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Significance: This study found that the unique properties of tear film breakup process in eyes with pterygium, combined with ocular surface parameters, further revealed specific dynamic mechanism. It suggested that the thickness of pterygium was especially valuable in deciding the necessity of surgical management., Purpose: This study aimed to explore the dynamic mechanism of tear film instability in eyes with pterygium., Methods: A paired-eye controlled cross-sectional study was conducted. Seventy-eight patients with nasal pterygium were enrolled. Fluorescein tear film breakup was observed. Several key parameters related to tear film quality were defined and analyzed, including total breakup area (mathematically derived from pixel size using MATLAB), breakup velocity, fluorescein breakup time, breakup location and pattern, tear meniscus height, score of fluorescein corneal staining, and meiboscore., Results: With comparable tear meniscus height, score of fluorescein corneal staining, and meiboscore between paired eyes (p > 0.05), eyes with pterygium had shorter breakup time, larger breakup area, and faster breakup velocity (p < 0.05). In eyes with pterygium, a positive correlation between meiboscore and pterygium parameters including length, thickness, and size was observed (p > 0.001). As the thickness increased, difference of breakup time and area between paired eyes increased (p = 0.02 and 0.046). Eyes with pterygium had more fixed inferonasal breakup location and often presented as dimple break (60%), whereas random break was the most common in contralateral normal eyes (62%). A unique breakup pattern named pterygium-induced local dimple break was found. It displayed as an irregular but vertical line-like shape appearing after lipid layer spreading, which was adjacent to the lower margin of pterygium and presented with unique properties including inferonasal breakup location, local breakup area, shorten breakup time, and faster breakup velocity., Conclusions: Eyes with pterygium showed a unique tear film breakup process and novel breakup pattern named pterygium-induced local dimple break . Dynamic mechanism played a significant role in tear film instability of eyes with pterygium rather than aqueous deficiency and increased evaporation., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2024 American Academy of Optometry.)

Purpose: To evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard., Methods: Cross-sectional study of participants from the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors., Results: A total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively., Conclusions: OSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

Dry eye disease (DED) is a widespread, multifactorial, and chronic disorder of the ocular surface with disruption of tear film homeostasis as its core trait. Conjunctival goblet cells (CGCs) are specialised secretory cells found in the conjunctival epithelium that participate in tear film formation by secreting mucin. Changes in both the structure and function of CGCs are hallmarks of DED, and imaging assessment of CGCs is important for the diagnosis, classification, and severity evaluation of DED. Existing imaging methods include conjunctival biopsy, conjunctival impression cytology and in vivo confocal microscopy, which can be used to assess the morphology, distribution, and density of the CGCs. Recently, moxifloxacin-based fluorescence microscopy has emerged as a novel technique that enables efficient, non-invasive and in vivo imaging of CGCs. This article presents a comprehensive overview of both the structure and function of CGCs and their alterations in the context of DED, as well as current methods of CGCs imaging assessment. Additionally, potential directions for the visual evaluation of CGCs are discussed., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To evaluate the effects of different pterygium surgery techniques on ocular surface (OS) in different follow-up periods., Methods: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and China Biology Medicine disc were searched for studies reporting pre- and post-operative OS parameters in pterygium., Results: A total of 33 articles were finally included. Three OS parameters showed relatively consistent changing trends after surgery including ocular surface disease index (OSDI), tear film break-up time (BUT), and score of corneal fluorescein staining (SCFS). They worsened significantly at 1w post-operation and then gradually improved: OSDI and BUT showed obvious improvement in 1 m post-operation (SMD =  - 0.58, 95%CI = [- 1.04, - 0.13]; SMD = 0.42, 95%CI = [0.06, 0.78]); SCFS was restored to preoperative levels in 3 m after surgery (SMD =  - 0.54, 95%CI = [- 1.16, 0.07]). Another parameter, Schirmer test without anesthesia (SIT), presented transient increase at 1w post-operation (SMD = 0.87, 95%CI = [0.27, 1.47]) and presented a relatively stable improvement after 1 m post-operation (SMD = 0.52, 95%CI = [0.16, 0.89]). All parameters in amniotic membrane graft (AMT) showed better improvement in early stage and they showed non-inferior improvements in the long term compared with conjunctival autograft (CAG). Limbal-conjunctival autograft (LCAG) made excellent improvement to OS in the long term while pterygium excision (PE) showed the worst OS. The type of pterygium (primary and secondary), diabetes mellitus (DM) status, and fixation method had certain effects on the results., Conclusions: OS of pterygium is deteriorated at 1w post-operation then gradually improved to preoperative levels after 1 m post-operation. Among various surgery techniques, LCAG had the best improvement to OS which especially displayed in the long-term outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Current scales for assessment of bulbar conjunctival redness have limitations for evaluating digital images. We developed a scale suited for evaluating digital images and compared it to the Validated Bulbar Redness (VBR) scale., Methods: From a digital image database of 4889 color corrected bulbar conjunctival images, we identified 20 images with varied degrees of redness. These images, ten each of nasal and temporal views, constitute the Digital Bulbar Redness (DBR) scale. The chromaticity of these images was assessed with an established image processing algorithm. Using 100 unique, randomly selected images from the database, three trained, non-physician graders applied the DBR scale and printed VBR scale. Agreement was assessed with weighted Kappa statistics (K w )., Results: The DBR scale scores provide linear increments of 10 from 10-100 when redness is measured objectively with an established image processing algorithm. Exact agreement of all graders was 38% and agreement with no more than a difference of ten units between graders was 91%. K w for agreement between any two graders ranged from 0.57 to 0.73 for the DBR scale and from 0.38 to 0.66 for the VBR scale. The DBR scale allowed direct comparison of digital to digital images, could be used in dim lighting, had both temporal and nasal conjunctival reference images, and permitted viewing reference and test images at the same magnification., Conclusion: The novel DBR scale, with its objective linear chromatic steps, demonstrated improved reproducibility, fewer visualization artifacts and improved ease of use over the VBR scale for assessing conjunctival redness., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To determine whether ocular phenotypic features of keratoconjunctivitis sicca (KCS) and/or participant-reported symptoms of dry eye disease are associated with depression in women participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA)., Design: Cross-sectional study., Methods: Women enrolled in the SICCA registry from 9 international research sites. Participants met at least 1 of 5 inclusion criteria for registry enrollment (including complaints of dry eyes or dry mouth, a previous diagnosis of Sjögren syndrome (SS), abnormal serology (positive anti-Sjögren syndrome antigen A and/or B [anti-SSA and/or anti-SSB]), or elevated antinuclear antibody and rheumatoid factor), bilateral parotid gland enlargement, or multiple dental caries). At baseline, participants had oral, ocular, and rheumatologic examination; blood and saliva collection; and a labial salivary gland biopsy (LSGB). They also completed an interview and questionnaires including assessment of depression with the Patient Health Questionnaire 9 (PHQ-9). Univariate logistic regression was used to assess the association between depression and demographic characteristics, participant-reported health, phenotypic features of Sjögren syndrome, and participant-reported symptoms. Mixed-effects modeling was performed to determine if phenotypic features of KCS and/or participant-reported symptoms of dry eye disease were associated with depression, controlling for health, age, country or residence, and sex and allowing for nonindependence within geographic site., Results: Dry eye complaints produced a 1.82-fold (95% confidence interval [CI] 1.38-2.40) higher odds of having depression compared to being symptom-free (P < .001). Additionally, complaints of specific