Dry Eye Group Research Articles

A preliminary study on the tear matrix metalloproteinase 9 point-of-care assay using a domestic kit

Objective: To compare the point-of-care assays for tear matrix metalloproteinase 9 (MMP-9) using domestic and InflammaDry kits, and to evaluate the feasibility of diagnosing dry eye with the domestic kit. Methods: It was a cross-sectional study. Thirty dry eye patients and 30 age-and sex-matched normal volunteers were continuously enrolled in this cross-sectional study from June 2022 to July 2022. Both domestic and InflammaDry kits were used to detect the tear MMP-9 levels. The positive rates were recorded for qualitative analysis, and the gray ratios of bands (the gray value of detection bands to that of control bands) were collected for quantitative analysis. The correlations of MMP-9 levels with age, ocular surface disease index, fluorescence tear break-up time, tear meniscus height, Schirmer's Ⅰ test score, corneal fluorescein staining score, and meibomian gland dropout were analyzed. The Mann-Whitney U test, paired Chi-square test, Kappa test, and Spearman's correlation coefficient were used for statistical analysis. Results: There were 14 males and 16 females (30 eyes) in the control group, and their age was (39.37±19.55) years. In the dry eye group, 11 males and 19 females (30 eyes), aged (46.87±17.85) years, had moderate to severe dry eye. The positive rates of MMP-9 in tear fluid were significantly different between dry eye patients (InflammaDry: 86.67%; domestic kit: 70.00%) and controls (InflammaDry: 16.67%, P<0.001; domestic kit: 6.67%, P<0.001). Although the sensitivity of the domestic kit was lower than that of the InflammaDry kit (70.0% vs. 86.7%, P=0.001), the specificity was higher (93.3% vs. 83.3%, P=0.001). In dry eye patients, the positive coincidence rate was 80.7% (21/26), the negative coincidence rate was 100% (4/4), and the total coincidence rate was 83.3% (25/30), with no significant difference between the two kits (McNemar test: χ2=3.20, P>0.05), and the results of both kits were consistent (Kappa=0.53, P=0.001). The Spearman's correlation coefficient showed the gray ratios using both kits were positively correlated with the corneal fluorescein staining score (InflammaDry: ρ=0.48, P<0.05; domestic kit: ρ=0.52, P=0.003). Conclusion: The performances of the domestic and InflammaDry kits are consistent in the point-of-care assay for tear MMP-9, and the domestic kit has lower sensitivity but higher specificity.

Evaluation of dry eyes in children with vernal kerato-conjunctivitis using clinical tests and ocular surface analysis.

To evaluate dry eyes in children with vernal kerato-conjunctivitis (VKC) and correlate it with symptoms, clinical findings, and ocular surface analysis (OSA) parameters. Children with clinically diagnosed VKC underwent complete ophthalmological examination, Schirmer's testing, modified ocular surface disease index (OSDI) scoring, Bonini grading, fluorescein tear-film break-up time (TBUT), VKC - Collaborative Longitudinal Evaluation of Keratoconus (CLEK) scoring, and OSA. Children with a TBUT of < 10 s were defined to have dry eyes. The above-mentioned parameters were compared between dry eye and non-dry eye VKC children. The mean age of the 87 children included in the study was 9.1 ± 2.9 years. Dry eyes were seen in 60.9% [95% confidence interval (CI); 51% to 71%]. The mean TBUT was 13.4 ± 3.8 and 5.9 ± 1.9 s in non-dry and dry eye groups, respectively (P < 0.001). The mean value of Schirmer's test was 25.9 ± 9.8 and 20.8 ± 8.6 mm in the non-dry and dry eye groups, respectively (P = 0.01). The two groups did not differ in their OSDI scores, Bonini grading, and CLEK scores. The OSA parameter of non-invasive break-up time (NIBUT) was 8.3 ± 3.2 s in non-dry eye group and 6.4 ± 2.9 s in dry eye group, P = 0.008. The lower lid Meibomian gland (MG) loss was 7.4% in non-dry eye group and 12.2% in dry eye group, P = 0.028. Other OSA parameters did not differ significantly among the two groups. Dry eyes are seen in two-thirds of pediatric VKC. Evaluation of dry eyes should be incorporated in their clinical evaluation. Among OSA parameters, NIBUT and lower lid MG loss are associated with dry eyes in pediatric VKC patients.

