Tracking Trends in Pharmacologic Therapy

By Melton, Ron; Thomas, Randall

New contenders and old favorites battle ocular infection, inflammation and allergies.

In our practices, we use antibiotics, steroids, combination drugs and allergy products to treat ocular infection and inflammation. In addition to the two workhorses in contemporary practice – fluoroquinolones and aminoglycosides – steroids give us an enormous advantage over the inflammatory response we now know underlies most ocular diseases.

Fluoroquinolones and aminoglycosides

Fourth-generation fluoroquinolones are potent, broad-spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase IV. These drugs are used mainly to prophylax against infection after refractive and cataract surgery rather than to treat infection. Ciprofloxacin (Ciloxan) and ofloxacin (Ocuflox) are PDA-approved to treat corneal ulcers, and levofloxacin (Quixin), gatifloxacin (Zymar) and moxifloxacin (Vigamox) are approved to treat bacterial conjunctivitis.

Although the fourth generation fluoroquinolones aren’t approved to treat “infectious” keratitis, moxifloxacin 0.5% and gatifloxacin 0.3% are emerging as the standard of care for this condition. Moxifloxacin is preservative-free and penetrates at higher concentrations than gatifloxacin, but some studies show that the latter has less corneal toxicity.1,2

Aminoglycosides, bactericidal drugs that inhibit protein synthesis, are effective against most common gram-positive and gram- negative bacteria. These drugs aren’t new, but their cure rates are similar to those of fluoroquinolones, and they cost much less.

Patients occasionally have toxic or allergic reactions while using gentamicin and less frequently with tobramycin, but aminoglycosides rarely cause toxicity when used properly. Most patients who present with an iatrogenic response to aminoglycosides use the drops aggressively for longer than a week. The key is to use these drugs aggressively for a few days and stop once the bacterial infection clears.

Steroids

Most cases of anterior segment eye disease are caused by inflammation (98%) and not infection (2%). Two corticosteroids we currently use to treat ocular inflammation are prednisolone acetate 1.0% (Pred Forte and Econopred Plus) and loteprednol etabonate (Alrex 0.2% and Lotemax 0.5%).

Prednisolone acetate 1.0% is a potent anti-inflammatory offering five times more potency than hydrocortisone. This agent has been widely used for years and is frequently recommended for treating severe anterior uveitis and episcleritis. Pharmacists may substitute a generic suspension for branded prednisolone 1.0%, but the literature reports and personal experience has shown that generic prednisolone is less effective, particularly for treating severe episcleritis or uveitis.

Loteprednol etabonate 0.5% is a site-specific, ester-based corticosteroid that also reduces inflammation associated with inflammatory eye disease. When applied to the eye, this agent exerts its biologic effect and is quickly converted into inactive metabolites. Therapeutically, loteprednol etabonate 0.5% is similar to prednisolone acetate 0.1% but elevates IOP very little, if at all.

Another condition characterized by ocular inflammation is allergic eye disease. Antihistamine/mast cell stabilizers offer prolonged receptor binding and some mast cell stabilization for patients with mild symptoms. Four drugs are available in this class: Olopatadine 0.1% (Patanol), ketotifen 0.025% (Zaditor), azelastine 0.05% (Optivar) and epinastine 0.05% (Elestat).

Loteprednol etabonate 0.2% works as well as these antihistamine/ mast cell stabilizers in patients with mild ocular inflammation associated with seasonal allergies.

In the past, we treated chronic uveitis, reduced inflammation after corneal transplant and controlled chronic immune herpes simplex stromal disease with prednisolone acetate 1.0%, but now, we prefer to treat these conditions with loteprednol etabonate 0.5%. This agent is highly effective and safer than older steroids, making it a good choice for patients who need long-term anti-inflammatory therapy.

Combination drugs

Several combination anti-infective/anti-inflammatory agents are available for treating ocular disease, but you always should assess these combinations according to their steroid component.

Two combination agents, tobramycin 0.3%-loteprednol etabonate 0.5% suspension (Zylet) and tobramycin 0.3%-dexamethasone (TobraDex), offer similar coverage against most ocular pathogens, but the Zylet has a broader safety margin regarding potential steroid-induced side effects. Both agents / suppress inflammation, but dexamethasone is more likely to elevate IOP than loteprednol.

Robust options

Even with strong standards of care in place for many of the anti- infective and anti-inflammatory drugs we use for ocular conditions, we still enjoy a great deal of discretion to prescribe the right treatment for the individual. Safer drugs give us long-term results for chronic problems, even as vigorous drugs eliminate infection and reduce inflammation faster than ever. We are fast approaching excellent control of these challenges to ocular health.

Steroids give us an enormous advantage over the inflammatory response we now know underlies most ocular diseases.

Loteprednol etabonate 0.5%… is a good choice for patients who need long-term anti-inflammatory therapy.

References

1. Kim DH, Stark WJ, O’Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients. Ophthalmology. 2005;112:1992-1996.

2. Solomon R, Donnenfeld ED, Perry HD, et al. Penetration of topically applied gatifloxacin 0.3%, moxifloxacin 0.5% and ciprofloxacin 0.3% into the aqueous humor. Ophthalmology. 2005;112:466-469.

By Ron Melton, O.D., F.A.A.O., Charlotte, N.C., and Randall Thomas, O.D., M.P.H., F.A.A.O., Concord, N.C.

Dr. Melton and Dr. Thomas are members of group practices in North Carolina. and adjunct faculty to several colleges of optometry. They have given many lectures and written articles on the topics of ocular differential diagnosis and medical management of eye diseases, which are available detailed on their Web site eyeupdate.com.

Copyright Boucher Communications, Inc. Mar 2006