Brown syndrome

Key Points at a Glance

Key Points of This Disease

• Brown syndrome is a vertical strabismus in which elevation of the eye in adduction is limited due to an abnormality of the superior oblique tendon-trochlea complex.
• It was first reported in 1950 by Dr. Harold Whaley Brown as “superior oblique tendon sheath syndrome”.
• It is classified into congenital and acquired types, accounting for about 2% of all strabismus.
• In congenital cases, spontaneous resolution occurs in up to 75-80%, and observation is the first choice.
• Acquired causes include rheumatic diseases, trauma, postoperative complications, and COVID-19 infection, among others.
• A positive forced duction test (FDT) is an important diagnostic finding indicating a mechanical cause and is essential for differentiating from inferior oblique palsy.
• If hypotropia in primary position, abnormal head posture, or diplopia is severe, superior oblique tendon lengthening or tenectomy may be considered.

1. What is Brown syndrome?

Brown syndrome is a form of vertical strabismus in which elevation of the eye in adduction is limited or impossible due to an abnormality of the superior oblique tendon-trochlea complex. It is also called superior oblique tendon sheath syndrome. It was first reported in 1950 by Dr. Harold Whaley Brown ¹⁾.

The limitation of elevation in adduction is basically a mechanical problem caused by the superior oblique tendon not sliding smoothly through the trochlea, resulting in a condition where the tendon becomes stiff and cannot stretch like a tendon.

Epidemiology:

• Accounts for about 2% of all strabismus. Some reports indicate 18.03% among 2,217 strabismus patients ¹⁾
• Familial incidence is 1 in 20,000 births ¹⁾
• Slightly more common in females (59%) ¹⁾
• Right eye slightly predominant (55-60.4%) ¹⁾
• Approximately 10% are bilateral¹⁾

Genetics:

Autosomal recessive or autosomal dominant inheritance with reduced penetrance has been reported¹⁾.

Q Is Brown syndrome hereditary?

A

Familial occurrence is relatively rare, affecting 1 in 20,000 births, and autosomal recessive or autosomal dominant inheritance with low penetrance has been reported¹⁾. Most cases are sporadic.

2. Main Symptoms and Clinical Findings

Eye movement photograph of Brown syndrome. In right upward gaze, the left eye shows limited elevation in adduction and a downward position.

Disserol CCD, et al. An uncommon cause of diplopia: do not forget Brown syndrome. Arq Neuropsiquiatr. 2024. Figure 1. PMCID: PMC11500302. License: CC BY.

Four-direction eye position photographs show that the eyes are generally aligned in primary gaze, but in right upward gaze, the left eye cannot elevate sufficiently and is positioned downward. This is a clinical finding characteristic of Brown syndrome, showing limited elevation in adduction.

Subjective Symptoms

• Vertical diplopia: May be constant, intermittent, or recurrent
• Orbital pain/tenderness: Particularly prominent in acquired cases. Pain increases with eye movement
• Abnormal head posture (AHP): Typically chin-up posture or turning the face to the unaffected side
• Clicking sensation: A clicking sensation may occur with tendon slippage during elevation in adduction
• Atypical symptoms: Reflex eye closure (“black curtain”) following acute pain has been reported in intermittent recurrent cases⁷⁾

Clinical Findings

Limited elevation in adduction is the defining finding of Brown syndrome.

Mild

Primary position: No vertical deviation

Adduction: No downshoot

Elevation: Limited only in adduction

Moderate

Primary position: No vertical deviation

Adduction: Downshoot present

Elevation: Clearly limited in adduction

Severe

Primary position: Hypotropia present

Adduction: Downshoot present

Abnormal head posture: Marked head tilt and face turn

Other important clinical findings are shown below¹⁾.

• V-pattern strabismus: Often presents with V-pattern exotropia in upgaze
• Widening of the palpebral fissure on adduction: Associated with Bell’s phenomenon
• Positive forced duction test (FDT): Confirms restricted passive elevation in adduction. Essential for diagnosing mechanical strabismus
• Abnormal head posture (AHP): Present in 59% of congenital BS¹⁾. Head tilt 44.2%, combined type 30.8%
• Amblyopia: Complicated in 15.9–21.7% of cases, but amblyopia due to BS itself is rare; usually due to anisometropia or strabismus¹⁾

3. Causes and Risk Factors

Brown syndrome is broadly classified into congenital and acquired types.

