Panel recommends treating ocular surface prior to any refractive procedure

The biggest risk factor for a poor outcome in refractive surgery is pre-existing dry eye, according to a panel of experts.

“We have taken a new approach of evaluating patients for ocular surface disease before considering any type of surgery, including cataract surgery,” Eric D. Donnenfeld, MD, OSN Cornea/External Disease Board Member, said at a panel gathered to address management of ocular surface disease. Patients who are being evaluated for LASIK and PRK overwhelmingly have preoperative dry eye, he said.

“We can improve the outcomes dramatically by managing these patients,” Donnenfeld said at OSN New York during the Dry Eye, Anti-inflammatory and Allergy Corneal Health Round Table, which he chaired.

Getting started

Donnenfeld kicked off the discussion with the case of a 43-year-old myopic woman with mild to moderate dry eye. The edited round table follows; the panelists discussed off-label use of some products.

Donnenfeld: In a myopic patient with active staining of the conjunctiva and cornea and with mild to moderate dry eye, what is the best refractive procedure? Many ophthalmologists would say PRK, and others would say no treatment, as would be expected, but there are additional options.

Douglas A. Katsev, MD: If the patient is 43 years old, it is hard to put in a phakic IOL. PRK, in my experience, causes less dry eye than LASIK, but certainly maximizing the tear film and treating with all appropriate medications and heat to the lids is the most important thing to do before getting started in any direction.

Donnenfeld: How common is it to have mixed mechanism disease, that is, both meibomian gland dysfunction (MGD) and aqueous deficiency, and how would you treat it?

Marguerite B. McDonald, MD, FACS: Michael Lemp published a paper proving that 86% of the patients with dry eye have concomitant MGD.

Donnenfeld: So this is the rule. In the past, we treated one or the other. We need to think about treating both of these diseases to maximize results. Let’s start by talking about aqueous-deficient dry eye. What would be your starting point for managing this patient?

Treating aqueous deficiency

Henry D. Perry, MD: I would start with non-preserved artificial tears and topical cyclosporine, which is sometimes underused in patients with mild dry eye disease. It is important in any type of chronic ocular surface disease, especially due to aqueous deficiency, to begin topical cyclosporine.

Donnenfeld: What if the patient does not want to wait 3 to 6 months for cyclosporine to hit full stride?

Perry: Then we also have nutritional supplements. Fish oil, especially omega-3, is helpful, and we can see results in as little as 2 weeks.

Donnenfeld: I like nutritional supplements as well. In our practice, we use second-generation omega-3 fish oils in which the natural triglyceride provides significantly greater DHA and EPA absorption than first-generation fish oils that have been converted with alcohol to an ethyl ester form. I believe brands such as Nordic Natural in stores and PRN in doctors’ offices, which is what I use, provide much better results.

In addition, we have been adding topical corticosteroids such as loteprednol when we initiate therapy. Combination immunomodulation does great work to get these patients comfortable, and it reduces burning and stinging.

McDonald: Some experts have recommended a run of topical steroids first and then starting Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan). I start patients on both simultaneously, largely because when patients have steroids first, they never want to start cyclosporine. They do anything they can to stay on the topical steroids, which do two things: they blunt or totally eliminate the stinging that often accompanies the induction of cyclosporine therapy, and they give immediate symptomatic relief. So patients have real belief that your suggested regimen is working. And in 4 to 6 weeks, you can turn this person from a suboptimal candidate for laser surgery into a pretty good candidate.

Donnenfeld: That is the key here. You need to evaluate these patients, and if they respond, they become good candidates for LASIK or PRK. If they do not respond, then you are probably best off doing nothing. There is a new steroid that will be coming out that I think is going to be exciting for this type of case, and that is loteprednol gel, which will be available in the first quarter of 2013. I think that will provide even more ocular surface coverage and better contact time.

Perry: In our office, when we start topical cyclosporine, we always start a low-dose corticosteroid. Several authors have shown the efficacy of increasing the success of topical cyclosporine with low-dose loteprednol, and it has been shown by two other groups that the concomitant use of steroids is beneficial, not only in the initial treatment, but also in allowing the success of the long-term use of topical cyclosporine.

Katsev: When you are going to start cyclosporine, patients need to know that they are going to be taking this medication for 4 to 6 months. They need to communicate to me that they are willing to take it that much. I also start topical steroids, so I need commitment for 4 to 6 months and I need to know that they understand the disease.

