Experts weigh in on the latest ocular surface disease diagnoses and treatments

Treatment varies, depending on who you ask.

On the topics of treating refractive ocular allergy, preventing and treating cystoid macular edema in an older, high-risk diabetic cataract patient, whether to use a strong steroid, when and how often to use a strong steroid, and anticipating an IOP spike, dealing with it or preventing it — even experts have different ideas on cases and care.

Armed with their expertise, pre-eminent eye care specialists dispensed their opinions on these cases in a stimulating Dry Eye, Anti-inflammatory and Allergy panel discussion at OSN New York.

Moderator Eric D. Donnenfeld, MD, OSN Cornea/External Disease Editorial Board member, led the panelists in tackling complicated cases regarding cornea health and ocular surface disease.

In diabetic patients, Eric D. Donnenfeld, MD, would use nonsteroidals to prevent cystoid macular edema. Image: DeVito Studios Ltd.

“External disease is something that everybody has a valuable opinion on,” Dr. Donnenfeld told the panel, presenting the first case for consideration: a 16-year-old white boy with a history of allergy who complains of itching, redness, pain and decreased visual acuity. He uses a topical antihistamine (Figure).

Michael B. Raizman, MD: There is some papillae here, and children can have papillae normally, but given the history, you would think about more severe allergy or perhaps even vernal conjunctivitis, even though the papillae are not giant-sized. It is not essential to make a specific diagnosis because your therapy is going to be gauged based on the severity of symptoms, not the diagnosis. Chances are, though, that this is more in the vernal category. Look at the cornea also. When there is allergy, keeping the cornea healthy is the No. 1 priority, so dealing with the cornea is the primary issue at this point.

A look under the lid of a 16-year-old white boy with a history of ocular allergies who complains of a 1-month history of itching, redness, pain and decreased visual acuity. The patient uses a topical antihistamine. Image: Donnenfeld ED

Dr. Donnenfeld: There is no exudate, no discharge, no purulence. It does not look infectious. It is a hard, plaque-like ulceration, almost shield-like.

Dr. Raizman: The plaque does not have to be shield-shaped, but you do have to clear that off. It will never heal unless you debride it. I see these patients daily, or every other day, and repeatedly debride the material that is going to accumulate. And then, of course, I add pharmacologic therapy on top of that.

Dr. Donnenfeld: So this 16-year-old with obviously severe allergies is on an antihistamine, but that is clearly not enough therapy. Some options are topical antihistamine, topical corticosteroid drops/ointment, mast cell stabilizer, cyclosporine, allergist referral/environmental changes, scraping of necrotic tissue, amniotic membrane graft, and subtarsal injection of corticosteroids.

Marguerite B. McDonald, MD, FACS: This is a pretty significant shield ulcer associated with vernal keratoconjunctivitis. The patient is already on a topical antihistamine, but a mast cell stabilizer, or a combination such as epinastine, would be a good addition. Topical corticosteroid in drop or ointment form could be added. Ointment would be fantastic here because these kids tear profusely and there would be increased contact time with a steroid ointment. Lotemax (loteprednol etabonate, Bausch + Lomb) would be ideal, and it is also very moisturizing. This child will need a lot of treatment, and cyclosporine emulsion four times a day is really useful with vernal and shield ulcers. And, of course, there is environmental modification.

Marguerite B. McDonald

If those things do not work, and it looks like the edge of the shield ulcer already has mucoid plaques, then the plaques have to be mechanically removed. You have to scrape that off and put on a hydrophilic contact lens. If that does not work, then you go on to the amniotic membrane graft. Subtarsal injection of corticosteroids is also a good idea, especially if you get those big cobblestone papillae.

Dr. Donnenfeld: Often in younger children, tearing is so profuse under these conditions that drops are ineffectual because of the reduced contact time. Using a steroid ointment can be a huge difference maker. The addition of loteprednol ointment is helpful under these circumstances.

This patient is going to require long-term corticosteroid therapy. Cyclosporine and mast cell stabilizers may play a role in long-term management, but steroids are obviously needed for the short term. There are three classes of steroids: super-strong steroids such as difluprednate, normal steroids such as prednisolone acetate and the weaker steroids.

Dr. Raizman: You have to be as aggressive as possible when the cornea is involved. I would use Durezol (0.05% difluprednate ophthalmic emulsion, Alcon) in this case, in combination with Lotemax ointment. I sometimes put these kids on oral prednisone 1 mg/kg/day, just to shut them down right away. They rub their eyes; they cannot help it. They are miserable. They cannot keep their eyes open. They cannot go to school. So a course of oral prednisone is also reasonable. More than half of the vernal patients do not have definable systemic allergies, so environmental controls are not as important. Having said that, if there are obvious allergies that these children know about, they have to be managed, and avoidance is difficult. It is best to get an allergist involved to help with avoidance strategies.

