Approaches to the Treatment of Dry Eye Disease - Vol 2

VOLUME 2

Approaches tothe Treatment ofDry Eye Disease

ContributorsSteve Arshinoff MDSheldon Herzig MDRichard Maharaj ODYvon Rhéaume OD

from the ophthalmic andoptometric perspectives

CSO ClinicalSurgicalOphthalmology

&

Volume 2

Approaches tothe Treatment ofDry Eye Diseasefrom the ophthalmic andoptometric perspectives

ContributorsSteve Arshinoff MDSheldon Herzig MDRichard Maharaj ODYvon Rhéaume OD

CSO ClinicalSurgicalOphthalmology

&

Applications and UsageThe authors and publisher have exerted every effort to ensure that the application and use of all medical drugs, devicesand procedures mentioned in this publication are in accord with current recommendations and practices. However, in viewof ongoing research, changes in regulations, and the constant flow of information relating to optometry and ophthalmol-ogy, the reader is cautioned to consult the package insert of any product for the approved indications and dosage recom-mendations, as well as for any changes, warnings or precautions prior to usage.

All Rights ReservedNo 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 retrievalsystem, 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®

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Copyright © 2015 Mediconcept Inc.

Steve Arshinoff, MD, FRCSCreceived his medical degree atBaylor College of Medicinein Houston, Texas, and thenattended the University ofToronto for his residency inophthalmology. He has beenin private ophthalmic grouppractice in Toronto, Canada,at York Finch Eye Associatesand Humber River RegionalHospital, since 1980. He has

academic appointments at the University of Torontoand McMaster University.

Dr. Arshinoff’s areas of special interest inophthalmology are primarily cataract and refractivesurgery. He is the author of over 240 peer-reviewedpublications and has lectured all over the worldon techniques of cataract and refractive surgery.He maintains an ongoing research commitment.Dr. Arshinoff has particular interest in simultaneousbilateral cataract surgery (SBCS), antibiotic pro-phylaxis for intraocular surgery and ophthalmicviscosurgical devices (viscoelastics).

Sheldon Herzig, MD, FRCSCcompleted his ophthalmologyresidency at the Universityof Toronto, after which hecompleted a fellowship incorneal and cataract surgeryat the Mary Shields EyeHospital in Dallas, Texas,where he was trained in themost advanced microsurgicaltechniques for cataract andrefractive surgery. Dr. Herzig

has been a member of the surgical staff at North YorkGeneral Hospital. In 1996, Dr. Herzig co-founded theHerzig Eye Institute with businesswoman CherryTabb. The Herzig Eye Institute and Dr. Herzig havetreated more than 150,000 patients from all overCanada, 42 states and 23 countries worldwide.Dr. Herzig has trained and treated several hundred ofthe world’s leading advanced cataract and refractivesurgeons. Since the initiation of laser vision correctiontechnology, Dr. Herzig has been recognized as a leaderin the use of laser technologies in refractive surgery.

Contributors

Richard Maharaj, ODcompleted his Doctor ofOptometry degree at theUniversity of WaterlooSchool of Optometry. Heentered private practice in2003 in the Toronto andHamilton regions, where hehas developed a successfulmedical optometry practiceworking collaboratively withophthalmology. He completed

his Fellowship of the American Academy ofOptometry in October 2012 a rare distinction amongCanadian optometrists. Dr. Maharaj is a staffoptometrist at Humber River Regional Hospital -York/Finch Eye Associates - an integrated medicaleye clinic.

Yvon Rhéaume, OD receivedhis Doctor of Optometrydegree from the Universityof Montreal School ofOptometry. Since 1973,Dr. Rhéaume has been inprivate practice in Montrealwith two associates, where hedeals mainly with ocularpathology and contact lenses.He is a Professor of OcularPathology and the Head of the

Ocular Pathology Clinics at the School of Optometry,University of Montreal. Dr. Rhéaume is an activemember of the Quebec Order of Optometrists, theQuebec Association of Optometrists, and the CanadianAssociation of Optometry. He serves as the editor-in-chief of the peer-reviewed journal, Clinical &Refractive Optometry.

Contents

Chapter 1: The Ophthalmic Approach to Dry Eye Disease

1.1 Rating Dry Eye Disease Patients Prior to Surgery ......................................................................................9

1.2 Effect of Dry Eye Disease on Surgical Outcomes ..........................................................................................10

1.3 Pre- and Post-Surgical Protocol for Treating Dry Eye Disease ................................................................11

1.4 Specific Treatment Recommendations ......................................................................................................12

1.5 Viscoadaptive Class of Eye Drops..............................................................................................................13

1.6 Meeting Report from the CSCRS Toronto MeetingA New Modality for the Treatment of Dry Eye Syndrome........................................................................15

Chapter 2: The Optometric Approach to Dry Eye Disease

2.1 Patients Presenting with Symptoms of Dry Eye Disease ..........................................................................22

2.2 Percentage of Patients Who Self-Medicate ................................................................................................22

2.3 Specific Treatment Recommendations ......................................................................................................23

2.4 The Need for Follow Up and Progress Reports ........................................................................................24

2.5 Meeting Report from the CRO Vancouver MeetingBlink Mechanics: Viscoadaptive Technology for the Ocular Surface ........................................................25

The Ophthalmic Approach to Dry Eye Disease 9

CRO: Drs. Arshinoff and Herzig, as ophthalmic surgeons, whatpercentage of your surgical candidates present with symptoms ofpre-existing Dry Eye Disease and in those patients does a moderateto severe rating affect your decision to perform particular types ofsurgical procedures?

