Article

Diagnostic Testing for Dry Eye Disease

REVIEW THE DEVICES AVAILABLE TO BEST EQUIP YOUR PRACTICE TO CARE FOR DED PATIENTS

The goal of any diagnostic testing is to help paint a clear picture of what is happening with your patient to guide your clinical decision-making. In the area of dry eye disease (DED), ultimately the goal of diagnostic technology should be to help clinicians identify the disease, and determine the level of severity according to the Delphi panel:1

  • Level 1: Mild to moderate symptoms and no signs; mild to moderate conjunctival signs
  • Level 2: Moderate to severe symptoms; tear film signs; mild corneal punctate staining; conjunctival staining; visual signs
  • Level 3: Severe symptoms; marked corneal punctate staining; central corneal staining; filamentary keratitis
  • Level 4: Severe symptoms; severe corneal staining, erosions; conjunctival scarring

When evaluating DED diagnostic testing, I recommend you separate it into different components: (Curious as to why I broke these out? See “Diagnostic Testing Categories,” right.)

  1. History and Questionnaires
  2. Tear Composition
  3. Ocular Surface Integrity
  4. Lid Structure and Function
  5. Serology

Let’s review the diagnostic equipment in each category. Consider first the diagnostic tools you need to help you identify the multifactorial nature of DED that will guide your treatment protocol.

Beyond the initial diagnosis, consider those technologies that will provide your practice with valuable information, ease of use, efficiency and/or patient education/empowerment through pictures, instead of words. These technologies can also serve to differentiate your practice and, thus, attract new patients and help ensure existing patients will return to your practice.

But don’t forget that you, as the clinician, are your own best diagnostic tool. We are trained investigators and observers. Put those Sherlock Holmes’ skills to good use!

DIAGNOSTIC TESTING CATEGORIES

Why do I separate the testing into these components? Historically, physicians would want to know whether the patient suffered from aqueous deficiency or evaporative dry eye disease. According to the Tear Film and Ocular Surface Society’s (TFOS) Dry Eye Workshop (DEWS) II, “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage and neurosensory abnormalities play etiological roles.” Multifactorial etiology makes the disease more complex, and, in many cases seen clinically, patients have some components of both aqueous deficient and evaporative disease. Diagnostic equipment shouldn’t be aimed at identifying whether the patient has aqueous deficient or evaporative dry eye disease. The correct combination of diagnostic tools should identify factors contributing to both. The very fact that dry eye disease is multifactorial demands that we know both.

HISTORY AND QUESTIONNAIRES

Asking the right questions sets you up for success with your diagnostic testing and decision-making. Therefore, a thorough case history is a must for any practice. My dialogue looks something like this, “Walk me through your typical day. I want to know how you use your eyes on an everyday basis. How do your eyes feel? Do they itch, water, burn? Do you use drops or feel like you should? Do they help?”

I educate patients that when our front surface is healthy, we are not aware of our eyes. Awareness is equal to a problem brewing, and, therefore, we must dig deeper. This information is paramount in identifying who has potential DED.

A validated questionnaire is also a must-have. Miss this, and the patient may not be identified or may be diagnosed later, which may create incredible inefficiencies at best and, at worst, allow the patient to advance to a higher degree of symptom/sign severity.

Options for a validated questionnaire:

  • Ocular Surface Disease Index (OSDI) (Available at bit.ly/OSDIded .)
  • Standardized Patient Evaluation of Eye Dryness and Ocular Surface Disease Index (SPEED) (Available bit.ly/SPEEDded .)
  • The Dry Eye Questionnaire (DEQ-5) (Available at bit.ly/DEQ-5 .)

TEAR COMPOSITION

What is the tear quality? Tears are a complex mix of proteins, mucins and lipids that regulate the front surface and provide homeostasis.2 The definition TFOS DEWS II references in “Diagnostic testing categories” is that ocular inflammation plays an etiological role in DED. Thus, it certainly behooves us, as clinicians, to understand this information.

Additionally, sometimes patients need convincing, and objective numbers can help with that conversation, hence the categorization.

  • Tear osmolarity. This diagnostic tool measures the saltiness of tears, or osmolarity. In reviewed literature, osmolarity readings above 308 mOsms/L or an inter-eye difference of >8 mOsm/L are an indication of mild osmolarity and loss of homeostasis.3,4
  • Matrix Metalloproteinase-9 (MMP-9). A nonspecific inflammatory marker that can be present in patients who have DED.5

OCULAR SURFACE INTEGRITY

We are already examining our patients with slit lamp biomicroscopy. The addition of the following tools with the examination allows for a clearer clinical picture of the multifactorial nature of DED and may elevate treatment strategies. These tools are all available for minimal or no investment, which is great news!

These represent the basic tools needed to gather pertinent information, but it’s worth noting that some diagnostic instruments give us this ocular surface data with built-in algorithms, which help increase efficiency and can provide that patient “wow” factor.

  • Tear meniscus height. This information tells us how much tear volume is present. The normal average is 0.2 mm.6
  • Lissamine green. This vital dye stains devitalized cells of the conjunctiva. Symptoms and conjunctival staining characterize Level 1 DED.1 No corneal signs will be present. Without this dye, you will miss Level 1 severity and may put off treatment until the patient progresses to Level 2 or 3.
  • NaFl (sodium fluoroscein). This vital dye stains corneal breaks and devitalized cells of the cornea. This is certainly an important indicator in establishing the health of the cornea.
  • TBUT. Measuring this provides data about the stability of the tears.
  • Phenol red thread test. A patient-preferred Schirmer’s test, it measures tear volume in 15 seconds with much less reflex tearing than Schirmer’s. The test is valuable when an objective measure of tear volume is needed on those true aqueous-deficient DED cases.

