Understanding the Prevalence of Ocular Surface Disease in Women

Perspectives from four female experts, who specialize in dry eye and OSD

Highlights from a special event held during ASCRS 2016 in New Orleans 
Organized by PentaVision and moderated by Kendall Donaldson, MD, MS.

#1 Most OSD patients are women, and OSD is costing them.

Dr. Donaldson: Most of the patients in our dry eye clinics are women, for many reasons. First, in the U.S., women make up about 51% of all adults and 56% of all people older than age 65. (1) According to the Beaver Dam Eye Study, women ages 48 to 91 are nearly 50% more likely than men to experience dry eye syndrome. (2) Women also make up 55% of the Medicare patient population and they live significantly longer than men. (3) In my practice, these differences translate into about 53% of my patients being women. Do you find that the bulk of your patients are women as well?

Cynthia Matossian, MD, FACS: Not only are the bulk of these patients women, but OSD directly impacts their daily lives. It impacts their reading speed and their productivity at work. This is a real disease, not just a nuisance. I’m so happy that OSD is finally getting its time on stage, so to speak, because for years it was viewed as a nuisance. Now, eyecare providers are paying attention and understanding that OSD poses a serious issue in the lives of their patients.

Marguerite McDonald, MD, FACS: We published a paper in Ocular Surface (4 ) about the international economic burden of dry eye disease. In the United States alone, the indirect costs are over $55 billion. Direct costs to the American healthcare system are $3.84 billion, on par with Asia and Europe. The costs include absenteeism and low work productivity. People are at work, but they aren’t functioning at full capacity because they’re struggling with their vision and comfort. Many of these people are paying hundreds of dollars per year to alleviate dry eye symptoms, and those with severe cases are spending thousands. That’s a serious problem with serious economic consequences. 

#2 Women’s hormonal changes worsen OSD. 

Dr. Donaldson: There have been some very interesting studies on hormonal changes with aging. I think we see a great deal of OSD related to these changes in women. 

Dr. McDonald: One of the hormonal changes that influences OSD is testosterone. Men start off with far more testosterone than women, but women do have some from the adrenal gland. Both sexes lose testosterone as they age, but only women’s testosterone levels often fall below the critical amount required for a healthy lacrimal gland. That reduces women’s aqueous tears.

Dr. Matossian: Because of a decrease in testosterone due to age, I prescribe off-label, compounded testosterone eye drops for both my female and male patients. Since more female patients suffer from dry eye, more of my women patients receive this prescription. They use the testosterone 0.05% ophthalmic drops two to four times a day. 

Dr. McDonald: And usually, by the time patients get testosterone eye drops, they’ve had plugs, so there is virtually no systemic absorption of the drops. As the nasolacrimal drainage system is occluded by the punctal plugs, there is no pathway for the testosterone drops to make contact with the nasopharyngeal mucosa. Another hormonal influence is hormone replacement therapy (HRT). The Women’s Health Study followed more than 25,000 women for a decade and concluded that HRT actually makes dry eye a little bit worse. (5) This isn’t conclusive, and we need more research, but it looks like HRT is not the answer.

Dr. Donaldson: The use of HRT also has been debated because of the associated risks. When I discuss HRT with patients, I often refer them back to their gynecologist to have a discussion about cancer and other risks, so they can weigh those risks against the benefits of HRT. But compounded testosterone drops may be worth a try in refractory patients because they are topical and thus avoid the systemic side effects associated with HRT. 

#3 Women are more susceptible to auto- immune diseases linked to OSD.

Dr. Donaldson: Certain autoimmune diseases increase the risk for OSD, and these diseases are more prevalent in women. How do these diseases affect our female patients?

Alice T. Epitropoulos, MD, FACS: Women are more susceptible to developing systemic autoimmune diseases that often are related to dry eye disease. These include Sjögren’s syndrome, rheumatoid arthritis, and lupus, as well as dermatological conditions, such as psoriasis and rosacea. One in 10 dry eye patients has Sjögren’s. What’s more, Sjögren’s is now thought to be much more prevalent than we thought, affecting more than 4 million Americans, 90% of whom are women. (6) Until recently, Sjögren’s was very difficult to diagnose because the traditional antibodies are non-specific. Auto- antibodies directed against Ro/SSA and La/SSB autoantigens are positive in only 40% to 50% of patients. (7,8) Now we have the Sjö test (Bausch + Lomb), which shows the four traditional biomarkers and three novel biomarkers. It allows for improved sensitivity and specificity, which means earlier diagnosis and treatment. 