Staining characteristics of the lid margin

Background Vital stains are very important for evaluation of Marx line (ML) location, regularity, and lid wiper epitheliopathy. ML score can be used to assess Meibomian gland function, whereas lid wiper epitheliopathy is considered an early indicator for tear film instability. Aim To evaluate staining characteristics of the lid margin in different disease conditions, such as dry eye, Meibomian gland dysfunction (MGD), and eyelid malposition using vital stains. Patients and methods A total of 80 patients aged between 40 and 60 years were included in this study. Patients were already diagnosed as having dry eye, MGD, and eyelid malposition (ectropion and entropion). Vital stains (fluorescein, rose Bengal, and Lissamine green) were used to assess the lid wiper area and ML position in these diseases. Results The included 80 participants comprised 44 females and 36 males aged from 40 to 60 years, with mean±SD of 45.10 ± 5.42 years for normal participants, and it was 47.35 ± 6.57 years for dry eye participants. ML was straight in 75% of normal group, but it was irregular in 65% of the dry eye group, 100% of the malposition group, and 70% of MGD group. Lid wiper epitheliopathy was mild degree in one-third of normal participants. In dry eye participants, it was moderate and severe (45% for each). Conclusion ML is irregular and moved gradually anterior to the eyelid margin with different diseases such as dry eye, MGD, and eyelid malposition. Lid wiper epitheliopathy provides information about the location of ML, and it can be easily seen by using the vital staining, and it is useful in the diagnosis of tear film instability.

Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain

Dry eye disease (DED) affects nearly 55% of people worldwide; several studies have proposed that central sensitization and neuroinflammation may contribute to the developing corneal neuropathic pain of DED, while the underlying mechanisms of this contribution remain to be investigated. Excision of extra orbital lacrimal glands established the dry eye model. Corneal hypersensitivity was examined through chemical and mechanical stimulation, and open field test measured the anxiety levels. Restingstate fMRI is a method of functional magnetic resonance imaging (rs-fMRI) was performed for anatomical involvement of the brain regions. The amplitude of low-frequency fluctuation (ALFF) determined brain activity. Immunofluorescence testing and Quantitative real-time polymerase chain reaction were also performed to further validate the findings. Compared with the Sham group, ALFF signals in the supplemental somatosensory area, secondary auditory cortex, agranular insular cortex, temporal association areas, and ectorhinal cortex brain areas were increased in the dry eye group. This change of ALFF in the insular cortex was linked with the increment in corneal hypersensitivity (p < 0.01), c-Fos (p < 0.001), brain-derived neurotrophic factor (p < 0.01), TNF-α, IL-6, and IL-1β (p < 0.05). In contrast, IL-10 levels (p < 0.05) decreased in the dry eye group. DED-induced corneal hypersensitivity and upregulation of inflammatory cytokines could be blocked by insular cortex injection of Tyrosine Kinase receptor B agonist cyclotraxin-B (p < 0.01) without affecting anxiety levels. Our study reveals that the functional activity of the brain associated with corneal neuropathic pain and neuroinflammation in the insular cortex might contribute to dry eye-related corneal neuropathic pain.

T-Cell Repertoire Analysis in the Conjunctiva of Murine Dry Eye Model.

Dry eye is closely related to the activation and proliferation of immune cells, especially T cells. However, the determination of the preferential T-cell clonotypes is technically challenging. This study aimed to investigate the characterization of T-cell receptor (TCR) repertoire in the conjunctiva during dry eye. A desiccating stress animal model was established using C57/BL6 mice (8-10 weeks, female). After 7 days of stress stimulation, the slit-lamp image and Oregon-green-dextran staining were used to evaluate the ocular surface injury. Periodic acid-Schiff staining was used to measure the number of goblet cells. Flow cytometry was used to detect the activation and proliferation of T cells in the conjunctiva and cervical lymph nodes. Next-generation sequencing was used to detect the αβ TCR repertoire of the conjunctiva. The αβ TCR diversity increased significantly in the dry eye group, including the higher CDR3 amino acid length, marked gene usage on TCR V and J gene segments, extensive V(D)J recombination, and distinct CDR3 aa motifs. More important, several T-cell clonotypes were uniquely identified in dry eye. Furthermore, these perturbed rearrangements were reversed after glucocorticoid administration. A comprehensive analysis of the αβ TCR repertoire in the conjunctiva of the dry eye mouse model was performed. Data in this study contributed significantly to the research on dry eye pathogenesis by demonstrating the TCR gene distribution and disease-specific TCR signatures. This study further provided some potential predictive T-cell biomarkers for future studies.

