.5 percent three times per day as needed. Naphazoline can be used every four hours as needed. Tetrahydrozoline can be used up to four times per day as needed.

Oxymetazoline hydrochloride 0.1 percent eyedrops hold promise for the treatment of acquired blepharoptosis in adults. This weak alpha-adrenergic agonist acts upon upregulated receptors in Müller's muscle. In a pooled analysis of two small, short-term trials of 304 total patients with acquired ptosis not related to congenital ptosis, Horner syndrome, myasthenia gravis, or mechanical cause, once-daily oxymetazoline was associated with improved visual fields compared with placebo at the two-week assessment [31]. While expected side effects may include local symptoms, acute angle closure glaucoma, and changes in blood pressure, adverse effects were similar in patients receiving oxymetazoline and vehicle eye drops in this analysis. Further studies to evaluate the best dosing frequency and to examine functional outcomes and quality of life over longer treatment durations are needed before routine use of this medication can be recommended. While approved by the US Food and Drug Administration (FDA) for this indication, insurance may not cover this medication.

Eyelid crutches inserted into eyeglasses are a temporizing measure for some patients.

Surgery — Surgery is indicated primarily in patients who have an obscured visual field due to ptosis. Surgery may also be considered for cosmetic reasons, but patients should be aware of the potential complications. (See 'Complications' below.)

Surgical approaches to the correction of ptosis include Müller muscle resection, levator muscle resection or advancement, and frontalis suspension:

●Müllerectomy may be considered for the treatment of Horner syndrome and for patients with milder degrees of ptosis (1 to 2 mm). Benefit may be predicted by installation of 10 percent neosynephrine or 2.5 percent phenylephrine eye drops, which stimulates Müller's muscle. Improvement of ptosis by 2 to 3 mm after 10 minutes predicts a better response to this surgery [32].

●If good levator function (LF) is present, advancement of the levator aponeurosis is commonly performed to ameliorate ptosis. The levator aponeurosis is disinserted, then it is reattached to the tarsus. If stretched thin, then the surgeon resects a portion of the aponeurosis before reinsertion [33].

●If there is severe, bilateral ptosis and poor LF, frontalis suspension surgery is usually preferred. Various synthetic or autologous materials are used to form a sling, which lies below the skin surface and connects the upper eyelid to the frontalis muscle [4].

Timing — In patients with third nerve palsy, an interval of 6 to 12 months before surgical intervention is advised because many will have spontaneous recovery. Similarly, patients with MG should have stable disabling ptosis for several months to years on maximal medical therapy before considering surgical therapy.

Surgery is often also delayed in patients with muscle disease. Because of the progressive nature of the disease, repeated procedures are likely. Also, these patients are at higher risk of surgical complications.

Complications — The most common troubling complication of ptosis surgery is lagophthalmos or failure of the eye to close completely. This in turn may lead to dry eye and exposure keratopathy [34]. This is more common in myopathic and neuromuscular junction disorders in which there is accompanying weakness of the orbicularis oculi. An impaired Bell's phenomenon (the superior rotation of the eyeball during eye closure in sleep and blinking) is also a risk factor for this complication. The presence of an impaired Bell's phenomenon as well as abnormal tear production or orbicularis oculi weakness will make the surgeon more reluctant to perform surgery and will lead to a more conservative surgical approach (ie, undercorrection).

Because of Hering's law of equal innervation, processes that produce bilateral but asymmetric ptosis may cause the less affected eye to appear normal. Postoperatively, the ptosis in this eye will be increased, perhaps apparent for the first time. Preoperatively, curtaining (see 'Examination' above) indicates that bilateral surgical repair is needed (picture 1). However, one report indicates that this may not be a sufficiently sensitive test [35].

Other complications of ptosis surgery include scarring, deformity of the lid crease, and asymmetry or under/overcorrection of the lid position.

SUMMARY AND RECOMMENDATIONS

●Etiologies – Blepharoptosis is a drooping of the upper eyelid.

Ptosis may be congenital or acquired. Acquired conditions may be related to disorders affecting the muscle tendon, muscle, neuromuscular junction, or nerve. (See 'Etiology and diagnosis' above.)

●Evaluation – Ptosis may be the presenting sign or symptom of serious neurologic disease.

Clinical history and neurologic examination will generally distinguish among the causes of ptosis (table 1). (See 'Etiology and diagnosis' above.)

Unilateral ptosis accompanied by ipsilateral extraocular movement impairment and/or mydriasis suggests a compressive third cranial nerve palsy. Emergent neuroimaging is required to exclude a posterior communicating artery aneurysm. (See 'Third nerve palsy' above.)

Horner syndrome typically produces ipsilateral ptosis, miosis, and anhidrosis; the diagnosis can be confirmed with apraclonidine eye drops. (See "Horner syndrome", section on 'Evaluation and diagnosis'.)

Ptosis can be the presenting feature of ocular myasthenia gravis (MG), which is suspected when the symptoms are variable or fatigue. (See 'Myasthenia gravis' above.)

Muscle disorders featuring ptosis include mitochondrial disease, oculopharyngeal dystrophy, and myotonic dystrophy. (See 'Myogenic' above.)

●Management – Patients with stable, disabling ptosis may be considered for oxymetazoline hydrochloride 0.1 percent eyedrops or surgery. Ptosis severity, levator function (LF), and underlying etiology are used to guide the selection of the surgical procedure. (See 'Surgery' above.)