Medication protocols for cataract surgery

Take-Home

A look at the growing options and enthusiasm for intracameral, as well as topical antibiotics for infection prophylaxis.

By Cheryl Guttman Krader

Although modern cataract surgery is extremely safe, postoperative endophthalmitis remains the most feared complication, and cystoid macular edema (CME) continues to be the most common cause of vision loss after routine cataract procedure.

In 2013, discussion continued about the role of intracameral versus topical antibiotics for infection prophylaxis, and cataract surgeons had several new options for use in controlling inflammation after cataract surgery.

Ophthalmology Times editorial advisory board members, Mark Packer, MD, and Randall J. Olson, MD, provided their thoughts on these topics.

When it comes to the debate about endophthalmitis prophylaxis regimens, Dr. Packer said he believes a key event this year was the publication of a study by Shorstein et al. [J Cataract Refract Surg. 2013; 39: 8-14] from Kaiser Permanente Northern California that showed the rate of postoperative infections decreased after the institution of intracameral antibiotic use.

“This is the first real evidence from a large United States study that confirms what the rest of the world’s cataract surgeons have already decided, which is that we should be using intracameral antibiotics,” said Dr. Packer, private practice, Bowie, MD, and clinical associate professor of ophthalmology, Oregon Health & Science University, Portland.

Topical vs. intracameral antibiotics

The retrospective study included data from over 16,000 procedures and compared the rates of endophthalmitis over three different time periods during which endophthalmitis prophylaxis protocols varied.

During 2007, only topical drops were used postoperatively. Intracameral cefuroxime was added except in patients with allergy or posterior capsule rupture during 2008 and 2009, while during 2010 and 2011, patients received both topical and intracameral antibiotics.

However, the intracameral agent could be cefuroxime, moxifloxacin, or vancomycin based on surgeon preference, and there were no exclusions to cefuroxime use.

Rates of postoperative endophthalmitis declined from 0.31% with topical antibiotic drop use to 0.14% with initiation of intracameral antibiotics, and then to just 0.01% during the last 2 years of the study.

“There may have also been some minor modifications in technique over the entire study period, but there were no dramatic changes that would account for this impressive reduction in endophthalmitis rates,” Dr. Packer said. “Although this was not a prospective, randomized study, the large numbers of cases makes the data pretty persuasive.”

Dr. Packer noted that the study did not have sufficient power to determine the relative effectiveness of the three different antibiotics used intracamerally. This was noted by Dr. Shortstein and colleagues who replied to a letter written by authors who calculated the rates of endophthalmitis associated with each individual antibiotic.

“During the last 2 years of the study, when the three different antibiotics were used, there was just one case of endophthalmitis in over 2000 procedures,” Dr. Packer said. “This data is a reminder of why we will never have an FDA-approved intracameral antibiotic for prevention of postoperative endophthalmitis. A study would need to enroll 250,000 subjects to be able to show statistically significant effectiveness, and that will never happen.”

The fact that all antibiotic prophylaxis for endophthalmitis, intracameral and topical, represents off-label use is an interesting situation, he said.

Based on review of the available evidence and its quality, the strongest support exists for using povidone-iodine antisepsis and intracameral antibiotics, Dr. Packer said.

“There has been a lot of discussion about the amount of money being wasted by the use of topical antibiotic prophylaxis, taking into account the cost of the fourth-generation fluoroquinolone antibiotics and the millions of cataract procedures performed annually,” he said. “However, most surgeons are continuing with topical drops rather than intracameral antibiotics due to medicolegal concerns.”

Both Dr. Packer and Dr. Olson-professor and chair, department of ophthalmology and visual sciences and CEO, John A. Moran Eye Center, University of Utah, Salt Lake City-noted that while the number of US surgeons using intracameral antibiotics remains low, it appears to be growing.

Moxifloxacin 0.5% ophthalmic solution (Vigamox, Alcon) is being used by some surgeons because it is a convenient, off-the-shelf, preservative-free formulation, and it appears to have good safety in terms of risks of toxic anterior shock syndrome (TASS) and CME according to several published reports, Dr. Packer added.

However, Dr. Olson cautioned that the newer formulation of moxifloxacin 0.5% (Moxeza, Alcon) has been associated with severe TASS when used intracamerally. An American Society of Cataract and Refractive Surgery press release during the year reported on 12 cases of TASS that occurred when a pharmacist substituted Moxeza for Vigamox without the surgeon’s knowledge.

“The new formulation of moxifloxacin contains other inactive ingredients, including xanthan gum, sorbitol, and tyloxapol, which has detergent and mucolytic properties, and its use inside the eye pretty much guarantees TASS,” Dr. Olson said.

Dr. Olson agreed that evidence is accumulating to support the use of intracameral antibiotics, although he noted that to his knowledge, there is nothing to show the superiority of intracameral versus topical antibiotics when both are used with best practice techniques.

