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A Glimpse of Dry Eye

Introduction

Dry eye (DED) is a multifactorial disease that results in symptoms of discomfort,visual disturbance and tear fi lm instability with potential damage to the ocular surface, accompanied by increased osmolarity of the tear fi lm and infl ammation. DED is a common clinical problem and is among the most frequent diagnoses in ophthalmology. It substantially affects quality of life because of the constant ocular discomfort and decrease in visual function.

Dry eye is recognized as a disturbance of the Lacrimal Functional Unit (LFU), an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them. This functional unit controls the major components of the tear fi lm in a regulated fashion and responds to environmental, endocrinological, and cortical infl uences. Its overall function is to preserve the integrity of the tear fi lm, the transparency of the cornea, and the quality of the image projected onto the retina.

Epidemiology

According to DEWS Report, prevalence of DED ranges from 5% to more than 30% at various ages. It has been estimated that about 3.23 million women & 1.68 million men of 50 years & above have dry eye.

Risk Factors

Well established risk factors for DED include: female sex, older age, postmenopausal estrogen therapy, a low diet in omega-3 fatty acids, refractive surgery, Vitamin A defi ciency & certain classes of systemic & ocular medications, including anti-histamines.

Symptoms

Common symptoms of DED are: irritation, tearing, burning, stinging, dry or foreign body sensation, mild itching, photophobia, blurred vision & increased frequency of blink. Symptoms usually have diurnal fl uctuation and may worsen later in the day.

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Classifi cation

The etiopathogenic classifi cation of dry eye disease comprises two major categories: Aqueous tear-defi cient dry eye (ADDE) & Evaporative dry eye (EDE).

Figure1. The DEWS Classifi cation of Dry Eye

Diagnosis

DED can be diagnosed largely on the basis of symptoms, but it has been documented that they do not necessarily refl ect the severity of the disease. Currently, there are no uniform criteria for the diagnosis of DED, nor a gold standard diagnostic test. Combinations of diagnostic tests have been used to assess symptoms and clinical signs.

Treatment

Dry eye treatment is a challenging task. The main objectives in treatment for patients with DED are to improve the patient’s quality of life, and to return the ocular surface and tear fi lm to the normal homeostatic state.

Dry Eye: Diagnosis

Dry eye is essentially a clinical diagnosis, combining information obtained from both the history and the examination and performing one or more tests to lend some objectivity to the diagnosis. No one test is suffi ciently specifi c to permit an absolute diagnosis of dry eye.

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Steps in the cycle of infl ammation in KCS

When the ocular surface and lacrimal glands are chronically irritated, T-cells become activated.

These activated T-cells recruit additional T-cells and cause an immune-based local infl ammation.

Cytokines are released in tears; this further irritates the ocular surface and blocks messages to the lacrimal gland.

As a result, normal tear secretion is reduced, and chronic dry eye syndrome symptoms develop.

Dry eye diagnosis based on the classifi cation can be roughly divided into three groups:

Aqueous Deficient Dry Eye: Tear Film Composition & Dynamics

Aqueous-defi cient dry eye is due to a lack of aqueous tear secretion by lacrimal tissue. An example is Sjögren’s syndrome, an autoimmune disorder that affl icts predominantly women. This syndrome is associated with extensive infl ammation in lacrimal glands, an immune-mediated dysfunction and/or destruction of acinar and ductal epithelial cells, and a signifi cant decline in aqueous tear output. Sjögren’s syndrome may be either primary (i.e. no associated connective tissue disease) or secondary (e.g. people with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]).

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Schirmer TestThe Schirmer test is used to test the aqueous tear production.

Procedure

Before the test, allow the patient to thoroughly blot the eyes to remove any excess tears

Place a thin strip of fi lter paper strip in the midportion of the lower eyelid

The eye is allowed to close for 5 minutes

After 5 minutes, assess the wetting on the fi lter paper

Schirmer test I: measures both basic and refl ex tearing

Interpretation

Normal value: > 10mm of wetting after 5 min

Positive for dry eye: < 10mm of wetting after 5 min

Schirmer test II: measures only refl ex tearing

Interpretation

Normal value: > 15mm of wetting after 5 min

Positive for dry eye: < 15mm of wetting after 5 min

Advantages

It is quick and simple

Disadvantages

Variable results

Low sensitivity, thus failure to measure basal secretions even when used without anesthesia

It measures the severity of eye dryness but does not establish its cause

Phenol Red Thread Test

The phenol red thread test is thought to be a test of tear volume. Phenol red is pH sensitive and changes from red to yellow when

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exposed to tears. Most likely, the phenol red thread test stimulates some refl ex tear production, measures uptake by the thread and is based upon tear fi lm composition.

Procedure

Place a crimped end of a 70-mm thread in the lower conjunctival fornix

Measure the value after 15 seconds

Interpretation

Normal value: 9-20mm

Positive for dry eye: < 9mm

Advantages

The phenol red thread causes less discomfort to the patient on insertion into the conjunctival sac thereby measuring more of basal tear secretion

Test time is very little, only 15 seconds, as compared to the Schirmer’s test (5 mins)

It can be easily prepared in the hospital/clinic.

