The lacrimal gland in Sjögren's syndrome: can we unravel its mystery using ultrasound?

According to a recent survey of patients with the autoimmune disease primary Sjögren's syndrome (pSS), dry eye symptoms are present in 95-98% of pSS patients. As one of the most disabling symptoms mentioned by pSS patients, dry eyes have demonstrable effects on quality of their life, leading to eye dryness, itching, and pain, with some patients describing as a recurrent sensation of sand or gravel in the eyes. The symptoms are matched only in prevalence by dry mouth and chronic fatigue. In contrast to the prevalence of dry eye symptoms in pSS and their burden on pSS patients, our comprehension of dry eye disease development is minimal; specifically how function of the tear-fluid producing gland the lacrimal gland (LG), manifests. The comparison becomes stronger again when we consider what we know about dysfunction of the salivary gland (SG) in pSS, for example the appreciation of the transcriptome of 'innately activated' B cells invading the SG, their complicity in formation of lymphoepithelial lesions, and the ability of the SG epithelium to actively contribute to the inflammatory milieu. The exploration of ultrasound imaging as an additional modality to garner information about SG dysfunction in pSS has opened many doors for non-invasive, repeatable imaging in pSS. Here we summarise SG histology and ultrasound phenotype briefly and then juxtapose this with available studies examining LG pathology and ultrasound, and our understanding of LG dysfunction in pSS.

Association Between Dry Eye Syndrome and Osteoarthritis Severity: A Nationwide Cross-Sectional Study (KNHANES V).

OBJECTIVE: Recently, several researchers reported an association between osteoarthritis and dry eye syndrome (DES) and suggested that they may be related to central sensitization. We investigated the association between DES, osteoarthritis pain, and radiographic severity. DESIGN: A nationwide, cross-sectional study. SETTING: The Fifth Korean National Health and Nutrition Examination Survey. SUBJECTS: 8,664 participants in this survey. METHODS: Osteoarthritis-associated radiographic changes were evaluated by trained radiologists. Multivariable logistic regression was performed to examine the relationship between osteoarthritis pain, radiographic severity, and DES. The odds ratios (ORs) of DES were analyzed in accordance with the presence of osteoarthritis-associated factors. RESULTS: Radiographic knee osteoarthritis was significantly associated with lower ORs for DES (OR = 0.80, P = 0.046, for diagnosed/self-reported DES; OR = 0.84, P = 0.034, for symptoms of DES). Knee pain or stiffness was significantly associated with higher ORs for DES (OR = 1.28, P = 0.020, for diagnosed/self-reported DES; OR = 1.29, P = 0.003, for symptoms of DES). In patients with symptomatic osteoarthritis, DES was not significantly associated with radiographic severity of osteoarthritis. In patients with nonsymptomatic radiographic osteoarthritis, DES was inversely related with radiographic severity (Ptrend = 0.012 for diagnosed/self-reported DES; Ptrend < 0.001 for symptoms of DES). CONCLUSIONS: Radiographic osteoarthritis showed a significant association with decreased DES. Patients with less pain and severe radiographic OA were more likely to have less DES. Our results suggest that the degree of pain caused by osteoarthritis and central sensitization may be closely associated with DES.

Diagnostic Capability of a New Objective Method to Assess Meibomian Gland Visibility.

SIGNIFICANCE: The diagnosis of dry eye disease and meibomian gland dysfunction (MGD) is challenging. Measuring meibomian gland visibility may provide an additional objective method to diagnose MGD. PURPOSE: This study aimed to evaluate the ability of new metrics to better diagnose MGD, based on measuring meibomian gland visibility. METHODS: One hundred twelve healthy volunteers (age, 48.3 ± 27.5 years) were enrolled in this study. Ocular surface parameters were measured using the Oculus Keratograph 5M (Oculus GmbH, Wetzlar). Subjects were classified according to the presence or absence of MGD. New metrics based on the visibility of the meibomian glands were calculated and later compared between groups. The diagnostic ability of ocular surface parameters and gland visibility metrics was studied through receiver operating characteristic curves. Logistic regression was used to obtain the combined receiver operating characteristic curve of the metrics with the best diagnostic ability. RESULTS: Statistically significant differences were found between groups for all ocular surface parameters and new gland visibility metrics, except for the first noninvasive keratograph breakup time and gland expressibility. New gland visibility metrics showed higher sensitivity and specificity than did current single metrics when their diagnostic ability was assessed without any combination. The diagnostic capability increased when gland visibility metrics were incorporated into the logistic regression analysis together with gland dropout percentage, tear meniscus height, dry eye symptoms, and lid margin abnormality score (P < .001). The combination of median pixel intensity of meibography gray values and the aforementioned ocular surface metrics achieved the highest area under the curve (0.99), along with excellent sensitivity (1.00) and specificity (0.93). CONCLUSIONS: New meibomian gland visibility metrics are more powerful to diagnose MGD than current single metrics and can serve as a complementary tool for supporting the diagnosis of MGD.

