Ординатура / Офтальмология / Английские материалы / Oxford American Handbook of Ophthalmology_Tsai, Denniston, Murray_2011

346 CHAPTER 11 Uveitis

Other viruses

Other common viruses that may cause an anterior or posterior uveitis include measles (with SSPE) mumps, rubella, EBV, CMV, and HTLV-1.

Subacute sclerosing panencephalitis (SSPE)

This rare neurodegenerative syndrome following measles infection exhibits a retinitis with focal pigmentary changes in the fovea ± papilledema or optic atrophy.

Human T-lymphotropic virus type-1 (HTLV-1)

This RNA retrovirus is common in Japan and parts of Africa and causes leukemia and tropical spastic paraparesis. It may cause uveitis in isolation (usually intermediate) or be secondary to leukemia (usually posterior with retinal vasculitis ± secondary infection, e.g., CMV).

Cytomegalovirus (CMV)

CMV retinitis is the leading cause of visual loss in AIDS, but may also occur in patients who are immunosuppressed from therapy (e.g., associated with organ transplants) or other disease (e.g., lymphoma). HIVand non-HIV- associated infections behave fairly similarly, both being dependent on the degree of immune system suppression/recovery.

Traditionally, HIV-associated CMV retinitis required lifelong maintenance therapy (cf. non-HIV disease). However, with antiretroviral therapy (ART)-induced immune recovery, this is no longer always necessary.

VIRAL UVEITIS (2) 347

Viral uveitis (2)

Acute retinal necrosis (ARN)

This is a rare syndrome of necrotizing retinitis caused by VZV, HSV1, and occasionally HSV2 infection (children). It may infect healthy individuals of any age. See Table 11.7 for diagnostic criteria.

Clinical findings

•Usually unilateral dVA, floaters, discomfort

•It begins predominantly as a peripheral disease comprising occlusive arteritis, full-thickness peripheral necrotizing retinitis (well demarcated, spread circumferentially), and marked vitritis ± AC activity.

•Complications: retinal detachment (in up to 75%; rhegmatogenous or tractional), ischemic optic neuropathy.

•Prognosis: second eye involvement occurs in around 30% (may occur simultaneously to several years later).

Investigations

• AC tap ± vitreous biopsy with PCR to identify viral DNA.

Treatment

•For all patients: antiviral (e.g., acyclovir IV dose 10 mg/kg 3x/day 2 weeks, then PO dose 3 months). Consider systemic steroids (treat inflammation), aspirin (treat arterial occlusion), and barrier laser photocoagulation (treat retinal breaks), but there is no clinical evidence of benefit for these additional therapies. Retinal detachment repair is challenging because of the necrotic retina and number of breaks; vitrectomy with silicone oil injection is most commonly used.

•If immunosuppressed: consider lifelong antiviral treatment.

Progressive outer retinal necrosis (PORN)

This very rare devastating necrotizing retinitis is caused by VZV infection in the context of immunosuppression (usually HIV with CD4+ T cell counts <50/mm3). See Table 11.17 for diagnostic criteria.

Clinical findings

•Uni/bilateral painless rapid dVA.

•Rapidly coalescing white areas of outer retinal necrosis (often central as well as peripheral) but with minimal or no vasculitis, retinitis, or vitritis (cf. ARN).

Treatment

This should be coordinated between an ophthalmologist with experience in HIV ocular disease and an infectious disease specialist. Options include intravenous ganciclovir or foscarnet with additional intravitreal ganciclovir, foscarnet, or fomivirsen. The prognosis is very poor, partly due to the extremely high rate of retinal detachment.

HIV-ASSOCIATED DISEASE: ANTERIOR SEGMENT 349

HIV-associated disease: anterior segment

The human immunodeficiency virus (HIV-1 and 2) is an RNA retrovirus that infects CD4+ T cells, causing the acquired immunodeficiency syndrome, AIDS. Worldwide, around 33 million people are infected with HIV, with around 4 million new infections and 3 million deaths per year. More than 25 million people have died of HIV since 1981 (United Nations AIDS report). Most of the infected people live in developing countries (notably Sub-Saharan Africa) and under socioeconomic deprivation.

Transmission may be via infected blood or other bodily fluids. Major risk factors include unprotected sexual intercourse, intravenous drug abuse, blood transfusion, and maternal infection (vertical transmission).

The main markers of disease are CD4 level and viral load. The CD4 level is a good indicator of HIV-induced immunocompromise and correlates with susceptibility to infections (Table 11.18). The viral load (i.e., RNA copies/mL) correlates with risk of progression.

Prognosis is greatly improved with antiretroviral therapy (ART). This regimen involves using at least three antiretroviral drugs, usually two nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.

