Orbital Apex Syndrome Secondary to Herpes Zoster Ophthalmicus

Clinical manifestations of empty sella syndrome include hypopituitarism cerebrospinal fluid rhinorrhea, headache, and visual abnormalities. A 21-year-old woman reported a 6-month history of worsening vision 3 years after decompression of a sellar-suprasellar Rathke cleft cyst. Her magnetic resonance imaging (MRI) showed a well-defined recurrent cyst in the sellar-suprasellar region causing chiasmatic compression. She underwent an endonasal, endoscopic decompression of the cyst, with subsequent improvement in her vision. A postoperative computed tomography confirmed good decompression of the cyst. Ten days after surgery, she reported sudden loss of vision in both eyes. MRI revealed an empty sella with herniation of both anterior cerebral arteries and optic chiasm into the sella. She underwent transnasal packing of the sellar floor with fat graft and bone plaques, and experienced gradual improvement in vision in her right eye.

Original Contribution Orbital Apex Syndrome Secondary to Herpes Zoster Ophthalmicus Florent Verhaeghe, MD, Max Villain, MD, PhD, Pierre Labauge, MD, PhD, Vincent Daien, MD, PhD Abstract: Orbital apex syndrome is a rare complication of herpes zoster ophthalmicus. In addition to our case, we review the clinical presentation, imaging findings, treatment options, and prognosis of 14 other reported cases. Magnetic resonance imaging of our patient demonstrated diffuse enhancement of the orbit involving the orbital apex, optic nerve and/or nerve sheath, extraocular muscles, and orbital soft tissues. There was significant clinical improvement with acyclovir and systemic corticosteroids, which seems to be preferred treatment for this disorder. Journal of Neuro-Ophthalmology 2016;36:147-151 doi: 10.1097/WNO.0000000000000349 © 2016 by North American Neuro-Ophthalmology Society I nfection of the ophthalmic branch of the trigeminal nerve by varicella zoster virus (VZV) is designated herpes zoster ophthalmicus (HZO). Ophthalmic manifestations occur in 50%-80% of cases, often as conjunctivitis, keratitis, and iritis (1-3). Extraocular muscle and optic nerve involvement are rare findings, but if present in combination with ophthalmic nerve involvement, they form the orbital apex syndrome (OAS). We report of case of OAS due to HZO and review other published reports in the literature. CASE REPORT An 80-year-old man, with a history of bilateral cataract surgery, myocardial infarction, and atrial fibrillation, had removal of a left corneal foreign body. Ten days later, he developed a left forehead vesicular rash with ocular pain. Department of Ophthalmology (FV, MV, VD), Hôpital Gui De Chauliac, Montpellier, France; Department of Neurology (PL), Hôpital Gui De Chauliac, Montpellier, France; National Institute for Health and Medical Research (INSERM) (VD), Montpellier, France. His ophthalmologist diagnosed keratitis of the left eye in the setting of HZO and prescribed oral acyclovir. One week later, the patient was evaluated in our eye emergency department. Visual acuity was 20/20, right eye and counting fingers, left eye. Examination of the left eye showed chemosis, punctuate keratopathy, and mydriasis with a loss of pupillary reaction to light and near stimuli. Intraocular pressure was normal and nasal aspect of the left optic disc was swollen. Examination of the right eye was unremarkable. The left eyelid was ptotic and left eye movement was limited in all directions (Fig. 1). His medications were fluindione, atenolol, and trandolapril. Normal laboratory results were obtained for the following tests: complete blood count, C-reactive protein, angiotensin-converting enzyme, antinuclear antibodies, and antineutrophilic cytoplasmic antibodies. A lumbar puncture was not performed as the patient was anticoagulated. Orbital magnetic resonance imaging (MRI) revealed involvement of the optic nerve and extraocular muscles (Fig. 2). The patient was treated with intravenous acyclovir (15 mg/kg, 3 times/day for 14 days). After 7 days of acyclovir therapy, visual acuity was 20/100, left eye, and ocular motility was improved. At this point, intravenous methylprednisolone 1 mg/kg per day was prescribed. After 15 days of treatment, visual acuity 20/50, left eye, and the patient was switched to oral valacyclovir and prednisone, tapered over 2 months. At 5 months, acuity in the left eye remained 20/50, the left pupil was larger than the right, left ptosis had resolved, and ocular motility had improved (Fig. 3). The left optic disc was pale. The authors report no conflicts of interest. DISCUSSION Address correspondence to Vincent Daien, MD, PhD, Service d'ophtalmologie, Hôpital Gui de Chauliac, CHU de Montpellier, 80, avenue Augustin Fliche 34295 Montpellier cedex 5, France; E-mail: [e-mail] We performed a literature search of MEDLINE and Google Scholar