MASQUERADE SYNDROMES

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Table 39-5.  Most Common Masquerade Syndromes That May Mimic Uveitis

Adapted from American Academy of Ophthalmology: Ophthalmology Basic and Clinical Science Course, Section 6, San Francisco, American Academy of Ophthalmology, 1997.

CT, Computed tomography; ERG, electroretinogram; EOG, electro-oculogram; ICG, indocyanine green; IVFA, fluorescein angiography; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; RPE, retinal pigment epithelium.

hemorrhages with white centers composed of leukemic cells or platelet–fibrin aggregates. Histopathologically, the choroid is the most commonly involved and may cause exudative retinal detachment. Intravenous fluorescein angiogram (IVFA) demonstrates multiple areas of hyperfluorescence similar to that found in VKH syndrome. Anterior segment findings include conjunctival mass, iris heterochromia, anterior chamber cell and flare, pseudohypopyon, spontaneous hyphema, and elevated intraocular pressure. Optic nerve infiltration and orbital involvement are common.30

58.How can a malignant melanoma produce inflammatory signs?

Necrotic tumors may elicit an intense inflammatory response associated with seeding of tumor cells into the vitreous cavity and anterior segment. Occasionally, melanophages or tumor cells that contain melanin produce a brown pseudohypopyon. Blockage of the trabecular meshwork by tumor cells may result in elevated intraocular pressure (melanomalytic glaucoma). Necrosis of the tumor may result in spontaneous vitreous hemorrhage. Other clinical findings include iris heterochromia and exudative

retinal detachment with shifting subretinal fluid. Ultrasound examination and IVFA help to establish the diagnosis.31

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Figure 39-3.  Pseudohypopyon caused by seeding of retinoblastoma cells in the anterior chamber. (From Shields JA, Shields CL: Intraocular Tumors: A Text and Atlas, Philadelphia, W.B. Saunders, 1992.)

Figure 39-4.  Yellow-white chorioretinal infiltrates in intraocular lymphoma. (From Shields JA, Shields CL: Intraocular Tumors: A Text and Atlas, Philadelphia, W.B. Saunders, 1992.)

Figure 39-5.  Leukemic infiltration of the optic nerve head, retina, and choroid in an 8-year-old child. (From Shields JA, Shields CL: Intraocular Tumors: A Text and Atlas, Philadelphia, W.B. Saunders, 1992.)

59.Describe other entities that may simulate anterior and/or posterior uveitis.

•Long-standing peripheral rhegmatogenous retinal detachment may produce a cellular reaction in the anterior or posterior chamber as well as PS.

•Retained intraocular foreign body associated with trauma may cause persistent anterior and/or posterior segment inflammation. CT or ultrasonography results should demonstrate the abnormality. Retained iron foreign bodies may lead to siderosis, retinal degeneration with an abnormal electroretinogram.

•Retinitis pigmentosa may present with vitreous cells and posterior subcapsular cataract. The “bone spicule” pigment deposition in the retina, attenuated retinal vessels, mottling and atrophy of the RPE, and waxy pallor of the optic nerve help to distinguish this disease from other disorders. The diagnosis can be confirmed with an extinguished electroretinogram and ring scotoma on visual field testing.32

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OCULAR MANIFESTATIONS OF ACQUIRED IMMUNE DEFICIENCY SYNDROME

60.Who is at greatest risk for developing acquired immune deficiency syndromerelated eye disease?

Patients with severely reduced CD4+ T-lymphocyte counts and associated immunosuppression are most likely to develop acquired immune deficiency syndrome (AIDS)-related eye disease. For this

reason, screening for opportunistic infections with dilated fundus examination is recommended every 3 months in patients with CD4+ counts less than 100 cells/μL.33

61.What is the most common ocular manifestation of AIDS?

