Assessment of tear film parameters in females with refractive errors using a single device: An observational study.

This observational study aimed to evaluate the use of a single portable device to assess the non-invasive tear break-up time (NITBUT), tear meniscus height (TMH), and lipid layer patterns (LLP) in young females with refractive errors (REs). The study was conducted at the College of Applied Medical Science (Female campus), Riyadh, Saudi Arabia between January 5, 2021 to May 15, 2021. Forty young females, with mean age of 23.0± 4.3 years with REs (-2.53 ± 2.05 D) and 40 females, mean age 23.8± 4.5 years with healthy eyes were recruited. The tests were administered in the following order: Ocular Surface Disease Index (OSDI), followed by NITBUT, TMH, and LLP. Significant differences (via Mann-Whitney U test) were noted in the median ocular surface disease index (OSDI; p˂0.001), NITBUT (p=0.035), TMH (p=0.009), and LLP (p˂0.001) scores between the study and control groups. Females with REs have significantly lower lipid layer, TMH, and NITBUT scores than those with healthy eyes.

Assessment of lipid layer patterns in domestic dogs and rabbits: an observational study.

Background: Maintaining a stable tear film is crucial for having healthy human and animal vision. Animals are expected to have thicker lipid layers than humans due to living in high-temperature and humid environments. Aim: The study aimed to evaluate the lipid layer patterns (LLPs) in Arabian dogs and rabbits using a non-invasive, practical, and easy-to-use device and compare them to humans with healthy eyes. Methods: The study included 75 domestic Arabian dogs (42 males and 33 females; mean ± SD = 6.1 ± 12.7 months) and 75 rabbits (37 males and 38 females; mean ± SD = 3.1 ± 3.4 months). In addition, 75 individuals with healthy eyes (39 males and 36 females; mean ± SD = 25.7 ± 5.0 years) were included for comparison. EASYTEAR View+ assessed the LLP in each animal's and individual's right eye. Results: The median LLP grades significantly differed between dogs and humans (Mann-Whitney U test, p < 0.001). Similarly, the LLP grades differed significantly between rabbits and humans (Mann-Whitney U test, p < 0.001). No significant difference (Mann-Whitney U test) in the LLP grades between dogs and rabbits was found. The analysis indicated that most dogs had either an A (34.7%) or a B grade (37.3%). Similarly, rabbits had predominantly A or 1 (46.7%) and B (30.7%) grades. On the other hand, humans had predominantly D (53.3%) and E (30.7%) grades. Conclusion: The EASYTEAR View+ has been employed to assess LLP in dogs and rabbits, and the measurements were compared to those of humans with normal ocular health. Dogs and rabbits have thinner lipid layers than healthy humans.

End-of-day assessment of asymptomatic versus highly symptomatic soft contact lens wearers.

PURPOSE: To investigate differences in key clinical parameters between asymptomatic and highly symptomatic soft contact lens (CL) wearers after 14 h of wear. METHODS: In this pilot investigation, Phase 1 identified asymptomatic (CLDEQ-8 score ≤ 7) and highly symptomatic (CLDEQ-8 score ≥ 20) subjects after fitting with nelfilcon A CLs. Phase 2 investigated the following over a single nelfilcon A CL-wearing day (14 ± 2 h): blinking characteristics, tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), tear film osmolarity and eyelid margin staining. Parameters for the two groups were compared using linear mixed models and post-hoc testing. The relationship between comfort scores and the clinical parameters was also investigated. RESULTS: Overall, 161 and 42 subjects were enrolled into Phase 1 and 2, respectively. Twenty-five asymptomatic and 17 symptomatic subjects completed Phase 2. Lower eyelid TMH was decreased after 14 h in symptomatic compared with asymptomatic subjects (least square mean [LSM] difference -0.04 mm, 95% CI: -0.07, -0.01). Osmolarity was lower in symptomatic than in asymptomatic subjects at fitting (LSM difference -9.89, 95% CI: -18.91, -0.86). Upper eyelid margin staining was greater after 14 h in symptomatic than in asymptomatic subjects (LSM difference 0.53, 95% CI: 0.01, 1.05) and greater after 14 h than baseline in the symptomatic group (LSM difference 0.61, 95% CI: 0.16, 1.07). There was a significant relationship between comfort and upper eyelid margin staining (r = -0.40, 95% CI: -0.63, -0.11) and blink rate (r = -0.31, 95% CI: -0.57, -0.003). CONCLUSION: The potential parameters most effective in differentiating asymptomatic from symptomatic wearers were upper eyelid margin staining and lower TMH. The parameter with the strongest relationship to comfort was upper eyelid margin staining, where higher comfort scores were associated with lower levels of staining.

