Panel examines NSAID use in surface ablation procedures

In part 2 of this Ocular Surgery News round table discussion, experts focus on the management of surface ablation patients and the use of nonsteroidal anti-inflammatory drugs.

Round Table Participants Moderator Richard L. Lindstrom Daniel S. Durrie Johnny L. Gayton Terrence P. O'Brien William B. Trattler

Richard L. Lindstrom, MD: What do you watch for in LASEK? What indicates things are not healing?

Johnny L. Gayton, MD: I would be sure that the topical anesthetic is stopped. I think that is critical. If they are not showing significant epithelial healing between day 5 and day 7, I will not only do occlusion, but I will also pressure patch them so that they are not doing anything additionally toxic to the cornea.

Most of them will respond very well that way, but occasionally, you are going to run into a person that you are going to have to do handholding for an extended period of time. And preservative-free artificial tears and a lot of reassurance because there is an occasional patient who is going to take a long time to heal. Otherwise, I think it is imperative that we watch them closely and keep them well-lubricated and keep them from getting a stromal melt even without an NSAID.

Dr. Lindstrom: Good thought. But let us say a patient is properly managed, and they have not used an NSAID or a topical anesthetic for more than 4 days or at more than the appropriate frequency. They heal or are healing a little bit slowly. You made your therapeutic plan and, when they were healing slowly, either discontinued medications and took the contact out or changed the contact. Have you had patients, then, who have not healed if you treated them that way? Has anyone had one who did not heal?

William B. Trattler, MD: What do you mean by not heal?

Dr. Lindstrom: Have you had a patient who came back at day 7 and still had an epithelial defect? You have seen some in consultation. I know everyone has seen patients in consultation or in certain situations where patients continued medications longer than they should have, contacts were not changed and so on. But for those patients who you managed according to the guidelines that you just described, have you had someone who then did not heal? And if so, what do we do next?

Daniel S. Durrie, MD: I had a patient last year who had been seen by somebody in my office at 5 days, and they changed some things. I saw them at day 7, and they still had an epithelial defect. I patched them, and they were healed the next day. I think it was something that was either getting put in the eye or just dryness. If you don’t get aggressive, they can get haze, and this gentleman did heal without haze.

Dr. Lindstrom: How long does an epithelial defect need to persist before you are likely to see haze?

Dr. Trattler: I recently had a similar case. The patient had a hyperopic refraction, and on day 5 the patient still had bilateral epithelial defects that were approximately 2.5 mm in diameter. I instructed the patient to stop using her topical NSAIDs along with the dilute anesthetic drops. However, on postoperative day 7, the persistent epithelial defects remained. I switched her bandage contact lens to one with a steeper base curve because this was a hyperopic laser treatment. I also reduced the Pred Forte (prednisolone acetate ophthalmic suspension 1%, Allergan) to once a day. As we talked about other possible causes of delayed epithelial healing, she mentioned that she used a fan over her bed at nighttime. Because she had been using the fan every night since her surgery, my concern was that the fan was causing significant evaporation, which was preventing her epithelium from healing.

Once she stopped the fan and in addition aggressively lubricated her eye, she was able to heal her epithelial defects. That patient ended up doing quite well.

After surface ablation, delays in epithelial healing can occur due to a variety of reasons. The key is to figure out the underlying cause for the epithelial delay and then figure out the best approach to heal the epithelium.

Terrence P. O’Brien, MD: I saw one recently. The epithelium finally healed, but it remained sort of a vortex keratopathy where there was an epithelial regeneration line that remained right in the center. There actually was some heaped-up, irregular epithelium that was affecting vision. Elsewhere the patient had a higher surface ablation for myopia and higher myopia, and I wondered in this case whether there was something to do with the change of the central curvature relative to the tarsal plate and the lid function.

The patient had had a prior blepharoplasty, and so I agree with Dr. Durrie. You have to get aggressive with those cases because even when the epithelium finally does smooth out, you can be left with some significant haze in the center.

Dr. Lindstrom: When do you start to worry that you might get a surface haze or scar that is worse than average? You are not worried at day 3. When do you start to get nervous?

Dr. Trattler: I think by day 6 or 7, if the persistent epithelial defect is still present, there is definitely a risk of early onset corneal haze. You therefore need to identify and treat these situations so that the epithelium heals in a timely manner.

