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

326 CHAPTER 11 Uveitis

Other causes

Although the vast majority of acute anterior uveitis is idiopathic or HLAB27 related, it is important to be keep an open mind. Atypical features may suggest an alternative diagnosis requiring different treatment. Important differential diagnoses include the following.

Herpes viral group (HSV, VZV, CMV) anterior uveitis

Consider this if there is unilateral persistent anterior uveitis with patchy iris atrophy, transillumination defects, and semidilated pupil, corneal hypoesthesia, and iIOP ± evidence of active or previous keratitis (p. 345).

Posner–Schlossman syndrome

Consider PSS with iIOP (40–80 mmHg), white eye, few keratic precipitates, minimal flare, occasional AC cells, no synechiae (PS or PAS), and open angle (p. 327). Gonioscopy may demonstrate evidence of keratic precipitates in the angle, suggesting a viral trabeculitis etiology (HSV, VZV, CMV).

Systemic disease

AAU is associated with a number of systemic diseases, some of which may be undiagnosed at the time of presentation. For example, a fibrinous uveitis in a middle-aged adult may be the first presentation of diabetes mellitus.

Systemic diseases to consider include diabetes, sarcoidosis, vascular disease (e.g., carotid artery stenosis), and renal disease (e.g., TINU, IgA nephropathy).

Table 11.10 Comparison of HLA-B27 positive vs. negative AAU

This table was published in Rothova A, et al. (1987). Clinical features of acute anterior uveitis. Am J Ophthalmol 103:137–145. Copyright Elsevier 1987.

ANTERIOR UVEITIS SYNDROMES 327

Anterior uveitis syndromes

Fuchs heterochromic iridocyclitis (FHI)

This is an uncommon, chronic, nongranulomatous anterior uveitis of unknown etiology. It typically affects young adults and there is no gender bias. It is unilateral in about 90%.

Clinical features

•Floaters, glare; dVA due to cataract ± vitreous opacities; often asymptomatic.

•White eye, white stellate keratic precipitates (KPs) over whole corneal endothelium, mild flare, few cells, iris atrophy (washed out, moth-eaten), transillumination defects, abnormal iris vessels, iris heterochromia (becomes bluer), iris nodules; no posterior synechiae; cataract (posterior subcapsular), vitritis, iIOP (10–15%).

•Gonioscopy: open angle; ± twig-like neovascularization of the angle; these may lead to hyphema in response to paracentesis or during cataract surgery (Amsler hemorrhages).

Treatment

•Inflammatory process: not usually necessary.

•Cataract: conventional phacoemulsification but with careful postoperative control of inflammation (p. 249).

•iIOP: treat as for POAG (p. 269), but it may require augmented trabeculectomy or drainage-tube surgery.

Posner–Schlossman syndrome (PSS)

This is an inflammatory glaucoma syndrome characterized by recurrent unilateral episodes of very high IOP. It typically affects young males. The suggested etiology is acute trabeculitis, perhaps secondary to HSV.

Clinical features

•Blurring of vision, halos, painless.

•iIOP (40–80 mmHg), white eye, few KPs, minimal flare, occasional AC cells, no synechiae (PS or PAS), open angle.

Treatment

•Inflammatory process: topical steroid (e.g., dexamethasone 0.1% or prednisolone acetate 1% 4x/day initially, titrating according to disease).

•iIOP: consider topical (e.g., B-blocker, A-agonist, carbonic anhydrase inhibitor) or systemic (e.g., acetazolamide) according to IOP level.

•Oral antiviral medication (acyclovir) for recurrent disease.

TINU

This is the rare association of tubulointerstitial nephritis (often presenting as acute renal failure) and uveitis. It typically affects young females (median age 15; F:M 3:1) but can occur at almost any age. It is commonly idiopathic but may be associated with drugs (NSAIDs, penicillin, furosemide) or infection (streptococci, staphylococci, etc).

The uveitis is usually anterior (80%) and bilateral (77%) and usually presents after the systemic disease (65%). The uveitis may recur or follow

328 CHAPTER 11 Uveitis

a persistent course in over 50%. Ocular complications include posterior synechiae, iIOP, and cataract.

In most cases the renal disease recovers, but chronic renal impairment occurs in 11%, with dialysis being required in 4%. The renal disease is commonly treated with systemic steroids; the uveitis may be treated as for idiopathic AAU.

