Case study: Superior orbital fissure syndrome caused by herpes zoster

Introduction

Approximately 1 million new cases of herpes zoster are reported annually in the US.¹ Of those cases, approximately 10% develop herpes zoster ophthalmicus (HZO), which translates to about 100,000 cases per year.¹ Cases are on the rise, most likely associated with the increase in the aging population. It is estimated that up to 50% of untreated patients with HZO will develop ocular complications.1 With timely diagnosis and proper treatment, ocular complications associated with herpes zoster can decrease from 29% to 2%.¹

Typical signs and symptoms of herpes zoster include unilateral burning pain, allodynia, headache, and vesicular rash. Typical herpes zoster ophthalmicus symptoms include eyelid edema, conjunctival injection, epiphora, eye pain, blurred vision, photophobia, and decreased visual acuity. These patients often present with ptosis associated with eyelid edema, mucopurulent conjunctivitis, anterior uveitis, keratitis, episcleritis, chemosis, and, at times, Hutchinson sign.¹ Retinal manifestations can include retinal detachment, acute retinal necrosis, progressive external retinal necrosis, and progressive outer retinal necrosis.² Neuro-ophthalmological complications include optic neuritis and ophthalmoplegia.²

Ophthalmoplegia occurs in 3.5% to 10% of HZO cases.² The primary manifestation is paralysis of cranial nerve (CN) III. Superior orbital fissure syndrome (SOFS), also known as Rochon-Duvigneaud syndrome, is a type of orbital apex disorder and involves dysfunction of multiple CNs, including CN III, IV, and VI, and the ophthalmic division of the trigeminal nerve V1.³ Orbital apex syndrome involves all the above-mentioned nerves as well as involvement of the optic nerve, CN II, which affects visual acuity and pupillary reflexes.³ Reported cases of SOFS associated with HZO appear to be less than 10%. However, resources are very limited to confirm this.

Case report

A 74-year-old White man presented to our office who had been previously diagnosed with herpes zoster on the right side of his face. He was treated in the hospital several months prior and released. The patient was seen by one of our MDs and diagnosed with episcleritis and ptosis in the right eye that started 2 months prior. The patient was already on valacyclovir 1 gm orally 3 times a day and was placed on prednisolone acetate 1% drops 4 times a day in the right eye. No other ocular involvement was noted at this time. Patient was given tapering instructions on the prednisolone drops and was given a 6-week follow-up appointment.

I saw the patient 2 months later with reduced vision in the right eye, peripheral vision concerns, intermittent horizontal diplopia, headache, numbness, and constant pressure on his face. The patient reported he had an MRI and CT scan, which were negative. He says he stopped the prednisolone drops because they were not helping. He finished the valacyclovir several weeks prior. He was trying to get an appointment with neurology, but the soonest he could be seen was several months out. Visual acuity in the right eye was reduced from 20/50+2 at his previous visit to 20/80. Left eye acuity was 20/20. Pupils were equal, round, and reactive in both eyes. No afferent pupillary defect in either eye. No nerve palsy and no tropia were noted in either eye. IOPs were normal at 17 and 12, respectively. Slit lamp exam showed ptosis in the right eye, grade 2 conjunctival injection, several fine keratic precipitates on the corneal endothelium, and rare cells in the anterior chamber. Dilated fundus exam revealed grade 2 nuclear sclerosis cataracts in both eyes. Nerve optical coherence tomography and Optos were performed as well, and no other pathology was noted (Figure 1a, 1b).

I diagnosed the patient with a continued episcleritis and mild iritis in the right eye. Since the patient said the prednisolone drops did not help, I prescribed Durezol drops 4 times a day and consulted with his primary care provider (PCP) and started him on prednisone 10 mg orally 3 times a day, as well as valacyclovir 1 gm 3 times a day. His PCP prescribed multiple pain management medications. However, there was no pain relief. The PCP was also working on a neurology referral.

