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Dry Eye 2: Evaluation

2 CPD in Australia | 0.5CD & 0.5G in New Zealand | 13 April 2016
 
EXCLUSIVE TO LUXOTTICA

Definition of Dry Eye

Dry eye has been defined by the 2007 International Dry Eye Workshop (DEWS) as:

"A multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with the potential to damage the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface."

Figure 1. DEWS Report 2007

The 2011 Meibomian Gland Dysfunction Workshop added another piece to the puzzle showing that abnormal meibomian gland function play a major role in altering the tear film leading to ocular surface disease, inflammation and clinical dry eye.

How many people report dry eye symptoms?

Dry eye is seen more often in older people, though younger people who perform excessive reading or computer work (reduced blinking) also experience the condition. The 2011 Allergan US Dry Eye Survey found that:

  • 48% of adults regularly experience dry eye symptoms
  • 42% of women aged 45 to 54 with dry eye experience blurred vision and difficulty reading
  • 30% of men and 19% of women over 55 have experienced dry eye symptoms for more than 10 years

Signs & Symptoms

It is important to remember that the symptoms of dry eye are non-specific. For example the dry eye symptoms of itchiness reported in the 2003 Melbourne VIP Study was later found to be due to be mostly due to hayfever!

The signs and symptoms of dry eye include:

  • ocular irritation / foreign body sensation
  • grittiness / burning
  • blurred vision / photophobia
  • reduced inferior tear prism height
  • reduced tear break up time
  • staining of the cornea with fluorescein
  • staining of the conjunctiva with lissamine green
  • reduced corneal sensitivity

The loss of visual acuity in dry eye is shown in Figure 1. Due to rapid TBUT and corneal exposure, people with dry eye can lose up to 3Snellen lines of visual acuity between blinks.

Figure 2 Reduction of Snellen acuity between blinks for normal and dry eye patients. From: Walker PW et al. 2007.

Clinical Assessment

For some optometrists, the evaluation of dry can be simply:

  • case history “What’s wrong?”
  • symptoms “I have a dry uncomfortable eye”
  • signs slit lamp exam with fluorescein staining

A thorough clinical assessment of dry eye can require more time due to the wide range of issues that need to be addressed.

Self-Reporting Questionnaires

Many dry eye referral centres use patient self-reporting questionnaires. These are valuable as they require the patient to reflect on and take ownership of their condition. A number of dry eye self-reporting questionnaires are available (e.g. McMonnies Dry Eye Questionnaire, CANDEES, OSDI). The Ocular Surface Disease Index (OSDI) is one of the most commonly used dry eye self-reporting questionnaires. The OSDI provides a quick, structured, validated questionnaire for assessing dry eye disease symptoms. Its ability to provide a single numeric descriptor to describe dry eye symptoms is valuable in monitoring change. Ideally perform the OSDI at diagnosis and repeat it after completing an intervention. The percentage change will enable the patient to clearly see the affectivity of the treatment.

Figure 3. OSDI is one of the most commonly used dry eye self-reporting questionnaires

History

The case history should identify risk factors associated with dry eye. Some are listed below.

Table 1. Common causes of dry eye

 

Figure 4. Always check for blepharitis in dry eye. Sjogrens syndrome is associated with severe dry eye

A systemised dry eye form will also help provide a consistent diagnostic routine. Here is an example from the Review of Optometry.

Figure 5. Diagnostic form for Dry Eye. From http://www.revoptom.com/content/d/dry_eye/i/990/c/18932/


Clinical Examination

The clinical examination for dry eye should include a thorough examination of the external eye.

TEARS - volume, meniscus height, break-up time (TBUT), osmolarity

LIDS & LASHES - disease, position, blink rate

GLANDS - morphology, secretions, expression

OCULAR SURFACE - staining of the ocular surface, inflammation

Figure 6. Diagnostic Tools in Dry Eye. From Alai M 2012.


Tear Volume

Schirmer Test

The Schirmer test (#1 without anaesthesia; #2 with anaesthesia) remains a common method for evaluating aqueous tear production. Note that this test should be performed after TBUT and ocular surface dye staining as the Schirmer test can disrupt tear film stability. Abnormal: <5mm wetting in 5 min.

