OSN round table, part 1: Treat dry eye before and after ocular surgery

Dry eye is a multifactorial progressive disease that worsens with time. At the European Society of Cataract and Refractive Surgeons meeting in Barcelona, Ocular Surgery News convened anterior segment surgeons from both sides of the Atlantic to address the challenges of diagnosing and treating ocular surface disease, particularly before and after ophthalmic procedures. In this first of two parts led by OSN Technology Section Editor William B. Trattler, MD, the round table participants compared the differences between what surgeons in the U.S. and those abroad are doing in their respective countries to diagnose and treat ocular surface disease preoperatively and to treat or prevent dry eye postoperatively.

William B. Trattler, MD: One of the things I explain to my patients is that dry eye is a progressive disease. It gets worse over time. If we do not stop the disease where it is now, then a year later it will get worse and worse.

Karl G. Stonecipher, MD: I don’t think I would establish just a dry eye practice, which some people are doing. I don’t see myself doing that. I am more focused on how to manage dry eye in relation to surgery. How am I going to make all these patients happy postsurgically? And how am I going to keep from creating unhappy patients?

 

Arthur B. Cummings, FRCS: Exactly, it is the way you manage it. There is another issue, too. It has been shown well in studies that osmolarity directly impacts biometry for cataract surgery, so if you are measuring someone using ocular biometry and his eyes are dry, then you are not going to put the right lens in. And then you have another problem when the patient is not seeing properly and he has dry eyes.

We just completed a study looking at how osmolarity impacts topography-guided LASIK. Topography-guided LASIK is coming to the U.S., and when it is launched, it is going to become huge. It is an incredible tool based on Placido topography, which is the reflection of rings off your tear film. What we are seeing is a good correlation between osmolarity and the number of maps that are validated by the laser software. If osmolarity is high, fewer maps are validated; if osmolarity is low, more maps are validated. So you are getting higher-quality data to drive the treatment linked to osmolarity.

Treatment variations

Stonecipher: I would like to hear what is different in Europe. What are you doing for treating dry eye that is different from what we in the U.S. are doing? If I have bad dry eyes on level 3 ITF (International Task Force on Dry Eye), what do you do?

Cummings: In Ireland, we would be more limited than you are, especially in terms of Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan), but we would use everything that is offered: plugs, combinations, omega-3.

Trattler: Cyclosporine just became available in Europe, and you have steroids. Are there any other medications that are specifically designed for dry eye that are available?

Aylin Kiliç, MD: In Turkey we have cyclosporine and also Restasis.

Image: Kiliç A

Wolfgang Riha, MD: So far, Restasis has not been easily available for us in Austria and Germany. It was complicated to get it through the pharmacy and then get it to our patients, so it was not widely used. But recently a Restasis-style cyclosporine was introduced, which will increase our use.

Béatrice Cochener, MD, PhD: There are not so many people who are using pure artificial tears. We are more looking for these combinations that can provide this great compromise — not too viscous that it impairs vision, but enough so that the patient does not need to put in the drop every hour. These new combinations of well-balanced solutions act on the different components of dry eye, including the lipid layer and providing osmoprotection.

Stonecipher: Do you use autologous serum?

Cummings: Very little. We are using all sorts of things, but many of them are preserved and that is another part of the problem. I often just go to the list of products that are not preserved.

Riha: I am a fan of autologous serum drops.

Cochener: When it is severe. It is not a first-line indication.

Riha: No, obviously not, but in hopeless cases, yes.

Cochener: I discovered that access to autologous serum is completely different from one country to the other. But it is good medicine because it is full of growth factors.

Trattler: In the U.S., we have the same challenges. Although some doctors can create autologous serum in their office, they cannot get paid for it. As well, it takes a lot of time and effort, and there is risk of infection. At our center, we use compounding pharmacies to help create autologous serum. Patients get their blood drawn, and we send it to the compounding pharmacy for sterile preparation.