Effects of Non-invasive Keratograph Break-Up Time on the Repeatability of Keratometry Measurements

Purpose: To evaluate the effects of the non-invasive keratograph break-up time on the repeatability of keratometric measurements derived using the Keratograph 5M in patients with dry eye syndrome.Methods: Thirty-six patients with dry eye and 30 controls were enrolled. We measured keratometric values twice in all subjects and explored whether the two measurements differed by more than 0.5 diopter (D) (the absolute value). We also evaluated the relationship between the absolute difference and the non-invasive keratograph break-up time (NIKBUT).Results: The intraclass correlation coefficients for astigmatism, flat keratometry (K), steep K, and mean K were all higher than 0.95 in patients, thus lower than in controls. The proportion of eyes with absolute differences over 0.5 D between the two keratometric values differed significantly between the dry eye and control groups in terms of the flat K and Kmax values (p = 0.033, 0.037). The average NIKBUT was negatively correlated with the absolute differences in Kmax and astigmatism (p = 0.030, R&lt;sup&gt;2&lt;/sup&gt; = 0.134 and p = 0.017, R&lt;sup&gt;2&lt;/sup&gt; = 0.160).Conclusions: In patients with dry eye syndrome, keratometric measurements are reliably repeatable, but slightly less so than in normal controls. The proportions of eyes exhibiting absolute keratometric differences over 0.5 D (two measurements) differed in the dry eye and control groups. The lower the non-invasive keratograph break-up time, the poorer the repeatability of keratometric measurements in the dry eye group. Therefore, care is required when obtaining keratometric values for such patients.

Evaluating the Differences Between Fluorescein Tear Break-up Time and Noninvasive Measurement Techniques.

To compare fluorescein tear break-up time (BUT) and noninvasive BUT measured using interferometry and corneal topography. We investigated 34 eyes of 34 patients with dry eye (mean age 39.2±8.3 years) and 16 eyes of 16 non-dry eye subjects (33.5±6.5 years). Tear film stability was measured using fluorescein BUT, noninvasive BUT (NIBUT)-DR1 with an interferometer, and noninvasive keratographic BUT (NIKBUT)-first and average using corneal topography. Correlations between fluorescein BUT and noninvasive BUT parameters were determined statistically. The noninvasive BUTs were compared between the dry eye and non-dry eye groups. The agreement between fluorescein and noninvasive BUTs was described using Bland-Altman analysis. Fluorescein BUT was significantly correlated with NIBUT-DR1, NIKBUT-first, and NIKBUT-average. The Bland-Altman analysis revealed bias and 95% limits of agreement between fluorescein BUT and noninvasive BUTs as follows: NIBUT-DR1: 2.07 s, -5.33 to 9.46 s; NIKBUT-first: 3.39 s, -5.46 to 12.24 s; NIKBUT-average: 6.61 s, -1.58 to 14.79 s. The noninvasive BUTs were significantly different between the two groups. When NIBUT-DR1, NIKBUT-first, and NIKBUT-average with Bland-Altman correction were used as an index for dry eye, the cut-off values were 7.1, 8.4, and 11.6 s, respectively. The sensitivities were 0.735, 0.818, and 0.727 and specificities were 0.500, 0.437, and 0.562, respectively. Fluorescein BUT and noninvasive BUTs were significantly correlated, and noninvasive BUTs had higher values than fluorescein BUT. Considering the differences between fluorescein BUT and noninvasive BUTs, noninvasive methods can be used as effective tool for diagnosing dry eye.

Categorization of the Aqueous Deficient Dry Eye by a Cut-Off Criterion of TMH Measured with Tearscope.

A decrease of the Tear Meniscus Height (TMH) has been proposed as a useful indicator for Aqueous Deficient Dry Eye (ADDE) categorization. The present study aimed to calculate a TMH cut-off criterion for the categorization or severity assessment of ADDE with the Tearscope. 200 participants with a previous Dry Eye Disease (DED) diagnosis according to TFOS DEWS-II criteria were recruited. TMH by slit-lamp illumination and Lipid Layer Pattern (LLP) with Tearscope were assessed to categorise the participants into the ADDE or the Evaporative Dry Eye (EDE) group. The ADDE group was also subdivided into Mild-moderate ADDE and Moderate-severe ADDE based on TMH with slit-lamp. Additionally, the TMH was measured by Tearscope (TMH-Tc). Receiver Operating Characteristics showed that the TMH-Tc have a diagnostic capability to differentiate between ADDE and EDE participants, and between Mild-moderate or Moderate-severe ADDE, with a cut-off value of 0.159 mm (AUC = 0.843 ± 0.035, p < 0.001; sensitivity: 86.4%; specificity: 75.4%) and 0.105 mm (AUC = 0.953 ± 0.025, p < 0.001; sensitivity: 98.1%; specificity: 80.0%), respectively. The present study proposed a cut-off criterion to differentiate between ADDE and EDE participants, or between ADDE severities through TMH assessed by Tearscope.

