The entity with the most similar ophthalmic findings to VKH is sympathetic ophthalmia. Like VKH, sympathetic ophthalmia can present with bilateral panuveitis and exudative retinal detachments. While the associated extraocular findings of VKH can occur in sympathetic ophthalmia, they are incredibly rare [15]. Furthermore, a preceding sympathizing event should be identifiable in review of the patient’s history when entertaining the diagnosis of sympathetic ophthalmia. This is classically thought to occur after penetrating ocular trauma, but the clinician should remember that ophthalmic surgery can also lead to sympathetic ophthalmia.

Uveal effusion syndrome and posterior scleritis are two other conditions in the differential of VKH. Uveal effusion syndrome, unlike VKH, has no intraocular inflammation. Posterior scleritis can be differentiated from VKH by the classic “T sign,” posterior flattening of the globe, on ultrasonography seen with posterior scleritis.

VKH can be divided into four clinical stages: prodromal, acute uveitic, chronic uveitic, and chronic recurrent stages. Patients can present at any of these stages with a variety of signs and symptoms so it is important to understand the characteristics of each stage.

The prodromal stage of VKH is defined by a nonspecific viral-like illness. Symptoms can include fever, nausea, dizziness, headache, retrobulbar pain, and meningism. There may also be cranial nerve palsies or optic neuritis, and a lumbar puncture may reveal a lymphocytic pleocytosis even at this early time point. The prodromal stage usually lasts only a few days before progressing to more severe disease manifestations.

The acute uveitic stage follows the prodromal stage with bilateral blurry vision. While some patients may present with sequential involvement of one eye and then the other, it is most common to have bilateral posterior uveitis in the acute uveitic stage. The intraocular inflammation is defined by multiple serious retinal detachments (Fig. 41.2), optic nerve head hyperemia and edema, and thickening of the choroid.

Fluorescein angiography highlights these findings showing early hypofluorescent spots followed by hyperfluorescent spots, along with leakage and pooling in the areas of exudative retinal detachment in late frames. Ultrasonography can demonstrate the associated choroidal thickening. Similarly, OCT can identify this same choroidal thickening while also confirming the presence and extent of serous retinal detachments.

Typically, months after the acute uveitic stage, the chronic uveitic, or convalescent, stage begins. This stage is defined by choroidal depigmentation, vitiligo, and poliosis. Choroidal depigmentation to a red-orange choroid in conjunction with a pale disc leads to the classic sunset glow fundus, a hallmark of this stage. There can also be additional foci of hypopigmentation in the mid-periphery, particularly inferiorly. In addition to vitiligo of the skin, patients may also develop perilimbal vitiligo, or Sugiura’s sign. This chronic uveitis/convalescent stage may last for months.

The chronic recurrent stage of VKH is defined by a low-grade panuveitis and intermittent recurrent episodes of granulomatous anterior uveitis. While anterior uveitis can occur in the acute stage, it is more common in the chronic recurrent phase of VKH. It is during this phase that iris nodules can arise. The most visually significant complication of this phase is choroidal neovascular membranes [16]. Additional complications secondary to recurrent bouts of inflammation can include posterior subcapsular cataract and glaucoma [17, 18].

VKH is defined by nonnecrotizing granulomatous inflammation of the uveal tract on histopathology. Uveal thickening arises from the infiltration of inflammatory cells, including lymphocytes, macrophages, and melanin filled multinucleated giant cells. Dalen-Fuchs nodules (Fig. 41.3) consist of epithelioid histiocytes that can accumulate in focal deposits between Bruch’s membrane and the RPE [19].

The characteristic uveal inflammation of VKH is thought to arise from an autoimmune T-cell response to antigens within the melanocytes [20, 21]. There are strong HLA associations across specific ethnic and regional demographics. The HLA-DR4 antigen shows the greatest association in Japanese patients. Meanwhile, the HLA-DR1 and HLA-DR4 antigens are associated with VKH in 84 % of Southern California Hispanics [22] and 89 % of Mexicans [23].

The mainstay of treatment and accepted first line agent in the acute phase is systemic corticosteroids. The severity of the intraocular inflammation along with the extraocular findings requires systemic immunosuppression. Early intervention with aggressive steroid regimens can limit the ocular complications. The steroids are typically dosed at 1.0–2.0 mg/kg/day of oral prednisone or pulsed intravenous methylprednisolone (1000 mg daily for 3 consecutive days) followed by high-dose oral corticosteroids [14]. A multicenter study on VKH treatment found intravenous corticosteroids and high-dose oral corticosteroids equally effective as the initial treatment [24]. Tapering of the steroids typically occurs over three to six months after initiation of treatment. A slow taper of the corticosteroids has been shown to improve outcomes [14].

While steroids are quite effective in the acute phase of VKH, relapsing and recurrent inflammation has proven more steroid resistant, often requiring immunomodulatory therapy [12]. These steroid-sparing agents are also employed in cases where the steroid-related side effects are not tolerable. Cyclosporine, dosed at 5 mg/kg/day, is generally the most preferred of these options [25]. Alternatives to cyclosporine can also include the antimetabolites (Methotrexate, Mycophenolate mofetil, and Azathioprine).