Ophthalmologic Manifestations of Ankylosing Spondylitis 

Ankylosing spondylitis is a chronic, progressive inflammatory disorder primarily affecting the axial skeleton. Ankylosing spondylitis is one of the seronegative spondyloarthropathies, a group of multisystem inflammatory diseases that affects the spine, peripheral joints, adjacent soft tissues, and extra-articular structures. Most of these disorders are associated with the human leukocyte antigen B27 (HLA-B27) antigen.^[1]

In addition to ankylosing spondylitis, the seronegative spondyloarthropathies include the following:

• Reactive arthritis (also referred to as Reiter syndrome)
• Inflammatory bowel disease-associated arthritis
• Psoriatic arthropathy
• Juvenile spondyloarthropathy
• Undifferentiated spondyloarthropathies

Several of these disorders share some clinical features, such as sacroiliitis, spondylitis, asymmetric peripheral arthritis, aortitis, clinically evident or occult bowel lesions, and uveitis. Acute anterior uveitis occurs in as many as 30% of patients at some time during the course of ankylosing spondylitis, particularly in persons with the HLA-B27 allele. Patients with ankylosing spondylitis who have peripheral arthritis also have a higher prevalence of uveitis.^[2]

Go to Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy for complete information on this topic.

Complications

Anterior and posterior segment inflammation is greater with uveitis associated with ankylosing spondylitis than it is with idiopathic uveitis, especially if ocular surgery is performed.

The exact role of HLA-B27 in the development of uveitis is not precisely known, but several theories for its role in disease exist. The oldest theory is that of molecular mimicry, in which an infectious agent triggers an immune response against autoantigens. The HLA-B27 antigen shares some amino acid homology with proteins from several gram-negative bacteria, including Yersinia enterocolitica, Shigella flexneri, and Chlamydia trachomatis, as well as from gram-negative bacteria found in the GI tract.

Other theories include the arthritogenic peptide theory, in which the immune response is directed against a peptide presented by HLA-B27; the altered self theory, in which a reactive sulfhydryl group on the HLA-B27 molecule interacts with other self peptides, thereby inducing antigenicity; and, finally, the theory that the HLA-B27 allele confers an altered immune response that directly relates to the disease.

HLA-B27 typing is not necessary to establish the diagnosis of ankylosing spondylitis, but it is a useful prognostic indicator in patients with uveitis.

Patients with ankylosing spondylitis and the HLA-B27 antigen tend to develop uveitis at a younger age, have a longer duration of ocular disease, and have more recurrences. Additionally, patients who are HLA-B27 positive appear to have more severe disease in terms of anterior chamber inflammation and vitreitis, resulting in a higher incidence of complications and the requirement for more aggressive therapy.

The ocular prognosis is dependent on the ability to control the inflammatory response.

The male-to-female ratio is estimated to be 2:1.

Ankylosing spondylitis usually begins during the second decade. The associated uveitis typically occurs at an earlier age than does idiopathic uveitis.

A thorough history should be taken.

Patients often complain of redness, pain, photophobia, blurry vision, and occasionally tearing. No history of ocular discharge is present.

Many cases of uveitis are unilateral, but the condition can be bilateral.

Attacks often are relatively acute in onset. Some patients may present with chronic symptoms of blurring and ocular hyperemia.

Past ocular history

Past ocular history should include the following:

• Previous episodes, duration, and treatment
• Previous complications (eg, cataract, glaucoma, cystoid macular edema [CME], epiretinal membrane)

Patients suspected of having ankylosing spondylitis should undergo a thorough physical examination, preferably by a rheumatologist.

A complete ophthalmic examination should be performed, with special emphasis on the following:

• Best-corrected distance and near acuity
• Pupil examination
• Slit-lamp examination
• Intraocular pressure - Often low during acute exacerbations, secondary glaucoma, hypotony, phthisis
• Dilated fundus examination - Vitreitis, CME, retinal vasculitis, epiretinal membrane

Slit-lamp examination may reveal the following:

• Conjunctiva and sclera - Conjunctival injection, watery discharge, no follicles or papillae
• Cornea - Small to medium keratic precipitates
• Anterior chamber - Cells and flare, fibrin, and/or hypopyon not uncommon
• Iris - Posterior synechiae, peripheral anterior synechiae, pupillary membrane, no nodules
• Lens - Posterior subcapsular cataract
• Vitreous - Anterior vitreous cells, vitreitis

Conditions to consider in the differential diagnosis of the ophthalmologic manifestations of ankylosing spondylitis include the following disorders:

• Sarcoidosis
• Nongranulomatous anterior uveitis
• Intermediate uveitis
• Ocular manifestations of syphilis

HLA-B27 typing

A positive result narrows the differential diagnosis to the seronegative spondyloarthropathies. This also may be a useful prognostic indicator for the severity of ocular disease.

