& Treatment Strategy. for Dry Eye Associated With MGD. A Diagnostic. December Published as a supplement to. INHERENTLY DIFFERENT See how

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1 Published as a supplement to December 2011 A Diagnostic & Treatment Strategy for Dry Eye Associated With MGD INHERENTLY DIFFERENT See how A promotional supplement supported by A Novel Diagnostic and Treatment Strategy for Meibomian a Novartis Gland company Dysfunction 1

2 A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction (MGD) faculty Penny Asbell, MD, is Professor in the Department of Ophthalmology at Mount Sinai School of Medicine and Director of the Cornea Service and Refractive Surgery Center, New York, NY. Mike T. Christensen, OD, PhD, is Associate Director for Optometry and Clinical Research at Alcon Laboratories, Fort Worth, TX. Roy S. Chuck, MD, PhD, is Chair of Ophthalmology and Visual Sciences at Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center, New York, NY. Gary Foulks, MD, is Professor of Ophthalmology and Visual Sciences at the University of Louisville and former director of Cornea/ External Disease service at the University of Louisville Kentucky Lions Eye Center, Louisville, KY. He is also former medical director of the Kentucky Lions Eye Bank and served as assistant dean for clinical trials research. Francis S. Mah, MD, is Associate Professor, Department of Ophthalmology and Pathology, University of Pittsburgh School of Medicine; Medical Director, UPMC Clinical Vision Research Center; Medical Director, The Charles T. Campbell Ophthalmic Microbiology Laboratory; Co-Director, Cornea, External Disease and Refractive Surgery Service; Director, Cornea, External Disease and Refractive Surgery Fellowship, UPMC Eye Center, Pittsburgh, PA. Jerry R. Paugh, OD, PhD, is Professor and Associate Dean for Research at Southern California College of Optometry, Fullerton, CA. Victor L. Perez, MD, is Associate Professor of Ophthalmology at Bascom Palmer Eye Institute, University of Miami, Miami, FL, with a secondary appointment in the Department of Microbiology and Immunology. Everardo Hernández-Quintela, MD, is in the Cornea and Refractive Surgery Services at the Hospital Luis Sánchez Bulnes, Universidad Nacional Autónoma de México, México City, México Cover Image: Getty Images/ Image Work/amanaimagesRF The views and opinions expressed by the participants of this supplement do not necessarily reflect the views and opinions of Ophthalmology Times Europe Alcon SYS:OT:07/11:HC 80346A Is the burgeoning instance of dry eye in the aging population adequately served by existing treatment approaches? Might clinicians benefit from a review of the etiology of blepharitis and additional options now available for its diagnosis and treatment? Recently, an expert panel convened to explore this multifactorial condition and assess the science that may yield symptom relief. Current State of Dry Eye Diagnosis & Treatment Topic: Is the classical three-compartment model (conjunctival cul-de-sac, preocular tear film, tear meniscus) of tear distribution and the three-part composition of the tear film (lipid, aqueous, mucin) still useful for clinicians? How about the distinctions between different forms of dry eye as lipid deficiency, including meibomian gland dysfunction versus aqueous deficiency? How do these distinctions affect the clinical evaluation and management of dry eye? 2 A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction A promotional supplement to Ophthalmology Times Europe

