JULY/AUGUST 2010 / www.optometrytimes.com3939Therapeutics&Co-Management

SPECIAL SECTION

By Jerry Nolfi, OD, MBA

How many times have you heard com-

plaints from your patients about burn-

ing, stinging, or itchy eyes? Or com-

plaints about eyes that are red and

feel like there is something in them?

Before you as the clinician get the chance

to seat such a patient behind a slit lamp

or thrill him or her with Shirmer strips,

chances are you are already thinking about

a diagnosis of dry eye. To support this pre-

diagnosis, all you need is objective clini-

cal evidence.

Yet, herein is where the problem lies.

Mildly symptomatic dry eye patients are

common in all practices. But, objective clini-

cal evidence is harder to find. Often, patients

(and clinicians) suffer through Schirmer test-

ing only to learn that the results are within

normal limits. Or, clinicians insert fluores-

cein drops only to discover limited corneal

or conjunctival staining.

Quest for a better wayIn many patients, dry eye is the diagnosis of

choice, but the limited and objective clinical

evidence remains inconclusive.

The TearLab Osmolarity System (TearLab

Corp.), which measures tear osmolarity to

diagnose dry eye disease (DED), received

significant attention after the 2007 Dry Eye

Workshop (DEWS) report, when tear osmolar-

ity was added to the definition of dry eye.1-2

The literature indicated that tear hyperosmo-

larity was the main source of ocular surface

inflammation, damage, and symptoms, which

initiated tear compensatory mechanisms.3 The

evidence was compelling that tear osmolar-

ity was likely the universal component and

a key diagnostic biomarker for DED.

The importance of tear osmolarityFrom their work on the tear film, Tomlinson,

et al. concluded:

The measurement of tear osmolarity ar-

guably offers the best means of capturing,

in a single parameter, the balance of input

and output of the lacrimal system. It is clear

from the comparison of the diagnostic effi-

cyclosporine therapy for 2 years, or switched

to the medication from artificial tears in the

second year of the trial, had significant better

outcomes in other study parameters, includ-

ing Schirmer’s test scores, tear break-up time,

and Ocular Surface Disease Index.

Goblet cells improved in those patients

who either received cyclosporine therapy for

2 years or switched to the medication from

artificial tears in the second year of the trial

(18% and 5.7%, respectively), and worsened

in patients who switched from cyclosporine

to artificial tears (8.4%).

“The topical administration of cyclospo-

rine 0.05% decreases the number of acti-

vated conjunctival T cells and expression of

inflammatory markers in [patients with] dry

eye, suggesting that [the drug] may target

the underlying inflammatory processes,” Dr.

Rao said. “This may explain, in part, its ef-

ficacy in patients with dry eye.”

Dry eye often can be a chronic condition,

and finding the right maintenance therapy for

the long term is paramount, he said. Therefore,

follow-up visits are important where the phy-

sician can alter the medications and the doses

and choose therapy according to symptoms

and the current level of severity of dry eye.

“Certainly, there are those patients who

feel comfortable when their medicine is ta-

pered or changed . . . to maximize therapeu-

tic outcomes,” Dr. Rao said. “Others are fine

with a steady regimen and are satisfied with

maintenance therapy. And as long as they can

avoid having to use extra medications or extra

artificial tears and remain symptom-free, a

lot of these patients will opt to use cyclospo-

rine as their maintenance therapy.”

Ophthalmologists often need to monitor

their patients with dry eye closely to keep

them free of symptoms. Cyclosporine appears

to be a good maintenance therapy for dry eye

in terms of both efficacy and tolerability in

the long term, thereby increasing the patients’

quality of life, Dr. Rao concluded.OP

See Diagnostics on page 40

New era in dry eye managementFocusing on new markers, tools can help clinicians successfully manage DED

Sanjay N. Rao, MDPhone: 312/553-1818; 866/922-8825

E-mail: sanjayrao@pol.net

Dr. Rao is a speaker for and receives research support from

Allergan. He also is a speaker for Bausch + Lomb and is on

the scientific advisory board for EyeGate Pharmaceuticals.

FYIFYI

Take-Home Message

Using the latest technology, in the form of the TearLab Osmolarity System, will help clinicians focus on the oft-presenting dry eye patient and the importance of tear osmolarity as a marker for dry eye disease.

| | | | | | | | |

275 290 305 320 335 350 365 380 400

Osmolarity (mOsms/L)

Normal Mild Moderate Severe The TearLab Osmolarity System. (Photo provided by TearLab Corp.)