Figure 7. Schirmer strip testing

Tear Function Index

The Tear Function Index is a modified Schirmer test (Xu et al, 1995). A Schirmer strip with a known amount of fluorescein is placed in the standard position and left for 3 minutes and the length of wet strip is measured. The difference is that the dilution of the yellow fluorescein is measured against a standard dilution panel (1:1 to 1:128). The TFI is the Schirmer length divided by the fluorescein dilution value. A TFI > 96 is normal. A TFI < 16 indicates Sjogren syndrome. A full explanation can be seen of the TFOS YouTube video <https://www.youtube.com/watch?v=E7GxM80MB84>. Abnormal: TFI values < 96.

Figure 8. Tear function Index testing

Phenol Red Thread Test

Phenol red thread testing is a practical alternative to the Schirmer test that takes only 15 seconds to complete. It is more comfortable and avoids reflex tearing. Abnormal: < 10mm wetting.

Figure 9. Phenol red thread testing

Tear Meniscus Height

Meniscometry (Yokoi & Komuro, 2004) measures the height of the tear meniscus. A striped target is projected onto the lower central tear film meniscus and images captured by a computer. These are then processed and the inferior tear meniscus height determined. The Oculus Keratograph 5M is the modern iteration of this method and allows fast and easy measurement of tear meniscus height. A normal value is 0.20 to 0.25mm. Abnormal: < 0.18 mm.  The Oculus Keratograph 5M is an advanced corneal topographer with a built-in real keratometer and a color camera optimised for external imaging. Unique features include examining the meibomian glands, non-invasive tear film break-up time and the tear meniscus height measurement and evaluating the lipid layer.

Figure 10. Tear meniscus height testing and Oculus Keratograph

An excellent TFOS video explaining how to assess the tear meniscus can be found on YouTube <https://www.youtube.com/watch?v=fdH2Kd67UjM>.

Tear Film Thickness

The LipiView interferometer measures the average thickness of the tear film in 5 minutes. A thin tear film is thought to suggest evaporative dry eye due to lipid deficiency from meibomian gland dysfunction.

Figure 11. Tear film thickness testing and LipiView

The LipiView II Ocular Surface Interferometer is an ophthalmic imaging device that is intended for use by a physician in adult patients to capture, archive, manipulate and store digital images of:

  • Specular (interferometric) observations of the tear film. Using these images, LipiView II measures the absolute thickness of the tear film lipid layer.
  • Meibomian glands under near-infrared (NIR) illumination.
  • The ocular surface and eyelids under white illumination.

TBUT

During the assessment of tear break up time (TBUT), fluorescein is applied to the tear film as a drop or via a moistened filter paper strip. Both of these methods are invasive as they add volume to the tear film, disrupt the ocular surface and induce reflex lacrimation. In research settings, a micropipette can be used to control the volume of fluorescein applied to the eye. A non-invasive TBUT (NIBUT) can be performed using corneal topography or keratometry mires (Maissa & guillon, 2010). Abnormal: < 10 seconds

Figure 12. TBUT testing and Distribution of TBUT in a normal population

 The Oculus Keratograph allows simple non-contact automated assessments of TBUT to be conducted.

Figure 13. TBUT testing with an Oculus Keratograph

Clinical Pearls for TBUT

  • Assess TBUT before performing fluorescein staining or expressing glands.
  • Touching the Schirmer strip to the lower palpebral conjunctiva gives less reflex tearing than placing the strip on the bulbar conjunctiva.
  • Wait 5 minutes after removing contact lenses before measuring TBUT.
  • Look at the position and pattern of the breakdown of the tear film. For example; a rapid tear break-up on the inferior cornea could indicate lagophthalmos

An excellent TFOS video explaining how to assess TBUT can be found on YouTube <https://www.youtube.com/watch?v=chHTGyKNNwY>

Tear Osmolarity

Tear osmolarity has become an important area of research in dry eye. Unfortunately measuring tear osmolarity was not possible clinically for many years due to many practical restrictions. This changed with the release of the TearLab. In office osmolarity testing is now possible.   