Optimal cutoff value of the dry eye-related quality-of-life score for diagnosing dry eye disease.

This retrospective study aimed to determine the optimal cutoff values of the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire for diagnosing dry eye disease (DED) and classifying DED severities. Participants completed the DEQS questionnaire, the Japanese version of the Ocular Surface Disease Index (J-OSDI) questionnaire, and DED examinations. DED was diagnosed according to the 2016 Asia Dry Eye Society diagnostic criteria based on DED symptoms (J-OSDI ≥ 13 points) and tear film breakup time ≤ 5 s. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the DEQS summary score for detecting DED and grading its severity. Among 427 patients, 296 (69.3%) and 131 (30.7%) were diagnosed with DED and non-DED, respectively. ROC analysis determined an optimal cutoff value of 15.0 points for DED diagnosis, with 83.5% sensitivity, 87.0% specificity, and an area under the curve of 0.915. The positive and negative predictive values for DEQS ≥ 15.0 points were 93.6% and 69.9%, respectively. DEQS cutoff values of 15.0, 20.0, and 26.8 points could be accepted for severity classification of DED subjective symptoms in clinical use and represent mild, moderate, and severe DED, respectively. Conclusively, the optimal cutoff values of DEQS enable DED detection and subjective symptom severity classification.

Association between systemic medication use and severity of dry eye signs and symptoms in the DRy eye assessment and management (DREAM) study.

PURPOSE: Some systemic medications are reported to be associated with dry eye disease (DED), yet their associations with the severity of DED signs and symptoms are not well studied. To evaluate these associations, we performed a secondary analysis of data from the DRy Eye Assessment and Management (DREAM) Study. METHODS: Participants (N = 535) were assessed for DED signs using tear break-up time (TBUT), Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, meibomian gland dysfunction (MGD), and tear osmolarity and DED symptoms using the Ocular Surface Disease Index (OSDI). We derived a composite signs severity score from the 6 DED signs and categorized participant-reported systemic medications into antidepressants, antihistamines, aspirin, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, statins, vitamin D3, and medications for diabetes mellitus, hypertension, hypothyroidism, migraine, and seizure. Generalized linear models were used to compare DED symptom and sign scores between medication users and non-users, with adjustment for factors associated with DED severity. RESULTS: Compared to non-users, antihistamine users had lower TBUT (p = 0.01) and higher OSDI score (p = 0.02); aspirin users had lower TBUT (p = 0.02); corticosteroid users had lower TBUT (p = 0.02), lower Schirmer test scores (p = 0.03), higher cornea fluorescein staining (p = 0.01), higher composite severity score (p = 0.01), and higher OSDI score (p = 0.03); seizure medication users had higher composite severity score (p = 0.02); vitamin D3 users had lower TBUT (p = 0.001) and greater MGD (p = 0.03); and diuretic users had less MGD (p = 0.03). CONCLUSIONS: Certain systemic medications may be associated with more severe DED. This may guide prescription practices in patients with DED.

A latent profile analysis of tear cytokines and their association with severity of dry eye disease in the Dry Eye Assessment and Management (DREAM) study.