The Impact of Artificial Tear Viscosity on the Results of Optical Coherence Tomography. / Einfluss der Tränenersatzmittel-Viskosität auf die Messergebnisse der optischen Kohärenztomografie.

BACKGROUND: In earlier studies, an irregular tear film could be responsible for artifacts in imaging procedures in ophthalmology. As a result, this study will investigate the influence of hyaluronic acid-containing tear substitutes of different viscosities on the measurement results of optical coherence tomography and on the non-invasive tear film break-up time. METHODS: The study included three sessions in which three hyaluronic acid tear substitutes of different viscosities (Hylo-Vision 0.1%, 0.2%, 0.3%, OmniVision GmbH, Puchheim, Germany) were applied to each subject. In 20 healthy volunteers, the non-invasive tear film break-up time was measured before and after the application of the tear substitutes using Keratograph 5M (Oculus GmbH, Wetzlar, Germany) and optical coherence tomography using 3D OCT-2000 (Topcon, Hamburg, Germany). RESULTS: The median age of the volunteers was 28.5 years. 11 women (55%) and 9 men (45%) were examined. The non-invasive tear film break-up time improved significantly (p = 0.027) after the application of 0.3% hyaluronic acid. In the study, no significant difference was found in all OCT parameters used before and after application of the different viscous hyaluronic acid-containing tear substitutes. CONCLUSION: In this study, no influence of tear substitutes containing different viscosities of hyaluronic acid on the measurement results of optical coherence tomography could be determined. Therefore, 0.1%, 0.2% and 0.3% hyaluronic acid can be applied to the patient to improve the corneal surface before the examination with optical coherence tomography, without influencing the measurement results of optical coherence tomography.

The correlation of cytokines and sensory hypersensitivity in mild dry eye patients characterized by symptoms outweighing signs.

Purpose: To explore the correlation of tear and conjunctival cytokines and sensory hypersensitivity in mild dry eye (MDE) patients characterized by symptoms outweighing signs (DESOS). Methods: The subjects comprised 39 patients with MDE characterized by DESOS, 18 patients with common MDE (CMDE), and 15 healthy controls. The patients with DESOS were randomly subdivided into two groups; the C-DESOS group received artificial tears only, and the G-DESOS group received artificial tears and 0.1% fluorometholone eye drops three times a day. Symptoms were assessed using the Ocular Surface Disease Index (OSDI) and the Neuropathic Pain Symptoms Inventory modified for Eye (NPSI-E) questionnaire. Ocular examinations and in vivo confocal microscopy (IVCM) were also employed. Tear and conjunctival cytokines were measured using Multiplex or RT-PCR on Days 0, 7, and 30. The correlation between the expression of cytokines and hypersensitivity status was analyzed. Results: Compared with the CMDE and control groups, the DESOS groups showed a significant increase in symptom scores and in the ratio of symptoms versus signs. IL-1 ß, IL-2, IL-6, and TNF-α in tears and conjunctiva increased in the DESOS groups compared to the CMDE and control groups, indicating a high correlation with hypersensitivity status in the DESOS groups. Glucocorticoid treatment significantly decreased the level of cytokines in tears and conjunctiva in the G-DESOS group and subsequently ameliorated the symptoms. Conclusions: Tear and conjunctival cytokines, including IL-1 ß, IL-2, IL-6, and TNF-α, were correlated with sensory hypersensitivity status in the DESOS groups, suggesting they play an important role in the discordance of symptoms outweighing signs.