ocular sensations were associated with a higher odds of depression including burning sensation (odds ratio 2.25, 95% CI 1.87-2.72, P < .001) compared to those without complaints. In both women with and without SS, the presence of symptoms of dry eyes and/or dry mouth rather than SS itself resulted in higher odds of depression. One particular ocular phenotypic feature of SS, a positive ocular staining score, was inversely correlated with depression., Conclusions: Participant-reported eye symptoms, particularly specific ocular sensations such as burning, were found to be positively associated with individual American College of Rheumatology/EUropean League Against Rheumatism (ACR/EULAR) SS criteria items., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Lissamine green (LG) staining of the conjunctiva is a key biomarker in evaluating ocular surface disease. The disease currently is assessed using relatively coarse subjective scales. Objective assessment would standardize comparisons over time and between clinicians., Objective: To develop a semiautomated, quantitative system to assess lissamine green staining of the bulbar conjunctiva on digital images., Design, Setting, and Participants: Using a standard photography protocol, 35 digital images of the conjunctiva of 11 patients with a diagnosis of dry eye disease based on characteristic signs and symptoms were obtained after topical administration of preservative-free LG, 1%, solution. Images were scored independently by 2 masked ophthalmologists in an academic medical center using the van Bijsterveld and National Eye Institute (NEI) scales. The region of interest was identified by manually marking 7 anatomic landmarks on the images. An objective measure was developed by segmenting the images, forming a vector of key attributes, and then performing a random forest regression. Subjective scores were correlated with the output from a computer algorithm using a cross-validation technique. The ranking of images from least to most staining was compared between the algorithm and the ophthalmologists. The study was conducted from April 26, 2012, through June 2, 2016., Main Outcomes and Measures: Correlation and level of agreement among computerized algorithm scores, van Bijsterveld scale clinical scores, and NEI scale clinical scores., Results: The scores from the automated algorithm correlated well with the mean scores obtained from the gradings of 2 ophthalmologists for the 35 images using the van Bijsterveld scale (Spearman correlation coefficient, rs = 0.79), and moderately with the NEI scale (rs = 0.61) scores. For qualitative ranking of staining, the correlation between the automated algorithm and the 2 ophthalmologists was rs = 0.78 and rs = 0.83., Conclusions and Relevance: The algorithm performed well when evaluating LG staining of the conjunctiva, as evidenced by good correlation with subjective gradings using 2 different grading scales. Future longitudinal studies are needed to assess the responsiveness of the algorithm to change of conjunctival staining over time.

Purpose: The aim of this study was to examine the tolerability of topical tocilizumab eyedrops in normal dogs and to assess whether this preparation alters tear film cytokine levels or conjunctival cytokine mRNA expression., Methods: Two percent tocilizumab eyedrops were administered to the right eyes and artificial tears to the left eyes of 10 dogs with no anterior segment pathology 3 times daily for 4 weeks. Portable slit-lamp examinations and Schirmer tear testing were performed at baseline and day 1 week 4, as well as 2 weeks after treatment (week 6). Schirmer strips were also used to collect tears for analyses of cytokine levels using multiplex bead array. Median levels of 8 cytokines in the tear film [interferon gamma (IFN-γ), tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, and IL-10] were compared among tocilizumab-treated and control eyes. Conjunctival biopsies from both eyes were collected at week 4, and mRNA levels of cytokines were also evaluated. Blood samples were collected at baseline and at the end of treatment to monitor for changes in complete blood count, basic metabolic panel, or liver function tests., Results: At week 4, conjunctival biopsies and tear samples showed no significant differences in either tear cytokine or mRNA levels for IFN-γ, TNF-α, IL-2, IL-6, IL-8, and IL-10. There was no evidence of local irritation or changes in bloodwork results from the topical tocilizumab formulation., Conclusions: Topical application of tocilizumab eyedrops was well tolerated when used on healthy dog eyes in this pilot study.