In my experience, I have found that early haze is not prevented by intraoperative mitomycin-C. The underlying cause of early corneal haze is different from late onset corneal haze. So even if you have treated your patient with prophylactic mitomycin-C, delays in epithelial healing can lead to loss of vision and a myopic shift due to early corneal haze.

Dr. Durrie: Seven days is when I am starting to worry. You will not always get haze if you get them to heal at 7 days, but you have a 50-50 chance that you are going to have some problems if they are not healed by then. It is important to be aggressive.

Dr. Lindstrom: We talked about how we are managing our own patients, but let’s say a patient is sent to you at day 10 with a non-healing epithelial defect. The patient did not have his or her medication discontinued, and they are starting to show some haze. Is your therapeutic regimen any different? For example, would you continue to use steroids, or would you use them more frequently vs. stopping them? What do you do if you see a haze patient?

Dr. O’Brien: In some of these cases, there is this very irregular, heaped-up, sick-looking epithelium. In some cases, I have gone back and performed a mechanical debridement. I have then started over with all the measures, replacing a new contact lens with appropriate base curve, eliminating preservatives, modifying the corticosteroid regimen and stopping the nonsteroidal. But sometimes you need mechanical debridement and then maybe, as you said, giving bacitracin or erythromycin ointment at night in addition to try to help.

Dr. Lindstrom: Did you apply mitomycin-C?

Dr. O’Brien: In those cases, they had applied mitomycin-C.

Dr. Lindstrom: You did not do it a second time?

Dr. O’Brien: I did not do it the second time.

Dr. Trattler: The challenge for these situations is that mitomycin-C does not appear to prevent early corneal haze. In my experience, I have found that the aggressive use of topical steroids can help reverse the reduction in vision from early corneal haze. Of course, the first step is to heal the epithelium, and once the epithelium has closed, you can restart topical steroids. I have been fortunate that in my experience, topical steroids have been helpful at significantly reducing the severity of the early corneal haze.

Dr. Durrie: I would like to echo that. Once you have it healed, these ones that go the 7 to 10 or 14 days need to be treated with steroids, or you are going to get not only a lot of haze, but you are going to get return of myopia and a patient that might be a –3 D with a bunch of haze, too.

Dr. Lindstrom: Would you use Pred Forte every 2 hours, and for how long?

Dr. Durrie: I have a tendency to use Pred Forte just four times a day. To me, that is a lot of steroid if you are going to be using it for a month or so. I will see them every couple of weeks and then taper it down, but it is mainly the fact that I know that they are going to be on at least 3 months of Pred Forte before they are off of it. I may even have 6 months of treatment down the road. It just takes a long time at a slow taper, but I do not put them on every 2 hours. That is a little overkill.

Dr. Trattler: I may put them on Pred Forte every 2 hours for the first 2 weeks. Once the haze starts responding, I will drop Pred Forte back to four times a day.

Dr. Lindstrom: And then how long?

Dr. Trattler: In these challenging cases, you have to work closely with the patient. I typically have patients return every 2 weeks, and on each visit I check their refraction, severity of the haze and their eye pressure. What you are looking for is a reduction of the myopic shift and improvement in their best corrected vision. As the patient responds to treatment, you can reduce the frequency of Pred Forte. As things improve, I usually switch to Lotemax (loteprednol etabonate, Bausch & Lomb) and eventually to FML (fluorometholone ophthalmic suspension 0.1%, Allergan). My strategy is to reduce the strength and frequency of the steroid. Every patient is, of course, different. And you are right, it can take a few months, but each patient-tapering regimen is a little different, depending on how quickly they respond.

Dr. Gayton: I am a steroid responder, and I ended up with bilateral posterior subcapsular cataract from steroids.

Dr. Lindstrom: Make sure to check your pressure.

Dr. Gayton: One of the things that I have found to be helpful in these patients that either have that epithelial swirl or have significant postop keratitis is the use of FML ointment. FML ointment is, as you know, a low-potency steroid, but because you are using it in ointment form, you can use it at night. I have had resolution of rather dramatic cases of keratitis and irregular epithelium just by adding that to my regimen. It is something to think about. I had a patient last week who improved from 20/100 to 20/40 in 2 days just by adding FML ointment.