Dr. Donaldson: Many times, when the SSA and SSB antibody tests were negative, patients were offered a biopsy, but no one wants a biopsy of the mucosa. The Sjö test can provide answers with a much less invasive blood test.

Dr. Epitropoulos: That’s right. We can also outsource the test so it doesn’t interfere with patient flow in the office. 

Dr. McDonald: After we had been using the Sjö test for a year, we looked at our results. In one office, 66% of patients tested positive. I realized that I should be ordering the test more often because obviously I was missing people, and the diagnosis really helped them.

Dr. Matossian: I’ve noticed when we’ve ordered the Sjö test in our office, we are able to diagnose Sjögren’s earlier in the disease process. Traditional biomarkers are positive as the disease progresses. Patients are testing positive for these novel biomarkers earlier, with some overlap right in the middle. Because Sjögren’s is a progressive disease, this is exciting information.

Dr. Donaldson: I think patients appreciate the diagnosis. They tell us that they feel validated. They know that there is a concrete reason for their frustrating symptoms, which is satisfying. It is a relief to know why they’re feeling the way they are.

Dr. Matossian: The feeling of validation is very strong. These women have gone from doctor to doctor, to surgeon to psychiatrist to GI specialist to gynecologist because they are desperate. They are suffering all over their bodies, and no one has been able to pinpoint a diagnosis. Now we have access to the Sjö test. We order a test in the laboratory, and our patients finally get a definitive answer.

Dr. McDonald: Our technicians report negative results to the patients, but when the results are positive, I make the call. I tell them, “This is not cancer. It won’t shorten your life. However, it does have a huge impact on quality of life, and it elevates your risk for non-Hodgkin’s lymphoma, which is cancer.” Five to 10% of Sjogren’s patients will develop this cancer. It is quite curable if caught early, but less so if caught late, so the internist should screen you on a regular basis for non-Hodgkin’s lymphoma. We mail a copy of the positive test results to patients and explain that they need to distribute the results to everyone on their healthcare team, including their internists — particularly for cancer screening purposes — and their dentists, who need to watch for dry mouth, caries, and halitosis. 

Dr. Epitropoulos: Another autoimmune disease affecting women is thyroid eye disease, or Graves’ disease. Although it can affect both men and women, thyroid eye disease is six times more common in women. (9) It usually begins when people are in their 20s and 30s and worsens with age. Dry eye disease can be multifactorial in these patients. It may be autoimmune from Graves’ disease or mechanical from exophthalmos, lid retraction, or incomplete blink, resulting in exposure keratopathy. Lacrimal gland dysfunction also can contribute to aqueous-deficient dry eye. Rheumatoid arthritis is another systemic disease that affects women two to three times more than men. (10) And even though more than 70% of patients with rheumatoid arthritis suffer from dry eye disease, only 12% are being treated. (11,12) Dry eye disease is clearly prevalent, underdiagnosed, and undertreated in patients with these conditions. We need to actively evaluate and treat these patients with ocular surface disease. Communication and referral to specialists including dermatologists, rheumatologists, and ophthalmologists for these systemic conditions can help to facilitate earlier access to appropriate treatment.

Dr. Donaldson: Many of these diseases come in clusters. Patients might have not only rheumatoid arthritis or Graves’, but possibly both, and other autoimmune or inflammatory conditions as well. It’s very important that we have relationships with rheumatologists and general practitioners for these cases. We have to set referral patterns and not just work in a vacuum as ophthalmologists.

Dr. Matossian: Educating the patient’s primary doctor is important as well. It’s shocking how often internal medicine and family practice physicians don’t understand the connection between rheumatoid arthritis, thyroid disease, and dry eye disease.

Dr. Donaldson: I’d add dermatologists to that mix for our patients with rosacea. I think patients feel more comfortable when they know we work in collaboration with their dermatologist or rheumatologist. Patients feel reassured and it creates a more effective and integrated care system. 

#4 Women have more elective procedures on their eyes.

Dr. Donaldson: In addition to the physiologic changes and medical conditions that may lead to OSD in women, women also increase their risk for OSD by having more elective ophthalmic procedures than men. What are some examples in your practices? 