Purpose: To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists., Design: Reliability analysis within a prospective, observational, multicenter cohort study., Methods: Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining., Results: Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90)., Conclusions: Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effect of soft contact lens (CL) wear on the morphology of the epithelial-lamina propria junction as well as the possible association with symptoms of discomfort., Methods: Ninety-two subjects were recruited, including 60 soft CL wearers, 16 previous wearers, and 16 non-wearers. Additionally, subjects were classified as symptomatic or asymptomatic using the Contact Lens Dry Eye Questionnaire 8 for the CL wearers (a score ≥ 12 was considered symptomatic) and the Dry Eye Questionnaire 5 for the previous wearers and non-wearers (a score ≥ 5 was considered symptomatic). In vivo confocal microscopy of the tarsal conjunctiva was performed on a single occasion. Papillae density, shortest diameter, longest diameter, area, circularity, lumen/wall brightness ratio, irregularity, reflectivity, inhomogeneous appearance of wall and inhomogeneous appearance of rete ridges were evaluated. Effects of CL wear, symptoms and their interaction were analysed using two-way analysis of variance. Correlations were investigated using Spearman's coefficient. Data are presented as mean (standard deviation) or median [interquartile range]., Results: Contact lens wearers, compared to previous wearers and non-wearers, showed higher circularity [0.65 (0.08) vs 0.59 (0.10) vs 0.57 (0.11), p = 0.003]. Subjects with symptoms, compared to asymptomatic participants, showed higher circularity [0.64 (0.08) vs 0.61 (0.10), p < 0.001] and lower irregularity (1.0 [0.7-2.0] vs 1.3 [1.0-2.3], p = 0.009). For previous wearers, those with symptoms showed greater density (135.4 [107.3-183.3] vs 87.5 [85.4-116.7], p = 0.013) and circularity [0.64 (0.07) vs 0.54 (0.10), p = 0.016]. For non-wearers, those with symptoms showed higher circularity [0.65 (0.08) vs 0.50 (0.08), p < 0.001]. DEQ-5 correlated with circularity (ρ = 0.55, p = 0.001)., Conclusions: Soft CL wear modifies papillae of the epithelial-lamina propria junction into a more rounded shape; however, CL cessation appears to resolve this alteration. Additionally, a more rounded papillae shape is associated with ocular symptoms in subjects not actively wearing CLs., (© 2019 The Authors Ophthalmic & Physiological Optics © 2019 The College of Optometrists.)

Purpose: To determine the changes in "ocular surface" and "pre-corneal tear film" in tobacco smokers. Study Design: Cross sectional, comparative. Place and Duration of Study: Holy Family Hospital, Rawalpindi Medical University, Rawalpindi, Pakistan from February 2022 to May 2022. Methods: Eighty four patients (42 smokers and 42 non-smokers) were selected for ocular evaluation. "Ocular surface" and "pre-corneal tear film" were assessed by "tear film break up time (TBUT)", "Schirmer test", "corneal punctate staining" and "corneal/conjunctival sensitivity" in both smokers and non-smokers. Chi square test and unpaired t-test were applied and p ≤ 0.05 was taken as significant. Results: Mean age of participants was 36.07 ± 5.75 years. There were 76.2% males and 23.8% females. In terms of age and gender, there was no statistically significant difference between smokers and non-smokers. In terms of TBUT (p = 0.000), corneal punctate staining (p = 0.000) and corneal/conjunctival sensitivity (p = 0.000) values were significantly lower in smokers as compared to non-smokers while in terms of "Schirmer test" there was no statistically significant difference between smokers and non-smokers (p-value of 0.827). Conclusion: Use of cigarettes results in multiple adverse effects in the "ocular surface" and "pre-corneal tear film" including unstable tear film, dry eyes, poor sensitivity of cornea as well as the conjunctiva making their eyes more prone to damage and disease. [ABSTRACT FROM AUTHOR]

Purpose: Aim of this study was to compare the efficacy of sodium hyaluronate (SH) and carboxymethyl cellulose (CMC) eye drops in treating mild to moderate dry eye disease in terms of relief of symptoms, mean change in tear film breakup time, Schirmer’s test, and impression cytology of conjunctiva from baseline. Methods: An observational study was carried out during a 2‑year period in our tertiary referral hospital. The study consisted of 60 patients randomly allotted to two groups to receive SH and CMC eye drops for an 8‑week period. Ocular surface disease index, tear film breakup time, and Schirmer’s test were performed at baseline visit and 4 and 8 weeks of treatment, and impression cytology of conjunctiva was performed at baseline and 8 weeks. Results: Significant improvement in patient symptoms, tear film breakup time, and Schirmer’s test from baseline was seen in both SH and CMC groups at 8 weeks posttreatment, whereas impression cytology of conjunctiva in both groups did not show significant improvement at 8 weeks of treatment. Data analysis using unpaired t‑test showed comparable results. Conclusion: Both CMC and SH demonstrated equal efficacy in treating mild to moderate dry eye disease. [ABSTRACT FROM AUTHOR]