Dr. Arshinoff: Patients with underlying Dry Eye Disease commonlypresent for unrelated procedures. The Dry Eye Disease percentage,of course depends upon the procedure under discussion, becauseophthalmologists perform different surgeries on patients that fall intodifferent age brackets. Strabismus surgery is most common in children,whereas the average cataract patient is usually around age 70. If weconfine ourselves to consideration of procedures on the most commonolder demographic of cataract/glaucoma/cornea/lid surgery procedures,estimates of Dry Eye Disease frequency still vary widely, depending uponfactors such as glaucoma patients having much greater pre-surgicalexposure to aggravating preservatives in their eye drops, geographic/seasonal differences (household dryness in winter considerably aggravatingsymptoms), and even things like whether simultaneous bilateral or unilateralprocedures are planned (symptoms are much reduced in bilateral surgicalpatients, because both eyes feel the same pre- and postoperatively). Ageneral estimate of patients presenting with moderate to severe Dry EyeDisease is 10% to 20%. So, the real question is: How should the surgeonapproach this problem? My own preference is to try to make things simpleand easy. If a given patient has Sjögren’s syndrome, a history of constantneed for artificial tears, even if only in winter, infero-nasal corneal stainingor scarring, Salzmann’s nodules, signs of previous trachoma, etc.,I note it on my chart, and advise the patient to consider simultaneousbilateral surgery (if they have bilateral cataracts), try to avoid surgery inDecember to February, and discuss with them, at the outset, their expectedincreased need for lubrication perioperatively.

Dr. Herzig: Very few of my patients who present for surgery actuallycomplain of dry eye symptoms. If a patient does have both dry eyesymptoms and findings, then it clearly is a problem that requires attentionbefore proceeding with surgery. I would not perform either cataract orrefractive surgery without both the subjective and objective evidence of aperson’s Dry Eye Disease being eliminated or significantly reduced.

1.1 Rating Dry Eye Disease Patients Prior to Surgery

Chapter 1: The Ophthalmic Approach to Dry Eye Disease

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

A general estimate of patients presenting with moderate to severe Dry Eye Disese is 10% to 20%.

10 Approaches to the Treatment of Dry Eye Disease

1.2 Effect of Dry Eye Disease on Surgical OutcomesCRO: In your opinion, if left untreated, can Dry Eye Disease adverselyaffect the overall outcome of particular types of surgical procedures?

Dr. Arshinoff: Surgical patients, having agreed to undergo surgery, a hugeexperience for them, are not likely to ignore Dry Eye Disease symptoms iftheir surgeon simply says “Don’t worry about it. You had it before, and youwill still have it later.” Patients usually do not understand that if they undergoa 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, everyocular complaint of a surgical patient must be discussed before surgery, andclear management plans and expectations should be established. So, forexample, 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 weconvince the patient to undergo refractive components of surgery, expectingto significantly reduce the need for spectacles, the first thing the patientnotices postoperatively is not their 20/20 distance vision, but their increasedtearing outside, now that they no longer wear spectacles. To make thingsworse, if the surgeon was inattentive to Dry Eye Disease when biometry wasperformed, significant errors often result from biometry on a dry cornea,covered with mucous and smeared, evaporated tear aggregates, so the patientmay also complain about not seeing 20/20, in addition to the tearing. Thepatient may also complain that the postoperative eye drops burn excessively,and may not take them as prescribed. Simply put, ignoring Dry Eye Diseasein cataract patients is a recipe for patient and doctor misery.

Dr. Herzig: Both cataract and refractive surgery can cause ocular dryness evenin previously asymptomatic patients. If a patient already has Dry Eye Diseasepreoperatively, surgery will almost always aggravate their condition.

Both surgeries also require meticulous refractive planning beforeproceeding. The presence of Dry Eye Disease preoperatively makes refractiveand corneal measurements impossible to measure accurately resulting in lessthan satisfactory outcomes. Continued Dry Eye Disease postoperativelyresults in an uncomfortable patient who is unhappy with their visual result.

Every ocular complaint of a surgical patient must be discussed before surgery, and clearmanagement plans and expectations should be established.

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


1.3 Pre- and Post-Surgical Protocolfor 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 patientsscheduled for surgery?

Dr. Arshinoff: Ophthalmology is complex, and Dry Eye Disease is amultifactorial disorder, with multiple causes and variable symptoms. It isdifficult to have a specific protocol for every patient, but attentiveness to anumber of issues is critical:

1. Examine the patient carefully, and decide upon, discuss, and notedecisions about management of ectropion, entropion, or any other lidissues (blepharitis, rosacea...) at the initial visit. If the patient and familyknow and understand that you intend to correct their abnormal lid positionat a second procedure a few weeks after their cataract surgery, they will bemuch more tolerant of postoperative symptoms. These patients are happyafter their cataract surgery, and very happy after their lids have also beenrepaired, when they see clearly and feel a lot better.

2. When performing biometry, attention should be paid to the tear filmand any dry eye symptoms. It is a good idea to perform topography on every-body and to administer one or more drops of a hypo-osmolar artificial tearbefore performing topography and biometry. The technician should be trainedto assess the tear film before performing every biometry, and should notify thesurgeon of any problems encountered that may affect accuracy.

3. All patients with Dry Eye Disease symptoms should becounselled about the beneficial effects of spectacles to reduce Dry EyeDisease symptoms, and the expected increase in symptoms if the patientchooses not to wear spectacles postoperatively. Artificial tears should beprescribed preoperatively and continued postoperatively, avoiding adminis-tration coincident with other agents.

Dr. Herzig: Pre- and post-surgical treatment protocols for patients withDry Eye Disease need to vary with the etiology and severity of the symp-toms and findings. The problem may simply require increasing a patient’suse of artificial tears or adding Restasis and steroid drops to their presentregimen.

Frequently these patients have meibomian gland dysfunction (MGD),the most common cause of evaporative Dry Eye Disease. They need toaggressively clean their lids consistently with or without the use of antibi-otic/steroid ointments. I have found the Lipiflow treatment to be the bestapproach to treat MGD but not all patients can afford it. Using Lipiflow hasallowed me to do refractive surgery on some Dry Eye Disease patients thatwould have been refused surgery in the past.

