Approaches to the Treatment of Dry Eye Disease by MediConcept

VOLUME 2

Approaches to the Treatment of Dry Eye Disease from the optometric and ophthalmic perspectives

Contributors Richard Maharaj OD Yvon RhĂŠaume OD Steve Arshinoff MD Sheldon Herzig MD

CRO

Clinical & Refractive Optometry

Volume 2 Approaches to the Treatment of Dry Eye Disease from the optometric and ophthalmic perspectives

Contributors Richard Maharaj OD Yvon RhĂŠaume OD Steve Arshinoff MD Sheldon Herzig MD

CRO

Clinical & Refractive Optometry

Applications and Usage The authors and publisher have exerted every effort to ensure that the application and use of all medical drugs, devices and procedures mentioned in this publication are in accord with current recommendations and practices. However, in view of ongoing research, changes in regulations, and the constant flow of information relating to optometry and ophthalmology, the reader is cautioned to consult the package insert of any product for the approved indications and dosage recommendations, as well as for any changes, warnings or precautions prior to usage. All Rights Reserved No part of this publication may be translated into any other language, reproduced, or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without prior written permission from the publisher. The following are the respective registered products of: Advanced Vision Research an Akorn Company: TheraTears®; Alcon: Systane®, Tears Naturale®; Allergan: Restasis®; I-MED Pharma: i-drop®; Novartis: HypoTears®; TearScience: Lipiflow® Prepared, printed and published online by: Mediconcept Inc. 2113 St. Regis Blvd. Suite 250 Dollard-des-Ormeaux, Quebec H9B 2M9 Canada Copyright © 2015 Mediconcept Inc.

Contributors

Richard Maharaj, OD completed his Doctor of Optometry degree at the University of Waterloo School of Optometry. He entered private practice in 2003 in the Toronto and Hamilton regions, where he has developed a successful medical optometry practice working collaboratively with ophthalmology. He completed his Fellowship of the American Academy of Optometry in October 2012 a rare distinction among Canadian optometrists. Dr. Maharaj is a staff optometrist at Humber River Regional Hospital York/Finch Eye Associates - an integrated medical eye clinic. Steve Arshinoff, MD, FRCSC received his medical degree at Baylor College of Medicine in Houston, Texas, and then attended the University of Toronto for his residency in ophthalmology. He has been in private ophthalmic group practice in Toronto, Canada, at York Finch Eye Associates and Humber River Regional Hospital, since 1980. He has academic appointments at the University of Toronto and McMaster University. Dr. Arshinoff’s areas of special interest in ophthalmology are primarily cataract and refractive surgery. He is the author of over 240 peer-reviewed publications and has lectured all over the world on techniques of cataract and refractive surgery. He maintains an ongoing research commitment. Dr. Arshinoff has particular interest in simultaneous bilateral cataract surgery (SBCS), antibiotic prophylaxis for intraocular surgery and ophthalmic viscosurgical devices (viscoelastics).

Yvon Rhéaume, OD received his Doctor of Optometry degree from the University of Montreal School of Optometry. Since 1973, Dr. Rhéaume has been in private practice in Montreal with two associates, where he deals mainly with ocular pathology and contact lenses. He is a Professor of Ocular Pathology and the Head of the Ocular Pathology Clinics at the School of Optometry, University of Montreal. Dr. Rhéaume is an active member of the Quebec Order of Optometrists, the Quebec Association of Optometrists, and the Canadian Association of Optometry. He serves as the editor-inchief of the peer-reviewed journal, Clinical & Refractive Optometry. Sheldon Herzig, MD, FRCSC completed his ophthalmology residency at the University of Toronto, after which he completed a fellowship in corneal and cataract surgery at the Mary Shields Eye Hospital in Dallas, Texas, where he was trained in the most advanced microsurgical techniques for cataract and refractive surgery. Dr. Herzig has been a member of the surgical staff at North York General Hospital. In 1996, Dr. Herzig co-founded the Herzig Eye Institute with businesswoman Cherry Tabb. The Herzig Eye Institute and Dr. Herzig have treated more than 150,000 patients from all over Canada, 42 states and 23 countries worldwide. Dr. Herzig has trained and treated several hundred of the world’s leading advanced cataract and refractive surgeons. Since the initiation of laser vision correction technology, Dr. Herzig has been recognized as a leader in the use of laser technologies in refractive surgery.

Contents

Chapter 1: The Optometric Approach to Dry Eye Disease 1.1 Patients Presenting with Symptoms of Dry Eye Disease ............................................................................9 1.2 Percentage of Patients Who Self-Medicate ..................................................................................................9 1.3 Specific Treatment Recommendations ......................................................................................................10 1.4 The Need for Follow Up and Progress Reports ........................................................................................11 1.5 Meeting Report from the CRO Vancouver Meeting Blink Mechanics: Viscoadaptive Technology for the Ocular Surface ........................................................12

Chapter 2: The Ophthalmic Approach to Dry Eye Disease 2.1 Rating Dry Eye Disease Patients Prior to Surgery ....................................................................................21 2.2 Effect of Dry Eye Disease on Surgical Outcomes ..........................................................................................22 2.3 Pre- and Post-Surgical Protocol for Treating Dry Eye Disease ................................................................23 2.4 Specific Treatment Recommendations ......................................................................................................24 2.5 Viscoadaptive Class of Eye Drops..............................................................................................................25 2.6 Meeting Report from the CSCRS Toronto Meeting A New Modality for the Treatment of Dry Eye Syndrome........................................................................26

Chapter 1: The Optometric Approach to Dry Eye Disease 1.1 Patients Presenting with Symptoms of Dry Eye Disease CRO: Drs. Rhéaume and Maharaj, as optometrists when a patient presents in your practice with symptoms consistent with Dry Eye Disease, do you begin by treating their symptoms, or do you begin by testing in order to confirm the presence of Dry Eye Disease? Dr. Rhéaume: Although symptoms are very important, I never rely on them only. I always begin by testing in order to confirm the presence of Dry Eye Disease. Testing for Dry Eye Disease will allow me to confirm the diagnosis, and more importantly to assess if I am dealing with a mild, moderate, or severe condition. Also, testing will allow me to get a clue as to the etiology of the Dry Eye Disease. Am I in the presence of a tear deficiency affecting the lipid, the aqueous, or the mucin layer; or am I dealing with a corneal irregularity secondary to an epithelial basal membrane dystrophy, a pinguecula or a pterygium? I will also be able to assess if there is a lid surfacing problem like an ectropion or an entropion and to evaluate the lid margin conditions for possible chronic blepharitis or meibomianitis. So for me, and for any given condition, testing is an absolute must.

