A novel technique of contrast-enhanced optical coherence tomography imaging in evaluation of clearance of lipids in human tears

Purpose: The aim of this work was to gather preliminary data in different conditions of healthy eyes, aqueous tear deficient dry eyes, obstructive meibomian gland disease (MGD) and non-obvious obstructive MGD (NOMGD) individuals, using a new, contrast-enhanced optical coherence tomography (OCT) imaging method to evaluate the clearance of lipids in human tears. Methods: Eighty-two adult patients presenting with complaints of ocular irritation were studied for abnormalities of the ocular surface and classified as healthy (n = 21), aqueous tear deficient dry eyes (n = 20), obstructive MGD (n = 15) and NOMGD (n = 26) individuals. A lipid-based tracer, containing an oil-in-water emulsion, was used to obtain an enhanced OCT imaging of the lower tear meniscus. After instillation, a dramatic initial increase of reflectivity of the lower tear meniscus was detected by OCT, followed by a decay back to baseline values over time. Based on this finding, the clearance of lipids was measured in real-time by Fourier-domain anterior segment OCT. Results: The differences in the clearance of lipids among the four groups as well as the correlations between symptom questionnaire score, standardized visual scale test, fluorescein break-up time, ocular surface fluorescein staining score, Schirmer I test scores were found to be statistically significant. The individual areas under the curve of the clearance of lipids calculated by the receiver operating characteristic curve technique ranged from 0.66 to 0.98, suggesting reliable sensitivity and specificity of lipid-enhanced OCT imaging. Conclusions: This new technique of contrast-enhanced OCT imaging of the tear film following lipid-based tracer instillation provides a measure of the clearance of lipids. The quantitative values found are in agreement with other methods of evaluation of the lacrimal system. An improvement of the clinician's ability in the diagnosis and understanding of abnormalities of the ocular surface may be achieved by this simple approach

A novel technique of contrast-enhanced optical coherence tomography imaging in evaluation of clearance of lipids in human tears.

PURPOSE: The aim of this work was to gather preliminary data in different conditions of healthy eyes, aqueous tear deficient dry eyes, obstructive meibomian gland disease (MGD) and non-obvious obstructive MGD (NOMGD) individuals, using a new, contrast-enhanced optical coherence tomography (OCT) imaging method to evaluate the clearance of lipids in human tears. METHODS: Eighty-two adult patients presenting with complaints of ocular irritation were studied for abnormalities of the ocular surface and classified as healthy (n = 21), aqueous tear deficient dry eyes (n = 20), obstructive MGD (n = 15) and NOMGD (n = 26) individuals. A lipid-based tracer, containing an oil-in-water emulsion, was used to obtain an enhanced OCT imaging of the lower tear meniscus. After instillation, a dramatic initial increase of reflectivity of the lower tear meniscus was detected by OCT, followed by a decay back to baseline values over time. Based on this finding, the clearance of lipids was measured in real-time by Fourier-domain anterior segment OCT. RESULTS: The differences in the clearance of lipids among the four groups as well as the correlations between symptom questionnaire score, standardized visual scale test, fluorescein break-up time, ocular surface fluorescein staining score, Schirmer I test scores were found to be statistically significant. The individual areas under the curve of the clearance of lipids calculated by the receiver operating characteristic curve technique ranged from 0.66 to 0.98, suggesting reliable sensitivity and specificity of lipid-enhanced OCT imaging. CONCLUSIONS: This new technique of contrast-enhanced OCT imaging of the tear film following lipid-based tracer instillation provides a measure of the clearance of lipids. The quantitative values found are in agreement with other methods of evaluation of the lacrimal system. An improvement of the clinician's ability in the diagnosis and understanding of abnormalities of the ocular surface may be achieved by this simple approach

Spectral-domain optical coherence tomography study on dynamic changes of human tears after instillation of artificial tears

