Evaporative Dry Eye Disease Research Articles

Phospholipid Nanoemulsion-Based Ocular Lubricant for the Treatment of Dry Eye Subtypes: A Multicenter and Prospective Study.

Dry eye disease (DED) is a multifactorial condition of the ocular surface (OS) characterized by loss of tear film homeostasis, ocular discomfort, and vision disturbances. Most available ocular lubricants target the aqueous deficiency of the tear, restoring only this layer, leaving the tear lipid stratum deficient, as occurs in most patients with evaporative DED. An innovative propylene glycol-hydroxypropyl guar enriched with a phospholipid nanoemulsion (PG-HPG-PH-N) is indicated to restore deficiencies in both the lipid and aqueous layers of the tear film, and its composition was designed to increase lubricant retention on the OS. The purpose of this study was to evaluate, through the Ocular Surface Disease Index (OSDI) and clinical assessment, the treatment of patients who had DED due to aqueous deficiency arising from mixed or evaporative DED subtypes with a PG-HPG-PH-N ocular lubricant at a reduced frequency of twice a day, in a prospective, multicenter, and single-arm study. Patients were screened from days - 7 to 0, and from day 1 (baseline and first day of treatment) to day 28 of treatment with this lubricant. After visit 1 (screening visit, days - 7 to 0), designed as pre-treatment OS assessment, patients returned to their research center on days 14 and 28 of treatment for a complete assessment, including anamnesis, the OSDI, corrected visual acuity, tear breakup time (TFBUT), OS staining evaluation, tolerability index, and environmental exposure questionnaire. Seventy patients were enrolled in this study (60 women, 10 men), with a mean age of 45 (range 27-64) years. TFBUT results showed an improvement in tear film stability as vital dyes sodium fluorescein and lysamine green showed a decrease in corneal staining after 14 and 28days of treatment. No significant adverse events were reported, demonstrating the good tolerability of the lubricant. The PG-HPG-PH-N nanoemulsion can be considered to be a safe and effective ocular lubricant for treating DED due to aqueous deficiency, both mixed and evaporative subtypes. Brazilian National Research Ethics Commission (ReBEC registration number 16055).

Comparative Analysis of Intense Pulsed Light Therapy in Patients with Meibomian Gland Dysfunction, with and Without Glaucoma Medication.

Background: This study assessed the efficacy of intense pulsed light (IPL) therapy for treating meibomian gland dysfunction (MGD), a key contributor to evaporative dry eye disease (DED), by comparing outcomes in patients with idiopathic MGD versus those with MGD induced by glaucoma medications. Methods: In a retrospective analysis of 45 patients, divided into groups based on glaucoma medication use (20 patients) and non-use (25 patients), all underwent four IPL sessions combined with meibomian gland expression (MGX) at 3-week intervals. Key metrics evaluated included Ocular Surface Disease Index (OSDI) scores, tear breakup time (TBUT), Schirmer I test scores, and meibography scores, pre- and post-treatment. Results: Significant improvements were observed in both groups across all parameters post-treatment, indicating enhanced tear film stability and meibomian gland function. The non-glaucoma group showed slightly greater improvements, suggesting the potential impact of glaucoma medications on MGD management. Conclusions: These findings underscore IPL therapy's effectiveness in improving DED symptoms and meibomian gland function, highlighting its utility as a treatment option for patients with MGD, including those on glaucoma medications.

The Effectiveness of E>Eye Intense Regulated Pulse Light Therapy in Treating Evaporative Dry Eye Disease among Southeast Asian Patients