Testing for Dry Eye Disease will allow me to confirm the diagnosis, and more importantly to assess if I am dealing with a mild, moderate, or severe condition. Dr. Maharaj: I approach all Dry Eye Disease patients by determining etiology with a comprehensive list of diagnostics. Only in this way can the appropriate therapy be prescribed. As the majority of Dry Eye Disease patients are of a mixed etiology (evaporative and/or aqueous, cicatricial), it is important to determine the prevailing cause as well as the duration of symptomology.

The majority of Dry Eye Disease patients are of a mixed etiology, i.e., evaporative and/or aqueous, cicatricial.

1.2 Percentage of Patients Who Self-Medicate CRO: What percentage of your first-time Dry Eye Disease patients present already self-medicating? In those patients, do you ever recommend that they change to a different treatment regimen? Dr. Rhéaume: I would say that a good 50% of my first-time Dry Eye Disease patients present already self-medicating. The reason for this is that many eye specialists simply tell their patients, “You have a Dry Eye Disease, go to the pharmacy and get yourself some artificial tears. You will be able to find out which one works best for you.” Also, because the artificial tears are over-thecounter products, many patients with symptoms of Dry Eye Disease will try different artificial tears without having seen an eye specialist. In those

The Optometric Approach to Dry Eye Disease

patients, I almost always recommend that they change to a different treatment regimen based on my examination findings. Most importantly, I tell my patients which product to get and to stick with my recommendation until they come back for their follow-up evaluation.

Most importantly, I tell my patients which product to get and to stick with my recommendation. Dr. Maharaj: Almost 100% of symptomatic patients are self-medicating ineffectively. Patients often reach for the nearest â&#x20AC;&#x153;red-freeâ&#x20AC;? eye drops which do little to treat the underlying cause. Most times, the products that my patients choose mask the redness with a vasoconstrictor but this does little to alleviate the discomfort they are experiencing. Depending on the etiology, I will switch to a preservative-free option first, a hyaluronate in most cases, and an oil emulsified option 3rd.

Most times, the products that my patients choose mask the redness with a vasoconstrictor but this does little to alleviate the discomfort they are experiencing.

1.3 Specific Treatment Recommendations CRO: When would you recommend a specific treatment to your Dry Eye Disease patients, and what do you base that recommendation on? Dr. RhĂŠaume: As much as possible, I try to recommend a specific treatment based on its ability to positively affect the layer of tears responsible for the Dry Eye Disease. For example, if I have a patient with Dry Eye Disease secondary to arthritis, I will most likely be able to identify the aqueous layer as being deficient. In this case, I would use regular artificial tears to immediately help the patient, but I would also prescribe drops with an immunosuppressant like cyclosporine to help relieve the immunologic attack on the main lacrimal glands. If I have a patient with a lid margin problem like a chronic blepharitis, along with the use of antibiotic/cortisone ointment, I would use artificial tears that more specifically enhance the lipid layer.

I recommend a specific treatment based on its ability to positively affect the layer of tears responsible for the Dry Eye Disease. Dr. Maharaj: Up to 86% of patients have meibomian gland dysfunction (MGD) as a contributing component of their Dry Eye Disease so managing the lipid layer will decrease evaporation which will preserve the aqueous layer. The mucin layer should not be negated either; which is why, once the lipid layer is stabilized, I often will add non-preserved hyaluronate to maximize the mucin layer.

Managing the lipid layer will decrease evaporation which will preserve the aqueous layer.

Approaches to the Treatment of Dry Eye Disease

1.4 The Need for Follow Up and Progress Reports CRO: Do you regularly follow the progress of your confirmed Dry Eye Disease patients who are receiving treatment? Dr. RhĂŠaume: I always want to follow patients who are receiving treatment. This is my line of conduct for any condition that I decide to treat. Of course, Dry Eye Disease being a chronic condition, I have to limit and schedule the follow-up visits in a timely manner. In general, I will schedule a first follow-up visit in one month. If on the first visit I prescribe a medicated ointment for chronic blepharitis, I will follow the patient in one week to evaluate the response to the treatment, and then have the patient back 3 weeks later. If I have a satisfactory therapeutic response at the first follow-up visit, I will recommend the patient to return every 6 months.

In general, I will schedule a first follow-up visit in one month. Dr. Maharaj: Yes, I follow my patients regularly, depending on the severity of their condition anywhere from 1 to 6 months after initiating therapy. This is crucial to ensure compliance and also so I can clinically judge whether there is improvement on the course of action taken.

I follow my patients regularly, depending on the severity of their condition.

The Optometric Approach to Dry Eye Disease

1.5 Blink Mechanics: Viscoadaptive Technology for the Ocular Surface Richard Maharaj, OD, FAAO This Meeting Report has been excerpted from a presentation given at the CRO Vancouver Meeting held on September 7, 2014.

INTRODUCTION While the body of Dr. Maharaj’s work is in Meibomian Gland Dysfunction, he noted that this presentation topic was focused on blink metrics in mild to moderate dry eye patients. There are two components in the discussion of the mechanics of blinking and viscoadaptive technologies. The first is what the eyelid does on a given blink. The second is the microanatomy involved in the blink at the inner and outer eyelid surface. Dr. Maharaj has observed that a blanket approach to treatment with artificial tears isn’t an effective model of care for the multifactorial dry eye patient. Following the artificial tear evolution and consideration of the chemical properties of various artificial tearproducts, industry has moved toward meibomian gland driven therapies with specific focus on lipid layer supplementation. Blink Mechanics and Viscoadaptive Devices In a normal functioning eye, the eyelid closes as the superior eyelid comes down and meets the bottom eyelid, grabs onto the lipid layer and the oil film rises with the upper lid to coat the tear film. This is clearly shown on video imaging with the Oculus keratograph 5M and looks very clear under slit lamp. The human body has evolved in such a way that this mechanism of action is responsible for achieving comfort, and in fact can be the source of discomfort, said Dr. Maharaj. He noted that one of the current focuses of the Tear Film & Ocular Surface Society (TFOS) is the mechanics and metrics of blinking. Computer vision syndrome is not surprisingly on the rise. A common at home tip for patients involves blinking 20 times every 20 seconds by looking 20 feet away or the 20-20-20 rule. When one looks at dry eye and ocular |surface disease, one realizes the role that the blink plays in it. Dr. Maharaj stated that understanding blink mechanics makes it easier to understand the mechanisms involved in the development of the dry eye. Mechanics of Dry Eye Disease Dr. Maharaj described rheology, the behavior of fluids in response to applied forces, which is different from Newtonian physics; fluids respond differently than solids. An appreciation of this difference is crucial in reviewing viscoadaptive technology and pseudoelastic viscoadaptive tears. While dry eye is a chronic condition for which there is no cure, ECPs can manage it. Dr. Maharaj counsels patients that they can be treated and progress to a point where they are more comfortable, where they may not notice their eyes on any given day or any given week, but by no means is it a cure. According to various worldwide studies over the past decade, the prevalence of dry eye ranges from 7 percent up to close to 50 percent, depending on the study. In Dr. Maharaj’s dry eye clinic, more than 90 percent of patients actually exhibit the condition in itself; however, in general eye care practices, dry eye as a condition is second only to cataracts. Pre-identification of the dry eye patient undergoing surgery and pretreatment is far more likely to result in patients having a better postoperative experience. When considering sending a 65-year-old patient to a cataract surgeon for cataract surgery, for instance, preparing the patient’s ocular surface has been

