Older man presents with headache, blurry vision and redness of right eye
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A 73-year-old man presented to the emergency department at Tufts Medical Center as a referral from an outside ophthalmologist.
The patient began experiencing a right-sided headache approximately 5 days before presentation, which was diagnosed by an outside provider as a migraine. Over the next several days, the patient developed an erythematous rash over his right forehead and scalp that was associated with right eyelid swelling and blurry vision. He was evaluated at an urgent care facility, where he was noted to have corneal dendrites on exam. He was started on valacyclovir and tobramycin/dexamethasone eye drops for presumed herpes zoster ophthalmicus (HZO) with instructions to follow up with an ophthalmologist in 2 days.
At the time of presentation, the patient reported pain along the right eyelid and forehead, blurry vision and redness of the right eye. He denied ocular discharge, flashes or diplopia. His review of systems was unremarkable, with no fever, weight loss/anorexia, myalgias, scalp tenderness or jaw claudication. His medical history was significant for hypertension, hyperlipidemia, type 2 diabetes and chronic kidney disease. His ocular history was significant for mild cataracts in both eyes in addition to nonproliferative diabetic retinopathy. His family history was noncontributory. The patient was a retired carpenter, currently married and living at home with his wife. He had no known drug allergies and denied use of alcohol, tobacco or recreational drugs.
Examination
Upon examination, the visual acuity was 20/200 in the right eye and 20/25 with correction in the left. The right pupil was mid-dilated and poorly reactive without relative afferent pupillary defect (RAPD); however, the left pupil was round, brisk and reactive. The patient had significantly reduced abduction of the right eye, but extraocular movements were otherwise full and painless bilaterally. Confrontation visual field and color vision testing were full in the left eye. However, given the significant visual impairment in the right eye, the patient was unable to complete these examinations. IOPs were within normal limits bilaterally.
External examination demonstrated an erythematous and vesicular rash over the right forehead and periorbital area with extension to the tip of the nose. Slit lamp examination of the right eye demonstrated reactive ptosis with mild conjunctival chemosis and diffuse corneal pseudodendrites. Anterior segment exam of the left eye was unremarkable. Dilated fundus exam of both eyes demonstrated pink and healthy-appearing optic nerves with a 0.4 cup-to-disc ratio and scattered dot-blot hemorrhages and microaneurysms in most quadrants bilaterally.
Source: Jonathan T. Caranfa, MD, PharmD, and Laurel N. Vuong, MD
Diagnostic imaging was performed to better elucidate the etiology of the decreased vision. OCT of the retinal nerve fiber layer showed normal optic nerve thickness (Figure 1). Ganglion cell complex analysis demonstrated full thickness bilaterally. Macular OCT demonstrated normal contour without intra- or subretinal fluid bilaterally.
MRI of the brain and orbits T1 fat-saturated postcontrast sequencing revealed abnormal enhancement of the right optic nerve and optic nerve sheath that extended posteriorly to the optic nerve chiasm (Figure 2).
What is your diagnosis?
The differential diagnosis in a patient experiencing progressive vision loss, minimally responsive pupil and MRI findings of optic nerve/retrobulbar enhancement must include infectious, inflammatory/autoimmune and neoplastic processes.
Infectious etiologies to consider include syphilis, tuberculosis and invasive fungal disease. Herpes simplex virus and varicella zoster virus (VZV) can cause inflammation of the optic nerve sheath, seen as a concomitant optic perineuritis. Inflammatory etiologies include sarcoidosis, granulomatosis with polyangiitis (formerly Wegener granulomatosis), rheumatoid arthritis, systemic lupus erythematosus and IgG4-related disease. With optic nerve involvement, as in this case, myelin oligodendrocyte glycoprotein optic neuritis should be part of the differential diagnosis. In any older patient with significant vision loss and headache, one must also consider giant cell arteritis. Finally, tumors (both benign and malignant) such as meningioma, leukemia, lymphoma, multiple myeloma and metastasis should be ruled out.
The differential diagnosis in a patient with sudden-onset abduction deficit suggestive of a sixth cranial nerve palsy should include microvascular (especially in the setting of known cardiovascular risk factors), traumatic and intracranial processes including stroke, demyelination or inflammatory disorders. Often, brain and orbital imaging in the form of MRI will be utilized to rule out these processes.
Workup and management
In general, patients with evidence of optic perineuritis/neuritis with retrobulbar inflammation would undergo extensive workup to rule out infectious, inflammatory and neoplastic causes as described above. However, given the classic presentation (dermatomal vesicular rash with corneal pseudodendrites) of HZO, the presence of retrobulbar optic nerve inflammation and cranial neuropathy was presumed to be related to herpes zoster, and therefore additional testing, including lumbar puncture, was deferred.