When performing biometry, attention should be paid to the tear film and any dry eye symptoms.


1.4 Specific Treatment Recommendations

CRO: If you recommend a specific Dry Eye Disease treatment orprotocol what do you base your recommendation on?

Dr. Arshinoff: Specific management of Dry Eye Disease perioperativelydepends upon the specific diagnosis. Lid malpositions should be corrected,if possible, preferably after the proposed intraocular surgery, to preventrecurrence of lid damage to the corrected lids by a lid speculum.Blepharitis and rosacea should be managed with lid scrubs with whicheverof the available agents the patient prefers. If very severe, simple oraltetracycline 250 mg po hs for two months is a wonderful treatment withminimal side effects. Severe cutaneous rosacea should be referred to adermatologist, not because an ophthalmologist cannot prescribe effectivetreatment, but because long-term follow-up is usually necessary. MGD canbe managed with massage, Lipiflow treatments, some of the forceps nowavailable, and oral tetracycline, as above, which liquefies meibomiansecretions. Severe Dry Eye Disease or Sjögren’s may require long-termRestasis. Once all of these have been assessed and managed, “simple dryeyes” are more easily managed with periodic artificial tears prn. There arenumerous tears on the market, and all of us have a preference for one kindor another. My rheology background makes me lean toward hyaluronic acidcontaining tears, but I allow the patient to choose what they like best froma few different classes of tears that I give them to try. New tears are alwaysappearing, because the market is huge and lucrative, and none, so far, isperfect. Tears are, in general, getting better. Preservative-free preparationshave the great advantage of being less damaging to the ocularsurface, and we will likely continue to see more and better non-preservedartificial tears.

Dr. Herzig: As previously mentioned, the most common cause of Dry EyeDisease is MGD. This affects primarily the lipid layer, which then affectsthe aqueous layer by causing more rapid evaporation. Since Dry EyeDisease also causes conjunctival pathology, there is always some lossof mucin as well. The goal of treatment is almost always to alleviate theMGD whether with regular lid scrubs or Lipiflow. Most patients alsoneed artificial tears, preferably non-preserved, with or without steroiddrops and Restasis. In some patients the addition of punctual plugs can bevery helpful.

Preservative-free preparations have the great advantage of being less damaging to theocular surface.

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


1.5 Viscoadaptive Class of Eye DropsCRO: Dr. Arshinoff, how would you categorize and describe thevarious types of artificial tear solutions available today and canyou describe their modes of action?

Dr. Arshinoff: In 2007, The International Dry Eye Workshop postulatedthat Dry Eye Disease is caused either by an aqueous deficiency or byevaporation. Which is why most all of the dry eye treatment choicesavailable today are Newtonian-based tear solutions that will either:a) replace water as for example: Hypotears, Theratears, and TearsNaturale, or b) reduce the rate of evaporation as for example: Systane.Successive iterations of the Systane family of tear products, with themost recent being Systane Gel Drops have progressively targetedreduced tear evaporation as their therapeutic mechanism of action.

However, another option has recently become available in theform 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 morecorrectly considered to be a blink-activated pseudoplastic elastoviscoussuspension of sodium hyaluronate chains, glycerol and free water.

As for its mode of action, the energy that is exerted with each blinkforces the suspension of sodium hyaluronate chains and glycerolmolecules to spread out evenly over the surface of the eye releasingglycerol for lubrication and water for hydration. When the blink isrelaxed, the suspension returns to its original state and is ready forthe next blink. In this way free water is delivered with each blink to theaqueous layer and glycerol reinforces the lipid layer.

The benefits of this type of “viscoadaptive” action are: prolongedresidence time on the cornea, smoother blinks with a higher degreeof comfort, very good corneal hydration, and measurably less tearevaporation.

i-drop is a blink-activated pseudoplastic elastoviscous suspension of sodium hyaluronatechains, glycerol and free water.

In this way free water is delivered with each blink to the aqueous layer and glycerolreinforces the lipid layer.


1.6 A New Modality for the Treatmentof Dry Eye SyndromeSteve A. Arshinoff, MD, FRCSC

This Meeting Report has been excerpted from a presentation given at the CSCRS Toronto Meeting held on November 9, 2013.

IntroductionDr. Arshinoff began his presentation by outlining the topics he would bediscussing, specifically: a review of past and current choices for the treatmentof 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 visco-adaptive eye drops.

Evolution of Dry Eye Treatment Approaches Dr. Arshinoff referenced the 2007 International Dry Eye Workshop at whichCommittee members developed a framework for the definition, classificationand mechanisms of dry eye (Fig. 1).

He noted that dry eye has become somewhat of a “catch-all” term whoseunderpinnings are the result of either excessive tear evaporation or decreasedtear production. Prior to the development of Restasis® (Allergan, Markham,ON), an anti-inflammatory form of artificial tears, pharmaceutical companiesresponded by providing watery artificial tears, replacing water, or by decreasing

Fig. 1 Etiology of dry eye

The Definition & Classification of Dry Eye DiseaseGuidelines 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

Asymptomatic

Dry EyeDisease

EvaporativeDry Eye

other

other

AqueousDeficientDry Eye

Lid-relatedDisease

Other OSD

MGD AnteriorBlepharitis

Allergic conjunctivitisChronic infectiveand non-infectiveKeratoconjunctivitisConjunctivitisPost-refractive

Prodromalstates

Non-Dry EyeDisease


evaporation. There are currently three types of eye drops available: 1) Anti-inflammatories such as Restasis; 2) Aqueous replacement, such as HypoTears®

(Novartis, Dorval, QC), TheraTears® (Advanced Vision Research, an Akorncompany, Ann Arbor, MI); and 3) Evaporation reducing agents, such asSystane® Gel Drops (Alcon, a Novartis company, Mississauga, ON).

