Anterior Segment: Session 04: Diagnostics: Tear Film /Dry Eye

Welcome. With this session, we begin our discussion of diagnostic evaluation for anterior segment disorders. In this

session, we'll discuss about tear film evaluation. We'll discuss about the

evaluation. We'll discuss about the types, pathogenesis, and treatment of dry eye disease in a later session.

Tear film evaluation is indicated in patients complaining of symptoms suggesting dry eye disease, which include symptoms of discomfort such as dryness, sticky eyelids, heaviness,

burning, aching, watering, or contact lens intolerance, and or visual symptoms suggestive of dry eye such as blurred or fluctuating vision. Dry eye evaluation

fluctuating vision. Dry eye evaluation should begin with providing patients with dry eye questionnaires, which allow comprehensive assessment of dry eye symptoms and their severity. Examples of

such questionnaires include the dry eye questionnaire five, the SPEED questionnaire, and the OSDI questionnaire. Each of these three

questionnaire. Each of these three questionnaires consider frequency of both symptoms of discomfort and visual symptoms, but only the OSDI questionnaire consider the frequency of

their occurrence during specific tasks and in specific environments. And it is important to note that assessment of severity of dry eye symptoms may not correlate with signs elicited in the

other tests which we are going to discuss. Evaluation of the tear film and

discuss. Evaluation of the tear film and for dry eye begins with a clinical examination, which evaluates the eyelid, tear film, lid margin, and conjunctiva,

and administration of certain tests in the clinic. Examination of the

the clinic. Examination of the periocular skin may reveal rosacea, which is associated with meibomian gland dysfunction or seborrheic dermatitis, which is associated with blepharitis.

Abnormalities of eyelid position, such as eyelid retraction, entropion, and ectropion are associated with tear film dysfunction, and so are abnormalities of

eyelid blink, particularly with regard to its frequency and completeness.

Laxity of the eyelids as shown being tested in these two photographs and in this photograph which shows a patient with floppy eyelids and lagophthalmos as

shown here in this photograph are also associated with tear film dysfunction.

Bell's reflex, which is the normal upward excursion of the eye on attempted closure of the eyelid, should also be assessed. So, this photograph shows a

assessed. So, this photograph shows a patient with lagophthalmos but with intact Bell's reflex.

The tear film, the lid margin, and the conjunctiva are examined on the slit lamp. The tear film should be examined

lamp. The tear film should be examined first. The height of the tear meniscus,

first. The height of the tear meniscus, as seen here in this photograph, is normally 0.5 mm and has an upper concave surface. The quality of the tear

surface. The quality of the tear meniscus and the pre-corneal tear film should be evaluated for the presence of debris and froth as shown here in this photograph, which suggests tear film

dysfunction.

Examination of the lid margin may reveal anterior blepharitis, which may be seborrheic, in which we find greasy scales along the eyelashes, or staphylococcal, in which we find

crust-like collarettes. Posterior

crust-like collarettes. Posterior blepharitis, in which there is rounding and irregularity of the posterior border of the eyelid margin along with telangiectasia, and which is associated

with meibomian gland dysfunction and trichiasis. Meibomian gland openings

trichiasis. Meibomian gland openings should be assessed for obstruction, as seen here in this photograph and surrounding telangiectasia.

Periglandular atrophy may make the meibomian gland openings more prominent, which is called pouting, as seen here in this photograph. And this photograph

this photograph. And this photograph shows obstruction of meibomian gland openings due to capping by droplets of oil secreted by the glands themselves.

The secretions of the meibomian glands needs to be evaluated after expressing them by applying sustained pressure immediately peripheral to the lower eyelid margin as shown here in this

photograph at several locations along the lid margin with the patient maintaining up gaze. First, we need to note whether the gland mouths are open or partially or totally closed.

Normally, the lipid expressed from each gland is transparent and flows freely.

In seborrheic MGD, the expressed lipid has a larger size, is opalescent, but flows freely. While in obstructive

flows freely. While in obstructive meibomian gland dysfunction, either lipid may not be expressed or the expressed lipid appears opaque, white to light yellow in color, and viscous like

toothpaste as seen here in these two photographs.

