Chlorambucil

A review of the treatment strategies that successfully combat this condition.

Anterior uveitis is the most common form of intraocular inflammation affecting the highly vascularized uveal tissue. However, anterior uveitis more precisely describes the presence of inflammation localized in the anterior chamber. Read on to learn more about this condition and the treatment strategies that keep it under control.

Reviewing the basics

Although often referred to synonymously, iritis and iridocyclitis are actually specific forms of anterior uveitis. Inflammation restricted to the iris is usually clinically considered a mild form of anterior uveitis known as iritis. Inflammation affecting both the iris and the ciliary body with possible "spillover" of white blood cells into the anterior vitreous is known as iridocyclitis.

We can further categorize anterior uveitis into acute, subacute and chronic forms.

* Acute uveitis. This form usually comes on suddenly, is symptomatic and persists for no more than eight weeks. If the inflammation recurs following the initial attack, especially while you're weaning the patient off her anti-inflammatory treatment, it is referred to as recurrent acute.

* Subacute uveitis. This is a form of anterior uveitis that's midway between acute and chronic with respect to the length of its presence and the clearing of the inflammation between exacerbations of inflammatory activity.

* Chronic uveitis. This form lasts longer than eight weeks, often for months or years, without clearing completely between exacerbations of inflammation. Its onset is often insidious and may be asymptomatic.

Identifying the telltale signs

Patients who have anterior uveitis will complain of ocular pain, red eye, photophobia, epiphora and blurred vision. In chronic anterior uveitis the eye may appear white and the patient may only experience mild or even no symptoms. Here's what to expect in your ocular findings.

* Injection. In acute anterior uveitis, injection results from a more diffuse hyperemia and a more specific circumciliary flush where the eye exhibits a reddened, violaceous hue immediately adjacent to the cornea and over the location of the ciliary body. This perilimbal injection encircles the cornea for 360 degrees and shows increased intensity closer to the limbus.

* White cells in the aqueous humor. The presence of extravasated white blood cells, along with protein and fibrin (flare) in the aqueous humor confirms the condition. Examine the anterior chamber using biomicroscopy-high magnification with a small, intense beam of white light directed obliquely through the aqueous. Grade both the number of cells you see and the amount of flare at each office visit so you can monitor the severity and response to therapy.

* Keratic precipitates. Clumps of white blood cells on the corneal endothelium are keratic precipitates (KPs). Small- to medium-sized white KPs are regarded as nongranulomatous.

New onset KPs are white and have a 3-D appearance. Old KPs are often pigmented and have a flattened, shrunken presentation. Large KPs that have a greasy, waxy "mutton fat" appearance are typically the result of granulomatous uveitis conditions. Iris nodules often accompany these "mutton fat" KPs.

* Additional findings. Other signs of anterior uveitis include pupillary miosis, low intraocular pressure (IOP), posterior synechiae (adhesions between the anterior lens surface and the iris), spillover cells in the anterior vitreous, hypopyon (layering of white blood cells) and plasmoid aqueous (high fibrin content causing no movement of cells in the anterior chamber).

Know the complications

Complications of anterior uveitis include posterior subcapsular cataract formation (especially seen in chronic anterior uveitis with prolonged topical steroid therapy), secondary glaucoma from the inflammatory process itself or prolonged topical steroid use and cystoid macular edema.

Taking treatment tips

Initiate therapy to alleviate symptoms and to avoid complications. The goals of treating anterior uveitis are:

* avoiding vision loss

* relieving ocular pain

* identifying the etiology of the inflammation

* preventing secondary complications such as posterior synechiae, cataracts, glaucoma, permanent iris vessel damage and phthisis bulbi

* reducing the severity and frequency of attacks or exacerbations of the uveitis.

Treatment can pose considerable risks when the condition involves a chronic process and you must administer drugs over a long period of time.

* Using corticosteroids. Corticosteroids remain the treatment of choice for patients who have acute anterior uveitis. Treat this type of inflammation with a strong topical preparation that provides good corneal penetration. The steroid of choice for initial therapy has been prednisolone acetate 1 % (Fred Forte). Because it's a suspension, instruct the patient to shake the bottle vigorously before use.

You may use topical corticosteroid solutions, such as prednisolone sodium phosphate 1 (Inflamase Forte) or dexamethasone phosphate 0.1% (Decadron Phosphate) for mild anterior uveitis. Both offer the advantage of not requiring shaking. Unfortunately, they don't penetrate the intact cornea as readily as an acetate product.

The strategy in the use of any steroid is to eliminate the inflammation as quickly and as completely as possible. Initial therapy therefore dictates using the topical agent every one to two hours while the patient is awake.

Another intensive therapeutic approach is to use one drop every minute for five minutes every hour. For mild to moderate cases, one drop four to six times daily may be a good regimen.