Retinal microvasculopathy that manifests clinically as cotton-wool spots (CWSs) (Fig. 39-6). Retinal microaneurysms and hemorrhages may be present. Most patients are asymptomatic. CWSs become

more common as the CD4+ T-lymphocyte count declines, reaching a prevalence of 45% in patients with counts <50 cells/μL.34

62.What is the most common ocular opportunistic infection in patients with AIDS?

Cytomegalovirus (CMV) is by far the most common cause of opportunistic ocular infection and most frequently results in necrotizing retinitis (Fig. 39-7). Varicella zoster, toxoplasmosis, and Mycobacterium avium occur less frequently.

63.What is the incidence of cytomegalovirus retinitis?

Among patients whose CD4+ count is less than 50 cells/μL, 20% per year develop CMV retinitis.

64.Describe the early symptoms of cytomegalovirus retinitis

Floaters that appear as numerous tiny black specks are often present early in the course of CMV retinitis. Pain and redness are not associated. Scotomas (blind spots) or visual loss may develop with more advanced stages of the disease.

65.How does cytomegalovirus retinitis present clinically?

Classic ophthalmologic findings of fulminant CMV retinitis include white areas of retinal necrosis with associated hemorrhage and minimal vitreous inflammation (see Fig. 39-7). The indolent or granular

Figure 39-6.  Cotton-wool spots are infarcts of the nerve fiber layer. Unlike early infiltrates of cytomegalovirus retinitis, they do not enlarge, do not have associated hemorrhage, and may resolve in several weeks.

Figure 39-7.  Cytomegalovirus retinitis is characterized by areas of retinal infiltrate with associated hemorrhage. Note the optic nerve involvement.

CHAPTER 39  UVEITIS  315

form, which is often less symptomatic, is characterized by peripheral retinal whitening with minimal associated hemorrhage.35

66.What are the more common entities in the differential diagnosis of cytomegalovirus retinitis?

The more common entities are progressive outer retinal necrosis, toxoplasmosis, syphilis, HIV retinitis, and cotton wool spots.

67.How is the diagnosis of cytomegalovirus retinitis made?

The diagnosis of CMV retinitis is made clinically when characteristic findings of fulminant or indolent retinitis are found in an immunosuppressed patient with CD4+ count <100 cells/μL. In the unusual case in which the diagnosis is in question, a vitreous biopsy with or without retinal biopsy for PCR analysis may be performed.

68.What is the initial treatment strategy for cytomegalovirus retinitis?

Treatment of CMV retinitis is given in two stages. The first stage is 2 to 6 weeks of induction therapy with ganciclovir (Fig. 39-8), valganciclovir, foscarnet, or cidofovir. These are antiviral agents that inhibit the viral DNA polymerase. Induction is discontinued after a healing response (consolidation or stabilization of the margins) begins. The second stage, maintenance therapy, consists of a lower dose of the medication that is continued until relapse occurs.

69.What is the strategy in the event of a relapse?

Despite maintenance therapy, CMV retinitis may relapse in persons who remain immunosuppressed. The mean interval to relapse varies from 2 to 8 months and depends on the medication used and the route of administration. If relapse occurs in patients taking oral or intravenous (IV) medication, reinduction with the same medication (2 to 6 weeks of high-dose IV or multiple intraocular injections) is indicated. When relapse develops in patients with ganciclovir implants, the implant is replaced.

70.Does resistance to antiviral medication develop?

Drug resistance is an emerging problem of great concern because of the limited number of available agents that are effective against CMV. Ganciclovir-resistant CMV has been reported in 27.5% of urine samples at 9 months. CMV UL97 mutation (a CMV DNA polymerase mutation that confers ganciclovir resistance) was detected in 30.8% of patients treated with ganciclovir over 3 months and in none treated less than 3 months. Resistance to foscarnet and cidofovir has also been reported. Owing to similarities in the mechanism of action, cross-resistance may develop with cidofovir and ganciclovir. Clinical resistance is defined as a lack of response to 6 weeks of induction therapy. A change in medication or combination therapy is indicated.36,37

71.How long should treatment be continued in patients with cytomegalovirus retinitis?