Objective: Since the effectiveness of E>Eye Intense Regulated Pulsed Light (IRPL) therapy in treating evaporative dry eye condition caused by meibomian gland dysfunction (MGD) has not been reported among the Southeast Asian population, this study aimed to retrospectively report the effectiveness of this treatment in addressing evaporative dry eye due to MGD among this population using Tear Check analyzer after three consecutive treatments.Material and Methods: This is a retrospective study involving 71 male and 107 female patients, aged between 28 and 83 with complaints of dry eye symptoms accompanied by clinical signs of MGD who have been treated with E>Eye IRPL. All patients were treated with IRPL in three consecutive treatments where five overlapping flashes of light were administered on the lower lid and temporal part of each eye on day 1, 15, and 45. Improvement in lower meibomian gland loss, Tear Film Stability Evaluation (TFSE), and non-invasive breakup time (NIBUT) were assessed using the Tear Check analyzer at baseline and after the third treatment session.Results: Repeated-measure ANOVA showed that the percentage of lower meibomian gland loss and TFSE score significantly improved post-treatment, indicating recovery of the meibomian gland and improved tear stability. McNemar Change Test also showed that the percentage of patients having NIBUT of lower than 6 seconds has significantly reduced post-treatment.Conclusion: E>Eye IRPL treatment is effective in evaporative dry eye disease caused by MGD among Southeast Asian patients after three consecutive treatments by restoring meibomian gland and tear stability post-treatment.

Meibomian gland lipid alterations and ocular surface sequela in Awat2 knockout murine model of meibomian gland dysfunction and evaporative dry eye disease

PurposeThere is an urgent need for animal models of meibomian gland dysfunction (MGD) and evaporative dry eye disease (EDED) to understand their pathophysiology and investigate novel therapeutics. This study sought to further define the acyl-CoA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mouse as a model of EDED using a combination of novel clinical, biochemical, and biophysical endpoints. MethodsWildtype and Awat2 KO mice between 1 and 18 months of age were used. Ocular examinations and advanced imaging were performed. The lipidomic composition and in situ melting temperature of meibum were determined. qPCR was performed to define ocular surface gene and pro-inflammatory transcript expression. Dynamic contact angle goniometry was performed to assess the adherence capability of the ocular surface. ResultsAwat2 KO mice have mild, white, hyperreflective corneal opacities of the anterior stroma and significantly enlarged apical epithelial cells (P=0.0004). In Awat2 KO meibum, wax esters were 9-10 times lower than in wildtype meibum. Additionally, meibum melting temperature increased from 32° to 47°C (P<0.0001), leading to impaired meibum secretion and dilation of the central duct. Awat2 KO corneal epithelia had significantly decreased mucin expression (Muc1 and Muc4, P=0.0043) and increased interferon-γ production (P=0.0303). Awat2 KO globes have a significantly shortened time of droplet adherence to their ocular surface (P=0.0053), indicating a decreased tear film adherence capacity. Wildtype corneal epithelia does not express Awat2, indicating that the EDED phenotype is secondary to the loss of Awat2 from the meibomian glands. ConclusionsAwat2 KO mice recapitulate many of features of human MGD and EDED, representing a model to test novel therapeutics.

Efficacy and Safety of Perfluorohexyloctane in Evaporative Dry Eye Disease Associated With Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Meibomian gland dysfunction (MGD) is the primary cause of evaporative dry eye disease (DED), which negatively affects the physical and mental quality of life of patients. We performed a meta-analysis of randomized controlled trials (RCTs) comparing perfluorohexyloctane to placebo for MGD in order to identify the best course of treatment for DED in these patients. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline recommendations and prospectively registered the study in PROSPERO (CRD42023442172). The PubMed, Cochrane, and Embase databases were searched for RCTs comparing perfluorohexyloctane to placebo on patients with DED associated with MGD. The statistical analysis was carried out using the "R" software. The mean difference (MD) with 95% CIs was computed using a random-effects model, and p < 0.05 was regarded as statistically significant. The study included 1,814 patients from four RCTs, of whom 972 (53.5%) received perfluorohexyloctane. Patients treated with perfluorohexyloctane had significantly lower total corneal fluorescein staining (tCFS) score (MD -1.09; 95% CI -1.37 to -0.82; p < 0.001; I2 = 0%), eye distress Visual Analogue Scale (VAS) (MD -9.69; 95% CI -12.01 to -7.36; p < 0.01; I2 = 0%), Ocular Surface Disease Index (OSDI) (MD -5.79; 95% CI -8.22 to -3.36 p < 0.01; I2 = 0%), and Eye Burning/Stinging Score (VAS) (MD, -7.16; 95% CI -9.55 to -4.80 p < 0.01; I2 = 0%). The meta-analysis results indicate that perfluorohexyloctane was effective and safe in treating evaporative dry eye, reducing tCFS, eye discomfort, OSDI, and burning sensation, despite the included studies only assessing short-term effects and excluding certain patient groups.