The following table compares the causes.

Classification	Main Causes
Congenital	Tendon shortening/loss of elasticity, trochlear malformation, fibrous bands
Acquired/Inflammatory	RA, juvenile idiopathic arthritis, SLE, post-COVID-19 trochleitis
Acquired/Traumatic/Iatrogenic	Orbital fracture/surgery, after scleral buckling surgery

Congenital:

The basic cause is structural abnormality of the superior oblique tendon-trochlea complex ¹⁾. Shortening and loss of elasticity of the tendon, trochlear malformation, tendon nodules, and fibrosis are observed. A recent explanation proposes the presence of a fibrotic strand originating from the posterior part of the SO tendon to the trochlear area and having the same insertion ¹⁾. An association with congenital cranial dysinnervation disorders (CCDDs) has also been reported.

There is also a report that elongation of the ZT distance (distance from the annulus of Zinn to the trochlea) is associated with the development of BS. In 12 normal children, the average was 37.1±1 mm (range 35.8–38.7 mm), whereas in BS patients it was elongated to 41.2 mm ⁶⁾.

Acquired:

• Peritrochlear scarring (direct impact to the trochlear area from frontal trauma, surgery, chronic sinusitis)
• Autoimmune/inflammatory diseases (RA, JIA, SLE) causing inflammation of the superior oblique tendon and trochlea
• Superonasal orbital mass (including complications of glaucoma drainage implants)
• Loss of elasticity of the superior oblique muscle due to thyroid eye disease or retrobulbar anesthesia
• Iatrogenic (after scleral buckling surgery, strabismus surgery, or sinus surgery)
• Trochleitis after COVID-19 infection: MRI shows swelling and Gd enhancement of the SO tendon sheath ⁵⁾⁸⁾
• Compression of the SO complex by titanium mesh after orbital wall fracture ORIF ⁴⁾
• Idiopathic: low-grade local edema/inflammation is presumed, and an embolic hypothesis has also been reported ¹⁾

Note that ocular myasthenia gravis has been newly reported to present with BS-like findings (AChR antibody positive) ³⁾, and should be included in the differential diagnosis.

Q Can Brown syndrome develop after COVID-19 infection?

A

In both adults and children, the development of Brown syndrome due to trochleitis after COVID-19 infection has been reported ⁵⁾⁸⁾. MRI shows swelling and gadolinium enhancement of the SO tendon sheath, and it improves with systemic corticosteroid administration. It can occur even in cases without multisystem inflammatory syndrome.

4. Diagnosis and Examination Methods

Diagnosis is a clinical diagnosis based on medical history and clinical findings¹⁾.

Main examination methods:

• Comprehensive strabismus angle measurement: Evaluate deviation in adduction, abduction, elevation, and depression directions
• Forced duction test (FDT): Positive for passive elevation limitation in adduction. Limitation becomes more pronounced with retropulsion. This is the most important test to confirm mechanical strabismus and differentiate from inferior oblique palsy (FDT negative). In children, it is performed under general anesthesia, and the degree of resistance varies by case.
• Binocular vision function evaluation: Assessment of stereopsis and fusion ability

Imaging diagnosis:

• CT: Useful for evaluating bone abnormalities and post-traumatic changes
• MRI: Excellent soft tissue contrast, useful for detecting compressive lesions, inflammation, and vascular abnormalities¹⁾. Horizontal and coronal sections of the trochlear region depict abnormalities of the SO tendon and trochlea. In COVID-19-related cases, T2 hyperintensity and tendon sheath Gd enhancement are characteristic⁵⁾. However, inflammation cannot be ruled out even if MRI is normal¹⁾.