PURPOSE. To analyze in vivo the dynamic changes induced by different artificial tears (ATs) in the precorneal tear film (PCTF) and lower tear meniscus (LTM) by using spectral-domain (SD) anterior segment optical coherence tomography (OCT). METHODS. We prospectively examined 42 normal human eyes by using SD-OCT imaging. On the day before OCT imaging, all enrolled subjects were evaluated for abnormalities of ocular surface. All tear film images were obtained before and after instillation of three different types of ATs (mucomimetic, lipid-based, and saline) in five serial scans: immediately (within 30 seconds), at the first, fifth, 10th, and 20th minute. Subjects received a drop of 35 μL in one randomly selected eye. All examinations were conducted in the same conditions of temperature, brightness, humidity, and time of day. RESULTS. Changes in the morphological pattern of both LTM and PCTF were associated with the type of artificial tear instilled on the ocular surface. Similarly, the radius of curvature (rc), the height (h), and the depth (d) showed dynamic variations depending on treatment. Although by the 20th minute, bothhand dreturned to baseline values in all groups, a significant difference in rc(compared with baseline) was detected for mucomimetic ATs (P = 0.04) and lipid ATs (P = 0.02). CONCLUSIONS. Spectral-domain OCT imaging has preliminarily proved to be a noninvasive tool to evaluate, in real time, the different changes induced by ATs instillation. An important stride in understanding the clinical response to various tear substitutes can be achieved by this objective and quantitative approach

Correlation between the aqueous tear clearance and the turnover of tear lipids in dry eye patients

Purpose: To determine by anterior segment spectral domain optical coherence tomography (OCT) the turnover of tear lipids in patients with aqueous tear deficient dry eyes (ATD) and its correlation with the aqueous tear clearance. Methods: Eighty-two adult patients presenting with complaints of ocular irritation were evaluated for abnormalities of ocular surface in the same sequence. It included clinical history, a symptom questionnaire (OSDI = Ocular Surface Disease Index), fluorescein tear break-up time (FTBUT), fluorescein staining of the cornea and conjunctiva graded according to the Oxford system (FSOS), standardized visual scale (SVST), Schirmer I test, and a slit lamp examination of the lid margins and meibomian glands. T A lipid-based artificial tear (LAT) was used as a tracer to obtain an enhanced OCT imaging of the lower tear meniscus (LTM) and to determine the clearance of tear lipids (CTL). Results: The correlations between CTL and OSDI, FTBUT, FSOS, Schirmer test scores, were found to be statistically significant (p<0.001, Spearman correlation coefficient was 0.79, -0.68, 0.58, -0.5 -0.43, respectively). Moreover, also a significant relationship between CTL and the aqueous tear clearance (SVST) was observed (Spearman correlation coefficient was 0.68, p<0.001). Conclusions: The results obtained with this new technique of contrast-enhanced OCT imaging of the ocular surface are in agreement with other classical tear tests. The reduced dynamics of tear lipids was associated with a slow aqueous tear clearance. This new finding could lead to a better understanding of the complex pathogenesis of dry eye syndrome and of its alterations

Effect of surface tension on tear meniscus curvature

Purpose: To determine by optical coherence tomography (OCT) the effect of surface tension on reliability of tear meniscus curvature measurements Methods: Dimensions of the lower tear meniscus (LTM) were obtained in normal humans eye (n=22). The radius of curvature was calculated in two way. In the classical approach (system n.1), operator inputs were provided to identify three touch points used to fit a circle (R). In the second approach (system 2), since tear molecules close to epithelia of cornea and conjunctiva could interact differently with them, two radii of curvature in the LTM were calculated: the inner radius (ri), where the tear touches the cornea, and the outer radius (re), where the tear touches the lid. Results: The average R was 496.59 ± 24.28 μm. The ri and re were 401.34 ± 32.12 μm, 563.10 ± 29.14 μm, respectively. Significant differences were found between ri and re (Wilcoxon Signed Ranks Test = -3.095, p = 0.002), as well as R and both ri and re (Wilcoxon Signed Ranks Test = -3.095, p = 0.002). Also considering the mean value (rM) between the two radii (ri and re) were revealed significant discrepancies (Wilcoxon Signed Ranks Test = - 2.585; p = 0.01). Conclusions: Preliminarily, our study has demonstrated the difficulty in obtaining a reliable approximation of the radius of curvature of meniscus by the classical system. The system 2, considering the effect of the surface tension on interaction between tears and epithelia, appears to offer a different measure with respect to system 1. Therefore, the second approach could be more representative of the real state of health of ocular surface and could be useful to achieve more reproducible and comparable measurements of tear meniscus curvature

