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Round table: NSAIDs, corticosteroids play big roles in cataract surgery
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At OSN New York 2013, Eric D. Donnenfeld, MD, OSN Cornea/External Disease Board Member, led a panel of experts and got their thoughts on the use of NSAIDs and corticosteroids before, during and after cataract surgery. Off-label uses were discussed.
Preoperative NSAIDs
Eric D. Donnenfeld, MD: Give us some of the pearls for maintaining pupillary dilation in routine cataract surgery.
Terry Kim, MD: More of us are using topical nonsteroidals for the off-label use of preventing cystoid macular edema (CME), but oftentimes we forget the value of using an NSAID preoperatively to maintain pupillary dilation. You get a lot of prostaglandin release from the incisions and other tissue manipulations during cataract surgery, and having that NSAID onboard ahead of time makes a big difference. We have some newer NSAIDs, such as Prolensa (bromfenac ophthalmic solution 0.07%, Bausch + Lomb) and Ilevro (nepafenac ophthalmic suspension 0.3%, Alcon), that are effective and safe with once-a-day dosing. So, these newer formulations make it easier to treat those patients who are at higher risk for intraoperative pupil constriction, ie, patients who are on Flomax (tamsulosin, Boehringer Ingelheim), and postoperative CME earlier, such as a week before surgery, to help maintain pupillary dilation during the case and protect against CME afterward.
Starting NSAIDs before cataract surgery helps maintain pupillary dilation during the procedure, according to Terry Kim, MD.
Image: Kim T
Donnenfeld: That is a great pearl. Hank Perry and I did a paper on the pharmacokinetics of NSAIDs, and we showed that, if you start your NSAID 1 hour before surgery, like some people do, you get minimal effect on the pupil. Starting a day ahead of time is good; starting 3 days ahead of time is even better. In high-risk cases, I do exactly what Terry does: I start a week preoperatively with my NSAID. What about preoperative corticosteroids? Do they play a role?
Richard L. Lindstrom, MD: There are good data that an NSAID preoperatively helps maintain pupillary dilation during surgery, and there are also good data that show that the complication rate of cataract surgery is correlated with pupil size. Having a large pupil is certainly a significant benefit. I do not know that the steroids help with regard to pupillary dilation, but they do help with regard to corneal clarity and inflammation in the early postoperative period. So, there is a synergistic benefit.
There is a new drug coming from a company called Omeros (OMS302), a combination of phenylephrine and ketorolac that can be added to the irrigating solution, which would give us our first U.S. Food and Drug Administration approved alternative. Phenylephrine is a more logical agent than epinephrine because of its alpha-adrenergic effects, so we do not get as much impact on the heart, although most of us do use epinephrine.
Eric D. Donnenfeld
Donnenfeld: The Omeros study has shown that pupillary dilation is maintained intraoperatively with this technique, and the number of patients with restriction is much reduced vs. controls in the phase 3 trials. This is an exciting new opportunity.
Kim: It is going to be timely to have something like this available to cataract surgeons, especially with all the issues we have been having with regulatory restrictions and the issues with compounding pharmacies. To have a product that is going to be specifically approved, not only for maintaining pupillary dilation but also for pain and discomfort during cataract surgery, is going to be valuable. Having something convenient that we can put right into the irrigating solution as opposed to the additional step of an intracameral injection will also be beneficial.
Donnenfeld: You bring up a good point. We are hearing that, in certain parts of the country, when an ASC is inspected, if you are using off-label drugs, such as intracameral epinephrine, you will be fined or closed down. What we routinely do off label now has to be reconfigured under this new FDA environment.
Lindstrom: Inspections depend on individual inspectors and vary from state to state. We own four ASCs, and we have been requested to do many things, not all of which have to do with improving quality of care, but we have not yet been told to stop putting epinephrine in the bottle. But I know surgeons around the country who have had that experience. So, if you own an ASC, expect to be audited. Whatever the inspectors request, you have to comply or they will shut you down.
Penny A. Asbell
Penny A. Asbell, MD, FACS, MBA: One of the easiest ways to prevent problems with the pupil is to dilate early. Depending on the setting, sometimes the drops are only started 5 minutes before the case starts, and the patient is not fully dilated. You need time. Sometimes I will put in a pledget if the patient is dilating slowly. I look for good dilation before I begin the case, rather than having to deal with it during the case.
Donnenfeld: What about patients on Flomax? Do you do anything differently?
Asbell: The key point is to know about it before you start the case, so get the full history. You can do a few technique changes, such as changing your incision by making a little bit longer tunnel than you might ordinarily, just to decrease the risk of iris prolapse.
Kim: I rely on my intracameral lidocaine and epinephrine Shugarcaine mixture. I believe the epinephrine provides a little rigidity to that iris muscle, which helps during the case, but otherwise, I am not doing anything differently preoperatively.
Donnenfeld: If the pupil is dilated to 9 mm, I still use intracameral epinephrine at the beginning of the case. I use it in every single case when I know the patient is on Flomax because you are much better off preventing pupillary constriction than trying to reverse constriction once it has already occurred.
