OASC | CATARACT SURGERY

CATARACT SURGERY: To Drop or Not to Drop?

Experts discuss new options for drug delivery in the ASC

By Desiree Ifft, Contributing Editor

Cataract surgery is one of the most frequently performed medical procedures in the United States, and with that comes great interest in anything that may further reduce complications or improve outcomes. This includes potential modifications of the perioperative medication protocol. Currently, surgeons can consider making several changes: switching from topical endophthalmitis prophylaxis to intracameral; adding or removing a nonsteroidal anti-inflammatory (NSAID) drop; or adopting the newest drug formulations and delivery methods designed to reduce or eliminate the need for patients to use pre- and/or post-op drops.

Endophthalmitis Prophylaxis

In 2007, the European Society of Cataract and Refractive Surgeons (ESCRS) published the results of a prospective multicenter randomized clinical trial designed to evaluate antibiotic prophylaxis for cataract surgery.¹ The key finding from the study was a fivefold reduction in the endophthalmitis rate for patients who were randomized to receive intracameral antibiotics at the end of the procedure compared with patients who didn’t receive intracameral antibiotics. Patients in the four treatment arms received either 1) no topical or intracameral antibiotics; 2) intracameral cefuroxime; 3) topical levofloxacin only; or 4) topical levofloxacin and intracameral cefuroxime. The rates of endophthalmitis (confirmed by culture) were 0.226% and 0.173% in the groups that did not receive intracameral cefuroxime (1 and 3), and 0.049% and 0.025% in the groups that received intracameral prophylaxis (2 and 4).

Shortly thereafter, the American Society of Cataract and Refractive Surgery (ASCRS) surveyed its membership to assess whether the ESCRS study had an impact on antibiotic prophylaxis practice patterns for cataract surgery, which, for many surgeons in the United States, had been prophylaxis with topical fluoroquinolones. While 16% of respondents reported they had been injecting intracameral antibiotics before the ESCRS study, and 7% of respondents reported they had recently started or planned to start injecting intracameral antibiotics, 77% did not plan to change their protocols.²

However, since that time, a significant number of studies, most retrospective/observational, have shown intracameral antibiotics injected at the end of cataract surgery to be efficacious in preventing post-op endophthalmitis, and in some studies, intracameral antibiotics were shown to be superior to drops. By the time ASCRS re-surveyed its membership in 2014, the body of evidence had apparently prompted more significant change. According to the 2014 study results, compared with 2007, the percentage of surgeons injecting intracameral antibiotics increased from 14% to 36%.³ (Sixty-five percent of the survey respondents were from the United States; 9% were from Europe.) The percentage of surgeons using any type of intracameral antibiotic, including those who were adding antibiotic to the irrigating bottle (16%) increased from 30% in 2007 to 50% in 2014. “This is a significant increase over the results from our 2007 survey,” says David F. Chang, MD, clinical professor at the University of California, San Francisco and advisory member and former chair of the ASCRS Cataract Clinical Committee.

Still, despite additional studies in favor of intracameral antibiotic injections, which have involved hundreds of thousands of patients around the world,^4-7 not everyone is convinced. A 2016 editorial in the journal Ophthalmology pointed to the limitations of retrospective studies, the existence of data that doesn’t support the intracameral approach as superior, increasing drug resistance, and other factors. The editorial went on to say that “The role of intracameral antibiotics remains controversial in the United States and in many other nations. ... The use of intracameral antibiotics should not be considered ‘standard of care’ in the United States, and the value of this strategy remains uncertain on the basis of currently available data.”⁸

Dr. Chang has a different view. “Although they are mostly retrospective studies, when taken as a whole, the published evidence that intracameral antibiotics lower the rate of endophthalmitis is overwhelming, in my opinion,” he says, adding, “I’ve used intracameral prophylaxis for more than 15 years with no complications.”