Cochener: Do they remove the platelets? There is a new preparation method that may have less ethical impact — that is, to keep the platelets but to deactivate them. It is interesting to see the evolution. We [the French] are not able to access this method, but the Spanish are increasing the quality of preparation.

Trattler: It is called platelet-rich plasma, or PRP. I have heard some discussions on this new technology. It is available in the U.S., but I have not yet prescribed it. The technology seems promising.

Preoperative therapeutics

Stonecipher: Are you introducing cyclosporine earlier?

Jennifer Loh, MD: I am, yes. Before cataract surgery, I look for symptoms and signs of dry eye. If I see any, I immediately start treatment.

The common treatment pattern that a lot of us use is to start a steroid and Restasis at the same time. I use a steroid for several weeks and then transition to only Restasis. So I will start that and make sure that their symptoms and their signs are improving before cataract surgery.

You may have a good point about the preservative. I have seen a difference between the generic surgical drops vs. brand. I recently had several patients who had their first eye done with brand-name drops — Durezol (difluprednate ophthalmic emulsion 0.05%, Alcon), Prolensa (bromfenac ophthalmic solution 0.07%, Bausch + Lomb) or Ilevro (nepafenac ophthalmic suspension 0.3%, Alcon) and Besivance (besifloxacin ophthalmic suspension 0.6%, Bausch + Lomb) — but for the second eye they decided to go with generics due to the lower cost. Many of the patients have come back saying, “My eye feels worse this time — irritated, dry,” and I believe it is because they are on generic ketorolac. I have gotten to the point where I usually tell them not to use the generic ketorolac after surgery because I find it can be toxic to the cornea.

Stonecipher: That is a great point. I did cataract surgery on a patient who has severe Sjögren’s disease. All the drops that had mucoadhesives in them, which I typically use, she could not tolerate. They would stick her eyes together, so the mucoadhesive you would think would be helpful was actually hurting her. So what we did was use viscoelastic in her eyes before we did each case. I used a whole — it is not cheap — vial of ProVisc (sodium hyaluronate, Alcon) in each of her eyes before I took her back to surgery.

I have been doing that on everybody at the end of surgery. At the end of each case, I put in the antibiotic and the steroid and then instill what is left of the viscoelastic. The next day, the patients look awesome. If you look at patients at an hour to 3 hours postop day of surgery, it is not their surgery that is creating their ocular surface disease or epitheliopathy, it is the anesthetic, especially tetracaine.

Dry eye after surgery

Riha: I see plenty of complaining patients after cataract surgery telling me about dry eye symptoms and fluctuating vision. This is much more of an issue than we thought, especially because we are doing more refractive procedures in an aging group these days. Twenty years ago, cataract surgery was cataract surgery. Now we do refractive procedures with premium IOLs that require a good surface. We have to think more about that.

Cochener: That is a key message: to think about the ocular surface before the surgery in order to prevent dry eye after the surgery because treatment in the past sometimes has been severe and too late. Ocular surface disease appears to be the most common complication of any refractive surgery that can impair quality of life and visual performance of the operated patient.

Stonecipher: And if patients have paid you all that money, they are not real happy.

Trattler: Dr. Cochener, why do you think patients have more dry eye after surgery?

Cochener: The dominant components of dryness after surgery are a combination of the neurogenic process — the more nerves cut, the greater the impact on the ocular surface — and inflammation related to surgical stress. Additional factors are the age of the patient and the previous condition of the ocular surface related to allergy, hormonal and lid changes by the aging process. In older eyes, meibomian gland dysfunction is a source of dryness by evaporation. In patients with presbyopic inlays, for instance, almost 50% complain of dryness, such that systematically we are placing plugs at the same time as the implantation.

Kiliç: I have observed after my surgeries that there is dry eye, not too much, but it may not be only preoperative dry eye disease but also can be related to change in the corneal shape after corneal ablation that can create dry eye syndrome. I have limited experience with inlays, but for those patients I remind them that there is a steep area and increased dryness, which is also possibly related to change in the corneal shape.