IgA nephropathy

This is a relatively common renal disease of children in young adults in which recurrent microor macroscopic hematuria may be related to respiratory tract infections. In some patients, episodes are associated with an anterior uveitis, which may be treated similarly to idiopathic AAU.

Schwartz syndrome

This is the uncommon association of anterior segment pseudo-inflamma- tion (mild) and iIOP (with an open angle) arising from a rhegmatogenous retinal detachment. Detachments most commonly associated with this syndrome are large in area (and macula-off), flat in height, and long in duration.

The postulated mechanism involves mechanical blockage of the angle by photoreceptor outer segments. Refer to a vitreoretinal surgeon for assessment and repair (p. 383). The iIOP and anterior uveitis may be treated medically in the interim and tend to resolve rapidly after surgical repair.

Kawasaki disease

This is an uncommon acute vasculitis of children, defined as fever ( 5 days) with four of the following five criteria: conjunctival injection, rash, desquamation of extremities, cervical lymphadenopathy, and mucosal changes (pharyngeal injection, cracked red lips, strawberry tongue).

An anterior uveitis is common in the first week of illness; rarely, disc edema and dilated retinal vessels are seen. Most seriously, cardiac abnormalities (notably coronary artery aneurysms) occur in 20% of patients.

Anterior segment ischemia

This is an uncommon but important cause of anterior uveitis, particularly in the elderly.

Clinical features

•Dull ache, usually unilateral.

•AC with significant flare/moderate cells, sluggish pupil; if part of ocular ischemic syndrome, there may also be dilated irregular retinal veins (not tortuous), attenuated retinal arterioles, midperipheral retinal hemorrhages, rubeosis, and posterior segment neovascularization.

•Investigate for carotid artery stenosis with carotid Doppler ultrasound and refer to a vascular surgeon if indicated.

UVEITIS WITH HLA-B27-RELATED ARTHROPATHIES 329

Uveitis with HLA-B27-related arthropathies

HLA-B27 is a type I major histocompatibility complex (MHC; Ch6) molecule: a cell surface polypeptide involved in presenting antigen to the immune system. There are 24 subtypes of HLA-B27, encoded by 26 different alleles. Subtypes vary by ethnic origin, and some are more highly associated with inflammatory disease, notably HLA-B*2705 (the ancestral type), B*2702 (more common in whites), and B*2704 (more common in Asians).

HLA-B27 is present in 8% of the general population but is seen in up to 50% of patients with acute anterior uveitis and is strongly linked to the seronegative spondyloarthropathies. This is a group of overlapping inflammatory conditions that, as the name suggests, are negative for rheumatoid factor (RF) and generally include an axial (spinal) arthritis. They may all be associated with uveitis.

Ankylosing spondylitis (AS)

AS is a chronic spondyloarthropathy, predominantly affecting the spine and sacroiliac joints. AS is more common in males and usually presents in early adulthood. Of those with AS, 95% are HLA-B27 positive; 25% will develop anterior uveitis. Of these, 80% will have involvement of both eyes, but nearly always sequentially.

Clinical features

•Ophthalmic: acute anterior uveitis; unilateral but may affect both eyes sequentially (alternating); rarely may become persistent.

•Systemic: axial arthritis, sacroiliitis, kyphosis, stiffness, enthesitis, aortic

regurgitation.

Treatment

•Ophthalmic: as in idiopathic acute anterior uveitis (p. 325).

•Systemic: investigation and treatment by rheumatologist. This may include lumbar-spinal X-ray (bamboo spine; sacroiliitis) and HLA-B27 status. Treatment may include oral NSAIDs and physical therapy.

•In advance diseases, immunosuppressive agents (methotrexate, azathioprine) and biological agents (etanercept, infliximab) may be beneficial for both systemic and ocular inflammation.

Reiter syndrome (reactive arthritis)

Reiter syndrome describes a reactive arthritis, urethritis (or cervicitis), and conjunctivitis occurring after a sexually transmitted or dysenteric infection. Candidates include Chlamydia, Yersinia, Salmonella, and Shigella. In patients with Reiter syndrome, 70% are HLA-B27 positive; 50% will develop conjunctivitis, and 12% will have anterior uveitis.

Clinical features

•Ophthalmic: bilateral mucopurulent conjunctivitis; acute anterior uveitis; keratitis (punctate epitheliopathy, supepithelial infiltrates).

