Intracameral medication: Is it worth the risk?

Primum non nocere. The familiar dictum “First, do no harm” is particularly applicable in the setting of intracameral medications in cataract and anterior segment surgery. Intracameral medication has multiple potential uses in these surgical procedures, including pupil dilation, anesthesia, and prevention of endophthalmitis/inflammation. Its advantages and disadvantages were highlighted in the “Spotlight on Cataract” session at the November 2007 American Academy of Ophthalmology meeting. One primary advantage is the ease of delivery. Multiple applications of topical drops are unnecessary when medication is delivered into the anterior chamber. This has the additional advantage of eliminating toxicity from topical medications, especially those with preservatives such as benzalkonium chloride (BAK), since intracameral medications are mostly preservative free. Another possible advantage is enhanced efficacy as the theoretically higher dose is at the site where the medication's action will take place. Finally, intracameral medications eliminate issues of patient compliance, including difficulties in obtaining and using postoperative drops properly. Of the potential disadvantages or complications associated with the use of intracameral medications, one of the most worrisome is the potential for toxic anterior segment syndrome (TASS).1 This acute, sterile postoperative inflammation is often secondary to anterior segment toxicity from medications or solutions placed in the anterior chamber during or immediately following cataract surgery. Corneal endothelial cells are very sensitive to any form of toxic exposure, and one of the earliest outbreaks of a TASS-like entity was the toxic endothelial cell destruction syndrome (TECDS).2 An important issue with intracameral medications is the proper concentration or dose of the medication. If the concentration is too high, there is potential toxicity. Examples of this toxicity are a concentration of 2% or greater in the case of lidocaine or 0.5% or greater in the case of bupivacaine, both of which can cause endothelial damage. Dilution errors in mixing antibiotic agents can be important. Some agents such as gentamicin have a very small therapeutic range and a high concentration can cause toxicity. In addition to issues of concentration or dose, medications that are custom mixed must have the proper pH. Custom-mixed medications must often be buffered to obtain a physiologic pH. When used intracamerally, an antibiotic agent such as vancomycin can be acidic if it is not properly buffered and mixed with a balanced saline solution. Osmolarity is also a potential issue with intracameral medications; an osmolarity that is too high or too low damages the corneal endothelium and other anterior segment structures. Any medication placed in the anterior segment during or at the conclusion of cataract surgery must be preservative free because preservatives are potentially toxic to the corneal endothelium. One preservative commonly used in topical medications is BAK, which can be toxic to the endothelium in even small doses. Some medications, such as epinephrine, which is used to dilate the pupil, are stabilized with bisulphites or metabisulphites; although not technically preservatives, these agents are potentially toxic to the corneal endothelium. In addition, if multiple medications are used for intracameral injections, the medications must be compatible when mixed for a single injection. Precipitation or other issues may be involved if 2 incompatible medications are used. Finally, drawing multiple doses from the same vial or syringe for intracameral injection during surgery raises the issue of multiple potential risks if the vial from which the medication is drawn is contaminated with bacteria or improperly mixed. One reason for the increased interest in the use of intracameral medications is the European Society of Cataract and Refractive Surgeons' recent report of the excellent efficacy of intracameral cefuroxime in the prevention of endophthalmitis.3 However, similar endophthalmitis rates have been obtained in the United States with intensive use of topical fourth-generation fluoroquinolones postoperatively. In this issue (pages 505–509), Liesegang provides an extensive review of intracameral antibiotic agents and the questions surrounding the use of these medications. He suggests that more research on safety and effectiveness is needed before we expose millions of eyes having cataract surgery each year to an intracameral antibiotic injection. The most important issue in the use of intracameral medications, especially for the prevention of endophthalmitis in the United States, is that no single-use, premixed doses for intracameral use are commercially available at this time. The issue of “homemade or kitchen pharmacies” raises potential problems with correct dosing, pH, osmolarity, preservatives, and sterility, all of which may lead to TASS. These issues must be addressed to eliminate errors in preparation and dilution. The recently published survey of members by the American Society of Cataract and Refractive Surgery's Cataract Clinical Committee4 found that 77% of respondents were not injecting intracameral antibiotics but 82% would likely do so if a reasonably priced commercial preparation were available. Cooperation between manufacturers and the U.S. Food and Drug Administration is necessary to allow the use of medications that are manufactured to high specifications for intracameral use in cataract surgery.