This study is to identify subgroups of DED patients with different tear cytokine profiles and compare their DED symptoms and signs among subgroups. Baseline tear cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17A, IFN-γ and TNF-α) were measured using a magnetic bead assay. DED symptoms were assessed by Ocular Surface Disease Index (OSDI) and signs were assessed by corneal and conjunctival staining, tear break-up time (TBUT), Schirmer's test, tear osmolarity and meibomian gland dysfunction (MGD). Latent profile analysis was performed to identify subgroups, and their scores of DED symptoms and signs were compared using generalized linear regression. Among 131 patients with total tear volume > 4 µl from both eyes, subgroup 1 (n = 23) significantly higher in IL-6 and IL-8 (all p < 0.001) and subgroup 2 (n = 108) significantly higher in IL-10 (p = 0.03), IL-17A (p < 0.001), and IFN-γ (p < 0.001). Both subgroups were similar in demographics and DED symptoms, but subgroup 1 had significantly more severe DED signs: higher conjunctival staining (3.38 vs. 2.69, p = 0.04), corneal staining (4.26 vs. 3.03, p = 0.03), lower Schirmer's test score (8.20 vs. 13.72, p < 0.001), and higher composite severity score of DED sign (0.62 vs. 0.45, p = 0.002). We identified two DED subgroups with different profiles of tear cytokines. Patients in these subgroups differed significantly in DED signs, supporting the inflammation's role in DED development and progression.

Association of Tear Cytokine Ratios with Symptoms and Signs of Dry Eye Disease: Biomarker Data from the Dry Eye Assessment and Management Study.

PURPOSE: To assess the relationship between tear inflammatory cytokine ratios (CRs) and signs and symptoms of dry eye disease (DED) to investigate the possible use of tear CRs, which may better address the complexity of cytokine interactions than absolute cytokine levels, as a DED biomarker. METHODS: Tear concentrations of IL-1b, IL-6, IL-8, IL-10, IL-17A, IFN-g, and TNF-a were measured using standardized procedures, as were DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)]. Ratios between pro-inflammatory (IL-1b, IL-8, IL-17A, IFN-g, and TNF-a) and anti-inflammatory (IL-10) cytokines were calculated. Given its opposing roles in inflammation, IL-6 was tested as both a pro- and anti-inflammatory cytokine. Correlations between CR and DED symptoms and signs were calculated using Spearman correlation coefficients (rho). RESULTS: At baseline, 131 patients, 80.2% female and mean age 54.2 years (SD 14.1, range 20-82), from 10 sites of the Dry Eye Assessment and Management study had sufficient tear volumes ≥4 µL for analysis. IL-6:IL-10, IL-8:IL-10, and TNF-a:IL-10 had some significant correlations, mostly with conjunctival or corneal staining or the composite sign severity score (IL-8:IL-10 and conjunctival staining: rho = 0.19, p = 0.03; IL-6:IL-10 and corneal staining: rho = 0.31, p < 0.001; IL-8:IL-10 and corneal staining: rho = 0.21, p = 0.01; IL-6:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; IL-8:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; TNF-a:IL-10 and corneal staining: rho = 0.29, p < 0.001; TNF-a:IL-10 and Schirmer test: rho = -0.23, p = 0.009). CRs had no significant correlation with DED symptoms. All significant correlations using IL-6 in the denominator (anti-inflammatory) produced counterintuitive results based on clinical understanding of the disease. CONCLUSIONS: Pro- to anti-inflammatory CR was weakly correlated with some DED signs and not with symptoms, as measured by OSDI. Future studies in different dry eye populations are needed and should address sampling biases and tear collection techniques.

A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model.

Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates.

Non-invasive assessment of the tear film after LASIK.