Parameter Estimation for Evaporation-Driven Tear Film Thinning.

Many parameters affect tear film thickness and fluorescent intensity distributions over time; exact values or ranges for some are not well known. We conduct parameter estimation by fitting to fluorescent intensity data recorded from normal subjects' tear films. The fitting is done with thin film fluid dynamics models that are nonlinear partial differential equation models for the thickness, osmolarity and fluorescein concentration of the tear film for circular (spot) or linear (streak) tear film breakup. The corresponding fluorescent intensity is computed from the tear film thickness and fluorescein concentration. The least squares error between computed and experimental fluorescent intensity determines the parameters. The results vary across subjects and trials. The optimal values for variables that cannot be measured in vivo within tear film breakup often fall within accepted experimental ranges for related tear film dynamics; however, some instances suggest that a wider range of parameter values may be acceptable.

Dynamics of Fluorescent Imaging for Rapid Tear Thinning.

A previous mathematical model has successfully simulated the rapid tear thinning caused by glob (thicker lipid) in the lipid layer. It captured a fast spreading of polar lipid and a corresponding strong tangential flow in the aqueous layer. With the simulated strong tangential flow, we now extend the model by adding equations for conservation of solutes, for osmolarity and fluorescein, in order to study their dynamics. We then compare our computed results for the resulting intensity distribution with fluorescence experiments on the tear film. We conclude that in rapid thinning, the fluorescent intensity can linearly approximate the tear film thickness well, when the initial fluorescein concentration is small. Thus, a dilute fluorescein is recommended for visualizing the rapid tear thinning during fluorescent imaging.

Tear film stability assessment by corneal reflex image degradation.

Tear film stability assessment is one of the main tests in dry eye diagnosis. However, to date, no test methodology has been adopted as the gold standard due to several reasons, such as the methods being invasive, subjective, or unfeasible for the clinical environment. In this paper, a method that overcomes the above-mentioned limitations for tear film stability measurements is presented, and is based on the degradation of corneal reflex images caused by breakups. The experimental setup, which is based on recording the corneal reflex image or the first Purkinje image, is described, as well as the method used to determine tear film stability by means of the associated breakup time (BUT) using corneal reflex image degradation. Images obtained through simulations of the experimental setup are also shown. Moreover, BUT measurements performed using both the conventional fluorescein method and the proposed method in nine healthy adults are presented. Both the experimental and simulation images show corneal reflex image degradation due to the appearance of breakups in the tear film, highlighting the potential of the method to assess tear film stability. We have shown that the corneal reflex image degrades when the tear film breaks up and, thus, the proposed method can be used to assess tear film stability.

Tear film imager for dynamic mapping of the human tear film.

Dry eye (DE) disease is a multifactorial disease of the outer ocular surface characterized by several ocular symptoms and mainly by tear film instability. We have developed an optical imaging system, the tear film imager (TFI), which is the first instrument that can directly image the muco-aqueous tear layer physical dimension in vivo and evaluate its parameters in a noninvasive mode with nanometer axial resolution. This instrument provides quantified information about many attributes of the tear film, including muco-aqueous layer thickness, lipid layer thickness, thickness change rate, and the break-up time. The TFI performances are based on simultaneous acquisition of large field of view (FOV) imagery and fast spectrometric measurement of the interference from the thin tear film sublayers. Herein, after describing the instrument and the methodology of the measurements, we use a tear film mock-up to quantify device accuracy (2.2 nm) and repeatability (0.25 nm standard deviation). In conclusion, we present a new technology for the assessment of the tear film with an unprecedented axial resolution and excellent accuracy and reproducibility.

Update on the association between dry eye disease and meibomian gland dysfunction.

Dry eye disease is one of the most common ophthalmic complaints; it results from the activity of various pathways and is considered a multifactorial disease. An important factor that contributes to the onset of dry eye disease is meibomian gland dysfunction. Meibomian gland dysfunction causes a disruption in the tear film lipid layer which affects the rate of tear evaporation. This evaporation leads to tear hyperosmolarity, eventually triggering the onset of dry eye disease. Dry eye disease and meibomian gland dysfunction are strongly associated with each other, such that many of their risk factors, signs, and symptoms overlap. This review aimed to provide an update on the association between dry eye disease and meibomian gland dysfunction. A stepwise approach for diagnosis and management is summarised.