Dr. Arshinoff cited Alcon’s development of successive iterations of Systaneeye drops based on a shift in direction from replacing water to preventingevaporation, a direction that merits further examination. This past decade, forexample, has seen a product evolution from Systane, to Systane Ultra, toSystane Balance, to Systane Gel Drops.

Rheology: Studying Fluid Behaviour Dr. Arshinoff presented an explanation of rheology, the science of how fluidsrespond to forces, or the mechanics of fluids, and how it works in the devicesophthalmologists use.

The study of rheology involves concepts relating to vis-cosity, elasticity and the cohesion/dispersion continuum. Hepointed out that rather than a straight line of correlating prop-erties, OVDs possess endless variation of the above proper-ties, such as viscosity changes under stress (Fig. 2).

Dr. Arshinoff stated that there are four different ways thatthe viscosity of fluids can respond to forces, the first of whichis Newtonian, which means that no matter how much forceyou expose the fluid to, its viscosity remains the same (Fig. 2).

Another example is the plastic response curve, fromwhich “plastic” materials derive their name. When exposed tovery high forces, plastics are fluid, but when exposed to verylow forces, they are solid. Imagine, suggested Dr. Arshinoff,trying to use a plastic OVD in ophthalmic surgery. Thesubstance is injected into the eye as a liquid, but once at rest,it turns solid, which would make surgery difficult. As a result,what is used instead are devices called pseudoplastic. In Figure 2, the blue linerepresents a pseudoplastic fluid which means that, like a plastic under highforces going through a syringe, it has very low viscosity. However, whensitting in the eye, the viscosity increases — reaching what is called a limitingor a zero-shear viscosity — remaining fluid. The graphlevels off and does not go higher than whatever the zero-shearviscosity is. The corollary is: The only useful visco-sitynumber for OVD classification is its zero-shear viscosity, asany other viscosity value is dependent upon the shear rate atwhich it was measured, which is often not disclosed by themanufacturer.

The pseudoplasticity graphs in Figure 3 illustrate thedifferent OVDs in common use in North America, although theHPMCs can easily be seen to not be very pseudoplastic. Notethat 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 theopposite of pseudoplastic, meaning that the more force it isexposed to, the more viscous it becomes. A classic exampleof a dilatant fluid is albumin (egg whites).

Table I Ophthalmic viscous Newtonian solutions

• Viscosity constant, independent of shear rate

• Exampleso Low pseudoplasticity Surgical OVDs (~ Newtonian)

- OcuCoat - I-Cel- HPMCs

o Topical artificial tears (± Newtonian) - Hypotears- Tears Naturale- Systane- GenTeal- Refresh- Tears Plus- Celluvisc

Rheometric Patterns of Fluid Behaviour: Viscosity

Fig. 2 Pseudoplasticity curves: rheometric patterns of fluid viscosityresponse to increasing force (shear rate).


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 orless horizontal, meaning that the viscosity does not change with changingshear rate, except for the very end, where the levels descend. What this indi-cates is that if you are going to use an HPMC OVD, it is going to behave moreor less the same in the eye, irrespective of the ambient shear rate. The surgeonwould have to push down very hard on the syringe, exposing it to a lot offorce, to inject the OVD through a cannula. For this reason, HPMC OVDs arepackaged 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 SolutionsNon-Newtonian solutions are used in intraocular surgery, most of which arepseudoplastic (Fig. 3). Highly pseudoplasticity means that they exhibit low vis-cosity at high shear, high visco-sity at low shear, and possess a limiting or zero-shear viscosity. Examples of this are Healon®, Healon GV® (Abbott MedicalOptics, Markham, ON) and i-Visc.

“Viscoadaptive” Artificial Tears:What It Means and What It DoesArtificial tears containing hyaluronic acid — a long enough chain that behaveslike a pseudoplastic material — were first developed twenty years ago; Hylashield.

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


Dr. Arshinoff stated that three terms — viscous, elasto-viscous and viscoadaptive — are used to describe the varioustreatments for dry eye. He noted that the term “visco-adaptive” may be confusing to some practitioners, as“viscoadaptive” when used to describe tears, has a differentmeaning than when the same term is used to describe intra-ocular OVDs.

With respect to intraocular surgical OVDs, visco-adaptive signifies that the behaviour of the OVD changesfrom a highly viscous cohesive — like a Super Healon orSuper Healon GV — to a pseudodispersive. However, Dr.Arshinoff pointed out, pseudodispersive is not the same asdispersive, hence thedifferent term: pseudo-dispersive means“fractureable solid under high stress.” Both i-Visc Phaco andHealon5, when they are absolutely stationary, can behave likefractureable solids when exposed to high frequency stresses.

The way you make it behave like a solid is by changing the ambientenvironment inside the anterior chamber. So if you increase your flow rate offluid 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 canchange our flow rate in the eye and make the OVD behave“like a dispersive,” but not through the same mechanism. Youcan make Healon5 or i-Visc Phaco behave like extremelyviscous “super" Healon GVs under low turbulent conditions,or, by increasing turbulence in the anterior chamber, theybehave as pseudodispersive fractureable solids.

Analysis of rheological behaviour generally looks attypical 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 ratesettings. However, Healon5 will initially behave as a viscous-cohesive, but with increasing flow rates above 25 cc/min,behaves as a fractureable solid.

Composition and Behaviourof Viscoadaptive Artificial TearsIn artificial tears, “viscoadaptive” refers to an elasto-viscous solution thatchanges under stress. There are chains of hyaluronic acid that are not as longas those that would be used in an intraocular OVD. When these chains areexposed to the force of blinking, they are more elastic thanthey are viscous. When you blink with an elastic in your eye,you blink and it compresses; it does not go anywhere. Whenyou open your eye, it comes back and stays there, becauseit is acting like a spring. This was the first concept in devel-oping a viscoadaptive tear.