OBJECTIVE: The aim of the study was to compare the assessment of the ocular surface using classic methods with the newly developed keratoscopy-based MYAH (Topcon EU, Visia Imaging, Japan) device after femtosecond laser-assisted in situ keratomileusis (LASIK). PATIENTS AND METHODS: This cross-sectional and observational study analyzed 80 eyes of 40 patients. Tear film and ocular surface evaluation were performed at baseline, postoperative week 1, and month 1. Measurements obtained using the Schirmer I test and invasive tear-film breakup time (I-TBT) were compared with non-invasive evaluation of the tear break-up time (NI-TBT), tear meniscus height (TMH) and blink analysis obtained using the MYAH device. Findings were correlated with the Ocular Surface Disease Index (OSDI) questionnaire in all subjects. RESULTS: The study included 80 eyes of 40 consecutive patients (21 males and 19 females) with a mean age of 26.6 ± 5.9 years (18-40 years) and a mean spherical equivalent value of -3.64 D (-9.63 to -0.25 D). There was a significant decrease in Schirmer I test (19.21 ± 8.4 vs. 16.61 ± 9.1 vs. 14.69 ± 9.86, p= 0.02, respectively) and I-TBT values (8.59 ± 3.4 vs. 7.4 ± 3.25 vs. 6.17 ± 3.01, p=0.03 respectively). OSDI values showed a significant increase after LASIK (11.56 ± 6.3 vs. 17.24 ± 7.5 vs. 14.71 ± 9.6, p=0.03, respectively). 5% level NI-TBT was significantly lower at 1 week 6.75 and 1 month 7.45 than baseline 13.2 at follow-up (p=0.037). Ocular protection index (6.6 vs. 2.3 vs. 2.6, p=0.009, respectively) and blink/minutes (18 vs. 17 vs. 15, p=0.002, respectively) values showed a statistically significant decrease. Our data detected a weak correlation between I-TBT and noninvasive first TBT, 5% level TBT parameters at month 1 follow-up. This study also found no correlation between contact lens use, older age, female gender, and pre-operative refractive error with the noninvasive MYAH dry eye parameters. CONCLUSIONS: This study demonstrated the ability of the new keratoscopy-based MYAH device to detect changes in the short term after LASIK surgery.

Intraobserver Repeatability Assessment of the S390L Firefly WDR Slitlamp in Patients With Dry Eye Disease: Objective, Automated, and Noninvasive Measures.

OBJECTIVES: To assess the intraobserver repeatability of automated, objective, and noninvasive measures obtained with the S390L Firefly WDR slitlamp. METHODS: This cross-sectional study included 50 eyes of patients with dry eye disease with a mean age of 55.06±12.96 years. Three consecutively repeated measures of the following variables were obtained: first noninvasive break-up time (F-NIBUT), average noninvasive break-up time (A-NIBUT), tear meniscus height, tear meniscus area (TMA), nasal ciliary hyperemia (NCIH), temporal ciliary hyperemia (TCIH), nasal conjunctival hyperemia (NCOH), temporal conjunctival hyperemia (TCOH), upper loss area meibomian gland (U-LAMG), lower loss area meibomian gland (L-LAMG), upper meibomian gland dysfunction grade (U-MGD grade), and lower meibomian gland dysfunction grade (L-MGD grade). Intraobserver repeatability was estimated with coefficient of variation (CoV), intrasubject standard deviation (SD) (S w ), and Bland-Altman plots. RESULTS: All variables showed no statistically significant differences in the repeated-measures analysis except for L-MGD grade ( P =0.045). F-NIBUT and A-NIBUT obtained the highest CoV with an average value of 0.48±0.41 [0.02-1.00] and 0.34±0.25 [0.02-1.00], respectively. The remaining variables showed CoVs between 0.04±0.11 [0.00-0.43] and 0.18±0.16 [0.00-0.75]. A-NIBUT, TMA, NCOH, and L-LAMG obtained an S w of 2.78s, 0.21 mm 2 , <0.001, and 4.11%, respectively. Bland-Altman plots showed a high level of agreement between pairs of repeated measures. CONCLUSION: The S390L Firefly WDR slitlamp has moderate intraobserver repeatability for F-NIBUT and A-NIBUT, which suggests that F-NIBUT and A-NIBUT are tests with high variability. The remaining variables show satisfactory intraobserver repeatability.

Morphological and functional assessment of the tear film and meibomian glands in keratoconus.