Dr. McDonald: We have known for years that LASIK can exacerbate dry eye, and we’ve gotten smarter about diagnosing dry eye in advance and controlling it before surgery. Surgical advances have reduced dry eye as well. We make smaller, thinner, beautifully centered flaps. We know that the exact location of the hinge is important so we don’t cut the trunk nerves at both 3 and 9 o’clock. In the past, thicker, larger flaps with small hinges required cutting all the nerve trunks, so LASIK could cause dry eye that lasted — in rare cases — up to 2 years. Today, it’s quite rare to find a case of LASIK-induced dry eye that lasts that long. With PRK, patients might have dry eye for a few weeks after surgery, at most. The larger problem is patients who have dry eye before LASIK. They often seek out the procedure because they can no longer comfortably wear contact lenses, which is a red flag for the presence of dry eye.

Dr. Matossian: More women than men have cosmetic procedures, such as eyelid surgery. If too much skin is removed during blepharoplasty or if the eyelid skin heals in an unpredictable way, patients can develop a gap between the upper and lower lids — the lids don’t come together tightly anymore — this may even occur years after successful surgery. We see two issues related to this problem. First, when the upper and lower lids don’t come together for a healthy blink, the meibomian glands don’t release oil to create the lipid layer on the tear surface. That leads to meibomian gland dysfunction and OSD. Second, if too much skin is taken, the gap causes exposure keratopathy. The cornea is exposed, so more tears evaporate. If a plastic surgeon doesn’t understand the causes of dry eye disease and doesn’t look into the patient’s other risk factors, such as previous LASIK, then these problems are more likely to occur. An oculoplastic surgeon may be more attuned to coexisting conditions related to OSD, including previous LASIK, thyroid disease, and other factors. When possible, it is important to help patients select a cosmetic surgeon.

Dr. Donaldson: The interesting thing is that we’re talking about the same group of patients. The same people who pursue LASIK also pursue lid procedures — sometimes multiple lid procedures. They are in tune with cosmesis. They try not to reveal that they’ve had these procedures. I’ve had both blepharoplasty patients and laser vision patients who don’t want to admit their surgical history. If patients had eyelid surgery 15 years ago, they think it doesn’t count any longer. They think that successful plastic surgery 15 years ago doesn’t affect their eyes today. But as the skin’s elasticity changes and the lower lids droop, OSD symptoms emerge. We tend to see an exposure pattern that makes patients become more symptomatic, even 15 years after surgery. Do you find you need to explain these risks to blepharoplasty patients?

Dr. Epitropoulos: I recently treated a patient who was miserable with dry eye. We did everything from medications to in-office procedures, and finally got the dry eye under control. Then she told me she was planning to have blepharoplasty. I had to warn her that this procedure might exacerbate her dry eye disease. She had no idea that dry eye was a possible side effect. That crucial piece of information seems to be missing from the plastic surgeon’s patient education.

#5 Cosmetics contribute to women’s OSD — and the latest trends are troubling. 

Dr. Donaldson: Cosmetics are a contributing factor to certain eye health problems, and, obviously, women use them much more than men. What makeup-related OSD problems do you see in your practice?

Dr. Matossian: Eye makeup is nothing new — both women and men have used it in various forms for centuries. Today, we are learning the costs of beautifying our eyes, and while mascara and other common products have their drawbacks, new trends are particularly concerning. Right now, eyelash extensions have reached an all-time high in popularity. These are synthetic lashes individually glued onto natural lashes. The glues are formaldehyde-based and often contain latex. Most patients have no idea that this is the case. Moreover, most extensions are applied in nail and hair salons where people aren’t adequately trained in eye hygiene. The result is an increased risk of blepharitis, chemical keratitis, and conjunctivitis from this procedure. False eyelashes are very popular now as well. People glue the strip of false eyelashes onto the edge of the eyelid, where the weight of the false lashes or the applied fixatives can cause problems on the lid margin. In addition, a study by the Georgia Tech Engineering Department found that the longer, Kim Kardashian-style lashes actually cause air to funnel down to the ocular surface, along with pollution and particulate matter in the environment. (13) Eyelash adornments, such as beads and crystals, have become a trend as well. They are attached with a very fine thread wrapped around the eyelashes. These different manipulations of the lashes cause something called traction alopecia. The weight of the ornaments attached to eyelashes damages the lashes and lids, causing lashes to fall out. The lashes are also pulled out during removal of the embellishments or the false lashes. The weight of the ornaments attached to eyelashes damages the lashes and lids, causing lashes to fall out. The lashes are also pulled out during removal of the embellishments or the false lashes.

