New Era in Dry Eye Management Focusing on New Markers, Tools Can Help Clinicians Successfully Manage DED

JULY/AUGUST 2010 / www.optometrytimes.com Therapeutics&Co-Management 39 SPECIAL SECTION New era in dry eye management Focusing on new markers, tools can help clinicians successfully manage DED

By Jerry Nolfi, OD, MBA Take-Home Message ow many times have you heard com- Using the latest technology, in the form of the TearLab plaints from your patients about burn- Osmolarity System, will help clinicians focus on the oft- ing, stinging, or itchy eyes? Or com- presenting dry eye patient and the importance of tear plaints about eyes that are red and osmolarity as a marker for dry eye disease. Hfeel like there is something in them? Before you as the clinician get the chance to seat such a patient behind a slit lamp Quest for a better way or thrill him or her with Shirmer strips, In many patients, dry eye is the diagnosis of chances are you are already thinking about choice, but the limited and objective clinical a diagnosis of dry eye. To support this pre- evidence remains inconclusive. diagnosis, all you need is objective clini- The TearLab Osmolarity System (TearLab cal evidence. Corp.), which measures tear osmolarity to

Figure 1. The Dry Eye Disease Severity Scale. (Graph provided by Jerry Nolfi, BSc, OD, MBA)

Normal Mild Moderate Severe | | | | | | | | | The TearLab Osmolarity System. 275 290 305 320 335 350 365 380 400 (Photo provided by TearLab Corp.) Osmolarity (mOsms/L) ity was likely the universal component and a key diagnostic biomarker for DED.

Yet, herein is where the problem lies. diagnose dry eye disease (DED), received The importance of tear osmolarity Mildly symptomatic dry eye patients are significant attention after the 2007 Dry Eye From their work on the tear film, Tomlinson, common in all practices. But, objective clini- Workshop (DEWS) report, when tear osmolar- et al. concluded: cal evidence is harder to find. Often, patients ity was added to the definition of dry eye.1-2 The measurement of tear osmolarity ar- (and clinicians) suffer through Schirmer test- The literature indicated that tear hyperosmo- guably offers the best means of capturing, ing only to learn that the results are within larity was the main source of ocular surface in a single parameter, the balance of input normal limits. Or, clinicians insert fluores- inflammation, damage, and symptoms, which and output of the lacrimal system. It is clear cein drops only to discover limited corneal initiated tear compensatory mechanisms.3 The from the comparison of the diagnostic effi- or conjunctival staining. evidence was compelling that tear osmolar- See Diagnostics on page 40 cyclosporine therapy for 2 years, or switched Rao said. “This may explain, in part, its ef- Ophthalmologists often need to monitor to the medication from artificial tears in the ficacy in patients with dry eye.” their patients with dry eye closely to keep second year of the trial, had significant better Dry eye often can be a chronic condition, them free of symptoms. Cyclosporine appears outcomes in other study parameters, includ- and finding the right maintenance therapy for to be a good maintenance therapy for dry eye ing Schirmer’s test scores, tear break-up time, the long term is paramount, he said. Therefore, in terms of both efficacy and tolerability in and Ocular Surface Disease Index. follow-up visits are important where the phy- the long term, thereby increasing the patients’ Goblet cells improved in those patients sician can alter the medications and the doses quality of life, Dr. Rao concluded.OP who either received cyclosporine therapy for and choose therapy according to symptoms 2 years or switched to the medication from and the current level of severity of dry eye. artificial tears in the second year of the trial “Certainly, there are those patients who (18% and 5.7%, respectively), and worsened feel comfortable when their medicine is ta- in patients who switched from cyclosporine pered or changed . . . to maximize therapeu- to artificial tears (8.4%). tic outcomes,” Dr. Rao said. “Others are fine FYI Sanjay N. Rao, MD “The topical administration of cyclospo- with a steady regimen and are satisfied with Phone: 312/553-1818; 866/922-8825 rine 0.05% decreases the number of acti- maintenance therapy. And as long as they can E-mail: [email protected] vated conjunctival T cells and expression of avoid having to use extra medications or extra Dr. Rao is a speaker for and receives research support from inflammatory markers in [patients with] dry artificial tears and remain symptom-free, a Allergan. He also is a speaker for Bausch + Lomb and is on eye, suggesting that [the drug] may target lot of these patients will opt to use cyclospo- the scientific advisory board for EyeGate Pharmaceuticals. the underlying inflammatory processes,” Dr. rine as their maintenance therapy.” JULY/AUGUST 2010 / Optometry Times 40 Therapeutics&Co-Management SPECIAL SECTION