Adding corticosteroids
Donnenfeld: Moving on. In the case of a 78-year-old man with an 18-year history of diabetes controlled on oral medication, no CME seen on optical coherence tomography but with background retinopathy, how long before cataract surgery would you treat with a topical NSAID?
Richard L. Lindstrom
Lindstrom: I start both topical NSAIDs and steroids a week before. Another thing that is potentially beneficial to a week of preoperative therapy with a steroid is that you clean up the ocular surface.
Asbell: Your patient here is diabetic, but I treat every cataract patient with topical NSAIDs preoperatively, both for pupil issues and to decrease the risk of CME or inflammation postoperatively. It is routine to use NSAIDs in all patients before cataract surgery and not just in higher-risk patients, such as those with diabetes.
Donnenfeld: NSAIDs do not treat inflammation. They prevent prostaglandins from being formed, and NSAIDs have no effect on preformed prostaglandins. That is why starting it preoperatively is so important because you have to exhaust the endogenous supply before you get the full effect. When you have pain, for example, from PRK, it is so much better to start your nonsteroidal before surgery than after surgery once you have already done your ablation. That makes a big difference.
Lindstrom: One disadvantage of using NSAIDs alone, which we learned in the early years of PRK when we thought using NSAIDs alone with a bandage contact lens would be a good idea, was that there was a significant incidence of corneal infiltrates. Looking at the cyclo-oxygenase pathway, NSAIDs work on the prostaglandin side, but you shunt things into the leukotriene side, which means that you recruit polymorphonuclear leukocytes. Steroids block that side. You are going to have more white cells, flare and cell if you use an NSAID alone; if you use it in combination with steroid, you can block both sides.
Donnenfeld: In a paper published in American Journal of Ophthalmology that looked at pretreating with corticosteroids, we found that by treating patients for just 2 hours before surgery with difluprednate, patients had significantly clearer corneas the next day, less endothelial cell loss at a month and less CME. That is my routine steroid now for cataract surgery. You can control inflammation in a much more significant way. Starting at 3 days to a week preoperatively does not affect the cataract surgery but is great for the ocular surface. The inflammation that the corticosteroid prevents occurs with the surgery itself, so pretreating even a couple of hours ahead of time is all that is needed for the cataract part.
NSAIDs after surgery
Donnenfeld: Same patient: 78-year-old patient with background diabetic retinopathy — a common occurrence. How long after cataract surgery would you treat with a topical NSAID?
Kim: If the patient had retinal thickening before the surgery, I would have first sent the patient to a retina specialist. It is not uncommon for these patients to get a subconjunctival injection of Kenalog (triamcinolone acetonide, Bristol-Myers Squibb) or even Avastin (bevacizumab, Genentech) and wait until the thickening resolves before undergoing cataract surgery.
But in this case, let’s say that the retinal thickening has resolved or the patient did not have it in the first place. I would recommend treating with an NSAID for at least 2 months after the cataract surgery. The classic Irvine-Gass syndrome has been reported at 6 to 8 weeks after cataract surgery, but we have all seen CME occur earlier. I have seen it occur as early as 3 to 4 weeks after surgery. These are the cases that you want to continue the NSAID at least throughout that period and sometimes longer — sometimes 4 to 6 months for severe cases of diabetic retinopathy, retinal occlusive disease such as CRVO or BRVO, epiretinal membrane, or perhaps a case complicated by iris prolapse or posterior capsule rupture. These are the cases when NSAIDs should be continued longer. This is also where you see the real benefit of NSAIDs that have once-a-day dosing and a much safer side effect profile.
Donnenfeld: Talk to me a little bit about intracameral triamcinolone. I think it is vastly underutilized by most ophthalmologists.
Kim: It is. We have a formulation of triamcinolone that is FDA approved called Triesence (triamcinolone acetonide, Alcon). For me, it is a little too concentrated, so I dilute it in half with some balanced salt solution. It helps you to visualize vitreous because sometimes, especially if it is an older patient, you may have a syneretic vitreous that is harder to visualize. It is much better to visualize the vitreous so you can remove it completely because residual vitreous that causes macular traction is definitely going to increase your risk factor for a more complicated CME case and probably for a more prolonged case of CME. In addition, I like the idea of delivering some of that steroid into the posterior segment where it probably helps treat the CME and hopefully prevents it from occurring altogether.
Lindstrom: Today, every busy cataract surgeon needs to own or have access to an OCT machine. We need to treat these patients until their macula is dry. Basically, we are going to do an OCT at 4 weeks, we are going to see what the macula thickness is, and then we are going to plan our therapy around that. Then we will need retinal consultation, and the patient will come back again in a month. We are going to look again and follow and monitor that long term, just like our retina colleagues do. Unless you want to get a consult on every one of these patients, which is certainly reasonable, but there are so many diabetics that to get a consult on every one of them, I think I would rather own an OCT and do my own OCT and screen for macular pathology.