Identification of Meibomian gland stem cell populations and mechanisms of aging.

Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identified markers for stem cell populations that maintain distinct regions of the gland and uncovered Hh signaling as a key regulator of stem cell proliferation. Consistent with this, human Meibomian gland carcinoma exhibited increased Hh signaling. Aged glands displayed decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.

Vectored Thermal Pulsation as a Treatment for Meibomian Gland Dysfunction: A Review Spanning 15 Years.

The LipiFlow Thermal Pulsation System received its first marketing clearance for the treatment of meibomian gland dysfunction (MGD) 13years ago. Since then, the evidence evaluating the effectiveness and safety of LipiFlow as a treatment for MGD has grown significantly. The objective of this comprehensive review was to summarize all clinical reports evaluating the effectiveness and safety of LipiFlow over the past 15years. The literature was systematically reviewed, and 55 unique articles had subjective (patient-reported outcomes) and objective (meibomian gland function, tear production, and ocular staining) outcomes for extraction. Data were collected from 2101patients and 3521 eyes treated with LipiFlow. Of these, effectiveness was evaluated in 2041patients and 3401 eyes, and safety was evaluated in 1448 patients and 2443 eyes. Taken together, the studies demonstrate that a single 12-min treatment with LipiFlow safely improves signs and symptoms of MGD and associated evaporative dry eye disease (DED), and the benefits persist up to 3years in some cases. The findings are corroborated by multiple meta-analyses and consensus guidelines. While some studies showed that daily eyelid hygiene, warm compress, and/or massage had a similar benefit to a single LipiFlow, these treatments were limited by inconvenience, discomfort, and non-compliance. The majority of studies evaluating safety reported no discomfort or pain associated with LipiFlow treatment, which supports the patient acceptability of LipiFlow therapy. All adverse events (AEs) related to LipiFlow were transient, non-vision-threatening, and did not require treatment. No studies reported serious AEs. The data obtained from 55 studies conducted globally overwhelmingly show that LipiFlow is effective and safe for the treatment of MGD and associated evaporative DED. The conclusions are supported by the diversity of the patient populations (geography, race, disease severity, and diagnosis), the large population treated with LipiFlow, the meta-analyses, and that this review analyzed all published clinical studies to date.

Confocal Microscopy of the Cornea in Aqueous-Deficient Dry Eye Disease-A Literature Review.

In vivo confocal microscopy (IVCM) is a vital tool in studying dry eye disease (DED), providing insights into morphological changes at ocular surface unit levels. This review presents the main differences in corneal structure between aqueous-deficient dry eye disease (AD-DED) and normal eyes. A comprehensive search of PubMed, Web of Science, Embase, and MEDLINE databases from January 2000 to December 2023 was conducted. The study selection process, as well as data selection and examination, were independently performed by two members of the review team. The review reveals a consistent decrease in corneal surface epithelial cell density in AD-DED cases compared to a control group, but conflicting data on basal epithelial cell density. Notably, the abnormal hyperreflectivity of keratocytes in patients with Sjogren's syndrome was recorded, and there was a significant keratocyte density in AD-DED subjects compared to evaporative DED and control groups. Studies also found a decrease in sub-basal nerve density, increased tortuosity, and the fragmentation of nerve fibers. Dendritic cell density and dendritic cell dendrites increase in AD-DED patients compared to healthy subjects. IVCM is a powerful tool for enhancing our understanding of the pathophysiological mechanisms underlying DED. However, the review underscores the urgent need to standardize the terminology, analysis, and units used for accurate interpretation, a crucial step in advancing our knowledge of DED.

Rosmarinic acid-grafted gelatin nanogels for efficient diquafosol delivery in dry eye disease therapy

Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the ROS production, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions.

Intense Pulsed Light Therapy for Dry Eye Disease: Analyzing Temporal Changes in Tear Film Stability and Ocular Surface between IPL Sessions.