Dr. Donaldson: Do you see many patients with permanent eyeliner in your practice?

Dr. Matossian: Permanent eyeliner, which is actually a tattoo applied in very small strokes along the upper and sometimes lower lids, is very common in Korea and Japan. The concern is that permanent eyeliner can cause meibomian gland dropout. (14,15)

Dr. Donaldson: I wasn’t familiar with some of these cosmetic practices, but when I asked my scrub techs if they had heard of them, they had. In fact, a few of them go every few weeks for eyelash extensions. Apparently, it has become very popular in recent years. Another cosmetic procedure we’ve seen in the news is conjunctival whitening, which is a bit controversial.

Dr. Matossian: People want to look youthful, awake, and alert, so they want their eyes to look whiter and less pink or red. As a result, they’re resorting to conjunctival whitening procedures. The whitening process is done with anti-metabolites, such as mitomycin C. In some cases, physicians have made a small incision into the conjunctiva, placed white tattoo ink in the sub-conjunctival space, and spread it to create a whiter appearance. These are very, very controversial procedures with a very high risk of complications. (16,17) The AAO does not condone conjunctival whitening.

Dr. Donaldson: Another cosmetic challenge to the ocular surface is the cosmetic contact lens. Real contact lenses can cause or exacerbate OSD, but exotic cosmetic lenses pose a particular threat because, often, they’re not fit properly by trained eyecare providers. Previously available at the mall or other random shops, access to these lenses — at least in the United States — is now better controlled. 

#6 Women are still underdiagnosed and doctor-shopping for answers.

Dr. Donaldson: Do you find that women with OSD have taken a lengthy route to diagnosis?

Dr. Epitropoulos: In my practice, the average patient with moderate to advanced dry eye has seen eight or nine eyecare practitioners. In fact, it’s the number one reason they left their previous eyecare practitioner; they didn’t have a therapeutic relationship. When we finally diagnose them, make that connection, and really educate patients about the disease, it goes a long way.

Dr. McDonald: I did a Medline search for the association between dry eye and depression. More than 80 published papers in the peer-reviewed literature link those two diseases. 

Dr. Donaldson: As physicians, we don’t always have time to spend with patients, which is probably why they see eight or nine doctors and get so frustrated. They just keep doctor-shopping. But, to have a dry eye center of excellence, you have to have someone — a physician or staff member — who truly loves to build relationships with patients. Fortunately, I have a technician who loves developing relationships with dry eye patients. She connects with them and enjoys spending the time, so we allow her longer time slots. She might perform a treatment or just talk and be supportive. Patients love it. They don’t even care if they see me — they want to come back to see her!

Dr. Matossian: When patients have support and hope, and they hear that there are treatment options that can help, it means the world to them. Again, they’ve been going from doctor to doctor. Nobody has believed in them. To find someone who listens to them and understands is an enormous relief. They become your best advocates, and they refer more patients to you.

Dr. Epitropoulos: It’s a long-term commitment, too. I tell my patients, “I won’t give up if you don’t give up.” They have to know we’ll stick with them until they find relief. 

#7 With a therapeutic relationship, women can get relief from chronic OSD. 

Dr. Donaldson: Dry eye and related OSD are chronic conditions and carry many of the other issues associated with chronic disease. Successful control requires a therapeutic relationship between patients and physicians.

Dr. McDonald: All of us on this panel have a dry eye center of excellence. The longer the dry eye center is open, the more desperate dry eye patients we attract, and we develop many therapeutic relationships with these patients. It’s a long-term situation. They come in with newspaper or magazine clippings or they email us: “Did you read this? Do you think it would help me?” I have three people who come once a week and many who come once a month. They are mostly middle-aged women, but the patients are trending younger as the face of dry eye changes due to the increased use of digital devices. These women are suffering. They need to know that we understand, we take OSD seriously, and we’re on their team. This is very different from, say, managing someone with glaucoma. That patient has to be convinced to use her drops because she doesn’t have any discomfort. OSD patients are chronically uncomfortable and kept from the activities they enjoy, so the relationship is very different.

