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    Improved form of brimonidine has fewer contraindications

    Gentler preservative provides better response for patients with ocular surface problems

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    Figure 1 Conjunctival inflammation treated with brimonidine tartrate 0.15% (Alphagan P, Allergan). By decreasing the amount of conjunctival inflammation, the success rate of surgery can be optimized. (Photo courtesy of Robert J. Noecker, MD)
    Brimonidine tartrate 0.15% (Alphagan P, Allergan) is a "new and improved" version of brimonidine 0.2% (Alphagan, Allergan). It continues to have an efficacy profile similar to the one ophthalmologists have grown used to with brimonidine 0.2%.

    In addition, the systemic safety profile is better than regular brimonidine 0.2%. However, the biggest benefits with brimonidine 0.15% are seen in the area of ocular surface health and tolerability.

    In the traditional treatment algorithm for glaucoma, brimonidine 0.15% has settled into a position as an excellent adjunctive agent and alternative to the prostaglandin/ prostamide class of drugs. When brimonidine 0.15% is used in conjunction with the prostaglandins latanoprost (Xalatan, Pharmacia) or travoprost (Travatan, Alcon), or the prostamide bimatoprost (Lumigan, Allergan), it provides excellent additional IOP reduction. Furthermore, when used in conjunction with these agents, concerns about diurnal peak-and-trough effects of brimonidine 0.2% are minimized.

    Prior studies have shown that brimonidine 0.2% is a better additive agent to latanoprost than timolol or dorzolamide (Trusopt, Merck). There are additional studies under way to confirm that this trend continues with brimonidine 0.15%. Furthermore, in comparison with the nonselective beta-blockers, brimonidine 0.15% has a superior safety profile, because there is minimal concern about cardiopulmonary side effects with brimonidine 0.15%.

    In those patients who need glaucoma therapy with multiple medications in order to control their IOP, the addition of brimonidine 0.15% to the regimen has minimal adverse effects on the ocular surface. In contrast to using a medication that has a relatively high amount of benzalkonium chloride (BAK), such as latanoprost (0.02% BAK), and then adding another twice-a-day medication that has a BAK content of 0.01%, such as timolol, the BAK load on the ocular surface can be better optimized using a combination of a low-BAK drug such as bimatoprost (0.005%) and brimonidine 0.15% (none).

    Minimal surface effects

    Optimizing the "BAK load" on the eye may be most important in patients with glaucoma who are about to undergo trabeculectomy. Long-term topical glaucoma therapy has been linked to bleb failure, along with beta-blockers, epinephrine compounds, and miotics. The amount of BAK in the drops is probably more important than the class of medications in patients treated with medical therapy. A preoperative switch to low- or no-BAK drugs such as brimonidine 0.15% may be indicated. By decreasing the amount of conjunctival inflammation, the success rate of surgery can be optimized.

    There are several types of patients in whom I consider brimonidine 0.15% to be the drug of first choice. In those patients who have compromised ocular surfaces (i.e., patients who have undergone corneal transplant or who have neurotrophic corneas, prior HSV infections, severe dry eye, or extensive histories of allergies with topical medications), brimonidine 0.15% may be the best choice for initial therapy.

    Who should use it?

    In those patients who have undergone prior corneal transplant, there is often concern about the relative neurotrophic state of the cornea and compromised ocular lubrication, either from the trauma of prior surgery or decreased corneal sensation. Often these patients have deficient tear production and relatively inflamed conjunctival surfaces.

    Because brimonidine 0.15% does not contain BAK, but rather the preservative Purite, it is much more benign to the ocular surface. With chronic use it does not cause an increase in ocular surface inflammation or an increase in the number of subconjunctival lymphocytes. As a result, chronic therapy with brimonidine 0.15% does not appear to have an adverse effect on the tear film or tear production in these patients, in whom surface lubrication is very important.