3 Dr. Foulks: We really can t separate three compartments. There is a dynamic distribution of meibum from the cul-de-sac into the tear meniscus and across the tear film with blinking of the lids. As for layers of the tear film, there are multiple interactions: proteins interact with the aqueous, the lipids, the mucins, and so on. There is the glycocalyx associated with the corneal epithelium; then the mucin layer, which has membraneassociated mucins that break off and contribute to a junctional layer with the aqueous layer, which has electrolytes and some proteins; then the lipid layer which then has two segments: one with proteins interacting with lipids within the aqueous layer and the other primarily lipids on the surface of the tear film. Some of the distinctions about the different forms of dry eye are more useful than others. Also, some of them overlap. For example, the lipid profile may not play the same role in posterior blepharitis versus anterior blepharitis. (See sidebar.) Topic: How does MGD fit into the categorization of blepharitis as anterior, posterior or mixed (Figure 1), and how does that factor into the choice of pharmacologic therapy? Dr. Asbell: When we examine patients, there are many who have MGD but not anterior blepharitis. Dr. Foulks: That s why I keep them separate. I m not sure that one leads to the other. There are Meibomian Gland Function: Thumbnail Review & Update McCulley et al have noted that There is growing laboratory and clinical evidence implicating the meibomian glands as playing a critical role in the pathogenesis of various ocular surface disorders such as chronic blepharitis and dry eye. 1 Meibomian glands are large sebaceous glands seen as parallel strands across the central margin of the tarsal plates of the upper and lower eyelids. These glands secrete an oily substance (meibum) composed primarily of lipids and proteins. Meibum is transported through a ductule to enter the tear meniscus at the inner lid border. Meibomian glands are regulated by sex hormones: agonistically by androgens and antagonistically by estrogens. 2 The complex mixture of lipids and proteins that comprises meibum is normally a clear liquid at body temperature, and it passes through the meibomian glands onto the posterior lid margin by secretory pressure and is pulled from the tear meniscus as a thin layer across the preocular tear film during blinking. 3 The lipid components of the meibum are partly water soluble (polar lipids) and partly insoluble (non-polar lipids), whose interactions are not yet well described, although they seem to have different roles in posterior blepharitis. 4,5 These secretions may also be affected by lipases produced by ocular bacteria. 1 In a recent review, Knop et al noted that, although meibomian gland dysfunction is often considered to be synonymous with posterior blepharitis, it typically appears without prominent inflammatory alterations of the lid margin. It is a discrete disease entity, they wrote, and a frequent cause of wetting deficiencies of the ocular surface leading to dry eye disease that deserves increased recognition by clinicians. They recommended inspection of the eyelids and lid margins with eversion to check for gland atrophy. Inspection of the meibomian orifices should include expression by mild mechanical compression of the lid to assess patency of the orifices and the quality of the meibum. 6 A promotional supplement to Ophthalmology Times Europe A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction 3

4 figure 1 Categorization of blepharitis and appearance in physical examination situations where you can argue that it does, but epidemiologic studies show that they occur separately as well. 7 POSTERIOR Anterior Dr. Mah: I agree that there is a group of patients that have both forms, but both are not necessarily from infection. Blepharitis has classically been described as being anterior, posterior, or mixed. Anterior Acute or chronic presentation, can have flare-up; typically bacterial involvement (collarettes, flakes and crusting). Posterior Chronic, can have flareup; most commonly called meibomian gland dysfunction (MGD). Mixed Elements of both anterior and MGD; could be the largest group. Photos courtesy of Kelly Nichols, OD, MPH, PhD, The Ohio State University, College of Optometry. Dr. Chuck: To me, MGD falls into the category of posterior blepharitis. However, it can often be seen as part of a mixed picture. Dr. Paugh: To my personal way of thinking, only anterior blepharitis is a distinct clinical entity, characterized by significant injection of the anterior eyelid margin. Posterior blepharitis and mixed blepharitis are not distinct sub-types. Dr. Foulks: It s possible that inflammation of the anterior lid causes secondary changes of the meibomian gland. However, the debate continues about the role of bacteria in MGD. You can culture bacteria and identify it in anterior blepharitis, but you re hard-pressed to find anything in the literature providing evidence of bacterial presence in the meibomian secretion in patients with anterior blepharitis. McCulley s group has worked for years showing that bacteria do have a place and a role in the pathogenesis of both posterior and anterior blepharitis. 8,9 They have connected MGD with dry eye, 1,10 but I don t know of a study that connects bacterial infection to MGD. When I was a fellow, Stephen Foster used to be constantly expressing the meibomian glands and culturing the secretions looking for staph. He didn t find it. mixed Dr. Paugh: I believe that MGD is characterized by a continuum of clinical severity, with gland secretions often compromised, becoming more viscous and turbid or opaque as the condition worsens. I support the idea of hypersecretory and hyposecretory 4 A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction A promotional supplement to Ophthalmology Times Europe