Michael B. Raizman

Henry D. Perry, MD: Sometimes systemic corticosteroids are necessary, and even though the patient is a child, a short course can be beneficial and may help turn the tide in your favor. This patient should respond well to topical corticosteroids. You do not have to go to the Durezol-type; regular Pred Forte (prednisolone acetate, Allergan) should work very well.

Preop NSAIDs, steroids

Dr. Donnenfeld: A 78-year-old diabetic male physician presented with decreased vision and wanted his cataract removed. His diabetes was controlled on oral medications, his vision was 20/60, and he had no significant overt macular edema. He had some background retinopathy and 3+ nuclear sclerotic cataracts. Cataract surgery was uneventful, and I initiated preoperative NSAIDs 3 days before surgery.

Robert J. Noecker, MD, MBA: A week is reasonable. In my practice, I see a lot of glaucoma patients on prostaglandin analogues, which bumps them into a higher risk category. For those patients, I sometimes start steroids preoperatively.

Robert J. Noecker

Dr. Perry: I agree. Preoperative steroids in this case are very important to help stabilize the ocular surface.

Dr. Donnenfeld: One day postop, this patient showed some corneal edema, but more importantly, at 1 month postop, optical coherence tomography showed significant cystoid macular edema (CME). This patient was treated aggressively with therapy, had an intravitreal steroid injection and did very well. Now he is coming in to have the second eye operated for cataract. Do I manage the second eye differently from the first?

Bromfenac, nepafenac and ketorolac are all good NSAIDs, but one of them is approved for once-a-day dosing (Bromday, bromfenac ophthalmic solution 0.09%, Ista Pharmaceuticals). Would it be reasonable to treat this patient with the approved once-a-day nonsteroidal, or should the frequency of therapy be increased to prevent CME?

More would certainly be more conservative. In the United States, the nonsteroidals are approved by the U.S. Food and Drug Administration for reducing cell and flare in the anterior chamber, which is not why we use it. We use it to prevent CME. In Europe, Nevanac (nepafenac ophthalmic suspension 0.1%, Alcon) was recently approved with CE mark for prevention of CME in patients with diabetes. By the way, a lot of these drugs are only approved for starting 1 day after surgery or 1 day before surgery; they are not approved for use for 3 days preoperatively.

Back to our patient’s second eye. We started him on preoperative difluprednate and a nonsteroidal 1 week preoperatively, and we have been very impressed. The second eye showed clearer corneas following surgery and less CME. We gave the nonsteroidal twice daily, and we gave the corticosteroid according to a dosing schedule that was published in American Journal of Ophthalmology.

I now pre-dose all of my patients with steroid, and I start them on an every 15-minute pulsed dose for four doses at home and then every 15 minutes in the surgery center before surgery. After surgery, I taper the dosing schedule from four times per day to twice a day for 2 weeks and then once a day.

In a study comparing corneal thickness in patients given prednisolone acetate vs. difluprednate published in American Journal of Ophthalmology, we show that corneas were thinner on the first postoperative day in the difluprednate group. Importantly, a lot of these subjects were diabetic, and there was less macular edema in this group.

Steroid-induced IOP spikes

Dr. Noecker: When you look at steroid response, certainly the more potent steroids are more likely to increase IOP. All other things being equal, the problem with steroid response is playing “catch-up.” That is, if the steroids are not used adequately to begin with, the dose is progressively increased over time. The point is that using more steroid early is probably a good thing. You do have a window for steroid response — usually a couple of weeks — with topical dosing. If you get rid of most of the inflammation, then if there is a pressure spike, it is probably OK to stop the steroid rather than letting the situation smolder until there is both inflammation and a steroid spike. Then you are stuck between a rock and a hard place. Hitting the inflammation hard, immediately postop, whatever the surgery, is a very good idea.

You also need to know your population. If you are working with a glaucoma population, you have a one in three incidence of steroid-induced pressure increase; in the general population, the incidence is probably only a few percent.

In the general population, the median at which you would see a pressure spike is probably a couple of weeks, so you do have that window to really hammer the inflammation. There is a dose-dependent element to the pressure spike as well: After an intravitreal injection, you might see it within a day. That is a very high dose. In general, the dosing regimen described gets to the point and really knocks down the inflammation. Then you can get off it if needed.