PURPOSE: To evaluate morphological and functional state of the meibomian glands (MG) in keratoconus patients. METHODS: One hundred eyes of 100 keratoconus patients and 100 eyes of 100 age-matched control subjects were included into this study. Ocular Surface Disease Index (OSDI) scores, non-invasive break up time (NIBUT), findings of meibography, staining with fluorescein of the ocular surface, tear film break-up time (TBUT), and Schirmer I test were documented in all patients' eyes and control eyes and were compared between the groups . RESULTS: The mean TBUT and NIBUT were significantly lower, corneal staining and OSDI scores were statistically greater in the keratoconus group (p < 0.05). The mean meiboscore, partial gland, gland dropout and gland thickening scores for upper/lower eyelids were significantly greater in keratoconus patients than controls (p < 0.05). The NIBUT measurements significantly correlated with MG loss in upper/lower eyelids (p < 0.05). The severity of keratoconus seemed to correlate with meiboscore, partial gland, gland thickening scores in upper/lower eyelids. CONCLUSION: Our data suggests that corneal ectasia in keratoconus is related with alterations in ocular surface, tear film function and MG morphology. Early screening and treatment of MG dysfunction may improve ocular surface quality and allow better disease management in keratoconus patients.

Role of instrumental factors in Meibomian gland contrast assessment.

PURPOSE: Meibomian gland contrast has been suggested as a potential biomarker in Meibomian gland dysfunction. This study analysed the instrumental factors related to contrast. The objectives were to determine whether the mathematical equations used to compute gland contrast (e.g., Michelson or Yeh and Lin), impact the ability to identify abnormal individuals, to ascertain whether contrast between the gland and the background could be an effective biomarker and to assess whether using contrast-enhancement on the gland image improves its diagnostic efficacy. METHODS: A total of 240 meibography images from 40 participants (20 controls and 20 having Meibomian gland dysfunction or blepharitis), were included. The Oculus Keratograph 5M was used to capture images from the upper and lower eyelids of each eye. The contrast of unprocessed images and those pre-processed with contrast-enhancement algorithms were analysed. Contrast was measured on the eight central glands. Two equations for contrast computation were used, and the contrast both between glands and within a gland were calculated. RESULTS: Significant differences were found between the groups for inter-gland area in the upper (p = 0.01) and lower eyelids (p = 0.001) for contrast measured with the Michelson formula. Similar effects were observed when using the Yeh and Lin method in the upper (p = 0.01) and lower eyelids (p = 0.04). These results were obtained for images enhanced with the Keratograph 5M algorithm. CONCLUSIONS: Meibomian gland contrast is a useful biomarker of disease related to the Meibomian glands. Contrast measurement should be determined using contrast-enhanced images in the inter-gland area. However, the method used to compute contrast did not influence the results.

Functional and morphological evaluation of the meibomian glands and ocular surface assessment at high altitude.

Purpose: To compare the function and morphology of the meibomian glands and the ocular surface of individuals from highland and lowland. Methods: This was a randomized controlled trial. The study was performed with 104 individuals (51 individuals from the highland and 53 individuals from the lowland). Detailed eye examinations comprising tear meniscus height, lipid layer grading, non-invasive Keratograph tear breakup time (NIKBUT), and scoring of the meibomian glands from the upper and lower eyelids of the individuals were performed by Keratograph 5M (OCULUS, Wetzlar, Germany). Symptoms related to dry eye disease were assessed using the Ocular Surface Disease Index (OSDI). Results: In the highland group, tear meniscus height was lower (P = 0.024), lipid layer grade, as well as all the meiboscores were higher (P < 0.05) than that in the lowland group. The OSDI (P = 0.018) and the percentage of dry eye disease were also higher as compared to that of the lowland group (P = 0.032). The first NIKBUT and average NIKBUT did not differ significantly between groups. The frequency of plugged meibomian gland orifices was greater in the lowland group compared to the highland group (P = 0.036). Conclusion: It was observed that dry eye disease was more common in the highland group. The morphological changes of meibomian gland dropout were significant in highlanders as demonstrated objectively with Keratograph 5M. Our study may raise a concern for environmental influences on ocular surface changes.

Assessment of the levels of interleukin-17 and interleukin-38 in thyroid-associated ophthalmopathy patients.

