Tear Osmolarity in the Diagnosis and Management of Dry Eye Disease

doi:10.1016/j.ajo.2010.10.032

American Journal of Ophthalmology

Volume 151, Issue 5, May 2011, Pages 792-798.e1

https://doi.org/10.1016/j.ajo.2010.10.032 Get rights and content

Purpose

To evaluate the use of tear osmolarity in the diagnosis of dry eye disease.

Design

A prospective, observational case series to determine the clinical usefulness of tear osmolarity and commonly used objective tests to diagnose dry eye disease.

Methods

A multicenter, 10-site study consisting of 314 consecutive subjects between 18 and 82 years of age. Bilateral tear osmolarity, tear film break-up time (TBUT), corneal staining, conjunctival staining, Schirmer test, and meibomian gland grading were performed. Diagnostic performance was measured against a composite index of objective measurements that classified subjects as having normal, mild or moderate, or severe dry eye. The main outcome measures were sensitivity, specificity, area under the receiver operating characteristic curve, and intereye variability.

Results

Of the 6 tests, tear osmolarity was found to have superior diagnostic performance. The most sensitive threshold between normal and mild or moderate subjects was found to be 308 mOsms/L, whereas the most specific was found at 315 mOsms/L. At a cutoff of 312 mOsms/L, tear hyperosmolarity exhibited 73% sensitivity and 92% specificity. By contrast, the other common tests exhibited either poor sensitivity (corneal staining, 54%; conjunctival staining, 60%; meibomian gland grading, 61%) or poor specificity (tear film break-up time, 45%; Schirmer test, 51%). Tear osmolarity also had the highest area under the receiver operating characteristic curve (0.89). Intereye differences in osmolarity were found to correlate with increasing disease severity (r² = 0.32).

Conclusions

Tear osmolarity is the best single metric both to diagnose and classify dry eye disease. Intereye variability is a characteristic of dry eye not seen in normal subjects.

Section snippets

Methods

A prospective, exploratory, multicenter study was undertaken at 10 sites in the European Union and the United States. The subject population consisted of randomly presenting subjects between the ages of 18 and 82 years of both sexes, including those with and without a history of dry eye disease. Investigators were instructed to recruit roughly a 2:1 ratio of presumed dry eye patients to normals. This report documents the results of the analysis of the initial 314 subjects, 15 of whom were

Results

Tear osmolarity was found to have a 72.8% sensitivity and 92.0% specificity at a cutoff value of 312 mOsms/L (i.e., values > 311 mOsms/L; Table 1). No other clinical sign exhibited more than 62% performance in both categories. Corneal staining, conjunctival staining, and meibomian grading lacked sensitivity (54.0%, 60.3%, and 61.2% respectively), whereas TBUT and Schirmer results lacked specificity (45.3% and 50.7%, respectively). The performance of osmolarity was consistent with earlier

Discussion

The development and availability of a new technology (TearLab; FDA 510(k) k083184) enables the clinician to collect and measure osmolarity in a 50 nL sample with minimal disturbance of the tear film.⁵ This microfluidic lab-on-a-chip device both collects tears and produces a reading within seconds before evaporation can influence solute concentration. This eliminates the need for sample transfer or user handling. This technique is applicable in the near-patient setting and overcomes many of the

Michael A. Lemp, a corneal specialist, is clinical professor of ophthalmology at Georgetown and George Washington universities, former chair of ophthalmology at Georgetown, and the author of 210 scientific papers and five books. He is retired from clinical practice but is active in clinical research in ocular surface disease. He is founding editor of The Ocular Surface, recipient of the Castroviejo medal, reviewer for eight journals and consultant for companies developing drugs and devices.