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

JULY/AUGUST 2010 / Optometry Times40 Therapeutics&Co-Management

SPECIAL SECTION

ciency of various tests for keratoconjuctivitis

sicca (KCS), used singly or in combination,

that osmolarity provides a powerful tool in

the diagnosis of KCS and has the potential

for being accepted as the gold standard for

the disease.4

Abnormal tear osmolarity is a failure of ho-

meostatic osmolarity regulation. The higher the

osmolarity, the more severe the dry eye. Histori-

cally, literature suggested a 316 mOsms/L cut-

off for more moderate-to-severe disease.5

However, based on the results of a 300-pa-

tient trial, presented at the 2009 annual meet-

ing American Academy of Ophthalmology,

osmolarity was found to have 88% specific-

ity, 75% sensitivity in mild/moderate disease

and 95% sensitivity in severe disease at a di-

agnostic cut-off of 308 mOsms/L.6

Therefore, osmolarity values above 308

mOsms/L are generally indicative of dry-

eye disease. Clinicians should examine all

points of subjective and objective data and

not rely only on cut-off values because they

are only guidelines.

It is important to note that this study dem-

onstrated that TearLab outperformed both

Schirmer’s testing and corneal staining with

respect to the sensitivity and specificity in

patients with the mild-to-moderate DED.6

Understanding and interpreting osmolar-

ity results in the clinical setting was critical

to proper diagnosis of our patients. It is well

understood that DED is usually of gradual

onset and progression, especially in the early

stages when full expression of markers may

be intermittent or missing.7

Below are some key observations for mildly

symptomatic patients with tear osmolarity

in the 308 to 316 mOsms/L range:

• Variability of osmolarity values between

eyes is a hallmark indicator of early DED. In

early disease, compensatory mechanisms—such

as frequent blinking and increased secretion of

aqueous—are intermittent and more frequent

in one eye, thereby reduc-

ing osmolarity asymmetri-

cally. Interocular variability

is a hallmark sign of early

disease. The eye with the

higher osmolarity result of

the two is the key diagnos-

tic indicator for DED.

• Large increases in tear

osmolarity in patients in

normal baseline can still

produce symptoms. Patients

with early disease may be

identified by spikes at sub-

sequent visits.

• Utilize other subjec-

tive and objective data to

classify patients properly.

Good clinicians always look

at all the data before they

make a diagnosis.

I frequently utilize the

Dry Eye Disease Severity

Scale (see Figure 1) when

counseling patients.

Combining the quantita-

tive osmolarity scale (275

to 400 mOsms/L) with a

qualitative range of severity makes it easier to

visualize and communicate to patients. The

diagram was placed in each exam room.

Reaping the benefitsNew diagnostic technologies in the office pro-

duce moments of anxiety, excitement, and

often frustration when things don’t go as

planned. The TearLab unit amazed my tech-

nicians and increased their confidence with

patient testing.

The TearLab system was designed as an

efficient, technician-administered test. From

sample taking to getting an answer literally

takes seconds. The benefits are many, and

include a quick learning curve (it took less

than 2 hours to set up the unit and train the

technicians). The unit also fits easily on an

exam room or pre-test area counter.

Initially, I narrowed our patient criteria to

middle-aged healthy adults in order to elimi-

nate potentially difficult subjects while my

technicians gained experience and confidence

with patient testing. Initially, they were hesi-

tant to place the pen tip into the lower tear

meniscus of the temporal part of the eye for

tear collection (see Figure 2).

However, those technicians with contact

lens experience were more at ease with per-

forming the test. By the tenth patient, all my

technicians were obtaining consistent and

repeatable results.

The compelling clinical feature of TearLab

is data it generates. These data make differen-

tial diagnosis and patient counseling effective

and efficient. This objective evidence results

in a more complete patient assessment.

Health Canada approval in 2009 acceler-

ated broad clinical acceptance of TearLab in

our practice. A clinical integration plan was

developed for TearLab (see Figure 3).

The plan identified patients in which per-

forming a tear osmolarity assessment was

clinically justifiable. The primary use of the

technology was for DED diagnosis. Did it make

sense to extend TearLab into contact lens fit-

ting and pre-op surgery workups?

Our contact lens fitting process usually

evaluates different contact lenses to determine

superior performance. Using TearLab along

with other factors, I selected the best lens for

patients based on the least impact on osmo-

larity. Integrating TearLab into the contact

lens fitting process made clinical sense.

Many refractive surgery patients experience

extended periods of dry eye postoperatively,

though they had no prior history of dry eye.

Although DED usually dissipates between

months 3 and 6 postoperatively, there are

patients who develop chronic dry eye after

refractive surgery and don’t seem to have

improvement.