5 MGD. Hypersecretory MGD, where there is copious oil but poor biochemical composition, is what used to be called by the general term blepharitis, meaning eyelid inflammation. Classic blepharitis was thoroughly studied by McCulley and coworkers from the late 1970s through the early 1980s. 11,12 They noted that 4 of the 6 sub-types they described had meibomian seborrhea as a major sign. 13 Seborrhea is an over-secretion of oil. Conversely, the less inflamed hyposecretory form of MGD that results from blockage of meibomian gland ducts or atrophy of glandular tissue is probably what most clinicians view as MGD, as it is much more common. The recommendation for expression of the glands will increase the actual diagnosis of patients suffering from MGD-related dry eye. Roy S. Chuck, MD, PhD Dr. Foulks: Anti-inflammatory therapy can be useful in posterior blepharitis. However, the present guidelines from the American Academy of Ophthalmology and the American Optometric Association don t reflect that. 14,15 Topic: A new paradigm for dry eye treatment is being suggested under the acronym SET, which stands for: S = Symptoms from patient history Scan for signs in examination E = Express the meibomian glands T = Treat the patient What do you think are the important elements of this approach to dry eye assessment (Figure 1) and management, especially in figure 2 Lipid-deficiency dry eye can be identified by reduced tear film break-up time Figure 2A Lipid-deficiency dry eye can be identified by reduced tear film break-up time. Figure 2B If untreated, dry eye can lead to damage of the corneal epithelium. These tests are widely used in the assessment of dry eye by both optometrists and ophthalmologists. Photos courtesy of Marianne Anderson, OD, Alcon Research, Ltd.. A promotional supplement to Ophthalmology Times Europe A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction 5

6 Meibomian Gland Expression: The Paugh Procedure Physical Setup The subject is seated, with the head resting comfortably at the slit-lamp. The examiner scans along both lower lids, using 10x to 16x magnification. The slit lamp illumination is used at a moderate level (essentially a white beam color). A sterile, wooden-stemmed, cotton-tipped applicator is used to press the lids against the globe right at the margin to express the gland contents. Wood is preferred rather than fiber or paper because it is more rigid. The tip of the applicator will cover approximately 5 glands at a time. The glands are expressed starting from the temporal aspect of the right eye and continuing to the extreme nasal extent. Nasal to temporal expression is undertaken for the left eye. Technique The examiner applies pressure at the tip of the applicator for 5 to 10 seconds, watching for the excreta to emerge through the slit lamp. Often there will be observed a sudden expulsion, akin to a small volcano erupting. Grading & Interpretation The color and viscosity of the excreta are observed. The examiner records a global average or summation of the appearance of the excreta from all glands from each lid. If the excreta are clear, it is helpful to observe the excreta against the relatively darker background of the iris as the excreta becomes invested into the tear film. A 4-point scale is useful, with at least 0.5 unit increments, as follows: Grade 0 Grade 1 Grade 2 Grade 3 = normal, clear oil expressed = opaque, diffusely turbid, normal viscosity = opaque, increased viscosity = inspissated (i.e., like toothpaste) Using this 4-point scale, Grade 1 or higher suggests Meibomian gland dysfunction. Procedure developed by Jerry R. Paugh, OD, PhD 6 A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction A promotional supplement to Ophthalmology Times Europe

7 figure 3 Clinical photographs of Meibomian glands Figure 3A Figure 3B Figure 3C (A) and (B) Partially occluded glands. (C) Gland drop out (atrophy) can be seen in the space circled in blue. Photos courtesy of Justin Webb, OD, Alcon Research, Ltd. light of the role of MGD in dry eye and posterior blepharitis? Dr. Chuck: This paradigm encourages something very basic in the science of medicine: recognition of disease. The recommendation for expression of the glands will increase the actual diagnosis of patients suffering from MGD-related dry eye. I think it is necessary for us to advocate this approach, especially from an educational standpoint. Dry eye is the most prevalent eye disease we see, and those patients with blepharitis make up a major subset. Having a routine paradigm that is easy to remember, sensible and short is key to diagnosis and treatment. Dr. Foulks: Most practitioners just examine the glands at the slit lamp and don t express. You really need to do the expression as part of the examination of all dry eye patients. The number of patients who have evaporative, MGD-related dry eye is very high. It is probably more prevalent than pure aqueousdeficiency dry eye. This has been my clinical impression. Dr. Paugh: If the S.E.T. approach helps the ophthalmic clinician do a better job of diagnosis, then I am all for it. Identifying eyelid signs (the S ) like notching, telangiectasia, orifice metaplasia, and so on is very important. The E for expression of the glands is spot-on. An altered gland secretion (i.e., viscous and increasingly opaque) is the most important indicator of MGD. Examination of the glands by meiboscopy is certainly helpful to identify atrophy, but the technique may be too onerous for the majority of practitioners. I think Steve Pflugfelder wrote one of the best papers ever on clinical assessment of dry eye. 16 He describes two categories of aqueous tear deficiency (ATD): Sjögren s and non-sjögren s, and two categories of MGD: inflammatory and atrophic. It was based on a small sample size, but we have followed that idea since about 2001 in our clinic and found it very useful. Most patients will basically fall into one of those four categories. The one other category I would add is a mixture of ATD and MGD. It s possible that, in some cases, the MGD stems from the inflammation due to ATD, but there are a number of patients that have major signs of both. Then we have the T for treatment. In mild to moderate cases of hyposecretory MGD, it makes sense to undertake warm compresses and eyelid massage to try to revitalize the natural function of the meibomian glands, but it is also useful to supplement the missing oils with a viable external supply. In more severe cases, the combination of eyelid massage, oil supplementation, and systemic tetracycline therapy (doxycycline, minocycline) is necessary. Ocular Examination To Express or Not to Express? Dr. Asbell: If you have a patient with MGD and don t A promotional supplement to Ophthalmology Times Europe A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction 7