Evaluation of the corneal epithelium in non-Sjögren's and Sjögren's dry eyes: an in vivo confocal microscopy study using HRT III RCM.

BACKGROUND: The corneal epithelium is directly affected in dry eye syndrome. Thus, we attempted to describe the morphological features and evaluate the cellular density within the corneal epithelial layers in patients with non-Sjögren's (NSDE) and Sjögren's syndrome dry eyes (SSDE) by in vivo confocal microscopy (IVCM). METHODS: Central cornea was prospectively imaged by IVCM in 68 clinically diagnosed aqueous tear-deficient dry eyes and 10 healthy age-matched control eyes. Morphological characteristics of corneal epithelial layers and cellular densities were evaluated by four trained graders from the Doheny Eye Institute. RESULTS: Corneal epithelium in dry eyes presents morphological changes such as areas of enlarged and irregular shaped cells. In comparison with controls, the density of superficial epithelial cells was decreased in both the NSDE (P < 0.05) and SSDE groups (P < 0.01); the density of the outer layer of wing cells was smaller but not significantly different in NSDE (P > 0.05), but was lower in the SSDE group (P < 0.01); the density of the inner layer of wing cells was decreased in both the NSDE (P < 0.05) and SSDE groups (P < 0.01) and the density of basal epithelial cells was lower in both the NSDE (P < 0.01) and SSDE groups (P = 0.01). For all cell counts, the interclass correlation coefficient showed good agreement between graders (ICC =0.75 to 0.93). CONCLUSIONS: IVCM represents a reliable technique for examining the corneal epithelial microstructural changes associated with dry eyes, as well as for objectively and reproducibly quantifying cell densities within all corneal epithelial layers.

Repeatability of Central Corneal Thickness Measurement Using Rotating Scheimpflug Camera in Dry and Normal Eyes.

PURPOSE: To compare the repeatability of central corneal thickness (CCT) measurement using the Pentacam between dry eyes and healthy eyes, as well as to investigate the effect of artificial tears on CCT measurement. METHODS: The corneal thicknesses of 34 patients with dry eye and 28 healthy subjects were measured using the Pentacam. One eye from each subject was assigned randomly to a repeatability test, wherein a single operator performed three successive CCT measurements time points-before and 5 min after instillation of one artificial teardrop. The repeatability of measurements was assessed using the coefficient of repeatability and the intraclass correlation coefficient. RESULTS: The coefficient of repeatability values of the CCT measurements in dry and healthy eyes were 24.36 and 10.69 µm before instillation, and 16.85 and 9.72 µm after instillation, respectively. The intraclass correlation coefficient was higher in healthy eyes than that of in dry eyes (0.987 vs. 0.891), and it had improved significantly in dry eyes (0.948) after instillation of one artificial teardrop. The CCT measurement fluctuated in dry eyes (repeated-measures analysis of variance, P<0.001), whereas no significant changes were detected in healthy eyes, either before or after artificial tear instillation. CONCLUSIONS: Central corneal thickness measurement is less repeatable in dry eyes than in healthy eyes. Artificial tears improve the repeatability of CCT measurements obtained using the Pentacam in dry eyes.

Application of CASIA SS-1000 Optical Coherence Tomography Tear Meniscus Imaging in Testing the Efficacy of New Strip Meniscometry in Dry Eye Diagnosis.