Length of therapy depends on the immune status of the patient. For patients who remain severely immunosuppressed (CD4+ count <100 cells/μL), treatment must be continued indefinitely. In patients whose

immune status is improved by highly active antiretroviral therapy (HAART) (see question 73), maintenance therapy may be discontinued if the retinitis is completely quiescent and CD4+ counts are >100 cells/μL.

Figure 39-8.  The intraocular ganciclovir implant is sutured to the sclera and extends into the vitreous cavity. The drug delivery system slowly releases ganciclovir over 8 months. It may be replaced when the drug supply is exhausted. Although it is not associated with the systemic toxicity seen with oral or intravenous therapy, the implant provides no prophylaxis against systemic cytomegalovirus (CMV) or CMV retinitis in the fellow eye.

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72.Name the main toxicities of the antiviral therapies

Ganciclovir: bone marrow toxicity with neutropenia and/or thrombocytopenia. Foscarnet: nephrotoxicity.

Cidofovir: nephrotoxicity, which may be ameliorated by concurrent probenecid and hypotony after either intravenous or intravitreal administration.

73.How has highly active antiretroviral therapy affected the natural history and treatment of cytomegalovirus retinitis?

HAART causes significant and sustained increases in CD4+ counts and remission of CMV retinitis. Dis-

continuation of maintenance therapy has been recommended for patients with completely quiescent retinitis and CD4+ count greater than 100 cells/μL. Other criteria include CD4+ elevation for at least 3 months, prolonged relapse-free intervals, HAART longer than 18 months, and reduced HIV and CMV viremia.38,39

74.What is immune recovery uveitis?

Immune recovery uveitis (IRU) is intraocular inflammation that develops as systemic immunity recovers. It is hypothesized that immunologic improvement leads to an inflammatory response directed at the CMV antigen. IRU typically develops in 10 to 20% of eyes with CMV within 1 month after HAART is initiated, but may occur up to 3 years later. Treatment of CMV retinitis with intravenous cidofo-

vir and large CMV lesion size increase the risk. Vision-threatening complications include macular edema, epiretinal membrane, cataract, optic disc edema, retinal neovascularization, and neovascular glaucoma. Treatment depends on the location and severity of inflammation and the presence of complications and usually requires local and or systemic corticosteroids. On occasion, observation or antiviral therapy may be indicated.40

75.What is progressive outer retinal necrosis?

Progressive outer retinal necrosis is an extremely aggressive form of retinitis in the AIDS population (Fig. 39-9). It primarily affects persons with CD4 counts less than 50 cell/μL. Caused by herpes zoster virus, it is temporally associated with herpes zoster skin lesions, which may or may not be in the periocular region. Prompt diagnosis and treatment are imperative to prevent blindness, which

develops in >80% of patients because of either relentless progression of infection or secondary retinal detachment.41

76.Why do retinal detachments develop in cases of infectious retinitis? Who is at risk?

Retinal infections may cause multiple necrotic retinal holes that over time lead to retinal detachment. Most AIDS-related retinal detachments develop as a complication of CMV retinitis and occur in 34% of patients with CMV. However, patients with progressive outer retinal necrosis are at highest risk; retinal detachments occur in 60 to 70% of these cases.

77.How are most AIDS-related retinal detachments repaired?

Lasers may be used to demarcate or wall off macula-sparing retinal detachments, especially in patients who are not well enough to tolerate surgery. Vitrectomy with silicone oil injection is often required in cases in which the macula is detached or retinitis is active. The silicone oil replaces the vitreous and tamponades the multiple necrotic holes to prevent redetachment.42,43

Figure 39-9.  Progressive outer retinal necrosis typically affects the outer retina with sparing of the retinal vessels. Note the areas of perivascular clearing and absence of associated hemorrhage.