Management of eye disease should be coordinated between an ophthalmologist with experience in HIV and an infectious disease specialist.

Conjunctival microvasculopathy

Microvascular abnormalities of the conjunctiva are common (see Table 11.19). The mechanism may be related to vascular damage due to high viral load. Irregular-caliber vessels are seen, which may be in a corkscrew pattern. Conjunctival microvasculopathy may be associated with abnormalities of the retinal microvasculature (p. 353).

Keratouveitis

VZV keratouveitis is common in HIV, with or without the typical dermatomal rash of HZO. The features include a moderate anterior uveitis, iIOP, and iris atrophy. Treatment is with systemic antiviral (e.g., acyclovir or famciclovir) (p. 177).

HSV keratouveitis is less common, with probably equal prevalence to that of the general population. In HIV patients, however, it tends to be limbal and more severe and have more recurrences, and dendrites may be larger and less defined. Treatment is with topical ± systemic antiviral (e.g., acyclovir) (p. 174).

Microsporidial keratouveitis presents with bilateral irritation and photophobia and punctate keratopathy, often with a follicular conjunctivitis and/ or an anterior uveitis.

HIV status is a relative contraindication for refractive surgery. There is an increased risk of dry eyes, postsurgical corneal infection, and reactivation of keratouveitis.

HIV-ASSOCIATED DISEASE: ANTERIOR SEGMENT 351

Anterior uveitis

Anterior uveitis is seen in over half of all patients with HIV. VZV and HSV tend to cause relatively mild inflammation (often with iIOP and iris atrophy). However, posterior uveitis associated with toxoplasma or syphilis may also cause significant anterior chamber inflammation.

Uveitis may also be caused by concurrent therapy, notably rifabutin (anti-atypical mycobacteria) and cidofivir (anti-CMV).

Mycobacterium tuberculosis

Mycobacterium tuberculosis is a rare cause of intraocular inflammation in HIV patients. This is an acid-fast obligate aerobe transmitted by aerosolized droplet. Tuberculosis should be ruled out in any HIV patient with a past history of TB exposure or symptoms of pulmonary TB with granulomatous anterior uveitis, choioretinitis, retinal vasculitis, and choroidal lesions.

Clinical findings

•Chronic granulomatous anterior uveitis.

•Papillitis.

•Intermediate uveitis.

•Choroidal tubercles and granulomas.

•Multifocal choroiditis or serpiginous like choroiditis.

•Retinal vasculitis.

Diagnostic testing

• Purified protein derivative (PPD) test.

Interpretation of the PPD test: In patients with HIV/AIDS, 5 mm induration is considered a positive reaction. Medical personnel or individuals in close contact with TB patients need reactions of only 10 mm induration to be counted as positive. Individuals with no risk factors or exposure to TB patients need >15 mm induration.

•Sputum culture.

•Bronchoscopy.

•Chest X-ray or CT scan.

•PCR with analysis of anterior chamber or vitreous sample.

•FA can be useful in evaluation of choroidal lesions and in confirming the presence of macular edema. Choroidal tubercles initially show hypofluorescene or very minimal hyperflourescence that increases in the late phases of disease.

•Quantiferon gold.

Treatment

Treat with rifampin, isoniazid, pyrazinamide, and ethambutol for 9–12 months. Unfortunately in HIV/AIDS, the choroiditis can progress despite this treatment.

HIV-ASSOCIATED DISEASE: POSTERIOR SEGMENT 353

yellow choroidal patches of 1/4 to 2 DD in size around the posterior pole with minimal vitritis. It is often asymptomatic. Treatment is with systemic co-trimoxazole or pentamidine.

Cryptococcus choroiditis

This rare condition is usually associated with cryptococcal meningitis and may be associated with an optic neuropathy or papilledema. It is characterized by multifocal off-white choroidal lesions, occasionally with a retinitis or endophthalmitis. Treatment is with a systemic antifungal (e.g., amphotericin-B or fluconazole).

Immune recovery uveitis

Eyes with inactive CMV retinitis may show a paradoxical worsening of inflammation as T-cell recovery takes place. The noninfectious inflammation is due to the reconstituted immune system responding to viral antigens present in the eye. Presentation includes moderate to severe vitritis, tractional retinal detachment, CME, and neovascularization.

Syphilis choroiditis/chorioretinitis

Coinfection with syphilis may occur via sexual transmission. Syphilis may cause protean ocular and systemic manifestations (p. 357).

HIV microvasculopathy

Around 75% of HIV-infected individuals develop microvascular abnormalities of the retina and/or conjunctiva (p. 349). It is not clear if this is due to HIV-induced thrombotic tendency or an immune phenomenon or is a direct result of HIV infection of the vessels.