Approaches to the Treatment of Dry Eye Disease

shown to contribute to their postoperative success. Patients that lack preoperative treatment have a four times greater risk of their dry eye worsening following surgery. In the next two to ten years, stated Dr. Maharaj, practitioners will see their role in the perioperative arena growing, and rightfully so. Based on current trends, he predicted greater discussion and use of triglyceride omega 3s for added systemic impact on meibomian gland disease. Dr. Maharaj discussed osmolarity as a dry eye metric that is important to understand in a general setting. Tear osmolarity is a valuable tool, relative to the Ocular Surface Disease Index (OSDI), corneal staining and Schirmer tear test and has been shown to be more sensitive and more specific than these other measures. When examining the correlation to the severity of the condition, osmolarity has the strongest correlation. To identify existing dry eye patients in a general practice, it is extremely relevant for patients that may not be symptomatic but are silently suffering. Those are the ones who may, in fact, have a hyperosmolar tear film, which means that they do have a higher component of salt and proteins like MMP-9 and other inflammatory cytokines in their tear film. If this inflammation is elevated and the patient is not symptomatic, the chronic inflammatory environment will eventually produce symptoms. Blink Mechanics Under a slit lamp, it is quite common for the lower eyelid to hang slightly lower than the iris, which is very common and produces infrequent, incomplete blinking. There are, however, some patients who don’t have this characteristic; they have a neat palpebral fissure, but the eyelid still doesn’t drop all the way down. In terms of blink mechanics, said Dr. Maharaj, what most patients think happens is that their lower eyelid and upper eyelid come together, touch and then move away. However, when one starts to examine the mechanics of a blink, one sees that this is, in fact, the opposite of what occurs (Fig. 1). The lower eyelid makes very little vertical movement; however, the superior eyelid does most of the travel and there’s actually a torsional component to it. That’s not even taking into consideration ethnicity, the thickness of the tear, the inner eyelid surface, or the lid wiper itself, the band of tissue that also impacts the way eyelids move. In Dr. Maharaj’s experience, examining the asymmetry between one eye and the other, one often sees anatomical and morphological changes in the meibomian gland of the eye that has a decreased blink rate and decreased blink completeness. In patients whose eyelids come together, there is a correlation with meibomian gland atrophy or Fig. 1 Mechanics of blinking. truncation: if the eyelids are not coming completely together, the gland orifice isn’t receiving any negative pressure to draw oil out of it, and if it’s not used, obstruction begins, prompting a cascade of events. Figure 2 depicts a breakdown of the blinking process, showing a superior component and a torsional component of the upper eyelid moving mainly up and down and slightly, with a minor rotation. However, the inner eyelid barely moves vertically; it actually has a nasal movement. This is an extremely complex movement with the forces being applied to the cornea and to the ocular surface, in addition to the forces being applied to the fluid between the eyelid and the cornea.

The Optometric Approach to Dry Eye Disease

Dr. Maharaj expressed his opinion that there are some more effective solutions for dry eye than artificial tears. Regardless of ethnicity or the shape of the eye, there is slight vertical movement on the superior eyelid; there is nasal and torsional movement of the superior eyelid; the inferior eyelid margin typically makes lateral movements. This produces a type of shearing force. What occurs is that rather than the front surface closing, it is the posterior lid margin that closes. The mucocutaneous junction otherwise known as the Line of Marx (LOM) forms a ridge that is not meeting up. Thereâ&#x20AC;&#x2122;s no seal of the superior and inferior LOM on lid. A quick test for this is the light test using a Fig. 2 Breakdown of blinking process. transilluminator (Fig. 3). With retroillumination similar to what is being depicted in the figure, a slight gap becomes apparent. Even in those patients who, under a microscope, appear to be blinking completely, they may, in fact, have inadequate lid seal which will exacerbate the condition. This will lead to increased friction, causing the lid wiper to become inflamed. In this case, the posterior lid surface is in direct opposition to the cornea with a thin pre-corneal tear film acting as a buffer between the two surfaces. The result is tissue with repetitive microtrauma causing eventual, epitheliopathy and lid inflammation. The meibomian glands are very closely associated to the lid wiper and this is where Meibomian Gland Dysfunction (MGD) can start in some patients. Dr. Maharaj stated that while it is important to distinguish between aqueous deficiency and evaporative dry eye, he does not view the situation as one or the other. This condition is very much a spectrum disease. At some point, MGD will lead to up-regulation of the lacrimal gland, eventually causing it to become inflamed, resulting in aqueous deficiency. All dry eye patients appear at some point Fig. 3 Transilluminator test. on this spectrum. Mechanics of Dysfunctional Blinking In terms of the MGD cycle, Dr. Maharaj stated that the TFOS DEWS algorithm is extremely complex; therefore, he has extracted some of the elements he feels are most relevant (Fig. 4). He suggests that practitioners examine the eyelid aperture of the blink first, looking for the lid seal. When the blink becomes dysfunctional, it results in lid wiper microtrauma due to friction. The resulting symptoms can include extreme pain, mild to severe contact lens intolerance and visual instability. This will lead to hyperosmolarity with an up-regulation in MMP-9 (Matrix metallopeptidase 9), salts and other proteins. Tear hyper-osmolarity drives the tear solutes toward the lid margin and meibomian glands and thus the evaporative and aqueous cycle begins. This process applies to the vast majority of mild to moderate dry eye patients and is therefore a good starting point in determining the goal of an artificial tear. Looking at the problems created by that cycle, the first thing that occurs is decreased blink rate and poor closure. Therefore, said Dr. Maharaj, the goal in tear film therapeutics should be aimed at increased residence time on the cornea with minimal effect on vision stability. Examining Fig. 4 Components of the TFOS DEWS algorithm.