The TearLab Osmolarity Test Card, in conjunction with the TearLab Osmolarity System, provides a quick and simple method for determining tear osmolarity using nanoliter (nL) volumes of tear fluid collected directly from the eyelid margin. The Test Card is held by the Osmolarity Test Pen, for safe collection.  The TearLab Osmolarity Test utilises a temperature-corrected impedance measurement to provide an indirect assessment of osmolarity. After applying a lot-specific calibration curve, osmolarity is calculated and displayed as a quantitative numerical value.

The TearLab Osmolarity Test Card at the tip that picks up approximately 50 nL of tear film at the tear meniscus, which is then placed in a portable, counter top system reader. In seconds, the reader converts the tear fluid to an osmolarity score expressed in mOsm/L, which is displayed on an LCD panel.  Abnormal: >316 mOsm/L indicates dry eye disease.

Figure 14. Tear osmolarity testing with a TearLab

Caution: While the DEWS and a number of dry eye referral centres strongly champion the use of tear osmolarity in dry eye management, there are still some questions about its utility. Clinicians should currently consider tear osmolarity testing as one part of a total diagnostic protocol.

Figure 15. Tear Osmolarity Distribution. From Tomlinson et al, 2006.

Blink rate

The relationship between the blink rate and the TBUT is termed the Ocular Protection Index (OPI). If the inter-blink interval (IBI) is greater than the TBUT, then the ocular surface will be exposed and tear evaporation can produce hyperosmolarity in the tear film. To determine the OPI, count the blinks per minute as the patient reads the distance letter chart. The mean blink rates can vary from 17 blinks / minute at rest to 4 blinks / minute while reading. This clearly explains why patients with a TBUT less than 10 seconds are often symptomatic. Have a look at this interesting video explaining the OPI and how it relates to clinical practice (<https://www.youtube.com/watch?v=iK14OlfW5ak>).

Figure 16. The Ocular protection Index

Ocular surface staining

Diagnostic staining using a range of vital stains including fluorescein, rose bengal or lissamine green can identify damage to the cornea and conjunctiva.

Fluorescein was first used on the eye in 1882 to reveal corneal epithelial defects. It is now used in many areas of ophthalmology and especially in retinal angiography. Fluorescein will be evenly distributed in the tear film during the blink and clearly shows areas of tear film break (TBUT). Cell membrane damage allows the dye to penetrate the cell and show as areas of increasing fluorescence. Fluorescein staining is particularly useful for observing damage to the cell walls of corneal epithelial cells (e.g. abrasions, ulcers).

Figure 17. Fluorescein strips TBUT pattern

Practitioners can use either regular low molecular weight fluorescein (e.g. Fluorets) or a higher molecular weight fluorescein (e.g. SoftGlo strips). Higher molecular weight fluorescein is useful when practitioners are concerned about staining a reusable contact lens.

Figure 18. Fluoret strips Hi molecular weight fluorescein (Soft Glo)

Rose bengal is a derivative of fluorescein. It was popularized by the Swedish physician Henrik Sjögren in the 1930s for diagnosing extreme dry eye (keratoconjunctivitis sicca). Rose bengal cannot stain the healthy ocular surface. In dry eye, rose bengal can penetrate and stain the ocular surface due to areas where the tear film breaks or there is an absence of normal protective tear components like mucin. Rose Bengal is also toxic and can damage the ocular surface as well as killing surface bacteria and viruses. This is important to remember if taking a tissue culture swab after staining with rose Bengal. The major clinical drawback of using rose Bengal is its significant sting on instillation.

Figure 19. Rose Bengal strips Rose Bengal staining in dry eye

Lissamine green has is widely used as a non-ophthalmic drug, cosmetic and food additive. Lissamine green has many names: wool green S; food green; acid green S; fast light green; pontacyl green S; cyanol green B; calcoid green S extra and pyronin G. It is a phenyl methane dye, unlike both fluorescein and rose bengal which are xanthine dyes.

Figure 20. Lissamine green strips Lissamine green staining in dry eye

Lissamine green preferentially stains membrane damaged or devitalized cells. Importantly, lissamine does not stain healthy ocular surface cells while both flourescein and rose bengal can in certain circumstances. Unlike rose bengal, lissamine green has no cellular toxicity properties. Unlike rose bengal, there is no stinging on instillation. The green colour of lissamine green is valuable clinically. Ophthalmic dyes are often used in red eyes. Lissamine green is visible with greater contrast on a red background, while rose bengal can be disappear by a red eye.