The second concept is to add something to the tear whichwill make it behave differently again under stress, whichresulted in glycerol, a small molecule, being added. Becausethe hyaluronic acid absorbs all the water, and there is no freewater in the solution, when compressed, the viscoadaptiveelastoviscous artificial tear solution excludes the glycerolfrom its structure, liberating it to the surface. As a result, as

Fig. 5 Dispersive and cohesive properties of non-Newtonian tear solutions.

Non-Newtonian Tear Solutions:Viscoadaptive?

Fig. 4 Behaviour changes in ophthalmic viscoadaptive OVDs.

Fig. 6 Viscoadaptive eye drops mode of action.

“Viscoadaptive” Eye Drops


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-drop® (I-MED Pharma, Montreal, QC) is the first product of its type on themarket, made of high-molecular weight hyaluronic acid and glycerol; it is anelastoviscous 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 acidbinding sites, so when you take these chains of hyaluronic acid and put it onyour cornea, it adheres to the corneal surface. Therefore, when blinking itremains fixed: it is stuck to the cornea. Together with the water layer andthe glycerol that moves in and out with blinking, the formula represents thepotential for an improved artificial tears product.

In 2003, the first viscoadaptive eye drop was launched in Canada,followed by Oasis Tears® (Oasis Medical, Glendora, CA) in 2009 — the firstviscoadaptive 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 asthe first non-preserved multidose viscoadaptive eye drops.

Patient Benefits of Viscoadaptive Artificial Tears Dr. Arshinoff summarized his presentation by describing the potentialadvantages of i-drop artificial tears. i-drop Pur artificial tears are pseudo-plastic elastoviscous tears, with a second molecule to increase lubrication.They exhibit polymer crowding, so there is no free water. In addition, they areblink 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 betterover the eye. It releases glycerol to increase lubrication and it lasts longer thanother drops in the i-Drop family of products. Dr. Arshinoff mentioned that asit launched only one year ago, there is not yet substantial clinical experienceto report.

The proposed patient benefits are: enhanced protection of the cornea;prolonged residence time on the cornea because of the binding sites; smootherto blinks; higher degree of patient comfort; very good corneal hydration;and less tear evaporation, which seems to be the direction in which othercompanies are moving in developing their eye drops.

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 actionis referred to as viscoadaptivity.

How Viscoadaptive Eye Drops Worki-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.

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.

GLYCERIN

HA

CROSS SECTION OF THE TEAR FILM

MUCINLAYER

AQUEOUSLAYER

LIPIDLAYER

Two Choices for Long Lasting Relief

VISCOADAPTIVE EYE DROPS

I-MED Pharma 800.463.1008www.osdcare.com

B

Enhanced Corneal Protection

Prolonged Residence Time

Smoother Blinks

Higher Degree of Comfort

Excellent Corneal Hydration

Reduced Tear Film Evaporation

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.

i-drop® Pur0.18% viscoadaptive HA Provides immediate, long lasting relieffor mild to moderate dry eye diseaseindicated for use with contact lenses

i-drop® Pur GEL0.3% viscoadaptive HA Provides immediate, long lasting relief for moderate to severe dry eye disease

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CRO: Drs. Rhéaume and Maharaj, as optometrists when a patient pres-ents in your practice with symptoms consistent with Dry Eye Disease, doyou begin by treating their symptoms, or do you begin by testing in orderto confirm the presence of Dry Eye Disease?

Dr. Rhéaume: Although symptoms are very important, I never rely on themonly. I always begin by testing in order to confirm the presence of Dry EyeDisease. 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 etiologyof the Dry Eye Disease. Am I in the presence of a tear deficiency affectingthe lipid, the aqueous, or the mucin layer; or am I dealing with a cornealirregularity secondary to an epithelial basal membrane dystrophy, a pin-guecula or a pterygium? I will also be able to assess if there is a lid surfacingproblem like an ectropion or an entropion and to evaluate the lid marginconditions for possible chronic blepharitis or meibomianitis. So for me, andfor any given condition, testing is an absolute must.

Dr. Maharaj: I approach all Dry Eye Disease patients by determining etiologywith a comprehensive list of diagnostics. Only in this way can the appropriatetherapy be prescribed. As the majority of Dry Eye Disease patients are of amixed etiology (evaporative and/or aqueous, cicatricial), it is important todetermine the prevailing cause as well as the duration of symptomology.

2.2 Percentage of Patients Who Self-Medicate

CRO: What percentage of your first-time Dry Eye Disease patientspresent already self-medicating? In those patients, do you ever recommendthat they change to a different treatment regimen?

Dr. Rhéaume: I would say that a good 50% of my first-time Dry Eye Diseasepatients present already self-medicating. The reason for this is that many eyespecialists simply tell their patients, “You have a Dry Eye Disease, go to thepharmacy and get yourself some artificial tears. You will be able to find outwhich one works best for you.” Also, because the artificial tears are over-the-counter products, many patients with symptoms of Dry Eye Disease will trydifferent artificial tears without having seen an eye specialist. In those

2.1 Patients Presenting with Symptomsof Dry Eye Disease

Chapter 2: The Optometric Approach to Dry Eye Disease

Testing for Dry Eye Disease will allow me to confirm the diagnosis, and more importantly toassess if I am dealing with a mild, moderate, or severe condition.

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

The Optometric Approach to Dry Eye Disease 23

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

Dr. Maharaj: Almost 100% of symptomatic patients are self-medicatingineffectively. Patients often reach for the nearest “red-free” eye drops which dolittle to treat the underlying cause. Most times, the products that my patientschoose mask the redness with a vasoconstrictor but this does little to alleviate thediscomfort they are experiencing. Depending on the etiology, I will switch to apreservative-free option first, a hyaluronate in most cases, and an oil emulsifiedoption 3rd.

