INTRACAMERAL CEFUROXIME

'How does subconjunctival injection compare with intracameral injection or topical drops in terms of pharmacokinetics?' This question is timely in the wake of recent developments surrounding intracameral cefuroxime discussed throughout this issue. The available data allow direct comparison of drug levels achieved after subconjunctival vs. intracameral injection.

The subconjunctival injection places the drug near the anterior surface of the eye, forming a depot beneath the conjunctival barrier adjacent to the sclera. Drug diffuses into adjacent ocular structures, but the injection port itself is thought to facilitate leakage back into the conjunctival sac1,2 bathing the external cornea with injected solution. Penetration through corneal layers to the aqueous humour is dependent on drug lipophilicity, hydrophilicity, and molecular size, among other factors. in contrast to topical drops that introduce interpatient variability in retained dose, subconjunctival and intracameral injections deliver a known finite dose.

Comparing ocular cefuroxime levels after various routes of administration

In 1996, Jenkins and associates3 measured anterior chamber cefuroxime concentrations after administration routes that included subconjunctival injection and frequent topical drops. Mean aqueous humour (Ah) cefuroxime levels 120-160 minutes after a 25mg subconjunctival dose reached 5.65 μg/ml, but only 2.16 μg/ml after a similar topical drop dose (see table). increasing the subconjunctival dose to 125mg raised Ah levels to 20.23 μg/ml at 12-24 minutes, with levels still rising at the last sampling time. in study eyes with a 10mm corneal wound, topical 12.5mg cefuroxime produced Ah peaks of 9.34 μg/ml at 12-24 minutes, whereas the same dose to a normal cornea produced lower levels of 0.05 μg/ml.

The authors concluded that, in an intact eye, only the subconjunctival route of administration produced Ah levels > 1 μg/ ml at 12-24 minutes post-dose, with levels rising slowly over time after either drops or subconjunctival injection. Nevertheless, the table shows that Ah cefuroxime levels after an intracameral injection exceed levels after subconjunctival injection, or after drops, even in the presence of a corneal wound.

A more recent study examined Ah moxifloxacin levels after a 1.0mg subconjunctival injection given at various times prior to cataract surgery.4 Ah levels reached 3.03 μg/ml one hour after injection (see table), dropping to 1.91 μg/ ml at three hours; 0.53 μg/ml at five hours; and 0.3 μg/ml at six hours post-dose. in comparison, topical drops given Q2h before surgery produced Ah levels of 2.28 μg/ml.5 subconjunctival vancomycin resulted in substantially higher Ah concentrations than did topical drops, despite the use of a higher drop concentration (see table).6,7

By direct injection into the anterior chamber, the intracameral injection bypasses corneal and external ocular barriers, and reduces interpatient variability in the delivered dose. high antibiotic levels are achieved instantaneously after intracameral injection, without delays due to drug diffusion. The cefuroxime 1.0mg intracameral injection delivers Ah levels at least 100 times greater than the highest subconjunctival dose (see table).

Nevertheless, Ejaz Ansari FRCOphth, MD points out that some centres continue use of postoperative subconjunctival antibiotics because endophthalmitis rates are perceived as relatively low and subconjunctival corticosteroids are also given. Luis Cordoves MD, of the hospital Universitario de Canarias, spain, however, finds that subconjunctival injection is often painful with current modes of topical anaesthesia, and emphasises that one study reported a three-fold reduction in postoperative endophthalmitis rates after 50mg subconjunctival cefuroxime was discontinued, and replaced with 1.0mg intracameral cefuroxime at the end of cataract surgery.8

It is important to recall that any discussion of measured ocular antibiotic levels implies correlation with bacterial MiCs and anticipated bactericidal effects over time. These “drug-bug†interactions vary considerably with bacterial strain and antibiotic. However, because the eye does not lend itself to multiple intraocular entries, and corneal layers are an intended barrier to the environment, we strive to deliver the highest, safe, single antibiotic dose whenever possible, so that meaningful intraocular antibiotic levels are sustained for as long a period of time as possible. To date, the intracameral injection remains the method of drug delivery that best accomplishes this goal.