Headache and Bilateral Optic Disc Edema as the Initial Manifestation of Vogt-Koyanagi-Harada Disease

A 31-year-old healthy Asian man presented with new headaches and blurred vision. He was found to have bilateral optic disc edema (ODE) and peripapillary subretinal fluid and was initially investigated for causes of raised intracranial pressure. After referral to neuro-ophthalmology, he received a diagnosis of Vogt-Koyanagi-Harada (VKH) disease and his symptoms, ODE, and vision improved promptly with prednisone treatment. HLA typing was performed and returned positive for the HLA-DRB1*04 subtype. Although VKH disease usually presents with granulomatous uveitis or serous retinal detachments, ODE may manifest early in the disease course. Those with ODE in VKH disease are believed to be older and female, but this case demonstrates that these findings were also seen in a young man.

Photo Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Headache and Bilateral Optic Disc Edema as the Initial Manifestation of Vogt–Koyanagi–Harada Disease Prem Nichani, MSc, Panos G. Christakis, MD, Jonathan A. Micieli, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 05/04/2022 FIG. 1. Color fundus photography and intravenous fluorescein angiography. At presentation, color fundus photography (A) and late-phase intravenous fluorescein angiography (B) revealed mild optic disc edema and multilobed serous peripapillary retinal detachments (black arrows), worse in the right eye than left eye. After treatment with prednisone for 3 months, color fundus photography revealed resolution of optic disc edema and serous retinal detachments (C). Abstract: A 31-year-old healthy Asian man presented with new headaches and blurred vision. He was found to have bilateral optic disc edema (ODE) and peripapillary subretinal fluid and was initially investigated for causes of raised intracranial pressure. After referral to neuro-ophthalmology, he received a diagnosis of Vogt–Koyanagi–Harada (VKH) disease and his symptoms, ODE, and vision improved promptly with prednisone treatment. HLA typing was performed and returned positive for the HLA-DRB1*04 subtype. Although VKH disease usually presents with granulomatous uveitis or serous retinal detachments, ODE may manifest early in the disease course. Those with ODE in VKH disease are believed to be older and female, but this case demonstrates that these findings were also seen in a young man. Faculty of Medicine (PN), University of Toronto, Toronto, Canada; Department of Ophthalmology and Vision Sciences (PGC, JAM), University of Toronto, Toronto, Canada; and Division of Neurology (JAM), Department of Medicine, University of Toronto, Toronto, Canada. The authors report no conflicts of interest. Journal of Neuro-Ophthalmology 2021;41:e128–130 doi: 10.1097/WNO.0000000000000917 © 2020 by North American Neuro-Ophthalmology Society Address correspondence to Jonathan A. Micieli, MD, Kensington Vision and Research Centre, 340 College Street, Suite 501, Toronto, ON M5T 3A9, Canada; E-mail: [e-mail] A e128 previously healthy 31-year-old Asian man developed new-onset neck and back pain and constant, mild nonNichani et al: J Neuro-Ophthalmol 2021; 41: e128-e130 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay positional holocephalic headaches. Two days later, he developed blurred vision in both eyes, right greater than left. He saw an optometrist who documented bilateral optic disc edema (ODE) and referred him urgently to the emergency department to rule out an intracranial mass. In the emergency department, he had a normal computed tomography scan of the brain without contrast and was referred for further evaluation. Neuro-ophthalmologic assessment revealed a visual acuity of 20/150 in the right eye and 20/70 in the left eye. There was no relative afferent pupillary defect; color vision was reduced in the right eye (7/14 Ishihara color plates) and normal in the left eye. Humphrey 24-2 SITA-Fast visual field testing showed enlarged blind spots in both eyes. Slit-lamp examination revealed a normal anterior segment without any inflammation, and a dilated examination revealed bilateral ODE and peripapillary subretinal fluid (Fig. 1), which were confirmed with optical coherence tomography (OCT; Fig. 2). Neurological examination was normal. His Asian background, new-onset headache, and bilateral ODE with peripapillary subretinal fluid were concerning for Vogt–Koyanagi–Harada (VKH) disease. He had no history of penetrating ocular trauma and no integumentary findings. Bloodwork including syphilis serology, angiotensin-converting enzyme, C-reactive protein, sedimentation rate, and chest x-ray were normal. Intravenous fluorescein angiography demonstrated bilateral peripapillary dye leakage and pooling in the subretinal space without retinal vasculitis. Lumbar puncture was deferred due to the absence of neurological findings and highly characteristic ocular signs of VKH. He was started on prednisone 60 mg daily; 1 week after treatment, his visual acuity improved to 20/40 in the right eye and 20/ 60 in the left eye as the subretinal fluid decreased, and his FIG. 2. Spectral domain optical coherence tomography (SD-OCT). SD-OCT revealed subretinal fluid involving the fovea at presentation (A) with some improvement 1 week after starting oral prednisone (B). A small cuff of subretinal fluid was still present at 1 month in the left eye (C) but resolved in both eyes after 3 months of oral prednisone (D). There was no recurrence of subretinal fluid 2 months after tapering off prednisone. OD, right eye; OS, left eye. Nichani et al: J Neuro-Ophthalmol 2021; 41: e128-e130 e129 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay headaches resolved