2.3 Specific Treatment Recommendations

CRO: When would you recommend a specific treatment to your Dry EyeDisease patients, and what do you base that recommendation on?

Dr. Rhéaume: As much as possible, I try to recommend a specific treatmentbased on its ability to positively affect the layer of tears responsible for theDry Eye Disease. For example, if I have a patient with Dry Eye Diseasesecondary to arthritis, I will most likely be able to identify the aqueouslayer as being deficient. In this case, I would use regular artificial tears toimmediately help the patient, but I would also prescribe drops with animmunosuppressant like cyclosporine to help relieve the immunologic attackon the main lacrimal glands. If I have a patient with a lid margin problem likea chronic blepharitis, along with the use of antibiotic/cortisone ointment,I would use artificial tears that more specifically enhance the lipid layer.

Dr. Maharaj: Up to 86% of patients have meibomian gland dysfunction(MGD) as a contributing component of their Dry Eye Disease so managing thelipid layer will decrease evaporation which will preserve the aqueous layer.The mucin layer should not be negated either; which is why, once the lipidlayer is stabilized, I often will add non-preserved hyaluronate to maximizethe mucin layer.

Most importantly, I tell my patients which product to get and to stick with my recommendation.

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

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

I recommend a specific treatment based on its ability to positively affect the layer of tearsresponsible for the Dry Eye Disease.


2.4 The Need for Follow Up and Progress Reports

CRO: Do you regularly follow the progress of your confirmed Dry EyeDisease patients who are receiving treatment?

Dr. Rhéaume: I always want to follow patients who are receivingtreatment. 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 andschedule the follow-up visits in a timely manner. In general, I will schedule afirst follow-up visit in one month. If on the first visit I prescribe a medicatedointment for chronic blepharitis, I will follow the patient in one week toevaluate the response to the treatment, and then have the patient back 3 weekslater. If I have a satisfactory therapeutic response at the first follow-up visit,I will recommend the patient to return every 6 months.

Dr. Maharaj: Yes, I follow my patients regularly, depending on theseverity 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 whetherthere is improvement on the course of action taken.

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

In general, I will schedule a first follow-up visit in one month.


2.5 Blink Mechanics: Viscoadaptive Technologyfor the Ocular SurfaceRichard Maharaj, OD, FAAO

This Meeting Report has been excerpted from a presentation given at the CRO Vancouver Meeting held on September 7, 2014.

INTRODUCTIONWhile 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 tomoderate dry eye patients. There are two components in the discussionof the mechanics of blinking and viscoadaptive technologies. The first is whatthe eyelid does on a given blink. The second is the microanatomy involved inthe blink at the inner and outer eyelid surface. Dr. Maharaj has observed thata blanket approach to treatment with artificial tears isn’t an effective model ofcare for the multifactorial dry eye patient.

Following the artificial tear evolution and consideration of the chemicalproperties of various artificial tearproducts, industry has moved towardmeibomian gland driven therapies with specific focus on lipid layersupplementation.

Blink Mechanics and Viscoadaptive DevicesIn a normal functioning eye, the eyelid closes as the superior eyelid comesdown and meets the bottom eyelid, grabs onto the lipid layer and the oil filmrises with the upper lid to coat the tear film. This is clearly shown on videoimaging 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 isresponsible for achieving comfort, and in fact can be the source ofdiscomfort, said Dr. Maharaj. He noted that one of the current focuses of theTear Film & Ocular Surface Society (TFOS) is the mechanics and metrics ofblinking.

Computer vision syndrome is not surprisingly on the rise. A common athome tip for patients involves blinking 20 times every 20 seconds by looking20 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. Maharajstated that understanding blink mechanics makes it easier to understand themechanisms involved in the development of the dry eye.

Mechanics of Dry Eye DiseaseDr. Maharaj described rheology, the behavior of fluids in response to appliedforces, which is different from Newtonian physics; fluids respond differentlythan solids. An appreciation of this difference is crucial in reviewing visco-adaptive technology and pseudoelastic viscoadaptive tears.

While dry eye is a chronic condition for which there is no cure, ECPs canmanage it. Dr. Maharaj counsels patients that they can be treated and progressto a point where they are more comfortable, where they may not notice theireyes 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 prevalenceof dry eye ranges from 7 percent up to close to 50 percent, depending on thestudy. In Dr. Maharaj’s dry eye clinic, more than 90 percent of patients actuallyexhibit the condition in itself; however, in general eye care practices, dry eye asa condition is second only to cataracts. Pre-identification of the dry eye patientundergoing surgery and pretreatment is far more likely to result in patientshaving a better postoperative experience.

When considering sending a 65-year-old patient to a cataract surgeon forcataract surgery, for instance, preparing the patient’s ocular surface has been


shown to contribute to their postoperative success. Patients that lack preoperativetreatment have a four times greater risk of their dry eye worsening followingsurgery. In the next two to ten years, stated Dr. Maharaj, practitioners will seetheir role in the perioperative arena growing, and rightfully so. Based on currenttrends, he predicted greater discussion and use of triglyceride omega 3s for addedsystemic impact on meibomian gland disease.

Dr. Maharaj discussed osmolarity as a dry eye metric that is important tounderstand in a general setting. Tear osmolarity is a valuable tool, relative tothe Ocular Surface Disease Index (OSDI), corneal staining and Schirmer teartest and has been shown to be more sensitive and more specific than these othermeasures.

When examining the correlation to the severity of the condition, osmo-larity has the strongest correlation. To identify existing dry eye patients in ageneral practice, it is extremely relevant for patients that may not be sympto-matic but are silently suffering. Those are the ones who may, in fact, have ahyperosmolar tear film, which means that they do have a higher component ofsalt and proteins like MMP-9 and other inflammatory cytokines in their tearfilm. If this inflammation is elevated and the patient is not symptomatic, thechronic inflammatory environment will eventually produce symptoms.