Loh: Along the lines of cataract surgery seeming to worsen dry eye, what about the effect of Betadine (povidone-iodine, Alcon) on the ocular surface? My partner is a medical retina specialist, and he has started giving artificial tear samples to all his patients who get injections for macular degeneration because their eye has been doused in Betadine for several minutes before the injection. Oftentimes, many calls I get at night from patients are those who have had injections with the complaint of foreign body sensation and irritation. So I wonder if the prevalence of dry eye after injections is something we could help create awareness among our retina colleagues.

Cummings: What I have seen with LASIK procedures when you are doing both eyes at the same time is that, when you put in anesthetic drops, by the time you are doing the second eye, you can already see the impact of your procedure on the first eye. The only thing that is happening at that time, really, is that the patient has stopped blinking the way he normally would, so the blink rate goes down because of the anesthesia. You do not have the same blink reflex. And once the patient has been hurt a little, it just takes a whole lot longer to recover. So I do not like the idea of doing it routinely, but maybe I should, at the end of the procedure, start putting in a whole swig of viscoelastic.

Preoperative diagnostics

Stonecipher: The biggest issue is in what you start doing earlier and what you need to be more aware of around surgery. One thing I learned from the PHACO study is that lissamine green before surgery is an easy way to look at people and quickly pick up dry eye. Do you do that? What do you do before surgery?

Trattler: At my center, we use the IOLMaster (Carl Zeiss Meditec) as well as Placido disc topography. A critical step is to evaluate the quality of both of those tests to ascertain whether ocular surface disease is impacting the results. I also use fluorescein stain of the cornea, and I determine tear breakup time. One teaching point is that when you place fluorescein stain on the cornea, if you wait a minute to 2 minutes, you will see much more uptake of fluorescein in people with ocular surface disease as compared to looking just after instillation of the dye.

Stonecipher: What we also learned is what we consider an abnormal tear breakup time may not be the same as what you were taught in medical school.

Cochener: Nobody knows what is a regular breakup time and what can be considered to be a reliable measurement. Quantification of quality is one of the key targets that we have nowadays, and that will take time because we need to validate new tools that could automatically count the tear breakup time and locate the tear rupture area.

Cummings: My optometrists see the patients before I do, and they will make a sketch after the fluorescein exam. They will note the tear breakup time, and they will make a sketch of where the punctate erosions are. Then I see the patient maybe 5 to 10 minutes later, so the fluorescein has been in there a little bit longer. Then I will see for the first time that there is a better uptake and that it is extremely linear, and it is so linear you know it is just coming from exposure at night with the patient sleeping with the eyelids slightly parted. So the timing of the fluorescein exam seems to be important, too.

Kiliç: Pre-existing dry eye disease is a major risk factor for post-LASIK dry eye of higher severity. The TearLab osmolarity system is one of my alternatives. But also, photorefractive surgery induces dry eye by causing increased tear osmolarity and inflammation of the ocular surface with various mechanisms. Even before surgery when all of the diagnostic devices are OK, after surgery, we can observe dry eye. These cases are also trouble for us.

Cochener: I don’t know if you have experience with the RPS (InflammaDry, Rapid Pathogen Screening) — the detection in terms of biomarkers of the metalloproteinase. We all agree that the MMP-9 is not a proper marker. But we are working hard, behind the door in the laboratory, to identify some new proteinases and cytokines that could be notified by the RPS concept. I think that is promising. When we are dealing with dryness, one looks for samples, but most of the time you do not have enough tears. So I think that having this concept is good to be able to do the measurements. I believe deeply that this new option will be useful and easy to perform in the future.

Trattler: Diagnostics are useful for evaluation of patients. Dr. Kiliç, are you using any specific diagnostics in your practices?

Kiliç: In my practice, clinical signs — whether there are any complaints — are considered first. But even when all of the parameters and measurements are OK, there is sometimes dry eye. Dry eyes are associated with minute punctate epithelial erosions of the cornea, usually detected by fluorescein or rose bengal. Sometimes clinical symptoms and diagnosis are not parallel, unfortunately, and after an operation, I observe some surprises. I would of course prefer to treat before surgery.