330 CHAPTER 11 Uveitis

•Systemic: oligoarthritis (typically knees, ankles, sacroiliac joints), enthesitis (including plantar fasciitis), aphthous oral ulcers, circinate balanitis, keratoderma blenorrhagica (scaling skin rash on the soles)

Treatment

•Ophthalmic: conjunctivitis—self-limiting; AAU—as above.

•Systemic: investigation and treatment by rheumatologist.

Inflammatory bowel disease

Of patients with ulcerative colitis (UC) and Crohn’s disease, around 5% will develop anterior uveitis.

Clinical features

•Ophthalmic: acute anterior uveitis; rarely epi/scleritis or retinal vasculitis.

•Systemic: gastrointestinal inflammation (patchy, transmural, anywhere from mouth to anus in Crohn’s; continuous, superficial, colorectal in UC), cholangitis, chronic active hepatitis, arthritis (oligoor AS-like), rash (erythema nodosum, pyoderma gangrenosum).

Treatment

•Ophthalmic: as in idiopathic acute anterior uveitis (p. 325).

•Systemic: investigation and treatment by gastroenterologist.

More recently, intramuscular etanercept has been demonstrated to have excellent activity against the gastrointestinal (GI) diseases, but with limited activity for ocular inflammation. Intravenous infliximab has demonstrated more clinical benefit for both GI and ocular inflammation.

Psoriatic arthritis

Of those with psoriasis, 10% will develop psoriatic arthritis, and of these, 10% will develop anterior uveitis.

Clinical features

•Ophthalmic: conjunctivitis; acute anterior uveitis; rarely keratitis (peripheral corneal infiltrates).

•Systemic: salmon-pink lesions with silvery scaling that may be in isolated plaques (more common on extensor rather than flexor surfaces)

or occur as a pustular rash (soles and palms or, more seriously, generalized); nail changes (pitting, onychlysis, oil drop). Arthritis may be axial (AS-like), oligoarthritis (Reiter’s-like), distal interphalangeal joints (osteoarthritis-like) with nail changes, symmetrical peripheral arthropathy (RA-like), or arthritis mutilans.

Treatment

•Ophthalmic: the conjunctivitis is self-limiting; treat anterior uveitis as in idiopathic AAU (p. 325).

•Systemic: investigation and treatment by dermatologist and rheumatologist.

UVEITIS WITH OTHER ARTHROPATHIES 331

Uveitis with other arthropathies

Juvenile idiopathic arthritis (JIA)

This condition describes an idiopathic arthritis of >6 weeks duration with onset before the age of 16 years. JIA may be subclassified into systemic, oligoarthritis ( 4 joints), polyarthritis (>4 joints) RF negative, polyarthritis RF positive, psoriatic, enthesitis related, and other/overlap (classification of the International League of Associations of Rheumatologists).

The term JIA is meant to replace juvenile chronic arthritis (JCA) and juvenile rheumatoid arthritis (JRA).

Of those with JIA, 20% will develop anterior uveitis, of which 70% will be bilateral and 25% will be severe sight-threatening disease. JIA is more common in females.

Clinical features

Ophthalmic

•Asymptomatic; rarely floaters; dVA from cataract.

•White eye, small KPs, AC cells/flare, posterior synechiae, vitritis, CME (rare). Complications include band keratopathy, cataract, inflammatory glaucoma, or phthisis bulbi.

•Arthritis: pattern may be oligoarthritis (<4 joints), polyarthritis (>4 joints), psoriatic type, or enthesitis related.

•Systemic: fever, rash, lymphadenopathy, hepatosplenomegaly, serositis.

In long-standing uveitis, chronic breakdown of the blood–aqueous barrier leads to persistent flare. AC cells are thus a better guide than flare to gauge the level of disease activity.

Screening

Patients diagnosed with JIA should be seen as soon as possible by an ophthalmologist. If ophthalmic examination is normal, regular follow-up is indicated according to risk (see Table 11.11).

Table 11.11 Recommendation for JIA-associated uveitis screening (American Uveitis Society)

332 CHAPTER 11 Uveitis

Treatment

•Uveitis: topical steroids and mydriatic; if systemic therapy is required, this should be directed by a pediatrician and pediatric rheumatologist. NSAID and steroid-sparing agents such as methotrexate are commonly used to minimize long-term steroid side effects. Biological agents such as etanercept and infliximab have demonstrated excellent activity against joint disease, with infliximab demonstrating better ocular control.

•iIOP: initially topical therapy. But up to two-thirds of patients may require surgery (commonly an antimetabolite-augmented trabeculectomy or a drainage-tube procedure).