Diagnostics ity results in the clinical setting was critical Continued from page 39 to proper diagnosis of our patients. It is well understood that DED is usually of gradual ciency of various tests for keratoconjuctivitis onset and progression, especially in the early sicca (KCS), used singly or in combination, stages when full expression of markers may that osmolarity provides a powerful tool in be intermittent or missing.7 the diagnosis of KCS and has the potential Below are some key observations for mildly for being accepted as the gold standard for symptomatic patients with tear osmolarity the disease.4 in the 308 to 316 mOsms/L range: Figure 2. The pen tip is put in the lower tear meniscus Abnormal tear osmolarity is a failure of ho- • Variability of osmolarity values between of the temporal part of the eye for tear collection. meostatic osmolarity regulation. The higher the eyes is a hallmark indicator of early DED. In (Photo provided by TearLab Corp.) osmolarity, the more severe the dry eye. Histori- early disease, compensatory mechanisms—such cally, literature suggested a 316 mOsms/L cut- as frequent blinking and increased secretion of Initially, I narrowed our patient criteria to off for more moderate-to-severe disease.5 aqueous—are intermittent and more frequent middle-aged healthy adults in order to elimi- in one eye, thereby reduc- nate potentially difficult subjects while my Figure 3. A clinical integration plan was developed for TearLab. ing osmolarity asymmetri- technicians gained experience and confidence (Chart provided by Jerry Nolfi, OD, MBA) cally. Interocular variability with patient testing. Initially, they were hesi- is a hallmark sign of early tant to place the pen tip into the lower tear Target Patient Population Clinical Purpose disease. The eye with the meniscus of the temporal part of the eye for higher osmolarity result of tear collection (see Figure 2). 1. Symptomatic Patients • Dry Eye disease (DED) – the two is the key diagnos- However, those technicians with contact burning, stinging, itching, etc. tic indicator for DED. lens experience were more at ease with per- • Differential diagnosis • Large increases in tear forming the test. By the tenth patient, all my osmolarity in patients in technicians were obtaining consistent and 2. Asymptomatic Patients • Identify mild DED • Family history normal baseline can still repeatable results. • Certain medications produce symptoms. Patients The compelling clinical feature of TearLab • Pregnant women with early disease may be is data it generates. These data make differen- identified by spikes at sub- tial diagnosis and patient counseling effective 3. New Patients > 50 years old • Baseline value sequent visits. and efficient. This objective evidence results • Utilize other subjec- in a more complete patient assessment. 4. Contact Lens (CL) Patients • Baseline value tive and objective data to Health Canada approval in 2009 acceler- • Determine CL effect on tear classify patients properly. ated broad clinical acceptance of TearLab in osmolarity Good clinicians always look our practice. A clinical integration plan was at all the data before they developed for TearLab (see Figure 3). 5. CL New Wearers Program • Customized contact lens ﬁ tting make a diagnosis. The plan identified patients in which per- • Determine patients at risk for DED I frequently utilize the forming a tear osmolarity assessment was • Determine CL effect on tear Dry Eye Disease Severity clinically justifiable. The primary use of the osmolarity Scale (see Figure 1) when technology was for DED diagnosis. Did it make counseling patients. sense to extend TearLab into contact lens fit- 6. Refractive Surgery Work-up • Determine patients at risk for DED Combining the quantita- ting and pre-op surgery workups? tive osmolarity scale (275 Our contact lens fitting process usually to 400 mOsms/L) with a evaluates different contact lenses to determine However, based on the results of a 300-pa- qualitative range of severity makes it easier to superior performance. Using TearLab along tient trial, presented at the 2009 annual meet- visualize and communicate to patients. The with other factors, I selected the best lens for ing American Academy of Ophthalmology, diagram was placed in each exam room. patients based on the least impact on osmo- osmolarity was found to have 88% specific- larity. Integrating TearLab into the contact ity, 75% sensitivity in mild/moderate disease Reaping the benefits lens fitting process made clinical sense. and 95% sensitivity in severe disease at a di- New diagnostic technologies in the office pro- Many refractive surgery patients experience agnostic cut-off of 308 mOsms/L.6 duce moments of anxiety, excitement, and extended periods of dry eye postoperatively, Therefore, osmolarity values above 308 often frustration when things don’t go as though they had no prior history of dry eye. mOsms/L are generally indicative of dry- planned. The TearLab unit amazed my tech- Although DED usually dissipates between eye disease. Clinicians should examine all nicians and increased their confidence with months 3 and 6 postoperatively, there are points of subjective and objective data and patient testing. patients who develop chronic dry eye after not rely only on cut-off values because they The TearLab system was designed as an refractive surgery and don’t seem to have are only guidelines. efficient, technician-administered test. From improvement. It is important to note that this study dem- sample taking to getting an answer literally Although there are many possible causative onstrated that TearLab outperformed both takes seconds. The benefits are many, and factors for this result, integrating a tear os- Schirmer’s testing and corneal staining with include a quick learning curve (it took less molarity assessment into refractive surgery respect to the sensitivity and specificity in than 2 hours to set up the unit and train the work-ups to identify asymptomatic, hyper- patients with the mild-to-moderate DED.6 technicians). The unit also fits easily on an osmolar tear patients proactively made clini- Understanding and interpreting osmolar- exam room or pre-test area counter. cal sense. JULY/AUGUST 2010 / www.optometrytimes.com Therapeutics&Co-Management 41 SPECIAL SECTION