Variability of autonomic nerve activity in dry eye with decreased tear stability

The autonomic nervous system plays a crucial role in the maintenance of homeostasis. Neurogenic inflammation due to decreased stability of tear film may induce changes in autonomic nerve activity, which could be associated with symptom expression.This study aimed to measure biological parameters that represent autonomic nerve activity in dry eye (DE)s caused by tear film dysfunction and investigate their relationship with symptom intensity. This prospective, cross-sectional, comparative study evaluated 34 eyes of 34 participants (mean age: 52.5 ± 13.4 years; range: 20-81 years) without keratoconjunctival damage. Nineteen eyes in the DE group showed DE symptoms and tear break-up time (TBUT) of ≤5 seconds (short TBUT DE); the 15 eyes in the non-DE group showed no DE symptoms. Autonomic nerve activity was measured for 10 minutes-starting and ending 5 minutes before and after instilling ophthalmic solution-and evaluated using the low-frequency component (LF) to the high-frequency component (HF) ratio of heart rate variability (autonomic balance). The pre-ophthalmic solution administration LF/HF ratio was not significantly different (P = 0.59) between the two groups, however, the standard deviation of the LF/HF ratio (LF/HF-SD) tended to be higher in the DE group than that in the non-DE group (P = 0.086). The DE symptom intensity was significantly related to LF/HF-SD (P = 0.005), which significantly decreased after ophthalmic solution administration in the DE group (P = 0.04). The large fluctuations in autonomic balance may be key for the understanding of the mechanism underlying DE symptoms.

The Incidence and Risk Factors for Dry Eye After Pediatric Strabismus Surgery.

This study aimed to investigate the incidence and risk factors for dry eye after pediatric strabismus surgery. Children aged 5-12years who underwent strabismus surgery were included in this single-center, prospective, cohort study. The ocular surface assessments were conducted 1day before and 1, 4, and 8weeks after surgery. The main outcome measures were the incidence of dry eye after strabismus surgery and associated risk factors. A total of 84 eyes (48 children) that underwent strabismus surgery were included in the study. The mean age at surgery was 7.21years. The incidence of dry eye was 47.62% at 1week, 10.71% at 4weeks, 0% at 8weeks after surgery. The preoperative tear breakup time (BUT) was lower in the dry eye group than that in the non-dry eye group (P ≤ 0.01). The univariate analysis showed that preoperative BUT was significantly associated with the incidence of dry eye after pediatric strabismus surgery (odds ratio [OR] 0.647, confidence interval [CI] 0.503-0.833, P ≤ 0.01). Dry eye commonly occurs after pediatric strabismus surgery. Tear film instability is more common than deficient aqueous tear production in patients with dry eye after surgery. Children with a low preoperative BUT are more likely to develop dry eye after strabismus surgery.

Evaluation of the repeatability of optical coherence tomography in patients with age-related cataract associated with dry eye.

To assess the repeatability of a new optical biometer (OA-2000, Tomey, Japan) based on swept-source optical coherence tomography (SS-OCT) and Placido-disk topography in dry eyes with cataracts. A cross-sectional study was performed. Two hundred sixteen eyes of 216 cataract patients were enrolled in our hospital from March 2020 to December 2020. According to the subjective symptoms and objective examination of dry eye, the patients were assigned to dry eye group and non-dry eye group. Axial length (AL), keratometry readings (K), lens thickness (LT), anterior chamber depth (ACD), central corneal thickness (CCT) and white-to-white (WTW) distance were measured by one skilled operator. The repeatability of each parameter based on within-subject standard deviation (Sw), repeatability limit of standard deviation (2.77Sw), coefficient of variation (CoV) and intra-class correlation coefficient (ICC) was evaluated. There was no significant difference in age and gender between the two groups. NiaBUT and NifBUT in the dry eye group were significantly lower than those in the non-dry eye group (p < 0.05). The ICC mean values of AL, K1, K2, Km, ACD, LT and CCT were all greater than 0.960, except WTW. In the dry eye group, except CCT and WTW, the Sw scores for other biometric parameters were lower than 0.201, 2.77Sw scores were lower than 0.557, CoV(%) was less than 1%, and ICC mean values were greater than 0.964. Among them, the Sw scores for AL, LT and ACD were lower than 0.035, the 2.77Sw scores were lower than 0.097, and the ICC mean values are greater than 0.990. The ocular biological parameters measured by SS-OCT have good repeatability for age-related cataract patients with dry eyes, in which the AL, LT and ACD are the highest repeatable. However, more attention should be paid for WTW in clinical application since repeatability influence.