PURPOSE: The objective of the study was to analyse the levels of IL-17 and IL-38 in the samples of unstimulated tears, orbital adipose tissues, and sera of patients diagnosed with active forms of TAO. The correlation of the levels of IL-17 and IL-38 with clinical activity score (CAS) was scrutinized. METHODS: A study was conducted at the Kazakhstan Scientific Research Institute of Eye Diseases (Almaty city, Kazakhstan). Study participants (n = 70) were sub-divided into 3 groups: (1) a group of patients diagnosed with active TAO (n = 25), (2) a group of patients with an inactive form of TAO (n = 28), and (3) a "control group" (patients diagnosed with orbital fat prolapse, n = 17). All patients underwent a clinical assessment and diagnostics. The activity of the disease and its severity were assessed using the CAS and NOSPECS scales. Thyroid function tests were performed, including the study of the levels of thyroid-stimulating hormone, triiodothyronine, free thyroxine, and antibodies to the thyroid-stimulating hormone receptor. IL-17 and IL-38 levels in non-stimulated tear samples, orbital tissue, and patients' sera were measured using commercial ELISA kits. RESULTS: The results showed that the number of former smokers prevailed among patients with active TAO (48%) in comparison with patients with inactive TAO (15.4%), p = 0.001. The concentration of IL-17 significantly increased in the samples of non-stimulated tears, adipose tissues of the orbit and sera of patients with active forms of TAO. The level of IL-38 was reduced in all types of samples (p ≤ 0.05). The results of a histological study of orbital adipose tissues in the group of patients with an active form of TAO showed the presence of focal infiltration with lymphocytes, histiocytes, plasma cells, severe sclerosis and vascular plethora. We observed an association between the CAS of patients with active TAO and the level of IL-17 in sera (r = 0.885; p = 0.001). On the contrary, a negative correlation was detected for the level of IL-38 in sera. CONCLUSIONS: The results highlighted the systemic effect of IL-17 and the local effect of IL-38 in TAO. We observed a significant increase in the production of IL-17, and a decrease in IL-38 in samples of sera and unstimulated tears (the active form of TAO). Our data indicate a correlation of IL-17 and IL-38 levels with the clinical activity of TAO.

Assessment of Laser Parameters to Improve Lid Tension-A Proof of Concept towards Lasercanthoplasty.

BACKGROUND: Preliminary clinical work indicates that increasing eyelid tension improves the function of the meibomian glands. The aim of this study was to optimize laser parameters for a minimally invasive laser treatment to increase eyelid tension by coagulation of the lateral tarsal plate and canthus. METHODS: Experiments were performed on a total of 24 porcine lower lids post mortem, with six lids in each group. Three groups were irradiated with an infrared B radiation laser. Laser-induced lower eyelid shortening was measured and the increase in eyelid tension was assessed with a force sensor. A histology was performed to evaluate coagulation size and laser-induced tissue damage. RESULTS: In all three groups, a significant shortening of the eyelids after irradiation was noticed (p < 0.0001). The strongest effect was seen with 1940 nm/1 W/5 s, showing -15.1 ± 3.7% and -2.5 ± 0.6 mm lid shortening. The largest significant increase in eyelid tension was seen after placing the third coagulation. CONCLUSION: Laser coagulation leads to lower eyelid shortening and an increase in lower eyelid tension. The strongest effect with the least tissue damage was shown for laser parameters of 1470 nm/2.5 W/2 s. In vivo studies of this effect have to confirm the efficacy of this concept prior to clinical application.

Association of Tear Cytokine Concentrations with Symptoms and Signs of Dry Eye Disease: Baseline Data from the Dry Eye Assessment and Management (DREAM) Study.

