Intermediate uveitis

Intermediate uveitis is a term created by the International Committee on Uveitis to encompass three separate entities: pars planitis, peripheral uveitis, and chronic cyclitis (inflammation of both the pars plana and pars plicata).6 While subtle differences exist between these three entities, for the purpose of this chapter they will be considered together.

CLINICAL PRESENTATION/DIAGNOSIS

Intermediate uveitis is generally an asymptomatic disease in children, but symptoms can include mild blurring of vision and pain in more advanced cases. Occasionally children will complain of floaters or distortion of their vision. This disease is bilateral in 80% of cases but is often asymmetric. Early in the course of the disease accumulations of white blood cells are seen in the anterior vitreous and are often termed ‘snowballs’.

Diagnosis is made clinically by an ophthalmologist by visualizing ‘snowballs’ or ‘snow banks’ (characteristic exudates over the pars plana). Many times diagnosis is made on routine screening of an asymptomatic child. Laboratory investigations are typically normal in these patients and often no causative agent is discovered. Testing is often directed towards Lyme disease, sarcoidosis, and tuberculosis, as each of these entities can present first with an intermediate uveitis and can be treated medically. Also, rare cases of toxocariasis have presented similarly and often an enzyme-linked immunosorbent assay (ELISA) test for Toxocara is performed.

MANAGEMENT/TREATMENT AND PROGNOSIS

As this is generally a benign, self-limited disease, treatment is only indicated when there is decreased vision (<20/40), or significant discomfort. Topical steroids are of little benefit, and periocular steroid injections are often used in cases of significant vision loss. In some cases, systemic immunomodulating therapy is needed. Mydriatic agents can be added to prevent scarring.

When early therapy is initiated for vision loss, most patients regain normal or near normal vision. Exceptions include cases where inflammation causes a posterior cataract to form on the lens, or cases of membrane formation on the retina secondary to chronic inflammation.7

Posterior uveitis

Toxoplasmosis

CLINICAL PRESENTATION/DIAGNOSIS

Toxoplasmosis is the most common form of posterior uveitis seen in children, accounting for at least 50% of cases. The infective agent is the intracellular protozoan Toxoplasma gondii. Cats are the definitive host, with human infection a result of ingestion of the encysted organism in undercooked meats. A large percentage of ocular toxoplasmosis infection occurs in the womb, when a previously uninfected woman is infected during pregnancy. Acquired forms occur, but ingestion of encysted protozoans in immunocompetent individuals usually does not lead to clinical disease. Active ocular toxoplasmosis appears as focal areas of inflammation over the retina and choroid (202). There is significant inflammation in the vitreous and this presentation is often called ‘headlight in the fog’. Central lesions in the retina can cause significant traction and scarring with resulting loss of vision.8

Diagnosis is generally made clinically; however, a laboratory diagnosis can be made with ELISA on undiluted serum. A positive IgM suggests recent infection but a positive IgG does not confirm the diagnosis. Many normal individuals have positive IgG titers without evidence of ocular toxoplasmosis.

MANAGEMENT/ TREATMENT AND PROGNOSIS

Triple therapy (pyrimethamine, a sulfonamide, and clindamycin) is initiated depending on the severity of the disease. Folinic acid is given to help prevent the myelosuppression associated with pyrimethamine. If there is severe inflammation systemic steroids can be given after 24 hours of antibiotic therapy. In immunocompetent individuals ocular toxoplasmosis is a self-limited disease and usually resolves in 1–2 months, so in many cases treatment of peripheral, nonvisionthreatening lesions is unnecessary.

Prognosis depends on the location of the lesion. Peripheral lesions have an excellent prognosis and old toxoplasmosis scars are a common incidental finding on routine ophthalmic exam. Macular lesions usually result in scarring with a scotoma (lack of vision) in the

area of the scar (203). Central lesions or lesions near the optic nerve often result in legal blindness. Recurrences are fairly common and usually occur at the edge of a previous scar. No treatment has been shown to prevent recurrence.

Toxocariasis

CLINICAL PRESENTATION/DIAGNOSIS

Ocular toxocariasis is caused by the canine roundworm Toxocara canis. Infection commonly occurs after ingestion of soil contaminated by the roundworm eggs. Ocular toxocariasis is more common in boys and usually there is a history of geophagia. Ocular involvement is usually unilateral and presents either as endophthalmitis or as a granuloma (peripheral or central). The endophthalmitis is often quite severe and can present with leukocoria (white pupil) and hypopyon.

Accurate diagnosis is important as toxocariasis is one of the most common conditions incorrectly diagnosed as retinoblastoma (with resulting removal of the eye). The most reliable

test for Toxocara antibodies is the ELISA test. Antibody testing of the aqueous or vitreous is more sensitive than serum testing.9 Ultrasound can also be useful in differentiating Toxocara granulomas from retinoblastoma.

