Superior Orbital Fissure Syndrome (SOFS) is a group of symptoms caused by compression of structures passing through the superior orbital fissure (oculomotor nerve, trochlear nerve, first branch of the trigeminal nerve, and abducens nerve). It is also known as Rochen-Duvigneaud syndrome, first described by Hirschfeld in 1858 and named by Rochen-Duvigneaud in 1896.
According to Japanese clinical guidelines, this condition is defined as “impaired movement of all extraocular muscles and sensory disturbances or irritative symptoms in the first branch of the trigeminal nerve due to a lesion near the orbital apex.” The key difference from orbital apex syndrome is that the optic nerve is not affected.
SOFS is a rare disease, occurring in approximately 0.3% of trauma patients 1). The most common cause is trauma (motorcycle accidents, zygomatic fractures, orbital fractures), and it often develops within 48 hours after facial trauma. Other causes include the following.
In 5.5% of HZO (herpes zoster ophthalmicus) cases, some form of nerve palsy occurs, and there are reports of associated SOFS 2). Congenitally narrow superior orbital fissure is also a risk factor.
The key differentiating factor is the presence or absence of optic nerve involvement. In superior orbital fissure syndrome, the optic nerve is not affected, so visual acuity and visual field are preserved. In orbital apex syndrome, in addition to the cranial nerves passing through the superior orbital fissure, the optic nerve passing through the optic canal is also affected, leading to decreased visual acuity and visual field defects.
Atypical cases without pupillary involvement (pupil-sparing oculomotor nerve palsy) also exist. A case of SOFS presenting as oculomotor nerve palsy without mydriasis after a bicycle fall in a 40-year-old man has been reported1). In vascular causes, conjunctival edema and vascular bruit are observed; in traumatic cases, subconjunctival hemorrhage and periorbital ecchymosis are seen.
In partial SOFS, only the central sector may be affected, resulting in damage limited to the oculomotor nerve, abducens nerve, and nasociliary nerve.
Yes. Taniguchi (2024) reported pupil-sparing SOFS, and atypical cases exist 1). Impaired orbital venous drainage due to displacement of the greater wing of the sphenoid bone is presumed to be the mechanism of pupil sparing. The absence of pupillary symptoms does not rule out SOFS.
Traumatic SOFS is the most common, typically occurring within 48 hours of facial trauma. It develops in 0.3–0.8% of trauma patients 1).
Major causes and characteristic risk information are shown below.
Clinical diagnosis is fundamental; the combination of ophthalmoplegia, ptosis, mydriasis, and sensory disturbance in the first division of the trigeminal nerve is key to diagnosis. It is distinguished from orbital apex syndrome by the absence of optic nerve dysfunction (decreased visual acuity or visual field defects).
The following shows the main differential diagnoses and key points for differentiation.
| Disease | Key points for differentiation |
|---|---|
| Orbital apex syndrome | Accompanied by optic neuropathy (decreased visual acuity and visual field defects) |
| Cavernous sinus syndrome | Horner syndrome and the second and third branches of the trigeminal nerve may also be affected. |
| Tolosa-Hunt syndrome | Painful ophthalmoplegia, responsive to steroids |
| Carotid-cavernous fistula | Pulsatile proptosis, “corkscrew” episcleral vascular dilation, elevated intraocular pressure |
Anti-GQ1b antibody is a marker for differentiation from Miller Fisher syndrome (in cases following HZO) 2). Repeat MRI after 6 months is recommended.
Treatment of the underlying disease is the highest priority, and earlier treatment leads to a better prognosis.
This is indicated when there is stenosis of the superior orbital fissure due to bone fragment displacement. Surgery as early as possible is recommended1), and in non-emergency cases, it is performed on average 10.7 days later. Surgical approaches include the external orbital route (lateral wall), external transethmoidal route (medial wall), and combined orbital-cranial approach (deep decompression).
This is indicated when there is no evidence of bone displacement and compression is mainly due to edema. The following regimen based on the spinal cord and nerve injury protocol is used1,4,5).
In the Taniguchi case, since more than 2 weeks had passed since injury, a low dose was selected: betamethasone 4 mg/day IV for 14 days followed by oral hydrocortisone for 2 months, with complete recovery after 6 months1).
Complete spontaneous recovery has been reported in 8 of 19 cases of traumatic SOFS. Conservative treatment may be chosen due to the risk of additional injury from surgical exploration.