PURPOSE: To describe tear concentrations of IL-1ß, Il-6, IL-8, IL-10, IL-17A, IFNγ and TNFα in tears, collected by microcapillaries, and their correlation with symptoms and signs in subjects with dry eye disease (DED) in the DREAM Study. METHODS: Cytokine levels of patients with moderate to severe DED were determined using a magnetic bead assay. Scores for Ocular Surface Disease Index, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer's test were obtained using standardized procedures. Associations of cytokines with each other and signs/symptoms were assessed with Spearman correlation coefficients (r). RESULTS: Assay results from 131 patient samples from 10 sites with tear volumes ≥ 4 ul were analyzed. Cytokine concentrations did not correlate with each other in a generally acknowledged pro-inflammatory/anti-inflammatory pattern, such as proinflammatory IL-17A and IFNγ were not inversely correlated to anti-inflammatory cytokine IL-10, and cytokines did not correlate with DED symptoms. Lower corneal staining was correlated with higher concentrations of IL-17A (r= -0.24, p = 0.006), IL-10 (r= -0.25, p = 0.005) and IFNγ (r= -0.33, p = 0.0001). Higher concentrations of IFNγ were associated with lower conjunctival staining (r= -0.18, p = 0.03). Higher concentrations of IL-17A were associated with higher TBUT scores (r = 0.19 p = 0.02). CONCLUSIONS: Cytokines IL-10, IL-17A and IFNγ were highly correlated with each other but weakly correlated with some DED signs. No key cytokines or definitive expression patterns were identified in this study of moderate to severe DED patients. Further studies addressing various biases, including methodological and sampling biases, and standardization of methodology for inter-laboratory consistency are needed to confirm and establish pathological and clinical relevance of tear cytokines in DED.

Association of Tear Osmolarity With Signs and Symptoms of Dry Eye Disease in the Dry Eye Assessment and Management (DREAM) Study.

Purpose: To determine the relationships of (1) tear osmolarity (TO) levels with the severity of signs and symptoms of dry eye disease (DED) and (2) changes in TO with changes in signs and symptoms. Methods: Patients (N = 405) with moderate to severe DED in the Dry Eye Assessment and Management (DREAM) Study were evaluated at baseline and at six and 12 months. Associations of TO with signs and symptoms were evaluated using Pearson correlation coefficient (r) and regression models. Results: The mean (standard deviation [SD]) TO was 303 (16) mOsm/L at baseline and 303 (18) mOsm/L at both six and 12 months. TO was higher in older patients (306 mOsm/L for ≥70 years vs. 300 mOsm/L for <50 years; P = 0.01) and those with Sjögren's disease (311 vs. 302 mOsm/L; P < 0.0001). TO did not differ between patients randomized to placebo and omega-3 fatty acid supplementation. TO was weakly correlated with conjunctival (r = 0.18; P < 0.001) and corneal staining scores (r = 0.17; P < 0.001), tear film break-up time (r = 0.06; P = 0.03), and Schirmer test score (r = -0.07; P = 0.02) but not with Ocular Surface Disease Index scores (r = 0.03; P = 0.40). Changes in signs and were not significantly correlated with change in TO at six or 12 months. Conclusions: Within DREAM, TO was weakly correlated with DED signs, explaining <5% variability in signs. Changes in tear osmolarity were not associated with changes in signs and symptoms of DED, indicating that the association may not be causal.

Assessment of meibomian gland drop-out and visibility through a new quantitative method in scleral lens wearers: A one-year follow-up study.

OBJECTIVES: To validate a previously developed algorithm based on the visibility of meibomian gland images obtained with Cobra fundus camera and to assess the changes in meibomian glands in scleral lens wearers over one year of lens wear. METHODS: Infrared meibography was obtained from the upper eyelid using the Cobra fundus camera in forty-three volunteers (34.2 ± 10.1 years). Meibographies were classified into 3 groups: Group 1 = good subjective gland visibility and gland drop-out < 1/3 of the total area; Group 2 = low visibility and gland drop-out < 1/3; and Group 3 = low visibility and gland drop-out > 1/3. Meibomian gland visibility metrics were then calculated using the developed algorithm from the pixel intensity values of meibographies. Repeatability of new metrics and their correlations with gland drop-out were assessed. Meibographies and ocular symptoms were also assessed after 1 year of scleral lens wear in 29 subjects. RESULTS: Gland drop-out percentage was not statistically different between groups 1 and 2 (p = 0.464). Nevertheless, group 1 showed higher grey pixel intensity values than the other groups. Statistically significant correlations were found between gland visibility metrics and gland drop-out percentage. Repeatability was acceptable for all metrics, coefficient of variation achieving values between 0.52 and 3.18. While ocular symptoms decreased with scleral lens wear (p < 0.001), no statistically significant differences were found in gland drop-out percentage (p = 0.157) and gland visibility metrics (p > 0.217). CONCLUSIONS: The proposed method can assess meibomian gland visibility in an objective and repeatable way. Scleral lens wear appears to not adversely affect meibomian gland drop-out and visibility while might improve dry eye symptoms after one year of lens wear. These preliminary results should be confirmed with a control group.

