Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm2, and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P = 0.172) and CNFD (21.46 ± 8.41, P = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).

Tear Film Lipid Layer Changes Following Combined Effect of Heated Eye Mask with Intense Pulsed Light Therapy for Evaporative Dry Eye: A Randomized Control Study.

Background: Dry eye disease (DED) is a complex ocular surface inflammatory disorder with a multifactorial etiology. Therapies such as intense pulsed light (IPL) and heated eye mask (HEM) have been reported to improve the tear film lipid layer (TFLL) and signs and symptoms of DED. Methods: This randomized study aimed to compare the effects of IPL combined with HEM (IPL+HEM) group, IPL group, and control group in participants with evaporative DED. All participants were examined at baseline (D0), day 21 (D21), day 42 (D42), and day 84 (D84) for noninvasive tear breakup time (NITBUT), TFLL, corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expressibility (MGEx), and Ocular Surface Disease Index (OSDI). Results: The mean age of participants was IPL+HEM: 28.06 ± 3.88 years, IPL: 29.88 ± 4.68 years, and control: 28.52 ± 3.77 years. At D84, significant improvements in TFLL (p < 0.05), noninvasive tear breakup time (NITBUT) (p < 0.05), corneoconjunctival staining (CS) (p < 0.05), MGQ (p < 0.05), MGEx (p < 0.05), and OSDI (p < 0.05) were found in the IPL+HEM and IPL groups, whereas the control group had no significant improvements. Furthermore, ΔTFLL significantly correlated with ΔNITBUT (r = -0.678, p < 0.001), ΔCS (r = 0.321, p < 0.001), ΔMGQ (r = 0.669, p < 0.001), ΔMGEx (r = 0.598, p < 0.001), and ΔOSDI score (r = 0.649, p < 0.001). Conclusions: IPL therapy in combination with HEM and IPL therapy only can significantly improve the quality of TFLL and clinically reduce the sign and symptoms of evaporative DED. However, IPL therapy in combination with HEM was found to be more effective than IPL therapy alone.

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

INTRODUCTION: 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). METHODS: 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), day 14 (D14), and day 28 (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). RESULTS: At day 28, 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. CONCLUSION: 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. TRIAL REGISTRATION: Clinical Trials Identifier: NCT05694026.

Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS.

Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%. Current chemotherapeutic strategies only benefit a minority (20-30%) of patients and there are no methods available to differentiate between responders and non-responders. We performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on albumin/IgG-depleted and non-depleted plasma samples from 23 patients with locally advanced OAC prior to treatment. Individuals were grouped based on tumour regression (TRG) score (TRG1/2/3 vs TRG4/5) after chemotherapy, and differentially abundant proteins were compared. Protein depletion of highly abundant proteins led to the identification of around twice as many proteins. SWATH-MS revealed significant quantitative differences in the abundance of several proteins between the two groups. These included complement c1q subunit proteins, C1QA, C1QB and C1QC, which were of higher abundance in the low TRG group. Of those that were found to be of higher abundance in the high TRG group, glutathione S-transferase pi (GSTP1) exhibited the lowest p-value and highest classification accuracy and Cohen's kappa value. Concentrations of these proteins were further examined using ELISA-based assays. This study provides quantitative information relating to differences in the plasma proteome that underpin response to chemotherapeutic treatment in oesophageal cancers. SIGNIFICANCE: Oesophageal cancers, including oesophageal adenocarcinoma (OAC) and oesophageal gastric junction cancer (OGJ), are one of the leading causes of cancer mortality worldwide. Curative therapy consists of surgery, either alone or in combination with adjuvant or neoadjuvant chemotherapy or radiation, or combination chemoradiotherapy regimens. There are currently no clinico-pathological means of predicting which patients will benefit from chemotherapeutic treatments. There is therefore an urgent need to improve oesophageal cancer disease management and treatment strategies. This work compared proteomic differences in OAC patients who responded well to chemotherapy as compared to those who did not, using quantitative proteomics prior to treatment commencement. SWATH-MS analysis of plasma (with and without albumin/IgG-depletion) from OAC patients prior to chemotherapy was performed. This approach was adopted to determine whether depletion offered a significant improvement in peptide coverage. Resultant datasets demonstrated that depletion increased peptide coverage significantly. Additionally, there was good quantitative agreement between commonly observed peptides. Data analysis was performed by adopting both univariate as well as multivariate analysis strategies. Differentially abundant proteins were identified between treatment response groups based on tumour regression grade. Such proteins included complement C1q sub-components and GSTP1. This study provides a platform for further work, utilising larger sample sets across different treatment regimens for oesophageal cancer, that will aid the development of 'treatment response prediction assays' for stratification of OAC patients prior to chemotherapy.