Although there are many possible causative

factors for this result, integrating a tear os-

molarity assessment into refractive surgery

work-ups to identify asymptomatic, hyper-

osmolar tear patients proactively made clini-

cal sense.

DiagnosticsContinued from page 39

Target Patient Population Clinical Purpose

1. Symptomatic Patients • Dry Eye disease (DED) –

burning, stinging, itching, etc.

• Differential diagnosis

2. Asymptomatic Patients

• Family history

• Certain medications

• Pregnant women

• Identify mild DED

3. New Patients > 50 years old • Baseline value

4. Contact Lens (CL) Patients • Baseline value

• Determine CL effect on tear

osmolarity

5. CL New Wearers Program • Customized contact lens fi tting

• Determine patients at risk for DED

• Determine CL effect on tear

osmolarity

6. Refractive Surgery Work-up • Determine patients at risk for DED

Figure 2. The pen tip is put in the lower tear meniscus of the temporal part of the eye for tear collection. (Photo provided by TearLab Corp.)

Figure 3. A clinical integration plan was developed for TearLab. (Chart provided by Jerry Nolfi, OD, MBA)

JULY/AUGUST 2010 / www.optometrytimes.com4141Therapeutics&Co-Management

SPECIAL SECTION

A 50-year-old patient may require greater

in-depth medical testing than a 25-year-old

patient. Recommending TearLab as part of

comprehensive baseline testing for this de-

mographic makes sense. Baseline osmolarity

testing helps to identify patients with early

DED so treatment can be initiated, reducing

the risk for ocular surface inflammation.

Both eyes must be tested to obtain an ac-

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 de-

velop 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-

port, the prevalence of dry eye is 5% to 30%

among patients aged 50 years and older.8 How

many patients does that represent in your

practice?

Creating a disease-specific specialty in your

practice is a strategic asset and an excel-

lent practice builder and referral generator.

Building a DED specialty including the latest

technology involves some simple planning

and execution, but can significantly increase

patient satisfaction and add real returns to

your bottom line.OP

References1. FDA 510(k) clearance allows TearLab to market

in the U.S. to clinical facilities categorized as high or moderate complex under the Clinical Laboratory Improvement Act of 1988 (CLIA ‘88). The company is now seeking a CLIA waiver.

2. Definition and Classification of Dry Eye. Report of the Diagnosis and Classification Subcommittee of the Dry Eye Workshop (DEWS). The Ocular Surface. 2007;5(2):75.

3. Definition and Classification of Dry Eye. Report of the Diagnosis and Classification Subcommittee of the Dry Eye Workshop (DEWS). The Ocular Surface. 2007;5(2):86.

4. Tear film osmolarity: Determination of a referent for dry eye diagnosis. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Investigative Ophthalmology & Visual Science. 2006;47:4314.

5. Tear film osmolarity: Determination of a referent for dry eye diagnosis. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Investigative Ophthalmology & Visual Science. 2006;47:4309-4315.

6. Foulks GN, Lemp MA, Berg M, Bhola R, Sullivan

BD. TearLab™ osmolarity as a biomarker for disease severity in mild-to-moderate dry eye disease. American Academy of Ophthalmology PO382, 2009.

7. Definition and Classification of Dry Eye. Report of the and Classification Subcommittee of the Dry Eye Workshop (DEWS). The Ocular Surface. 2007;5(2):75-92.

8. The epidemiology of dry eye disease: Report of the Epidemiology Subcommittee of the International Dry Eye Workshop (2007). The Ocular Surface. 2007;5(2):96.

Jerry Nolfi, BSc, OD, MBA,is a private practice optometrist and co-founder of Toronto Eye Care Optometric Clinic. Dr. Nolfi is based in Toronto, Ontario, Canada. Readers may contact

him at jnolfi@torontoeyecare.com.

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CI manifestswith symptoms

that includediplopia, eyestrain,

headaches,blurred vision,

and difficultyconcentrating.

resources, and the economy. It is clear that thispreviously underappreciated condition nowshould be regarded as a serious public healthproblem that is worthy of diagnosis and ef-cle, dry eye disease is a major and increasinghealth-care problem due to its prevalence andeffects on patients’ quality of life, health-carebased vision therapy with a trained therapistresources, and the economy. It is clear that thispreviously underappreciated condition now

themost effective form of treatment for conver-gence insufficiency (CI) in children is office-based vision therapy with a trained therapistresources, and the economy. It is clear that thispreviously underappreciated condition nowshould be regarded as a serious public healthproblem that is worthy of diagnosis and ef-cle, dry eye disease is a major and increasinghealth-care problem due to its prevalence andeffects on patients’ quality of life, health-care