MANAGEMENT/TREATMENT AND PROGNOSIS

Peripheral lesions with minimal inflammation are not generally treated. Steroids have been shown to decrease the sequelae of the acute inflammation associated with posterior pole lesions and endophthalmitis. Antihelminthic agents and laser treatments generally increase the level of inflammation with the death of the worm and are not indicated.

Prognosis is poor in cases of endophthalmitis or macular involvement. Endophthalmitis often results in cataract, synechiae formation, and can result in retinal detachment (204).

Macular granulomas commonly cause traction on the retina and significantly decreased vision (205, 206). Peripheral lesions generally do not cause significant visual loss after the inflammation has subsided.

Vogt–Koyanagi–Harada syndrome

CLINICAL PRESENTATION AND DIAGNOSIS

Vogt–Koyanagi–Harada syndrome (VKH) is a multisystem disease, seen more frequently in darker pigmented individuals, that generally presents in three stages. The first stage is commonly mistaken for a viral infection, with flu-like symptoms, headache, and tinnitus or hearing loss. Stage 2 is the ophthalmic stage where patients develop bilateral panuveitis (whole uveal tract), hyperemia of the optic disc, and serous retinal detachments (207). This stage is often when the patient presents with pain, photophobia, and decreased vision. During stage 3, the convalescent stage, dermatologic manifestations appear. These include poliosis (whitening/graying of a patch of hair), vitiligo (208), and alopecia (loss of hair). Stage 3 ophthalmic disease is characterized by retinal depigmentation, proliferation of retinal pigment epithelium, which can cause a puckering of the macula (209), and development of peripheral yellow/white deposits under the retina (Dalen–Fuchs nodules).

Diagnosis is made based on clinical findings since the exact cause of VKH is unknown. Systemic autoimmune response to retinal, uveal, and cutaneous melanocytes has been proposed as a mechanism of the disease, although this is currently unproven. Laboratory studies are usually not helpful in making the diagnosis, but a lumbar puncture with pleocytosis is supportive. Ophthalmic ultrasound during active inflammation shows findings consistent with panuveitis (inflammation throughout the uvea).

MANAGEMENT/TREATMENT AND PROGNOSIS

The mainstay of treatment during the active ophthalmologic stage is systemic corticosteroids. Most cases respond quite well to steroids, with rapid resolution of ocular inflammation and subretinal fluid. Cases that are only partially responsive to corticosteroids are often treated with concomitant cyclosporine.

Prognosis is guarded in these patients. Sometimes the inflammation follows a benign course and resolves entirely after steroid treatment. In others there are frequent recurrences, and the complication rates are high. Complications of chronic uveitis in VKH patients include cataracts, glaucoma, and retinal neovascularization.

Sympathetic ophthalmia

CLINICAL PRESENTATION AND DIAGNOSIS

Sympathetic ophthalmia is an uncommon bilateral panuveitis seen after penetrating ocular trauma or surgery. It presents in both eyes, with the injured eye (exciting eye) often developing inflammation first, and the uninjured eye (sympathizing eye) following weeks to months later. Sympathetic ophthalmia most frequently develops within 3 months (70%) of the original injury; however, it may develop in as short as 5 days and as long as 42 years. More than 90% of cases manifest within the first year. Patients generally present with pain, decreased vision, and photophobia in both eyes.10

The mechanism of disease is unknown, but the consensus is that the immune system is somehow sensitized to uveal antigens during the trauma or surgery and the immune system develops a systemic response to the entire uvea. Laboratory investigations are generally not useful. Fluorescein angiography can be performed (showing multiple foci of retinal leakage and late pooling of dye). However, the diagnosis is most often made clinically.

MANAGEMENT/TREATMENT AND PROGNOSIS

Treatment of sympathetic ophthalmia is controversial. Sympathetic ophthalmia can be prevented with early removal of the injured eye if there is no visual potential. Because of the rarity of sympathetic ophthalmia, if there is any potential vision, removal is not always recommended. High-dose systemic steroids, along with topical and periocular injections, are recommended. Cyclosporine can help in unremitting cases. Once inflammation has

207

207 Panuveitis with serous retinal detachments inVKH.(Courtesy of Peter Buch,CRA.)

208Vitiligo as a manifestation of VKH. (Courtesy of James Sanfilippo,MD.)

209 VKH-associated macular pucker from an epiretinal membrane in an otherwise quiet eye. (Courtesy of Peter Buch,CRA.)

commenced, some studies recommend removal of the inciting eye. This is controversial, however, and other studies have shown no benefit of removal.

Visual prognosis is good with up to 75% of patients retaining good vision (>20/50). Many of those patients require long-term steroids to retain that vision, since recurrences are common. Complications of chronic inflammation in sympathetic ophthalmia include cataract, glaucoma, retinal detachment, and retinal scarring.

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