McDonald: With loteprednol etabonate starting at the same time as cyclosporine, I prescribe four times a day for 2 weeks, twice a day for 2 weeks, and then the patient is off the loteprednol while the cyclosporine continues.

Donnenfeld: That is the Asclepius Panel recommendation.

Kenneth R. Kenyon, MD: I continue to believe that it is important to definitively diagnose aqueous-deficient dry eye by determining if the patient, in fact, has aqueous deficiency. Back in the day, we performed basic secretion Schirmer tests with topical anesthetic. Three decades later, I continue to use this same test to screen for aqueous deficiency. The notion that a patient with a basic secretion Schirmer score of perhaps 10 mm in 5 minutes has an aqueous-deficient dry eye and therefore deserves Restasis and/or punctum occlusion is simply incorrect. In such a case, other mechanisms of ocular surface disease, such as MGD, exposure or decreased corneal sensation, must be investigated.

I am sure we all have our differing views, but I will say that it is important to be clear when you are doing a pre-laser vision correction workup to have space on your diagnostic forms for both lids and tear functions. It will keep you out of trouble; it will keep you out of malpractice suits. I am certainly concurrent with everything else that has been offered about various medical and pharmaceutical therapies, but a Schirmer test tells me a heck of a lot and then allows me to decide whether to go down the route of plugs or even punctum cauterization, which after the inflammatory component of the surface is under control, is a time-honored valid therapy.

Donnenfeld: Punctal plugs work fairly well in aqueous-deficient dry eye. You want to stabilize the ocular surface first. If you want to make a patient unhappy, in my experience, put a punctal plug in someone with significant MGD. Those patients are just miserable. So, when do you start punctal plugs in these patients?

Kenyon: I have become cognizant of the notion that you do not want to create an ocular surface cesspool, as it were, by totally denying all aqueous and, hence, other toxic waste outflow. But after you get the surface in good anti-inflammatory status, then it is time to intervene with punctum occlusion, whether by a homemade “quick and dirty” 3-mm length of 5-0 chromic suture or with more extended duration intracanalicular inserts such as Oasis or semi-permanent silicone plugs. These are all variations on the theme. But first it is anti-inflammatory and then it is punctal occlusion, if you, in fact, have a true aqueous-deficient component.

Anti-inflammatories in glaucoma

Donnenfeld: Do you find that anti-inflammatory therapy, notably cyclosporine, plays a role in glaucoma management?

Robert J. Noecker, MD, MBA: Without a doubt. When you look at the demographic information, these are two diseases with parallel comorbidities. In the general population, a rough statistic for ocular surface disease in age-matched controls is around 15% vs. around 50% in the glaucoma population. The argument is that glaucoma therapy tends to make people worse.

Donnenfeld: A lot of glaucoma specialists resist the idea of early surgery, but for the corneal specialist, often the best thing to do is to get the patient off the glaucoma drops. Often, I will recommend something simple, like laser trabeculectomy or selective laser trabeculoplasty in phakic patients or an iStent (Glaukos) if the patient is having cataract surgery, to get a patient off of a glaucoma medication.

Noecker: Certainly SLT and laser interventions are easier to do. And now we have microinvasive glaucoma surgeries, which are lowering the bar in terms of not causing significant morbidity commonly associated with glaucoma surgery.

The other point is that it is an amazing time in glaucoma medical therapy because there are so many options to avoid the common preservative we talk about: benzalkonium chloride (BAK). If it is not possible from a formulary standpoint to eliminate BAK, then every new formulation has less and less BAK than the formulation had 5 or 10 years ago. You can have people on a preservative-free prostaglandin or a non-BAK alternative preservative prostaglandin. You can have them on preservative-free dorzolamide timolol. You can have them on preservative-free timolol alone. You can have alternatively preserved brimonidine. So you could do a whole treatment regimen without ever having to worry about the preservative effect. Active ingredients certainly and pH also play a role, but the preservative is the common denominator.

Donnenfeld: As a corneal specialist, if you can get patients off of these drops for a lifetime, the quality of life and the improved vision are significant.

Meibomian mechanism

Donnenfeld: Because we are talking about a mixed mechanism of ocular surface disease, let’s move on to the management of MGD. What would be your first line of therapy for managing someone with MGD?