Bulbar conjunctiva may show congestion in dry eye disease and surface irregularities of the bulbar conjunctiva such as pinguecula, pterygium, conjunctivochalasis,

or an elevated bleb can interfere with tear film stability. Congestion and mild papillary reaction of the palpebral conjunctiva can occur in dry eye disease and scarring of the palpebral

conjunctiva is found in cicatrizing conjunctival disorders such as Steven-Johnson syndrome, ocular cicatricial pemphigoid, and chemical burns, which are associated with severe

dry eye. Tear breakup time and vital dye

dry eye. Tear breakup time and vital dye staining of the ocular surface are the two most important clinical tests to evaluate for tear film dysfunction. Tear

breakup time or TBUT is the time interval between last complete blink and first appearance of a random dry spot in the precorneal tear film. It is

important that this test should be performed before manipulation of eyelids or application of any eye drops. This

test is performed by instilling fluorescein into the eye, following which the patient is asked to blink several times, and then keep eyes open.

When the precorneal tear film is examined with a white beam and cobalt blue filter, the random dry spots, as seen here in this photograph, start appearing in the pre-corneal tear film.

Only a minimal amount of fluorescein-containing drop is recommended, as the volume of the drop itself can affect the result. An average

of multiple readings is considered. A

TBUT of less than 10 seconds is considered marginal, and a TBUT of less than 5 seconds is considered abnormal.

TBUT is decreased in both aqueous-deficient and evaporative dry eye. It is important to note that if

eye. It is important to note that if there is an irregular zone on the corneal surface, a dry spot appears in that area every time the test is performed, and so that spot is not

random and should not be considered to measure TBUT.

Ocular surface staining with vital dyes is the other important clinical test to evaluate for tear film dysfunction, in which vital dyes are used to assess the health of corneal and conjunctival

epithelium.

Fluorescein is usually used to assess the cornea, as seen here in this photograph, and it stains the epithelialized areas. Whereas, rose

epithelialized areas. Whereas, rose bengal and lissamine green are usually used to assess the conjunctiva, as seen here in these two photographs, and they

stain the epithelialized, as well as devitalized, areas. We have discussed

devitalized, areas. We have discussed about these vital dyes in more detail in the previous session. Several systems

are available to grade ocular surface staining with vital dyes. In the van Bijsterveld system, rose bengal is used to grade severity of staining in each of three zones: the nasal bulbar

conjunctiva, the temporal bulbar conjunctiva, and cornea in each eye. And

a score of zero is given for no staining, one for sparsely scattered staining, two for densely scattered staining, and three for confluent spots of staining. In the Oxford system, rose

of staining. In the Oxford system, rose bengal, lissamine green, or fluorescein can be used to grade severity of staining of the cornea and conjunctiva.

The grade of staining is ascertained by referring to a chart of standard diagrams. In the National Eye Institute Industry Workshop System, fluorescein is

used to grade severity of staining in each of five zones of cornea, as shown here in this diagram, and lissamine green is used to grade severity of staining in each of six zones of

conjunctiva, as shown here in this diagram in each eye. And the score for each zone is determined by comparing with a set of reference standards. In

the Ocular Surface Staining or OSS system, fluorescein is used to grade severity of staining of cornea, and lissamine green is used to grade severity of staining of conjunctiva. In

this system, grading is done by counting number of dots of staining, and the scale for cornea and conjunctiva are different. For corneal fluorescein

different. For corneal fluorescein staining, one additional point is given if there are confluent dots of staining, staining in pupil- lary area, and or

presence of filaments. The rate of tear production is estimated either with the Schirmer test or by the phenol red test.

The Schirmer test is performed with a standardized filter paper strip, as shown here in this photograph. 5 mm of the rounded end of which is folded and placed in the inferior cul-de-sac at the

junction of middle and lateral thirds of the lower eyelid margin of each eye, as shown here in this photograph. With the

Schirmer strip in place, the patient is allowed to keep the eyes either open or closed or to blink normally. And the

environment in which the test is performed should not have strong air currents or low humidity. And the extent of wetting in millimeters of the remaining portion of the strip after a

certain time interval is noted. Schirmer

test can be performed in three ways.

Schirmer 1 test, which is the most commonly performed Schirmer test, is done without application of anesthetic, and is said to assess both basal and reflex tear secretion and a wetting of

less than 5 mm after 5 minutes is said to be diagnostic of aqueous tear deficiency. The basic secretion test is

deficiency. The basic secretion test is done following application of topical anesthetic with excess of the anesthetic wiped following application and the basic secretion test is said to assess

basal tear secretion. With the basic secretion test, a wetting of less than 5 mm after 5 minutes is considered to be diagnostic of aqueous tear deficiency

and so the parameters of both the Schirmer 1 test and the basic secretion test are the same.