Dr. Donaldson: Once, when I was preparing to give a lecture on dry eye, I went on some of the chat sites for dry eye patients. Several of them were on disability for dry eye. People were discussing suicide. This can be an incapacitating condition, and sometimes people feel helpless and hopeless, so they just give up. It places an even greater responsibility on us to make a long-term commitment to their care.  

#8 With greater awareness in the medical community, women will find the help they need.

Dr. Donaldson: The purpose of this discussion is to spread awareness of the prevalence of OSD among women, as well as the unique health factors that influence their disease. As physicians and our clinical teams learn more, we hope that will translate into more physicians — and practices — diagnosing and treating these patients. The work is both challenging and rewarding. We also need to raise awareness among patients. Many times, I’ve had patients start talking in my waiting room and realize, “Wow! This woman’s eyes are burning, red, and irritated and she can’t work. She has the same problem I do!” The diagnosis is completely unfamiliar to many people. It is up to us spread the word, because dry eye can be incapacitating and life-altering. It also helps patients to know that other people are experiencing what they’re experiencing, so any dry eye center of excellence can benefit from a support group. It’s another component of the supportive, long-term relationship and care that we need to provide to ensure that patients are getting the help they need for this chronic disease. ■

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Dr. Donaldson: In the last 5 years or so, our profession has paid a great deal more attention to the ocular surface. When I think back to my years in residency, it wasn’t something we talked about. In fact, we virtually ignored dry eye. We didn’t consider dry eye to be part of a patient’s diagnosis, and we usually moved on to address the patient’s other complaints. Now, with a better understanding of the role of the ocular surface and new diagnostic technologies and treatment strategies at our disposal, we’re looking much more closely at the ocular surface.

Tear Osmolarity.

Dr. Donaldson: One tool at our disposal is osmolarity testing. What is your experience with this modality?

Dr. McDonald: Hyperosmolarity is the central pathophysiological pathway by which dry eye damages the ocular surface and leads to apoptosis, or programmed cell death, and the downward spiral we know so well. This concept and tear osmolarity testing are key to understanding dry eye — to diagnosing it and to monitoring response to treatment.

Dr. Matossian: I agree. We look not only at the tear osmolarity number for each eye, but also at the inter-ocular difference. Patients like tracking their numbers. We write their results on a business card-sized form and give it to them. This way, they’re able to follow the trend in their numbers over time and come to understand whether their treatment is working.

Dr. McDonald: I explain to patients, “If you’re normal, you have plenty of reserves. Your score is low and you have the same tear osmolarity score almost every day, whether you had a quiet day or took a Claritin or had a glass of wine or sat on the front of a speedboat on the Fourth of July. But if you have dry eye, your score is higher, and you have no reserve, so there’s huge variability from one moment to the next as you encounter these physiological challenges.” People used to say, “Ten minutes ago it was 327. Now, it’s 296. It’s a crummy test.” No, it’s a crummy disease. That’s really how much the osmolarity is fluctuating. This test has won all sorts of awards for precision and repeatability in test solutions, so we can be sure that this variability is, in fact, exactly what’s going on. And that’s why, from moment to moment, dry eye patients can have vision problems. They’re driving along, reading a sign, and suddenly they can’t read it. This is a real phenomenon.

Dr. Donaldson: That’s a great point. Tear osmolarity has great variability, and we see that variability in the test. When it first came out, I think some practitioners didn’t know how to interpret the results. They saw the variability and thought the test wasn’t working. But variability is a characteristic of the disease. We can’t interpret the test results in a bubble — we need to take the whole picture into account. Dr. McDonald: It’s a sensitive test, too. If eyes are more than 8 milliosmoles different from each other, even if they are in the normal range, it is a sign of tear film instability, and the patient has dry eye.

MMP-9 Testing

Dr. Donaldson: Is anyone using MMP-9 as part of their diagnostic testing?

