Another difficulty in determining disease chronicity arises when a patient cannot recall or was not aware of when his or her iritis started, usually because it is asymptomatic. Here again, the examination can usually answer the question. Examination findings suggesting that iritis has been longstanding include (a) band keratopathy and (b) loss of contour to the iris face, often with a washout of the iris color. Posterior synechiae, even many clock hours of them, are unfortunately not helpful, since they can form very quickly in very severe iritis and so do not indicate a long-standing process, unless occlusio pupillae (a fibrovascular membrane in the papillary space) has developed, which is, however, rare in developed countries.

Determining Whether Anterior Uveitis Is Bilateral or Unilateral

For a patient with AU, the process of ascertaining an etiology thus involves working sequentially through the first three of these categories, with the fourth category being the repository for undiagnosed disease.

Category 1: Iritis Syndromes

Category 2: Iritis Secondary to Other Eye Problems

Management Step 3: Treat for Immediate Control

With very few exceptions, AU can and should be treated with topical corticosteroids. In the United States, the most popular eyedrop for this purpose is prednisolone acetate 1%, although dexamethasone 0.1% or prednisolone sodium phosphate 1% are reasonable alternatives. We do not recommend using other medications or lower concentrations of these medications. The only possible exception is difluprednate 0.05%, which is a much newer corticosteroid eyedrop that appears to belong among the potent corticosteroid agents just mentioned. Its optimal dosing has not been firmly established, so we will not include it in this discussion, acknowledging that it may play a role in iritis therapy eventually.

Standard Treatment Regimen for Achieving Immediate Control in Most Forms of Iritis

• Begin with hourly corticosteroid eyedrops (as named above) while awake—usually at least 14 drops per day, and use these for at least 1 week. We generally do not schedule follow-up within that week, since it will be too soon to make any useful therapeutic decisions.

In follow-up at 1 week, the number of anterior chamber cells/high-power field (hpf) should be half of what it was at initial presentation. If it is not, then suspect that the patient is not using the eyedrops or that the condition may be infectious—typically herpetic (see “special cases,” discussed below).

• Continue hourly therapy with weekly visits until there are five or fewer cells/hpf. This may mean a few weeks of hourly therapy, with assessment each week anticipating that the number of anterior chamber cells/hpf will decrease by half at each visit.
  
• Once there are five or fewer cells/hpf in the anterior chamber, reduce the dose frequency to every 2 hours. Reevaluate every 2 weeks, and as long as the inflammation is not increasing, decrease the corticosteroids to every 2 hours for 2 weeks, four times per day for 2 weeks, three times per day for 2 weeks, two times per day for 2 weeks, one time per day for 2 weeks, and then discontinue the therapy. Thus, the increments in our standard eyedrop taper are: every 1 hour, every 2 hours, four times per day, three times per day, two times per day, one time per day, and then stopping the drug.
  
• If the disease flares during this period, one needs to consider using either a slower taper or periocular corticosteroid injections, as described below.
  
• Use cycloplegia, typically homatropine 5% twice daily, until there are fewer than five cells/hpf in the anterior chamber and then discontinue it.

Treatment Regimens for Immediate Control in Special Cases of Iritis

• Hypopyon iritis. This condition, which usually indicates that the patient carries the HLA-B27 gene, can require many weeks of hourly eyedrop therapy before being amenable to taper. It is important to verify that the uveitis is truly an anterior process. Assuming it is, we recommend two modifications to the standard treatment regimen described above.

Firstly, in addition to hourly corticosteroid eyedrops, we often prescribe oral corticosteroids, equivalent to prednisone 1mg/kg/day, continuing these for the first 7 days, or we use periocular injections as an alternative to oral corticosteroids. The injectable options are dexamethasone 2 mg, 0.5 mL, which will leave the eye in roughly 24 hours, or betamethasone phosphate/acetate 3 mg, 0.5 mL, which will leave the eye in roughly 10 days. Patients should use their eyedrops as per the standard regimen if either of these is used. If the patient has taken corticosteroids before and is not known to be a brisk corticosteroid-IOP responder, we often inject triamcinolone acetonide 20 mg, 0.5 mL, in the subtenon space. This will remain around the eye for several months, so that the patient can use corticosteroid eyedrops four times per day instead of hourly. (This approach is also advantageous for patients who are unable to use hourly eyedrops.)