completely. A slow taper of the prednisone was scheduled over 3 months to reduce risk of recurrence. His visual acuity improved further to 20/30 in both eyes 1 month after treatment and 20/20 in both eyes 5 months after presentation, without any evidence of disease recurrence after stopping prednisone. HLA typing was performed and returned positive for the HLADRB1*04 subtype, further supporting the diagnosis of VKH (1). VKH disease is an uncommon, but important systemic autoimmune condition that occurs in genetically susceptible individuals, predominantly those of Asian, Middle Easterners, and Native American descent (2). It is a diagnosis usually made by ophthalmologists since granulomatous uveitis and serous retinal detachments are the most common presenting clinical features (2). Less commonly, ODE may be the only clinical manifestation, and this is believed to occur predominantly in females (3). Yang et al (4) reported a case of a 40-year-old woman with mild headache and blurred vision with ODE in both eyes and peripapillary subretinal fluid. Her symptoms and ODE resolved after a 4-month course of prednisone. Le et al (5) reported a case of a 69-year-old Polish-Australian woman with ODE and leptomeningeal enhancement that was diagnosed after she developed vitiligo despite a normal brain biopsy. Okunini et al (3) reported 14 patients with mainly ODE, and 13 of these patients were female and had a much older mean age (54.6 vs 40.5 years) compared to those with serous retinal detachments. Our case was unique in that the patient with early ODE was male and young. The ODE in VKH disease is believed to be a result of peripapillary choroidal thickening and focal areas of leakage at the level of the retinal pigment epithelium (4). In these cases, OCT with enhanced-depth imaging can help in the detection of peripapillary subretinal fluid and thickening of the choroid (4). ODH has been found to predominate in patients with small cup-to-disc ratios, and extensive optic disc swelling in VKH disease can also compromise the microvasculature of the optic nerve head result in ischemic optic neuropathy (6). Headache in patients with ODE suggests raised intracranial pressure. However, this patient’s visual acuity was reduced out of the proportion to the ODE. A careful examination of the peripapillary optic nerve revealed areas of subretinal fluid, and this could easily be missed with direct ophthalmoscopy, further supporting the importance of slit-lamp biomicroscopy, indirect ophthalmoscopy, or fundus photography in routinely evaluating all patients with ODE. Although severe ODE can also result in peripapillary subretinal or intraretinal fluid, this patient had mild ODE, as evidenced by the visibility of the retinal vessels on the optic nerve itself. The mechanism of the headache was likely a result of aseptic meningitis because e130 pleocytosis is the most common finding in the cerebrospinal fluid (2). The diagnosis of VKH disease is a clinical one, and therapy with prompt therapy with high-dose oral corticosteroids and immunosuppression is essential to prevent vision loss (2). The diagnosis was made in our case, given his Asian background, serous peripapillary retinal changes, the exclusion of other inflammatory ocular conditions with intravenous fluorescein angiography, and ancillary blood testing and his HLA-DRB1*04 subtype (1). He also had an excellent response to prednisone. The diagnosis of VKH can be challenging because patients may also present with headache, auditory, integumentary findings, or have rarer focal neurologic signs such as cranial neuropathies, hemiparesis, aphasia, and acute transverse myelitis (2). A high index of suspicion is required in these cases, especially in those of Asian, Middle Easterners, and Native American background. In conclusion, headache and ODE may be the initial manifestation of a uveomeningeal syndrome such as VKH disease. A careful fundus examination is required to detect serous retinal detachments, which are highly the characteristics of the disease. Although patients with predominant ODE are believed to be female and of older age, this case demonstrates that it was also seen in a young man. STATEMENT OF AUTHORSHIP Category 1: a. conception and design: J. A. Micieli and P. G. Christakis; b. acquisition of data: P. Nichani, P. G. Christakis, and J. A. Micieli; c. analysis and interpretation of data: P. Nichani, P. G. Christakis, and J. A. Micieli. Category 2: a. drafting the manuscript: P. Nichani; b. revising it for intellectual content: P. G. Christakis and J. A. Micieli. Category 3: a. final approval of the completed manuscript: P. Nichani, P. G. Christakis, and J. A. Micieli. REFERENCES 1. Shi T, Lv W, Zhang L, Chen J, Chen H. Association of hla-dr4/hladrb1∗04 with vogt-koyanagi-harada disease: a systematic review and meta-analysis. Sci Rep. 2014;4:1–7. 2. Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol. 1995;39:265–292. 3. Okunuki Y, Tsubota K, Kezuka T, Goto H. Differences in the clinical features of two types of Vogt-Koyanagi-Harada disease: serous retinal detachment and optic disc swelling. Jpn J Ophthalmol. 2015;59:103–108. 4. Yang HK, Park KH, Kim JS, Hwang JM. Bilateral disc edema in a patient with Vogt-Koyanagi-Harada disease. Can J Ophthalmol. 2014;49:e54–e56. 5. Le TA, Simon S, Gilhotra T, Hissaria P. Vogt-Koyanagi-Harada syndrome presenting with bilateral optic disc swelling and leptomeningeal enhancement. BMJ Case Rep. 2019;12:e229719. 6. Nakao K, Abematsu N, Mizushima Y, Sakamoto T. Optic disc swelling in Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2012;53:1917–1922. Nichani et al: J Neuro-Ophthalmol 2021; 41: e128-e130 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.