Dr. Matossian: We test for MMP-9, which stands for matrix metalloproteinase 9, a biomarker for inflammation. It’s a very simple test to perform. In fact, my technicians handle it. The key is that they have to perform the test before or 2 hours after any drops have been instilled in the eye. The test looks a bit like a pregnancy test. Technicians dab the tip on the conjunctiva, then stop and ask the patient to blink. This process is continued along the entire length of the lower eyelid. Once activated, it takes approximately 10 minutes for the result. If a red line appears, then the test is positive for MMP-9, which means there is inflammation. Even a faint red line is considered a positive test. I turn up the lights in the exam room and hold a muscle light toward the display window so the patient can see the red or reddish line. I have them hold the test so they feel more engaged in their own test results. Everyone understands a positive test, and when patients see it, they feel prepared for a more aggressive treatment program. The other way I use this test is to check if patients are compliant with their use of cyclosporine (Restasis, Allergan). If they’re using cyclosporine BID, this test should be negative. So, if patients assure you that they’re using Restasis, but their osmolarity numbers don’t look great and their symptoms aren’t improving, you can use this test to check compliance. When I find that it’s positive, we have another discussion. “Are you really using the cyclosporine twice a day as you’re supposed to?” That’s when the truth comes out. “Oh, well, I’ve forgotten it,” or, “I use it occasionally,” then we take the opportunity to re-educate the patient about cyclosporine. We stress that cyclosporine cannot be used on an as-needed basis. They have to adhere to the prescribed dosing instructions. 

Dr. Donaldson: Sometimes, if a patient has a positive MMP-9 test while taking cyclosporine, I supplement it with a steroid or serum tears. I move up to the next level of topical treatment.

Dr. McDonald: I also use the MMP-9 test to differentiate dry eye from other inflammatory conditions. MMP-9 is a non-specific marker for inflammation. If a patient is positive for MMP-9 but has normal osmolarity, that person doesn’t have dry eye, but some other condition is inflaming the eye. I tell myself that I must have missed something. I go back and look again to find signs of allergic conjunctivitis, epithelial basement membrane dystrophy, conjunctival chalasis, or another inflammatory problem.

Dr. Epitropoulos: The use of point-of-care testing, such as MMP-9 or tear osmolarity, underscores how important it is that we establish protocols for dry eye testing in our practices. We can’t use these point-of-care tests to analyze the tears once patients have had drops or lights in their eyes, so we need to test early in the visit. That begins with a validated dry eye questionnaire as patients walk in the door. If they’re symptomatic, then we empower our technicians to automatically test for tear osmolarity and MMP-9. We may be able to bill for the test — if we have that protocol in place and the patient has symptoms or signs.

Dr. Donaldson: Our protocol is similar. Patients complete the Ocular Surface Disease Index (OSDI) questionnaire, and, if they score high enough, they undergo MMP-9 testing. By the time I see the patient, I already know what the test revealed about the presence of inflammation. Having that in place saves a great deal of time. 

Meibography

Dr. Donaldson: How about meibography? Are we all using that as well?

Dr. Epitropoulos: We know that 86% of our dry eye patients have meibomian gland dysfunction (MGD). (1) It’s important to evaluate for this disease by examining the lids and lashes as part of every routine ophthalmic evaluation. I perform meibography on many of my patients who are symptomatic, although I know that means I’m missing some cases in patients who are asymptomatic. Meibography is an excellent tool to identify this disease, and can be performed after drops have been instilled. We can actually educate our patients, show them what their glands look like compared with healthy glands, and convey the message that this is a progressive disease. If it’s not treated, it can cause glandular atrophy and loss of function. There are two meibography units on the market: The Keratograph 5M (Oculus) and the LipiView II (TearScience). I use the LipiView II, which analyzes the lipid layer, records the number of partial or complete blinks, and also obtains high-definition images of the meibomian glands.

Dr. McDonald: Both the Keratograph 5M and the LipiView II overlap in the area of meibography. The Keratograph 5M offers additional tests to help diagnose and evaluate dry eye. But there’s no way to overstate the importance of showing that meibography picture to the patient. It can shock patients into compliance. And if I’m recommending that the patient undergo a thermal pulsation treatment, such as LipiFlow (TearScience), I say, “You know, when these last few glands are gone, they’re gone. They produce a critical component of the tear film. We don’t think they can be resuscitated, and you’ve already lost 80% of them.” Meibography is an incredibly effective tool.

Dr. Donaldson: Patients really like to see the disease. It induces compliance when they can picture what’s going on, whether they see it in meibography images or even slit lamp photos. It’s extremely effective to show them Demodex crawling on their lashes — they’re instantly compliant with their treatment regimen and their follow-up appointments (hoping to see eradication of the mites that previously inhabited their lashes). The combination of diagnostic data and imaging techniques helps us learn what we need to know and it also helps patients visualize and understand what’s causing their symptoms, making them more compliant with treatment.

