Article Date: 9/1/2006

CONTINUING MEDICAL EDUCATION
 

Using NSAIDS and Other Agents To Manage Retinal Disease
Panelists discuss the expanding use of these drugs in nontraditional applications.

Dr. Heier: Because NSAIDs are being used more frequently to manage perioperative inflammation, retinal specialists may benefit from an awareness of their potential. I'd like to talk about how you are using NSAIDs in your practices, if at all.

POST-OP RETINAL CARE

Dr. Yoser, MD: As a medical retinologist, I don't perform surgery. Therefore, my colleagues and I don't use them for their indicated purpose. I do, however, find a benefit in using an NSAID for a patient who has undergone selective laser trabeculoplasty (SLT) for glaucoma. I find that bromfenac ophthalmic solution 0.09% (Xibrom) is outstanding in these situations. I use it for a few days after the procedure to keep the patient more comfortable and also to respond to the pressure spike that can sometimes result from SLT.1 The drug helps me achieve my best possible outcome.

As another intuitive off-label application, you can use the drug after retinal laser treatments — particularly panretinal laser treatments — if patients complain of pain.2 In these cases, I turn to bromfenac ophthalmic solution 0.09% to maximize outcomes and patient comfort, using the treatment for 5 to 7 days after the laser procedure.

Dr. Orellana: I use bromfenac ophthalmic solution 0.09% after vitrectomies because of its long-acting properties. With a drop of this NSAID and a drop of atropine, I find that patients feel a lot more comfortable than they would feel otherwise. Those who did not receive the drops in the past reported a lot of discomfort during the first postoperative evening. My patients now are much happier.

Dr. Heier: I do not use NSAIDs in many cases. Listening to what we have discussed today, I wonder if we retinal specialists are a bit behind the curve of progress. Traditionally, we have not expected the outcomes of our surgeries to match those of anterior segment surgeons. Now, however, our outcomes have improved for post-retinal detachment repairs and other procedures.3 We are beginning to more fully appreciate the occurrence of CME.

NSAIDs effectively block cyclo-oxygenase, which is the enzyme that converts arachidonic acid to prostaglandins. As we all know, the release of prostaglandins is generally believed to be the factor that propagates postoperative inflammation. We know prostaglandins are responsible for a number of other undesirable effects, such as miosis, lower pain thresholds and photophobia. NSAIDs can help us manage these challenges as our surgical practices continue to evolve. 

USING CORTICOSTEROIDS

Dr. Heier: How do intraocular corticosteroids fit into your treatment regimen for CME?

Dr. Yoser: Some of us find we can use intravitreal triamcinolone acetonide (Kenalog) to treat macular edema in selected cases, not just in macular degeneration. At the same time, we must remember the risk of complications associated with corticosteroids, such as endophthalmitis4 and secondary cataract development. The most challenging issue is intraocular pressure spikes that may linger for weeks, or even up to a year or more, after an injection.5

Obviously, we cannot use triamcinolone injections on high-risk patients, and we need to follow up vigilantly after administering corticosteroids to all patients. It would be ideal if, in the future, we could use a sterile, single-use vial containing the drug in its purest form. This would reduce the risk of pressure spikes. 

Some other options will become available. For instance, fluocinolone acetonide intravitreal implant (Retisert) is already helping our uveitis patients. Of course, dexamethasone (Posurdex) is being studied for age-related macular degeneration, diabetic retinopathy and macular edema. And there may be other indications for corticosteroids in the future.

TAKING THE LEAST-INVASIVE ROUTE

Dr. Heier: Dr. Rho, at which stage do you consider using either periocular or intraocular corticosteroids?

David S. Rho, MD: I perform periocular and intravitreal steroid injections as rescue therapy for CME, not as primary therapy. There is always a risk and benefit ratio associated with any intervention. So your goal should be to treat a condition with the most elegant — and least risky — approach. If you can avoid potential complications, such as those associated with topical corticosteroids, then that approach would be considered a good first line of therapy. They're a very safe, effective method of treatment.

If, however, you don't get the efficacy or the response you wish, then you have to consider adding a higher level of treatment, whether it is combination therapy with topicals or rescue therapy with a periocular or intravitreal corticosteroid injection.

As we all know, any time we perform a procedure, even on a routine basis, we take on some degree of risk. You would be doing your patients a disservice if you were to put them at risk for endophthalmitis or a pressure spike when they may have been more easily and safely managed with topical combination therapy or topical monotherapy. My preference is always to start with the lowest, least invasive therapy, conservatively, and then to build upon that, as needed.

Dr. Heier: That sounds like a very sensible approach. Dr. Orellana, how long will you try topical therapy before moving to intraocular corticosteroids?

Dr. Orellana: My answer varies depending on the patient. Sometimes you know at the outset of treatment a patient will not be a candidate for an injection. A history of glaucoma or the previous administration of a corticosteroid injection might rule it out. However, as a general rule, I start patients on the least invasive treatment, and one that ensures their compliance as much as possible.

