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Ophthalmology Management
Article Date: 4/1/2016
Diagnosing dry eye: It’s now a fine art
Research has led to better, more diverse ways to reach a diagnosis, let
alone more knowledge about DED itself.
BY MARK B. ABELSON, MD, CM, FRCSC, FARVO, DAVID W. RIMMER,
MS, ARON SHAPIRO AND GEORGE OUSLER, III
This article briefly examines how decades of research have advanced the accuracy and precision of tools used
to diagnose dry eye. Arming the patient with knowledge about his condition, such as it is a chronic disease and
not a random phenomenon, will greatly improve compliance to therapy and life style changes needed
to
adequately manage this trying disease.
Patient history
Proper diagnosis starts with the doctor-patient relationship. A careful examination and history will lead to a
focused diagnosis of dry eye and a treatment plan that encourages patient compliance. Patients may not be
aware of dry eye but may complain of symptoms. Patients may notice changes in symptoms at different times
of day, or with different visual tasks and environmental conditions. Dry eye can develop in association with
systemic diseases such as diabetes, systemic lupus and rheumatoid arthritis, or with medications such as oral
antihistamines and antidepressants.
Schirmer’s test
Schirmer’s test without anesthetic is the gold standard for evaluating tear production.1
A clinician can conduct
a more patient-friendly tear volume estimation by looking at the tear meniscus height during a slit lamp
exam.2
Fluorophotometry measures tear production less invasively by capturing the rate of fluorescein dye
dilution from the tear film. Heckley and colleagues showed that an improved fluorophotometry technique (with
decreased drop volume and concentration, and blink synchronization) was superior to the Schirmer’s test for
measuring aqueous secretion.3
Ocular surface staining
Ocular surface staining is a common, though sometimes problematic, diagnostic test. Fluorescein staining
visualizes the effects of desiccation on the corneal surface.4 But large amounts of fluorescein can make it
difficult to distinguish staining due to oversaturating the epithelium.5
Assessments should be made
approximately 3 to 5 minutes after drop instillation. Patients with severe dry eye may demonstrate high levels
of staining yet experience minimal symptoms due to decreased corneal sensitivity.6,7
Lissamine green and
rose bengal are also valuable dyes. Krenzer and colleagues observed a greater change in ocular surface
staining with lissamine green than with rose bengal.6
The Ora Calibra Corneal and Conjunctival Staining scale is a validated scale for use in clinical trials.
Investigators grade staining
with scores ranging from 0 to 4; these scales divide each eye into five
areas: the
inferior, superior and central regions relative to the cornea, and the temporal and nasal regions relative to the
conjunctiva. Each area is graded separately; the sum of the three corneal regions generates a corneal sum
score, and addition of the nasal and temporal conjunctival scores generates a combined total score. The
inferior corneal surface usually displays the most staining, as it is exposed to the elements more than other
regions due to decreased and incomplete blinks.9
Staining assessments have since been improved with the
addition of automated image analysis via a continuous numerical scale. This system provides a consistent
output of data across sites in multicentered studies.10
Tear film breakup time (TFBUT)
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TFBUT, or time between the last complete blink and the first appearance of tear film breakup, is a widely used
test.11
Historically, TFBUT was measured with ~50 µL of sodium fluorescein, which greatly exceeds average
tear volume (~6-7 µL).12
From this, a dry eye diagnosis was determined as a TFBUT < 10 seconds. This
methodology has been improved by using lower quantities of
sodium fluorescein (1–5 µL).12
This recalibrated
technique affords more reproducible and physiologically relevant diagnostic reference values whereby TFBUT is
≥5 seconds in healthy patients (mean = 7.1 ± 1.17 seconds) and
<5 seconds in dry eye patients (mean = 2.2
± 0.82).12,13
Symptomatic tear-film breakup time (SBUT)
Approximately 70% of patients with dry eye report ocular awareness and discomfort after TFBUT. The
Symptomatic Tear Film Breakup Time (SBUT), or time to patient-reported ocular discomfort, is a diagnostic
tool that can be performed anywhere. Patients are asked to blink twice, then to stare without blinking for as
long as possible until they become
aware of discomfort. Dry eye patients with low corneal sensitivity have
a
longer SBUT, thus these patients may be at greater risk of ocular surface exposure.14 This is a particularly
useful home test for patients to determine the status of their tear film.
Blink rate, patterns and visual function
In 1977, Abelson and Holly linked partial or incomplete blinks to the development of punctate keratopathy.8
Subsequent video evidence showed that complete blinking was noted in 80% of normals and in 7.5% of those
with punctate keratitis. This was the first time blinking was proposed to have an etiological basis in ocular
surface disease.
Blink is a contributing factor to dry eye and one of the few objective endpoints available that incorporates both
signs and symptoms.15 Average blink rate is 8.0 blinks/minute and the interblink interval (IBI), is about 7.5
seconds.15
To ensure that the ocular surface remains protected, ensure that the TFBUT matches or exceeds
the IBI. The larger the interval between tear film breakup and the following blink, the greater potential for
damage to the ocular surface.
The Ocular Protection Index (OPI) was developed with the division of TFBUT by IBI. A protective OPI score
<1.0 indicates breakup and exposure before blinking, whereas an OPI score ≥1.0 indicates a protected
surface, with breakup occurring after blink time.15
The OPI 2.0 system was developed to assess TFBUT and
IBI simultaneously, implementing fully automated software algorithms that provide real-time measurements of
corneal exposure, known as breakup area.16
Blink patterns are particularly useful in the clinical diagnosis of dry eye. Dry eye patients have extended blink
closure times — more
than six times longer than those of normal subjects. This is similar to
those who
describe microsleeps as fatigue states, and may be due to subconscious compensatory mechanisms.17
Dry eye
subjects also blink more, blink longer and spend a great deal of time with their eyes closed — all likely to
affect visual function.