In Tolosa-Hunt syndrome, prednisolone 50–60 mg/day is given for the first 3 days. Orbital pain improves dramatically, but early dose reduction may lead to relapse.
Treatment combining intravenous acyclovir 30 mg/kg/day with steroids (IVMP 1000 mg/day followed by oral PSL 0.5 mg/kg/day) and IVIg (400 mg/kg/day for 5 days) has been reported 2). Although there was no immediate response to immunotherapy, ocular motility restriction improved after 4 months 2).
If no improvement is seen after 6 months, consider strabismus surgery or levator advancement.
It is effective when the main cause is edematous compression without bone fragment displacement. The method used is a methylprednisolone 30 mg/kg bolus followed by 5.4 mg/kg/h continuous infusion for 48 hours, according to the spinal cord injury protocol 1,4,5). Many reports have shown its effectiveness, but evidence from RCTs is lacking.
The superior orbital fissure is a fissure about 22 mm long and 2–8 mm wide formed between the greater and lesser wings of the sphenoid bone, connecting the orbital cavity and the middle cranial fossa. Its shape is pear-like, with a broad base on the nasal side near the sphenoid body and a tip pointing to the upper temporal side. Anteriorly, there is the annulus of Zinn (common tendinous ring).
Lateral sector (outside the tendinous ring)
Structures passing through: Lacrimal nerve, frontal nerve, trochlear nerve, superior ophthalmic vein.
Clinical significance: The trochlear nerve is protected above the annulus of Zinn and is the least susceptible to damage.
Central sector (within the annulus of Zinn)
Structures passing through: Superior and inferior divisions of the oculomotor nerve, nasociliary nerve, abducens nerve, sympathetic plexus. The ciliary ganglion is also located here.
Clinical significance: The abducens nerve is the most vulnerable and prone to injury due to its long intracranial course and proximity to the greater wing of the sphenoid.
Inferior sector
Structures passing through: Inferior ophthalmic vein.
Clinical significance: Isolated injury affects orbital venous drainage.
Just above the superior orbital fissure lies the optic canal, through which the optic nerve and ophthalmic artery pass. The optic canal is a structure independent of the superior orbital fissure, and the absence of optic nerve involvement is a defining feature of SOFS.
Compression by bone fragments or space-occupying lesions causes inflammation and compression of adjacent neural tissues. Because the muscle cone is surrounded by intermuscular septa and Tenon’s capsule, its volume is relatively fixed, making fragile neural structures susceptible to damage from edema, hemorrhage, or tumors.
The mechanisms of traumatic SOFS are mainly (1) direct compression by displaced bone fragments and (2) secondary compression due to hematoma or swelling1).
As a mechanism of pupil-sparing, a hypothesis has been proposed that orbital venous drainage disturbance due to displacement of the greater wing of the sphenoid bone primarily damages the central part of the oculomotor nerve (where vascular supply runs from periphery to center), sparing the pupillary fibers running on the nerve surface1).
In HZO-associated SOFS, microinfarction due to varicella-zoster virus vasculopathy (direct viral invasion of endothelial cells → thrombotic events in small vessels) is presumed as the mechanism2). Direct viral invasion, post-infection immune mechanisms, orbital abscess, and cavernous sinus thrombosis have also been proposed2).
Taniguchi et al. (2024) reported the first case of SOFS presenting with pupil-sparing oculomotor nerve palsy 1). A 40-year-old man developed atypical SOFS after a zygomatic fracture from a bicycle fall. Displacement of the greater wing of the sphenoid bone causing impaired orbital venous drainage was hypothesized as the mechanism of pupil sparing. After reduction of the zygomatic fracture, CT confirmed enlargement of the superior orbital fissure, and complete recovery occurred at 6 months following intravenous betamethasone 4 mg/day for 14 days.
Takahashi et al. (2025) reported a case of a 79-year-old woman who developed delayed SOFS 32 days after the onset of HZO 2). The onset occurred after varicella-zoster virus DNA in cerebrospinal fluid became negative, and small-vessel varicella-zoster virus vasculopathy was hypothesized as the mechanism. After treatment with IVMP + PSL + IVIg, improvement was seen at 4 months. Only 5 previous cases of SOFS after HZO have been reported, making it an extremely rare complication.
Chen et al. (2010) evaluated 33 cases of traumatic SOFS and reported complete recovery in 24–40% with steroid treatment and 21.4% without treatment 3). Treatment guidelines for traumatic SOFS have not been established, and large-scale studies are difficult due to the rarity of the disease.