Dr. Durrie: I want to echo what Dr. Gayton said about cataracts because I had a patient who was not a slow epithelial healing patient. This was a highway patrolman who went skiing and got his eyes sunburned. He got late haze, and I had to treat with steroids for 3 or 4 months. This patient was in his late 20s, and I treated him pretty aggressively with steroids, tapered him down and, in spite of that, he got bilateral posterior subcapsular cataracts of visual significance. So you need to mind your steroids, too. I thought he was doing a great job getting rid of his haze in one area and gave him a secondary problem.

Dr. Trattler: But does that make you want to use mitomycin-C more frequently in patients?

Dr. Durrie: This patient had mitomycin-C. He was a patient who went out and did not wear his sunglasses and got his eyes sunburned. We still need to tell patients that they really need to make sure that they do not get a high exposure to UV light for that first full year because it could still happen, although it is rare.

Dr. O’Brien: Another adjunctive maneuver you can do in that hypothetical situation Dr. Lindstrom mentioned is that if this is not your patient, you can also have them at least begin systemic vitamin C. I usually give 1,500 mg per day, but our own patients would have already been on that. If someone comes in with this arrest of healing, you can switch him or her over to systemic vitamin C, 1,500 mg per day, in addition to increasing the steroid.

Dr. Lindstrom: Any other comments?

Dr. Trattler: I would like to clarify what I found with Nevanac (nepafenac ophthalmic suspension 0.1%, Alcon) and delays in epithelial healing in patients undergoing surface ablation. In two randomized, double-masked studies comparing Nevanac and Acular LS (ketorolac tromethamine ophthalmic solution 0.4%, Allergan) after surface ablation, I found that delays in epithelial healing and early corneal haze were more common in the Nevanac-treated eyes. The key teaching points from these studies were that placement of Nevanac directly on the stromal bed before contact lens placement was a risk factor for delays in epithelial healing. As well, the use of Nevanac beyond 3 days was a separate risk factor for delays in epithelial healing.

However, there are a number of randomized, double-masked studies that have found that Nevanac, when placed after the bandage contact lens and used for 3 days or less, does not appear to delay epithelial healing. In addition, everyone participating here has reported that they are successfully using Nevanac for patients undergoing surface ablation, and everyone is placing Nevanac in the eye only after the bandage contact lens and limiting the use of Nevanac to 3 days or less.

As surgeons, we all use medications that have side effects. By understanding how to safely use a particular medication, we can avoid serious adverse events that can lead to poor visual outcomes.

Interestingly, there are also some regional differences in how doctors use NSAIDs. In New York, I am aware that some surgeons have successfully soaked their bandage contact lens in both their topical antibiotic and topical nonsteroidal of choice without experiencing issues in epithelial healing. Unfortunately, one surgeon who switched from soaking their bandage contact lens with their typical NSAID to Nevanac ended up experiencing severe delays in epithelial healing. I wonder how common it is for surgeons to soak their bandage contact lens in a nonsteroidal before surface ablation?

Dr. Gayton: I have heard of that, but it is not anything that I would advocate.

Dr. O’Brien: Right, and I think that is, again, an uncontrolled delivery where you could get potentially high concentrations. It could be deleterious.

Dr. Gayton: That is one of the issues. I think that when we were talking about generic diclofenac and the vehicle that it was in, there was some talk that it may well be holding the NSAID up against the cornea for extended periods of time at higher concentration, causing corneal melting. I don’t see why soaking a contact lens in an NSAID would even be beneficial because you have already reached the amount of medication needed with an eye drop to inhibit the enzyme.

Dr. O’Brien: Correct.

Dr. Trattler: I would agree. I have never done that myself. But the key thing is that although any NSAID can have some toxicity issues, in general they are safe and effective, especially if you use them as we have discussed.

Dr. O’Brien: I would agree. I think we might want to specifically avoid a rigid recipe that would imply that if there is any slight deviation from that it is a deviation of a standard.

Dr. Lindstrom: I agree.

Dr. O’Brien: And just as you say, these are loose guidelines.

Dr. Trattler: Absolutely.

Dr. O’Brien: The main point is that nonsteroidals are safe and, when used properly, can be beneficial in this setting.