Blurred vision and keratitis are known to affect visual function.18
Dry eye patients are known to maintain their
best corrected visual acuity for shorter periods of time than patients without dry eye.19,20
The interblink
interval visual acuity decay (IVAD) test measures visual
acuity decay during the interblink interval. By
studying visual function also through a battery of reading tests, it was shown that subjects with dry eye had
significantly lower reading rates and poorer quality of vision.21,22
Some recent research on dry eye:
Yamagami S et al. Evaluation of Tear Meniscus Dynamics Using Anterior Segment Swept-Source Optical
Coherence Tomography After Topical Solution Instillation for Dry Eye. Cornea. 2016
Mar 16.
www.ncbi.nlm.nih.gov/pubmed/26989953
The authors found SS-OCT a valuable tool in quantifying early-phase fluid dynamics.
Sheppard JD et al. Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular
Pressure.
Adv Ther. 2016 Mar 17
www.ncbi.nlm.nih.gov/pubmed/26984315
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Data show, the authors say, that optical ophthalmic corticosteroid loteprednol etabonate has a “favorable IOP-safety
profile,” both long- and short-term.
Goyal S, Hamrah P. Understanding Neuropathic Corneal Pain-Gaps and Current Therapeutic Approaches. Semin
Ophthalmol. 2016;31:59-70.
A summary of the pathophysiology of neuropathic corneal pain, a systematic approach to diagnosing these patients, and
current treatments.
Redness pattern
Redness is used as a diagnostic indicator, however little attention has been given to patterns which can vary
greatly according to location,
hue or depth of color, and intensity. Redness is characterized by the presence of
fine horizontal conjunctival vessels in the exposed ocular surface. We have incorporated a grading system into
clinical studies of dry eye.23
Recently, an automated computer system has been developed that records the
same characteristics measured in the clinical scale and grades images collected in multi-centered clinical trials
to minimize variability and provide a statistically powerful dataset.
Miscellaneous tests
Other diagnostic techniques include confocal microscopy, impression cytology, tear film biomarker analysis and
meibomian gland status.
The inevitable lifestyle changes
It is important that the clinician spends time with patients and informs them about the necessary lifestyle
changes to maintain a healthy
ocular surface. Patients should treat their eyes like an African Violet; the time to
water is before it dries up, not afterward. Symptoms
such as burning represent early onset damage, so it’s
important that patients understand that they need to regularly use lubricants and other agents. Teaching
patients about situational awareness is also critical. They should be told about exacerbating factors like the
level of humidity, strong winds, dust and toxins in the air, avoiding prolonged visual tasks and extended
contact lens wear. Patients should be aware of the time of day when dry eye symptoms are worse. Patients
should also exhibit common sense: a fireplace in winter, fumes of any kind, or direct airflow should be
avoided. Similarly, it is very important to remain well hydrated and reduce the use of ocular drying
medications such as antihistamines, if possible. These lifestyle changes
are important because once symptoms
of dry eye emerge, it can take up to two weeks to normalize the epithelial surface.
Summary
The diagnosis of dry eye begins with a careful examination and thoughtful questioning. A battery of objective
dry eye tests should be performed to accurately diagnose patient subtypes. Refinement of diagnostic tools may
help clinicians develop a more comprehensive clinical picture and a well-tailored treatment plan that will
encourage patient compliance. New medications are being developed that target different mechanisms of
action underlying dry eye disease. These face difficult regulatory hurdles, therefore, testing requires sensitive
assessments that can detect changes in clinical endpoints. OM
REFERENCES
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Clin Exp Ophthalmol, 1903. 56: p. 197-291.
2. Lim, K.J. and Lee JH. Measurement of the tear meniscus height using 0.25% fluorescein sodium. Korean J
Ophthalmol, 1991. 5(1): p. 34-36.
3. Heckley C, Lane, K, Welch D, Ousler W. Updated fluorophotometry technique correlates wiith signs and
symptoms of dry eye better than Schirmer’s test. Investigative Ophthalmol & Visual Science, 2013. 54(15).
4. Pflüger, Zur Ernährung der cornea. Klin Monatsbl Augenheilkd, 1882. 20: p. 69-81.
5. Abelson, MB, et al. Alternative
reference values for tear film break up time in normal and dry eye populations.
Adv Exp Med Biol. 2002. 506(Pt B): p. 1121-1125.
6. Xu, KP, Yagi Y, and Tsubota K. Decrease in corneal sensitivity and change in tear function in dry eye. Cornea,
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1996. 15(3): p. 235-9.
7. Bourcier, T., et al., Decreased
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populations during exposure to a controlled adverse environment. Adv Exp Med Biol. 2002. 506(Pt B): p. 10571063.
14. Abelson MB, O.G., Welch D, Nentwig B, Symptomatic break-up time (SBUT) in dry eye patients with normal vs.
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16. Abelson, R, et al. Validation and verification of the OPI 2.0 System. Clin Ophthalmol. 2012;6. p. 613-22.
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About the Authors
Marc Abelson, MD, CM, FARVO is emeritus surgeon, Mass Eye and Ear Infirmary, and chief
scientific officer of Ora Inc.
Aron Shapiro is vice president for Anti-Infectives, Glaucoma, and Retina at Ora Inc.
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George W. Ousler is vice president for Dry Eye at Ora Inc.
David Rimmer is a medical writer at Ora, Inc.
Ophthalmology Management, Volume: 20 , Issue: April 2016, page(s): 48-50
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