Riha: The problem I face is that, working in a high-volume private practice, diagnostics have to be fast, effective, and basically easy and cheap. If you have something that costs you more than 100 per patient and takes some time, then it is difficult to implement as a standard.

What I started using recently is the HD Analyzer (Visiometrics), which basically gives you a 20-second period for measuring the patient’s quality of vision. It shows nicely and reproducibly how the tear film impacts the visual quality of this patient.

Diagnosing and grading dry eye is a difficult issue, and we still have not solved it 100%, even on an academic level. We are far away from implementing [point-of-care diagnostics] in everyday high-volume routines, but it is absolutely needed. I hope for progress in the coming years.

Cochener: Don’t you think that the OSI [objective scatter index], the index that provides the optical quality analysis system, is still a problem? It is an indirect effect of the diffusion of light through all the media of the eye, but as soon as you have an unclear crystalline lens or a macula problem, that will also increase the OSI. That means that you need first to make sure that nothing beside the ocular surface can induce scatter.

Riha: That is a good point. I am not talking about the absolute OSI. I am talking about the relative change over time. You might have a dense cataract, but this does not change over the short time of the test. I like the 20-second period that determines blinking rate and the relative change of optical quality. Absolute OSI, obviously, is influenced by many other factors.

Trattler: Dr. Loh, you have a busy cataract practice. How are you diagnosing dry eye before surgery?

Loh: I am in a private practice, and we do not have access to the TearLab osmolarity test. So I mainly base my decision off of patients’ complaints and symptoms. I take a history, and then I use ...

Cochener: Are you using a specific questionnaire?

Loh: No, that is a good point. I actually do not use a questionnaire, partly because of the high volume of our practice and, unfortunately, the limited amount of time we can spend with the patient. Also, I have many patients who speak different languages in our practice so having one questionnaire in English would not help, and some of my patients are more indigent and literacy can be a problem. So I mainly just speak to the patients, understand their symptoms, perform fluorescein testing, look at staining, and then make a decision from there. Of course, I always want to ask about systemic diseases and medications they are using. From that alone I will initiate dry eye treatment. Also, I look at the biomicroscopy. I look at the eyelids, too, paying special attention to the meibomian glands and any blepharitis involved.

Pre-existing dry eye

Trattler: A growing challenge we face as surgeons is that patients coming in for surgery, whether for refractive lens exchange or cataract surgery, often have pre-existing dry eye. The first round of tests (biometry/topography) may not be accurate. For this reason, when I diagnose ocular surface disease, I often start therapy and then bring patients back for repeat testing. For example, patients with ocular surface disease may receive topical steroids twice a day for 2 to 3 weeks. If the ocular surface disease is more advanced, patients may also be placed on topical cyclosporine. Punctal plugs can also play a role when the tear volume is very low. If the patient is already scheduled for surgery, I bring them back for one more visit. It is important to note that many patients will end up with a significant change in both the magnitude and axis of their astigmatism, which can result in changes in the planned IOL power, as well as changes in surgical planning for the degree of astigmatism.

Cochener: People need to be aware of that. IOL power miscalculation, especially astigmatism correction, is related to that when the baseline for calculations do not take into account these ocular surface problems. That is key.

Kiliç: If there is irregular topography, I put in artificial tears before taking topography measurements, and then I repeat measurements. Sometimes there is a big difference in the results even when there is no sign of a dry eye. If I see any difference, then I am more sensitive to be careful with the ocular surface. But, always, I put in a drop and then repeat the measurements.

Loh: Others have said that sometimes putting an artificial tear in right before the test is not as accurate as treating the dry eye for several weeks first because the placement of the tear at that moment can alter the shape of the ocular surface. I have been advised to treat the dry eye first.