8 figure 4 Identifying MGD in the physical examination of the eye by expression of the glands Figure 4A express the gland during the exam, you ll miss it, right? Dr. Perez: Yes, and that s an important point. In addition to looking for meibomian gland atrophy (Figure 3) you have to express the meibomian gland to identify MGD, which epidemiological studies show will be present but not obvious in some of your dry eye patients It s something like a stress test. People can have serious cardiovascular disease that you ll never see until they get on the treadmill. Dr. Mah: It s a good, efficient approach to add gland expression to what we do already. If I were to add one test, I think gland expression is probably the best choice. Dr. Hernández-Quintela: I would like to stress the importance of the epidemiology. One study states: obstructive meibomian gland dysfunction is the most common cause of evaporative dry eye. 22 So, that s something that the general practitioner must know. Next, we need to teach all of our residents and colleagues exactly what we re saying here today. Figure 4B Dr. Asbell: I would recommend expressing the glands in the middle of the lower lid. The upper lid is too hard to get to. Dr. Chuck: There are probably as many ways to express the meibomian glands as there are eye care practitioners. However, at the very least, physical pressure be it via device or finger needs to be applied to the glands. One mistake that people make is that they ll sometimes press on the lid and stop because they don t see anything. You really need to do the old press and pause for 5 or 6 seconds before you start seeing anything coming out (Figure 4). Figure 4C In the top photograph, expression has just been initiated. In the photograph in the middle, meibum is just starting to appear. In the bottom photograph, a yellow, thick meibum appears. This fluid is quite different from the clear, colorless and smooth corn oil look of normal meibum. Photos courtesy of Justin Webb, OD, Alcon Research, Ltd. Dr. Paugh: Gland expression is paramount in making a diagnosis, and I have developed a procedure that I teach to all my students at Southern California College of Optometry and to any practitioners who ask for advice. (See sidebar.) Dr. Foulks: It is important for the clinician not only in evaluating dry eye, but also in any patient with any ocular surface complaints, to carefully examine the meibomian glands and express the glands with a maintained pressure to produce secretions. Without applying pressure, you can t evaluate what 8 A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction A promotional supplement to Ophthalmology Times Europe

9 The formulation facilitates a very rapid and uniform coverage of the ocular surface with comfort upon insertion as well as minimal blur. is going on with the glands. Once you start doing this more often, you might find MGD in patients who have not been complaining about dry eye. MGD is actually quite common, and it is often missed. Mike T. CHRISTEnsen, OD, PhD of Ophthalmology, 14 and similar recommendations are made in the Optometric Clinical Practice Guidelines of the American Optometric Association. 15 Is this what you see in actual practice? Dr. Asbell: I think people do use anti-inflammatories in posterior blepharitis as well as for anterior, or at least, it is considered. Dr. Foulks: That seems to be increasingly true when choosing topical treatment of posterior blepharitis rather than oral doxycycline. I think that the use of anti-inflammatories and antibacterials in both types of blepharitis are now part of the continuum of practice. Dr. Chuck: We use anti-inflammatories for posterior blepharitis as well, and they are very effective. Dr. Mah: I have a question related to that. If you have anesthetized the eye for a Goldman tonometry as part of the normal examination, would that be a good time to do the expression? figure 5 Emulsion Composition of SYStane balance Lubricant Eye Drops Dr. Asbell: It is typical that that s been done by the time you would be ready to do the lid expression. Dr. Hernández-Quintela: I would also recommend not delegating the gland expression to the technician, even if he or she is putting in the anesthetic. The time saved would not be worth the clinical information lost. Treating the Patient Topic: Both lid hygiene and antibiotics (oral or topical) are recommended for both anterior and posterior blepharitis, but anti-inflammatories are only recommended for anterior blepharitis in the Preferred Practice Patterns of the American Academy The SYSTANE BALANCE formulation is different from systane and systane ULTRA Lubricant Eye Drops in the addition of mineral oil and a proprietary anionic phospholipid which are emulsified and combined with the HP-Guar/borate technology used in previous systane products. This new formulation is specifically designed to provide ocular surface protection, 20,21 stabilise the tear film, 20 and supplement meibum secretions with lipid. 19 Illustration courtesy of Alcon Research, Ltd. A promotional supplement to Ophthalmology Times Europe A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction 9