Key points for differential diagnosis:

Disease	FDT	Characteristic findings
Inferior oblique palsy	Negative	SO overaction, A-pattern strabismus
Double elevator palsy	Positive in both adduction and abduction	Elevation limitation in all directions
Orbital fracture	Positive in both adduction and abduction	History of trauma, infraorbital hypoesthesia
Myasthenia gravis	Negative (restrictive-like findings)	AChR antibody positive3)

Obtaining a family history is also important to rule out familial Brown syndrome¹⁾.

5. Standard treatment

Observation

In congenital Brown syndrome, observation is the first choice. Spontaneous improvement is seen in up to 75-80% of cases, and the basic policy is not to rush into surgery¹⁾.

• 60 congenital cases followed for 46 months: 10% had complete spontaneous remission (remission age 4-15 years)¹⁾
• 32 congenital cases: 75% showed spontaneous improvement¹⁾
• 10 cases of acquired idiopathic (mean follow-up 13 years): 30% achieved complete remission¹⁾

Pharmacotherapy (for acquired cases)

Corticosteroids are effective for inflammatory acquired Brown syndrome.

• Systemic administration: In adults after COVID-19, IV methylprednisolone 1g × 3 days followed by oral prednisone 64 mg tapered (reducing by 16 mg every 2 days) led to improvement in 2 months⁵⁾. In a pediatric case (12 years old), a Medrol Dosepak taper resulted in pain resolution after 1 month and improvement of diplopia after 4 months⁸⁾
• Peritrochlear steroid injection: 84.6% (11/13) of trochleitis cases showed complete improvement (triamcinolone 1 ml, mean 22.45 days later)¹⁾
• NSAIDs: Ibuprofen 400 mg three times daily may be used as adjunctive therapy³⁾
• Cases with concomitant myasthenia gravis: A case report showed improvement with pyridostigmine 180 mg³⁾

Surgical treatment

Surgery is considered in the following cases¹⁾.

• Hypotropia in primary position
• Significant abnormal head posture
• Significant diplopia
• Significant downward deviation on adduction
• Binocular vision dysfunction

Tendon lengthening

Silicone expander method (Wright method): Marked improvement in 3 of 4 cases. The SO tendon is lengthened by 10 mm.

Z-plasty lengthening: Performed with Mersilene 5-0 suture in a case of sequential bilateral BS. If insufficient, conversion to complete tenotomy is performed ⁶⁾.

The advantage is that the risk of iatrogenic superior oblique palsy can be reduced.

Tenectomy

SO tendon tenotomy/tenectomy: Most effective initial surgery in a retrospective study of 38 cases. AHP resolution rate 81.5% ¹⁾.

There is a risk of iatrogenic superior oblique palsy due to overcorrection. Careful postoperative monitoring is required.

Other surgical techniques

SO tendon split lengthening: Significant improvement in hypotropia and elevation limitation in 15 severe BS cases ¹⁾. Overcorrection in 2 of 20 cases (10%) in a retrospective study.

SO tendon thinning: Effective in 21 eyes with thickened SO tendon ¹⁾.

Revision surgery for iatrogenic BS: A case where the SO complex was released by repositioning titanium mesh after orbital fracture ORIF ⁴⁾.

Precautions in treatment

• Iatrogenic superior oblique palsy may occur after SO tendon tenotomy/tenectomy. Tendon lengthening can reduce this risk.
• Congenital BS often improves during observation, so the need for surgery should be carefully assessed.
• If acquired and the underlying disease is clear, treatment of the primary disease should take precedence.

Q Can it heal naturally without surgery?

A

In congenital cases, spontaneous improvement is observed in up to 75–80%, so the basic approach is observation without rushing to surgery ¹⁾. In acquired idiopathic cases, complete remission is reported in 30%. However, in severe cases (hypotropia in primary position, significant abnormal head posture), surgical intervention is considered.

Q Is there a risk of superior oblique palsy after surgery?

A

Iatrogenic superior oblique palsy can occur after SO tenotomy or resection. Tendon lengthening procedures (silicone expander technique, Z-tenotomy) are thought to reduce this risk, and lengthening procedures have been increasingly chosen in recent years ¹⁾. Careful postoperative follow-up is necessary.

6. Pathophysiology and Detailed Mechanisms

Dysfunction of the superior oblique tendon–trochlea complex is the main mechanism of Brown syndrome ¹⁾.