Effect of blinking on repeatability of measurements of tear meniscus curvature

Purpose: To determine by optical coherence tomography (OCT) the influence of blinking on repeated measurements of tear meniscus curvature (TMC). Methods: Normal human (n = 21) eyes were imaged to get dimensions of the lower tear meniscus (LTM). On the day before the OCT imaging, all enrolled subjects were tested by McMonnies questionnaire, fluorescein tear break-up time (FTBUT), fluorescein staining of ocular surface, Schirmer I test, a slit examination of the lid margins and meibomian glands. All ocular surface images were obtained immediately (method 1) or 2 seconds (method 2) after a blink, and were repeated on the next day. All examinations were conducted in the same conditions of temperature, brightness, humidity and time of the day. Results: The average TMC was 646.90 ± 513.43 μm and 563.10 ± 24.28 μm, by method 1 and 2, respectively. In the second case, reliability analysis has revealed a good consistency of measurements (ICC=0.99, p<0.01). Conversely, no significant agreement was obtained for measurements by method 1 (ICC=0.4, p=0.39). Comparing the two systems, we did not found a significantly statistical correlation between the results (ICC=0.09, p=0.39). Conclusions: Blinking plays a crucial role in dynamic distribution human tears and in determining changes of dimensions of tear meniscus. The standardization of OCT imaging of the ocular surface appears to be necessary to aim a significant repeatability of tear meniscus measurements and a better comparability of results

A novel OCT technique to measure in vivo the corneal adhesiveness for sodium carboxymethylcellulose in humans and its validity in the diagnosis of dry eye

Purpose. The purpose of this work was to gather preliminary data on tear film stability, and the adhesive properties of the corneal surface in dry eye patients and control group subjects, using a new, minimally invasive optical coherence tomography (OCT) imaging method. Methods. We screened 85 human subjects for dry eye and classified them in two groups, as dry eye or normal patients. Sodium carboxymethylcellulose (NaCMC) adhesiveness over the central cornea was measured using Fourier domain anterior segment OCT. The corneal adhesiveness for NaCMC was compared between the two groups, correlated with classical tests, and analyzed for diagnostic validity and repeatability. Results. The corneal adhesiveness for NaCMC median and mode values was fair (between 1 and 3 minutes) for dry eye subjects (n 1/4 36) and borderline (between 3 and 5 minutes) for control group subjects (n 1/4 49), and was significantly different between the two groups (P < 0.001). Significant correlations were observed between the corneal adhesiveness measures and dry eye patients' symptoms (P < 0.001), Schirmer I test (P < 0.001), ocular surface staining (P < 0.001), and, particularly, fluorescein break-up time (P < 0.001). The area under the receiver operating characteristic curve was 0.94 (P < 0.001), suggesting reliable sensitivity and specificity of OCT imaging. A statistically significant intraclass correlation (ICC) value of 0.99 was found for measurements of corneal adhesiveness on two subsequent days at the same time (P < 0.001). Conclusions. This minimally invasive, novel technique of OCT imaging of the corneal surface following NaCMC drop instillation provides a measure of corneal adhesiveness. This technique may improve the clinician's ability in the understanding and diagnosis of the dry eye syndrome

Evaluation of the adhesive properties of the cornea by means of optical coherence tomography in patients with meibomian gland dysfunction and lacrimal tear deficiency.

The aim was to determine the influence of meibomian gland dysfunction (MGD) and aqueous tear deficiency dry eye (ADDE) on the adhesive properties of the central cornea by means of optical coherence tomography (OCT), and to investigate the relationship between corneal adhesiveness and classical tear tests, as well as the reliability of results, in these lacrimal functional unit disorders.Prospective, case-control study.Twenty-eight patients with MGD and 27 patients with ADDE were studied. A group of 32 healthy subjects of similar age and gender distribution served as a control group. The adhesive properties of the anterior corneal surface were measured by OCT, based on the retention time of adhesion marker above it, in all participants.An excellent (≥5 minutes), borderline (within 3-5 minutes), fair (within 1-3 minutes) and poor (<1 minute) values of corneal adhesiveness were found, respectively, in 0%, 7.1%, 64.3% and 28.6% of MGD, in 0%, 7.4%, 63% and 29.6% of ADDE, and in 31.3%, 65.6%, 3.1% and 0% of healthy patients. The differences in time of corneal adhesiveness between MGD and healthy patients, as well as between ADDE and healthy patients, were found to be statistically significant (p<0.001; p<0.001; respectively). Conversely, no statistical significant differences between MGD and ADDE were found (p = 0.952). Data analysis revealed a statistically significant correlation between corneal adhesiveness and clinical tests of dry eye, as well as an excellent degree of inter-rater reliability and reproducibility for OCT measurements (p<0.001).ADDE and MGD share similar abnormalities on OCT imaging. Decreased adhesive properties of the anterior cornea were identified as a common feature of MGD and ADDE. This simple OCT approach may provide new clues into the mechanism and evaluation of dry eye syndrome