Introduction

Vogt–Koyanagi–Harada (VKH) disease is a granulomatous multisystem inflammatory disorder that classically affects the uvea, the inner ear, the meninges, and the skin and hair. We report three patients who presented with initial findings suggestive of optic neuritis, who underwent brain imaging studies and CSF analysis. All three were subsequently diagnosed with VKH disease with the aid of fluorescein angiographic imaging of the retina, despite the absence of the characteristic meningismus, or auditory and cutaneous manifestations of this systemic disease.

Methods

We performed a retrospective review of the medical records of three consecutive cases with similar clinical findings and similar initial and final diagnosis.

Case reports

Case 1

A 35-year-old Hispanic woman with no previous medical problems reported sudden onset of headache, sensitivity to light, and bilateral visual loss followed by an episode of left upper extremity weakness, which had resolved after 1 week. She had no neck stiffness. Although her initial diagnosis was optic neuritis and demyelinating disorder, a lumbar puncture after a CT scan of the head was negative. Because her symptoms continued to progress, three weeks after the onset of symptoms she was referred to the eye clinic. Her visual acuity was 20/400 in both eyes, color vision was reduced in the right eye, and light brightness appreciation was normal. Ophthalmic examination revealed bilateral swollen, hyperemic optic discs with blurring of the disc margin and several flame-shaped hemorrhages (Figs. 1A, B). A few anterior chamber cells and vitreous cells were present in both eyes. An MRI of the brain was normal, and repeat CSF analysis showed an elevated lymphocyte fraction at 90% (normal: 40–80%). No oligoclonal bands were present. A fundus fluorescein angiogram showed pinpoint hyperfluorescent spots at the level of the retinal pigment epithelium in both eyes (Fig. 1C) that led to diagnosis of VKH disease. She was treated with oral prednisone, 100 mg day−1. Two weeks later, her visual acuity had improved to 20/30 in both eyes, and the optic nerve swelling and the cells in the anterior chamber and vitreous had greatly diminished. There were no extraocular findings, for example tinnitus, vitiligo, poliosis, or alopecia.

Fig. 1
figure 1

(A) Clinical picture of right eye (case 1) revealing optic disc swelling with focal hemorrhage. (B) Optic disc of the left eye (case 1) shows optic nerve swelling. (C) Fluorescein angiography shows leakage in the optic disc and pinpoint leaks at the level of RPE (case 1). (D and E) Clinical pictures of right and left eyes, respectively, showing optic disc swelling (case 3). (F) Fluorescein angiography reveals optic disc leakage and multiple foci of hyperfluorescence spots in the adjacent areas (case 3)

Full size image

Case 2

A 35-year-old Hispanic woman with no significant previous medical problems developed blurred vision and experienced visual distortion for one week. She also reported floaters and flashing lights in both eyes. These symptoms were preceded by a cold and rhinorrhea. She later developed headaches and pain on eye movement. Visual acuity was 20/200 in the right eye and 20/100 in the left eye. She was found to have bilateral optic disc swelling. Optic neuritis of a post-viral inflammatory cause was suspected. An MRI of the brain was unremarkable. Analysis of CSF revealed a lymphocyte fraction of 92% and an absence of oligoclonal bands. Over the next week her vision deteriorated to counting fingers in each eye, and there were few cells in the vitreous cavities. Fundus fluorescein angiography revealed hyperfluorescence of the optic nerve heads with leakage of the dye in the late phase of the angiogram. Neuroretinitis or VKH disease was considered, and oral treatment with 100 mg day−1 prednisone was initiated. Her vision improved; but when the prednisone was reduced from 100 to 60 mg day−1, visual deterioration recurred. Her steroid dose was maintained at 100 mg day−1 for the next 3 weeks. Her visual acuity improved to 20/100 in the right eye and 20/70 in the left eye although the optic discs remained hyperemic and swollen. At this stage, fundus fluorescein angiogram revealed bilateral disc leakage with pinpoint hyperfluorescent dots and subsequent subretinal fluid accumulation. These findings led to the diagnosis of VKH disease. She was started on a daily dose of cyclosporine 5 mg day−1 and the prednisone was gradually reduced. Six months after her initial presentation, her visual acuity improved to 20/25 in the right and left eyes. There were no extraocular abnormal findings.