To describe the experience in a recently created ocular graft-versus-host disease unit in a tertiary hospital and to detail ocular surface features and complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study included all patients who underwent allo-HSCT, with or without chronic GVHD and were being monitored in the Hematopoietic Stem Cell Transplantation Unit in the UNICAMP Clinical Hospital (Campinas, Sao Paulo, Brazil) from 2015 to 2020. Patients were concomitantly evaluated by hematology and ophthalmology teams of the Ocular GVHD Unit. Hematologists performed a comprehensive systemic evaluation searching and grading mouth, skin, lungs, gastrointestinal tract, liver and genitalia GVHD. While ophthalmologists evaluated ocular symptoms through specific questionnaire (Ocular Surface Disease Index—OSDI) and a protocol of distinct ocular surface parameters for dry eye disease (1) and ocular complications, which encompassed meniscometry, non-invasive tear break-up time (NITBUT) measurement, conjunctival hyperemia quantification, meibography, fluorescein and lissamine staining and Schirmer's test. Patients were diagnosed with chronic GVHD using the National Institutes of Health (NIH) Consensus Criteria for Chronic Graft-versus-Host Disease. The International Chronic Ocular GVHD Consensus Group (ICOGCG) score was obtained at the onset of ocular disease presentation or afterwards. A total of 82 patients underwent allo-HSCT (97.6% full matched and 2.4% haploidentical), mainly for cases of leukemia and 73.2% had chronic GVHD. Mean onset time for chronic GVHD was 232 ± 7.75 days. The mouth, skin, and eyes were the main organs involved (63%, 50%, and 48%, respectively). Symptom scores and all ocular surface parameters differ in patients with and without chronic GVHD and along different timepoints of the follow-up. Ocular complications mostly involved were severe DED and meibomian gland dysfunction, conjunctival scarring, cataract and infections resulting in keratitis and corneal perforation. As therapeutic strategies, 73% patients received preservative-free lubricants, 27% autologous serum, 48% topical steroids, 27% oral tetracycline derivatives, 22% mucolytic eye drops and 3 patients needed bandage contact lens. Ocular GVHD is a complex and challenging disease with varied manifestations, resulting in a broad range of ocular test endpoints, and inconsistent treatment responses. The main ocular presentations were dry eye, meibomian gland dysfunction and cataracts. The therapeutic approach often involves topical steroids and autologous serum tears. It is important to monitor these patients closely, so the ocular GVHD Unit may improve the care, providing prompt identification of ocular manifestations and faster treatment of complications. [ABSTRACT FROM AUTHOR]

Differentiating patients with Sjögren's syndrome (SS)‐associated dry eye from non‐SS dry eye is critical for monitoring and appropriate management of possible sight‐ or life‐threatening extraglandular complications associated with SS. We tested whether reduced tear levels of immunoregulatory thrombospondin (TSP)‐1, which also inhibits matrix metalloproteinase (MMP)‐9, would reflect SS pathogenesis aiding the identification of patients with SS‐dry eye. Total of 61 participants, including healthy controls (n = 20), patients with non‐SS dry eye (n = 20) and SS‐dry eye (n = 21) were enrolled prospectively. Tear TSP‐1 and MMP‐9 levels were measured using a custom magnetic bead‐based multi‐plex assay in a masked manner. Analyte concentrations were assessed further according to ocular surface and tear film parameters. Relative to median tear TSP‐1 (308 ng/ml) and MMP‐9 (1.9 ng/ml) levels in the control group, significantly higher proportion of patients with SS‐dry eye than non‐SS had lower tear TSP‐1 levels (55% vs. 29%, odds ratio [OR] = 3, 95% confidence interval [CI] = 1.64 to 5.35, p < 0.05) and higher tear MMP‐9 levels (65% vs. 24%, OR = 5.8, 95% CI = 4.46 to 19.81, p < 0.05), respectively. The tear TSP‐1/MMP‐9 ratio was significantly reduced in patients with SS‐dry eye compared to non‐SS (B = −2.36, 95% CI = −3.94 to −0.0.79, p < 0.05), regardless of tear MMP‐9 levels. Patients with a lower ratio were 2.3 times more likely to have SS (OR = 0.28, 95% CI = 0.1 to 0.75, p < 0.05). This ratio showed significant inverse correlations with clinical parameters (conjunctival and corneal staining scores). Our results denote that tear TSP‐1/MMP‐9 ratio can be useful in identifying patients with dry eye with underlying SS and used as a screening test. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied. Methods: In this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed. Results: The study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild. Conclusions: This study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications. Trial Registration: ClinicalTrials.gov, NCT03688802. [ABSTRACT FROM AUTHOR]