Association of Dry Eye Diseases and Auditory Sensitivity.

This study aimed to evaluate the association between dry eye and inner ear diseases in a Korean population. Methods: Data from the Korean National Health and Nutrition Survey (KNHANES V, 2010–2012), a national cross-sectional health examination and survey, were collected by the Korea Centers for Disease Control and Prevention. The association between dry eye and inner ear disease was determined using the chi-square test and logistic regression analysis. The individuals were divided into two age groups (<60 and ≥60 years). Results: In total, 17,542 individuals (n = 11,932 in the <60 years group and n = 5610 in the ≥60 years group) were enrolled. After adjusting for confounding factors, the logistic regression model revealed that the associated factors were dizziness and loss of balance experience (OR, 1.315; 95% CI, 1.143–1.513), self-awareness of abnormal voice (OR, 1.372; 95% CI, 1.120–1.679), subjective hearing discomfort (OR, 1.278; CI, 1.084–1.506), and tinnitus (OR, 1.265; 95% CI, 1.101–1.453). The inversely associated factor for dry eye was bilateral hearing loss (OR, 0.497; 95% CI, 0.367–0.672). The hearing threshold was lower in the dry eye group than in the non-dry eye group (p < 0.05). Conclusions: Tinnitus was associated with dry eye and bilateral hearing loss was inversely associated with dry eye. These results suggest that hypersensitivity of the senses and nerves, which is neuropathic hyperesthesia, is one of the main mechanisms of dry eye. Treatment of neuropathy may help in treating dry eye associated with dizziness or tinnitus.

Changes in the tear film and meibomian gland morphology between preclinical dry eye and normal subjects represented by ocular surface disease index scores

Tear film and MG morphology play an essential role in detecting dry eyes and Meibomian Gland Dysfunction (MGD). Previous studies have reported these changes in cases diagnosed with dry eyes. However, it is important to study these changes among subjects with symptoms of dry eyes without signs. Hence, this study evaluated the changes in the tear film and meibomian gland (MG) morphology among subjects with pre-clinical dry eye and compared it with the normals defined by the Ocular Surface Disease Index score. One hundred and fifty subjects were enrolled in this prospective cross-sectional study. All the subjects completed the Ocular Surface Disease Index (OSDI) questionnaire and the Computer Vision Syndrome Questionnaire (CVS-Q). Tear film tests such as non-invasive break-up time (NIBUT), tear meniscus height (TMH), lipid layer pattern, Schirmer's test, and corneal staining were performed. Images were captured from both the upper and the lower eyelids to study the MG morphology. TMH, MG length, thickness, loss, and tortuosity were measured using ImageJ software. Subjects were differentiated into two groups based on an OSDI threshold score of ≥13 as preclinical dry eye and normals. Among all the subjects, 43.6% of them were categorized as pre-clinical dry eye, and 56.4% as normals. In the pre-clinical dry eye group, a significant reduction in NIBUT (Z = −2.13, p = 0.03) and MG length of the lower lid (Z = −2.58, p = 0.01) was found when compared to normals. TMH, Schirmer's test, and MG width did not vary among both groups (p > 0.05). Similarly, MG loss and tortuosity score was higher in the pre-clinical dry eye group, but did not show any statistical significance (p > 0.05). The majority of the young individuals presenting for the regular eye examination may have pre-clinical dry eye based on their OSDI scores. Hence, it is important to administer the OSDI questionnaire and perform non-invasive tests such as NIBUT and IR imaging of MG as a part of the routine eye examination.

