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Subspecialties Cornea / Ocular Surface, Imaging & Diagnostics

Putting Dry Eye to the Test

An abnormal tear film underlies ocular surface symptoms associated with dry eye disease (DED). Measuring osmolarity at the point of care, therefore, has become a recommended tool in the diagnosis of ocular surface disease (1, 2, 3, 4). The measurements derived from osmolarity testing also provide an objective value for determining the severity of disease and for assessing the efficacy of treatments. When DED improves, osmolarity numbers go down – but how useful is a normal osmolarity result in making a diagnosis?

What does a normal tear test tell us?
In 2018, my colleagues at Weill Cornell Medicine, Department of Ophthalmology, and I conducted a prospective observational cohort study to explore the diagnostic utility of normal tear osmolarity in patients with symptoms suggestive of DED (5). Our aim was to evaluate for the presence of any alternate ocular surface disease (OSD) in patients with DED-like symptoms but with normal tear osmolarity.

We evaluated 100 patients who reported one or more symptoms indicative of potential DED and subsequently underwent tear osmolarity testing (TearLab). Included patients had a normal tear osmolarity test (value < 308 mOsm/L in each eye, and an inter-eye difference < 8 mOsm/L). The main outcome measure was the presence of any alternate diagnosis to explain the patient’s symptoms.

Among these patients, the mean tear osmolarity was 293.40 mOsms/L ( ± 6.82), with a mean absolute difference of 2.85 mOsms/L ( ± 1.98) between the eyes. A possible alternate diagnosis was established in 89 percent of patients with normal tear osmolarity testing. The most frequent diagnoses included anterior blepharitis (26 percent) and allergic conjunctivitis (21 percent). Our study highlights the diagnostic value of a normal osmolarity with an extremely high proportion of patients exhibiting an alternate OSD diagnosis to account for their symptoms.

Figure 1. Anterior blepharitis with lid scurf.

Figure 2. Meibomian gland disease.

DED is not a simple disease – nor is it a simple diagnosis.

Overlapping conditions call for different treatments
DED is not a simple disease – nor is it a simple diagnosis. The signs and symptoms of dry eye can overlap with other conditions – most often blepharitis and allergic conjunctivitis (see Figures 1 and 2). Measuring tear osmolarity is an important diagnostic step that provides diagnostic information no matter the result. A normal test can alert the clinician that there is likely a different OSD cause for the DED-like symptoms. Other alternate causes for irritation can be epithelial basement membrane dystrophy, keratoneuralgia, contact lens intolerance, conjunctivochalasis, and computer vision syndrome/situational DED (see box: DED-like symptoms, actual diagnosis).

In a study of 100 patients with DED-like symptoms and normal tear osmolarity, the most frequent OSD diagnoses included:

  •  anterior blepharitis (26%)
  • allergic conjunctivitis (21%)
  • epithelial basement membrane dystrophy (EBMD) (8%)
  • contact lens intolerance (6%)
  • conjunctivochalasis (5%)
  • neuropathic pain (4%)
  • computer vision syndrome (4%)

As part of my diagnostic workup for OSD, I also test for matrix metalloprotease-9 (InflammaDry; Quidel), which indicates inflammation on the surface of the eye. The slit-lamp exam is, of course, the cornerstone of any workup. If I know the patient has normal osmolarity, during the exam I can be honing in on evidence of other disease, with blepharitis or allergic conjunctivitis likely culprits. I will ask directed questions about their symptoms to elicit a specific setting or situation like computer use that might be contributing to the eye symptoms.

Point-of-care testing provides the data needed to help uncover the underlying cause of symptoms.

Ultimately, as eye care specialists, we want to drill down to the underlying cause of the patient's discomfort so that we can ensure our treatments are targeted and effective. If we treat dry eye and the patient has allergic conjunctivitis, we have not made an accurate diagnosis and our patient will still have symptoms. Point-of-care testing provides the data needed to help uncover the underlying cause of symptoms – and that’s why it is so important. For patients with multiple diagnoses, we should be treating each root cause of their symptoms.