BD. TearLab™ osmolarity as a biomarker for A 50-year-old patient may require greater disease severity in mild-to-moderate dry eye Author Info disease. American Academy of Ophthalmology in-depth medical testing than a 25-year-old Jerry Nolfi, BSc, OD, MBA, patient. Recommending TearLab as part of PO382, 2009. 7. Definition and Classification of Dry Eye. Report is a private practice comprehensive baseline testing for this de- of the and Classification Subcommittee of the optometrist and co-founder mographic makes sense. Baseline osmolarity Dry Eye Workshop (DEWS). The Ocular Surface. of Toronto Eye Care testing helps to identify patients with early 2007;5(2):75-92. Optometric Clinic. Dr. Nolfi DED so treatment can be initiated, reducing 8. The epidemiology of dry eye disease: Report is based in Toronto, Ontario, the risk for ocular surface inflammation. of the Epidemiology Subcommittee of the Canada. Readers may contact International Dry Eye Workshop (2007). The him at [email protected]. Both eyes must be tested to obtain an ac- Ocular Surface. 2007;5(2):96. curate diagnosis because DED is bilateral, but typically asymmetrical. I decided to im- plement a simple, inexpensive introductory level fee for testing both eyes. By doing so, patient objections are limited due to cost, and acceptance rates are over 90% in the first 5 months of 2010. The osmolarity data allow patients to under- stand their level of the disease and to gauge treatment effectiveness at follow-up visits. Patient compliance with treatment protocols has increased by making patients aware of a quantitative benchmark. TearLab represents an opportunity to develop a dry eye specialty within an existing practice. Consider the number of patients who complain about dry eye symptoms on a daily basis. According to the DEWS re- Begin a FREE subscription port, the prevalence of dry eye is 5% to 30% among patients aged 50 years and older.8 How to Optometry Times.. many patients does that represent in your practice? Creating a disease-specific specialty in your www.optometrytimes.com/subscribe practice is a strategic asset and an excel- (Enter priority code 99HA) lent practice builder and referral generator. Building a DED specialty including the latest technology involves some simple planning • Practice Management Bringing Ey and execution, but can significantly increase e Hea lth in to Focus www.optometry times.com Combined March 2009 • Primary Care Optometry effort W Vol. 1, No. 1 patient satisfaction and add real returns to ‘Doubleteamin your bottom line.OP g’showneffective • Industry News and FastTrack forchildhood visiond Office-basedtherapy, home isorder reinforcement besttherapeutic References • Contact Lenses effectfor co nvergenceinsufficiency CImanife ByNancyGroves sts ReviewedbyEricB withs orsting, OD,MS,FAAO,FCOVD, ymptoms 1. FDA 510(k) clearance allows TearLab to market Marjean Kulp,OD,M S,and Mi tchell S .Scheim OD,FAAO an, thatinclude • CE Center diplopia, eyestrain, in the U.S. to clinical facilities categorized as Philadelphia—Research ers have concluded t hat the mosteffective fo h rmoftreatment for conver- eadaches, genceinsuffici ency( CI) i n child ren i soffice- based visio nt blurredvisi high or moderate complex under the Clinical herapywith atrained therapist on, resources,andthe e • Glaucoma conomy.Itis c lear thatt andd tan previousl his ifficulty yundera . Brit ppreciate dcondition now J should beregardedasas