Dr. Lindstrom: We have achieved some useful general guidelines here, which include that most of you are seeing your patients at 4 to 6 days, and you are expecting them to be healed. You are using topical NSAIDs no more than four times a day for 4 days maximum, and most of you no more than four times a day for 3 days maximum.

Dr. O’Brien: Right.

Dr. Lindstrom: If you are not seeing things well-healed at the time you expect them to be healed, depending on your methodology, which is 4 to 6 days, you are changing things and getting the patient off of toxic meds, either discontinuing them or changing the contact lens. You are seeing the patients daily if they are not healed at 4 to 6 days, and if you have a non-healing epithelial defect at a week, you are pretty nervous about it.

Dr. O’Brien: Absolutely.

Dr. Lindstrom: I would suggest that if a relatively low-volume comprehensive ophthalmologist who is not doing refractive surgery routinely sees a patient at a week with a large non-healing epithelial defect, they might want to make a phone call or send an e-mail, maybe get a consultation, to get some help.

Dr. Gayton: Just as steroids are potent medications, we need to remember that NSAIDs, likewise, are potent medications. They are safe and effective, but they also need to be treated with respect because people can have delayed healing. They can have toxicity issues. Clearly they should be used, but we need to be cautious when using them and watch for these things.

Dr. Trattler: Would you want to use the word caution? Topical steroids have a wide variety of side effects, from cataract formation to elevated eye pressure. But we understand the side effects, and therefore we safely use topical steroids routinely. The same thing goes for nonsteroidals. We use them routinely, and they are really beneficial to our patients in both cataract and refractive surgery. So rather than use the word “cautious,” perhaps we should say that surgeons typically use topical NSAIDs in a wide variety of situations, and the key is for the surgeon to understand their side effect profile. Sometimes NSAIDs get a bad rap, but all drops have toxicity and risk to them.

Dr. Lindstrom: That is right, but it is the same guidelines we teach. We do not teach people to use steroids four times a day and never check anybody’s pressure. We do not teach people to use NSAIDs four times a day and never look for epithelial defects.

Dr. Trattler: Absolutely.

Dr. Lindstrom: And so you need to know the things that can go wrong and watch for them. I would like to see more of our colleagues use NSAIDs. That would be in the best interests of their patients, but maybe they need to know what to look for and how to get out of trouble when they have the outliers that are not responding the way they want.

For more information:

• Daniel S. Durrie, MD, can be reached at Durrie Vision, 5520 College Blvd., Suite 200, Overland Park, KS 66211; 913-491-3737; fax: 913-491-9650; e-mail: ddurrie@durrievision.com. Dr. Durrie is a paid consultant for Alcon and a clinical investigator for IntraLase.
• Johnny L. Gayton, MD, can be reached at 216 Corder Road, Warner Robins, GA 31088-3604; 478-923-5872; fax: 478-929-6266; e-mail: eyesightwr@aol.com. Ocular Surgery News was unable to confirm whether Dr. Gayton has a direct financial interest in the products mentioned in this article or if he is a paid consultant for any companies mentioned.
• Richard L. Lindstrom, MD, is the Chief Medical Editor of Ocular Surgery News. He is in private practice at Minnesota Eye Consultants, 710 E. 24th St., Suite 106, Minneapolis, MN 55404-3810; 612-813-3600; fax: 612-813-3660; e-mail: rllindstrom@mneye.com. Dr. Lindstrom is a consultant for Alcon and Bausch & Lomb.
• Terrence P. O’Brien, MD, can be reached at Bascom Palmer Eye Institute, 7108 Fairway Drive, Palm Beach Gardens, FL 33418; 561-515-1544; fax: 561-515-1588; e-mail: tobrien@med.miami.edu. Dr. O’Brien is a non-salaried ad hoc consultant for Alcon, Allergan, AMO/VISX, Bausch & Lomb, Inspire, ISTA and Santen.
• William B. Trattler, MD, can be reached at 8940 N. Kendall Drive, #400, Miami, FL 33176; 305-598-2020; fax: 305-274-0426; e-mail: wtrattler@earthlink.net. Dr. Trattler is a consultant for Allergan and Inspire. He performs research for Allergan, Ista and Vistakon and receives speaking honoraria from Allergan and Inspire.