April 2016




New technology in cataract surgery

Inside look: New drugs for cataract surgery

by Maxine Lipner EyeWorld Senior Contributing Writer

The dexamethasone punctal plug

The dexamethasone punctal plug has a fluorescent component that makes it possible to see in the eye.

Source: Shamik Bafna, MD

The injection of Tri-MoxiThe injection of Tri-Moxi can reduce or eliminate the need for postoperative drops.

Source: Ahad Mahootchi, MD

Physicians discuss innovative medications for inside the eye during phacoemulsification

When it comes to cataract surgery, one new approach gaining momentum is to add the medicine to the irrigating solution during the procedure or inside the eye after the lens has been replaced. The new drug Omidria (Omeros, Seattle) as well as dropless cataract surgery are making inroads. With the dropless approach, practitioners inject combination agents such as Tri-Moxi (triamcinolone and moxifloxacin, Imprimis, San Diego) and Tri-Moxi-Vanc (triamcinolone, moxifloxacin, and vancomycin, Imprimis) at the end of the procedure to forestall or minimize the need for postoperative medications. In addition, there is movement toward using a sustained-release dexamethasone punctal plug (Ocular Therapeutix, Bedford, Massachusetts) to treat inflammation related to cataract surgery. EyeWorld took a closer look at these.

Focus on Omidria

Richard Lindstrom, MD, adjunct professor emeritus, University of Minnesota, Minneapolis, routinely uses Omidria for his cataract patients. His rationale here is multifaceted. Number 1, it works, he said. It helps maintain pupillary dilation during surgery and reduces discomfort during surgery and in the immediate postoperative period. Number 2, he said, there is pass-through reimbursement. This means that it costs my patients nothing and it costs me nothing, Dr. Lindstrom said. As Thomas Gustafson, PhD, explained in the September 2015 issue of ASC Focus,1 with transitional pass-through, in addition to paying for the facility fee, for a limited time (usually 3 years), Medicare offers additional reimbursement for innovative drugs, devices, and biologics. The idea is to allow access to these unique products, such as Omidria, initially without having to fit another expenditure into the usual facility fee payment.

In Dr. Lindstroms view, another factor in the case for using Omidria is that its a chance to invest in innovation for practitioners like himself who advocate for new technologies. Part of Omidrias appeal is that it helps maintain a larger pupil during surgery, Dr. Lindstrom explained. Its intended to retain pupillary dilation during surgery and reduce pain and discomfort during surgery and in the immediate postoperative period, he said. But we know that there is data in the literature to support a lower complication rate in patients who have larger pupils. Also, if the patient is more comfortable, it makes for easier surgery.

Because of what Omidria has to offer, a significant number of practitioners use this for their high-risk patients, Dr. Lindstrom noted. Such patients would include those with intraoperative floppy iris syndrome (IFIS) because these individuals are hard to dilate and have pupils that tend to come down during surgery. Still, in many cases it can be hard to tell ahead of time who will benefit. The reality is that its sometimes hard to predict which patient is going to be difficult, he said.

However, not everyone is convinced that Omidria is the answer. Although it is off label, David F. Chang, MD, clinical professor of ophthalmology, University of California, San Francisco, and in private practice, Los Altos, California, continues to routinely place epinephrine in the irrigation bottle to maintain pupil dilation, which he has found to be highly effective. In 2014 we published our findings2 that if there is no epinephrine in the bottle, there is a 45% rate of severe IFIS and a 1214% rate of moderate to severe IFIS in patients whove never take alpha blockers, he said. I do think it is important to add an alpha agonist to the irrigation bottle. Dr. Chang pointed out that there is a huge cost discrepancy. Epinephrine costs about $4 per vial, and lacking any evidence that Omidria is superior to epinephrine at maintaining mydriasis, I personally cant justify using a product that is more than 100 times more expensive, he said. Although he is glad the Centers for Medicare & Medicaid Services (CMS) has a program to subsidize patient access to newly developed drugs, in this case with a $4 alternative that he has successfully used for decades, the new Omidria formulation doesnt address an unmet need in his practice.