Rear 4-min Schirmer test, a modified indicator of Schirmer test in diagnosing dry eye

This study aims to investigate the reliability and efficacy of rear 4-min Schirmer test, as a supplement indicator, in assessing tear secretion and diagnosing dry eye. 180 participants were enrolled in this study. Schirmer test I without anaesthesia was performed once on both eyes to determine the value of normal Schirmer test. The values of tear secretion were recorded at each minute. Other examinations included the following: the ocular surface disease index (OSDI), the standard patient evaluation of eye dryness (SPEED), fluorescein stain, tear film break-up time (BUT), and Meibomian gland (MG) secretion grading. The participants were divided into dry eye (DE) group and non-dry eye (ND) group. The values of the 2-min Schirmer test, rear 3-min Schirmer test, rear 4-min Schirmer test, and 5-min Schirmer test were 5.36 ± 4.63, 5.57 ± 2.11, 7.21 ± 4.13, and 10.93 ± 6.30, respectively, in the DE group. These indicators were 8.25 ± 6.80, 2.73 ± 2.31, 7.36 ± 3.42, and 11.84 ± 6.16, respectively, in the ND group. The rear 4-min Schirmer test had a significant correlation with OSDI and SPEED in the DE group (r = − 0.242/ − 0.183) and in the ND group (r = − 0.316/ − 0.373). Meanwhile, the rear 4-min Schirmer test had a stronger connection with fBUT (r = 0.159) and MG secretion (r = − 0.162) in the DE group and also had higher accuracy in diagnosing severe DE and borderline DE. In conclusion, the rear 4-min Schirmer test may be a supplement indicator in assessing tear secretion and diagnosing DE.

Preoperative dry eyes disease in cataract patients with deficient tear break up time: evaluation of OSDI questionnaire, its subcategories and Keratograph 5M device results.

To evaluate preoperatively dry eye disease (DED) in patients with pathological Tear Break Up Time (TBUT), utilising subjective Ocular Surface Disease Index (OSDI) with its subcategories and objective Keratograph 5M characteristics. Fifty-four cataract patients were included in this prospective study having a screening slit lamp TBUT of less than 10s and more or equal to 5s. Subjective evaluation of DED was performed with OSDI questionnaire and objective evaluation with Keratograph 5M. Tear Meniscus Height (TMH), bulbar and limbal redness and meibography grade were evaluated. Further analysis of OSDI subcategories, Visual Function Related (VFR), Ocular Symptoms related (OS) and Environmental Triggered (ET), was performed with linear and logistic multivariate regression models. Age, gender and logMAR visual acuity (VA) were also included in our models. Following the initial TBUT screening we identified 27(50%) normal and 27(50%) dry eye patients, using OSDI questionnaire. There was no statistical difference in TMH (p = 0.64), bulbar redness (p = 0.54), limbal redness (p = 0.72) and meibography grade (p = 0.25), between normal and dry eye OSDI group. In our regression analysis, average logMAR VA was highly associated with a higher total OSDI score (p < 0.001) and with a higher OSDI-VFR score (p < 0.001).Female gender was associated with a higher OSDI-ET score (p = 0.03).Multivariate logistic regression models were performed by sorting patients into 2 categories of normal and dry eye group according to their total OSDI,OSDI-VRF,OSDI-OS and OSDI-ET score. An increase in logMAR VA increased the odds of having abnormal total OSDI score (p = 0.007) and OSDI-VFR score (p = 0.006).Females had increased odds of having abnormal OSDI-ET score (p = 0.044). Clinicians should be aware of OSDI limitations when screening cataract patients for dry eyes, as there is high correlation with VA. Female patients were more susceptible to environmental factors. Keratograph results should be interpreted with caution when they are evaluated in conjunction with OSDI during preoperative assessment of DED in cataract patients.

Evaluations of wavefront aberrations and corneal surface regularity in dry eye patients measured with OPD Scan III.