(This test is not practised in India due to lack of its availability and standardization).

Meniscometry

Meniscometry is used to help diagnose aqueous tear defi ciency.

Procedure

A rotatable projection system with a target comprising black and white stripes is projected onto the lower central tear fi lm meniscus

Images are recorded and then transferred to a computer to calculate the radius of curvature

The radius of the curvature of the tear meniscus is linearly related with the tear volume

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Interpretation

Normal value: 0.19+0.05mm

Positive for dry eye: 0.10+0.04mm

(This test is not practised in India due to lack of its availability and standardization).

Fluorescein Meniscus Time (FMT)

FMT is a measure of the rate at which a fl uorescent tear meniscus is formed using 2% sodium fl uorescein.

Procedure

A drop of 2% sodium fl uorescein is placed in the lateral canthus of the eye

The natural fl ow of tears towards the lacrimal duct draws the dye along the lower eyelid in a medial direction as it is diluted with the tears produced by the lacrimal gland

Using a slit lamp and a cobalt-blue light fi lter and a stop watch, the time taken for the fl uorescent meniscus to fi ll the lateral half of the lower eyelid is measured in seconds

Advantages

More sensitive test with good reproducibility

Reliable in diagnosing aqueous tear defi ciency

Disadvantages

The use of fl uorescein might cause refl ex tearing, resulting in great variation

Evaporative Dry Eye: Tear Film Lipid Measurement

Evaporative dry eye is most often caused by meibomian gland dysfunction and lipid insuffi ciency, thereby promoting increased evaporation and decreased stability of the tear fi lm.

Phospholipase A2 Measurement

Phospholipids are the most important class of lipids in maintaining stability of the tear fi lm. Phospholipase A2 is the enzyme that hydrolyzes the phospholipids.

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The test is done by time-resolved fl uoroimmunoassay. The level of phospholipase is signifi cantly decreased in dry eye patients.

Interpretation

Normal value: 432.1+/–225.1 mg/L of phospholipids

Positive for dry eye: 218.6+/–183.3mg/L phospholipids

(This test is not practised in India due to lack of its availability and standardization.)

Meibometry

The lipid content of the preocular tear fi lm is delivered from the meibomian glands and is reduced in diseases associated with meibomian dysfunction.

Meibometry can be performed via laser interferometery or absorptive spectroscopy

It directly measures the lipid content of the tear fi lm.

(This test is not practised in India due to lack of its availability and standardization).

Tear Film Breakup Time

Tearfi lm break-up time (TFBUT) is determined by measuring the time lapse between instillation of fl uorescein and appearance of the fi rst dry spots on the cornea. It is measured prior to instillation of any anesthetic eye drops.

Procedure

A fl uorescein strip is moistened with saline and applied in the lower eyelid fornix and then removed

The patient is asked to stare straight ahead and not blink

The tear fi lm is observed under slit lamp microscope and the time that elapses between the last blink and the appearance of the fi rst break in the tear fi lm is recorded with a stopwatch

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Interpretation

Normal value: TFBUT > 10secs

Positive for dry eye: TFBUT < 10secs

Ocular Protection Index

Ocular Protection Index (OPI) can be used to quantify the interaction between the interblink interval (IBI) and TFBUT. The OPI is calculated by dividing TFBUT by the IBI.

Interpretation

Normal value: OPI >1

Positive for dry eye: OPI < 1

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Mucin Deficiency Dry Eye: Ocular Surface Evaluation

A variety of vital stains have been utilized for detection of surface damage of the corneal and conjunctival epithelium.

Fluorescein Staining

Fluorescein diffuses between corneal or conjunctival cells that have been disrupted due to dryness, degeneration or death. It stains the cornea more than the conjunctiva. This causes a greenish staining when viewed through a cobalt blue fi lter and is graded upon severity.

Procedure

A moistened tip of the fl uorescein-impregnated paper strip is applied to the inferior conjunctival fornix

The patient is then asked to blink several times

The presence and pattern of staining is accessed with cobalt blue exciter fi lter

After dye is applied cobalt lamp is used

Lamp allows cornealimperfections to be seen

Interpretation

Normal: If the test result is normal, the dye remains in the tear fi lm on the surface of the eye and does not adhere to the eye itself.

Dry eye: Staining of the corneal and conjunctival cells.

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Advantages

Well tolerated

Causes minimal irritation

Relatively non-toxic to corneal epithelial cells

Disadvantages

Rapid penetration of fl uorescein into the corneal stroma in the presence of epithelial defects can blur the margin of the staining

Rose Bengal Staining

Rose Bengal stains not only dead and devitalized cells but also healthy cells that are protected inadequately by a mucin coating. Patients with severe rose Bengal staining indicate their inability to produce tears in response to sensory evaluation. Early or mild cases of dry eye are detected more easily with rose Bengal than with fl uorescein staining, and the conjunctiva usually is stained more intensely than the cornea.