But the basic secretion test has been found to be more objective and reliable than Schirmer 1 test. The Schirmer 2 test is done without application of anesthetic and in this test with the

Schirmer strips in place, the nasal mucosa is irritated with a cotton-tipped applicator and so the Schirmer 2 test is said to assess reflex tear secretion and

a wetting of less than 15 mm after 2 minutes is considered abnormal in Schirmer 2 test. In phenol red test, 3

mm bended of a 75 mm thread impregnated with phenol red dye is placed in lateral 1/5 of inferior cul-de-sac as seen here in this photograph.

The phenol red dye converts from yellow to orange in color upon exposure to the mildly alkaline tear. The thread of phenol red test causes much less irritation than the strip of Schirmer

test and so the phenol red test does not require anesthetic to measure basal secretion and with the phenol red test, a wetting of less than 10 mm after 15

seconds is considered diagnostic of aqueous tear deficiency. The tear

clearance tests, which we have discussed in oculoplasty section, assess the adequacy of drainage of tears through the puncta into the nasolacrimal system.

Then we have the diagnostic tests and equipments available to evaluate the tear film, but these diagnostic tests should be performed prior to application of topical anesthetics and or vital dyes

and prior to performing the Schirmer test, but it is important to remember that the findings on these diagnostic tests generally do not correlate with the symptoms of dry eye disease.

Meibography enables assessment of structure of the meibomian glands. In

contact meibography, an everted eyelid is transilluminated from the skin surface and the palpebral conjunctival surface is examined in this transilluminated light as shown here in

this photograph. In this technique, the

this photograph. In this technique, the meibomian glands appear dark with their intervening spaces appearing light.

Presently, non-contact meibography is the more favored technique of meibography and for this several devices are available. Instead of

are available. Instead of transillumination non-contact meibography uses reflectance of infrared light from palpebral conjunctival surface of an everted eyelid. With this

technique, the meibomian glands appear as light structures with their intervening spaces appearing dark as shown here in this photograph. And

normally, the meibomian gland appear as long structures which are uniformly spaced with minimal tortuosity as shown here.

Green Study Group defined the various abnormal appearances of meibomian glands on non-contact meibography which are described by these terms and represented here in this corresponding

The appearance of the meibomian glands on non-contact meibography can be graded by various schemes such as the meibo score method and the meibo grade method.

The meibo score method grades the extent of gland drop out for each eyelid and the meibo grade method grades gland distortion and shortening in addition to grading gland drop out. Some of these

devices such as Keratograph 5M and LipiView can measure thickness of the lipid layer of tear film, and assess blink characteristics. The thickness of

blink characteristics. The thickness of the lipid layer of the tear film is assessed by projecting polarized light with the light reflected from the tear film creating interference patterns. And

the interference pattern created depends on the thickness and stability of the tear film. And the blink characteristics

tear film. And the blink characteristics these machines can assess include frequency and completeness of blink with this photograph showing an incomplete blink.

NIBUT is the non-invasive technique of assessing tear breakup time. NIBUT does

not require fluorescein application, and as we have mentioned, the volume of fluorescein containing drop used to stain the tear film for the traditional TBUT test may itself alter the test

results. The NIBUT device projects a

results. The NIBUT device projects a pattern, either a grid or Placido rings, as shown here in this photograph on the cornea. And as in the traditional TBUT

cornea. And as in the traditional TBUT test, the patient is asked to blink several times, and then to keep the eye open. And the time interval between the

open. And the time interval between the last complete blink and the onset of degradation of the image of the pattern on the eye is considered as NIBUT. And

studies have found NIBUT results to be more reproducible than traditional TBUT results. Several devices can estimate

results. Several devices can estimate the height of the tear meniscus, such as Keratograph 5M and CA 800, as well as anterior segment OCT, which in addition

to assessing the height of the tear meniscus can also assess surface this area of the tear meniscus, as well as thickness of the pre-corneal tear film.

Hyperosmolarity of tear film is a characteristic of dry eye disease, and osmolarity of tears is primarily determined by electrolyte concentration in the mucoaqueous component of tear

film. The TearLab osmolarity system, as

film. The TearLab osmolarity system, as shown here in this photograph, can estimate tear osmolarity by collecting only 15 nanoliters of tear from the inferior temporal tear meniscus with the

help of a card on top of the pen of the device. And after collection of the

device. And after collection of the sample, when the pen along with the test card is docked on the machine, the display of the machine gives the reading of tear osmolarity. Normal upper limit

of tear osmolarity is considered to be 308 mOsm/L, and the reading of more than 326 mOsm/L indicates severe tear hyperosmolarity.