Perry: The first thing is be sure of the diagnosis, as Dr. Kenyon said. I like to express the glands to get a feeling for the consistency and where we are in terms of the MGD in that particular patient. Heat is essential to melt the fats to get them flowing, and it is important that we remember that in this particular disease the change from long-chain fatty acids to free fatty acids with the inflammation leads to saponification or a soap formation. The problem is that there is too much detergent in the tears. Artificial tears can do a lot to help, and topical cyclosporine, topical steroids and nutritional supplements are also helpful. Lid hyperthermia is essential. Oral doxycycline changes the equilibrium constant from free fatty acids back to long-chain fatty acids and helps decrease the inflammation, as does topical azithromycin. Pulsed light therapy also helps in terms of heating, but there have been some disasters that occurred when the iris was fried by mistake.

Donnenfeld: I have become a big believer in nutritional supplements. What do you recommend to your patients who have MGD?

Richard M. Awdeh, MD: The increased importance of nutritional supplements is clear, both to us as a society and to us in clinic and with our patients. I will recommend that patients go on a vitamin therapy or TheraTears (Akorn) type of nutritional supplement, but additionally I ask patients to review their diet for rich foods — chocolates, cheeses, wines, caffeine, nuts — and I will ask them to modify their diet.

For these patients, I do not like putting them on an oral systemic therapy unless we get to that point, and if we do, then we will put them on oral doxycycline 100 mg two times per day for a few weeks and then switch to 100 mg daily. We ask them to take it with a snack and avoid sun exposure and ambient sun.

We have had success with topical azithromycin, again doing a staged approach, starting a low-dose steroid and then tapering the steroid down as the azithromycin has time to work.

With topical cyclosporine, there are instances when patients are not comfortable with it. We have a compounding pharmacy that creates the topical cyclosporine in different concentrations and in different vehicles, including a corn oil, for instance. We sometimes notice a good response in patients who were previously intolerant.

Kenyon: Half of my blepharitis and meibomitis patients do well simply with a warm compress for 5 minutes and erythromycin. That is traditional. Another 25% with any hint of rosacea will be knocked off with low-dose doxycycline or minocycline, which can go on benignly for years. So all this is good stuff, including LipiFlow (TearScience), but there is still a lot out there in the traditional armamentarium.

LipiFlow expression

Donnenfeld: Consider the case of a 55-year-old patient with a long history of tired eyes, no medications, no corneal or conjunctival staining, drinks heavily, 2+ MGD, shortened tear break-up time who is treated with hot compresses, nutrition and LipiFlow. Patients who have marginally compensated ocular surfaces respond by blinking more often, and when they blink more often, they develop tired eyes. He had the therapy, the tired eyes got better, and the blinking reduced.

Kenyon: I have no proprietary interest here, but one of my practice partners, Jack V. Greiner, MD, has been doing studies for TearScience, so I have watched developments with interest. I believe LipiFlow works, but it is pricey.

Having said that, Greiner has done follow-up studies on some of his patients for more than 2 years, and this single 12-minute pulsed heat therapy does indeed unblock the glands. Whether it is by the subjective surveys such as the Ocular Surface Disease Index and the Standard Patient Evaluation of Eye Dryness, or all the objective measures, LipiFlow therapy does seem to have a protracted effect. So despite the self-pay “sticker shock” disadvantage, you can at least reassure patients that they will benefit for at least a year or perhaps longer.

McDonald: When we do hot compresses at home, most of that heat is wicked away by the lid structures, which are highly vascular. So little of the externally applied heat gets all the way back to where we want it to — the meibomian glands. But with the LipiFlow system, the heat is applied from the tarsal plate conjunctival side of the lid, so that the altered meibum becomes liquefied; then gentle pulsations start and the altered meibum is extruded. It is a much more effective way to apply heat, and to a much higher temperature — though still to a controlled and comfortable degree — than patients could ever get at home.

Tears and optimizing the surface for surgery

Donnenfeld: Consider the same patient who is going to have LASIK or PRK who had mixed mechanism ocular surface disease and is now better. Let’s talk about what can be done surgically.

Literature now shows that making thin planar flaps gives better results. Bevel and side cuts provide better adhesion. Flaps can be smaller. In the old days, we were making 9.5-mm flaps for myopes. In a patient with a small pupil, you can go down to 8.1- or 8-mm flaps. You have half the surface area; half the corneal nerves are cut. There are a lot of ways for surgical modification. I do not think personally that there is now a big difference between PRK and small-flap LASIK with advanced techniques. In the old days when we made 150-µm flaps there was a big difference, but now I think PRK and LASIK are both reasonable techniques for managing these patients.

Awdeh: I agree. The key is to get the patient to baseline before surgery and to make sure that their symptoms have improved. Make sure that your objective is such that the patient is also true to the Schirmer’s test and staining of the cornea.