Approaches to the Treatment of Dry Eye Disease

the attributes of a topical treatment that allows it to last longer on the eye is essential. For instance, how it interacts with the eyelid surfaces with the shearing forces previously discussed, and whether or not it stabilizes the tear film. Current Dry Eye Treatments The goal of therapy is long-term stability, which is a very important part of the tear chemistry — an essential element. As an immunomodulator — a targeted anti-inflammatory therapy — Restasis® (cyclosporine ophthalmic emulsion, Allergan Canada, Markham, ON), is extremely effective, noted Dr. Maharaj, at addressing aqueous deficient dry eye. At the 2011 MGD workshop, MGD became defined as perhaps the leading cause of dry eye disease around the globe. With this, replacing the lipid layer became the utmost priority. The term “viscoadaptive” was introduced; Dr. Maharaj remarked that it appears to be a confusing term. When doctors refer to the viscosity of a solution, they know what it means in terms of thicker or thinner. Intraoperatively, it has a different meaning than visco-adaptive on the external eye. In rheology, the study of forces on fluids is very different when compared to forces on solids because fluids are very much like air; the forces are more or less Newtonian. One can pass one’s hands through it without resistance. However, with a fluid like glass, the forces that need to be applied to get it to move like a liquid are very, very high. The three tenets are understanding viscosity, understanding elasticity, and then examining the cohesive and dispersive nature of fluids. Dr. Maharaj stated that there are four patterns of Rheometric Patterns of Fluid Behaviour: Viscosity rheometric behavior of fluids (Fig. 5); namely Newtonian, pseudoplastic, plastic and dilatant. In Figure 5 the further to the left on the x axis, the lower the shear forces being applied; the further to the right, the higher the shear force. The y axis relates to viscosity. The solution can be a liquid which will be lower down on the graph or, it can behave like glass or a fractureable solid which will appear higher on the graph. Newtonian Tear Solutions Many fluids are pseudo-Newtonian; they’re not quite Newtonian; however, they possess more or less these same characteristics. On the other hand, plastics when exposed to a great force can carry liquid-like characteristics. Fig. 5 Variations in applied force. As shown in Figure 5, fluid-like behaviors or low viscosity behaviors at a certain force will become more viscous. The term for this is zero shear rate. Past the zero shear rate it becomes a fractureable solid. The zero shear rate of a pseudoplastic material is important in surgery (intra-operative surgery is really where it all evolved from) because there has to be a point at which it doesn’t become more viscous. If it did, it would harden in the anterior chamber making surgery very difficult. Pseudoplastics have evolved and have been adapted to the ocular surface specifically because of this fact. Dr. Maharaj stated that this is particularly important when considering artificial tears: The eyelid moves around and applies shear forces. Viscous solutions that still have Newtonian-like behavior with long and short branched polymers behave in more or less a Newtonian fashion. Pseudoplastic or viscoadaptive solutions will behave differently to the various moments in a blink.

The Optometric Approach to Dry Eye Disease

Non-Newtonian Tear Solutions Regarding blink forces, instead of a tear solution progressing from a cohesive fluid to a hard solid, it actually moves from a cohesive fluid to an elastic material. In the process of blinking, the eyelid comes down and compresses. It squeezes the material down. One example of this type of fluid is hyaluronic acid (HA). In order to make it a dispersive substance, one can add a shortchain branched molecule that is not bound to the HA that can actually separate from the HA by force. What happens with an artificial tear with HA and a short-chain branched polymer is exposed to blink forces, the HA separates — it binds with the water found in the aqueous component of tears — and it excludes the short branched polymer present. A hyaluronate and glycerin solution during the blinking process will almost behave like a contact lens — a fractureable solid — in the eye when the eyelid closes because it is applying a high amount of shear force. When the eyelid opens, the solution returns to a fluid state. In terms of applying these forces to an artificial tear, considIntraocular OVD Pseudoplasticity eration needs to be given to the way the eyelid moves with a HA-based eye drop compared to a Newtonian solution like methylcellulose, for example. In the surgical context, the pseudoplastic curves of some of the ophthalmic viscoadaptive devices used in intraocular surgery are shown in Figure 6. The curves vary depending on the device used. Dr. Maharaj noted that some examples currently used in surgery were actually used to derive hyaluronic-based eye drops. Healon® 5 (sodium hyaluronate, AMO, Markham, ON) and iVisc® (sodium hyaluronate, I-Med Pharma, Montreal, QC), for instance, are commonly used. Depending on the shear forces applied, the liquid will eventually reach a certain viscosity and not go past that point. Artificial tears such as Tears Fig. 6 Pseudoplastic curves of viscoelastic devices. Naturale® (ocular lubricant, Alcon Canada, Mississauga, ® ON), Systane (lubricant eye drops, Alcon Canada, Mississauga, ON), GenTeal® (lubricant eye drops, Alcon Canada, Mississauga, ON), all have a very simple linear Newtonian movement on the eye regardless of the eye’s blink mechanics. Features of Pseudoplastic Elastovicous Tears The first Canadian pseudoplastic elastoviscous tear is known as i-drop® (I-Med Pharma, Montreal, QC). It is distinguished by its high molecular weight sodium hyaluronate combined with a short-chain branched polymer, glycerin. The interesting feature of HA is that all the cells in the body, including those of the cornea, have hyaluronic binding sites. The HA in the eye drop binds to these binding sites, anchoring the tear onto the ocular surface. The HA actually combines with the water found in the tears. It excludes the glycerin which rises to the surface as the eyelid blinks. The glycerin provides a lubricating surface to the blink, decreasing friction on the ocular surface. Once the eyelid reaches down to the bottom, and the eyelid comes up and the solution returns to its original low viscosity. As a result of this process, the residence time is high. The tear mimics all three layers of the tear film simply by virtue of its physical properties. Dr. Maharaj uses this approach in his general patients, in order to prolong residence time, decrease evaporation and create visual stability. A high molecular weight hyaluronic-based drop allows this. From a rheological perspective, pseudoplastic elastoviscous tears, or PETs, produce the desired effect, mimicking naturally occurring tears.