PURPOSE: To investigate the applicability of CASIA SS-1000 anterior-segment optical coherence tomography (AS-OCT) imaging parameters in testing the efficacy of the new strip meniscometry (SM) namely "Strip Meniscometry Tube" (SMTube) in the diagnosis of dry eyes. METHODS: Forty-three eyes of 22 patients (4 men and 18 women) with definite dry eye disease (DED) and 49 eyes of 28 normal controls (6 men and 22 women) were studied. All subjects underwent symptom questionnaires, SMTube, the Schirmer-1 test, tear film break-up time measurement, vital staining examinations, as well as tear meniscus height (TMH) and TM area (TMA) measurements using an AS-OCT system. We evaluated the cutoff values for the diagnosis of DED, looked into the correlations between TMH, TMA, and SMTube scores and checked the sensitivity and specificity of these parameters in the diagnosis of DED. RESULTS: The mean values of TMH, TMA, and SMTube scores in the patient group were 0.138±0.102 mm, 0.013±0.015 mm and 1.4±2.3 mm, whereas those for the control group were 0.27±0.10 mm, 0.033±0.025 mm and 5.8±2.8 mm, respectively. The differences between both groups were significant (P<0.001). The cutoff values of TMH, TMA, and SMTube for DED were 0.197 mm, 0.020 mm and 3.8 mm, respectively. SMTube had significant correlations with TMH (r=0.82, P<0.001) and TMA (r=0.86, P<0.001). CONCLUSIONS: The SMTube was useful in DED diagnosis, the validity of which could be effectively evaluated by the CASIA SS-1000 AS-OCT TM parameters.

An Automated Grading and Diagnosis System for Evaluation of Dry Eye Syndrome.

This article describes methods used to determine the severity of Dry Eye Syndrome (DES) based on Oxford Grading Schema (OGS) automatically by developing and applying a decider model. The number of dry punctate dots occurred on corneal surface after corneal fluorescein staining can be used as a diagnostic indicator of DES severity according to OGS; however, grading of DES severity exactly by carefully assessing these dots is a rather difficult task for humans. Taking into account that current methods are also subjectively dependent on the perception of the ophtalmologists coupled with the time and resource intensive requirements, enhanced diagnosis techniques would greatly contribute to clinical assessment of DES. Automated grading system proposed in this study utilizes image processing methods in order to provide more objective and reliable diagnostic results for DES. A total of 70 fluorescein-stained cornea images from 20 patients with mild, moderate, or severe DES (labeled by an ophthalmologist in the Keratoconus Center of Yildirim Beyazit University Ataturk Training and Research Hospital) used as the participants for the study. Correlations between the number of dry punctate dots and DES severity levels were determined. When automatically created scores and clinical scores were compared, the following measures were observed: Pearson's correlation value between the two was 0.981; Lin's Concordance Correlation Coefficients (CCC) was 0.980; and 95% confidence interval limites were 0.963 and 0.989. The automated DES grade was estimated from the regression fit and accordingly the unknown grade is calculated with the following formula: Gpred = 1.3244 log(Ndots) - 0.0612. The study has shown the viability and the utility of a highly successful automated DES diagnostic system based on OGS, which can be developed by working on the fluorescein-stained cornea images. Proper implemention of a computationally savvy and highly accurate classification system, can assist investigators to perform more objective and faster DES diagnoses in real-world scenerios.

Image-based quantitative analysis of tear film lipid layer thickness for meibomian gland evaluation.

BACKGROUND: Dry eye syndrome is one of the most common ocular diseases, and meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye syndrome. When the tear film lipid layer becomes thin due to obstructive or hyposecretory meibomian gland dysfunction, the excessive evaporation of the aqueous layer can occur, and this causes evaporative dry eye syndrome. Thus, measuring the lipid layer thickness (LLT) is essential for accurate diagnosis and proper treatment of evaporative dry eye syndrome. METHODS: We used a white LED panel with a slit lamp microscope to obtain videos of the lipid layer interference patterns on the cornea. To quantitatively analyze the LLT from interference colors, we developed a novel algorithm that can automatically perform the following processes on an image frame: determining the radius of the iris, locating the center of the pupil, defining region of interest (ROI), tracking the ROI, compensating for the color of iris and illumination, and producing comprehensive analysis output. A group of dry eye syndrome patients with hyposecretory MGD, dry eye syndrome without MGD, hypersecretory MGD, and healthy volunteers were recruited. Their LLTs were analyzed and statistical information-mean and standard deviation, the relative frequency of LLT at each time point, and graphical LLT visualization-were produced. RESULTS: Using our algorithm, we processed the lipid layer interference pattern and automatically analyzed the LLT distribution of images from patients. The LLT of hyposecretory MGD was thinner (45.2 ± 11.6 nm) than that of dry eye syndrome without MGD (69.0 ± 9.4 nm) and healthy volunteers (68.3 ± 13.7 nm) while the LLT of hypersecretory MGD was thicker (93.5 ± 12.6 nm) than that of dry eye syndrome without MGD. Patients' LLTs were statistically analyzed over time, visualized with 3D surface plots, and displayed using 3D scatter plots of image pixel data for comprehensive assessment. CONCLUSIONS: We developed an image-based algorithm for quantitative measurement as well as statistical analysis of the LLT despite fluctuation and eye movement. This pilot study demonstrates that the quantitative LLT analysis of patients is consistent with the functions of meibomian glands clinically evaluated by an ophthalmologist. This approach is a significant step forward in developing a fully automated instrument for evaluating dry eye syndrome and for providing proper guidance of treatment.

