Wednesday, May 17, 2006

Clinical Treatment of Ocular Rosacea

By Roger M. Kaldawy, MD, John E. Sutphin, MD, And Michael D. Wagoner, MDEdited By Sharon Fekrat, MD, And Ingrid U. Scott, MD, MPH

Ocular involvement is common in rosacea. Ocular irritation is usually worse upon awakening and when performing prolonged visual tasks such as reading, driving or using the computer. At such times, one solution however temporary, may be found with blinking of the eyes. The severity of ocular rosacea does not always correlate with the severity of cutaneous changes. It is important that ophthalmologists recognize the spectrum of clinical findings of ocular rosacea and provide appropriate therapeutic intervention.

Tear film disturbances are responsible for the vast majority of symptoms in ocular rosacea. The reduced amount and altered character of meibomian gland secretions result in destabilization of the lipid portion of the tear film and increased tear evaporation rates. More than one-third of patients with rosacea also have impaired aqueous tear secretion, further contributing to ocular surface desiccation.The most serious complications of ocular rosacea probably result from reactions of the sclera, limbus and cornea to staphylococcal endotoxins or cell-mediated hypersensitivity responses to staphylococcal antigens. The variability in response of patients with ocular rosacea to these immune reactions may account for the extreme variability in clinical signs and symptoms associated with this disorder.

 The eyelid margin may be erythematous and thickened, with telangiectatic vessels around meibomian gland orifices, which are often plugged with thickened, yellowish secretions. Multiple calcific concretions may be seen on the palpebral conjunctiva, along with sequelae of previous treated and untreated chalazia.The tear film, which may have decreased height and increased debris, may break up rapidly between blinks. The conjunctiva may be chronically hyperemic with inferior palpebral follicles. Mucopurulent discharge may be present if acute staphylococcal blepharoconjunctivitis is present. Recurrent episcleritis is not uncommon, but scleritis is rare.Punctate epithelial erosions are frequently present, especially inferiorly. Occasionally, peripheral corneal infiltrates may occur. These focal areas of limbal stromal inflammation may be single or multiple, may or may not have associated epithelial defects and are often associated with limbal vascularization, particularly after multiple recurrent episodes.Rarely, there may be circumferential extension of limbal stromal inflammation with development of an epithelial defect, stromal thinning with potential perforation and/or microbial superinfection. Peripheral corneal vascularization may progress toward the visual axis with lipid deposition, scarring and opacification at the leading edge; this may result in severe visual impairment in neglected cases.

Tetracycline derivatives are the mainstay of therapy for ocular rosacea. Our standard regimen is to start with 100 milligrams of doxycycline orally twice a day for one month, after which it is used once daily for at least two more months.Therapeutic response. Patients are advised that there will be a delayed therapeutic response of several weeks. At three months, the medication is adjusted according to the therapeutic response: For marked improvement, the medication can be tapered to 100 mg every other day for the next three months. For mild to moderate improvement, 100 mg is continued on a daily basis. After six months, patients may go on “doxycycline vacations” for two to three months. Eventually symptoms will recur in most cases, and periodic reinstitution of low maintenance doses is necessary.Systemic vs. topical. For patients who can’t tolerate systemic tetracycline therapy, topical metronidazole gel (NetroGel) 0.75 percent twice daily or 1 percent daily, applied to the eyelids, has been shown to be safe and effective.Side effects. The major side effect that compromises the ability to use doxycycline is gastrointestinal disturbance. This is probably dose-related; it is ameliorated by taking the medication with food and is better tolerated with time. Photosensitivity may be a problem in some patients. All patients are advised to avoid excessive sun exposure and to use appropriate skin screening agents until their response to doxycycline is known.Contraindications. Doxycycline is contraindicated in pregnant women, nursing mothers and children under the age of 8.

Tetracycline derivatives are most effective when used in conjunction with the following three-step approach:

1. Normalize tear film disturbance.
Warm compresses. These help further minimize meibomian gland obstruction and improve lipid flow into the tear film.
Punctal occlusion. Temporary or permanent occlusion is useful if aqueous tear production is deficient.
Artificial tear substitutes. These are useful until ocular surface wetting, punctate epitheliopathy and variable vision during prolonged visual tasks have improved.

2. Control bacterial overgrowth.
Lid hygiene. This is part of a long-term maintenance program to minimize meibomian gland obstruction, improve lipid flow into the tear film and control bacterial overgrowth.
Topical antibiotics. These are useful in the first month of treatment to reduce bacterial flora. Generally, they should be used when acute mucopurulent blepharoconjunctivitis, marginal corneal infiltrates or peripheral ulcerative keratitis are present.

3. Control inflammatory and hypersensitivity reactions.
Topical corticosteroids. These are useful in the first month of treatment to reduce ocular surface inflammation. Generally, they should be used if marginal corneal infiltrates, peripheral ulcerative keratitis without progressive thinning and/or vascularization are present.
Topical progestational steroids. Compounded medroxyprogesterone 1 percent may be used if peripheral ulcerative keratitis with progressive thinning is present.
In addition, topical progestational steroids are useful in conjunction with corticosteroids for treating progressive vascularization.

Dr. Kaldawy is assistant professor of ophthalmology at Boston University; Drs. Sutphin and Wagoner are both professors of clinical ophthalmology at the University of Iowa, Iowa City.