Approaches to the Treatment of Dry Eye Disease

Curves

The problem of decreased blink rate and closure requires that a topical tear increases the residence time on the eye, which i-drop achieves. This is accomplished through decreasing friction on the ocular surface with unbound glycerin and stabilization of the tear film via HA. This decreases evaporation and stabilizes the tear film, providing patients substantially greater comfort. Dr. Maharaj stated that the last benefit of some of the new drops coming to market, i-drop being one of them, is that they are packaged in a multi-dose, non-preserved bottle. He views the lack of preservatives as an important benefit. The bottle form may make it more convenient for patients. The first clinical study of hyaluronan eye drops was undertaken in 1982. At the time, HA was found to have a much longer residence time. This led to the Hylan™ Surgical Shield (Elastoviscous Hylan Surgical Shield, 0.45%) which surgeons were using during surgery to coat and protect the ocular surface. Dr. Maharaj suggested that when addressing the ocular surface, practitioners ought to carefully consider the true etiology of the condition and all available solutions. With an abundance of products on the market and patients not knowing which to choose, Dr. Maharaj suggested that eye care professionals make very specific patient recommendations. It is now known that patients are blinking less frequently and less completely, which Dr. Maharaj noted are facts that need to be addressed when weighing treatment options for dry eye. He stated that the best way to achieve this is to provide patients the most successful available products, rather than simply telling them to modify their blink behavior and to use the nearest artificial tear. In Dr. Maharaj’s Dry Eye Clinic, a very discrete and direct protocol is used. He instructs his patients, “Follow my specific instructions or you won’t feel better. That’s why I’m being specific.” He takes this approach because if one tells patients to use any artificial tear, they will. This leaves the decision of choosing the topical up to the patient. As a health provider is it imperative to educate patients to make an informed decision. Conclusion Dr. Maharaj concluded his presentation by emphasizing the importance of providing patients a specific recommendation to their individual dry eye problem. The tear film ought to be addressed as a mechanism, as opposed to an element that must be supplemented.

The Optometric Approach to Dry Eye Disease

How Viscoadaptive Eye Drops Work i-drop ® Pur and i-drop ® Pur GEL are the world’s first and only, viscoadaptive, multi-dose, preservative-free, eye drops. They are both combinations of viscoadaptive sodium hyaluronate (HA) and glycerine molecules; and they are available in two different concentrations of HA for use with varying degrees of dry eye disease. i-drop® Pur contains 0.18% viscoadaptive HA and is indicated for use with mild to moderate dry eye disease as well as with contact lenses. i-drop® Pur GEL contains 0.3% viscoadaptive HA and is indicated for use with moderate to severe dry eye disease.

LIPID LAYER

GLYCERIN HA

AQUEOUS LAYER

MUCIN LAYER

CROSS SECTION OF THE TEAR FILM

Both formulations of i-drop® contain long chained HA molecules that trap and hold glycerin and any available free water in a soluble suspension on the surface of the cornea. With each blink, the eyelids exert a physical force on the tear film pushing the glycerin and water out of suspension. This action enables the glycerin to reinforce the lipid layer, the water to hydrate the aqueous layer, and the HA to supplement the mucin layer. Then, as the eyelids relax and re-open, the glycerin and water return to suspension and they are ready for the next blink. This pseudoplastic elastoviscous action is referred to as viscoadaptivity.

Viscoadaptive eye drops enhance the three natural layers of the tear film and are remarkably comfortable and long lasting for the patient. It is also why i-drop® Pur and i-drop® Pur GEL are highly effective at hydrating and lubricating the cornea while reducing tear film evaporation, which are generally recognized as being the principle factors required to improve the symptoms associated with dry eye disease.

Two Choices for Long Lasting Relief i-drop®, the world’s first and only viscoadaptive, multi-dose, preservative-free, eye drop is now available in two concentrations. i-drop® Pur for treating mild to moderate dry eye disease, and i-drop® Pur GEL for treating moderate to severe dry eye disease.

VISCOADAPTIVE EYE DROPS s Enhanced Corneal Protection s Prolonged Residence Time s Smoother Blinks s Higher Degree of Comfort s Excellent Corneal Hydration s Reduced Tear Film Evaporation

i-drop® Pur GEL 0.3% viscoadaptive HA Provides immediate, long lasting relief for moderate to severe dry eye disease i-drop® Pur 0.18% viscoadaptive HA Provides immediate, long lasting relief for mild to moderate dry eye disease indicated for use with contact lenses

I-MED Pharma

800.463.1008 www.osdcare.com www .osdca are.com

Chapter 2: The Ophthalmic Approach to Dry Eye Disease 2.1 Rating Dry Eye Disease Patients Prior to Surgery CRO: Drs. Arshinoff and Herzig, as ophthalmic surgeons, what percentage of your surgical candidates present with symptoms of pre-existing Dry Eye Disease and in those patients does a moderate to severe rating affect your decision to perform particular types of surgical procedures? Dr. Arshinoff: Patients with underlying Dry Eye Disease commonly present for unrelated procedures. The Dry Eye Disease percentage, of course depends upon the procedure under discussion, because ophthalmologists perform different surgeries on patients that fall into different age brackets. Strabismus surgery is most common in children, whereas the average cataract patient is usually around age 70. If we confine ourselves to consideration of procedures on the most common older demographic of cataract/glaucoma/cornea/lid surgery procedures, estimates of Dry Eye Disease frequency still vary widely, depending upon factors such as glaucoma patients having much greater pre-surgical exposure to aggravating preservatives in their eye drops, geographic/ seasonal differences (household dryness in winter considerably aggravating symptoms), and even things like whether simultaneous bilateral or unilateral procedures are planned (symptoms are much reduced in bilateral surgical patients, because both eyes feel the same pre- and postoperatively). A general estimate of patients presenting with moderate to severe Dry Eye Disease is 10% to 20%. So, the real question is: How should the surgeon approach this problem? My own preference is to try to make things simple and easy. If a given patient has Sjögren’s syndrome, a history of constant need for artificial tears, even if only in winter, infero-nasal corneal staining or scarring, Salzmann’s nodules, signs of previous trachoma, etc., I note it on my chart, and advise the patient to consider simultaneous bilateral surgery (if they have bilateral cataracts), try to avoid surgery in December to February, and discuss with them, at the outset, their expected increased need for lubrication perioperatively.

A general estimate of patients presenting with moderate to severe Dry Eye Disese is 10% to 20%. Dr. Herzig: Very few of my patients who present for surgery actually complain of dry eye symptoms. If a patient does have both dry eye symptoms and findings, then it clearly is a problem that requires attention before proceeding with surgery. I would not perform either cataract or refractive surgery without both the subjective and objective evidence of a person’s Dry Eye Disease being eliminated or significantly reduced.

Very few of my patients who present for surgery actually complain of dry eye symptoms.