Regarding the diplopia and ptosis of his right upper eyelid, AchR binding, blocking, and modulating blood work was performed to rule out myasthenia gravis. Sedimentation rate and C-reactive protein blood work were also performed. All tests were normal. Previous MRI and CT scans were negative.

The patient was seen 5 days later for a follow-up. A 24-2 visual field test showed fixation errors as well as an inferior positioning artifact, but was otherwise unremarkable for both eyes. (Figure 2a, 2b). Visual acuity improved to 20/40 in the right eye, and, objectively, ocular signs had improved. Subjectively, there was no improvement in his symptoms. I consulted again with his PCP, who, at my request, ordered another MRI of the brain and orbits with and without contrast, as well as a magnetic resonance angiogram (MRA) of the head and neck with and without contrast. All current therapy was continued, and the patient was scheduled for another one-week follow-up.

The follow-up examination revealed a slight decrease in acuity again at 20/60 in the right eye. However, the episcleritis and iritis had objectively improved. Patient reported no improvement in the postherpetic facial pain, numbness, ptosis, or diplopia. The symptoms started affecting his mental health, and he expressed to me that maybe it was “time to be with his friends” who had died before him. I recommended we do a quick taper off the topical and oral prednisone and finish the valacyclovir, as the current therapy was not helping.

The repeated MRI was again negative. However, the MRA showed severe stenosis of the P2 segment of the posterior cerebral artery (PCA). I believe I had determined the source of the diplopia as stenosis of the PCA can disrupt the neural pathways that control eye movements and contribute to diplopia.

I referred the patient to a neuro-ophthalmologist in a university setting. The MD ordered a computed tomography angiogram (CTA) of the head, which was negative, thus disproving the results of the stenosis seen on the MRA. The neuro-ophthalmologist did not have an answer as to why the MRA showed stenosis of the PCA.

The patient was ultimately diagnosed with SOFS affecting CN IV, VI, and V1 of the trigeminal nerve. The patient was started on low-dose pregabalin to help with the postherpetic neuralgia symptoms. He was fitted with a Fresnel Prism for the diplopia and restarted on the prednisolone drops 4 times a day in the right eye for 7 days, followed by a slow taper, as well as artificial tears to help with corneal hypoesthesia and dryness. I consulted with the neuro-ophthalmologist and added Oxervate 6 times a day in the right eye for 8 weeks as well. The patient has been seen for several more follow-ups and continues to improve.

Discussion

The SOF is the area between the greater wing of the sphenoid inferiorly and the lesser wing of the sphenoid superiorly. There are 3 regions within the SOF, based on their location relative to the common tendinous ring, also called the annulus of Zinn. The superior region outside the annulus of Zinn contains the lacrimal nerve, the frontal nerve (branches of CN V1), and the trochlear nerve, as well as the superior ophthalmic vein. The central area of the SOF lies within the annulus of Zinn and contains the superior and inferior branches of the oculomotor nerve (CN III), the nasociliary nerve (another branch of CN V1), as well as the abducens nerve (CN VI). The inferior aspect of the SOF, outside the annulus of Zinn, houses the inferior ophthalmic vein (Figure 3).⁴

Insult to the areas within the SOF (whether due to injury, compression, inflammation, infection, or ischemia) can result in signs and symptoms of SOFS. Symptoms can include ptosis, ophthalmoplegia, anhidrosis, a dilated and nonreactive pupil, corneal hypoesthesia, superior eyelid and/or forehead anesthesia, and proptosis. Upper eyelid ptosis will be noted if the superior division of CN III is involved due to either partial or complete paralysis of the levator palpebrae superior muscle.³ Damage to CN III, IV, and/or VI can cause partial or complete ophthalmoplegia. Innervation by these nerves to the extraocular muscles control globe retraction, and loss of their function can result in proptosis as well.³ Anhidrosis, anesthesia of the superior lid and lower forehead, as well as corneal hypoesthesia, can result if sympathetic innervation along CN V1 is damaged. Pupillary dilation may occur due to loss of parasympathetic innervation to the eye.³