Henry D. Perry

Dr. Perry: In our practice we have been using Durezol for the last year, and we have noticed occasionally some patients with significant pressure responses. Because we see our patients at a 2-week window, those are patients for whom we would either decrease the Durezol or add a temporary glaucoma medication, depending on the situation.

Dr. Donnenfeld: In the FDA trial, published by Korenfeld and colleagues in 2009, there was a 2.8% incidence of pressure spikes at 1 month on four-times-a-day dosing. I think that is normative data in a normal population without known glaucoma.

Managing vitreous loss

Dr. Donnenfeld: Managing vitreous is so important. One of the real advances in vitreous management has been the use of triamcinolone to stain the vitreous. Sometimes you just miss a strand, and that staining makes all the difference. In every case of vitreous loss, even when if I am absolutely certain that I have removed all the vitreous, I put in triamcinolone, just because it quiets down the eye so significantly. I find this to be a real difference maker. When you lose vitreous and you use triamcinolone, the next day the eyes come back and they are 20/25 or 20/20; they are quieter than my conventional surgery.

About 50% of the vitrectomies that I do are pars plana bimanual vitrectomy. I start by taking out the vitreous that I see in the anterior chamber, remove a little bit of cortex, and clean up the eye as best I can. I ask myself, “Is the vitrectomy complete?” Then I inject triamcinolone into the anterior chamber, irrigate out, and maybe there is a strand that I would have missed otherwise.

Dr. Raizman: I do the same, as much for the anti-inflammatory effect as for the staining of the vitreous. I also think about the increased risk of endophthalmitis. There is a debate about whether you should put these patients on any additional antibiotics, but they are clearly at greater risk. I agree that you need to follow these patients closely.

Dr. Donnenfeld: If you want to improve your result on your most difficult cases, this is probably the simplest thing you can do to give yourself better results. You will have better surgical skills because you will manage the vitreous appropriately, and you will have better postoperative results because the inflammation will be controlled.

Dr. Perry: The only other caveat is that I make sure all patients with vitreous loss see a vitreoretinal surgeon within 2 weeks for evaluation of the peripheral retina.

Do you change your intraoperative and postoperative management if you lose vitreous during cataract surgery?

Lindstrom's Perspective
Prophylaxis may be key in treating ocular surface disease, inflammation

References:

• Donnenfeld ED, Holland EJ, Solomon KD, et al. A multicenter randomized controlled fellow eye trial of pulse-dosed difluprednate 0.05% versus prednisolone acetate 1% in cataract surgery. Am J Ophthalmol. 2011;152(4)609-617.
• Korenfeld MS, Silverstein SM, Cooke DL, Vogel R, Crockett RS; Difluprednate Ophthalmic Emulsion 0.05% (Durezol) Study Group. Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain. J Cataract Refract Surg. 2009;35(1):26-34.

• Eric D. Donnenfeld, MD, can be reached at Ophthalmic Consultants of Long Island, 2000 N. Village Ave., Rockville Centre, NY 11570; 516-766-2519; fax: 516-766-3714; email: eddoph@aol.com.
• Marguerite B. McDonald, MD, FACS, can be reached at Ophthalmic Consultants of Long Island, 360 Merrick Road, Lynbrook, NY 11563; 516-766-2519; email: margueritemcdmd@aol.com.
• Robert J. Noecker, MD, MBA, can be reached at Ophthalmic Consultants of Connecticut, 75 Kings Highway Cutoff, Fairfield, CT 06824; 203-366-8000; fax: 203-330-4598; email: noeckerrj@gmail.com.
• Henry D. Perry, MD, can be reached at Ophthalmic Consultants of Long Island, 2000 N. Village Ave., Suite 302, Rockville Centre, NY 11570; 516-766-2519; fax: 516-766-3714; email: hankcornea@aol.com.
• Michael B. Raizman, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St. Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; email: mraizman@tufts-nemc.org.
• Disclosure: Dr. Donnenfeld is a consultant for Abbott Medical Optics, Alcon Laboratories, Allergan, AqueSys, Bausch + Lomb, CRST, Elenza, Glaukos, Inspire, Lacripen, LenSx, Merck & Co., Odyssey, Pfizer, QLT, TearLab, TLC Laser Centers, TrueVision and WaveTec. Dr. McDonald is a consultant for Bausch + Lomb. Dr. Noecker is a consultant for Alcon Laboratories, Allergan and EndoOptiks. Dr. Perry has no relevant financial disclosures. Dr. Raizman is a consultant for Abbott Medical Optics, Alcon Laboratories, Allergan, Avedro, Bausch + Lomb, Ista Pharmaceuticals and Ocular Therapeutix, and has ownership interest in Avedro, EyeGate and Ocular Therapeutix.