Francis S. Mah, MD, a cataract, corneal, and refractive surgeon with Scripps Health in California, believes cataract surgery in the U.S. is in the middle of a paradigm shift toward intracameral and away from topical prophylaxis. Currently, his perioperative regimen for patients not at increased risk of infection or cystoid macular edema (CME) is an antibiotic drop and an NSAID drop in the pre-op holding area; povidone iodine 5% (around the eyelid and a drop in the eye); a 0.15 mL intracameral injection of compounded Dex-Moxi (dexamethasone 150 mcg and moxifloxacin 750 mcg, Ocular Science) at the conclusion of the procedure; and an NSAID drop, Ilevro (nepafenac ophthalmic suspension 0.3%, Alcon), once a day for 4 weeks; and a steroid drop, Durezol (difluprednate ophthalmic emulsion 0.05%, Alcon), once a day for 4 weeks. (For patients at high risk for CME, based on peak incidence data, he adds the NSAID drop for 3 days pre-op and extends the post-op NSAID drop to 2 months.) In addition to the research supporting the use of intracameral antibiotics, Dr. Mah sees costs and compliance as reasons to change. “The cost of medications has become onerous for patients, and their compliance with often complicated post-op drop regimens is questionable. Delivering antibiotics intracamerally at the end of surgery reduces or eliminates the number of post-op medications patients need to purchase and use, which lowers their costs, and we don’t have to worry about poor compliance adversely affecting surgical outcomes,” he says. The cost of the compounded steroid/antibiotic Dr. Mah injects, $20 per patient, is absorbed by the ASC.

P. Dee Stephenson, MD, FACS, president of the American College of Eye Surgeons and founder of Stephenson Eye Associates in Venice, Fla., is among the surgeons not injecting intracameral antibiotics as part of their cataract surgeries. Focused on premium refractive cataract surgery, she prescribes Besivance (besifloxacin ophthalmic suspension 0.6%, Bausch + Lomb) twice a day and Prolensa (bromfenac ophthalmic solution 0.07%, Bausch + Lomb) once a day for 3 days prior to surgery. In the pre-op holding area, she uses povidone iodine 5% (around the eyelid and a drop in the eye). Intraoperatively, she mixes powdered vancomycin into the BSS bottle, and, when appropriate, utilizes Omidria (phenylephrine and ketorolac 1% / 0.3%, Omeros). Postoperatively, she has patients use Besivance twice a day for 14 days, Prolensa once a day for 6 weeks, and Lotemax (loteprednol etabonate ophthalmic gel 0.5%, Bausch + Lomb) four times a day for 2 weeks, three times a day for a week, twice a day for a week, and once a day for a week. The $3.14 per gram cost of the antibiotic for the BSS is absorbed by the ASC.

Dr. Stephenson hasn’t had a case of endophthalmitis in the past 15 years, but says the studies showing intracameral antibiotics can lower the risk haven’t escaped her attention. Her reasons for not using intracameral antibiotics are largely medicolegal. “Most surgeons in my area don’t use them,” she says. “Drops are the local standard of care. I’m not sure I’d be backed up medicolegally if I were working outside of that and a patient developed endophthalmitis or toxic anterior segment syndrome (TASS) related to the off-label injection.” Fluids and medications used during surgery are among the several suspected causes of TASS. Dr. Stephenson also says the use of intracameral antibiotics is more widespread in Europe because surgeons there have access to an approved formulation for this purpose, Aprokam (cefuroxime, Thea Pharmaceuticals), which isn’t the case in the United States.

Which antibiotic is best suited for intracameral prophylaxis is another important question, Dr. Stephenson continues. Several properties must be considered, including potency, duration of action, range of bacteria types killed or inhibited, penetration and safety in ocular tissue, and likelihood of causing anaphylaxis. Dr. Chang and colleagues recently published the largest retrospective study to date that shows the efficacy of intracameral moxifloxacin in reducing the rate of endophthalmitis.⁹ According to the results of the 2014 ASCRS survey, among surgeons using intracameral antibiotics, 37% overall and 52% of American surgeons were using vancomycin, and 33% overall and 31% of American surgeons were using moxifloxacin.³

However, Dr. Chang and others have switched from intracameral vancomycin to moxifloxacin because of the recently published moxifloxacin study and the emergence of increasing numbers of cases of postoperative hemorrhagic occlusive retinal vasculitis (HORV).¹⁰ He’s part of a joint ASCRS-American Society of Retina Specialists task force that was formed following the initial report of HORV. “Based on approximately 30 total cases, the association with vancomycin is very convincing and is probably due to a rare, delayed Type III hypersensitivity,” he explains. “Because the retinal vasculitis and visual loss are delayed, many of these patients are bilaterally blind after receiving vancomycin in both eyes following cataract surgery. I now use compounded moxifloxacin (1 mg/0.1 mL) from Leiter’s Compounding Pharmacy, an FDA-registered pharmacy. The compounded product has a very stable shelf life and is less expensive than a bottle of Vigamox (moxifloxacin hydrochloride ophthalmic solution 0.5%, Alcon). California is one of 33 states that doesn’t require a written prescription for each patient.” Dr. Chang notes that Vigamox isn’t manufactured with the intent of intracameral injection and can’t be autoclaved.