Dr. Epitropoulos: I want to point out that in addition to the diagnostic testing we’ve discussed for patients with dry eye complaints, there is the issue of asymptomatic patients. A prevalence study showed that 47% of patients diagnosed with dry eye are asymptomatic. (2) We should look for this disease in all of our patients and screen every surgical patient as well. Dr. Donaldson: I started doing that a few months ago. Just incorporating OSDI, tear osmolarity, and MMP-9 testing for all of our preoperative patients has made a huge difference for us. We’re doing our best to identify at-risk patients before surgery. If we have an unhappy patient after surgery, we can re-address the measurements and treatment we initiated before surgery. Patients reflect back on the fact that we have been paying attention to this problem throughout the surgical process (beginning before their procedure). ■

References

1. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012;31(5):472-478.

2. McDonald MB. Prevalence of dry-eye symptoms versus dry-eye disease in general and refractive surgery populations. Paper presented during the annual meeting of the American Society of Cataract and Refractive Surgery; April 2014; Boston, MA.

Dr. Donaldson: Just as we’ve witnessed the development of new diagnostic technologies for dry eye, we’ve also seen new medications and therapies that allow us to bring even difficult cases under control so patients can lead better lives. Some therapies are in use already, and many more are in the pipeline. 

From the Dependable to the Exciting

Dr. Donaldson: If MMP-9 testing is positive, most of my patients begin treatment with a combination of cyclo- sporine (Restasis, Allergan) and loteprednol (Lotemax, Bausch + Lomb). I’m instituting cyclosporine much earlier than I did a few years ago in an effort to decrease inflammation before it causes long-term tissue damage on the ocular surface. The goal is to break the cycle of inflammation and worsening dry eye, so treating preemptively instead of telling everyone to use artificial tears until late in the disease course is a more effective approach. I’m also pleased that we now have many exciting treatments in the pipeline for dry eye, and some are close to reaching the market. We may be able to try some innovative new medications in the near future, including Lifitegrast (Shire) for the treatment of signs and symptoms of dry eye disease in adults. Another dry eye treatment in the pipeline is the Oculeve Intranasal Tear Neurostimulator (Allergan), which is a non-invasive nasal device designed to increase tear production in patients with dry eye disease. There are least 10 other drugs in the pipeline for dry eye. It’s very exciting to follow their progress and envision all of the new options for our patients in the future. We’ll have more help for patients who have been struggling for a long time. While we’re making big strides in understanding and diagnosing dry eye, our arsenal of treatments is moving ahead at a swift pace as well.

Prokera Amniotic Membranes

Dr. Donaldson: We have many new treatment modalities. One is the use of amniotic membranes such as Prokera (Bio-Tissue). How is it working for your patients?

Dr. McDonald: On an average day, I put in two to four Prokera amniotic membranes. It’s for desperate dry eye patients and it works beautifully. Prokera is a ring of polymethyl methacrylate with amniotic membrane suspended across the center. You insert it and leave it on the eye for 5 to 7 days. Usually we do one eye at a time. I’ve found that most patients get weeks or months of relief. Once in a while, I get a patient who is very dry with 4 + filaments, and I have to put in the amniotic membranes again and again — two or three sets in a row — to make the patient feel comfortable for a few months. I was taught that I should splint the lid with tape when using Prokera, but I’ve never had to tape any of my patients and it stays in. Patients usually prefer to forgo the tape.

Dr. Donaldson: I tape everybody. I joke with my patients that it makes quite a fashion statement. I basically use a half-width piece of plastic medical tape that fits lengthwise over the upper lid to create a tape tarsorrhaphy. It’s actually minimally noticeable and reasonably acceptable aesthetically. This limits upper lid excursion so that the patient blinks halfway and there is less rubbing over the surface of the Prokera ring. The thinner Prokera Slim has been a huge advance in comfort, as well. I really haven’t had a patient complain of discomfort with Prokera since I’ve been using the Prokera Slim in combination with a tape tarsorraphy.