Dry eye disease (DED), a prevalent condition with a multifactorial etiology, significantly impacts global health by causing discomfort and visual disturbance. This historical cohort study evaluates the efficacy of Intense Pulsed Light (IPL) therapy on meibomian gland dysfunction (MGD)-related evaporative DED. The study involved 110 patients (220 eyes) who underwent IPL therapy. Ethical approval was secured, and informed consent was obtained from all participants. A Tearcheck® (ESWvision, Houdan, France) device was used for ocular surface evaluation, measuring tear film stability (NIFBUT, NIABUT), tear film quantity (CTMH, TTMH), and inflammation (OSIE). The study assessed tear film and ocular surface health across multiple IPL sessions. Significant improvements were observed in subjective symptoms (EFT score increased from 29.10 ± 8.87 to 35.91 ± 7.03, p < 0.01), tear film stability (NIFBUT increased from 9.37 ± 6.04 to 10.78 ± 5.83 s, p < 0.01; NIABUT increased from 11.07 ± 4.98 to 12.34 ± 4.66 s, p < 0.01), and tear film surface evaluation (TFSE score decreased from 337.78 ± 414.08 to 206.02 ± 240.44, p < 0.01). Tear film quantity remained unchanged (CTMH and TTMH, p > 0.05). IPL therapy is a promising treatment for DED, improving symptoms and ocular surface health. Further research is warranted to explore long-term efficacy and optimization.

One Soul and Several Faces of Evaporative Dry Eye Disease.

The ocular surface system interacts with, reacts with, and adapts to the daily continuous insults, trauma, and stimuli caused by direct exposure to the atmosphere and environment. Several tissue and para-inflammatory mechanisms interact to guarantee such an ultimate function, hence maintaining its healthy homeostatic equilibrium. Evaporation seriously affects the homeostasis of the system, thereby becoming a critical trigger in the pathogenesis of the vicious cycle of dry eye disease (DED). Tear film lipid composition, distribution, spreading, and efficiency are crucial factors in controlling water evaporation, and are involved in the onset of the hyperosmolar and inflammatory cascades of DED. The structure of tear film lipids, and subsequently the tear film, have a considerable impact on tears' properties and main functions, leading to a peculiar clinical picture and specific management.

Efficiency of Combining Heated Eye Mask with Intense Pulsed Light Therapy as a Treatment Option for Evaporative Dry Eye Disease.

Background and objectives: The study aimed to establish the efficiency of combining the Posiforlid heated eye mask with intense pulsed light therapy (IPL), as a treatment strategy for evaporative dry eye disease. Materials and methods: This study included 110 patients, respectively 220 eyes, diagnosed with evaporative dry eye disease, patients between 18 and 86 years old, divided into two study groups. The first one, the control group, consisted of 73 patients treated with IPL therapy, and the second of 37 patients, who underwent IPL therapy associated with Posiforlid heated eye mask. Subjective evolution was assessed using an eye fitness test (EFT) regarding symptomatology. Objective assessment of the ocular surface was performed by tear film stability evaluation (TFSE), non-invasive first break-up time (NIFBUT), non-invasive average breakup time (NIABUT), ocular surface inflammatory evaluation (OSIE), measuring of the central tear meniscus height (CTMH) and thinnest tear meniscus height (TTMH). The assessment was performed at the beginning of the IPL treatment, during the IPL sessions, at the end of the IPL treatment, and afterward, at 3, 6, and 12 months. Results: Tear film stability has increased in both study cases, but no statistically significant difference was observed between the two groups studied. For the control group, tear film stability evaluation (TFSE) started from 310.56 ± 389.54 at baseline (time 1 presentation) to 114.40 ± 122.90 after 12 months, and for the heated mask group, from 391.11 ± 456.45 (time 1 presentation) to 97.38 ± 105.98 after 12 months. NIABUT increased from 10.72 ± 4.90 seconds to 14.79 ± 3.72 seconds in the control group, and from 11.11 ± 5.08 seconds to 15.84 ± 2.26 seconds in the second group. OSIE decreased, as expected, from 7.18 ± 7.93 percent in the control group to 2.24 ± 2.38 percent after 12 months and from 7.42 ± 7.77 percent to 2.47 ± 2.50 percent in the Posiforlid group. Although significantly lower, there was no significant difference between the two studied groups. No statistically significant changes were registered in the studied quantitative parameters. Using the EFT test, great improvements were registered regarding symptomatology, with a score increasing from 29.99 ± 8.60 to 39.10 ± 5.08 in the control group and from 27.35 ± 9.24 to 38.35 ± 4.62 in the other group. Again, the same statistical result was registered on this variable. Conclusions: The improvement of tear film stability, ocular surface inflammatory condition, and subjective symptoms during IPL therapy sessions and the first year of observation after the completion of the treatment was not necessarily increased by the additional use of a heated eye mask. Abbreviations: IPL = intense pulsed light therapy, EFT = eye fitness test, NIFBUT = non-invasive first break-up time, NIABUT = non-invasive average break-up time, OSIE = ocular surface inflammatory evaluation, TFSE = tear film stability evaluation, CTMH = central tear meniscus height, TTMH = thinnest tear meniscus height, DED = dry eye disease, MGD = meibomian gland dysfunction, SD = standard deviation.

