Uveitis• 22 chapPosteriorr

Treatment modalities

Due to its chronic and recurrent course, MCP can result in permanent visual loss even with corticosteroid therapy. The use of immunosuppressive drugs (methotrexate, cyclosporine and/or azathioprine, and chlorambucil), instead of low-dose corticosteroids, was associated with a significant (83%) reduction in the risk of posterior-segment complications and with a significant (92%) reduction in the risk of blindness. Improved visual outcome among patients with MCP is obtained by reducing the risk of sight-threatening posterior-pole complications, especially CNV.34 Sirolimus, an immunosuppressive agent with antiangiogenic properties, has been demonstrated to reduce fluid and leakage associated with CNV associated with MCP.35 Subfoveal and juxtafoveal CNV may be treated successfully using photodynamic therapy, with most treated patients experiencing stabilized or improved visual acuity.36

SARCOIDOSIS

Diagnostic features

Ocular sarcoidosis involves both anterior and posterior segments and may affect up to 50% of patients with systemic sarcoid. Involvement of the anterior segment occurs in 85% of ocular sarcoid patients and may manifest as conjunctival “millet seed” nodules, granulomatous anterior uveitis, iris nodules, secondary glaucoma, and posterior synechiae. Posterior-segment involvement may manifest as vitritis, intermediate uveitis, posterior or panuveitis. When vitritis is present, cellular infiltration and accumulation may produce the appearance of snowballs or “string of pearls.” Periphlebitis with yellowish perivenous exudates (candle wax drippings) is a hallmark of sarcoidosis. Punched-out focal or multifocal choroidal lesions have also been reported. Retinal ischemia may result in neovascularization and should be differentiated from other nonuveitic causes such as retinal vein occlusion, diabetes mellitus, and sickle-cell retinopathy.

FA may demonstrate retinal vascular staining, retinal neovascularization, or CME. ICGA may additionally demonstrate hypofluorescent choroidal lesions, leakage from choroidal blood vessels, or diffuse late zonal hypofluorescence.

Almost all organ systems can be affected by sarcoidosis, with the lung being the most frequently involved extraocular site. Definitive diagnosis is established by histopathologic evidence of classic noncaseating granulomas. Biopsy material can be collected from ocular and orbital structures such as conjunctiva and lacrimal gland, and from nonocular organ systems involved. Blood and imaging studies are less invasive, and are used by clinicians to make a presumptive diagnosis of sarcoidosis. Angiotensin-converting enzyme (ACE) is secreted by macrophages within granulomas and is useful in monitoring disease activity. Levels may be increased in serum, tears,37 and aqueous humor.38 In patients with suspected ocular sarcoidosis but with normal or equivocal chest radiograph, serum ACE level combined with wholebody gallium scan increases the diagnostic specificity to 100%.39A chest computed tomography is also useful in suspected sarcoidosis with negative radiographs.40 Other studies used in the evaluation of patients with suspected sarcoidosis include serum lysozyme, serum and urinary calcium levels, and skin testing to demonstrate anergy; other imaging tools include gadolinium-enhanced magnetic resonance imaging41 and positron emission tomography.42

Treatment modalities

Systemic corticosteroids are a mainstay of treatment and are indicated for anterior and posterior uveitis, neovascularization, and orbital disease refractory to topical steroids. Early use of systemic steroids may be sight-saving. Periocular steroids may be helpful, especially in the treatment of CME. Methotrexate, azathioprine, cyclosporine, and mycophenolate mofetil have been shown to be effective in controlling

sarcoidosis-associated uveitis, enabling decrease or discontinuation of oral corticosteroid. Refractory ocular sarcoidosis, despite systemic immunosuppressive therapy, has been found to respond to anti-TNF monoclonal antibody (infliximab),32 and humanized immunoglobulin monoclonal antibody (daclizumab).43 Retinal neovascularization responds well to panretinal photocoagulation. IVTA may be useful in resolving refractory CME.

SERPIGINOUS CHOROIDOPATHY

Diagnostic features

SPC is a rare, idiopathic, bilateral, chronic, progressive, recurrent inflammation of the RPE, choriocapillaris, and choroid. SPC affects patients of both genders and all races and predominantly presents between ages 30 and 60. The presenting symptoms of SPC include painless blurring of central vision and scotoma formation. A mild vitritis may be observed. In active disease, the fundus exhibits striking focal or multifocal, cream or gray-colored, deep retinal lesions of varying sizes with irregular borders. These lesions involve both RPE and choroidal layers. As the active lesion resolves, the involved areas develop areas of RPE and choroidal atrophy containing hyperpigmented clumps. New lesions usually occur at the borders of the inactive lesions. These lesions usually begin in the peripapillary area and extend outward in a serpentine pattern.

There is no confirmatory laboratory test for SPC, but the peripapillary, serpentine fundus lesions are characteristic. However, macular serpiginous and atypical ampiginous variants can be other presentations. On FA, active lesions exhibit blocked fluorescence in early frames and diffuse leakage and staining in late frames. Although FA can differentiate active from healed lesions, ICGA is useful in monitoring disease progression and response to therapy. ICGA can reveal sub­ clinical lesions not detectable clinically or by FA. ICGA is better at demonstrating persistent choroidal activity even with angiographic disappearance of retinal activity.44 VF testing may show scotomas, which are usually dense in active lesions and become less dense as the lesions resolve.45

Treatment modalities

Systemic or periocular corticosteroids may resolve active disease but do not prevent disease progression46 nor influence long-term visual outcomes, which depend on prevention of recurrences and resulting macular involvement. Mixed results are reported with CSA monotherapy, but treatment may result in clinical remission and disease cessation in some patients. Azathioprine combined with corticosteroids,47 or triple-agent therapy with CSA, azathioprine, and prednisone,48 has been reported to result in rapid remission of active disease. Alkylating agents (cyclophosphamide or chlorambucil), initially combined with oral corticosteroids, were also shown to be effective in controlling inflammation and inducing remission in patients who failed to respond to oral corticosteroids or triple-agent therapy.49 Long-term therapy with azathioprine, CSA, and cyclophosphamide was noted to prolong remission.50 Use of interferon alpha-2a has been reported for SPC unresponsive to other immunomodulatory therapy.51

VOGT–KOYANAGI–HARADA SYNDROME

Diagnostic features

VKH is a multiorgan disease affecting different organ systems, including ocular, nervous, auditory, and integumentary. VKH has worldwide distribution but is more common among darkly pigmented races such as Asians, blacks, Hispanics, and Native Americans. Females are slightly more affected than males.

Pharmacotherapy to Amenable Diseases Retinal • 3 section