Kiliç: In my country, sometimes patients want surgery immediately. We have to be sure about dry eye if we perform surgery with patient pressure immediately because sometimes preoperative dry eye treatment is necessary. If there is no sign of dry eye, we are taking measurements. If we are sure that there is no dry eye, the patient can undergo the operation.

Loh: It is tough in the U.S. as well. Patients want instant gratification and instant surgery. It is hard in this competitive environment if a patient comes to you and you say, “No, we need to treat your dry eye,” which they do not think they have, “for a month or two months.” They may just go to another ophthalmologist. But what I try to emphasize and what I find patients respond to more is if you tell them that treating the dry eye will actually improve their vision. If you say, “Oh, maybe it will help your eyes feel better,” I find they are not as convinced. But once I say, “If we do your surgery the way your eye is now, you probably will need to wear glasses afterward,” or “Your vision won’t be as good,” or, especially if they want a multifocal lens or a toric lens, I will say, “All this money and time you’re spending is not going to be worth it,” then I find them much more encouraged to follow the treatment and be more compliant.

Cochener: As soon as you detect any dry eye and you do the surgery, you can expect some increase in functional symptoms that can drive a patient crazy. However, if you detect dry eye, it does not mean that you will not do the surgery, but you will prepare this risky patient before surgery and may treat him for a longer period after the surgery.

• For more information:
• Béatrice Cochener, MD, PhD, can be reached at Department of Ophthalmology, University of Brest, CHU Morvan-5, Av. Foch, 29609 Brest Cedex, France; email: beatrice.cochener-lamard@chu-brest.fr.
• Arthur B. Cummings, FRCS, can be reached at Wellington Eye Clinic, Suite 36 Beacon Hall, Beacon Court, Sandyford, Dublin, Ireland; email: abc@wellingtoneyeclinic.com.
• Aylin Kiliç, MD, can be reached at Dunyagoz Eye Hospital, Istanbul, Turkey; email: aylinkilicdr@gmail.com.
• Jennifer Loh, MD, can be reached at South Florida Vision Associates, 2900 Cypress Creek Road, Suite 1, Fort Lauderdale, FL 33309; email: jenniferlohmd@gmail.com.
• Wolfgang Riha, MD, can be reached at Sehkraft Augenzentrum Maus, Wolfsstraße 16, 50667 Köln, Germany; email: riha@sehkraft.de.
• Karl G. Stonecipher, MD, can be reached at Laser Defined Vision, 1002 N. Church St., Greensboro, NC 27401; email: stonenc@aol.com.
• William B. Trattler, MD, can be reached at Baptist Medical Arts Building, 8940 N. Kendall Drive, Suite 400-E, Miami, FL 33176; email: wtrattler@gmail.com.

Disclosures: Cochener reports she is a consultant to Abbott Medical Optics, Alcon, Bausch + Lomb, ReVision Optics, Santen and Thea. Cummings reports he is a consultant to Alcon WaveLight and TearLab. Kiliç reports no relevant financial disclosures. Loh reports she is a paid consultant to Allergan, AMO, Bausch + Lomb and TearScience. Riha reports he is a consultant to AcuFocus. Stonecipher reports relevant financial disclosures for Alcon, Allergan, Alphaeon, Bausch + Lomb and Shire. Trattler reports he is a consultant and/or speaker for Abbott Medical Optics, Alcon, Allergan, Oculus and Shire.

One on One with A. John Kanellopoulos, part 1

William B. Trattler, MD: The focus for OSN and this round table was on the impact of dry eye on surgical results. One topic we did not talk about was epithelial mapping. When do you use it, how do you use it, and how do you interpret it?

A. John Kanellopoulos, MD: We have, of course, used the usual history, slit lamp exam, Schirmer’s and tear breakup time as a means to evaluate our post-refractive surgery patients who complain. But it was only when we used epithelial mapping and identified the magnitude and the refractive sequelae of dry eye that all this story lit up for us, illuminating not only how poor our diagnostic tools are, but also our management. We basically have artificial tears, blepharitis management and maybe an anti-inflammatory component of cyclosporine. We have no other tools to address dry eye.