Intravitreal experience

Jeffrey Liegner, MD, Eye Care Northwest, Sparta, New Jersey, who was one of the creators of the Tri-Moxi and Tri-Moxi-Vanc intravitreal approach, explained that the need for this sprang from a confluence of events around 2010. At that time, Medicare had given instructions that all medications be single-use only. We had to find something in a unit dose, and in the case of vancomycin, the smallest one came in a 500-mg vial. We would use 25 mg and throw out the rest of itthat didnt make any sense. The other contributing factor was soaring prices for the topical eye drops. They were ridiculously expensive, and the prices were going up rapidly, particularly the antibiotics, Dr. Liegner said. Also, insurance formularies became much more restrictive. Sometimes without telling us they were forcing us into generics, less functional or lower performing drugs, and that was unacceptable, he said. Dr. Liegner considered the idea of injecting the medication into the eye and inquired about what the retina specialists were using for patients with infections. Moxifloxacin was the big one at that time, and vancomycin was always a favorite, he said, adding that for inflammation they confirmed that they were using triamcinolone. He then set out to create a formulation that was PH proper, which would be held in solution and could be delivered at a dose that cataract surgeons could use. This led to the development of the 2 intravitreal drugs made by Imprimis, Tri-Moxi and Tri-Moxi-Vanc. The technique takes patient compliance out of the equation. Dr. Liegner wonders whether lack of compliance causes infection or if it may be due to inadequate placement of drops. The intravitreal injection of medication assures physicians that the drugs are delivered exactly where they are needed. There are 2 primary techniques for using thispars plana and transzonular. Dr. Liegner estimates that 60% of physicians use a transzonular injection approach, and 40% use the pars plana approach. But it is the transzonular approach that he views as preferable. People who do transzonular never go to pars plana, he said. He thinks that the advantage of the transzonular approach is that it takes much less time, and there is no perforation of the eye or broken capillaries, hemorrhages, or pain associated with the injection. While many express concerns about the possibility of elevated intraocular pressure with the approach, Dr. Liegner has not found this to be a big concern. We have studied this, and there seems to be less than one-tenth of 1% of individuals who have a steroid response of elevated IOP, he said. Putting the medication in the eye can also fog the vision initially. For the first 48 hours, youre not going to have that fabulous vision that some surgeons crave, Dr. Liegner said. Some patients see floaters for 23 weeks before the medicine gets absorbed. Dr. Liegner finds that the need for rescue drops in cases where intravitreal drugs have been used is dose-dependent. In his practice, the rate is about 2.6% of cases.

Dr. Lindstrom views the approach, which costs $20 for Tri-Moxi and $25 for Tri-Moxi-Vanc, as a huge financial boon for patients, since this is administered during the procedure and is currently bundled into the facility fee payment. It saves patients sometimes hundreds of dollars, he said. Dr. Chang uses intracameral moxifloxacin, but in the absence of clinical studies he prefers topical postoperative anti-inflammatory drops. Unless you do a fellow eye study comparing intravitreal injection in 1 eye to topical drops in the other, we simply have anecdotal impressions regarding our anti-inflammatory regimens, Dr. Chang said. He uses generic topical NSAID and prednisolone acetate twice a day for 4 weeks in most of his cataract patients because it is easy to explain and remember. He refers patients to GoodRx.com to purchase these generics often at lower costs compared to their drug plans. Dr. Chang pointed out that every patient is different. We published a study3 showing that younger age and increasing axial length are separate and additive risk factors for a steroid response, he said. Dr. Chang therefore cautions against injecting triamcinolone in young myopes. I use loteprednol when the patient has these risk factors or glaucoma and NSAID only for extreme axial myopes. He also individually varies and adjusts the anti-inflammatory treatment regimen. I would love to see studies comparing the rates of rebound iritis, subclinical cystoid macular edema (CME), and steroid response with intravitreal triamcinolone versus topical combination therapy. Richard Lewis, MD, Sacramento Eye Consultants, Sacramento, California, likewise stressed the importance of having studies on the use of intravitreal agents versus drops. He also pointed out that there may be medical-legal considerations with this approach. Theres always a concern that if you use an intracameral antibiotic and the patient gets endophthalmitis, you could be liable because you didnt have him or her on drops, Dr. Lewis said, adding that while he is not aware of a lawsuit, he could imagine an argument that endophthalmitis doesnt manifest until about 2 days postoperatively. This is usually the result of a wound leak. One could argue that intracameral antibiotics arent sufficient, he said. There is also the question of whether the triamcinolone injected steroid is sufficient. Is it enough steroid? Is it lasting 23 weeks to prevent CME and other inflammatory problems? That has not been studied, he said.