Retinal microvasculopathy

In the retina there may be tortuosity of the vessels with cotton-wool spots, telangiectasia, intraretinal hemorrhages, and venous or arterial occlusions. These clinical findings are noninfectious in nature and are related to HIV viremia-associated damage of the retinal vasculature.

354 CHAPTER 11 Uveitis

Mycobacterial disease

Tuberculosis

Worldwide, more than 1 billion people are infected by Mycobacterium tuberculosis, a facultative intracellular bacterium. Tuberculosis (primary or post-primary) develops in around 10%, and of these individuals ocular disease develops in around 1%.

Widespread chronic inflammation develops with characteristic caseating granuloma. This immune reaction or occasionally direct ocular penetration may lead to uveitis.

Ocular TB may be difficult to diagnose because of its protean manifestations and the frequent absence of any clinical or radiological evidence of respiratory disease.

Clinical features

Ophthalmic

•External: lid abscess, conjunctival infiltration/nodules, phlyctenulosis, scleritis (usually anterior necrotizing), interstitial keratitis

•Anterior: typically granulomatous anterior uveitis with mutton-fat KPs, iris granuloma, posterior synechiae, but can be nongranulomatous

•Posterior: vitritis, vasculitis (periphlebitis ± BRVO or CRVO ± ischemia), macular edema, choroidal granuloma (usually multifocal around the posterior pole ± inflammatory retinal detachment); optic neuropathy; Eales’ disease (retinal vasculitis with neovascularization and high risk of vitreous hemorrhage, typically in young males)

Systemic

•Respiratory system: pneumonia, pleural effusion, fibrosis.

•GI: ileocaecal (may obstruct), peritoneum (ascites).

•GU: sterile pyuria, epididymitis, salpingitis + infertility (in females).

•CNS: meningitis, CNS tuberculoma (may mimic tumor).

•Skeletal: arthritis, osteomyelitis.

•Skin: lupus vulgaris.

•Cardiovascular system: constrictive pericarditis, pericardial effusion.

•Adrenal: hypoadrenalism (Addison’s disease).

•Lymph nodes: lymphadenopathy, scrofula.

Investigation

•Microbiology: sputum, early-morning urine (acid-fast bacillus, stains with Ziehl–Neelsen stain).

•Chest X-ray: classically apical infiltrates or cavitation; also consolidation, pleural effusion, hilar lymphadenopathy; normal in 50% of cases of ocular TB.

•Tuberculin testing: standard testing involves intradermal injection of 0.1 mL of 1:1000 strength tuberculin PPD (i.e., 10 tuberculin units) and measuring the induration 72 hours later. Interpret with caution (see Box 11.2), as the response can be highly variable with up to 17% false negatives and BCG vaccination inducing false positives (but usually only if within 5 years). A 1:10,000 strength tuberculin PPD may be used if active TB is suspected, since an intense reaction may become necrotic.

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•QuantiFERON-TB Gold is a newly developed blood test that can differentiate previous TB exposure from BCG vaccination and other atypical myobacteria exposure.

Box 11.2 Interpretation of Mantoux testing (CDC recommendations, 2005)

•For high-risk individuals (immunosuppressed, contacts of active TB, typical CXR changes), the test is considered positive if induration5 mm.

•For moderate risk (e.g., health workers, those with chronic disease, children, immigrants from endemic areas), induration must be 10 mm.

•For low risk, the test is only considered positive if induration 15 mm.

Treatment

Standard unsupervised treatment

If patient adherence or compliance is likely to be good, treatment is unsupervised with a daily regimen, usually using combination tablets. The initial 2 months of therapy consists of rifampin, isoniazid, pyrazinamide, and ethambutol. Continuation treatment for 4 additional months is with rifampin and isoniazid only.

Supervised and extended treatment

Otherwise, directly observed therapy (DOT) is instituted, with higher doses of the same drugs given three times per week. Treatment may be prolonged for 9 months if the patient is immunosuppressed or has disseminated disease.

Additional treatment

For ocular complications such as CME, retinal vasculitis, and persistent inflammation, consider oral corticosteroids but only if the patient is on effective anti-TB treatment.

Monitoring

Urinalysis and liver function tests (LFTs) should be checked before starting treatment with rifampin, isoniazid, and pyrazinamide. VA should be checked before starting treatment with ethambutol and the patient advised to report any visual disturbance (dVA, dcolor vision, dvisual field).

Leprosy (Hansen disease)

Worldwide, around 15 million people have leprosy, of whom about twothirds are in Asia. The spectrum of leprosy is cased by the interaction of the obligate intracellular bacterium Mycobacterium leprae with the host’s immune system.

A poor cell-mediated immune response leads to the lepromatous form, which is generalized and commonly affects the eyes. A strong response leads to tuberculoid leprosy, which is more localized and rarely affects the eye.