    A similar effect is seen in patients who suffer from dry eye. This is an increasingly common problem as the population ages, and it can be exacerbated by environmental conditions. Though the environment seen in the southwestern region is drier than that in the east, in the wintertime many patients with dry eye have exacerbations from the decreased humidity in indoor heating or in automobile heating systems. Often changes on the ocular surface such as conjunctival injection/hyperemia and punctate keratopathy are mistaken for infectious conjunctivitis or an allergic reaction to medications.

    Dry eye

    In contrast to medications that contain BAK and have an increasingly toxic effect with multiple types of medications being used, when brimonidine 0.15% is used the toxicity seen on the ocular surface is very similar to that seen when using a relatively gentle artificial teardrop (Refresh Tears, Allergan).

    In patients who have had conjunctival scarring from multiple surgeries and often an associated poor-quality tear film, brimonidine 0.15% may be much gentler on the ocular surface. Many times these patients have a deficient number of goblet cells due to the prior trauma of surgery. BAK-containing eyedrops often can decrease the number of active goblet cells and lead to problems in surface wettability. By using the pH-neutral brimonidine 0.15% with no BAK, the ocular surface can be preserved and kept healthy.

    In post-cataract or LASIK patients who may be using a high number of artificial tears, steroids and/or NSAIDs, and antibiotics, the use of brimonidine 0.15% as prophylaxis against pressure spikes and/or to continue treating preexisting glaucoma may be beneficial. It is most likely that it is the detergent action of BAK in topical medications that leads to problems with the flap following LASIK.

    When brimonidine 0.15% is applied to the cornea prior to dosing, the worry about the adverse effects of BAK and flap positioning is minimized. Furthermore, at the low concentration of Purite preservative in brimonidine 0.15%, there appears to be no effect on cellular migration or epithelial healing. In this setting, brimonidine 0.15% is probably the optimal drug to use to minimize the adverse effects of eyedrops on the healing ocular surface.

    A 62-year-old black man was seen at a veteran's hospital for treatment of his glaucoma. The patient had cupping of 0.90, extensive visual field loss in both eyes, and a history of intolerance to most ocular medications. He could not tolerate medical therapy with latanoprost, dorzolamide, brinzolamide (Azopt, Alcon), pilocarpine, or brimonidine 0.2%.

    Case report

    He experienced severe shortness of breath with the use of nonselective beta-blockers and experienced only minimal IOP reduction with betaxolol (Betoptic, Alcon). A trial of acetazolamide (Diamox, Wyeth) resulted in depression, nausea, and paresthesias. Phospholine iodide decreased his vision so excessively that he could not ambulate in unfamiliar places. The patient underwent multiple sessions of argon laser trabeculoplasty but without prolonged reduction of his IOP. The patient continued to have visual field loss with IOPs in the mid-20s.

    He underwent trabeculectomies in both eyes and had severe allergic conjunctivitis and eyelid swelling with his postoperative medications, including atropine, prednisolone, and ofloxacin. The patient needed to have special preservative-free formulations made of these medications to minimize the allergic reactions.

    Following the surgery, the patient had IOPs of 18 mm Hg OU, and over the next year was thought to have continued degradation in his visual fields. He was given a trial of preservative-free timolol but experienced wheezing once again, was intolerant, and could not take the medication. The patient then started treatment with brimonidine 0.15% and had reduction of his IOP down to 14 mm Hg in both eyes. Over the past year his visual fields have stabilized, and there was no recurrence of the allergic conjunctivitis seen with his prior topical therapy.

    This patient appears to have been intolerant to all BAK-containing medications. Consideration was given to using glaucoma medications without preservatives, including preservative-free timolol, phospholine iodide, timolol gel (Timoptic-XE, Merck), and brimonidine 0.15%.

    Discussion

    Due to the patient's pulmonary status, the nonpreserved beta-blocker, while benign to the ocular surface, was not tolerated systemically. The patient could not tolerate the induced myopia associated with phospholine iodide due to his phakic status. Timolol gel, with its BAK-related preservative, was considered but once again rejected on the basis of systemic grounds.

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    Robert J. Noecker, MD
    Dr. Noecker, vice chair, University of Pittsburgh Medical Center Eye Center, and director, Glaucoma Service and associate professor of ...

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