This class of ophthalmic drugs is highly useful and rivals the pure topical corticosteroids in the treatment of the acute red eye. As with most drugs, there are clear indications and clear contraindications, with a gray zone in between.
In order to prescribe a combination drug with clinical precision, one has to have a masterful understanding of both antibiotics and corticosteroids. As many as half of all red eyes that we see are treated with a combination drug, rather than either a steroid or antibiotic alone. This observation clearly acknowledges two clinical realities:
- The need for topical antibiotics alone is relatively low.
- Almost all acute red eyes have a significant inflammatory component.
So, how does the astute clinician choose between a pure steroid and a combination drug? The answer is relatively straightforward, but, as always, there are exceptions to generalizations. The pivotal issue is the integrity of the corneal epithelium. If the corneal epithelium is intact, there is little or no reason for prophylaxis against opportunistic bacterial pathogens. This is because an intact epithelium is itself a firewall of defense. If there is significant epithelial compromise, then a combination drug may perfectly match the clinical need.
Remember that the conjunctiva will be inflamed in any patient presenting with an acute red eye. Simply put, the eye is red because it is inflamed. Also, the conjunctiva will be inflamed in almost all cases in which keratitis is present. With either keratitis (with an intact epithelium) or non-infectious conjunctivitis, we almost always use a topical steroid.
If the accurate diagnosis of bacterial conjunctivitis is made, the decision is whether to prescribe an antibiotic or a combination drug. The prime determinants are twofold: 1) The severity of the infection. 2) The degree of conjunctival injection. If the infection presents with marked mucopurulence, we would likely treat with a pure antibiotic, such as moxifloxacin (and perhaps even culture if the infection was severe). If the infectious expression was only mild to moderate, the degree of conjunctival injection would be the overriding issue in choosing between an antibiotic and a combination drug such as Zylet (loteprednol/tobramycin, Bausch & Lomb), TobraDex (dexamethasone/ tobramycin, Alcon), or Maxitrol (dexamethasone/neomycin/ polymyxin B, Alcon). We stress again that bacterial infection is uncommon, especially relative to the numerous expressions of non-infectious conjunctivitis.
An exception is the patient who presents with what appears to be a low grade bacterial conjunctivitis (i.e., minimal discharge), yet with moderate to marked conjunctival injection. The patient usually complains that the affected eye was “stuck together when I woke up.” Commonly, by the time the patient arrives at your office, any excess debris may have been cleaned from the lids and lashes. Further, blinking has moved considerable mucopurulent debris down the nasolacrimal system so that the objective slit lamp findings reveal only minimal microparticulant debris in the lacrimal lake; a clear, non-staining cornea; and/or a red eye. Here is where a combination product is used mainly to address the conjunctival inflammation, while concurrently eliminating any infectious component, even when the cornea is uninvolved.
When there is significant corneal epithelial compromise, we almost always use a combination drug. For most cases, the choice of drug class is that simple.
The first blockbuster, highly effective combination antibiotic/ corticosteroid was Maxitrol, containing neomycin, polymyxin B and dexamethasone. Maxitrol became a real workhorse in primary eye care. However, the occasional neomycin reaction, while not a major issue, prompted investigation into a “new and improved” combination drug. Thus was born TobraDex, which replaced the neomycin and polymyxin B with tobramycin. This drug, like Maxitrol, enjoyed market dominance, though from time to time, and again not a major issue, intraocular pressure increases prompted an investigation into a “new and improved” combination drug.
Thus was born Zylet. Keeping the highly efficacious tobramycin, the dexamethasone was replaced with a newer generation, esterbased corticosteroid, loteprednol. Now with Zylet, we have excellent antibiosis along with the safety and potency of loteprednol. It is available in 5ml and 10ml bottles.
Now that we have 90% of this topic covered, we need to spend the bulk of this article discussing other various exceptions and modifications to this rather simple decision tree. The best way to teach the concepts for drug class choice is perhaps by looking at a few specific clinical entities.
Thygeson’s Superficial Punctate Keratopathy (SPK)
This not-so-uncommon keratitis is seen in young to middle-aged patients. The classic symptoms are foreign body sensation, photophobia and lacrimation. This idiopathic condition has cycles of exacerbation and remissions over the course of 10 to 20 years, until it finally abates. It is during these exacerbations when symptoms prompt the patient to seek medical attention.
This usually bilateral keratitis shows several tiny, usually central, subtle (but readily seen) staining defects with fluorescein dye. (Note that about 20% of cases are unilateral, so differentiating Thygeson’s from herpes simplex must be done; here is where corneal sensitivity testing can be useful. Also, the Thygeson’s eye will generally be white, or minimally injected, whereas the herpetic eye will generally be considerably injected.)
If the patient is significantly symptomatic, a topical corticosteroid readily suppresses the keratitis and its attendant symptoms. If the presenting symptoms are tolerable, then artificial tears and patient education are likely all that is needed. However, the teaching point here is that even though there is some punctate staining in acute Thygeson’s SPK, all that is needed is a topical steroid. This is the uniform recommendation in authoritative textbooks.
While 1% concentrations of topical steroids are indicated in most inflammatory eye conditions, Thygeson’s is steroid sensitive. Therefore, our drug of choice in these cases is Alrex (loteprednol