Most of my patients have jobs. Some tend to forget to take their drops to work, or it may not be convenient for them to administer the drops throughout their workday. I start these patients with bromfenac ophthalmic solution 0.09% because of the b.i.d. dosing schedule, and that usually helps with the compliance issues. After 2 weeks, an improvement of two lines of vision is not unusual. If patients are doing well, I keep them on the NSAID and continue to follow them. If they are not doing well, we begin talking about other available options, including the combination of the NSAID with a topical corticosteroid or an intravitreal triamcinolone injection if they can safely tolerate it.

WHEN TO TERMINATE NSAIDS

Dr. Heier: I am not so eager to move to the next level of treatment. What about waiting a minimum of 8 to 12 weeks before terminating NSAID therapy? I have seen patients who have not responded significantly to NSAIDs until 6 to 8 weeks after surgery, occasionally even longer.

I'm not sure if this represents a natural course of disease, or an indication for a longer treatment phase. Either way, because I have seen enough of these patients respond after the first 4 weeks, I don't think it is worth taking on the risk associated with an intraocular injection until I have given the NSAID adequate time to work.

We have patients who fail with topical therapy and intraocular injections, sometimes after a positive response to a corticosteroid injection that eventually leads to complications. At that point, we start to look for another cause of the persistent edema, such as complications of anterior segment surgery, and we explore surgical solutions.

A few years ago, there were two studies that focused on refractory CME treated with vitrectomies.7,8 Both studies found a dramatic improvement of edema in response.

But I have not experienced this kind of success. About 60% to 70% of my patients respond to this surgery. There is always a group that goes through all of these steps and don't respond to the surgery. These patients typically have very bad edema, with vision at 20/200 or worse. We have tried to help them with intraocular lens exchanges, but this may not even work. Refractory inflammation becomes an issue.

ROLE OF ANTI-VEGF FACTORS

Dr. Heier: One last area that is gaining a lot of interest is the role of vascular endothelial growth factor (VEGF) inhibitors in managing retinal diseases. Dr. Yoser, do you think anti-VEGF factors play a role in the development of pseudophakic CME?

Dr. Yoser: They probably do. Obviously, this is being studied. These agents — such as bevacizumab (Avastin), pegaptanib sodium injection (Macugen) and ranibizumab (Lucentis) — act differently from corticosteroids and NSAIDs. The challenge will be gathering the needed data in well-designed studies to determine whether they can be used effectively for specific conditions.

Right now, the focus of research for these treatments is on macular degeneration. Therefore, we need to rely on more than anecdotal evidence. Some clinicians likely will try these medications off-label for CME if other therapies fail.

Dr. Heier: Have any of you tried the anti-VEGF therapies — most likely bevacizumab at this time — for refractory CME?

Dr. Rho: I have not.

Dr. Orellana: I have not as yet.

Dr. Heier: I have for a couple of patients after intraocular corticosteroids failed to help them. I tried bevacizumab, which produced very little response. I think anti-VEGF factors may play a role in managing these patients, but I'm not sure to what extent. We are talking about an inflammatory process, not the ischemic disease that these agents were designed to target.

Ensuring coverage

Seth Yoser, MD: I find we can be most successful with NSAIDs if we individualize our care. For example, we will always face cost issues. You have to consider if the treatment will be short- or long-term. With bromfenac ophthalmic solution 0.09% (Xibrom), you will need to decide between a 2.5-mL and a 5-mL bottle.

You may want to talk to the patient about his health insurance to ensure the treatment is covered. Some plans require preauthorization before the patient can be reimbursed. Fortunately, 90% of all formularies cover bromfenac and ketorolac (Acular) on a national insurance basis.6 It's important to document your exam and diagnostics, and tailor your treatment according to your patient's needs and expectations.

Jeffrey S. Heier, MD: You mentioned that the bottle is smaller, but it is also important to note that you need only half as much bromfenac than you need of some other agents. Bromfenac requires only b.i.d. dosing, as opposed to the t.i.d. and q.i.d. dosing required by other agents.

REFERENCES

1.   Harasymowycz PJ, Papamatheakis DG, Latina M, et al. Selective laser trabeculoplasty (SLT) complicated by intraocular pressure elevation in eyes with heavily pigmented trabecular meshworks. Am J Ophthalmol. 2005;139:1110-1113.

2.   McDonald HR, Schatz H. Macular edema following panretinal photocoagulation. Retina. 1985;5:5-10.

3.   Anderson NG, Fineman, MS, Brown GC. Incidence of intraocular pressure spike and other adverse events after vitreoretinal surgery. Ophthalmology. 2006;113:42-47.

4.   Moshfeghi D, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol. 2003;136:791-796.

5.   Wingate RJ, Beaumont PE. Intravitreal triamcinolone and elevated intraocular pressure. Aust N Z J Ophthalmol. 1999;27:431–432.

6.   Wolters Kluwer Health Data IQ06.

7.   Pendergast SD, Margherio RR, Williams GA, et al. Vitrectomy for chronic pseudophakic cystoid macular edema. Am J Ophthalmol. 1999;128:317-323.

8.   Harbour JW, Smiddy WE, Rubsamen PE, et al. Pars plana vitrectomy for chronic pseudophakic cystoid macular edema. Am J Ophthalmol. 1995;120:302-307.



Ophthamology Management, Issue: September 2006