Blink MechanicsUnder a slit lamp, it is quite common for the lower eyelid to hang slightlylower than the iris, which is very common and produces infrequent, incom-plete blinking. There are, however, some patients who don’t have this charac-teristic; they have a neat palpebral fissure, but the eyelid stilldoesn’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 eyelidcome together, touch and then move away. However, when one starts toexamine the mechanics of a blink, one sees that this is, infact, the opposite of what occurs (Fig. 1). The lower eyelidmakes very little vertical movement; however, the superioreyelid does most of the travel and there’s actually atorsional component to it. That’s not even taking intoconsideration ethnicity, the thickness of the tear, the innereyelid surface, or the lid wiper itself, the band of tissue thatalso impacts the way eyelids move.

In Dr. Maharaj’s experience, examining the asymmetrybetween one eye and the other, one often sees anatomicaland morphological changes in the meibomian gland of theeye that has a decreased blink rate and decreased blinkcompleteness. In patients whose eyelids come together,there is a correlation with meibomian gland atrophy ortruncation: if the eyelids are not coming completely together,the gland orifice isn’t receiving any negative pressure todraw 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 superiorcomponent and a torsional component of the upper eyelid moving mainly upand down and slightly, with a minor rotation. However, the inner eyelid barelymoves vertically; it actually has a nasal movement. This is an extremelycomplex movement with the forces being applied to the cornea and to theocular surface, in addition to the forces being applied to the fluid between theeyelid and the cornea.

Fig. 1 Mechanics of blinking.


Dr. Maharaj expressed his opinion that there are somemore effective solutions for dry eye than artificial tears.Regardless of ethnicity or the shape of the eye, there isslight vertical movement on the superior eyelid; thereis nasal and torsional movement of the superior eyelid; theinferior eyelid margin typically makes lateral movements.This produces a type of shearing force. What occurs is thatrather than the front surface closing, it is the posterior lidmargin that closes. The mucocutaneous junction otherwiseknown as the Line of Marx (LOM) forms a ridge that is notmeeting up. There’s no seal of the superior and inferiorLOM on lid. A quick test for this is the light test using atransilluminator (Fig. 3). With retroillumination similarto what is being depicted in the figure, a slight gapbecomes apparent.

Even in those patients who, under a microscope, appear to be blinkingcompletely, they may, in fact, have inadequate lid seal which will exacerbate thecondition. This will lead to increased friction, causing the lid wiper to becomeinflamed. In this case, the posterior lid surface is in direct opposition to the corneawith a thin pre-corneal tear film acting as a buffer betweenthe two surfaces. The result is tissue with repetitive micro-trauma causing eventual, epitheliopathy and lid inflamma-tion. The meibomian glands are very closely associated to thelid wiper and this is where Meibomian Gland Dysfunction(MGD) can start in some patients. Dr. Maharaj stated thatwhile it is important to distinguish between aqueousdeficiency and evaporative dry eye, he does not view thesituation as one or the other.

This condition is very much a spectrum disease. At somepoint, MGD will lead to up-regulation of the lacrimalgland, eventually causing it to become inflamed, resulting inaqueous deficiency. All dry eye patients appear at some pointon this spectrum.

Mechanics of Dysfunctional BlinkingIn terms of the MGD cycle, Dr. Maharaj stated that the TFOS DEWS algorithm isextremely complex; therefore, he has extracted some of the elements he feels aremost relevant (Fig. 4). He suggests that practitioners examine the eyelid aperture ofthe blink first, looking for the lid seal. When the blink becomes dysfunctional, itresults in lid wiper microtrauma due to friction. The resultingsymptoms can include extreme pain, mild to severe contactlens intolerance and visual instability. This will lead to hyper-osmolarity with an up-regulation in MMP-9 (Matrix metal-lopeptidase 9), salts and other proteins. Tear hyper-osmolaritydrives the tear solutes toward the lid margin and meibomianglands and thus the evaporative and aqueous cycle begins.This process applies to the vast majority of mild to moderatedry eye patients and is therefore a good starting point indetermining the goal of an artificial tear.

Looking at the problems created by that cycle, the firstthing that occurs is decreased blink rate and poor closure.Therefore, said Dr. Maharaj, the goal in tear film thera-peutics should be aimed at increased residence time on thecornea with minimal effect on vision stability. Examining

Fig. 2 Breakdown of blinking process.

Fig. 4 Components of the TFOS DEWS algorithm.

Fig. 3 Transilluminator test.


the attributes of a topical treatment that allows it to last longer on the eye isessential. For instance, how it interacts with the eyelid surfaces with the shearingforces previously discussed, and whether or not it stabilizes the tear film.

Current Dry Eye TreatmentsThe goal of therapy is long-term stability, which is a very important part of thetear chemistry — an essential element. As an immunomodulator — a targetedanti-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 lead-ing cause of dry eye disease around the globe. With this, replacing the lipidlayer became the utmost priority.

The term “viscoadaptive” was introduced; Dr. Maharaj remarked that itappears to be a confusing term. When doctors refer to the viscosity of asolution, 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 comparedto forces on solids because fluids are very much like air; the forces are moreor 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 tomove like a liquid are very, very high. The three tenets are understandingviscosity, understanding elasticity, and then examining the cohesive anddispersive nature of fluids.

Dr. Maharaj stated that there are four patterns ofrheometric behavior of fluids (Fig. 5); namely Newtonian,pseudoplastic, plastic and dilatant. In Figure 5 the furtherto the left on the x axis, the lower the shear forces beingapplied; the further to the right, the higher the shear force.The y axis relates to viscosity. The solution can be a liquidwhich will be lower down on the graph or, it can behavelike glass or a fractureable solid which will appear higheron the graph.

