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

336 CHAPTER 11 Uveitis

Table 11.13 Causes of retinal vasculitis

ACE, angiotensin-converting enzyme; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; Ca, calcium; CBC, complete blood count; CMV, cytomegalovirus; CXR, chest-X-ray; dsDNA, double-stranded DNA; HIV, human immunodeficiency virus; HRCT, high-resolution computed tomography; HSV, herpes simplex virus; HTLV-1, human T-cell lymphotropic virus type 1; LP, lumbar puncture; PCR, polymerase chain reaction; PPD, posterior polymorphous dystrophy; TPHA, treponema pallidum hemagglutination assay; VDRL, venereal disease research lab test; VKH, Vogt–Koyanagi–Harada syndrome; VZV, varicella zoster virus.

Table 11.14 Diagnostic pointers in retinal vasculitis

SARCOIDOSIS 337

Sarcoidosis

This relatively common granulomatous multisystem disorder may be life threatening. The eye is affected in up to 25% of patients. Of these, anterior uveitis occurs in 60%, and posterior segment disease occurs in 25% of patients. Sarcoid affects up to 0.1% of the population, being higher in females and with peaks in the third and sixth decades. It is more common in African Caribbeans, Irish, and Scandinavians.

The cause of sarcoidosis is unknown; there is PCR evidence for several agents (including atypical mycobacteria) that may trigger the disease in susceptible individuals. The TH1 response predominates in typical sarcoid granuloma, although it appears that a transition to the TH2 response underlies progressive pulmonary fibrosis.

The presentation may be acute or insidious. An acute presentation, typically with erythema nodosum and bihilar lymphadenopathy (BHL), has a better prognosis. The course tends to be self-limiting, although steroids may hasten recovery. An insidious presentation is more commonly followed by a relentless progression to pulmonary fibrosis.

Clinical features

Ophthalmic

•Anterior uveitis (2/3 are persistent, 1/3 acute; unilateral or bilateral; ‘granulomatous’): limbal injection, mutton-fat keratic precipitates, AC flare/cells, posterior synechiae, vitreous cells; iris granulomas and nodules.

•Intermediate uveitis: vitreous cells, snowballs, snowbanking.

•Posterior uveitis: CME (most common cause of dVA), periphlebitis (± patchy sheathing ±“candle wax dripping”), occluded vessels (especially BRVO), retinal neovascularization, choroidal neovascularization, retinal, or preretinal nodules (probably granuloma), pigment epithelial changes, disc swelling (from inflammatory papillitis, optic nerve granuloma, or papilledema secondary to CNS disease). Peripheral multifocal chorioretinitis (small punched-out atrophic spots) is highly suggestive of sarcoidosis.

•Complications: cataract, glaucoma (irisk with duration of active disease).

Systemic

•Respiratory system: often asymptomatic despite CXR changes, dry cough, dyspnea; BHL, parenchymal disease.

•Cardiovascular system: pericarditis, cardiomyopathy, conduction defects, cardiac failure, cor pulmonale.

•Skin: erythema nodosum (red, tender, elevated lesions typically on the shins; commonest in younger females); cutaneous granuloma (nontender; nodules, papules, macules; almost anywhere including the lids); lupus pernio (uncommon, bluish plaque, typically on the face or ears).

•Joints: arthritis (common in acute sarcoid); bone cysts (usually in the digits).

338CHAPTER 11 Uveitis

•Glands: swelling of any of lacrimal, salivary, parotid, and submaxillary glands, lymphadenopathy, hepatosplenomegaly.

•Central nervous system (neurosarcoidosis, more common in patients with posterior uveitis): cranial nerve palsies (most commonly CN VII; can be bilateral), peripheral neuropathy, myopathy, aseptic meningoencephalitis (typically basal leptomeninges); CNS granuloma may mimic a tumor; optic nerve involvement may present as atypical optic neuritis.

Investigations

The diagnosis is essentially clinical but may be supported by investigations such as serum angiotensin-converting enzyme (ACE) (see also Box 11.1), imaging, and ideally typical histology. In some cases, it may be difficult to distinguish neurosarcoidosis from MS.

•Serum ACE (commonly elevated in active sarcoid because of synthesis by activated macrophages), serum Ca2+ (less commonly elevated).

•CXR: abnormal in >90% with ocular sarcoid: stage 0 (normal); stage 1 (BHL only); stage 2 (BHL + parenchymal disease); stage 3 (parenchymal disease only).

•High-resolution CT of the thorax has high sensitivity and specificity; it is particularly useful in those with normal CXR.