databases for articles published in English or French from 1966 to August 2015 using the search terms "orbital Verhaeghe et al: J Neuro-Ophthalmol 2016; 36: 147-151 147 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Eyelid ptosis, pupillary mydriasis, and complete ophthalmoplegia of the left eye are present. conditions, clinical features, treatment, and clinical course and articles not written in English or French. We added our case to 14 other published reports of OAS due to HZO (Table 1). Clinical Background The mean age of patients was 68.1 years (range, 29-81 years; 11 women [73.3%]). This age of occurrence is older than that seen with all VZV eye complications (mean age, 62.6 years) (4). The risk of OAS increased with immunosuppressive disease or therapy (n = 5, 33.3% of cases): one had diabetes mellitus (5), one had AIDS (2), one had treated chronic lymphocytic leukemia (6), one had multiple myeloma (7), and one had Hodgkin disease (8). Our patient had a foreign body in the left cornea 10 days before HZO occurred. Arda et al (9) reported a similar case of ocular trauma preceding OAS. Clinical Examination FIG. 2. Postcontrast coronal (A) and axial (B) fatsuppressed T1 magnetic resonance imaging reveals enlargement and enhancement of the extraocular muscles in the left orbit and enhancement of the left optic nerve and optic nerve sheath (arrows). apex syndrome," "ophthalmoplegia," and "herpes zoster ophthalmicus." We also included articles found from references in the case reports. Cases of OAS were defined by ophthalmoplegia with ptosis and visual loss due to optic nerve involvement. We excluded cases with inadequate documentation of the underlying systemic The mean interval between the appearance of a vesicular rash and ophthalmoplegia was 10 days (range, 0-40 days). In total, 6 cases (40.0%) occurred in the first week of the zoster rash. Visual acuity was usually seriously impaired with only 1 reported patient with acuity better than 20/200. The fundus is usually normal with only 4 of the 15 cases (26.7%) demonstrating optic disc edema (6,8). Patient Evaluation Cerebrospinal fluid (CSF) testing was documented in 4 cases, revealing lymphocytic meningitis (1,6,8,10). A previous review showed 88% prevalence of aseptic meningitis FIG. 3. Five months after onset of left orbital apex syndrome, left ptosis has resolved and left eye movements are improved. 148 Verhaeghe et al: J Neuro-Ophthalmol 2016; 36: 147-151 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Verhaeghe et al: J Neuro-Ophthalmol 2016; 36: 147-151 TABLE 1. Cases of orbital apex syndrome secondary to Herpes zoster ophthalmicus Clinical Findings Case Reports Laboratory Results Age/Gender Immunosuppression Initial BVA Time Between Rash and OAS CSF 80/M 78/M 75/M 67/F 81/F 29/F 80/F 70/F 71/F 63/F 67/F 72/F 63/F 54/F 72/F - Diabetes mellitus - - - AIDS - - - Multiple myeloma - Chronic lymphocytic leukemia - Hodgkin disease - CF 20/400 CF 20/100 20/40 20/640 HM CF 20/200 20/200 N/A 20/200 CF N/A N/A 7d 9d 1d 30 d 16 d ,14 d 2 1/2 wks Same time 12 d Same time 2d 14 d 10 d 2d 2 wk N/A N/A N/A Lymphocytic meningitis Lymphocytic meningitis N/A N/A N/A N/A N/A Lymphocytic meningitis N/A N/A Lymphocytic meningitis Lymphocytic meningitis Our case Lee et al (5) Arda et al, (9) Paraskevas et al, (10) Kurimoto et al, (1) Saxena et al, (2) Ugarte et al, (3) Baha ali et al, (19) Shirato et al, (20) Dhingra et al, (6) Krasnianski et al, (12) Chang-Godinich et al, (7) Bourke and Pyle (13) Kattah and Kenerdell (8) Kattah and Kenerdell Imaging Findings Technique Our case Lee et al (5) MRI MRI Arda et al, (9) Paraskevas et al, (10) Kurimoto et al, (1) Saxena et al, (2) Ugarte et al, (3) Baha ali et al, (19) Shirato et al, (20) Dhingra et al, (6) Krasnianski et al, (12) Chang-Godinich et al, (7) Bourke and Pyle (13) Kattah and Kenerdell (8) Kattah and Kenerdell MRI MRI MRI MRI MRI CT MRI MRI MRI MRI CT N/A CT Extraocular Muscles Soft Tissues Thickening enhancement Optic nerve and orbital apex enhancement Thickening enhancement Optic nerve sheath, orbital apex enhancement Thickening Swelling Thickening enhancement Optic nerve sheath, brainstem hypersignal Enhancement Optic nerve and orbital apex enhancement Thickening Retrobulbar fat swelling Enhancement Optic nerve enhancement - - Enhancement Optic nerve and orbital fat enhancement Thickening - Thickening - - - Thickening - N/A N/A - - Outcome Antiviral Steroids Final VA Ptosis and Ocular Motility Recovery IV IV PO PO 20/40 20/100 Partial Partial IV IV IV PO PO PO N/A IV IV PO PO No No PO IV PO PO PO PO PO PO IV PO IV PO PO CF 20/20 20/20 20/25 20/30 20/40 20/200 HM 20/20 20/25 20/20 N/A N/A Partial Total Partial Partial Total Partial Partial None Total Partial Total N/A Total CF, counting fingers; CT, computed tomography; CSF, cerebrospinal fluid; HM, hand movements; MRI, magnetic resonance imaging; N/A, not available, OAS, orbital apex syndrome; PO, per os; VA, visual acuity. 