Lissamine green is particularly useful in identifying lid wiper epitheliopathy. The lid wiper is the area just posterior to the meibomian glands on the superior lid. It wipes the ocular surface during the blink. Lid wiper epitheliopathy occurs during in dry eye and in contact lens wear and is thought to result from mechanical friction between the marginal conjunctiva and the contact lens / ocular surface. Lid wiper epitheliopathy is found in 67 to 80% of symptomatic contact lens wearer but only in 13 to 32% of asymptomatic wearers (Efron N et al, 2013).

Figure 21. Lid wiper epitheliopathy

Grading of Ocular Staining

A standardized method of recording ocular staining recording system should be used. The Oxford Scheme is widely used and is recommended (Asbell & Lemp, 2006). It is recommended that the reader view the excellent TFOS video on staining and grading of the ocular surface in dry eye (<https://www.youtube.com/watch?v=chHTGyKNNwY>).

Figure 22. Oxford Staining Scheme

Here is an example of a Dry Eye recording sheet from Review of Optometry

Figure 23. Example of a Dry Eye Evaluation Card

International Workshop on Meibomian Gland Dysfunction 2011

The International Workshop on Meibomian Gland Dysfunction 2011 (Nicholls KK et al., 2011) reviewed the impact of abnormal meibomian gland function in dry eye. Hypo- or hypersecretion can influence the stability of the tear film leading to ocular inflammation and ultimately ocular surface disease.

Figure 24. Role of meibomian gland function in dry eye.

Assessing normal function

Performing meibomian gland expression on healthy normal patients is useful to gain an appreciation of the normal appearance and viscosity of meibum. Normal meibum is a clear oily liquid. A clean finger, cotton tip applicator or constant pressure device (Tear Science meibomian gland applicator applies 1gm/sq mm) is applied to the centre of the lower lid until meibum is expressed. This usually takes about 3-5 seconds. As the quality worsens, the meibum becomes increasingly opaque and expression requires more pressure.

The Mathers scale can be used to describe the expression material for:

  • Clarity
  • Colour
  • Viscosity
    • 1 - free flowing liquid
    • 2 - slightly viscous but still free flowing
    • 3 – thickened
    • 4 - toothpaste consistency (Mathers et al, 1991)

Figure 25. Tear Science meibomian gland applicator

While digital expression works well, the preferred method currently is to use a Mastrota paddle (left image below). Note that there is some concern at present that excessive pressure during gland expression may damage the lids and glands.

Figure 26. Mastrota paddle Forceps

Meibography

Meibomian gland dropout can be viewed using transillumination. This is done by everting the lid over a transilluminating light source and viewing the glands through the everted mucosal surface. The number of dysfunctional glands can be assessed. The procedure can be viewed on the TFOS YouTube video (<https://www.youtube.com/watch?v=RbneuP9iHtI>). Noncontact infrared meibography, for example as used in the Oculus Keratograph, is another method for evaluating meibomian gland morphology and drop out.

Figure 27. Meibography Oculus Keratograph

Inflammation

Both the DEWS and MGD Workshop place inflammation as a central mechanism in the pathophysiology of dry eye. A number of “stick” tests have been developed to enable in-office assays for inflammatory mediators. One example applicable to dry eye is Inflammadry that detects elevated levels of matrix metalloproteinase-9 (MMP-9) in the tears. It was approved by the US Food and Drug Administration (FDA) in November 2013. The test yields a positive result if the level of MMP-9 is >40 ng/mL. The role of this assay in clinical practice for the diagnosis and management of dry eye is yet to be determined. Some practices in Australia have trialled this technology. The key feedback is the Australian patients do not currently feel that optometry should assay the tears for inflammation. Perhaps this will change in the future as optometry increases its role in primary eye care and management of ocular disease. Abnormal: MMP-9 >40 ng/mL.

Figure 28. Inflammadry stick assay for MMP-9

Clinical resource

Perhaps the best clinical resource for the diagnosis and management of dry eye is the 2006 book edited by Asbell & Lemp. Highly recommended!