•MRI of the brain or optic nerves (ideally fat suppressed, gadolinium enhanced, T1) and LP in suspected neurosarcoid.

•Gallium 67 scan: typical uptake pattern is lacrimal and parotid glands (panda appearance) or mediastinum (lambda sign).

•Biopsy: transbronchial, endobronchial, or conjunctival biopsy may reveal the typical noncaseating granulomata of whorls of eipthelioid cells surrounding multinucleate giant cells. Bronchoalveolar lavage (BAL) may show lymphocytosis with high CD4+/CD8+ ratio, but low specificity.

•FA: include ischemia (hypofluorescence), leakage from periphlebitis, new vessels, CME (hyperfluorescence), peripheral patchy hyperand hypofluorescence.

•ICG: choroidal stromal vasculitis, early lobular hypofluorescence, late hyperfluorescence (focal or diffuse).

Treatment

•Ophthalmic: anterior segment inflammation—as for idiopathic AAU; posterior segment inflammation—periocular steroid injection or systemic therapy (see below); cataracts—conventional surgery but with tight control of inflammation; glaucoma—medical ±surgical (antimetabolite-augmented trabeculectomy, glaucoma tube shunt).

•Systemic: investigation and treatment by a physician (usually

respiratory); oral corticosteroids (proven short-term benefits)

±steroid-sparing agents such as methotrexate, azathioprine, and cyclosporine. In patients with recalcitrant diseases or who are intolerant of immunosuppression, biological therapy such as intravenous infliximab is an alternative option.

SARCOIDOSIS 339

Sarcoidosis syndromes

•Heerfordt’s syndrome (uveoparotid fever): parotid/submandibular gland enlargement, CN VII palsy, uveitis.

•Lofgren’s syndrome: fever, erythema nodosum, BHL.

•Mickulicz’s syndrome: diffuse swelling of lacrimal/salivary glands (most commonly due to sarcoidosis).

Box 11.1 Differential diagnosis of elevated serum ACE

•Child (peaks at 13 years of age, adult level by 18 years)

•Sarcoidosis.

•Mycobacterial infection (including leprosy and tuberculosis).

•Certain chronic lung diseases (including berylliosis, silicosis, farmer’s lung, histoplasmosis, lymphangiomyomatosis).

•Gaucher disease.

340 CHAPTER 11 Uveitis

Behçet’s disease

Possibly first recognized by Hippocrates, the modern description of this disease dates from the Greek Adamantiades and the Turk Behçet. It is an idiopathic, chronic multisystem autoimmune disease and vasculitis characterized by recurrent episodes of acute inflammation. The common ophthalmic presentation is of a sight-threatening panuveitis and retinal vasculitis (see Table 11.15 for diagnostic criteria).

Prevalence is highest along the traditional Silk Route, peaking in Turkey, where up to 0.4% of the population may be affected. It typically affects young adults. There is some geographical variation of risk factors, including gender, family history (more significant in Middle Eastern countries), and the HLA-B51 allele (more significant in Japan with a relative risk of 6.7).

Clinical features

Ophthalmic

•Anterior uveitis: acute anterior nongranulomatous uveitis, typically with hypopyon.

•Posterior uveitis: vitiritis; macular edema; retinal infiltrates, hemorrhage, edema; occlusive periphlebitis ±BRVO or CRVO, neovascularization ± vitreous hemorrhage or tractional retinal detachment, diffuse capillary leakage.

•Complications: cataract, glaucoma, end-stage disease (optic atrophy, retinal atrophy with attenuated vessels; high risk of blindness).

Systemic

•Oral ulceration (aphthous or scarring).

•Genitourinary (GU) (genital ulceration).

•Skin lesions: erythema nodosum, pseudofolliculitis, papulopustules, acneiform rash.

•Joints: arthritis (mono/poly).

•Vascular: thromboses (venous > arterial), including superficial thrombophlebitis, superior (SVC) or inferior (IVC) vena cava obstruction.

•GI: nausea, vomiting, abdominal pain, bloody diarrhea.

•CNS: meningoencephalitis, sinus thrombosis ±intracranial hypertension, cranial or peripheral neuropathies, focal CNS signs.

Investigations

•Positive pathergy test: sterile pustule appearing 24–48 hours after oblique insertion of 20-gauge needle.

•MRI, MRA, MRV of the brain if there are neurological features.

Treatment

Coordinate care with PCP and rheumatologist; give systemic corticosteroids (e.g., initially 1–2 mg/kg/day prednisone PO). Consider adding ster- oid-sparing agents, including cyclosporine, azathioprine, and chlorambucil. New therapy with IV infliximab has demonstrated excellent success in treating systemic and ocular inflammation related to Behcet’s disease.