Secondly, we taper the corticosteroid eyedrops by one increment each month, rather than every 2 weeks, since very aggressive iritis is well known to recur if a very slow taper is not used.

Management Step 4: Treat for Long-Term Control

We consider long-term control to be the process of keeping a patient’s eyes inflammation free after the initial inflammatory episode has been treated. This is by far the most challenging aspect of uveitis therapy.

Certainly, in many cases, a patient’s iritis may not recur after the initial treatment is tapered; the disease is quiescent, and no long-term control therapy is required. Frequently, however, the iritis recurs either during the initial corticosteroid taper or within 3 months of stopping it; this disease is chronic, and long-term control measures are needed.

The two general approaches to long-term control of AU are corticosteroids and immunosuppressives.

Corticosteroids

Corticosteroids are an acceptable means of maintaining long-term control of iritis if (a) the dose required is low and likely to be well tolerated and (b) the patient’s iritis is not believed to be associated with a systemic disease.

We occasionally use corticosteroid eyedrops long-term if complete control of iritis is maintained with three or fewer drops per day (one drop three times per day), a dose that many patients can take for several months before developing side effects. It is important to be certain that the inflammation is indeed controlled when using corticosteroid eyedrops for a longterm, since the worst mistake a clinician could make, we feel, is to use these drops for a longterm and still tolerate inflammation (we generally do not tolerate more than two cells/hpf), thereby subjecting a patient to the undesirable effects of both disease and drugs.

• Periocular corticosteroid injections are an effective means of maintaining long-term control in some patients with iritis, provided they are not needed too frequently—which to us means one triamcinolone 20 mg injection roughly every 6 months. This approach is helpful in enabling patients to avoid the use of corticosteroid eyedrops when they would otherwise require these agents four times per day or more.

IOP elevation is common when corticosteroids are used for a long time in any form, and IOP-lowering eyedrops are frequently required as adjunct therapy.

Not uncommonly, patients with chronic uveitis will not tolerate corticosteroids, because of intractable IOP elevation or posterior subcapsular cataract. In this case, we resort to immunomodulatory therapy.

• Ankylosing spondylitis
  
• Reiter syndrome (reactive arthritis)
  
• Inflammatory bowel disease
  
• Psoriatic arthritis
  
• Postinfectious or reactive arthritis

Ankylosing Spondylitis–Associated AU

Incidence

• Patients with AS usually have a positive family history; males are more frequently affected (80% males), and 88% are positive for HLA-B27.
  
• There is a 25% chance that an HLA-B27-positive patient with AS will develop AU.

Clinical Findings

• Women often show minimal back symptoms
  
• Low back pain more than 3 months unrelieved by and often worse after rest
  
• Decreased lumbar motion as the disease progresses
  
• Aortitis in 5% of patients, other patients developing pulmonary apical fibrosis and chest wall pain or stiffness

Diagnostic Testing

• The HLA-B27 test establishes the presence of the gene.
  
• CT scan or X-ray will demonstrate changes of the lumbosacral spine or pubic symphysis.

Treatment

• Physical therapy to help preserve spinal and neck mobility
  
• Oral NSAIDS
  
• Oral corticosteroids or immunomodulatory agents including methotrexate or tumor necrosis factor alpha antagonists

Reiter Syndrome–Associated AU

The diagnostic triad for Reiter syndrome consists of urethritis, conjunctivitis, and arthritis. The condition occurs most frequently in young adult males (90%), and 85% to 95% are HLA-B27 positive. Reiter syndrome may be triggered by episodes of urethritis caused by Chlamydia or Ureaplasma urealyticum or by diarrhea or dysentery caused by Campylobacter, Shigella, Salmonella, and Yersinia. Arthritis starts within 30 days of infection in 80% of patients.

Clinical Findings

Ocular findings

• Early on, may have a mucopurulent papillary conjunctivitis
  
• Severe chronic recurrent acute attacks of iritis (50%)
  
• Heavy flare, early synechiae
  
• Subepithelial keratitis may leave scars

Systemic findings