INTERMEDIATE UVEITIS

Intermediate uveitis is an idiopathic syndrome of intraocular inflammation centered around the peripheral retina and pars plana. The average age at onset is during the third decade of life, but intermediate uveitis is a common cause of uveitis in children. It represents between 4% and 16% of cases in a uveitis referral practice and 16% to 33% of all uveitis cases in children.

Symptoms

Most commonly, a patient with intermediate uveitis presents with unilateral, painless blurring of vision with floaters. A more dramatic loss of vision may occur in patients with cystoid macular edema (CME), vitreous hemorrhage, or even retinal detachment. Anterior segment symptoms of inflammation are mild and rare but may include pain, redness, and photophobia. While initial symptoms are often unilateral, the disease is ultimately bilateral in 80% of cases.

Clinical Features

Intermediate uveitis is defined by fibrocellular exudative aggregates in the anterior vitreous base over the pars plana and anterior retina. These aggregates may coalesce to form a distinctive “snowbank.” Chronic cases may develop neovascularization within or bridging the snowbank as well as vitreous hemorrhage. The intraocular inflammation often leads to CME, the most common cause of visual loss. The vitreous cells often lead to development of epiretinal membrane formation. Acute inflammation may be associated with focal areas of phlebitis and venous dilation. Resultant ischemia may lead to neovascularization and serous and rhegmatogenous retinal detachment. Often, optic nerve edema is present, and neovascularization of the disc may occur.

Ancillary Testing

Fluorescein angiography is important in the evaluation of CME and may be helpful in monitoring response to therapy. Fluorescein angiography is useful in the investigation of cases with phlebitis and/or retinal ischemia.

Pathology/Pathogenesis

The cause of intermediate uveitis is unknown but is presumed to be autoimmune.

Treatment/Prognosis

The majority of patients with intermediate uveitis do well. The final visual outcome depends mostly on macular involvement. Chronic CME, epiretinal membrane formation, and retinal detachment are associated with poorer visual outcome. The most common complications include visually significant cataract, chronic CME, retinal neovascularization, epiretinal membrane, and retinal detachment.

Corticosteroids are very effective in the treatment of the inflammation associated with intermediate uveitis. Systemic and periocular administration is usually required. Neovascularization of the vitreous base requires cryotherapy or panretinal laser photocoagulation. Antimetabolite and immunosuppressive therapy may be required for recalcitrant disease.

Systemic Evaluation

No diagnostic test is available for intermediate uveitis. Diagnostic testing is undertaken primarily to rule out other causes of posterior uveitis.

Intermediate uveitis may be associated with the development of multiple sclerosis. There is a reported 20% chance of developing multiple sclerosis or optic neuritis during a 5-year period after diagnosis with intermediate uveitis. Testing for HLA-DR2 and magnetic resonance imaging of the brain may be indicated in patients with unexplained weakness or optic neuritis.

Visual loss in patients with intermediate uveitis is caused by vitreous floaters and cystoid macular edema. The fundus details in this photograph are poor because

of vitreous inflammation.

Perivascular sheathing may be seen in patients with intermediate uveitis. The inflammation usually produces a periphlebitis. Peripheral retinal ischemia and retinal neovascularization may develop.

Fluorescein angiography reveals cystoid macular edema in a patient with intermediate uveitis.

Aggregation of vitreous cells may result in the formation of vitreous “snowballs.” This patient had numerous opacities in the inferior vitreous.

Multifocal choroiditis and panuveitis (MCP) is a syndrome simulating presumed ocular histoplasmosis syndrome but includes vitreous inflammation, anterior uveitis, and active choroidal lesions. Punctate inner choroiditis (PIC) is a similar syndrome characterized by myopia, photopsia, and scotomas in women, with the choroidal lesions largely confined to the posterior pole. Punctate inner choroiditis has no associated vitritis. These two syndromes likely represent a continuum

of severity of one syndrome. Some patients with MCP or PIC may go on to develop localized or widespread subretinal fibrosis.

Symptoms

Patients may present with decreased vision due to floaters and vitritis. Acute choroidal lesions beneath the macula center, cystoid macular edema (CME), or exudation secondary to choroidal neovascularization may cause decreased vision. Retinal pigment epithelial metaplasia and the formation of fibrotic scars in the macula may also cause loss of vision. Some patients may develop peripheral visual field loss not corresponding to focal areas of choroiditis.

Clinical Findings

Punched-out chorioretinal scars with pigmented borders within the posterior pole and periphery similar to those found in presumed ocular histoplasmosis syndrome are typically found in patients with MCP. These lesions are usually 50 µm to 100 µm in diameter. Acute lesions are yellow-white and primarily involve the choroid and outer retina. There is the frequent development of macular and juxtapapillary choroidal neovascularization, which is the most frequent cause of severe visual loss. The presence of vitritis and/or iritis is an important requirement for the definition of MCP, excluding a diagnosis of presumed ocular histoplasmosis syndrome. Some patients initially classified as having PIC may go on to develop vitritis.

The disease is usually bilateral but may be asymmetric, with delayed development of disease in the second eye. There is a predilection for women, and most are affected within their third decade of life.

Ancillary Testing

Fluorescein angiography may demonstrate lesions within the macula that are not visible by ophthalmoscopy. Acute lesions demonstrate early hypofluoresence with late hyperfluorescent staining. Such lesions may develop in the course of observation of a patient. The fluorescein angiogram may demonstrate CME, leakage from acute

lesions within the macula, and choroidal neovascularization arising from juxtapapillary or macular scars.

Visual field testing may demonstrate peripheral visual field loss not corresponding to acute choroiditis. Enlarged blind spots have also been reported.

Electrophysiologic study has yielded variable results. Some patients with MCP may have severely reduced electroretinograms, while others may have normal findings. Multifocal electroretinography may demonstrate decreased function within the macula.

Pathology/Pathogenesis

The cause of this disorder is unknown. It has been hypothesized that an exogenous pathogen stimulates an immune response. Subsequent exacerbations may occur without an inciting pathogen.

Treatment/Prognosis

Multifocal choroiditis and panuveitis tends to be a chronic disorder lasting months to years. Visual prognosis is guarded. Severe visual loss may occur due to disciform macular scarring, macular fibrotic scarring, atrophy, or chronic CME.

The use of systemic or periocular steroids may be effective in controlling MCP. Some authors have reported success in the treatment of choroidal neovascularization with corticosteroids, although this may be the natural course of regression of some lesions. Corticosteroids are recommended for treatment of acute infiltrative choroidal lesions within the macula causing visual loss or for the treatment of CME.

Systemic Evaluation

No systemic association has been found. A generalized systemic evaluation for infectious and autoimmune causes of uveitis should be performed.

Multiple acute areas of deep chorioretinal infiltration appear yellow-white. A moderate vitritis is present.

The most common cause of vision loss in patients with multifocal choroiditis and panuveitis is choroidal neovascularization. Note the subretinal blood and fluid in the fovea.

Inactive lesions of multifocal choroiditis are difficult to distinguish from presumed ocular histoplasmosis syndrome. The chorioretinal scars may become more pigmented over time, and subretinal fibrosis is common.

Early venous-phase angiogram of the same patient reveals a classic choroidal neovascular membrane.

The finding of subretinal fibrotic bands is suggestive of multifocal choroiditis rather than presumed ocular histoplasmosis syndrome.

Diffuse subretinal fibrosis syndrome is believed to be an advanced form of multifocal choroiditis with panuveitis.