•Cataract: aim to defer surgery until the eye has been quiet for a minimum of 3 months, although weigh this against the risk of

amblyopia in younger children. There is considerable debate over the specifics of surgery, including whether to implant a lens or leave the patient aphakic.

•Band keratopathy: chelation with EDTA or excimer phototherapeutic keratectomy.

Relapsing polychondritis

This is a rare condition of recurrent inflammation of cartilage affecting the ear, nose, and, most seriously, the trachea and larynx (risk of respiratory obstruction). The ophthalmic features include anterior uveitis, epi/scleritis, and, rarely, corneal involvement (keratoconjunctivitis sicca or peripheral ulcerative keratitis). Anterior uveitis may be treated similarly to that in idiopathic AAU.

INTERMEDIATE UVEITIS 333

Intermediate uveitis

The term intermediate uveitis refers to uveitis in which the vitreous is the major site of inflammation. The term pars planitis may be used when there is snowbank or snowball formation occurring in the absence of an associated infection or systemic disease (i.e., idiopathic).

Intermediate uveitis accounts for around 10% of all cases of uveitis. It is bimodal, being most common in young adults, but with a second peak in the elderly. Males and females are equally affected. It is bilateral in 80% but is often asymmetric.

Clinical features

•Floaters, dVA (may indicate macular edema); may be asymptomatic.

•Vitritis (cells, “snowballs”), exudation at the ora serrata (“snowbanking”, commonly inferior but can be 360*), peripheral periphlebitis, rarely vitreous hemorrhage. Some anterior chamber activity is common.

•Complications: cystoid macular edema (CME), optic nerve edema, cataract, tractional retinal detachment, peripheral retinal neovascularization, cyclitic membrane, vitreous hemorrhage.

Investigation

Consider CBC, urinalysis, ESR, VDRL, TPHA, urinalysis, CXR for all patients. Further investigation should be directed by clinical indication (see Table 11.12). OCT or FA may be helpful to confirm CME.

Treatment

•Observation: if no CME and stable VA >6 months, then monitor only

•Topical: if significant AC activity, control with topical corticosteroids

and mydriatics (e.g., cyclopentolate 1% 1–2x/day).

•Periocular/systemic: if CME or visually disabling floaters, consider periocular corticosteroid (e.g., orbital floor/subtenons

methylprednisolone/triamcinolone 40 mg); intravitreal fluocinolone acetonide implant (Retisert) for unilateral disease; or oral corticosteroids (e.g., prednisone initially 1 mg/kg/day and titrating down) 9other immunosuppresives (e.g., methotrexate, azathioprine, cyclosporine) for bilateral or resistant disease.

•Surgical: options include cryotherapy (double freeze–thaw technique; there is some benefit for peripheral snowbanking with associated neovascularization) and vitrectomy/lensectomy (may benefit those with resistant disease and disabling media opacity).

RETINAL VASCULITIS 335

Retinal vasculitis

Retinal vasculitis comprises inflammation of the retinal vasculature. It may be a primary ocular disease or secondary to either infection or systemic disease.

Clinical features

•dVA, floaters, positive scotomas; may be asymptomatic if peripheral.

•Perivascular sheathing of arteries, veins, or capillaries; retinal hemorrhages; vitritis; disc swelling, CME.

•Complications: BRVO or CRVO, neovascularization, vitreous hemorrhage, ischemic maculopathy, tractional retinal detachment (TRD).

Investigations

Use FA for vessel wall staining, vascular leakage, skip lesions, widespread capillary leakage, new vessel leakage, disc leakage, petalloid macular leakage, enlarged foveal avascular zone (FAZ) (ischemia), vascular occlusion, and capillary dropout.

Consider CBC, urinalysis, ESR, VDRL, TPHA, ANA, ANCA, and CXR for all patients. Further investigation should be directed by clinical indication (see Tables 11.13 and 11.14).

Treatment

Where possible, the underlying disease is treated (e.g., with antibiotics for infective cases). However, in most instances, immunosuppression is required.

Corticosteroids are first line and may be periocular, oral (e.g., prednisone 1–2 mg/kg), or IV (e.g., pulsed methylprednisolone 500–1000 mg three doses on alternate days).

Cyclosporine and azathioprine tend to be used second line, although methotrexate, mycophenolate, tacrolimus, infliximab (mainly in Behcet’s disease), and cyclophosphamide (mainly in Wegener’s granulomatosus) also have their place.