Ocular surface assessment and morphological alterations in meibomian glands with non-contact meibography in electronic cigarette smokers.

PURPOSE: The study aimed to evaluate the ocular surface and meibomian gland morphology in electronic cigarette (e-cigarette) smokers. METHODS: The upper and lower eyelids of 25 male e-cigarette smokers and 25 healthy male non-smoker patients were evaluated using Sirius meibography. Meibomian glands loss was automatically calculated using Phoenix meibography imaging software module, with the result obtained as percentage loss. Ocular Surface Disease Index (OSDI) questionnaire, tear breakup time test, and Schirmer II test were administered and performed in all cases. RESULTS: The mean e-cigarette smoking duration was 4.9 ± 0.9 (range, 3.4-7) years. While the mean Schirmer II test value was 9.16 ± 2.09 mm in e-cigarette group, it was 11.20 ± 2.14 mm in control group (p=0.003). Mean tear breakup time was 6.96 ± 2.31 seconds in e-cigarette group and 9.84 ± 2.13 seconds in control group (p=0.002). The mean OSDI value was 28.60 ± 6.54 and 15.16 ± 7.23 in e-cigarette and control groups, respectively (p<0.001). In Sirius meibography, the average loss for the upper eyelid was 23.08% ± 6.55% in e-cigarette group and 17.60% ± 4.94% in control group (p=0.002), and the average loss for the lower eyelid was 27.84% ± 5.98% and 18.44% ± 5.91%, respectively (p<0.001). Additionally, a significant positive correlation was identified between the loss rates for both upper and lower eyelid meibography with e-cigarette smoking duration (r=0.348, p<0.013 and r=0.550, p<0.001, respectively). CONCLUSION: Long-term e-cigarette smoking causes damage to the meibomian glands; therefore, meibomian gland damage should be considered in ocular surface disorders due to e-ci-garette smoking.

Tear film layers and meibomian gland assessment in patients with type 1 diabetes mellitus using a noninvasive ocular surface analyzer: a cross-sectional case-control study.

PURPOSE: To assess the tear film layers and Meibomian glands by a noninvasive ocular surface analyzer in patients with and without type 1 diabetes mellitus (T1DM). METHODS: Eighty-eight participants were enrolled in this study: 44 patients with T1DM without diabetic retinopathy, and 44 patients as a control group, between 18 and 49 years old. Limbal and bulbar redness classification, lipid layer thickness (LLT), tear meniscus height (TMH), first and mean noninvasive tear break-up time (FNIBUT and MNIBUT, respectively), and Meibomian glands loss (MGL) were assessment through the ICP Ocular Surface Analyzer (OSA). Schirmer's I test (SIT), the fluorescein tear break-up time test (TFBUT), OSDI and SPEED questionnaires, and percentage of glycosylated hemoglobin (HbA1c) were also tested. RESULTS: The T1DM group showed higher limbal and bulbar redness (p = 0.010) and lower LLT (p < 0.001), TMH (p < 0.001), FNIBUT (p < 0.001), MNIBUT (p < 0.001), SIT (p = 0.001), and TFBUT (p < 0.001) than the control group. A higher percentage of MGL was found in the T1DM group in the upper (p = 0.097) and lower (p < 0.001) eyelids. No significant differences were found in dry eye symptoms across the OSDI and SPEED questionnaires between the two groups. CONCLUSION: Patients with T1DM without signs of retinopathy showed involvement of the mucoaqueous and lipid layers of the tear film, as well as a higher percentage of MGL, using a noninvasive analyzer. Dry eye disease in people with T1DM cannot be ruled out by anamnesis and subjective symptom questionnaires alone; therefore, these patients should undergo regular anterior pole examinations.