BEHÇET’S DISEASE 341

Table 11.15 Criteria for diagnosis of Behçet’s disease (International Study Group for Behçet’s Disease, 1990)

Diagnostic (classification) criteria

Must have: • Recurrent oral ulceration (minor, major, or herpetiform)3xin 12 months

Plus two of: • Recurrent genital ulceration (aphthous or scarring)

•Eye lesions: uveitis (anterior, posterior, or cells in the vitreous) or retinal vasculitis

•Skin lesions: erythema nodosum, pseudofolliculitis, or papulopustular lesions; or acneiform rash (in postadolescent patient not on corticosteroids)

•Positive pathergy test

342 CHAPTER 11 Uveitis

Vogt–Koyanagi–Harada disease

Vogt–Koyanagi–Harada disease (VKH) is a multisystem inflammatory disease affecting the eyes (bilateral granulomatous panuveitis), ears, brain, skin, and hair (see Table 11.16). It is thought to be a T-cell-mediated autoimmune disease directed against melanocyte antigen(s).

Prevalence is higher in darker-skinned races, including Asians, Native Americans, Hispanics, and those from the Middle and Far East. It is more common in women in their third and fourth decade, but may occur in either sex at any age.

It is associated with HLA-DR4, notably HLA-DRB1*0405, which recognizes various melanocyte proteins. VKH may arise after cutaneous injury, presumably via liberation of melanocyte antigens.

Clinical features

There is often a prodrome of fever, meningismus, and auditory symptoms for a few days before blurring or profound visual loss from the uveitis develops.

Ophthalmic

•Anterior uveitis: bilateral granulomatous anterior uveitis, posterior synechiae, iris nodules, AC shallowing.

•Posterior uveitis: multifocal choroditis, multifocal detachments of sensory retina, exudative retinal detachments, choroidal depigmentation (“sunset glow fundus”), Dalen–Fuchs nodules

(peripheral yellow-white choroidal granulomas), subretinal fibrosis.

•Complications: cataract, glaucoma, choroidal neovascular (CNV) membrane.

Systemic

•Cutaneous: late features—vitiligo, alopecia, poliosis.

•Auditory: tinnitus, deafness, vertigo.

•Neurological: sterile meningitis (headache, neck stiffness), encephalitis, (convulsions, altered consciousness), cranial neuropathies (including ocular motility disturbance).

Investigations

•FA: focal areas of delay in choroidal perfusion, multifocal areas of pinpoint leakage, large placoid areas of hyperfluorescence, pooling within subretinal fluid, and optic nerve staining.

•Ultrasound: low to medium reflective diffuse choroidal thickening.

•Lumbar puncture (not always required): lymphocytic pleocytosis.

Treatment

Coordinate care with PCP; start high-dose systemic corticosteroids (e.g., 1–2 mg/kg/day prednisone PO or methylprednisolone 1 g/day IV for 3 days). For resistant or recurrent disease consider adding steroid-sparing agents such as methotrexate, azathioprine, and cyclosporine.

VOGT–KOYANAGI–HARADA DISEASE 343

Table 11.16 Diagnostic criteria for Vogt–Koyanagi–Harada disease

1No history of penetrating ocular trauma or surgery preceding initial onset of uveitis

2No clinical or laboratory evidence suggestive of other ocular disease entities

3Bilateral ocular involvement

aEarly

1)Diffuse choroiditis (focal subretinal fluid or bullous serous retinal detachments)

2)If fundus findings equivocal, then there must be characteristic FA findings (see Investigations) AND diffuse choroidal thickening (in the absence of posterior scleritis on US)

bLate

1)History suggestive of prior presence of early features AND two or more of the following:

2)Ocular depigmentation (sunset glow fundus or Sugiura sign)

3a) Nummular chorioretinal depigmented scars

3b) Retinal pigment epithelium clumping/migration

3c) Recurrent or chronic anterior uveitis

4Neurological and auditory findings

aMeningismus (malaise, fever, headache, nausea, abdominal pain, neck and back stiffness)

bTinnitus

cCSF pleocytosis

aAlopecia

b Poliosis

cVitiligo

Complete VKH requires all criteria (1 to 5).

Incomplete VKH requires criteria 1 to 3 AND either 4 or 5.

Probable VKH (isolated ocular disease) requires criteria 1 to 3.

Reprinted with permission from Read RW, et al. (2001). Revised diagnostic criteria for Vogt–Koyanagi–Harada disease. Am J Ophthalmol 131:647–652.