“Certainly it seems more and more surgeons are adopting intracameral antibiotics, and it is worth noting that Jim Gills, MD, has had good results injecting both a corticosteroid and antibiotic intracamerally at the end of the case with no further medication use postoperatively,” he said. “I expect that if a company went to the time and trouble of conducting a study to get FDA approval for a unit-dose intracameral antibiotic, the technique would expand dramatically and very quickly. However, it doesn’t seem that any company is interested in pursuing that indication.”

A well-sealed incision is critical for endophthalmitis prophylaxis, and in September, members of the FDA Ophthalmic Devices panel of the Medical Devices Advisory Committee voted in favor of recommending the safety of a topical hydrogel incision sealant (ReSure Sealant, Ocular Therapeutix). However, the 11 members were split in their votes on its efficacy and whether the sealant’s benefits outweighed its risks.

The manufacturer was seeking an indication for intraoperative management of clear corneal incisions with a wound leak demonstrated by a Seidel test, and for prevention of postoperative fluid egress following cataract or intraocular lens placement surgery. Several members who voted no or abstain on the safety and benefit risk issues did not think the submitted data supported preventive use.

Dr. Olson said it will be interesting to see how well the sealant is adopted by cataract surgeons should it become available. However, he noted that historically, products for cataract surgery that add expense without having convincing evidence to show they make a big difference in outcomes do not achieve widespread use.

Controlling pain and inflammation

Toward the end of 2012, the FDA approved a new gel formulation of loteprednol etabonate 0.5% (Lotemax Gel, Bausch + Lomb) for treatment of postoperative inflammation and pain following ocular surgery. Compared with the suspension formulation, the gel has a more physiologic pH, lower concentration of preservative, and contains demulcents.

In addition, surgeons have two new topical NSAIDs at their disposal. A new once-daily version of nepafenac (nepafenac 0.3%; Nevanac, Alcon) gained FDA approval in the latter part of 2012. It is formulated with a 3-fold higher concentration of active ingredient than the original product and in a vehicle containing guar gum.

In April, a new formulation of bromfenac (bromfenac 0.07%; Prolensa, Bausch + Lomb) was approved by the FDA. It is indicated for once daily administration and formulated in a vehicle that has a lower pH and is designed to improve corneal penetration of the active ingredient.

Whether the new versions of these products offer major benefits is unclear. Dr. Olson said he is not aware of any studies showing superiority, although he admitted these are not easy studies to do considering the efficacy of the earlier versions.

“It could be that we have pushed the limit as far as we can go so that any incremental improvement is difficult to demonstrate,” he said. “What we can say is that there are new products for controlling pain and inflammation after cataract surgery and theoretical reasons why they may be superior. However, there are no clinical studies to show that they will decrease CME and especially clinically significant CME.”

Dr. Packer noted it is interesting that in the studies leading to approval of the new NSAID formulations, corticosteroid treatment was allowed as rescue therapy but was not given routinely.

“Most cataract surgeons treat patients with both an NSAID and a corticosteroid,” he said. “However, as a result of the design of these FDA studies, we can see how effective a single daily drop of a topical NSAID is for controlling pain and inflammation.”

However, Dr. Packer added that he thinks it is probably better to use the two types of drugs in combination to avoid the situation of having even an occasional patient complaining about significant postoperative discomfort.

He noted that at the end of 2012, he and colleagues from his previous practice in Oregon published a retrospective study reviewing the development of CME among nearly 2,900 eyes operated on over a period of 5 years [Packer M, et al. J Cataract Refract Surg. 2012; 38(12): 2108-11]. They found only three cases (0.1%) of acute CME diagnosed within 3 months after surgery.

“Throughout this entire period, all patients were being treated with an NSAID and a corticosteroid,” Dr. Packer said. “This data shows that it is possible to achieve very low levels of CME with the use of both drops and importantly at a level that is much lower than the rate of 1 to 3% considered as acceptable in the FDA grid.”

Dr. Packer also said surgeons should keep in mind the possibility that when patients bring their prescriptions to the pharmacy, they may get a different medication as a substitution.

In some states, substitution is allowed regardless of how the prescription is marked and the substitution may even be with a different medication within the same class.

“If a patient comes for a postop visit complaining bitterly about stinging with the postoperative medication, find out if the pharmacist dispensed something other than what you prescribed,” Dr. Packer said.

Mark Packer, MD

E: mark@markpackerconsulting.com

Dr. Packer is a consultant to Advanced Medical Optics, Inc., Allergan, Inc., Bausch & Lomb Surgical, Inc., and Ista Pharmaceuticals.

Randall Olson, MD

E: randallj.olson@hsc.utah.edu

Dr. Olson has no relevant financial interests to disclose.