Epithelial mapping has become the single most important tool of every ophthalmology patient we see. If I had to choose one image, besides my clinical exam, for evaluating ophthalmology patients, that would be an OCT side-by-side, eye-by-eye stromal cornea thickness and epithelial map because that gives me all the information I need. It is a screening tool for corneal irregularity and keratoconus. Where I live, almost one out of every 20 patients has keratoconus, so we screen everybody.

At the same time, you get a feel for the epithelium. In clinical reality, this is the second most important anterior segment diagnostic step, besides the autorefraction, that we do. We obtain the anterior segment OCT and get a stromal and epithelial map on every patient, every time they come to the office.

Trattler: Which company do you work with?

Kanellopoulos: We have worked with all three generations of Optovue OCTs, and we are now working with the beta software that gives us a 9-mm map and a 9-mm epithelial map. I think it will be shortly coming into commercial use as well.

Trattler: What about diagnosing dry eye?

Kanellopoulos: It would be an exaggeration to say an ophthalmologist needs this map to diagnose dry eye, but it is an objective way to follow dry eye. The corneal epithelium, we have come to realize, is a homogeneous metric. Any disturbance of epithelium, even if the standard deviation changes by 1 µm, is significant in indicating that something is going on and is manifesting in the surface.

There is correlation between Schirmer’s and tear breakup and a diagnosis of dry eye, but these are crude tests. They are kind of on/off tests at best. And when educating patients, epithelial mapping is a better way to follow progress and show improvement.

Trattler: Patient education and setting expectations are critical for all the new therapies.

Kanellopoulos: Absolutely. It is our blackboard for assessing and conveying any information on any surface irregularity in every patient. It is a more tangible metric.

Trattler: We have two different OCT devices at our center, but they are both versions for imaging the macula. We have not yet added corneal mapping functionality to our devices at our center. Are you using one?

Kanellopoulos: I am using the Oculus Keratograph. It is very helpful. All OCTs will be able to do this; it is just a matter of time before this becomes available in every OCT platform. Spectral-domain OCTs are able to map more accurate detail. In addition to OCT, there are a lot of topographers that are using infrared wavelength to image the lipid layer and the surface, as well as the level of conjunctival inflammation.

Trattler: Something the round table participants talked about was platelet-rich plasma (PRP) therapy. It is available in Europe but not in the U.S. yet. When do you use PRP?

Kanellopoulos: We use it in 100% of the combined topographic-guided PRK cross-linking keratoconus patients (Athens protocol procedures). So by default every patient gets a blood sample spinned, and our lab prepares the PRP for them. It has made a lot of difference. It helps a lot with re-epithelializing and reducing the intense sometimes external disease we would see the first month (slow re-epithelization, surface epithelial white clumps and/or even Salzmann’s nodules sometimes). We selectively use it in patients with severe Sjögren’s disease and patients with transient or permanent limbal stem cell insufficiency. Even in some PRK patients who may not respond optimally, but that is a minority — less than 5%, I would guess. We use it in some trauma patients and chemical injury patients; it is quite common in our office. I think we prescribe it at least once a day.

Trattler: Is it similar to the standard autologous serum?

Kanellopoulos: It is a higher concentration of autologous. I pick a more viscous solution, which is also more lubricating. So besides the platelets being able to play a kinetic role in the healing, there is a biomechanical role as well.

 

A. John Kanellopoulos, MD, director of the LaserVision Clinical and Research Institute in Athens, Greece, and Clinical Professor of Ophthalmology at NYU School of Medicine, can be reached at 115 E. 61st St., New York, NY 10065; email: ajk@brilliantvision.com. Disclosure: Kanellopoulos reports financial disclosures for Alcon, Allergan, Avedro, Optovue and Zeiss.

William B. Trattler, MD, can be reached at Baptist Medical Arts Building, 8940 N. Kendall Drive, Suite 400-E, Miami, FL 33176; email: wtrattler@gmail.com. Disclosure: Trattler reports no relevant financial disclosures.