Antinuclear antibody

Antinuclear antibody (ANA) results are negative in ankylosing spondylitis but positive in many patients with collagen vascular diseases. Also, the results are positive in children with juvenile idiopathic arthritis (JIA) who are at high risk to develop uveitis.

Rheumatoid factor

Most patients with JIA are rheumatoid factor (RF) negative.

Complete blood count

A mild anemia may be noted in some patients with a seronegative spondyloarthropathy, JIA, or collagen vascular disease.

Lyme titer

Lyme titer is useful only in patients with a history of a tick bite and a rash typical for erythema chronicum migrans.

Purified protein derivative

Purified protein derivative (PPD) should be performed to rule out tuberculosis as a cause of the uveitis.

Angiotensin-converting enzyme

Angiotensin-converting enzyme (ACE) often is elevated in patients with sarcoidosis.

Fluorescein angiography

Fluorescein angiography may be useful in patients with CME and/or retinal vasculitis.

Other tests

The Venereal Disease Research Laboratory (VDRL) test and the fluorescent treponemal antibody absorption (FTA-ABS) test should be performed to rule out syphilis as a cause of the uveitis.

The objectives of treatment for patients with uveitis include the reduction of inflammation (corticosteroids), the relief of symptoms (cycloplegics and anti-inflammatories), and the preservation or restoration of vision.

Corticosteroids

Corticosteroids decrease the recruitment of inflammatory cells and alter cell function. They may be administered topically, via periocular injection, or systemically, and then tapered slowly.

Topical steroids are used to treat disease limited to the anterior segment. Prednisolone acetate 1% is most effective in reducing anterior chamber inflammation. Adverse effects include cataract formation and increased intraocular pressure. Therapeutic levels of corticosteroids cannot be achieved in the vitreous via the topical route; therefore, this method of administration is ineffective for posterior segment disease. An alternative route of delivery may be considered when the anterior uveitis is severe or unresponsive to topical treatment. However, before injecting depot steroids, a 4- to 6-week course of topical steroids may be useful to ensure that the patient is not a steroid responder.

Periocular corticosteroids may be used to treat severe anterior uveitis, intermediate uveitis, or CME. Complications include cataract formation and increased intraocular pressure, which may be refractory to all forms of therapy, short of surgical removal of the injected material.

Systemically administered corticosteroids may be considered for vision-threatening uveitis unresponsive to maximal topical and periocular therapy. An internal medicine or rheumatology consultation is advisable in the management of these patients.

If systemic treatment is required, it is necessary to determine whether medical contraindications to systemic corticosteroids exist, particularly in children and in elderly patients. Systemic corticosteroids suppress growth in children. They may exacerbate diabetes mellitus in susceptible individuals. Weight gain and fluid retention are expected effects. Electrolyte imbalance is a common complication. Long-term hazards include osteoporosis, compression of the spine, gastrointestinal hemorrhage, and reduction in immune response to infection, especially tuberculosis.

Cycloplegics

Cycloplegics reduce ciliary spasm and pain and prevent the development of posterior synechiae. Drugs and dosing include the following:

• Tropicamide 1%, 3 times a day (mild disease)
• Homatropine 5%, 2-4 times a day (moderate to severe inflammation, hypopyon)

Immunomodulatory therapy

Immunomodulatory therapy is often useful in patients who are unresponsive to short courses of corticosteroids, in patients with chronic uveitis, or in patients who develop adverse effects from corticosteroid therapy.

A number of agents have been used, including methotrexate, azathioprine, cyclosporin A, mycophenolate mofetil, cyclophosphamide, and chlorambucil. Myelosuppression and secondary infection are among the most common adverse effects of these agents.

Tumor necrosis factor-alpha (TNF-alpha) inhibitors may be useful in patients with the seronegative spondyloarthropathies, including ankylosing spondylitis. Available TNF-alpha inhibitors include infliximab, etanercept, and adalimumab. These agents may be useful in reducing the number of flares of anterior uveitis in patients with ankylosing spondylitis. Adalimumab has been shown to reduce the rate of anterior uveitis flares by at least 50% in a large open-label study.^{[3, 4, 5, 6, 7]}

A rheumatologist, an internist, or an oncologist is an essential member of the team in the management of patients treated with immunomodulatory agents.

Rheumatology

Early evaluation for all patients with suspected ankylosing spondylitis is essential to avoid delays in diagnosis and treatment of the systemic disease. Ongoing communication with the rheumatologist is critical for managing patients who require immunomodulatory therapy.