Figure 29. An excellent in office reference

 

The 2007 Report of the International Dry Eye WorkShop (DEWS)

The 2007 Report of the International Dry Eye WorkShop (DEWS) on the research of a large number of contributors.  The survey way conducted over a long period of time and included

  • collection of data,
  • presentation of summary reports in a conference format,
  • harmonization of reports by a writing team with interactive commentary by the entire group of participants in an international workshop.

The objective of the International Dry Eye WorkShop was to deliberate on all current knowledge of dry eye disease and to update, in critical and evidence-based fashion, the concepts and information presented in the 1995 National Eye Institute/Industry Workshop (Lemp MA. Report of the National Eye Institute/Industry Workshop on Clinical Trials in Dry Eye. CLAO J 1995;21:221-32).

Participants were selected based upon their level of contribution to previous dry eye workshops, history of being published in peer-reviewed journals,  and associations with experts in the dry eye field. Sponsorship for The International Dry Eye WorkShop was secured by The Tear Film & Ocular Surface Society (TFOS), who also organised and administered the WorkShop.

To address specific areas within Dry Eye subcommittees were formed.  Subcommittees were formed to specifically study:

  • Definition and Classification
  • Epidemiology; Diagnosis
  • Research
  • Clinical Trials
  • and Management and Therapy.

 

 

The International Workshop on Meibomian Gland Dysfunction

Meibomian gland dysfunction (MGD) is considered to be the main cause of dry eye disease.

Despite the prevalence of Meibomian gland dysfunction around the world, effecting the eye health of millions of people, there is no international consensus on the definition, classification, diagnosis, or therapy for MGD.

The International Workshop on Meibomian Gland Dysfunction was created by The Tear Film and Ocular Surface Society to achieve such consensus.

The objectives of the workshop were to:

  • conduct an evidence-based evaluation of meibomian gland structure and function in health and disease;
  • develop a contemporary understanding of the definition and classification of MGD;
  • assess methods of diagnosis, evaluation, and grading of the severity of MGD;
  • develop recommendations for the management and therapy of MGD;
  • develop appropriate norms of clinical trial design to evaluate pharmaceutical interventions for the treatment of MGD; and
  • create a summary of recommendations for future research in MGD.


 

 
REFERENCES
  • 2007 Report of the International Dry Eye WorkShop (DEWS). The Ocular Surface 2007: 5; 65-138.
  • Allergan Dry Eye Survey 2011. http://www.thedryeyereview.com/2012/04/new-allergan-survey-shows-48-have-dry-eye-symptoms/
  • Asbell PA & Lemp MA (eds). Dry Eye Disease: The Clinician's Guide to Diagnosis and Treatment. 2006. Thieme.
  • Bilkhu P, Naroo S, Wolffsohn J. Use of fluorescein in optometric practice. Optometry Today CET 25/04/14. http://www.optometry.co.uk/uploads/articles/cet-2014/april_25_2014_c-36209.pdf
  • Efron N, Jones L, Bron AJ et al. The TFOS International Workshop on Contact Lens Discomfort: Report of the Contact Lens Interactions With the Ocular Surface and Adnexa Subcommittee. Invest Ophthalmol Vis Sci. 2013;54:TFOS98–TFOS122.
  • Maissa C & Guillon M. Tear film dynamics and lipid layer characteristics—Effect of age and gender. Contact Lens & Anterior Eye 2010;33:176–182.
  • Mathers WD et al. Meibomian gland morphology and tear osmolarity: changes with Accutane therapy. Cornea 1991:10;286-290.
  • McCarty CA et al. The Epidemiology of Dry Eye in Melbourne, Australia. Ophthalmology 1998; 705:1111-1119.
  • Nicholls KK et al. The International Workshop on Meibomian Gland Dysfunction. Invest Ophthalmol Vis Sci 2011:52;1922-1929.
  • Xu K, Yagi Y, Toda I, Tsubota K. MD Tear Function Index: A New Measure of Dry Eye. Arch Ophthalmol. 1995;113:84-88.
  • Yokoi N & Komuro A. Non-invasive methods of assessing the tear film. Exp Eye Res 2004:78; 399-407.

' a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with the potential to damage the ocular surface '