It's better to start with a high rate of instillation and decrease as the inflammation lessens then to start with a low rate and have to increase it. This principle applies to both the topical and systemic administration of steroids.

Maintain steroid administration until the active inflammation has been eliminated or, if the anterior uveitis is chronic, until it has been reduced to a minimum. Tapering should only begin once the inflammation is grade 1 + or less. A complete taper may take as few as two to four weeks to complete in patients who have mild anterior uveitis, or as long as six to eight weeks if the inflammation is severe.

An example of a typical drug taper is as follows: Give one drop every two hours for three days, then one drop every four hours for three days, then one drop twice a day for three days and finally, one drop once a day for three days. Then discontinue the steroid or have the patient apply it every other day for several more days. A sudden withdrawal of the steroid can result in a rebound inflammatory response, which would then require a larger dose of steroid for an even longer period of time because of longer lasting inflammatory activity.

See the patient every day or two initially to monitor the therapeutic response. Check IOP at least weekly. A steroid-induced rise in IOP occurs in as many as 30% of patients. If there's a significant increase in IOP, add antiglaucoma medications to help regulate the pressure. Don't use either cholinomimetics such as pilocarpine or prostaglandins such as latanoprost (Xalatan) because they can exacerbate intraocular inflammation and, in the case of prostaglandins, produce cystoid macular edema.

If the patient's IOP remains elevated despite the administration of antiglaucoma medication, switch him to one of the "soft steroids" - rimexolone 1% (Vexol) or loteprednol etabonate 0.5 % (Lotemax) -they show less propensity to elevate IOP.

Injectable periocular corticosteroids such as triamcinolone acetomide (Kenalog) or betamethasone are especially helpful in cases of anterior uveitis that are severe, chronic, recurrent or resistant to topical steroid therapy alone.

Oral prednisone is more often indicated for patients who have anterior uveitis that's associated with a systemic inflammatory disorder. The usual dosage of oral prednisone starts at l.Omg/kg/day and tapers slowly as the condition improves.

Another formulation consisting of methylprednisolone (Medrol DosePak) comes in a package of programmed delivery of oral steroid tapered over six days of therapy. It's a convenient method to increase therapeutic result when used for short-term treatment. Comanage long-term systemic steroid therapy with the patient's family physician or rheumatologist, if he's been diagnosed with an underlying inflammatory condition.

* Mydriatic cycloplegic drugs. This is the other key group of topical agents essential in the successful treatment of anterior uveitis. They help relieve ciliary spasm and pain by immobilizing the pupil. They prevent posterior synechiae and help stabilize the blood-aqueous barrier, thereby preventing additional protein leakage and flare.

Short-acting agents are usually best because they permit a varying pupillary diameter, avoiding a fixed, dilated pupil as you get with atropine 1% use. The best agents include homatropine 2.0% or 5.0% and scopolamine 0.25%.

Weaker agents, such as cyclopentolate 1% (Cyclogyl) and tropicamide 1% (Mydriacyl), tend to be too weak for moderate-to-severe anterior uveitis. Also, cyclopentolate causes a burning sensation upon instillation and may cause a psychotropic response in susceptible individuals.

* NSAIDs. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) can also play a role in the treatment of anterior uveitis. They work best in selflimiting mild cases such as traumatic- and postoperative cataract surgery-induced uveitis. While they're not as effective as steroids, they're a reasonable option in known steroid responders. But first try one of the soft steroids before abandoning steroids completely. Examples of topical NSAIDs include ketorolac 0.5% (Acular) and diclofenac (Voltaren).

* Immunosuppressive therapy. Finally, you may need immunosuppressive therapy in cases where steroids aren't effective or if the uveitis results in severe inflammation associated with a specific systemic disease. The drugs include the antimetabolites such as azathioprine (Imuran) and methotrexate, the T-cell activity inhibitor, cyclosporine and the alkylating agents such as cyclophosphamide (Cytoxan) and chlorambucil (Leukeran).

Tackle uveitis aggressively

Acute anterior uveitis is the most commonly seen type of intraocular inflammation. The vast majority of cases are idiopathic. You can easily manage most such cases with topical corticosteroids and a short-acting cycloplegic agent. Remember to treat aggressively at first then taper as the inflammation subsides. OM

Dr. Christensen has a partnership practice in Midwest City, Okla. He's a diplomate in the Cornea and Contact Lens Section of the American Academy of Optometry. He's also a member of National Academies of Practice.

By Leonid Skorin, Jr., O.D., D.O., F.A.A.O., F.A.O.C.O., Albert Lea, Minn.

Dr. Skorin is adjunct professor of neuroophthalmology at Midwestern University in Chicago. He is a staff

ophthalmologist at the Albert Lea Eye Clinic Mayo Health System.

Copyright Boucher Communications, Inc. Nov 2002
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