SOFS manifests as a compression of structures within the SOF and is a rare syndrome. Trauma is the most common cause, and 0.3% of patients with skull or facial fractures may develop this condition.³ However, any condition that compresses the structures within the SOF can precipitate SOFS, including metastatic lesions, with breast cancer in women being the most common.³ Infections such as syphilis, meningitis, and herpes zoster can cause inflammation leading to SOFS. Other causes include aneurysms and pseudoaneurysms. It is believed that the only risk factor for the development of SOFS is an anatomically narrow SOF. If SOFS involves the optic nerve, it is referred to as orbital apex syndrome.³

Workup

Workup for patients presenting with these signs and symptoms varies depending on the possible etiology of the suspected SOFS. If it is trauma-related, a CT scan is recommended to assess for fractures to the zygomatic and/or orbital bones. CT is also useful for assessing the size of the SOF. For better visualization of soft tissues and nerve structures, an MRI with and without contrast, with fat-suppressed images of the orbits, is recommended when inflammatory, infectious, or neoplastic causes of SOFS are concerned. Neoplastic lesions may reveal metastasis or meningiomas, and an infectious process may reveal orbital cellulitis or a subperiosteal abscess.³ MRA and CTA can both identify any vascular abnormality. However, CTA may be more reliable. A complete blood count with differential, metabolic panels, and blood cultures is considered standard of care when an infectious process is suspected. If meningitis is suspected, a lumbar puncture may also be warranted. Generally, the SOF is challenging to access surgically.³

Treatment options vary depending on the cause of SOFS. SOFS related to trauma usually involves steroids, fracture repair, and/or evacuation of a hematoma. Megadose steroid use for treatment of SOFS associated with traumatic brain injury must be assessed regarding risks and benefits, as the CRASH study has shown an association with an increased risk of death and disability with megadose steroid use.³

SOFS associated with infection are appropriately treated with antibiotics, antivirals, or antifungals. Steroids may or may not be coupled with this, along with sinus debridement and washout. Vascular causes of SOFS are treated according to the cause, along with minimally invasive procedures as needed.³

Conclusion

Cases of SOFS associated with herpes zoster are rare, with limited literature on reported cases. The mechanism causing ophthalmoplegia in HZO cases is unclear. Hypotheses are many and include the following:

• Perivascular and perineural inflammation detected on histological studies, showing inflammation of vascular and neural tissue of ocular tissues
• Cytopathic damage to neural tissue
• Cranial nerve compression due to edema of the orbital soft tissues
• Presence of microinfarct to the cranial nerves²

Recovery time from SOFS ophthalmoplegia associated with HZO with steroids and oral antivirals, on average, is 4.4 months, with a range of 2 weeks to 1.5 years.³ Complete recovery of ophthalmoplegia has been reported at 76.5%.² This case report demonstrates the importance of vaccination to reduce the incidence of severe complications associated with HZO. This can be achieved by educating our patients about the vaccine, as well as providing information regarding access to the vaccine.

References

1. Lewis K, Palileo B, Pophal C, Yasmeh J, Glendrange R. Herpes zoster ophthalmicus. EyeNet Magazine. January 1, 2020. Accessed April 29, 2026. https://www.aao.org/eyenet/article/herpes-zoster-ophthalmicus-pearls

2. González KM, Herrera Q, Isai J. Superior orbital fissure syndrome secondary to ophthalmic herpes zoster. Pan-Amer J Ophthalmol. 2022;4(1):45. doi:10.4103/pajo.pajo_41_22

3. Heinzman Z, Ahmed B, Linton E. Superior orbital fissure syndrome. EyeRounds. January 26, 2024. Accessed April 29, 2026. https://eyerounds.org/cases/355-Superior-Orbital-Fissure-Syndrome.htm

4. Spalton DJ, Hitchings RA, Hunter PA. Atlas of Clinical Ophthalmology. Lippincott Williams & Wilkins; 1984.