The Ophthalmic Approach to Dry Eye Disease

2.2 Effect of Dry Eye Disease on Surgical Outcomes CRO: In your opinion, if left untreated, can Dry Eye Disease adversely affect the overall outcome of particular types of surgical procedures? Dr. Arshinoff: Surgical patients, having agreed to undergo surgery, a huge experience for them, are not likely to ignore Dry Eye Disease symptoms if their surgeon simply says “Don’t worry about it. You had it before, and you will still have it later.” Patients usually do not understand that if they undergo a procedure to fix “X”, it will fix only “X”, and their ocular concerns “A, B, & C” will be no better, and maybe a bit worse, after their surgery. So, every ocular complaint of a surgical patient must be discussed before surgery, and clear management plans and expectations should be established. So, for example, if the patient has chronic tearing when outside in the cold and wind, due to lax eyelids, it will be, at best, the same postoperatively. Once we convince the patient to undergo refractive components of surgery, expecting to significantly reduce the need for spectacles, the first thing the patient notices postoperatively is not their 20/20 distance vision, but their increased tearing outside, now that they no longer wear spectacles. To make things worse, if the surgeon was inattentive to Dry Eye Disease when biometry was performed, significant errors often result from biometry on a dry cornea, covered with mucous and smeared, evaporated tear aggregates, so the patient may also complain about not seeing 20/20, in addition to the tearing. The patient may also complain that the postoperative eye drops burn excessively, and may not take them as prescribed. Simply put, ignoring Dry Eye Disease in cataract patients is a recipe for patient and doctor misery.

Every ocular complaint of a surgical patient must be discussed before surgery, and clear management plans and expectations should be established. Dr. Herzig: Both cataract and refractive surgery can cause ocular dryness even in previously asymptomatic patients. If a patient already has Dry Eye Disease preoperatively, surgery will almost always aggravate their condition. Both surgeries also require meticulous refractive planning before proceeding. The presence of Dry Eye Disease preoperatively makes refractive and corneal measurements impossible to measure accurately resulting in less than satisfactory outcomes. Continued Dry Eye Disease postoperatively results in an uncomfortable patient who is unhappy with their visual result.

If a patient already has Dry Eye Disease preoperatively, surgery will almost always aggravate their condition.

Approaches to the Treatment of Dry Eye Disease

2.3 Pre- and Post-Surgical Protocol for Treating Dry Eye Disease CRO: Do you currently use (or would you consider using) a pre- and post-surgical protocol for treating Dry Eye Disease patients scheduled for surgery? Dr. Arshinoff: Ophthalmology is complex, and Dry Eye Disease is a multifactorial disorder, with multiple causes and variable symptoms. It is difficult to have a specific protocol for every patient, but attentiveness to a number of issues is critical: 1. Examine the patient carefully, and decide upon, discuss, and note decisions about management of ectropion, entropion, or any other lid issues (blepharitis, rosacea...) at the initial visit. If the patient and family know and understand that you intend to correct their abnormal lid position at a second procedure a few weeks after their cataract surgery, they will be much more tolerant of postoperative symptoms. These patients are happy after their cataract surgery, and very happy after their lids have also been repaired, when they see clearly and feel a lot better. 2. When performing biometry, attention should be paid to the tear film and any dry eye symptoms. It is a good idea to perform topography on everybody and to administer one or more drops of a hypo-osmolar artificial tear before performing topography and biometry. The technician should be trained to assess the tear film before performing every biometry, and should notify the surgeon of any problems encountered that may affect accuracy. 3. All patients with Dry Eye Disease symptoms should be counselled about the beneficial effects of spectacles to reduce Dry Eye Disease symptoms, and the expected increase in symptoms if the patient chooses not to wear spectacles postoperatively. Artificial tears should be prescribed preoperatively and continued postoperatively, avoiding administration coincident with other agents.

When performing biometry, attention should be paid to the tear film and any dry eye symptoms. Dr. Herzig: Pre- and post-surgical treatment protocols for patients with Dry Eye Disease need to vary with the etiology and severity of the symptoms and findings. The problem may simply require increasing a patientâ&#x20AC;&#x2122;s use of artificial tears or adding Restasis and steroid drops to their present regimen. Frequently these patients have meibomian gland dysfunction (MGD), the most common cause of evaporative Dry Eye Disease. They need to aggressively clean their lids consistently with or without the use of antibiotic/steroid ointments. I have found the Lipiflow treatment to be the best approach to treat MGD but not all patients can afford it. Using Lipiflow has allowed me to do refractive surgery on some Dry Eye Disease patients that would have been refused surgery in the past.

The Ophthalmic Approach to Dry Eye Disease

2.4 Specific Treatment Recommendations CRO: If you recommend a specific Dry Eye Disease treatment or protocol what do you base your recommendation on? Dr. Arshinoff: Specific management of Dry Eye Disease perioperatively depends upon the specific diagnosis. Lid malpositions should be corrected, if possible, preferably after the proposed intraocular surgery, to prevent recurrence of lid damage to the corrected lids by a lid speculum. Blepharitis and rosacea should be managed with lid scrubs with whichever of the available agents the patient prefers. If very severe, simple oral tetracycline 250 mg po hs for two months is a wonderful treatment with minimal side effects. Severe cutaneous rosacea should be referred to a dermatologist, not because an ophthalmologist cannot prescribe effective treatment, but because long-term follow-up is usually necessary. MGD can be managed with massage, Lipiflow treatments, some of the forceps now available, and oral tetracycline, as above, which liquefies meibomian secretions. Severe Dry Eye Disease or Sjögren’s may require long-term Restasis. Once all of these have been assessed and managed, “simple dry eyes” are more easily managed with periodic artificial tears prn. There are numerous tears on the market, and all of us have a preference for one kind or another. My rheology background makes me lean toward hyaluronic acid containing tears, but I allow the patient to choose what they like best from a few different classes of tears that I give them to try. New tears are always appearing, because the market is huge and lucrative, and none, so far, is perfect. Tears are, in general, getting better. Preservative-free preparations have the great advantage of being less damaging to the ocular surface, and we will likely continue to see more and better non-preserved artificial tears.

Preservative-free preparations have the great advantage of being less damaging to the ocular surface. Dr. Herzig: As previously mentioned, the most common cause of Dry Eye Disease is MGD. This affects primarily the lipid layer, which then affects the aqueous layer by causing more rapid evaporation. Since Dry Eye Disease also causes conjunctival pathology, there is always some loss of mucin as well. The goal of treatment is almost always to alleviate the MGD whether with regular lid scrubs or Lipiflow. Most patients also need artificial tears, preferably non-preserved, with or without steroid drops and Restasis. In some patients the addition of punctual plugs can be very helpful.

Most patients also need artificial tears, preferably non-preserved, with or without steroid drops.

