Abstract Dry eye, also known as keratoconjunctivitis sicca, can be due either to insufficient tear production or excessive tear evaporation, both resulting in tear hyperosmolarity that leads to ...symptoms of discomfort and ocular damage. Additionally, the severity of dry eye symptoms appears to be correlated to lipid layer thickness. It is now generally recognized that increased evaporation due to a compromised lipid layer is one of the most common etiologies for hyperosmolarity of the tear film. Thus, therapies targeted at replenishing or stabilizing the lipid layer are key to the treatment of dry eye, either as monotherapy or in conjunction with therapies designed to enhance aqueous production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Relationships between tear film lipid (TFL) layer composition, structure, and function could provide insight into the etiology of dry eye. The molar ratio of cholesteryl ester (CE)/wax ester (WE) was ...measured in meibum from normal donors (Mn) and compared with meibum from donors with meibomian gland dysfunction (MMGD).
CE/WE was measured using nuclear magnetic resonance spectroscopy.
CE/WE was distributed into two populations with 81% distributed near 0.55 and 19% near 0.3. CE/WE were higher in donors 13 to 19 years old compared with donors 1 to 12 years old and 20 to 88 years old. CE/WE for MMGD was 30% lower, 0.34 ± 0.04, compared with Mn, 0.49 ± 0.04. There were no sex differences in CE/WE. There were no significant racial differences between the CE/WE ratios for Asians and Caucasians. The CE/WE ratio was higher for blacks and lower for Hispanics compared to Caucasians. Due to the small number sampled, confirmation of the later racial results is needed. The packing of CE and WE in the TFL layer was proposed.
Although MMGD contains much less CE than Mn, factors other than the CE content, such as the levels of saturation and/or proteins, may be responsible for the higher order of MMGD. In addition to saturation, CE could contribute to the increase in order of Mn between 0 and 20 years of age. Observed changes in the meibum content of CE alone is not likely to influence tear film stability.
A prospective, multisite clinical study (10 sites in the European Union and the United States) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease ...severity.
Three hundred fourteen consecutive subjects between the ages of 18 and 82 years were recruited from the general patient population, 299 of which qualified with complete datasets. Osmolarity testing, Schirmer test without anesthesia, tear film breakup time (TBUT), corneal staining, meibomian dysfunction assessment, and conjunctival staining were performed bilaterally. A symptom questionnaire, the Ocular Surface Disease Index (OSDI), was also administered to each patient. Distributions of clinical signs and symptoms against a continuous composite severity index were evaluated.
Osmolarity was found to have the highest correlation coefficient to disease severity (r(2) = 0.55), followed by conjunctival staining (r(2) = 0.47), corneal staining (r(2) = 0.43), OSDI (r(2) = 0.41), meibomian score (r(2) = 0.37), TBUT (r(2) = 0.30), and Schirmer result (r(2) = 0.17). A comparison of standard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospectively defined normal and dry eye groups. Fully 63% of the subjects were found to be poorly classified by combinations of clinical thresholds.
Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate, and severe categories. Other tests were found to be informative in the more severe forms of disease; thus, clinical judgment remains an important element in the clinical assessment of dry eye severity. The results also indicate that the initiation and progression of dry eye is multifactorial and supports the rationale for redefining severity on the basis of a continuum of clinical signs. (ClinicalTrials.gov number, NCT00848198.).
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Purpose: To evaluate the relationship between signs and symptoms of dry eye disease (DED) in a clinic‐based population.
Methods: In a retrospective analysis, clinical signs and symptoms were ...evaluated for 344 subjects (n = 82, normal; n = 263, dry eye), across 11 sites from the EU and United States. Pearson correlations between signs and symptoms (r2) and an independent components analysis (ICA) mixing matrix were derived from the data set. Similar analysis was performed on an independent data set from 200 subjects in a previous study in Munich, Germany.
Results: No correlations above r2 = 0.17 were found between any signs and symptoms, except for corneal and conjunctival staining, which reported an r2 = 0.36. In the multisite study, the average r2 for osmolarity (0.07), tear breakup time (0.12), Schirmer test (0.09), corneal (0.16) and conjunctival staining (0.17), meibomian grading (0.11) and Ocular Surface Disease Index® (0.11) were consistently low. Among patients who showed evidence of DED by consensus of clinical signs, only 57% reported symptoms consistent with a diagnosis of DED. Similar results were observed in the Munich‐based study data set. Each component of the ICA mixing matrix exhibited minimal residual information.
Conclusions: No consistent relationship was found between common signs and symptoms of DED. Each type of measurement provides distinct information about the condition of the ocular surface. These results also demonstrate that symptoms alone are insufficient for the diagnosis and management of DED and argue for a consensus of clinical signs that better reflect all aspects of the disease.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PURPOSE:Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been ...identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic characteristics of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution and oral doxycycline treatment.
METHODS:Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid–lipid interaction strength, conformation, and phase transition parameters, and meibum protein content were measured using Fourier transform infrared spectroscopy and principal component analysis. Terpenoids, short-chain CH3 moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (H-NMR) spectrometer.
RESULTS:Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. Compared with 4 weeks of azithromycin treatment reported in our previous study, oral doxycycline treatment was slightly less effective in improving foreign body sensation and the signs of plugging and secretion. In subjects with clinical evidence of MGD, changes in ordering of the lipids and phase transition temperature were brought closer to normal with azithromycin treatment than doxycycline treatment. Treatment with doxycycline but not azithromycin restored the Fourier transform infrared spectroscopy–principal component analysis scores and relative area of the H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the H-NMR resonance at 5.2 and 7.9 ppm to normal levels. The levels of meibum protein and meibum lipid oxidation were not influenced by azithromycin or doxycycline treatment.
CONCLUSIONS:The mechanism of action of doxycycline may be different from that of azithromycin in therapy of MGD. It is notable that when carotenoids in meibum are low, as in MGD, the tear film is unstable and patients have the signs and symptoms of dry eyes. When carotenoids are restored with azithromycin and doxycycline treatment, tear film stability is restored and patients no longer have the signs and symptoms of dry eyes.
PURPOSE:To evaluate in a general clinic-based cohort of patients with dry eye disease (DED) the distribution of patients with aqueous-deficient or evaporative subtype of DED.
METHODS:Schirmer tests ...and meibomian gland dysfunction (MGD) (Foulks–Bron scoring) were evaluated in both eyes of 299 normal subjects and DED patients (218 women and 81 men) across 10 sites in the European Union and the United States. Using the more severe measurement of the 2 eyes, subjects were considered to have pure aqueous-deficient dry eye (ADDE) with Schirmer values of <7 mm and MGD grades of ≤5. Patients were classified as purely evaporative dry eye with MGD grades of >5 and Schirmer values of ≥7 mm. Subjects were placed into the mixed (hybrid) category if they exhibited both a low Schirmer value of <7 and evidence of MGD with a grade >5.
RESULTS:Of the 224 subjects classified with DED using an objective, composite, disease severity scale, 159 were classified into 1 of 3 categories79 were classified with only MGD, whereas only 23 were classified as purely aqueous deficient, and 57 showed evidence of both MGD and aqueous deficiency. Overall, 86% of these qualified DED patients demonstrated signs of MGD. The remaining 65 patients showed evidence of DED through other clinical signs, without overt evidence of MGD or ADDE, possibly because of the inherent variability of these signs.
CONCLUSIONS:The proportion of subjects exhibiting signs of evaporative dry eye resulting from MGD far outweighs that of subjects with pure ADDE in a general clinic-based patient cohort.
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