Tear and Saliva Metabolomics in Evaporative Dry Eye Disease in Females.

Accurate diagnosis of dry eye disease (DED) is challenging, and even today there is no gold standard biomarker of DED. Hypothesis-free global metabolomic studies of tears from DED patients have great potential to discover metabolites and pathways affected in the pathophysiology of DED, and to identify possible future biomarkers. These metabolites and biomarkers could be important for diagnosing and monitoring disease as well as for new therapeutic targets and strategies. As DED is associated with dry mouth, this study aimed to perform metabolomic analyses of tears and saliva from patients with decreased tear film break-up time but normal Schirmer test, and age-matched controls with both tear production and stability within physiological range. We applied strict inclusion criteria to reduce sampling bias in the metabolomic analyses and selected only age-matched females with Schirmer test values between 10-15 mm/5 min. The tear film analysis arm included 19 patients (with tear film break-up time 0-5 s) and 12 controls (with tear film break-up time 10-30 s), while the salivary analysis arm consisted of a subset which included 18 patients and six controls. Metabolomic analyses were performed using liquid chromatography and high-resolution mass spectrometry. Analyses using a global database search detected a total of 56 metabolites in tear samples that were significantly different between the groups. Of these, several have known associations with DED. These metabolites are present in meibum and have anti-oxidative characteristics or associations with the ocular microbiome, and altered concentrations suggest that they may play a significant role in DED associated with decreased tear film stability. In saliva, hypotaurine levels were lower among patients with tear film instability. In this pilot study, we found different levels of several metabolites in patients with decreased tear film break-up time that may have associations with DED. Future studies are required to replicate our findings and clarify the exact roles of these metabolites.

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulated. The largest change was observed in cystatin-SN, which was downregulated in MGD and correlated negatively with tear meniscus height. The downregulation of cystatin-SN was confirmed with targeted mass spectrometry by single reaction monitoring (SRM). Eighteen immunoglobulin components involved in B cell activation, phagocytosis, and complement activation were downregulated in MGD including Ig alpha-1 chain C region, immunoglobulin J chain, immunoglobulin heavy variable 3-15, and Ig mu chain C region. The changes in cystatin-SN and immunoglobulin chains are likely to result from the inflammatory changes related to tear film evaporation, and future studies may assess their association with the meibum quality.

Addressing excessive evaporation: an unmet need in dry eye disease.

Dry eye disease (DED) is a common condition in which tear film abnormalities result in a damaging cycle of tear hyperosmolarity, desiccating stress, inflammation, and ocular surface injury. In a healthy tear film, meibum produced by the meibomian glands forms a lipid layer that stabilizes the tear film and protects against aqueous tear evaporation. Excessive tear evaporation due to a deficient lipid layer is believed to be the most common cause of DED, and most evaporative DED is associated with meibomian gland dysfunction (MGD); this highlights the pathophysiologic importance of the dysfunctional tear lipid layer. Current treatments for DED may be used to supplement hyperosmolar aqueous tears, lubricate the ocular surface, increase meibum flow, decrease inflammation, promote tear production, or otherwise decrease clinical signs of ocular surface damage and/or improve symptoms. Until now, no prescription eye drop has directly addressed the excessive evaporation that occurs in most patients with DED. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO™; Bausch + Lomb) is a preservative-free eye drop that has demonstrated the ability to form a long-lasting barrier that inhibits evaporation in preclinical studies. FDA approval of PFHO was based on results from 2 pivotal clinical trials (GOBI [NCT04139798] and MOJAVE [NCT04567329]) in patients with DED and clinical signs of MGD which demonstrated consistent improvements in both signs and symptoms of disease, with a safety profile similar to that of saline eye drops. PFHO is the first and only FDA-approved eye drop that directly targets tear evaporation in patients with DED, thereby promoting ocular surface healing and providing symptomatic relief.