And variability of tear osmolarity over time and between the two eyes is said to be more important than the actual osmolarity. Tear osmolarity has been

osmolarity. Tear osmolarity has been found to be not affected by age, race, and hormonal changes, but has been found to be elevated following sleep

deprivation, fasting, and dehydration, and in high-altitude environments.

InflammaDry is another proprietary test which estimates levels of the inflammatory marker matrix metalloproteinase 9 in the tear film, which is increased in dry eye disease.

But the levels of this inflammatory marker can also be elevated in other inflammatory conditions of the eye, such as allergy and infections. For this

test, sample is collected from six to eight sites on the palpebral conjunctiva with the sample collector, which is then attached to the test cassette, and then the tip of the test cassette is dipped

into a vial containing a buffer.

Detection of both a blue and a red line in the result window of the test cassette indicates a positive result corresponding to MMP-9 levels equal to

or more than 40 ng/mL in the tear film, and detection of only a blue line in absence of a red line indicates negative result with lowered

MMP-9 levels in the tear film. But if

neither blue line nor red line is seen, it indicates an invalid test.

Tear Scan is another proprietary test which estimates lactoferrin level in the tear film, which is decreased in dry eye disease. and lactoferrin levels in the

disease. and lactoferrin levels in the sample is assessed colorimetrically by reacting the sample with reagent. These

three proprietary tests are also called point-of-care tests because they can biochemically analyze the tear film without the help of a laboratory.

Functional visual acuity is impaired in dry eye, and functional visual acuity can be evaluated by estimating visual acuity during rapid presentation of

optotypes or during reading assignments of at least 30 minutes, but these are used in research settings. Corneal

sensation may be decreased or increased in dry eye disease, and corneal sensation can be assessed in the clinic with a cotton-tipped applicator as we have discussed in the previous session

or with a cotton bonnet esthesiometer.

The Sjö test is another proprietary test used to detect for traditional antibodies and three tissue-specific autoantibodies related to Sjögren's syndrome from blood obtained with a

finger prick, but definitive diagnosis of Sjögren's syndrome requires minor salivary gland biopsy as we'll be discussing in a subsequent session. To

recap the salient points, dry eye questionnaires enable assessment of frequency and severity of symptoms related to tear film dysfunction, but severity of symptoms may not correlate

with signs elicited on clinical examination and diagnostic tests.

Clinical examination for tear film dysfunction includes assessment of tear film with respect to the tear meniscus height and presence of debris and or

foam in the tear meniscus and or the pre-corneal tear film. Assessment of the periocular skin, whether rosacea or seborrheic dermatitis is present.

Assessment of lids, whether retraction, laxity entropion ectropion or lagophthalmos is present, and the frequency and completeness of eyelid blinking. Assessment of the margins,

blinking. Assessment of the margins, whether anterior blepharitis, posterior blepharitis, or trichiasis is present.

Assessment of meibomian glands, whether obstruction and/or pouting of the openings of the meibomian glands is present, and the nature of the manually expressed secretions from the meibomian

glands, conjunctival scarring, which occurs in cicatrizing conjunctival disorders, which are associated with severe dry eye, and corneal sensation.

Tear production rate can be assessed with Schirmer test, in which wetting of 5 mm or less of the Schirmer's strip after 5 minutes is considered as

abnormal, or phenol red test. Two

important clinical tests for tear film dysfunction are the tear breakup time and ocular surface staining with vital dyes. Tear breakup time estimates the

dyes. Tear breakup time estimates the time interval from the last complete blink to the first appearance of a random dry spot on the cornea after staining of the ocular surface with

fluorescein, with a value of less than 5 seconds being considered as abnormal.

Staining of the ocular surface with vital dyes, specifically fluorescein for the cornea and rose bengal or lissamine green for the conjunctiva, can be graded

by various systems. Diagnostic tests available for evaluating the tear film include non-invasive assessment of tear breakup time or INIBUT, which does not

require application of fluorescein dye.

Meibography, which evaluates the structural characteristics of meibomian glands, with or without assessment of the thickness of the lipid layer of the tear film, assessment of tear film

thickness and tear meniscus height, point-of-care tests, which are proprietary tests which allow assessment of osmolarity, matrix metalloproteinase-9 levels, and

lactoferrin levels of the tear film in the clinic, and assessment of corneal sensation with Cochet-Bonnet esthesiometer.

Thank you for listening.