NSAIDs for Inflammation Control

Controlling postoperative pain and inflammation and preventing CME are important goals for an increasing number of cataract surgeons, especially those who provide premium procedures. In a 2014 survey of ASCRS members, 41.2% of respondents strongly agreed that low-to-moderate inflammation can significantly impact variability in visual acuity and quality results, and 40.2% reported using both topical NSAIDs and steroids at 1 day post-op.¹¹ According to Dr. Mah, the percentage of surgeons who prescribe a topical NSAID at some point surrounding cataract surgery is close to 70%.

Last year, the American Academy of Ophthalmology (AAO) published an Ophthalmic Technology Assessment regarding topical NSAIDs and cataract surgery. While the report concluded “Cystoid macular edema after cataract surgery has a tendency to resolve spontaneously” and called into question the strength of the evidence in support of NSAID use in routine cases,¹² proponents of the strategy have been undeterred. Regarding the AAO report, Dr. Mah says, “The authors correctly state that NSAID use typically has no effect on visual outcomes after 3 months; but they also correctly state that it does make a difference prior to 3 months. This may mean faster visual recovery, which is beneficial for patients, and arguably, for example, one of the main reasons phaco overtook extracapsular extraction as the predominant method of cataract surgery. Many studies have shown a reduced incidence of CME when topical NSAIDs are used, and although Snellen visual acuity may not be adversely affected, I would argue that there is an impact on aspects of vision that haven’t traditionally been measured, such as contrast sensitivity.”

Dr. Mah and Dr. Stephenson maintain that the evidence in favor of NSAIDs is strong and in line with their clinical experiences. They say both confirm for them that even patients considered low-risk can develop CME, which adversely affects quality of vision; NSAIDs reduce CME rates in both low- and high-risk patients; and NSAIDs, either alone or in combination with steroids, can prevent CME and control inflammation more effectively than steroids alone.^13-18

Dr. Mah wouldn’t be surprised if the use of NSAIDS with cataract surgery, whether it be before, during, and/or after, continues to increase. As he sees it, “With the high expectations for superb vision that we’re aiming to fulfill, we really can’t afford for our patients to have drawbacks like inflammation and CME, which we know are largely preventable.”

Finding New Options

According to Dr. Stephenson, the use of Omidria as an integral part of cataract surgery, especially femtosecond laser-assisted cataract surgery, is increasing. The phenylephrine/ketorolac formulation, added to the intraoperative irrigating solution, is FDA approved for use during cataract surgery or IOL replacement to maintain pupil size by preventing intraoperative miosis and to reduce postoperative ocular pain. It’s the first commercially available product from the Omeros PharmacoSurgery platform, the idea of which is to address the consequences of surgical-site trauma (pain and the release of prostaglandins causing miosis) pre-emptively during surgery rather than being forced to handle them intraoperatively and postoperatively. In the setting of cataract surgery, Omidria is a new way to improve the surgeon and patient experience, and potentially outcomes, via something that is under the surgeon’s control — rather than the patient’s. In October 2014, the Centers for Medicare & Medicaid Services (CMS) determined that Omidria qualifies as a pass-through drug under the Outpatient Prospective Payment System. As a result, effective Jan. 1, 2015, ASCs can bill Medicare $465 per single-patient-use vial of Omidria. This pass-through remains in effect for 2 to 3 years.

Omidria is one option following the trend away from patient drop therapy and toward novel methods of drug delivery, as are the Dex-Moxi Dr. Mah uses, and agents such as Tri-Moxi (triamcinolone-moxifloxacin, Imprimis) and Tri-Moxi-Vanc (triamcinolone-moxifloxacin-vancomycin, Imprimis). These proprietary compounded formulations are available as single, injectable doses to be administered transzonularly at the conclusion of ocular surgery. In a recent investigator-initiated study that prospectively compared rates of post-op CME between a traditional steroid and NSAID drop regimen and Tri-Moxi-Vanc combined with a post-op NSAID drop, the post-op CME rate was 1.5% in the traditional group (n=600) versus 0.5% in the Tri-Moxi-Vanc plus post-op NSAID drop group (n=600) (p=0.003).¹⁹

According to CMS policy, Tri-Moxi and Tri-Moxi-Vanc aren’t eligible for separate reimbursement for surgeons or ASCs. Based on a recent analysis conducted by Andrew Chang & Co, Imprimis asserts that if the policy were changed to allow cataract surgery patients to choose and pay for the dropless options, Medicare, Medicaid, and patients would save $2.1 to $13 billion between 2016 and 2025, with savings most likely around $8.7 billion.²⁰ The company says it plans to devote time and other resources to seeking reimbursement and patient pay opportunities for these products. ■

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