What is the appropriate evaluation and first‑line treatment for unilateral blepharospasm?

Unilateral Blepharospasm: Evaluation and Treatment

Critical First Step: Rule Out Secondary Causes

Unilateral blepharospasm is NOT typical primary blepharospasm and requires immediate investigation for secondary causes, as true primary blepharospasm is almost always bilateral. 1, 2, 3

Red Flags Requiring Urgent Workup

• Unilateral presentation is highly atypical - primary blepharospasm presents bilaterally in the vast majority of cases, with only 23 of 100 patients in one series having movements truly localized to the orbicularis oculi 2
• Neuroimaging is mandatory - obtain brain MRI with contrast to exclude structural lesions, particularly if there are any additional neurological signs 4
• Consider hemifacial spasm - this presents unilaterally in the third or fourth decade with intermittent spasmodic contractions of facial nerve-innervated muscles, has different pathophysiology than dystonia, and may indicate vascular compression of the facial nerve 3

Essential Differential Diagnoses to Exclude

• Ocular surface disease - perform comprehensive ophthalmologic examination including slit-lamp biomicroscopy to rule out blepharitis, dry eye, corneal pathology, or conjunctival irritation that could trigger reflex blepharospasm 4
• Eyelid malignancy - sebaceous carcinoma can present with unilateral eyelid inflammation and requires biopsy if there is marked asymmetry, resistance to therapy, focal lash loss, or loss of normal eyelid margin anatomy 4, 5
• Ocular mucous membrane pemphigoid - chronic unresponsive unilateral blepharitis with conjunctival cicatricial changes requires immunofluorescence studies 4, 5
• Thyroid eye disease - can present as new-onset symptoms with positive examination findings 4
• Neuropathic pain - consider if symptoms are disproportionate to objective findings 4

If True Unilateral Blepharospasm is Confirmed

First-Line Treatment: Botulinum Toxin Type A

Botulinum toxin type A injection is the treatment of choice for blepharospasm, with meaningful improvement in over 85% of patients. 1, 3

• Effects typically last 3-4 months before requiring repeat injection 6
• Injection should target the orbicularis oculi muscle, with particular attention to pretarsal portions if apraxia of eyelid opening is present 7
• Some patients may require myectomy in addition to substantial doses into pretarsal orbicularis oculi for adequate control 7

Bridging Therapy During Botulinum Toxin Wear-Off

Apraclonidine 0.5-1% ophthalmic solution (2 drops to affected eye) provides transient improvement for 2-4 hours and can be used as short-term management while awaiting botulinum toxin injection 6

• Works by causing contraction of Müller's muscle to counteract eyelid closure 6
• Well-tolerated with no significant adverse effects in clinical studies 6

Oral Medications (Limited Efficacy)

Response to oral medications is inconsistent, but 69% of trials result in some improvement, with only 22% showing marked and persistent benefit 2:

• Clonazepam - most useful specifically for blepharospasm symptoms 2
• Tetrabenazine, lithium, or trihexyphenidyl - more useful for oromandibular dystonia if present 2
• These should be considered adjunctive rather than primary therapy 1

Common Pitfalls to Avoid

• Do not assume bilateral disease - unilateral presentation demands investigation for secondary causes before accepting a diagnosis of primary dystonia 1, 2
• Do not skip neuroimaging - structural lesions must be excluded, particularly in atypical presentations 4
• Do not overlook ocular surface disease - blepharitis, dry eye, and other irritative conditions can mimic or trigger blepharospasm and require specific treatment 4
• Do not delay ophthalmology referral - patients with visual loss, moderate-to-severe pain, or severe chronic redness require specialist evaluation 4