Recent advances in age-related meibomian gland dysfunction (ARMGD)

Meibomian glands (MGs), located within the tarsal plate of the eyelid, secrete meibum which is the lipid-rich secretion necessary for stabilizing the tear film and preventing tear evaporation. Changes in the quality and quantity of meibum produced causes MG dysfunction (MGD), the leading cause of evaporative dry eye disease (EDED). MGD is an underdiagnosed disease and it is estimated that, in the US, approximately 70 % of the population over 60 have MGD. Three forms of MGD occur based on their meibum secretion: hyposecretory, obstructive, and hypersecretory MGD. The pathophysiology of MGD remains poorly understood, however aging is the primary risk factor. With age, MGs undergo various age-related changes, including decreased acinar basal cell proliferation, hyperkeratinization, MG atrophy, and eventual MG drop-out, leading to age-related MGD (ARMGD). Additionally, studies have suggested that MGs can suffer inflammatory cell infiltration and changes innervation patterns with aging, which could also contribute towards ARMGD. This review focuses on how the aging process affects the MG, and more importantly, how age-related changes to the MG can lead to MG atrophy and MG drop-out, ultimately leading to ARMGD. This review also highlights the most recent developments in potential therapeutic interventions for ARMGD.

Diagnostic Performance of the Tear Meniscus Osmolarity Measurement for Dry Eye Disease in Rheumatoid Arthritis Patients.

The aim of our study was to evaluate the diagnostic capacity of the tear meniscus osmolarity measurement for dry eye disease (DED) in patients with rheumatoid arthritis (RA), using a portable osmometer based on electrical impedance and an integrated circuit technology (TearLab® (Escondido, CA, USA)). We included 101 RA patients, 81 patients with DED and 20 without DED (controls). We measured tear osmolarity and assessed other clinical diagnostic tests as suggested by the TFOS DEWS II composite reference standard diagnostic criteria for DED using Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), fluorescein tear break-up time (F-TUBT), ocular surface staining (SICCA score), and other clinical parameters to classify DED subtypes. We analyzed the agreement between osmolarity and the TFOS DEWS II composite reference standard for DED diagnosis. We conducted receiver operating characteristic (ROC) curve analyses using the DED variable and its subtypes as dependent variables and the continuous variable for osmolarity or the inter-eye difference in osmolarity as independent variable. Sensitivity, specificity, and area under the curve for all potential cut-off points were obtained and reported from ROC curves. We found that tear meniscus osmolarity had a low diagnostic capacity for DED (AUC = 0.57). Tear meniscus osmolarity measurement had a sensitivity of 35% and a specificity of 80% with a kappa level of agreement of 0.08 compared to the TFOS DEWS II composite reference standard. The low diagnostic capacity of the tear meniscus osmolarity was similar for aqueous-deficient DED and for evaporative DED, being only fair for severe DED with a 57% sensitivity and 80% specificity and a kappa level of agreement of 0.36. Our findings suggest that in patients with RA, tear meniscus osmolarity measured by the TearLab® showed low sensitivity, low specificity, and limited agreement with the TFOS DEWS II composite reference standard for DED diagnosis.

The Combined Impact of Intense Pulsed Light Combined and 3% Diquafosol Ophthalmic Solution on Evaporative Dry Eye: A Randomized Control Study.