Newtonian Tear SolutionsMany fluids are pseudo-Newtonian; they’re not quiteNewtonian; however, they possess more or less these samecharacteristics. On the other hand, plastics when exposed toa great force can carry liquid-like characteristics.

As shown in Figure 5, fluid-like behaviors or lowviscosity behaviors at a certain force will become moreviscous. The term for this is zero shear rate. Past the zeroshear rate it becomes a fractureable solid. The zero shear rate of a pseudoplasticmaterial is important in surgery (intra-operative surgery is really where it allevolved from) because there has to be a point at which it doesn’t become moreviscous. If it did, it would harden in the anterior chamber making surgery verydifficult. Pseudoplastics have evolved and have been adapted to the ocularsurface specifically because of this fact.

Dr. Maharaj stated that this is particularly important when consideringartificial tears: The eyelid moves around and applies shear forces. Viscoussolutions that still have Newtonian-like behavior with long and short branchedpolymers behave in more or less a Newtonian fashion. Pseudoplastic orviscoadaptive solutions will behave differently to the various moments in a blink.

Rheometric Patterns of Fluid Behaviour: Viscosity

Fig. 5 Variations in applied force.


Non-Newtonian Tear SolutionsRegarding blink forces, instead of a tear solution progressing from a cohesive fluidto 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 hyaluronicacid (HA). In order to make it a dispersive substance, one can add a short-chain branched molecule that is not bound to the HA that can actuallyseparate from the HA by force. What happens with an artificial tear with HAand a short-chain branched polymer is exposed to blink forces, the HAseparates — 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 willalmost behave like a contact lens — a fractureable solid — in the eye whenthe eyelid closes because it is applying a high amount of shear force. Whenthe eyelid opens, the solution returns to a fluid state. Interms of applying these forces to an artificial tear, consid-eration needs to be given to the way the eyelid moves witha HA-based eye drop compared to a Newtonian solutionlike methylcellulose, for example.

In the surgical context, the pseudoplastic curves ofsome of the ophthalmic viscoadaptive devices used inintraocular surgery are shown in Figure 6. The curves varydepending on the device used. Dr. Maharaj noted that someexamples currently used in surgery were actually used toderive hyaluronic-based eye drops. Healon® 5 (sodiumhyaluronate, AMO, Markham, ON) and iVisc® (sodiumhyaluronate, I-Med Pharma, Montreal, QC), for instance,are commonly used. Depending on the shear forcesapplied, the liquid will eventually reach a certain viscosityand not go past that point. Artificial tears such as TearsNaturale® (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 theeye regardless of the eye’s blink mechanics.

Features of Pseudoplastic Elastovicous TearsThe first Canadian pseudoplastic elastoviscous tear is known as i-drop®

(I-Med Pharma, Montreal, QC). It is distinguished by its high molecularweight sodium hyaluronate combined with a short-chain branchedpolymer, glycerin. The interesting feature of HA is that all the cells in thebody, including those of the cornea, have hyaluronic binding sites. The HA inthe eye drop binds to these binding sites, anchoring the tear onto the ocularsurface. The HA actually combines with the water found in the tears.

It excludes the glycerin which rises to the surface as the eyelid blinks. Theglycerin provides a lubricating surface to the blink, decreasing friction on theocular surface. Once the eyelid reaches down to the bottom, and the eyelidcomes up and the solution returns to its original low viscosity. As a result ofthis process, the residence time is high. The tear mimics all three layers of thetear film simply by virtue of its physical properties.

Dr. Maharaj uses this approach in his general patients, in order to prolongresidence time, decrease evaporation and create visual stability. A highmolecular weight hyaluronic-based drop allows this. From a rheologicalperspective, pseudoplastic elastoviscous tears, or PETs, produce the desiredeffect, mimicking naturally occurring tears.

Intraocular OVD Pseudoplasticity Curves

Fig. 6 Pseudoplastic curves of viscoelastic devices.


The problem of decreased blink rate and closure requires that a topi-cal tear increases the residence time on the eye, which i-drop achieves.This is accomplished through decreasing friction on the ocular surface withunbound glycerin and stabilization of the tear film via HA. This decreasesevaporation and stabilizes the tear film, providing patients substantiallygreater comfort.

Dr. Maharaj stated that the last benefit of some of the new dropscoming to market, i-drop being one of them, is that they are packagedin a multi-dose, non-preserved bottle. He views the lack of preservativesas an important benefit. The bottle form may make it more convenientfor patients.

The first clinical study of hyaluronan eye drops was undertaken in1982. At the time, HA was found to have a much longer residence time.This led to the Hylan™ Surgical Shield (Elastoviscous Hylan SurgicalShield, 0.45%) which surgeons were using during surgery to coat andprotect the ocular surface.

Dr. Maharaj suggested that when addressing the ocular surface,practitioners ought to carefully consider the true etiology of the conditionand all available solutions. With an abundance of products on the marketand patients not knowing which to choose, Dr. Maharaj suggested that eyecare professionals make very specific patient recommendations.

It is now known that patients are blinking less frequently and lesscompletely, which Dr. Maharaj noted are facts that need to be addressed whenweighing treatment options for dry eye. He stated that the best way to achievethis is to provide patients the most successful available products, rather thansimply telling them to modify their blink behavior and to use the nearestartificial tear.

In Dr. Maharaj’s Dry Eye Clinic, a very discrete and direct protocol isused. He instructs his patients, “Follow my specific instructions or youwon’t feel better. That’s why I’m being specific.” He takes this approachbecause if one tells patients to use any artificial tear, they will. This leavesthe decision of choosing the topical up to the patient. As a health provideris it imperative to educate patients to make an informed decision.

ConclusionDr. Maharaj concluded his presentation by emphasizing the importance ofproviding patients a specific recommendation to their individual dry eyeproblem. The tear film ought to be addressed as a mechanism, as opposedto an element that must be supplemented.

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Approaches to the Treatment of Dry Eye Disease - Vol 2