LID STRUCTURE AND FUNCTION

Eyelids are an integral piece of the puzzle in identifying and treating DED. Here is where your Sherlock Holmes’ muscles are fully flexed. Blink rate, eyelash extensions, make-up, critters (aka Demodex), blepharitis (anterior and posterior) and laxity are all important to uncover with diagnostic testing.

  • Eyelid morphology. Performed with the slit-lamp, this is a basic diagnostic test.
  • Meibomian gland expression. Expression is important in understanding the quality of meibum and quantity of the glands that are functioning. Diagnostic tools: cotton swab, fingertip or meibomian gland evaluator.7
  • Blink rate. Identifying patients who have a partial blink, full blink and how many times they blink is important to evaluate because proper blinking facilitates meibomian gland functionality.8 Blink rate tests include: BlinkCam (BlinkCam), iPEDA (Ophthalmic Resources) and LipiView (Johnson & Johnson Vision), which also measures the thickness of the lipid layer.
  • Meibography. This diagnostic tool images the integrity of the meibomian glands using infrared cameras. This can be a powerful tool to help patients understand how these glands can impact their disease process. Several instruments are on the market that offer meibography, with other diagnostic testing and algorithms, such as non-invasive TBUT, tear meniscus height, blink rate, corneal topography and videography. I’ve listed some of these instruments here for your perusal:
    • Antares (Lumenis)
    • LipiScan, LipiView II (TearScience/Johnson & Johnson Vision)
    • Keratograph 5M (Oculus)
    • Easytear view+ (Easytear)
    • DC-4 and/or SL-D701 (Topcon)
    • Meibox (Box Medical Solutions)

Lissamine staining of the conjunctival tissue: Level 1.
Image courtesy of Whitney Hauser, O.D.

Inferior corneal staining not encroaching the visual axis: Level 2
Image courtesy of Mile Brujic, O.D.

SEROLOGY

When patients have other symptoms, such as dry mouth and joint pain, along with their DED, Sjögren’s syndrome testing is warranted. Patients can have primary Sjögren’s or secondary Sjögren’s, meaning it co-exists with another primary autoimmune disease, such as rheumatoid arthritis, lupus or scleroderma. Serology is paramount in identifying these patients so that broader systemic conditions, such as non-Hodgkin’s lymphoma, can be identified.

  • Sjogren’s syndrome test. SS-A(RO), SS-B (La) and proprietary biomarkers (SP-1, IgA, IgC, IgM) (Quest Diagnostics). (Also, Sjö, Bausch + Lomb)

IN PRACTICE

Once you have acquired the diagnostic tests that you consider your must-haves, master and incorporate them into your clinic flow with the correct support from your team. Then consider adding the technologies that will provide your practice with the most value. (When investing in diagnostic devices, in general, consider your options. Drs. Marlon J. DeMeritt and Diana L. Shechtman outline the topic of diagnostic device acquisition in “Equipment Question,” from Optometric Management April 2017, http://bit.ly/2OLYMXP .)

A DED center with all the bells and whistles could look like this:

  • Case history
  • Validated symptom questionnaire
  • Tear osmolarity
  • Non-invasive TBUT
  • Tear meniscus height
  • Meibography
  • Digital photography and videography
  • Corneal and conjunctival staining with lissamine green and NaFL
  • Serology

Give yourself, your team and your patients every opportunity to have a successful DED practice with a solid implementation protocol. (Dr. Craig Thomas outlines a step-by-step process for implementing technology in “Your Tech Implementation Plan,” from OM August 2015, http://bit.ly/2M53am1 .)

CREATE YOUR PROTOCOL

Keep in mind that your must-have diagnostic devices and, ultimately, your protocol may be a little bit different from mine or those of other practices, as each practice is different in terms of a number of factors, including size, business practices and patient demographics. What’s important is to have a repeatable, consistent approach to testing that will allow you to best treat your patients.

By combining your knowledge and skills with information derived from the diagnostic tools you choose to use, you can develop a recipe for continued success in DED care for you and your patients. OM

REFERENCES

  1. Behrens A, Doyle JJ, Stem L, et al. Dysfunctional tear syndrome: a Delphi approach treatment recommendations. Cornea. 2006; 25: 900-7
  2. Dartt DA, Willcox MD. Complexity of the tear film: Importance in homeostasis and dysfunction during disease. Exp Eye Res. 2013; 117: 1-3.
  3. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci. 2006; 47: 4309-15
  4. Lemp MA. Bron AJ, Baudouin C, et al. Tear osmo-larity in the diagnosis and management of dry eye disease. Am J of Ophth. 2011; 151: 792-798.
  5. Messmer EM, von Lindenfels V, Garbe A, Kampik A. Matrix Metalloproteinase 9 Testing in Dry Eye Disease Using a Commercially Available Point-of-Care Immunoassay. Ophthalmology. 2016; 123: 2300-08
  6. Tung CI, Perin AF, Gumus K, Pflugfelder SC. Tear meniscus dimensions in tear dysfunction and their correlation with clinical parameters. Am J of Ophth 2014; 157: 301–10.e1.
  7. Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Cornea. 2008; 27:1142-7.
  8. Korb DR, Baron DF, Herman JP, et al. Tear film lipid layer thickness as a function of blinking. Cornea. 1994l; 13:354-9.