The patient was initiated on systemic corticosteroids in the form of IV methylprednisolone 250 mg every 6 hours for 3 days and transitioned to oral prednisone 60 mg per day. He was continued on antiviral medication in the form of valacyclovir 1 g three times per day for a total treatment course of 10 days.
Discussion
HZO is caused by a double-stranded DNA virus (VZV) that, when reactivated from a dormant state in the sensory dorsal ganglion, begins replicating in the nerve cells. Subsequently, virions travel down the axons to the skin or ocular adnexa, resulting in a local inflammatory response. HZO specifically results from reactivation along the trigeminal nerve in a V1 distribution, leading to ocular symptoms such as eye pain, tearing, redness, photophobia and/or decreased visual acuity. These symptoms are associated with a painful vesicular dermatomal rash involving the scalp, forehead, eyelids and periorbital tissue. Before vesicular eruptions, patients typically experience fever, malaise, headache and/or pain.
While many ophthalmologists are familiar with the typical manifestations of HZO including conjunctivitis, epithelial/interstitial keratitis and uveitis, severe manifestations such as cranial neuropathies can occur in rare instances. In a recent retrospective analysis, Maher and colleagues identified 37 patients with diagnosed VZV and cranial nerve neuropathy, noting optic nerve involvement most commonly (32%) followed by oculomotor (24%), trigeminal (22%), trochlear (14%) and abducens (11%). Of these individuals, those who were considered immunocompromised were significantly less likely to experience cranial neuropathies compared with the immunocompetent patients. Many cases of HZO show non-granulomatous inflammation of the corneal epithelium, iris, trabecular meshwork, ciliary body or choroid; however, autopsy results have demonstrated severe granulomatous inflammation resulting in tissue necrosis and occlusive vasculitis.
Diagnosis of HZO is often made clinically with some providers utilizing corneal and eyelid scrapings tested via Tzanck smear to aid in confirming the diagnosis. Alternatively, immunohistochemical assays specific for VZV in addition to polymerase chain reaction testing may be obtained. When atypical features such as decreased vision unexplained by clinical exam findings, pupillary abnormalities or cranial neuropathies are present, brain and/or orbital imaging should be obtained as outlined above.
Treatment of HZO is centered around antiviral therapy with oral acyclovir 800 mg five times a day, famciclovir 500 mg three times a day or valacyclovir 1,000 mg three times a day typically used. In cases of dissemination to the central nervous system or otherwise high-risk disease, intravenous acyclovir is often employed. While controversial, high-dose IV or oral corticosteroids can be initiated to help hasten clinical recovery, with at least one author demonstrating positive results in a patient with HZO and optic neuritis.
Clinical course continued
The patient was followed closely with significant improvement in visual acuity measured at 20/30 (from initial 20/200) in the right eye 1 week after initiating corticosteroid and antiviral therapy. The right pupil was noted to be slightly more reactive but was still mid-dilated without RAPD. Motility examination revealed persistent abduction deficit in the right eye. The patient was continued on oral prednisone 60 mg per day tapered over the course of 10 days. Upon follow-up several months later, his visual acuity remained stable, measuring 20/30 without evidence of recurrence of his optic perineuritis. The right pupil was noted to be brisk and reactive without RAPD. The patient’s abduction deficit had significantly improved, but some slight abduction limitations were still present.
- References:
- Buchbinder SP, et al. J Infect Dis. 1992;doi:10.1093/infdis/166.5.1153.
- Hedges TR 3rd, et al. Ophthalmology. 1982;doi:10.1016/s0161-6420(82)34842-3.
- Hirota A, et al. BMC Ophthalmol. 2023;doi:10.1186/s12886-023-02938-w.
- Liesegang TJ. Ophthalmology. 2008;doi:10.1016/j.ophtha.2007.10.009.
- Maher MD, et al. J Neurol Sci. 2022;doi:10.1016/j.jns.2022.120262.
- Schmader K. Clin Geriatr Med. 2007;doi:10.1016/j.cger.2007.03.003.
- Singh P, et al Nepal J Ophthalmol. 2016;doi:10.3126/nepjoph.v8i1.16142.
- For more information:
- Edited by Jonathan T. Caranfa, MD, PharmD, and Angell Shi, MD, of New England Eye Center, Tufts University School of Medicine. They can be reached at jcaranfa@tuftsmedicalcenter.org and ashi@tuftsmedicalcenter.org.
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