Woman referred for acute progressive visual loss in both eyes

Jeffrey Chang

Vivek Chaturvedi

A 36-year-old woman was referred to the New England Eye Center with acute bilateral disc edema. She was experiencing headaches and acute progressive visual loss starting in her right eye, which was followed by acute progressive visual loss in the left eye. The vision in each eye deteriorated over the time course of 1 week. Associated symptoms included dizziness and tinnitus.

Her ocular history was significant for an asymptomatic right orbital wall fracture that was not surgically repaired. Medical problems included hypertension and liver cirrhosis due to alcoholism. The patient was taking clonidine and had no known drug allergies. Family history revealed that the patient’s father was a Navajo Native American.

Examination

On examination, best corrected visual acuity was hand motion in the right eye and 20/200 in the left eye. The patient was unable to see color plates. The pupil in the right eye showed a relative afferent pupillary defect. Extraocular eye movements were full, and IOP was normal in both eyes. Anterior segment examination showed bilateral 1+ conjunctival injection, fine keratic precipitates, as well as 2+ cell and flare in the anterior chamber of both eyes. There were 1+ cells in the vitreous of both eyes.

Figure 1. Fundus photo of the right eye.

Figure 2. Fundus photo of the left eye. Images: Brenner-Semela L, Hedges TR, McCabe F

Figure 3. OCT of the right eye.

Figure 4. OCT of the left eye.

Dilated fundus examination showed bilateral disc edema and serous retinal detachments in both eyes, as well as flame-shaped hemorrhages in the left eye (Figures 1 to 4).

What is your diagnosis?

Bilateral visual loss, edema

Given the presentation and clinical findings, our differential diagnosis included inflammatory conditions such as Vogt-Koyanagi-Harada syndrome and sarcoidosis, although the serous retinal detachments would be unusual for sarcoidosis. There were no iris nodules, and the fundus did not show sheathing of peripheral retinal veins. Furthermore, a uveitis workup including sarcoidosis, lupus and Wegener’s was negative.

Sympathetic ophthalmia, which presents identically to Vogt-Koyanagi-Harada syndrome, requires a history of penetrating ocular trauma. Malignant hypertension can present with flame-shaped hemorrhages, disc edema and serous retinal detachments, and should be considered in the differential diagnosis. However, the patient’s blood pressure was well-controlled on medication. Infectious causes such as Lyme disease should be considered, as well as idiopathic uveal effusion syndrome. Neoplastic causes, especially intraocular lymphoma, need to be ruled out. MRI of the brain and MRA of the head and neck were normal. A lumbar puncture (performed by neurology) showed pleocytosis (365 white blood cells with 95% lymphocytes) and elevated protein (88 mg/dL). The opening pressure was not recorded at that time.

This patient presented with Vogt-Koyanagi-Harada syndrome.

Discussion

Vogt-Koyanagi-Harada (VKH) syndrome is an idiopathic multisystem inflammatory disease with bilateral uveitis. Both Vogt (1906) and later Koyanagi (1929) described patients with bilateral anterior uveitis with vitiligo, poliosis, alopecia and dysacousia. Harada described a case of posterior uveitis with exudative retinal detachment and pleocytosis of cerebrospinal fluid in 1926.

Today, VKH is considered a single entity of bilateral granulomatous panuveitis variably associated with vitiligo, alopecia, poliosis, auditory dysfunction and central nervous system involvement.

The disease is thought to be a T-cell mediated autoimmune disorder against melanocytes, specifically against tyrosinase proteins of all organ systems. There is a genetic predisposition in pigmented individuals, such as Asians, Hispanics, Native Americans, Asian Indians and Middle Easterners. Women are affected more often than men. VKH is most common in the third to fifth decade of life.

The disease evolves in four phases. A prodromal phase with nonspecific symptoms is followed by the uveitic phase, lasting from 3 to 5 days, which presents with blurred vision, photophobia, ocular pain, bilateral granulomatous uveitis, choroiditis, exudative retinal detachments and disc edema. Upon treatment, the convalescent phase is characterized by improvement of the uveitis, subsiding serous retinal detachments and loss of melanocytes, before the disease enters the chronic/recurrent phase, which is often associated with complications due to the disease itself or due to the treatment of VKH with steroids (Table).

Complications include cataracts, glaucoma, choroidal neovascular membranes and subretinal fibrosis. The diagnostic workup for VKH includes a lumbar puncture, typically associated with lymphocytic predominance and elevated protein. Blood work and neuroimaging should be performed to rule out malignancy and other systemic disease. A fluorescein angiogram typically shows patchy areas of delayed choroidal perfusion with pinpoint spots of staining, window defects and optic nerve head leakage.

The diagnostic criteria for VKH have been revised, and the disease has been categorized into the following groups: probable VKH (criteria 1 to 3), incomplete VKH (criteria 1 to 3 and either 4 or 5) and complete VKH (fulfilling all criteria 1 to 5).

The revised diagnostic criteria are:

1. No history of penetrating ocular trauma.

2. No evidence of ocular/systemic disease.

3. Bilateral ocular disease (early or late manifestations).

4. Neurologic/auditory findings.

5. Integumentary findings.

Treatment

Systemic corticosteroids are the mainstay of therapy for VKH. Therapy should be started early with a slow taper. Despite treatment, recurrences and complications are common. Immunomodulatory therapy with cyclosporine or other cytotoxic agents should be considered.

As mentioned above, the differential diagnosis of VKH syndrome includes other causes of posterior uveitis and panuveitis, particularly sympathetic ophthalmia, primary intraocular lymphoma, ocular Lyme borreliosis, sarcoidosis and others.

Our patient was started on oral steroid treatment. Her vision improved to 20/400 in the right eye and 20/60 in the left eye within 3 weeks. The serous retinal detachments subsided, and the bilateral disc edema improved markedly. A repeat lumbar puncture showed a cell count of 12 and a normal protein level (Figures 5 to 7).

Figure 5. Follow-up fundus photos, 3 weeks later.

Figure 6. Follow-up OCT right eye, 3 weeks later.

Figure 7. Follow-up OCT left eye, 3 weeks later.

Rheumatology was consulted to help with management of corticosteroid therapy and to consider treatment with immunomodulators. The patient is currently followed and managed interdisciplinarily by ophthalmology, rheumatology and neurology as well as otolaryngology.

References:

• Andreoli CM, Foster CS. Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin. 2006;46(2):111-122.
• Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol. 1995;39(4):265-292.
• Read RW. Vogt-Koyanagi-Harada disease. Ophthalmol Clin North Am. 2002;15(3):333-341.
• Read RW, Holland GN, Rao NA, et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature. Am J Ophthalmol. 2001;131(5):647-652.
• Read RW, Rechodouni A, Butani N, et al. Complications and prognostic factors in Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2001;131(5):599-606.

• Linda Brenner-Semela, MD, Thomas R. Hedges III, MD, and Frank McCabe, MD, can be reached at Tufts Medical Center, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.

• Edited by Jeffrey Chang, MD, and Vivek Chaturvedi, MD. Drs. Chang and Chaturvedi can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.