Kim: The other issue is that of subclinical CME. A good study by John Wittpenn and colleagues published in the American Journal of Ophthalmology looked at how some of these patients do get subclinical CME, and it only takes 10 µm of thickening on OCT to have a visual effect on contrast sensitivity. Studies have shown that NSAIDs are beneficial in preventing this from happening. In today’s era of refractive cataract surgery, we are spending all this time with accurate biometry and tuning the ocular surface, so it makes a lot of sense to prevent any CME rather than having to treat it.
Asbell: Even if a patient is not a diabetic, there is definitely subclinical macular inflammation that you may not be able to pick up at the slit lamp or even on OCT, so I do not wait for a change in OCT findings. I use NSAIDs for 2 months postoperatively routinely.
Donnenfeld: Do you worry about preop steroids potentiating infection before surgery, especially in a patient with diabetes?
Asbell: Steroids do not cause infection. They may, however, decrease the immune response in the reaction that is attempting to get rid of the infection. Like everything else in life, there is a risk-benefit in all decisions. But, from experience and the published data, I think you can use a low-dose steroid once a day, maybe up to 3 days before surgery or maybe right before, although I would like to hear what other people think. Inflammation is a cascade, starting at the top with phospholipids from the cell membranes that are broken down to prostaglandin and then to leukotriene. The reason we always go back to steroids is because they start at the top of the cascade, preventing the production of downstream inflammatory mediators. Everything else we talk about is treating further down the cascade, typically toward the bottom of the breakdown products.
Lindstrom: I use an antibiotic as well. I am pretty tuned in to ocular surface disease, and there are pretty effective treatments to use for meibomian gland disease in the antibiotic-steroid combinations: Tobradex (tobramycin and dexamethasone, Alcon) and Zylet (loteprednol and tobramycin, Bausch + Lomb).
Steve Lane and colleagues have shown that you get an extraordinarily rapid response with an antibiotic-steroid when treating ocular surface disease that is related to meibomian gland disease or blepharitis. So I like to clean that up. Frank Bucci showed that if you just do lid hygiene, you increase the number of bacterial colonies, but if you do lid hygiene in combination with an antibiotic, whether an ointment or a drop, you clean up the ocular surface, but you get the additional benefit of reduced intraoperative inflammation. I call that ocular surface preparation. I used to do it in patients with significant ocular surface disease, and then I decided that all of my cataract patients had significant ocular surface disease, so now I do it as a routine. I give Tobradex four times a day for a week preop along with lid hygiene.
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Do you change your phaco technique and pharmaceutical management in patients with Fuchs’ dystrophy?
Stay away from the endothelium
Douglas A. Katsev
I stay away from the endothelium as much as I can and use as much viscoelastic as I feel I need. I do the cataract surgery in almost all of these cases, so I look at my IOL calculations ahead of time to make sure that I end up with a slightly myopic result, about –1 D to –0.75 D for a Descemet’s stripping endothelial keratoplasty. I have used Healon5 (sodium hyaluronate 2.3%, Abbott Medical Optics) a lot in the past, but whatever you are used to is the best thing to use, rather than altering what you do for these special patients. Otherwise, all of the sudden, you are doing something that you are not used to, and then that causes a chain of events that causes problems. So, I pretty much stay with my same viscoelastic and phaco deep, being careful not to bring up chips to the anterior chamber, and staying deep to divide and conquer, all in the bag.
In my phaco cases, I often prescribe Lotemax (loteprednol, Bausch + Lomb) four times a day because of the additional effect on the surface of the cornea with minimal concern about pressure increases. If the patient does miss a drop or two each day, he has enough anti-inflammatory protection, but if he gets it in four times a day, then his surface/dryness seems to be improved, without, in my experience, seeing IOP spikes.
Douglas A. Katsev, MD, practices at Sansum Santa Barbara Medical Foundation, Calif. Disclosure: Katsev is a consultant for Abbott Medical Optics and Bausch + Lomb. He receives fees for non-CME services from Alcon and Allergan, and he has ownership interest in TruVision.
Use same best routine every time
J. Bradley Randleman
You perform your best surgical technique every time. That is generally going to be the same technique every time. If you do something dramatically different from your usual technique to try to protect the endothelium, and in doing so increase the rate of other complications, such as posterior capsular rupture, you have not done anyone any favors. It is healthy to maintain some flexibility in your surgical technique, but in general, it is ideal to become as reproducible as possible.
In patients with Fuchs’, I do not change anything. I do not want any of my patients to have any more corneal swelling postoperatively than they would otherwise. I use a flip technique standardly, even in Fuchs’ cases. It can be a great technique, but you do have to perform it intelligently. In a dense lens, you should not flip all the way up right next to the endothelium and try to emulsify it there, whether or not the patient has Fuchs’. The goal of the flip technique is to get in and out very quickly, so you have less turbulence with less fluid flow that will also affect the endothelium.
J. Bradley Randleman, MD, practices at Emory Vision, Atlanta, and is editor-in-chief of the Journal of Refractive Surgery, a SLACK Inc. publication. Disclosure: Randleman has no relevant financial relationships.