To compare the wavefront aberrations and corneal surface regularity between dry eye (DE) patients and normal subjects and assess its diagnostic performance for DE measured with OPD Scan-III. Fifty right eyes of 50 DE patients and 31 right eyes of normal subjects were included. The examinations for ocular surface including logarithm of the minimum angle of resolution best-corrected distance visual acuity (logMAR BCVA) the ocular surface disease index (OSDI), tear film break-up time (TBUT) and corneal fluorescein staining (CFS). OPD Scan-III was used to measure anterior corneal aberrations including total corneal aberrations, high order aberration (HOA), coma, trefoil, spherical aberration (SA), standard deviation of corneal power (SDP), surface regularity index (SRI) and surface asymmetry index (SAI). Statistical analysis were assessed with nonparametric tests and Spearman's correlations. All parameters were also analyzed for sensitivity, specificity, and receiver operating characteristics (ROC) curves. Wavefront aberrations parameters including total corneal aberrations, HOA, coma, trefoil, and SA in DE group were significantly higher than those in normal group (P<0.001). Corneal surface regularity parameters including SRI and SAI in DE group were significantly higher than both in normal group (P<0.05). All the wavefront aberrations parameters had significant correlations with ocular surface parameters (P<0.05). The logMAR BCVA had positive correlations with SAI and SRI (all P<0.001). CFS scores had positive correlations with SAI and SRI (all P<0.001). All the wavefront aberrations parameters showed good diagnosis sensitivity and specificity, however, the corneal regularity parameters showed only good specificity but poor sensitivity. The cut-off value selected for trefoil in diagnosis DE showed the highest area under the curve (AUC, 0.921) values as compared to the other parameters with sensitivity of 0.955 and specificity of 0.867. Wavefront aberrations and corneal surface regularity are increased in DE patients and also correlated with ocular surface parameters. Wavefront aberrations parameters have potential to be indicators to diagnosis and monitor DE.

The Effect of Past Cataract Surgery within the Medium to Long-Term Period on Patients with Dry Eye Disease.

This study investigates the effects of cataract surgery on dry eye parameters of patients with dry eye disease (DED) in the medium- to long-term post-surgical period (6 months to 5 years). A cross-sectional study was conducted on 438 eyes on first visit to a tertiary clinic (219 eyes with cataract surgery within timeframe, i.e., pseudophakic dry eye group, 219 comparison eyes without such history, i.e., comparison dry eye group). Parameters evaluated include Ocular Surface Disease Index (OSDI) and standard examination for DED. A significantly greater proportion of pseudophakic dry eye group (50%) experienced frequent blurred vision (≥1 episode per week) compared to dry eye control group (38%) (OR = 1.66, 95%CI 1.13, 2.44). Those with ocular discomfort before surgery were more likely to experience blurring at least once a day. However, a significantly greater proportion of the pseudophakic dry eye group (34%) had Schirmer’s I >8mm compared to the comparison group (25%) (OR = 0.605, 95% CI 0.398, 0.921), though the difference was not clinically significant (7.51 mm versus 6.51 mm, p > 0.05). Other DED signs (e.g., overall OSDI score, Tear Break-up Time) were not found to be worse among pseudophakic dry eye group. Pre-operative counselling and preventative measures should be undertaken, especially those with suggestive symptoms pre-operatively.

Detection of the spontaneous blinking pattern of dry eye patients using the machine learning method

Objective: To establish a method to record the spontaneous blink pattern with a machine learning model, and to clarify the spontaneous blink pattern in patients with dry eye. Methods: It was a cross-setional study.We selected 357 dry eye patients (102 males and 255 females), aged (46.2±13.3) years, who visited corneal specialist clinics of Beijing Tongren Eye Center in 2019, as the dry eye group. The control group enrolled 152 normal controls, including 32 males and 120 females, aged (48.1±13.9) years. All participants completed the Ocular Surface Disease Index questionnaire, blink video capture, lipid layer thickness measurement, tear break-up time measurement, corneal fluorescein staining, and Schirmer Ⅱ test. Based on the assembled model built using UNet image segmentation algorithm and ResNet image classification algorithm, single frames of the blink video were analyzed, and then the palpebral opening height of each frame was obtained in order to establish a spontaneous blink wave. Finally, the characteristics of spontaneous blinks in dry eye patients were analyzed based on different types of complete blinks (types A, B and C) and partial blinks (types Ⅰ, Ⅱ and Ⅲ). Independent sample t test and Wilcoxon rank-sum test were used to judge if there was significant difference between the dry eye group and the normal group. Results: The accuracy of the segmentation model and the classification model was 96.3% and 96.0%, respectively, and the consistency with the manual analysis was 97.9%. In dry eye patients, the number of blinks was 30 (18, 42)/min, which was higher than that in normal controls [20 (9, 46)/min] (U=18 132.50, P=0.002). The number of complete blinks in dry eye cases was significantly lower than that in normal controls [6 (3, 24)/min vs. 12 (3,33)/min; U=12 361.00, P=0.016], and the number of partial blinks was significantly higher than that in normal controls [15 (6, 27)/min vs. 3 (0, 10)/min; U=22 839.00, P<0.001]. In complete blinks, the proportion of type A blinks in dry eye patients was significantly higher than that in normal controls [53.7% (2 796/5 177) vs. 39.3% (633/1 698); χ²=101.83, P<0.001]; in partial blinks, the proportion of type Ⅱ blinks in dry eye patients was significantly higher than that in normal controls [36.0%(2 334/6 477) vs. 29.6%(126/426); χ²=6.99, P=0.007]. The average interblink interval of dry eye patients was 1.2 s, which was not significantly different from that of normal controls (1.1 s; U=15 230.00, P=0.093). The eyelid closed phase of dry eye patients was 0.8 s, which was significantly shorter than that of normal controls (1.3 s; U=16 291.50, P=0.006). There were no significant differences in eyelid closing phase, early opening phase and late opening phase between the two groups (all P>0.05). Conclusions: In dry eye patients, the number of partial blinks increased, the number of complete blinks decreased, and the duration of eyelid closed phase shortened significantly. The main blink patterns of dry eye patients included type Ⅱ partial blinks with a reduced closure amplitude and type A complete blinks with a shortened closure time.