Approaches to the Treatment of Dry Eye Disease

2.5 Viscoadaptive Class of Eye Drops CRO: Dr. Arshinoff, how would you categorize and describe the various types of artificial tear solutions available today and can you describe their modes of action? Dr. Arshinoff: In 2007, The International Dry Eye Workshop postulated that Dry Eye Disease is caused either by an aqueous deficiency or by evaporation. Which is why most all of the dry eye treatment choices available today are Newtonian-based tear solutions that will either: a) replace water as for example: Hypotears, Theratears, and Tears Naturale, or b) reduce the rate of evaporation as for example: Systane. Successive iterations of the Systane family of tear products, with the most recent being Systane Gel Drops have progressively targeted reduced tear evaporation as their therapeutic mechanism of action. However, another option has recently become available in the form of a non-Newtonian artificial tear solution with “viscoadaptive” properties that will both hydrate the cornea and reduce evaporation. Marketed under the trade name i-drop, this artificial tear is more correctly considered to be a blink-activated pseudoplastic elastoviscous suspension of sodium hyaluronate chains, glycerol and free water.

i-drop is a blink-activated pseudoplastic elastoviscous suspension of sodium hyaluronate chains, glycerol and free water. As for its mode of action, the energy that is exerted with each blink forces the suspension of sodium hyaluronate chains and glycerol molecules to spread out evenly over the surface of the eye releasing glycerol for lubrication and water for hydration. When the blink is relaxed, the suspension returns to its original state and is ready for the next blink. In this way free water is delivered with each blink to the aqueous layer and glycerol reinforces the lipid layer.

In this way free water is delivered with each blink to the aqueous layer and glycerol reinforces the lipid layer. The benefits of this type of “viscoadaptive” action are: prolonged residence time on the cornea, smoother blinks with a higher degree of comfort, very good corneal hydration, and measurably less tear evaporation.

The Ophthalmic Approach to Dry Eye Disease

2.6 A New Modality for the Treatment of Dry Eye Syndrome Steve A. Arshinoff, MD, FRCSC This Meeting Report has been excerpted from a presentation given at the CSCRS Toronto Meeting held on November 9, 2013.

Introduction Dr. Arshinoff began his presentation by outlining the topics he would be discussing, specifically: a review of past and current choices for the treatment of dry eye; the variety of treatment modalities available for dry eye syndrome; rheology; intraocular aophthalmic visco-surgical device (OVD) properties; and their comparison to the unique composition and behaviour of viscoadaptive eye drops.

The Definition & Classification of Dry Eye Disease Guidelines from the 2007 International Dry Eye Workshop Michael A. Lemp, MD and Gary N. Foulks, MD, FACS Major Etiological Causes of Dry Eye Ocular Surface Disease Symptomatic Prodromal states Asymptomatic NonDry Eye Disease

Dry Eye Disease

Aqueous Deficient Dry Eye

Lid-related Disease

Evaporative Dry Eye other

MGD

Anterior Blepharitis other

Fig. 1 Etiology of dry eye

Evolution of Dry Eye Treatment Approaches Dr. Arshinoff referenced the 2007 International Dry Eye Workshop at which Committee members developed a framework for the definition, classification and mechanisms of dry eye (Fig. 1). He noted that dry eye has become somewhat of a “catch-all” term whose underpinnings are the result of either excessive tear evaporation or decreased tear production. Prior to the development of Restasis® (Allergan, Markham, ON), an anti-inflammatory form of artificial tears, pharmaceutical companies responded by providing watery artificial tears, replacing water, or by decreasing

Approaches to the Treatment of Dry Eye Disease

Other OSD Allergic conjunctivitis Chronic infective and non-infective Keratoconjunctivitis Conjunctivitis Post-refractive

evaporation. There are currently three types of eye drops available: 1) Antiinflammatories such as Restasis; 2) Aqueous replacement, such as HypoTears® (Novartis, Dorval, QC), TheraTears® (Advanced Vision Research, an Akorn company, Ann Arbor, MI); and 3) Evaporation reducing agents, such as Systane® Gel Drops (Alcon, a Novartis company, Mississauga, ON). Dr. Arshinoff cited Alcon’s development of successive iterations of Systane eye drops based on a shift in direction from replacing water to preventing evaporation, a direction that merits further examination. This past decade, for example, has seen a product evolution from Systane, to Systane Ultra, to Systane Balance, to Systane Gel Drops. Rheology: Studying Fluid Behaviour Dr. Arshinoff presented an explanation of rheology, the science of how fluids respond to forces, or the mechanics of fluids, and how it works in the devices ophthalmologists use. The study of rheology involves concepts relating to vis- Table I Ophthalmic viscous Newtonian solutions cosity, elasticity and the cohesion/dispersion continuum. He • Viscosity constant, independent of shear rate pointed out that rather than a straight line of correlating prop• Examples erties, OVDs possess endless variation of the above propero Low pseudoplasticity Surgical OVDs (~ Newtonian) ties, such as viscosity changes under stress (Fig. 2). - OcuCoat Dr. Arshinoff stated that there are four different ways that - I-Cel the viscosity of fluids can respond to forces, the first of which - HPMCs is Newtonian, which means that no matter how much force o Topical artificial tears (± Newtonian) you expose the fluid to, its viscosity remains the same (Fig. 2). - Hypotears Another example is the plastic response curve, from - Tears Naturale which “plastic” materials derive their name. When exposed to - Systane very high forces, plastics are fluid, but when exposed to very - GenTeal low forces, they are solid. Imagine, suggested Dr. Arshinoff, - Refresh trying to use a plastic OVD in ophthalmic surgery. The - Tears Plus substance is injected into the eye as a liquid, but once at rest, - Celluvisc it turns solid, which would make surgery difficult. As a result, what is used instead are devices called pseudoplastic. In Figure 2, the blue line represents a pseudoplastic fluid which means that, like a plastic under high forces going through a syringe, it has very low viscosity. However, when sitting in the eye, the viscosity increases — reaching what is called a limiting or a zero-shear viscosity — remaining fluid. The graph levels off and does not go higher than whatever the zero-shear viscosity is. The corollary is: The only useful visco-sity Rheometric Patterns of Fluid Behaviour: Viscosity number for OVD classification is its zero-shear viscosity, as any other viscosity value is dependent upon the shear rate at which it was measured, which is often not disclosed by the manufacturer. The pseudoplasticity graphs in Figure 3 illustrate the different OVDs in common use in North America, although the HPMCs can easily be seen to not be very pseudoplastic. Note that the top red line depicts i-Visc® Phaco (I-MED Pharma, Montreal, QC) as “almost plastic.” Returning to Figure 2, the fourth fluid behaviour type, represented by the pale blue line, is dilatant. Dilatant is the opposite of pseudoplastic, meaning that the more force it is exposed to, the more viscous it becomes. A classic example Fig. 2 Pseudoplasticity curves: rheometric patterns of fluid viscosity response to increasing force (shear rate). of a dilatant fluid is albumin (egg whites).

The Ophthalmic Approach to Dry Eye Disease

Fig. 3 Pseudoplasticity curves of intraocular OVDs in common use in North America.