This paper aims to investigate the efficacy of circularly polarized light smartphones in affecting dry eye symptoms and asthenopia through a comparison with linearly polarized smartphones. One hundred twenty participants were randomly divided into four groups. Dry eye and asthenopia symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Computer Vision Syndrome Scale 17 (CVSS17), Convergence Insufficiency Symptom Survey (CISS), and visual analogue scale (VAS). Objective ocular examinations were assessed by confusion flicker frequency (CFF), tear meniscus height (TMH), noninvasive break‐up time (NIBUT), conjunctiva redness, fluorescein tear break‐up time (FTBUT), corneal fluorescein staining, and the Schirmer I test. Tests were performed before and after a reading task. Subjective evaluations including the OSDI, CVSS17, and CISS were all significantly increased after reading on a linearly polarized smartphone, whereas no change was observed in the circular polarization groups in both light and dark environments. A significantly enlarged VAS was shown in all of the four groups, but a significant increase in ΔVAS only appeared in the linear polarization groups. There were significant decreases in TMH, NIBUT, conjunctiva redness, FTBUT, and CFF after reading on a linearly polarized smartphone but the circularly polarized smartphone had lesser effects on these parameters. Our study indicated that reading on linearly polarized smartphones may cause dry eye disorder, asthenopia, and ocular discomforts, whereas circularly polarized smartphones appears to minimize these adverse effects on eye dryness and visual fatigue in light and dark environments. [ABSTRACT FROM AUTHOR]

Dry eye (DE) disease is a multifactorial disease in which uncontrolled inflammation can lead to corneal epithelium lesions and symptoms of discomfort. The aim of the present study was to evaluate the efficacy of two cyclosporine emulsions in a mouse model of DE with corneal epithelium lesions. Six- to 9-week-old female C57BL/6 N mice were housed in a controlled-environment room to induce DE. Following DE development, mice were instilled with: QD 0.1%CsA cationic emulsion (CaEm), BID 0.05%CsA anionic emulsion (AEm), or left untreated. Aqueous tear production and corneal epithelium lesions were assessed throughout the experiment. At the end of the treatment period, left eyes were sampled, fixed, and stained for histology, while the cornea, conjunctiva, and lacrimal gland of right eyes were sampled for transcriptomic analysis. Corneal lesion scores were reduced by 10.4%, 18.4%, and 10.9% at day 6, 10, and 14, respectively, with CaEm (QD), and by 2.6%, 3.0%, and 5.5% at day 6, 10, and 14, respectively, with AEm (BID). Histology demonstrated that 7 out of 10 DE mice presented moderate to severe ocular lesions, while only 2 and 5 out of 10 mice presented slight to moderate ocular lesions when treated with the CaEm (QD) and AEm (BID), respectively. The transcriptomic profile analysis suggests that a different set of inflammatory genes are modulated in the cornea, conjunctiva, and lacrimal gland upon DE development. In addition, the two emulsions distinctively modulate the gene expression profile. This study demonstrates that both emulsions were effective at reducing corneal lesions, with the CaEm (QD) being slightly better than the AEm (BID). Interestingly, this study suggests that ocular tissues may not respond similarly to a dry environment and that a different set of genes is modulated by the two formulations in the ocular tissues. [ABSTRACT FROM AUTHOR]