Progress in tear microdesiccate analysis by combining various transmitted-light microscope techniques.

BACKGROUND: Tear desiccation on a glass surface followed by transmitted-light microscopy has served as diagnostic test for dry eye. Four distinctive morphological domains (zones I, II, III and transition band) have been recently recognized in tear microdesiccates. Physicochemical dissimilarities among those domains hamper comprehensive microscopic examination of tear microdesiccates. Optimal observation conditions of entire tear microdesiccates are now investigated. One-µl aliquots of tear collected from individual healthy eyes were dried at ambient conditions on microscope slides. Tear microdesiccates were examined by combining low-magnification objective lenses with transmitted-light microscopy (brightfield, phase contrasts Ph1,2,3 and darkfield). RESULTS: Fern-like structures (zones II and III) were visible with all illumination methods excepting brightfield. Zone I was the microdesiccate domain displaying the most noticeable illumination-dependent variations, namely transparent band delimited by an outer rim (Ph1, Ph2), homogeneous compactly built structure (brightfield) or invisible domain (darkfield, Ph3). Intermediate positions of the condenser (BF/Ph1, Ph1/Ph2) showed a structured roughly cylindrical zone I. The transition band also varied from invisibility (brightfield) to a well-defined domain comprising interwoven filamentous elements (phase contrasts, darkfield). CONCLUSIONS: Imaging of entire tear microdesiccates by transmitted-light microscopy depends upon illumination. A more comprehensive description of tear microdesiccates can be achieved by combining illumination methods.

[Evaluation of tear film and meibomian gland function in dry eye patients using Keratograph 5M].

Objective: To assess the application of Keratograph 5M in evaluating tear film and meibomian gland function in patients with dry eye. Methods: A total of 144 eyes were recruited in the study, in which 72 eyes were from patients diagnosed with dry eye and 72 eyes were from healthy subjects. All subjects finished following tests or examinations:ocular surface disease index (OSDI) to evaluate eye symptoms; Keratograph 5M examination to obtain tear meniscus height (TMH), noninvasive tear break-up time (NIBUT) including first NIBUT (NIBUT-Fir) and average NIBUT (NIBUT-Ave), and infrared meibography; and fluorescein sodium staining to obtain fluorescein tearbreak-up time (FBUT). Results: Dry eye group had higher OSDI score than healthy control group, but its TMH, NIBUT-Fir and NIBUT-Ave were lower than those in healthy control group (all P<0.01). Total meiboscore in dry eye group was higher than that in healthy control group (P<0.01), and it showed a significant correlation with NIBUT-Fir and NIBUT-Ave (r=-0.449 and -0.398, P<0.01), but no correlation with ages was observed (r=0.031, P>0.05). The NIBUT-Fir and NIBUT-Ave showed a significant correlation with FBUT (r=0.833 and 0.727, P<0.01). Conclusion: Keratograph 5M is a convenient, accurate and non-invasive method to assess the function of tear film and meibomian gland, and the new meibography scoring system can evaluate the function of meibomian gland objectively and succinctly.

In vivo confocal microscopy of bulbar conjunctiva in patients with Graves' ophthalmopathy.