10 Viscosity (cps) Dr. Paugh: In severe cases of MGD-related anterior blepharitis (very rare in our clinical setting) and MGD-related posterior blepharitis (much more common, i.e., cases in which there is greater than grade 3 on a 4-point scale of corneal fluorescein staining), we use anti-inflammatories and systemic tetracycline therapy. Sometimes, all this is still ineffective. Dr. Foulks: In terms of emulsion eye drops available in the UK, we currently have the SYSTANE lubricant eye drop for which there is a new formulation called SYSTANE BALANCE Lubricant Eye Drops. In addition to the propylene glycol, the emulsion composition of figure In vitro rheology of SYStane balance Lubricant Eye Drops 19 ATE ph 7.0 ATE ph 7.8, no sorbitol Shear Rate (1/sec) Viscosity and shear rate change with time after instillation in conjunction with the change in ph as sorbitol is diluted. 19 SYSTANE BALANCE Lubricant Eye Drops has some components that other lubricant eye drops don t. These include HP-Guar/borate, which helps reduce friction and coat the surface of the cornea, as well as an anionic phospholipid to help stabilize the tear film lipid layer. That is something new, and it seems to offer some significant advantages over what we ve had until now. I have had some experience with it, and found it effective in controlling both the signs and symptoms of dry eye in MGD patients. A New Therapeutic Option SYStane balance Lubricant Eye Drops Dr. Christensen: SYSTANE BALANCE Lubricant Eye Drops is a combination of lipids with other compounds homogenized in a process that produces a sub-micron particle emulsion that both remains stable and avoids coalescence (Figure 5). 19,20 This formulation was developed to address dry eye symptoms associated with meibomian gland dysfunction. The components of this formulation have been combined to provide superior ocular surface protection, 20,21 stabilise the tear film, 20 and supplement the natural meibum. 19 In vitro rheology data (Figure 6) simulates the change in viscosity of SYSTANE BALANCE Lubricant Eye Drops after a drop is administered to the eye. Upon instillation in the eye, viscosity decreases as a function of shear rate, which is indicative of rapid mixing or thinning. After several blinks, as ph increases and sorbitol is diluted, there is enhanced viscosity from strengthening of the HP-Guar crosslinking. 19 The blue line represents what would happen after several blinks as you have an equilibration of the ph of the formulation. So, it s formulated at ph 7.0, but we know that, over several blinks, since the tear film is slightly alkaline, you have a slight increase in the ph and you get a dilution of the sorbitol (sorbitol is highly water soluble), enhanced viscosity, and a muco-mimetic layer on the ocular surface. 19 The relevance of this experimental data is that the formulation facilitates a very rapid and uniform coverage of the ocular surface with comfort upon insertion as well as minimal blur. With the combination of the excellent rheology, improvement in TFBUT, and the haze profile, the formulation of SYSTANE BALANCE Lubricant Eye Drops will be a good option for those MGD patients whose needs have not been met. Disclosures Dr. Christensen is employed by, and Drs. Asbell, Chuck, Foulks, Mah, Paugh and Perez are paid consultants for and/or receive research support from, Alcon Laboratories, Inc. Dr. Hernández-Quintela has no relevant disclosures. 10 A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction A promotional supplement to Ophthalmology Times Europe