Aggressive approach to pre-op therapy 
For our presurgical patients, we want the surface of the eyes to be pristine so we can obtain accurate biometry and keratometry measurements. Because our refractive decisions – and outcomes – depend on these values, they must be precise. Another reason why patients should have an optimally pretreated ocular surface is because the surgery itself can lead to an increase in dryness and irritation, especially in the postoperative period. If a patient has irritation after surgery, he or she may think that something “went wrong” with the procedure. For these reasons, we must treat any pre-existing conditions before moving ahead with surgery.

Rather than using a step-wise approach that might take a lot longer to achieve results, I am aggressive in presurgical therapy; for example, I will not hesitate to prescribe prescription drops to tamp down inflammation to rapidly reverse ocular surface changes and get the patient comfortable faster. 

Thanks to the members of the American Society of Cataract and Refractive Surgery (ASCRS) Cornea Clinical Committee, we now have a treatment algorithm specifically intended for optimized surgical outcomes (6). The targeted approach is meant to help surgeons efficiently diagnose and treat visually significant OSD before any form of refractive surgery is performed. Importantly, the algorithm can be used regardless of whether the patient complains of symptoms. We know signs and symptoms are poorly correlated and, notably, older patients do not report them on traditional questionnaires.

The ASCRS algorithm uses a specially designed modified questionnaire created for this purpose: the ASCRS-Modified Preoperative OSD Standardized Patient Evaluation of Eye Dryness (SPEED) II questionnaire. The extra questions added to the SPEED questionnaire help screen for other non-DED subtypes of OSD. Also, to address the interplay between patient expectations and the implications of paying out of pocket for premium technology, the group adapted items from the Cataract and Refractive Lens Exchange Questionnaire developed by Steven J. Dell. The algorithm identifies tear osmolarity and MMP-9 as essential to the initial screening (see sidebar: The ASCRS algorithm at a glance). 

The ASCRS algorithm at a glance

  • Osmolarity. Tear hyperosmolarity (TearLab) is central to the modern definition of DED.
  • MMP-9. The enzyme MMP-9 (InflammaDry; Quidel) plays a key role in the breakdown of the ocular surface. 
  • Further diagnostic tests can be done to identify OSD subtypes, such as lipid layer thickness, meibography, noninvasive tear breakup time, quantification of tear meniscus height, tear lactoferrin levels, topography or tomography, aberrometry, and Objective Scatter Index (HD Analyzer, Visiometrics).
  • Clinical Exam. Consider the mnemonic, look, lift, pull, push, for the quick focused ocular surface exam.

Normal tear tests can prevent a misdiagnosis of DED by prompting the eye care provider to look beyond to other forms of OSD. Physicians can more effectively – and efficiently – care for their OSD patients by using point-of-care diagnostics to guide an exploration of a patient’s underlying causes of signs and symptoms. Therapies can be more personalized and targeted, specialists can avoid prescribing unnecessary sometimes costly treatments that leave patients still suffering, and needless office visits may be avoided.


Ashley Brissette is a consultant for Alcon, Allergan, Bruder, Carl Zeiss, Eyeance, Kala and Sun. 

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  1. DEWS, “Research in dry eye: report of the research subcommittee of the International dry eye WorkShop”, Ocul Surf, 5, 179 (2007). PMID: 17508121.
  2. M Lemp et al., “Tear osmolarity in the diagnosis and management of dry eye disease”, Am J Ophthalmol, 151, 792 (2011). PMID: 21310379.
  3. H Liu et al., “A link between tear instability and hyperosmolarity in dry eye”, Invest Ophthalmol Vis Sci, 50, 3671 (2009). PMID: 19324847.
  4. M Lemp, “Advances in understanding and managing dry eye disease”, Am J Ophthalmol, 146, 350 (2008). PMID: 18599017.
  5. A Brissette et al., “The utility of a normal tear osmolarity test in patients presenting with dry eye disease-like symptoms: A prospective analysis”, Contact Lens Ant Eye, 42, 185 (2018). PMID: 30236650.
  6. C Starr et al., “ASCRS Cornea Clinical Committee. An algorithm for the preoperative diagnosis and treatment of ocular surface disorders”, J Cataract Refract Surg, 45, 669 (2019). PMID: 31030780.
About the Author
Ashley Brissette

Assistant Professor of Ophthalmology at Weill Cornell Medicine, New York Presbyterian Hospital, New York.

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