Embryological background:

Sevel’s study showed that the superior oblique muscle, tendon, and trochlea develop from a common mesenchymal tissue ¹⁾. This finding explains the natural course of congenital BS, which gradually improves with growth. An association with congenital cranial dysinnervation disorders (CCDDs) has been proposed, but many cases do not show limitation of depression in adduction, so it cannot explain all cases ¹⁾.

Fibrotic strand hypothesis:

A recent hypothesis proposes the existence of a fibrotic strand originating from the posterior part of the SO tendon to the trochlear area and inserting at the same site as the SO tendon ¹⁾. Variations in insertion can explain not only typical elevation limitation in adduction but also atypical patterns of elevation impairment.

ZT distance elongation hypothesis:

Elongation of the ZT distance (distance from the annulus of Zinn to the trochlea) is proposed to cause anterior displacement of the trochlea, increasing traction on the reflected SO tendon and impairing telescoping ⁶⁾. The ZT distance in patients (41.2 mm) was significantly longer than in normal children (37.1 ± 1 mm).

COVID-19-related mechanisms:

Possible mechanisms include direct viral invasion of skeletal muscle via ACE2 receptors, or immune-mediated myotoxicity and autoimmunity triggered by cytokine release ⁵⁾. Onset approximately 3 weeks after infection is consistent with a reactive response.

---

7. Recent Research and Future Perspectives

For patients: Please read this

The following content is currently in the research stage or under clinical trials, and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

New association with myasthenia gravis

It has been newly reported that ocular myasthenia gravis can present with BS-like findings ³⁾. A mechanism by which AChR receptor blockade causes symptoms similar to restrictive strabismus has been suggested, and the need to include myasthenia gravis in the differential diagnosis for BS patients with vertical strabismus has been pointed out.

New theories on intermittent and recurrent BS

Based on a report of intermittent and recurrent BS (a 5-year-old boy who experienced spontaneous remission within one day), two new theories have been proposed ⁷⁾.

Shilo et al. (2022) proposed two new theories: the “Stretch theory” (repeated stretching of a congenitally short SO tendon leads to tendon sheath thickening → stenosing tenosynovitis) and the “Avoidance theory” (acute pain → avoidance of eye movement → reduced tendon stretching → rapid spontaneous remission) ⁷⁾.

Research on the association between ZT distance and onset

Further validation through prospective studies is expected regarding the association between ZT distance and BS onset ⁶⁾. It is anticipated to be used as a predictive indicator for the onset of congenital BS.

---

8. References

1. Khorrami-Nejad M, Azizi E, Tarik FF, Akbari MR. Brown syndrome: a literature review. Ther Adv Ophthalmol. 2024;16:1-13.
2. Disserol CCD, Maieski A, de Moraes STEH, Yared J. An uncommon cause of diplopia: do not forget Brown syndrome. Arq Neuro-Psiquiatr. 2024;82(10):s00441787798.
3. Wang AT, Goodwin T. Novel association of ocular myasthenia gravis with Brown syndrome in an adult. J Surg Case Rep. 2025;2:rjaf059.
4. Lee JJ, Patil N, Schimmel T, Benson MD, DeSerres JJ. Acquired Brown syndrome as a postoperative complication of orbital wall fracture repair with metallic mesh. Plast Surg. 2025:1-4.
5. Kiziltunç PB, Seven MY, Atilla H. Diplopia due to acquired Brown syndrome after COVID-19 infection. J AAPOS. 2021;25:366-368.
6. Bagheri A, Abbasnia E, Abrishami A, Tavakoli M. Sequential presentation of bilateral Brown syndrome: report of a case with an interesting imaging finding. J Curr Ophthalmol. 2021;33:201-204.
7. Shilo V, Ronen R, Daniel R. “Black curtain, Brown window” - A case of recurrent intermittent idiopathic Brown syndrome with atypical presenting symptoms. Am J Ophthalmol Case Rep. 2022;25:101378.
8. Haliyur R, Firl K, Nadimpalli S, Halawa A, Jacobson A. Acquired Brown syndrome following COVID-19 infection in a child. J AAPOS. 2022;26:273-275.