Newtonian Solutions in Ophthalmic Products Examples of ophthalmic viscous solutions that are almost Newtonian (Table I) are the low pseudoplasticity surgical ophthalmic viscoelastic devices (OVDs), such as i-Cel® (I-MED Pharma, Montreal, QC), OcuCoat® (Bausch & Lomb, Vaughan, ON) and Cellugel® (Alcon, a Novartis company, Mississauga, ON), the two bottom curves in Figure 3. The curves representing these are more or less horizontal, meaning that the viscosity does not change with changing shear rate, except for the very end, where the levels descend. What this indicates is that if you are going to use an HPMC OVD, it is going to behave more or less the same in the eye, irrespective of the ambient shear rate. The surgeon would have to push down very hard on the syringe, exposing it to a lot of force, to inject the OVD through a cannula. For this reason, HPMC OVDs are packaged with larger cannulas than other OVDs. In terms of artificial tears, examples that are more or less Newtonian include: HypoTears, Tears Naturale, Systane, GenTeal® (Alcon, a Novartis company, Missi-ssauga, ON), and Refresh® (Allergan, Markham, ON). Non-Newtonian Solutions Non-Newtonian solutions are used in intraocular surgery, most of which are pseudoplastic (Fig. 3). Highly pseudoplasticity means that they exhibit low viscosity at high shear, high visco-sity at low shear, and possess a limiting or zeroshear viscosity. Examples of this are Healon®, Healon GV® (Abbott Medical Optics, Markham, ON) and i-Visc. “Viscoadaptive” Artificial Tears: What It Means and What It Does Artificial tears containing hyaluronic acid — a long enough chain that behaves like a pseudoplastic material — were first developed twenty years ago; Hylashield.

Approaches to the Treatment of Dry Eye Disease

Dr. Arshinoff stated that three terms — viscous, elastoviscous and viscoadaptive — are used to describe the various treatments for dry eye. He noted that the term “viscoadaptive” may be confusing to some practitioners, as “viscoadaptive” when used to describe tears, has a different meaning than when the same term is used to describe intraocular OVDs. With respect to intraocular surgical OVDs, viscoadaptive signifies that the behaviour of the OVD changes from a highly viscous cohesive — like a Super Healon or Super Healon GV — to a pseudodispersive. However, Dr. Arshinoff pointed out, pseudodispersive is not the same as dispersive, hence thedifferent term: pseudo-dispersive means “fractureable solid under high stress.” Both i-Visc Phaco and Fig. 4 Behaviour changes in ophthalmic viscoadaptive OVDs. Healon5, when they are absolutely stationary, can behave like fractureable solids when exposed to high frequency stresses. The way you make it behave like a solid is by changing the ambient environment inside the anterior chamber. So if you increase your flow rate of fluid in the anterior chamber, you are exposing the OVD to turbulence. The very viscous OVD will behave like a solid and will fracture like a solid. The term viscoadaptive was designed to mean that we can change our flow rate in the eye and make the OVD behave Non-Newtonian Tear Solutions: “like a dispersive,” but not through the same mechanism. You Viscoadaptive? can make Healon5 or i-Visc Phaco behave like extremely viscous “super" Healon GVs under low turbulent conditions, or, by increasing turbulence in the anterior chamber, they behave as pseudodispersive fractureable solids. Analysis of rheological behaviour generally looks at typical flow rates between 10 and 45 cc/min. In Figure 4, Viscoat® (Alcon, a Novartis company, Mississauga, ON) behaves as a dispersive throughout those flow rate settings; and Healon GV behaves as a cohesive across those flow rate settings. However, Healon5 will initially behave as a viscouscohesive, but with increasing flow rates above 25 cc/min, behaves as a fractureable solid. Fig. 5 Dispersive and cohesive properties of non-Newtonian tear solutions. Composition and Behaviour of Viscoadaptive Artificial Tears In artificial tears, “viscoadaptive” refers to an elasto-viscous solution that changes under stress. There are chains of hyaluronic acid that are not as long as those that would be used in an intraocular OVD. When these chains are exposed to the force of blinking, they are more elastic than they are viscous. When you blink with an elastic in your eye, “Viscoadaptive” Eye Drops you blink and it compresses; it does not go anywhere. When you open your eye, it comes back and stays there, because it is acting like a spring. This was the first concept in developing a viscoadaptive tear. The second concept is to add something to the tear which will make it behave differently again under stress, which resulted in glycerol, a small molecule, being added. Because the hyaluronic acid absorbs all the water, and there is no free water in the solution, when compressed, the viscoadaptive elastoviscous artificial tear solution excludes the glycerol from its structure, liberating it to the surface. As a result, as Fig. 6 Viscoadaptive eye drops mode of action.

The Ophthalmic Approach to Dry Eye Disease

soon as you blink with these tears, the glycerol comes to the surface, reinforcing your lipid layer and providing better tear lubrication. Dr. Arshinoff noted that it is a different interpretation of viscoadaptivity. i-dropÂŽ (I-MED Pharma, Montreal, QC) is the first product of its type on the market, made of high-molecular weight hyaluronic acid and glycerol; it is an elastoviscous solution of hyaluronic acid. Glycerol is excluded during blink, thereby lubricating the tears during the blinking process (Figs. 5, 6). An additional advantage is that every human cell has hyaluronic acid binding sites, so when you take these chains of hyaluronic acid and put it on your cornea, it adheres to the corneal surface. Therefore, when blinking it remains fixed: it is stuck to the cornea. Together with the water layer and the glycerol that moves in and out with blinking, the formula represents the potential for an improved artificial tears product. In 2003, the first viscoadaptive eye drop was launched in Canada, followed by Oasis TearsÂŽ (Oasis Medical, Glendora, CA) in 2009 â&#x20AC;&#x201D; the first viscoadaptive hyaluronan-based eye drop launch in the United States. In 2013, i-drop Pur and i-drop Pur Gel (I-MED Pharma, Montreal, QC) were approved as the first non-preserved multidose viscoadaptive eye drops. Patient Benefits of Viscoadaptive Artificial Tears Dr. Arshinoff summarized his presentation by describing the potential advantages of i-drop artificial tears. i-drop Pur artificial tears are pseudoplastic elastoviscous tears, with a second molecule to increase lubrication. They exhibit polymer crowding, so there is no free water. In addition, they are blink responsive in that they are elastic, so they stay in the eye. They adhere to the cornea and the blink energy allows them to spread better over the eye. It releases glycerol to increase lubrication and it lasts longer than other drops in the i-Drop family of products. Dr. Arshinoff mentioned that as it launched only one year ago, there is not yet substantial clinical experience to report. The proposed patient benefits are: enhanced protection of the cornea; prolonged residence time on the cornea because of the binding sites; smoother to blinks; higher degree of patient comfort; very good corneal hydration; and less tear evaporation, which seems to be the direction in which other companies are moving in developing their eye drops.

Approaches to the Treatment of Dry Eye Disease

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