Donnenfeld: Dr. McDonald, you wrote one of the definitive articles on using cyclosporine in these patients. How long do you continue cyclosporine after LASIK, and does it really affect the visual results?

McDonald: Yes. There are now at least five papers in the peer-reviewed literature documenting that whether you are old or young, male or female, and dry or not, you will have a better post-LASIK clinical outcome with a preop run-in of cyclosporine and using it for at least 3 months afterward. One of those papers is ours, using cyclosporine in extremely dry eye patients, who are considered very high- risk LASIK candidates. It made a big difference in the percentage of patients who achieved 20/20 uncorrected vision and in the percentage that needed an enhancement, both in favor of the cyclosporine-treated group.

Kenyon: Based on your work, I use Restasis for at least a month preop in any patient with a Schirmer test value of less than 5 mm basic secretion. I can continue it for up to 3 months postop. I always do LASIK in these patients because I think that their ocular surface is less compromised from the beginning, so the neurotrophic component of creating a LASIK flap is far offset by the need for the epithelium to regenerate in a potentially drier environment. If you do everything that we have described here to optimize the ocular surface first, then you will not get into trouble later with ocular surface difficulties, whether due to a single mechanism or a combined mechanism.

Donnenfeld: Ed Manche just published a paper in Ophthalmology, in which LASIK was done in one eye and PRK in the other eye, and patient healing was evaluated. There was no difference in dry eye between the two groups, and the healing was better in the LASIK group because of the problems of epithelial remodeling.

With the emphasis on optimizing the ocular surface and minimizing preop dry eye, what is the value of the Schirmer test in particular before conducting refractive surgery?

Popularity of Schirmer test eroding

Ocular surface optimization should be considered an integral part and package of current day refractive surgery in order to deliver the optimal visual outcome, meet our patients’ high expectations, and convert them to satisfied customers. In this endeavor there are various venues to pursue with regard to pre-refractive surgery detection of dry eyes, and one age-old test is the Schirmer test. Since its entry into this arena, Schirmer test rapidly gained popularity among clinicians, primarily driven by the fact that it is readily available, is relatively inexpensive, is easy to perform, and lacks clinically noticeable side effects. However, like everything else in life, its sustained popularity as an aqueous tear deficiency test has been slowly eroding, as reflected by one of the ASCRS surveys that reported 70% of the surgeons are not using pre-refractive surgery Schirmer test.

So why is there a change of heart toward Schirmer test? It is multifactorial, and some of the reasons may be attributed to the fact that the results can be quite variable. Based on the Schirmer test, one report showed that 17% of asymptomatic subjects would be misdiagnosed as dry eye patients. A more recent study showed that subclinical tear deficiency indicated by low Schirmer test values did not influence PRK outcomes in patients matched by age and magnitude of refractive correction.

It is important to listen to patient symptoms of dry eye, look for clinical biomicroscopic signs of dry eyes even in those asymptomatic individuals, and consider incorporating some of the newer, technology-driven dry eye tests that may be suitable in your refractive surgery

Thomas John, MD, is an OSN Cornea/External Disease Board Member. Disclosure: John has no relevant financial disclosures.

Schirmer test still relevant

Dry eye continues to be a significant problem and a cause of dissatisfaction after laser surgery. There are a lot of reasons why these patients might have dry eyes, but the key reason is preop dry eye disease. So when we are thinking about laser, we should be thinking about preop diagnosis of dry eye disease. In a study that asked physicians what they do to evaluate patients before refractive surgery, as expected nearly 100% of physicians said they perform corneal topography, but only 30% of the physicians performed Schirmer’s. We may argue that Schirmer’s isn’t the best dry eye test; nonetheless it is interesting to see that the physicians were not thinking about that. That’s a take-home message. Let’s think about it before the laser, not afterward.

Excerpted from Asbell PA, Gadaria N, Lee K-I. “The Ocular Surface and Its Impact on LASIK and PRK” presented at OSN New York, Nov. 16-18, 2012.

Penny Asbell, MD, MBA, FACS, is OSN Contact Lenses Section Editor. Disclosure: Asbell receives research funding from, is on the speakers bureau for or consults for the following: NIH, Toni and Martin Sosnoff Fund, Alcon, Allergan, Aton, Bausch + Lomb , Merck, Inspire, Clinical Research Consultants, Johnson and Johnson, Pfizer, Santen, Research to Prevent Blindness and Vistakon Pharma.