concen ilip Laboratory Improvement Act of 1988 (CLIA ‘88). erious p ublichealth trating. Ph problemthatisw orthy o fdiagnosi sand ef- cle,dryeyedisea sei tal Vision/ s a major an dincrea i health- sing careproblemduetoits pre The company is now seeking a CLIA waiver. valencea es/Dig effectsonp nd • Cornea / External Disease atients’qualityoflife, health-care based visi on the tty Imag rapywith a tr ai e ned th erapis N G resources,and the ec t ewer knowledge 2. Definition and Classification of Dry Eye. onomy. Itis c lear tha t this previousl yunderappr eciatedconditionnow the mo steffective f orm o ftreatmentfor conver- combined wi th h Dr ome r ein y ey forcement. e a s Report of the Diagnosis and Classification TheC er onvergenc io • Student Center eInsu us fficienc yTreatment Trial (CITT) d emonst ratedthatoffice-based vergence/a ccommodative therapy( pub OBVAT) with li Subcommittee of the Dry Eye Workshop ho c h me reinforcement was mor ealthp eeffec roblem tivet han B See yDebra A. Scha um Convergence onpage 42 berg, ScD ,OD,MPH, andGerdG resources,and th e eco eerling, MD ,PhD nomy.Itis cl ear thatthis (DEWS). The Ocular Surface. 2007;5(2):75. • Inside previouslyundera Cataract, Refractive, Retina ppreciated condition n should b ow onsiderabl eregardedasaseri eprogresshasbeen ma ous publi chealth 6 Editorialria de problemthatiswo l inthe pa st15 yearsregardin rthyof diagnosis and ef- 3. Definition and Classification of Dry Eye. gknowl- fective tr eatmen W edge o ntheepidemi t. elcome t othepremiereissue C ologyofdryeye disease.Asw of OptometryTimes edescribeinthisa See Tear Film on page16 —orisit déj àvu? cle,drye rti- ByMarkL. Dl yediseaseisamajor an Low-Vision Solutions ugoss,GroupEditor dincreasing Report of the Diagnosis and Classification • health-careproble mdu etoitsprevalenceand 36 Glaucomaoma effectsonpatients’ quali tyoflife,health-care the mo steffective for Whenis a caset moftreatment f or co nve Subcommittee of the Dry Eye Workshop rulyglaucoma? genceinsuffi r- If a definitiv ciency(CI) in c hildre special section ediagnosis se emselusive, based visi nisoffice- gath ontherapyw er c orroboratingevidence. ith a t rained th erapist resources,and th • And Much More! ByMurrayFingeret,OD eeconomy.Itis clear thatthis (DEWS). The Ocular Surface. 2007;5(2):86. previousl yunderap precia tedconditionn 40 should ber ow SpSpeciaecialSececttion:V egarded as aserious publ EEEE proble ichealth mthatisworth yofd Get into a ‘ NewYorksta iagnosi sand ef- teof mind.’ Preview cle,dryeyedisease is a maj 4. Tear film osmolarity: Determination of a allt rts on page 10 hat’snew a tthisyear’sVisio or an dincreasing nExpoEast. health-careproblemd By Christi naPhillis uetoitsprevalenceand effectson pa tien ts’qua sta lityof life, health-care referent for dry eye diagnosis. Tomlinson A, Getty Imag es Khanal S, Ramaesh K, Diaper C, McFadyen A. Investigative Ophthalmology & Visual Science. 2006;47:4314. Optometry Times delivers news and information of a clinical, 5. Tear film osmolarity: Determination of a practical and structured nature in a timely and accurate manner referent for dry eye diagnosis. Tomlinson A, for members of the optometric community. Khanal S, Ramaesh K, Diaper C, McFadyen A. Investigative Ophthalmology & Visual Science. Don’t miss out. Begin your free subscription today! 2006;47:4309-4315. 6. Foulks GN, Lemp MA, Berg M, Bhola R, Sullivan Brought to you by the Advanstar Eye Health Group