BACKGROUND/PURPOSE: To investigate the bulbar conjunctival changes in patients with Graves' ophthalmopathy (GO) using in vivo confocal microscopy. METHODS: A total of 15 GO patients and 15 control patients were recruited. Images of the superior site and temporal bulbar conjunctivas were taken by the Heidelberg Retina Tomograph/Rostock Corneal Module. The conjunctival thickness and cell density of superior epithelium, basal epithelium, Langerhans cells, and goblet cells were analyzed. Conjunctival impression cytology was performed to assess the grading of squamous metaplasia of the conjunctival epithelium. RESULTS: The superficial epithelial cell density in the superior bulbar conjunctiva of the GO group was 856.93 ± 461.68 cells/mm(2), which was significantly lower than that in the control group (1581.13 ± 556.34 cells/mm(2); p = 0.002). However, the difference in superficial epithelial cell density in the temporal bulbar conjunctiva between the two groups was not statistically significant. No significant differences in conjunctival thickness and the basal epithelial cell density were noted between the two groups. Increased Langerhans cell density and reduced goblet cell density were noted in the GO group. Impression cytology of the conjunctival epithelium revealed significantly higher degree of squamous metaplasia in the GO group. The superficial epithelial cell density in the upper bulbar conjunctiva showed negative correlation with marginal reflex distance in the GO group. CONCLUSION: GO patients suffered from more severe bulbar conjunctival damage and inflammation with the superior site than the temporal site. In vivo confocal microscopy can be a rapid and noninvasive tool for the quantitative evaluation of ocular surface changes in patients with GO.

In Vivo Human Lacrimal Gland Imaging Using an Ultrasound Biomicroscopy.

PURPOSE: In the present study, we introduce human lacrimal gland imaging using an ultrasound biomicroscopy (UBM) with a soft cover and show their findings. METHODS: The representative UBM findings of palpebral lobes in seven subjects (four with non-Sjögren dry eye syndrome, one with Sjögren syndrome, and two healthy subjects) were described in this study. To prolapse the palpebral lobe, the examiner pulled the temporal part of the upper eyelid in the superotemporal direction and directed the subject to look in the inferonasal direction. We scanned the palpebral lobes longitudinally and transversely using UBM. We used an Aviso UBM with a 50 MHz linear probe and ClearScan. RESULTS: In UBM of two healthy subjects, the echogenicity of the lacrimal gland was lower than that of the sclera and homogeneous. But the parenchyma of a patient with Sjögren dry eye syndrome was quite inhomogeneous compared to the healthy subjects. In two patients with dry eye syndrome, we were able to observe some lobules in the parenchyma. We could find excretory ducts running parallel at the surface of the longitudinal section in some subjects. In the longitudinal UBM scan of a subject, we observed a tubular structure at a depth of 1,500 µm that was considered a blood vessel. It ran from the superonasal to the inferotemporal direction. In a subject, we observed a large cyst beneath the conjunctiva. CONCLUSIONS: Lacrimal gland imaging using UBM has both advantages of optical coherence tomography and sonography, and could be useful for evaluating dry eye syndrome.

Comparing meibomian gland visibility on optical coherence tomography and Keratograph 5M images using objective and subjective grading methods.

PURPOSE: To investigate if there is a visible difference in meibomian gland (MG) length between images captured with the Visante optical coherence tomography (OCT; wavelength = 1,310 nm) and the OCULUS Keratograph 5M (K5M; wavelength = 880 nm). METHODS: Adults between 18 and 40 years were recruited. Baseline dry eye disease was evaluated with the Standard Patient Evaluation of Eye Dryness (SPEED) and tear meniscus height and tear breakup time with the K5M. Right upper and lower eyelid MGs were imaged with the K5M and Visante OCT. Each image was graded with the 0 to 3 meiboscore scale. The central 5 MGs were evaluated with ImageJ for percent gland length visibility. RESULTS: Thirty participants were analyzed with a median (interquartile range [IQR]) age of 23.0 (5.0) years (53.3 % female). Overall, participants were asymptomatic and had normal tear films. Meiboscores based on K5M and Visante OCT was significantly different for the lower eyelid (0[1] vs 1[2]; p = 0.007) but not the upper eyelid (0[1] vs 0[1]; p = 1.00). The mean percent gland visibility of the upper eyelid (82.7[9.6] vs 75.2[13.5]; p < 0.001) and the lower eyelid (81.2[12.7] vs 64.1[17.6]; p < 0.001) were significantly greater on the Visante OCT than the K5M images, respectively. CONCLUSION: OCT images had significantly greater percent visible MG lengths than the K5M images. This suggests viable segments of the MGs may be missed with typical imaging, which may explain how it is possible that studies have found less post-treatment MG atrophy.