Case of the Month

Edited by Robert N. Johnson, MD

Case History

A 58-year-old Chinese woman presented with the complaint of progressive blurred vision in both eyes, and headache of 3 days duration.

On examination, visual acuity was 20/40 in the right eye and 10/200 in the left eye. The anterior segment examination showed no inflammation and mild cataract in each eye. Dilated examination revealed clear vitreous, mild disc hyperemia, and multifocal serous detachments involving the macula in both eyes (Figures 1-4). Wide-field fundus autofluorescence showed areas of hyperautofluorescence corresponding to the locations of the serous detachments (Figures 5 and 6). Fluorescein angiography revealed multiple focal areas of leakage at the level of the retinal pigment epithelium and sub-retinal pooling of dye (Figures 7 and 8). Spectral domain optical coherence tomography confirmed the serous retinal detachments (Figures 9 and 10). A- and B-scan ultrasonography revealed axial lengths of 22.21 mm in the right eye and 21.86 mm in the left eye, and diffuse choroidal thickening in both eyes (Not shown).

Differential Diagnosis

Posterior scleritis, sympathetic ophthalmia, Vogt-Koyanagi-Harada disease, central serous chorioretinopathy, uveal effusion syndrome, nanophthalmos, hypertensive choroidopathy, chronic kidney disease, leukemic choroidopathy.

Additional History, Diagnosis, and Clinical Course

The patient had no past ocular history, including no history of ocular trauma or surgery. She denied neck stiffness, tinnitus, or other auditory disturbances. The patient’s blood pressure was within normal limits and recent blood work performed elsewhere revealed a normal complete blood count and normal renal function, making hypertension, chronic kidney disease, or leukemia unlikely causes. Posterior scleritis and sympathetic ophthalmia were ruled out given the lack of fluid in sub-Tenon’s space on B-scan and lack of ocular surgical/trauma history, respectively. Given the patient’s Asian race, concomitant headache, and classic posterior segment findings, the diagnosis of Vogt-Koyanagi-Harada disease was made.

After ruling out syphilis and active TB infection, the patient was started on systemic prednisone, 60 mg daily with a slow taper. Within 2 weeks of initiating therapy, the serous detachments had resolved (Figures 11 and 12). At 6 weeks follow-up, the serous detachments remained resolved with 20/40 vision in each eye.

Discussion

Vogt-Koyanagi-Harada disease (VKH) is a bilateral granulomatous panuveitis that is characterized in the acute stage by serous retinal detachments and symptoms of meningeal irritation, and also may be accompanied by auditory disturbances. In later stages patients may develop depigmentation of the choroid, and cutaneous signs such as poliosis and vitiligo.¹

VKH is more common in Asian, Latino, and Native American individuals. In one study of 51 cases of VKH from Northern California, 41% of patients were Asian.² In Japan, it has been reported to account for 7% of all identifiable uveitis cases.³ It tends to affect individuals between the ages of 20 and 50.¹ The exact pathogenic mechanism of VKH is unknown. However, it is likely related to an autoimmune response directed against melanocyte antigens in genetically susceptible indviduals.⁴ Certain HLA-DR4 loci have been associated with an increased risk of VKH.⁵

Classically, VKH manifests in sequential stages.¹ The prodromal stage is characterized by a non-specific viral-like illness, which may include meningismus symptoms such as neck stiffness, headache, and photophobia. Patients may also develop tinnitus or dysacusis. The acute uveitic stage follows shortly thereafter and features bilateral posterior choroidal thickening with serous retinal detachments, disc hyperemia, and RPE alterations that manifest as multiple pinpoint leaks on fluorescein angiography. VKH is a bilateral disease, however patients may present with unilateral findings, with the fellow eye becoming involved a few days later. Delays in involvement of the fellow eye from 11 months to 6 years later have been reported,⁶ however these cases are very unusual. During the chronic uveitic, or convalescent, stage, de-pigmentation of the choroid occurs (“sunset glow” fundus). Patients may also develop integumentary signs including poliosis and vitiligo. Individuals who had preexisting perilimbal melanosis prior to the development of VKH may develop perilimbal vitiligo (Sugiura sign) in the convalescent stage. The chronic recurrent stage is characterized by recurrent granulomatous anterior uveitis. Late causes of vision loss include cataract, glaucoma, choroidal neovascularization, and subretinal fibrosis.⁷

Initial treatment is with high dose systemic corticosteroids (e.g., prednisone 1-2 mg/kg/day) with a gradual taper over months.⁴ Intravenous methylprednisolone (typically 1 gm/day for 3 days) may also be tried if oral steroid therapy fails. Noncorticosteroid immunosuppressive therapy may be required to control recurrent or refractory inflammation. Nearly two-thirds of patients treated with early and aggressive systemic corticosteroid therapy retain 20/40 of better visual acuity.¹

References

1. Goto H, Rao PK, Rao NA. Vogt-Koyanagi-Harada Disease. In: Ryan SJ, Schachat AP, Sadda SR, eds. Retina. Fifth ed. Elsevier:1326-1336.
2. Ohno S, Char DH, Kimura SJ, et al. Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol 1977;83:735-740.
3. Ohguro N, Sonoda KH, Takeuchi M, Matsumura M, Mochizuke M. The 2009 prospective multi-center epidemiologic survey of uveitis in Japan. Jpn J Ophthalmol 2012;56:432-435.
4. Read RW, Rao NA, Cunningham ET Jr. Vogt-Koyanagi-Harada disease. Curr Opin Ophthalmol 2000;11:437-432.
5. Shi T, Lv W, Zhang L, Chen J, Chen H. Association of HLA-DR4/HLA-DRB1*04 with Vogt-Koyanagi-Harada siease: A systematic review and meta-analysis. Sci Rep 2014;10:6887.
6. Roe RH, Rathinam SR, Wong RW, McDonald HR, Jumper JM, Cunningham ET Jr. Delayed fellow eye involvement in patients with Vogt-Koyanagi-Harada disease. British Journal of Ophthalmology 2009;93:701-702.
7. Luo I, Rechdouni A, Rai NA, Johnston RH, Margolis TP, Cunningham ET Jr. Subretinal fibrosis in patients with Vogt-Koyanagi-Harada disease. Ophthalmology 2000;107:1721-1728.