Case 3

A 25-year-old Hispanic man with no significant past medical history presented to another hospital with a three-week history of headaches and acute painful loss of vision of the right eye of 7 days’ duration. Visual acuity was 20/60 in the right eye and 20/25 in the left eye. Examination revealed bilateral optic disk swelling. His initial workup was unremarkable, including a CT of the head and orbit, lumbar puncture (normal opening pressure, protein, and glucose levels), complete blood cell count, and chemistry profile. The patient was referred for further evaluation five days later. Visual acuity had diminished to 6ft/200 and 8ft/200 in the right and left eyes, respectively. Slit-lamp examination disclosed cells in the anterior chamber and vitreous. Dilated fundus examination revealed optic disk swelling (Figs. 1D, E), and focal serous retinal detachments in both eyes. Fluorescein angiography revealed leakage of the optic disc and multiple foci of hyperfluorescence spots in the adjacent areas (Fig. 1F). The patient was diagnosed with VKH disease and started on oral prednisone 100 mg day−1. Three months later, the patient’s headaches had resolved and his visual acuity had improved to 20/25 in both eyes, the oral steroids were gradually reduced over a 6-month period.

Discussion

In this series the initial diagnosis for all three patients was bilateral optic neuritis. The differential diagnosis of such a bilateral process includes Devic’s disease, immune-mediated optic neuropathy, nutritional amblyopia, Jamaican optic neuropathy, and Leber’s hereditary optic neuropathy [1–4]. Similarly, VKH disease can present with bilateral optic disc changes, usually in conjunction with extraocular changes, for example tinnitus and meningismus. Because choroidal inflammation is a primary and essential component of VKH disease, in the absence of extraocular changes, fluorescein angiography findings and ultrasound examination for choroidal thickening will lead to the proper diagnosis of VKH disease [5]. CSF pleocytosis has also been found helpful in the diagnosis of VKH [6]. It has also been reported that indocyanine green angiography sensitively detects subclincal choroidal involvement and might be useful in cases such as those reported here, showing only a partial clinical picture [7]. With this series, however, brain imaging results were normal, and it was the fluorescein angiography that led to correct diagnosis.

Vogt–Koyanagi–Harada disease occurs more frequently in Asians and Hispanics than in whites [8]. In the acute uveitic stage of VKH disease choroiditis may cause papillitis, which is similar in appearance to optic neuritis. Three categories of VKH disease have recently been described, and all three characteristically show choroiditis [9]. In the first or complete category of VKH disease, the presence of neurologic/auditory symptoms and integumentary features, for example vitiligo, poliosis, or alopecia, are helpful in reaching a diagnosis. In the second category, known as incomplete VKH disease, either neurologic/auditory or integumentary manifestations are present. In the third category, or probable VKH disease, the absence of these extraocular features may make the diagnosis of VKH disease more difficult [9]. The three patients reported here can be categorized as probable VKH disease. Other ocular features of probable VKH disease include bilateral serous retinal detachments and vitritis or anterior chamber cells. None of these was a prominent feature in any of the three cases.

Vogt–Koyanagi–Harada disease should be considered in the differential diagnosis for causes of bilateral optic disc swelling, even in the absence of the characteristic extraocular manifestations of this disease. This is particularly true when the neuroimaging studies reveal no abnormality, and when CSF analysis does not show pleocytosis. In such cases fluorescein angiography of the retina is highly useful in the diagnosis of VKH disease, as shown in all three cases. Vogt–Koyanagi–Harada disease usually responds to early treatment with high-dose systemic corticosteroids. The treatment should be started early and sustained for the first 6 months to prevent sight-threatening complications of the disease.