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Analysis of the mucosal chemokines CCL28, CXCL14, and CXCL17 in dry eye disease: An in vitro and clinical investigation
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Mucosal chemokines have antimicrobial properties and play an important role in mucosal immunity. However, little is known about their expression on the ocular surface. This study aimed to analyze the expression of the mucosal chemokines CCL28, CXCL14 and CXCL17 in corneal and conjunctival epithelial cells under in vitro dry eye (DE) conditions, and in conjunctival samples from healthy subjects and DE patients. Human corneal epithelial cells (HCE) and immortalized human conjunctival epithelial cells (IM-HConEpiC) were incubated under hyperosmolar (400–500 mOsM) or inflammatory (TNF-α 25 ng/mL) conditions for 6 h and 24 h to measure CCL28, CXCL14, and CXCL17 gene expression by RT-PCR and their secretion by immunobead-based analysis (CCL28, CXCL14) and ELISA (CXCL17). Additionally, twenty-seven DE patients and 13 healthy subjects were included in this study. DE-related questionnaires (OSDI, mSIDEQ and NRS) evaluated symptomatology. Ocular surface integrity was assessed using vital staining. Tactile sensitivity was measured with Cochet-Bonnet esthesiometer, and mechanic and thermal (heat and cold) sensitivity using Belmonte's non-contact esthesiometer. Subbasal nerve plexus and dendritic cell density were analyzed by in vivo confocal microscopy. Conjunctival cells from participants were collected by impression cytology to measure mucosal chemokines gene expression by RT-PCR. Our results showed that HCE and IM-HConEpiC cells increased CCL28, CXCL14, and CXCL17 secretion under hyperosmolar conditions. The gene expression of CCL28 was significantly upregulated in conjunctival samples from DE patients. CCL28 expression correlated positively with symptomatology, corneal staining, heat sensitivity threshold, and dendritic cell density. CXCL14 expression correlated positively with age, ocular pain, conjunctival staining, tactile sensitivity, and image reflectivity. CXCL17 expression correlated positively with corneal staining. These results suggest that corneal and conjunctival epithelial cells could be a source of CCL28, CXCL14, and CXCL17 on the ocular surface and that CCL28 might be involved in DE pathogenesis.
Diagnosing dry-eye: Which tests are most accurate?
2023, Contact Lens and Anterior Eye
To demonstrate how the likelihood of making a correct diagnosis of dry eye disease varies according to the clinical test methods used.
The probability of a person having dry eye, given that they return a positive test, was calculated for a range of standard tests, using the Bayes-Price rule. Global specificity and sensitivity values for each test were estimated by employing the Beta distribution to combine all relevant data obtained from a literature review.
At an assumed prevalence of 11.6%, the single test with the highest probability of a correct diagnosis was corneal staining (probability = 0.28) and the lowest was the ocular surface disease index - OSDI (0.14). The best combination of symptoms with a single test of tear film homeostasis was the 5-item dry eye questionnaire (DEQ-5) + corneal staining (0.42) while OSDI + tear film break up time (TBUT) was the worst (0.23). The simultaneous observation of conjunctival and corneal staining was associated with a probability of 0.49. The probability of a correct diagnosis increased with the number of positive tests, up to a maximum of 0.90 when all of DEQ-5, conjunctival and corneal staining, osmolarity and TBUT were positive.
A significant risk of misdiagnosis is associated with using any single test for dry eye disease, or the minimum TFOS DEWS II criterion of symptoms plus any single test of tear film homeostasis. To minimize this risk, the maximum number of tests available should be performed and the results used to inform diagnosis. The simultaneous occurrence of conjunctival and corneal staining should be considered a key outcome and be specified in future guidelines.
Dry eye clinical practice patterns of UK optometrists
2023, Contact Lens and Anterior Eye
In light of the increased roles of optometrists working in primary care in the UK, this research study aimed to gain an insight into perceptions of dry eye disease (DED), knowledge and confidence in diagnosis and management, and satisfaction with currently available treatment options.
Links to an online survey were distributed to optometrists across the UK via optometry websites newsletters, conferences, and local optical committee data bases, between October 2021 and July 2022. The anonymous questionnaire contained a variety of question types including multiple choice, likert-type scale, and free text questions.
The survey was completed by 131 optometrists, with a broad range of experience, who reported examining 33.3 ± 31.0 dry eye patients per month. Forty-eight percent of respondents were involved in the provision of an extended service. Fluorescein tear breakup time, corneal fluorescein staining, and anterior lid assessment were the most used clinical procedures, both for diagnosis and monitoring purposes. Sixty percent of respondents reported that they believed their patients were satisfied/managed with artificial tear alone, with the availability of a preservative free option being the top consideration, particularly with increasing severity. Of the 18.7% of respondents who held Independent prescriber status, 68% felt this had widened their ability to diagnose and treat DED. This was evidenced by an increase in steroid recommendation for moderate and severe disease.
Although dry eye disease was perceived to be an important condition, opinions varied widely regarding knowledge and confidence in diagnosis and management. Involvement in an extended service did not alter patient management. However, an increase in therapeutic management and the employment of a stepwise approach to management has been identified.
Tear-film evaporation flux and its relationship to tear properties in symptomatic and asymptomatic soft-contact-lens wearers
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With soft-contact-lens wear, evaporation of the pre-lens tear film affects the osmolarity of the post-lens tear film and this can introduce a hyperosmotic environment at the corneal epithelium, leading to discomfort. The purposes of the study are to ascertain whether there are differences in evaporation flux (i.e., the evaporation rate per unit area) between symptomatic and asymptomatic soft-contact-lens wearers, to assess the repeatability of a flow evaporimeter, and to assess the relationship between evaporation fluxes, tear properties, and environmental conditions.