11 References 1. McCulley JP, Shine WE. The lipid layer of tears: dependent on Meibomian gland function. Exp Eye Res Mar;78(3): Knop E, Knop N, Schirra F. [Meibomian glands. Part I: anatomy, embryology and histology of the Meibomian glands]. Ophthalmologe Oct;106(10): Knop E, Knop N, Schirra F. [Meibomian glands. Part II: physiology, characteristics, distribution and function of Meibomian oil]. Ophthalmologe Oct;106(10): Shine WE, McCulley JP. Meibomianitis: polar lipid abnormalities. Cornea Nov;23(8): Shine WE, McCulley JP. Polar lipids in human Meibomian gland secretions. Curr Eye Res Feb;26(2): Knop E, Knop N, Brewitt H, Pleyer U, Rieck P, Seitz B, Schirra F. [Meibomian glands: part III. Dysfunction - argument for a discrete disease entity and as an important cause of dry eye]. Ophthalmologe Nov;106(11): Lemp MA, Nichols KK. Blepharitis in the United States 2009: a surveybased perspective on prevalence and treatment. Ocul Surf Apr;7(2 Suppl):S1-S Dougherty JM, McCulley JP. Comparative bacteriology of chronic blepharitis. Br J Ophthalmol Aug;68(8): McCulley JP, Shine WE. Changing concepts in the diagnosis and management of blepharitis. Cornea Sep;19(5): Uchiyama E, Aronowicz JD, Butovich IA, McCulley JP. Pattern of vital staining and its correlation with aqueous tear deficiency and Meibomian gland dropout. Eye Contact Lens Jul;33(4): Bowman RW, Dougherty JM, McCulley JP. Chronic blepharitis and dry eyes. Int Ophthalmol Clin. 1987;27(1): McCulley JP, Sciallis GF. Meibomian keratoconjunctivitis. Am J Ophthalmol. 1977;84(6): (Abstract) 13. McCulley JP, Dougherty JM. Blepharitis associated with acne rosacea and seborrheic dermatitis. Int Ophthalmol Clin. 1985;25(1) American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Patterns Committee. Dry Eye Syndrome. 2008: American Academy of Ophthalmology, San Francisco, CA. 15. American Optometric Association Consensus Panel. Care of the Patient with Ocular Surface Disorders: Reference Guide for Clinicians. 2003: St. Louis, MO. 16. Pflugfelder SC, Tseng SC, Sanabria O, Kell H, Garcia CG, Felix C, Feuer W, Reis BL. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea Jan;17(1): Korb DR. Survey of preferred tests for diagnosis of the tear film and dry eye. Cornea Jul;19(4): Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Cornea Dec;27(10): Ketelson HA, Davis J, Meadows D. Characterization of an anionic lipid stabilized ocular emulsion containing HP-Guar. Poster #6250 presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL, May 2-6, Christensen MT, Blackie CA, Korb D et al. An Evaluation of the Performance of a Novel Lubricant Eye Drop. Poster #1009 Presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL, May 2-6, Foulks G, Sindi C, Griffin J. Efficacy Evaluation of a Novel Emulsion-Based Anionic Phospholipid-Containing Artificial Tear in Meibomian Gland Dysfunction Subjects. Poster presentation at the 6th International Conference of the Tear Film & Ocular Surface Society. Florence, Italy, September A promotional supplement to Ophthalmology Times Europe A Diagnostic & Treatment Strategy for Dry Eye Associated With Meibomian Gland Dysfunction 11

12 A new twist for your patients with dry eye associated with MGD SCAN & SEE the unique formulation of Systane Balance SYSTANE BALANCE Lubricant Eye Drops Unique formulation with the LipiTech TM System restores the lipid layer. (1) Stabilizes the natural tear film for extended TFBUT. (2) Decreased dosing from baseline. (3) 1. Ketelson HA, Davis J, Meadows DL. Characterization of an Anionic Lipid Stabilized Ocular Emulsion Containing HP-Guar. E-Abstract 6264, Invest. Ophthalmol. Vis. Sci. 2010;51;E-Abstract Korb D, Blackie C, Meadows D, Christensen M, Tudor M. Evaluation of extended tear stability by two emulsion based artifi cial tears. Presented at the Tear Film and Ocular Surface Society meeting; September 2010; Florence, Italy. 3. Data on file. N=46 Alcon Research, Ltd Novartis AG Date of preparation: July 2011 SYB:OT:07/11 (HC)