Sustained-release plug

Another option currently being studied is use of a punctal plug filled with dexamethasone, which is put in the puncta of the eyelid at the time of cataract surgery, according to Shamik Bafna, MD, Cleveland Eye Clinic, Cleveland. Once you finish removing the cataract and have placed the lens, you dilate the punctum and place the plug in position, he said. The plug will elute the active ingredients over the next 4 weeks. One of the key features of the dexamethasone punctal plug is a fluorescent component. Even though the patient cant see the plug, its possible to shine a cobalt blue light over the eye to ensure that it hasnt migrated or left the eyelid, Dr. Bafna said, adding that after the medication has gone out of the plug, the device is reabsorbed and extrudes out of the basal lacrimal system. In Dr. Bafnas view, the dexamethasone punctal plug has several advantages over traditional postoperative drops. I think the biggest advantage is one of compliance in the sense that when patients have to use drops after cataract surgery, theres always the question of whether they are using drops appropriately or not, he said. After surgery, many times patients eyes appear fine to them and they may prematurely stop taking the drops on their own. Another factor for some may be cost, with patients wondering whether they need to spend the money for drops.

Another big factor in terms of steroid medication is the fact that many times this comes in the form of a suspension. If you dont shake the bottle at least 20 to 30 times, you wont have an appropriate dosage, Dr. Bafna said. The benefit of the plug is there will be a consistent dose released for the next 34 weeks, and the patient wont have to think about it. He has found that its a convenience for the patients who took part in the FDA phase 3A and 3B study. In the study, we were only allowed to enroll 1 eye, and many of those patients complained that they had to use drops in their second eyethey wished that we could have put a plug in their other eye as well, Dr. Bafna said.

In the phase 3A study for which Dr. Bafna was an investigator, results were clear-cut. We found that there was a statistically significant improvement in both pain and inflammation with the plug compared to placebo, he said. In the phase 3B study, they determined that when it came to pain, there was statistical significance; in terms of inflammation, while the plug performed equally well, 2 patients in the placebo group did better than expected. As a result, statistical significance was not achieved for inflammation in the phase 3B trial. Those 2 patients were taking systemic, oral anti-inflammatory medication, and the thought process is that this is the reason those patients ended up doing better, Dr. Bafna said, adding that the company is planning to resubmit another study to the FDA using tighter exclusion criteria.

The dexamethasone punctal plug is something that Dr. Bafna envisions could be utilized for the vast majority of patients. For others, it could be used in conjunction with other medication such as nonsteroidal anti-inflammatories to prevent CME. If a patient had diabetic retinopathy at the time of cataract surgery, [we may] place the plug but may also have the patient use a nonsteroidal drop at the same time to try to prevent CME, Dr. Bafna said. But the vast majority of cataract patients could do fine with the plug alone. The hope is in 2016 the product will be available, Dr. Bafna said. Going forward, he thinks that different medication-eluting plugs can be utilized for other ocular indications such as glaucoma or even seasonal allergies. Its possible that we could deliver that same medication through the plug and help in a compliance situation where they dont have to use drops on a daily basis, he concluded.

New drugs article summaryReferences

1. Gustafson T. Transitional pass-through payments. ASC Focus. September 2015;89.

2. Chang DF, et al. Prospective masked comparison of intraoperative floppy iris syndrome severity with tamsulosin versus alfuzosin. Ophthalmology. 2014;121:829834.

3. Chang DF, et al. Risk factors for steroid response among cataract patients. J Cataract Refract Surg. 2011;37:675681.

Editors note: Dr. Bafna has financial interests with Ocular Therapeutix. Dr. Chang has no financial interests related to his comments. Dr. Lewis has financial interests with Aerie Pharmaceuticals (Bedminster, New Jersey), Alcon (Fort Worth, Texas), Allergan (Dublin), and Omeros. Dr. Liegner has financial interests with Imprimis. Dr. Lindstrom has financial interests with Alcon, Abbott Medical Optics (Abbott Park, Illinois), Bausch + Lomb (Bridgewater, New Jersey), Imprimis, Omeros, and Ocular Therapeutix.

Contact information

Bafna: drbafna@clevelandeyeclinic.com
Chang: dceye@earthlink.net
Lewis: rlewismd@pacbell.net
Liegner: liegner@embarqmail.com
Lindstrom: rllindstrom@mneye.com

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