344 CHAPTER 11 Uveitis

Sympathetic ophthalmia

Sympathetic ophthalmia is a rare bilateral granulomatous panuveitis that bears remarkable parallels to VKH but differs in being causally related to antecedent ocular trauma or surgery. Although this response to injury can occur within a few days or over 60 years later, it usually arises between 1 and 12 months after injury.

It appears to be a T-cell-mediated response to an ocular antigen, presumably liberated during the initial insult. It occurs in 0.1% cases of penetrating ocular trauma and in 0.01% cases of routine vitrectomy. In one prospective study, the most common cause of sympathetic ophthalmia was ocular (particularly vitreoretinal) surgery.

Clinical features

Ophthalmic

•Anterior: bilateral granulomatous anterior uveitis with mutton-fat keratic precipitates, posterior synechiae.

•Posterior: vitritis, choroidal infiltration, Dalen–Fuchs nodules, macular edema, exudative retinal detachment; the inciting eye may be phthisical.

•Complications: cataract, secondary glaucoma, end-stage disease (optic atrophy, chorioretinal scarring).

Systemic

Features are the same as for VKH, but systemic involvement is less common.

Prevention

After trauma, there is a short window of opportunity (~10 days) in which enucleation would could prevent sympathetic ophthalmia. This may be the best option for blind, painful eyes with no hope of useful vision. However, for the many traumatized eyes with visual potential, there is now a strong trend to preserve the eye whenever possible.

Treatment

Once inflammation has developed, the role of enucleation of the exciting eye is controversial; some suggest that it may favorably modify the disease if performed within 2 weeks of initial symptoms.

Immunosuppression is started with high-dose systemic corticosteroids (e.g., 1–2 mg/kg/day prednisone PO or methylprednisolone 1 g/day IV for 3days). For resistant or recurrent disease or unacceptable steroid side effects, consider adding steroid-sparing agents, such as methotrexate, azathioprine and cyclosporine.

With aggressive treatment, 60% of patients may achieve 20/60 in the sympathizing eye.

VIRAL UVEITIS (1) 345

Viral uveitis (1)

Herpes simplex virus

HSV1 (very rarely HSV2) may cause an anterior uveitis that is usually associated with keratitis but may be isolated.

Clinical

•Anterior: unilateral persistent anterior uveitis with KPs, posterior synechiae, and patchy iris atrophy (with transillumination defects); semidilated pupil ± corneal scarring, keratitis, iIOP, or dcorneal sensation (p. 174). The uveitis may be granulomatous.

•Glaucoma is common (secondary to trabeculitis or blockage by inflammatory debris).

•Posterior (rare): healthy individuals may get acute retinal necrosis (ARN) (see below); those with disseminated HSV or HSV encephalitis may get an occlusive vasculitis (usually bilateral) with relatively few hemorrhages but commonly complicated by retinal detachment.

Treatment

•If there is keratitis, then antiviral coverage is generally required (p. 174).

•For isolated anterior uveitis, titrate topical steroids according to inflammation and taper very slowly (frequency/potency), as HSV uveitisis highly steroid sensitive and relapses are common; add a cycloplegia.

•Treat associated iIOP with topical glaucoma drops.

•For frequent recurrences, consider long-term oral antiviral prophylaxis.

Varicella zoster virus

Primary VZV infection (chickenpox) commonly causes a widespread vesicular rash that may be associated with keratitis (superficial, disciform, or stromal), mild anterior uveitis, and very occasionally necrotizing retinitis. Reactivation (shingles) usually occurs in the elderly or immunosuppressed and frequently affects CN V1 (ophthalmic branch), known as herpes zoster ophthalmicus (HZO).

Of this group, up to 40% have anterior uveitis, with an increased risk if the nasociliary branch is involved (Hutchinson sign: vesicles at side of the nose). Typical ocular inflammation (e.g., disciform keratitis with anterior uveitis) may also occur without the rash (HZO sine herpete).

Clinical

•Anterior: unilateral anterior uveitis with KPs, posterior synechiae, and segmental iris atrophy (with transillumination defects) ± conjunctivitis, keratitis, epi/scleritis; the uveitis may be granulomatous.

•Glaucoma is common (up to 40%).

•Posterior: ARN or PORN may develop (see below).

Treatment

•For isolated anterior uveitis, titrate topical steroids according to inflammation and taper very slowly (frequency/potency), as VZV uveitis is highly steroid sensitive and relapses are common with steroid withdrawal; add cycloplegia.

•For HZO, see p. 177.