Investigation of changes in the activity and function of dry eye-associated brain regions using the amplitude of low-frequency fluctuations method.

Objective: The local characteristics of spontaneous brain activity in patients with dry eye (DE) and its relationship with clinical characteristics were evaluated using the amplitude of low-frequency fluctuations (ALFF) method.Methods: A total of 27 patients with DE (10 males and 17 females) and 28 healthy controls (HCs) (10 males and 18 females) were recruited, matched according to sex, age, weight and height, classified into the DE and HC groups, and examined using functional magnetic resonance imaging (fMRI) scans. Spontaneous brain activity changes were recorded using ALFF technology. Data were recorded and plotted on the receiver operating characteristic (ROC) curve, reflecting changes in activity in different brain areas. Finally, Pearson correlation analysis was used to calculate the potential relationship between spontaneous brain activity abnormalities in multiple brain regions and clinical features in patients with DE. GraphPad Prism 8 (GraphPad Software, Inc.) was used to analyze the linear correlation between the Hospital Anxiety and Depression Scale and ALFF value.Results: Compared with HCs, the ALFF values of patients with DE were decreased in the right middle frontal gyrus (MFG)/right inferior orbitofrontal cortex (OFC), left triangle inferior frontal gyrus, left MFG, and right superior frontal gyrus. In contrast, the ALFF value of patients with DE was increased in the left calcarine.Conclusion: There are significant fluctuations in the ALFF value of specific brain regions in patients with DE versus HCs. This corroborates previous evidence showing that the symptoms of ocular surface damage in patients with DE are related to dysfunction in specific brain areas.

Serum vitamin D level and micro-ribonucleic acid-146a expression pattern in dry eye disease associated with rheumatoid arthritis in an Egyptian population

Aim The aim of this research was to study serum vitamin D and micro-ribonucleic acid-146a (miRNA-146a) expression in dry eye disease (DED) associated with rheumatoid arthritis (RA) and their clinical correlations to DED parameters. Setting and design This is an observational cross-sectional study that was conducted at Cairo University, Cairo, Egypt. Patients and methods The study participants were divided into three groups: group A, DED/RA (n=35); group B, non-DED/RA (n=36); and group C, non-DED/non-RA (n=35). All participants were assessed for ocular surface disease index, tear breakup time (TBUT), serum level of vitamin D, and miRNA-146a expression. In the DED group (with TBUT˂10 s), DED evaluation was performed, including Schirmer I test, corneal and conjunctival scoring, and impression cytology. Results The mean serum vitamin D level was 17.1±16.2 ng/ml in group A, 35.1±13.4 ng/ml in group B, and 38.1±8.7 ng/ml in group C, with a statistically significant difference (P˂0.001). The mean miRNA-146a expression was 4.7±1.5 in group A compared with 4.8±1.8 in group B (P=0.959) and 1.0±0.1 in group C (P˂0.001, compared with each of groups A and B). In group A, serum vitamin D level showed a significant moderate negative correlation to each of impression cytology grading (r=−0.456, P=0.019) and miRNA-146a expression (r=−0.387, P=0.041). Both serum vitamin D and miRNA-146a expression showed nonsignificant correlations to ocular surface disease index, TBUT, Schirmer I test, and corneal and conjunctival scoring. Conclusion DED associated with RA showed a statistically significantly lower serum level of vitamin D, which was negatively correlated to impression cytology grading and miRNA-146a expression. Expression of miRNA-146a did not differ between the dry eye and non-dry eye RA groups.