Dr. McDonald: Bio-Tissue just came out with the Prokera Slim Clear. It has a 6-mm hole in the center, over the visual axis. It is designed so that the eye can see fairly normally. There is a little less amniotic membrane on the surface of the eye, but it is much more tolerable — especially for people who are trying to work. I’m still doing one at a time with the new design, but I’m planning to see if it’s possible to send people to work with two of the Prokera Slim Clears in place.

Thermal Massage Therapy

Dr. Donaldson: We now have several different ways to apply heat and massage to the eyelids to express the meibomian glands and improve the tear film. In our clinic, we’ve had great results with MiBoFlo ThermoFlo (MiBo) and LipiFlow (TearScience). Are you seeing good results from thermal pulsation therapy?

Dr. McDonald: I started to use BlephEx (RySurg) right before performing a LipiFlow (TearScience) treatment; that really helps express all of the altered meibum. This “one-two punch” works well because once we’ve used the BlephEx to remove that thin fibrovascular membrane — an almost invisible layer that’s closing off the meibomian gland orifices — we’re able to get even better results from LipiFlow.

Dr. Epitropoulos: Conventional options, such as warm compresses and artificial tears, are very good supplemental treatments, but they aren’t therapeutic because they don’t address meibomian gland obstruction. Once I’ve addressed the meibomian glands using LipiFlow, not only does the patient get relief from dry eye, but supplemental treatments have a better chance of working as well. LipiFlow is becoming one of the treatments of choice when there is evidence of meibomian gland dysfunction. Data show that if we can get to these glands early, they will respond better than if we wait until the glands are atrophied and non-functional. According to TearScience, during FDA clinical trials for LipiFlow, 80% of patients noticed a symptomatic improvement from dry eye, and the effect lasted for 9 to 15 months. I also tell patients that about 20% don’t notice any improvement in their symptoms, but if we can address the meibomian gland obstruction, I think we’re still helping to prevent progressive damage.

Dr. McDonald: To all my patients, I say, “It’s a slow miracle. It does work. You will get a little bit better every day, but it takes 6 months to reach maximum benefit; you will hold the benefit for an average of a year, with a range of 6 to 36 months (though almost everyone gets at least a year of benefit).” I have them come back 3 months after LipiFlow, and inevitably we see a better tear osmolarity score and a negative MMP-9 test. That concrete evidence shows patients that it was worth them spending out of pocket for a procedure not covered by their insurance. It really enhances their perceived value of the treatment. And by the time they come back 6 months after the treatment, they feel the improvement.

Dr. Donaldson: These therapies are making a profound difference for people. One of my patients made a video about how our Ocular Surface Center made life so much more comfortable for him. After 15 years of suffering with dry eye, finally, in our practice, the ocular surface staff listened and understood. LipiFlow and MiBoFlo ThermoFlo improved the disease and his symptoms dramatically. These therapies are helping people with a frustrating chronic disease they previously thought they’d have to struggle with for life. Intense

Pulsed Light Therapy

Dr. Donaldson: Intense Pulsed Light (IPL) therapy is a newer treatment for dry eye. We’ve adapted it from dermatologists, who noticed that dry eye sometimes improved after rosacea patients were treated with IPL. What has been your experience with IPL?

Dr. Matossian: I have been using IPL for many years. It works very well. We put a bib on our patients that we call “the lobster bib,” then we apply lidocaine gel across the cheeks. Next, I spread a copious layer of ultrasound gel from ear to ear and cover the patient’s eyes with protective goggles. Using a handheld device, I proceed with the IPL from tragus to tragus to close off the abnormal telangiectatic blood vessels that are leaking pro-inflammatory mediators and strangling the meibomian glands. By killing those off, we improve the health of the meibomian glands. Immediately after treatment, I manually express the meibum, moving from the lateral area of the lower lid to the inner canthus. With a cotton-tipped applicator and my thumb, I work all the meibomian glands; I can see what’s coming out. I comment on the color, the consistency, and the amount. Over time, qualitative improvement of the meibum is clearly visible.

Dr. Donaldson: How many treatments do you typically need to achieve a good response?

Dr. Matossian: I start with a series of four single treatments every 4 to 5 weeks. Thereafter, it’s one treatment about every 6 months for maintenance. IPL is an out-ofpocket procedure.

Dr. Donaldson: It sounds like it works very well, and it’s exciting to think of all the therapies we’re employing for dry eye patients. This wasn’t happening a decade ago. It’s rewarding to treat people who have been suffering without relief, sometimes for years. ■