Aim: To discuss the immunological mechanism in electroacupuncture (EA) treatment of dry eye syndrome (DES) by targeting the changes in conjunctival cytokine expression profile. Method: Eligible DES patients were randomized into an EA group (EAG) or an acupuncture group (AG). The ocular surface disease index (OSDI), amount of tear production, and tear film break-up time (BUT) were observed to evaluate the efficacy. Conjunctival cells were collected from both effective and invalid cases to observe the expressions of cytokines by protein microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional cluster and signaling pathway analysis of the differentially expressed proteins. Enzyme-linked immunosorbent assay (ELISA) was used to verify the specific differential proteins. Result: After treatment, OSDI dropped and BUT extended in both groups, and the tear production increased only in the EAG (all P <.01). Compared with the AG, the improvement in tear production was more significant in the EAG (P <.01). There were 17 differentially expressed conjunctival cytokines between the effective and invalid cases in the EAG, and those expressed higher than the limit of detection (LOD) included monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), regulated on activation in normal T-cell expressed and secreted (RANTES) and tissue inhibitor of metalloproteinases 1 (TIMP-1). GO analysis showed that the differential cytokines were mainly involved in cellular interaction, signaling pathways and reactions to stimuli. KEGG analysis revealed that the signaling pathways of these cytokines were mainly responsible for interactions between cytokines or between cytokines and their receptors, such as Jak-STAT signaling pathway, chemokine signaling pathway, and tumor necrosis factor signaling pathway. Conclusion: EA can effectively treat DES by improving the symptoms, increasing tear secretion and extending BUT, which is possibly related to its regulation on the conjunctival cytokine expressions. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED) is characterized by a loss of homeostasis of the tear film. It goes along with ocular symptoms, in which ocular surface inflammation and damage play etiological roles. High-mobility group box 1 protein (HMGB1) is a pro-inflammatory protein found in the tear fluid during conjunctivitis, blepharitis and DED. Glycyrrhizin binds to HMGB1, inhibiting cytokine activities, thus potentially improving DED. Aim: To assess the efficacy and tolerance of glycyrrhizin in moderate DED. Methods: Multicenter, open-label, prospective, nonrandomized clinical pilot study of glycyrrhizin 2.5% eye drops twice daily over 28 days in adult patients with moderate DED using standard evaluation parameters. Results: The overall mean age of the 37 patients included was 59.6±19.0 years, 70.3% of the patients were female and 77.0% of the patients had an Oxford score of II. After 28 days, 60.8% of the patients had an Oxford score of 0 or I; a significant mean improvement in the score of 0.97±0.86 (P<0.001) from 2.20±0.44 at day 1 to 1.23±0.88 at day 28 was observed. Tear break-up time and Schirmer scores had significantly improved while the number of patient-reported symptoms had significantly decreased (all P≤0.010). A large majority of patients still had a few spots on their naso-bulbar conjunctiva (86.1%), temporal-bulbar conjunctiva (81.4%) and cornea (84.7%). The investigators considered that DED had improved in 71.6% of the patients. Patients appreciated the eye drops for their efficacy and good tolerance profile, leading to a decreased use of artificial tears. No changes in intraocular pressure and visual acuity were observed; glycyrrhizin 2.5% eye drops were safe, with only one patient reporting a moderate, transient treatment-related contact allergy leading to the withdrawal of the patient. Overall, two patients reported three adverse events, two (moderate contact allergy in both eyes) were related to the eye drops and experienced by the same patient; treatment was stopped; the third event was not treatment-related. Conclusion: In this pilot study, glycyrrhizin 2.5% eye drops were well tolerated and provide a good clinical benefit to patients with moderate DED after 28 days of continued daily use. [ABSTRACT FROM AUTHOR]

Biomarkers provide a powerful and dynamic approach to improve our understanding of the mechanisms underlying ocular diseases with applications in diagnosis, disease modulation or for predicting and monitoring of clinical response to treatment. Defined as measurable indicator of normal or pathological processes, biomarker evaluation has been used extensively in drug development within clinical settings to better comprehend effectiveness of treatment in ocular diseases. Biomarkers in the eye have the advantage of access to multiple ocular matrices via minimally invasive methods. Repeat sampling for biomarker assessment has enabled reproducible objective measures of disease process or biological responses to a drug treatment. This review describes the usage of biomarkers with respect to four commonly sampled ocular matrices in clinic: tears, conjunctiva, aqueous humor and vitreous. Issues that affect the evaluation of biomarkers are discussed along with opportunities to leverage biomarkers such that ultimately, they can be used for customized targeted therapy. [ABSTRACT FROM AUTHOR]