Closed-chamber evaporimeters commonly used in ocular-surface research do not control relative humidity and airflow, and, therefore, misestimate the actual tear-evaporation flux. A recently developed flow evaporimeter overcomes these limitations and was used to measure accurate in-vivo tear-evaporation fluxes with and without soft-contact-lens wear for symptomatic and asymptomatic habitual contact-lens wearers. Concomitantly, lipid-layer thickness, ocular-surface-temperature decline rate (i.e., °C/s), non-invasive tear break-up time, tear-meniscus height, Schirmer tear test, and environmental conditions were measured in a 5 visit study.
Twenty-one symptomatic and 21 asymptomatic soft-contact-lens wearers completed the study. A thicker lipid layer was associated with slower evaporation flux (p < 0.001); higher evaporation flux was associated with faster tear breakup irrespective of lens wear (p = 0.006). Higher evaporation flux was also associated with faster ocular-surface-temperature decline rate (p < 0.001). Symptomatic lens wearers exhibited higher evaporation flux than did asymptomatic lens wearers, however, the results did not reach statistical significance (p = 0.053). Evaporation flux with lens wear was higher than without lens wear but was also not statistically significant (p = 0.110).
The repeatability of the Berkeley flow evaporimeter, associations between tear characteristics and evaporation flux, sample-size estimates, and near statistical significance in tear-evaporation flux between symptomatic and asymptomatic lens wearers all suggest that with sufficient sample sizes, the flow evaporimeter is a viable research tool to understand soft-contact-lens wear comfort.
International survey on dry eye diagnosis by experts
2023, Heliyon
To evaluate patterns and opinion from international experts with respect to dry eye disease (DED) diagnosis in clinical practice.
An online survey was distributed to worldwide DED experts. The use of diagnosis tests was evaluated including: symptoms questionnaires, functional tests, tear stability, tear volume, tear composition, surface damage and inflammation, and eyelid assessment. After the subjective importance of symptoms, tear break up time (TBUT), non-invasive TBUT, Schirmer's test, tear meniscus height, tear osmolarity, tear metalloproteinase 9, blepharitis assessment and non-contact meibography was evaluated according to likert scale.
The survey was sent to 109 experts, and 77 completed the questionnaire (rate of response = 70.6%). Most of the participants were from North America (27%) and Europe (40%). A majority of respondents (73%) diagnose DED using clinical signs and symptoms, but not fulfilling a specific criteria. Seventy-six participants (98.7%) use symptoms questionnaires. All participants evaluate damage to ocular surface, and fluorescein staining is the most frequent method used (92%). Also, all the respondents perform meibomian gland and blepharitis assessment. On the other hand, only 69.8% evaluate tear composition, being osmolarity the most common test used (66.2%). Regarding to the importance of tests, TBUT (p = 0.002) and Schirmer's (p = 0.021) were found to be more important to experts from Europe than North America. No differences were found in any other test (p > 0.05).
This survey offers updated and day-to-day diagnostic clinical practice by DED worldwide experts. The results highlight the importance of symptoms and clinical signs, but not necessarily following a strict criteria.
Age Associations with Dry Eye Clinical Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study
2023, Ophthalmology Science
To evaluate how increasing age is associated with dry eye disease (DED) signs and symptoms in the Dry Eye Assessment and Management (DREAM) study. This study was undertaken to better understand how DED signs and symptoms differ across decades of life with goals to help assess detection and treatment of DED.
Secondary analysis of the DREAM study.
One hundred twenty, 140, 185, and 90 participants aged < 50, 50 to 59, 60 to 69, and ≥ 70 years, respectively.
We performed a secondary analysis of data from the DREAM study, a multicenter randomized clinical trial, to evaluate the effect of omega-3 fatty acid supplementation for the treatment of DED. At baseline, 6 months, and 12 months follow-up, participants underwent an assessment of DED symptoms and signs using Ocular Surface Disease Index, Brief Pain Inventory, tear break-up time (TBUT) (in seconds), Schirmer test with anesthesia (mm/5 minutes), conjunctival staining, corneal staining, meibomian gland dysfunction evaluation, and tear osmolarity (mOsm/l). Multivariable generalized linear regression models were used to compare DED symptoms and signs across the 4 age groups among all participants and by sex.
Scores of DED symptoms, individual signs, and composite scores of DED signs.
Among 535 patients with DED, increasing age was significantly associated with worse TBUT (P = 0.01), corneal staining (P < 0.001), a composite severity score of DED signs (P = 0.007), and tear osmolarity (P = 0.001). Similar significant differences were found across 4 age groups of 334 women in TBUT, corneal staining score, composite severity score of DED signs, and tear osmolarity (all P < 0.05) but not in men.
We found that corneal staining, TBUT, tear osmolarity, and a composite severity score of DED signs were significantly more severe with increasing age in women but not in men; worsening symptoms did not increase with increasing age.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Original articleTear Osmolarity in the Diagnosis and Management of Dry Eye Disease

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Ocul Surf

Ocul Surf

Exp Eye Res

Epidemiology of dry eye disease

Methodologies to diagnose and monitor dry eye disease

Ocul Surf

The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity

Invest Ophthalmol Vis Sci

The definition and classification of dry eye disease

Ocul Surf

An objective approach to severity in dry eye disease

Invest Ophthalmol Vis Sci

Survey of preferred tests for the diagnosis of the tear film and dry eye

Cornea

An information-maximization approach to blind separation and blind deconvolution

Neural Comp

Tear film osmolarity: determination of a referent for dry eye diagnosis

Invest Ophthalmol Vis Sci

Comparison of human tear film osmolarity measured by electrical impedance and freezing point depression techniques

Cornea

Original article
Tear Osmolarity in the Diagnosis and Management of Dry Eye Disease