Procedure

A stain is applied into the conjunctival sac

After a wait of 2mins, the degree of stain is quantitated by microscopic examination

Depending upon the staining, grading & severity of dry eye is diagnosed

Advantages

Dye is diffi cult to see on the cornea against the background of a dark iris

Also, it causes pain on instillation in patients with dry eye

Disadvantages

Intrinsic toxicity to corneal epithelial cells

Positive Rose Bengal Stain

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Typical dotted staining of the conjunctiva by Rose Bengal

Lissamine Green Staining

Lissamine green staining combines the advantages of fl uorescein and Rose Bengal staining; it stains healthy epithelial cells that are not protected by a mucin layer (similar to Rose Bengal) and also stains degenerating or dead cells (similar to fl uorescein).

Procedure

A stain is applied into the conjunctival sac

After a wait of 2mins, the degree of stain is quantitated by microscopic examination

Depending upon the staining, grading & severity of dry eye is diagnosed

Advantages

It avoids the pain, discomfort, and corneal toxicity associated with Rose Bengal

Disadvantages

Less sensitive and more transient, so it is more diffi cult to appreciate on slit lamp examination.

Lissamine Green Staining

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Interpretation of the staining techniques

The interpretation is based on two factors: the intensity and the location.

According to Van Bijsterveld grading system, the intensity is based on the scale of 0 to 3 in three areas: nasal conjunctiva, temporal conjunctiva and cornea. The maximum possible score with this grading system is 9.

Interpretation

Normal: No staining –Grade - 0

Mild dry eye: >1/3 =Grade-1

Moderate dry eye: >2/3 =Grade-2

Severe dry eye: >3/3 =Grade-3

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Rose Bengal staining revealing severe dry eye

Tips on using vital dyes for staining the ocular surface• The time to use one of the dyes is after the external eye exam

and refraction.

• In the case of Rose Bengal, use an anesthetic drop fi rst.

• If the patient has mild dry eye, the dye will permeate the nasal bulbar conjunctiva and possibly the superior edge of the lower lid as well.

• In more severe cases, the staining may be more intense and involve the cornea as well as the temporal bulbar conjunctiva.

Tear Osmolarity Test – A General Test For Dry Eye

Testing tear osmolarity is an effective and objective assessment for dry eye disease.

Tear osmolarity test measures the osmolarity of tears and aids in the diagnosis of dry eye disease.

A new tear osmolarity testing system, the TearLab Osmolarity System uses a novel approach that concentrates laboratory functions on a single chip that requires less than 50 nL of tear fl uid in order to measure tear osmolarity.

The system is about the size of a telephone which absorbs a tiny, 50-nl tear sample via capillary action and measures the osmolarity of the tears.

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Procedure

The system uses a handheld pen on which the ophthalmologist or technician needs to place the noninvasive laboratory chip test card.

After the tear sample is collected (usually in less than 30 seconds), the device produces the measurement of osmolarity in less than 1 minute.

Interpretation

Scale of dry eye disease classifi cations with corresponding osmolarity measurements

Normal Marginal 1 1 3 4

Osmolarity reading (msOm)

275 to 301

302 to 312

313 to 323

324 to 332

333 to 345

346 +

Note: Measurements of osmolarity are based on the classifi cation system established in the Dry Eye Workshop Report.

High osmolarity correlates with severe dry eye.

Advantages

Easy to use

Provides fast results

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REFERENCES

1. Seminars in Ophthalmology, May 2010, Vol. 25, Pages 84-93

2. The Ocular Surface, April 2007, Vol. 5, No. 2,75-81

3. Korean J Ophthalmol,1991, Vol 5:34-36

4. Invest Ophthalmol Vis Sci 2004; 45: E-Abstract 98

5. http://emedicine.medscape.com/article/1210417-diagnosis Last accessed on 29/09/10

6. Dry eye: a practical guide to ocular surface disorders and stem cell surgery by Amar Agarwal

7. http://www.gendermedicine.com/Uploads/assets/sullivan.pdf

8. http://www.aios.org/proceed09/paper2009/LAC/Lac8.pdf

9. http://www.answers.com/topic/schirmer-s-test

10. Survey of Ophthalmology, March 2001, Volume 45, (2): S221-S226

11. Eye (2002) 16, 594-600

12. Management of Complications in Refractive Surgery, edited by Jorge L. Alió, Dimitri T. Azar

13. http://www.medhelp.org/medical-information/show/417/Fluorescein-eye-stain?page=1

14. http://www.jdosmp.org/lectures/sd_des.htm

15. Cornea, Volume 1 by Jay H. Krachmer, Mark J. Mannis, Edward J. Holland

16. http://www.chillibreeze.com/articles_various/dry-eye-disease.asp

17. American Journal of Ophthalmology May 2008;Volume 145(5): 795-800

18. Optometry Times, Jul 1, 2009, By: Jennifer A. Webb

19. Cataract & Refractive Surgery Today, April 2009; 1:1-2

20. P & T Digest, Dry Eye Syndrome; Pg no.18

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Notes

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