The primary objective of this study is to assess whether the combination of intense pulsed light (IPL) with 3% diquafosol (DQS) ophthalmic solution is more effective than intense pulsed light in alleviating signs and symptoms of dry eye disease (DED). This randomized study included 66 participants with evaporative dry eye (EDE) who received IPL + DQS therapy (n = 44 eyes), IPL therapy (n = 44 eyes), or sham therapy (n = 44 eyes). All participants were examined at baseline (D0), day14 (D14), and day28 (D28) for non-invasive break-up time (NITBUT), tear-film lipid layer (TFLL), corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expression (MGEx), and ocular surface disease index (OSDI). At day28, comparison among the IPL + DQS therapy, IPL therapy, and sham therapy found significant differences in the mean NITBUT (12.03 ± 1.27 versus 10.47 ± 3.48 versus 4.57 ± 0.46; p < 0.001), TFLL (2.09 ± 0.29 versus 2.27 ± 0.45 versus 2.89 ± 0.65; p < 0.001), CS (1.43 ± 0.82 versus 1.93 ± 1.32 versus 3.52 ± 1.00; p < 0.001), MGQ (1.55 ± 0.66 versus 1.91 ± 0.77 versus 2.66 ± 0.53; p < 0.001), MGEx (1.27 ± 0.45 versus 1.75 ± 0.44 versus 2.41 ± 0.50; p < 0.001), and OSDI score (19.36 ± 7.01 versus 24.77 ± 4.68 versus 42.61 ± 7.49; p < 0.001); significant improvements in NITBUT, TFLL, CS, MGQ, MGEx, and OSDI were found in the IPL + DQS therapy and IPL therapy, while the sham therapy had no significant improvements. Combining 3% diquafosol ophthalmic solution with intense pulsed light was superior to IPL therapy alone in relieving the signs and symptoms of patients with severe evaporative DED. Clinical Trials Identifier: NCT05694026.

Ocular Surface Evaluation in Immunoglobulin G4–Related Ophthalmic Disease

To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. Cross-sectional, matched case-control comparison study. This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P=.0187), lid margin telangiectasia (P=.0360), lid-parallel conjunctival folds (P=.0112), papillae (P=.0393), meibomian gland plugging (P=.0001), meibomian gland expressibility (P=.0001), and meibum quality (P=.0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P=.001 and .0003), and tear meniscus height (P=.0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P=.0166) and Schirmer test results (P=.0243) were lower in IgG4-ROD patients. Upper (r=0.336, P=.0140) meibomian gland dropouts and NITBUT (r=-0.293, P=.0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r=-0.341, P=.0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Gene expression signatures in conjunctival fornix aspirates of patients with dry eye disease associated with Meibomian gland dysfunction. A proof-of-concept study

BackgroundMeibomian gland dysfunction (MGD) is one of the most common conditions in ophthalmic practice and the most frequent cause of evaporative dry eye disease (DED). However, the immune mechanisms leading to this pathology are not fully understood and the diagnostic tests available are limited. Here, we used the nCounter technology to analyze immune gene expression in DED-MGD that can be used for developing diagnostic signatures for DED. MethodsConjunctival cell samples were obtained by aspiration from patients with DED-MGD (n = 27) and asymptomatic controls (n = 22). RNA was purified, converted to cDNA, preamplified and analyzed using the Gene Expression Human Immune V2 panel (NanoString), which includes 579 target and 15 housekeeping genes. A machine learning (ML) algorithm was applied to design a signature associated with DED-MGD. ResultsForty-five immune genes were found upregulated in DED-MGD vs. controls, involved in eight signaling pathways, IFN I/II, MHC class I/II, immunometabolism, B cell receptor, T Cell receptor, and T helper-17 (Th-17) differentiation. Additionally, statistically significant correlations were found between 31 genes and clinical characteristics of the disease such as lid margin or tear osmolarity (Pearson's r < 0.05). ML analysis using a recursive feature elimination (RFE) algorithm selected a 4-gene mRNA signature that discriminated DED-MGD from control samples with an area under the ROC curve (AUC ROC) of 0.86 and an accuracy of 77.5%. ConclusionsMultiplexed mRNA analysis of conjunctival cells can be used to analyze immune gene expression patterns in patients with DED-MGD and to generate diagnostic signatures.