149 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Case Reports Therapy Original Contribution in HZO with ophthalmoplegia (11). Although a search for VZV-DNA by polymerase chain reaction may be done with CSF analysis, the diagnosis of OAS due to HZO is primarily based on clinical findings. High-resolution MRI should be performed for any case of OAS, with fat-suppressed sequences. In the present case report, MRI typically shows diffuse enhancement of the orbital apex involving the optic nerve, extraocular muscles are swollen, consistent with myositis (3,5,9,10,12,13). Treatment All reported patients were treated with systemic acyclovir and steroids except 2 cases in the preantiviral era (8). Although no rigorous clinical trials have studied the efficacy of these treatments, intravenous acyclovir combined with oral steroids seems to be effective therapy. Intravenous acyclovir was beneficial with optic nerve involvement in 3 of 7 cases (42%) recovering acuity of 20/20, but only 1 of 5 cases treated with oral therapy had similar improvement in acuity. OAS developed in our patient while on oral acyclovir, as has been reported previously (3,7,10). Systemic corticosteroid therapy is used to treat the inflammatory response to VZV. In most reports, steroids are prescribed after 48 hours of antiviral medication. Treatment duration is empiric and patients are commonly on antivirals and steroids for 2-6 months, depending on clinical recovery. Prognosis More than half of the patients (n = 9, 60.0%) showed partially recovered visual acuity, but complete resolution was rare (n = 4, 26.7%). Prognosis is favorable for ocular motility and ptosis: 5 patients showed total recovery (33%) and 8 showed partial recovery (53%). Pathophysiological Hypotheses During HZO infection, VZV is reactivated in the trigeminal ganglion and migrates along the ophthalmic division of the trigeminal nerve spreading to the dermatome. Reactivated virus causes inflammation of the trigeminal axons. Ugarte et al (3) suggested a pathological mechanism whereby the virus spreads from the trigeminal nerve to the other nerves within the orbital apex. OAS may be due to immunoreactions against inactive or replicating viral antigens, nerve damage, direct cytopathic effects of the virus, ischemia due to occlusive vasculitis, or most likely from a combination of these factors. MRI findings demonstrate that the inflammation is diffuse, involving the entire orbital cavity. The histologic feature in HZO is perineuritis and perivasculitis of the long ciliary nerves and arteries (14-16). This may lead to demyelination (17), and demyelination of the third, fourth, and fifth cranial nerves has been shown at 150 autopsy and several of the vessels supplying those nerves showed perivascular monocytic infiltrates (18). Optic neuropathy and ophthalmoplegia in OAS are likely the combined result of direct neural injury by the virus, reactive inflammation, demyelination, and perivasculitis. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: F. Verhaeghe and V. Daien; b. Acquisition of data: F. Verhaeghe and V. Daien; c. Analysis and interpretation of data: F. Verhaeghe and V. Daien. Category 2: a. Drafting the manuscript: F. Verhaeghe and V. Daien; b. Revising it for intellectual content: F. Verhaeghe, V. Daien, P. Labauge, and M. Villain. Category 3: a. Final approval of the completed manuscript: F. Verhaeghe, V. Daien, P. Labauge, and M. Villain. REFERENCES 1. Kurimoto T, Tonari M, Ishizaki N, Monta M, Hirata S, Oku H, Sugasawa J, Ikeda T. 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The pathology of ophthalmoplegia in herpes zoster ophthalmicus. Neuroophthalmology. 1984;4:75-80. 19. Baha Ali T, Moutaouakil A, Ouaggag B, Khoumiri R, Aderdour L, Hassani R, Raji A, Jamali A. Orbital apex syndrome secondary to herpes zoster infection. A case report [in French]. Bull Société Belge Ophtalmol. 2008:39-43. 20. Shirato S, Oshitari T, Hanawa K, Adachi-Usami E. Magnetic resonance imaging in case of cortical apex syndrome caused by varicella zoster virus. Open Ophthalmol J. 2008;2:109- 111. Images in Neuro-Ophthalmology Cavernous hemagioma of the optic nerve - chiasmal junction. Top panel: the optic discs are normal in appearance. Middle panel: Postcontrast coronal T1 (A) and axial FLAIR (B) magnetic resonance imaging shows the lesion with heterogeneously increased signal. Blooming (arrow) within the lesion is seen on gradient echo sequence (C). Bottom panel: Intraoperative view shows the cavernous hemangioma at the right optic nerve-chiasmal junction prior to (A,B) and after (C) complete resection. (Courtesy of Jessica Tong, Andrew Davidson, Clare Fraser. Sydney, Australia). Verhaeghe et al: J Neuro-Ophthalmol 2016; 36: 147-151 151 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.