The effect of intense pulsed light combined with topical 0.05% cyclosporin an eyedrops in the treatment of Sjögren's syndrome related dry eye.

OBJECTIVES: This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjögren's Syndrome-related dry eyes (SS-DE). RESEARCH DESIGN AND METHODS: In this prospective, randomized trial included, 60 individuals with SS-DE symptoms were randomized to receive topical eye drops containing either 0.1% sodium hyaluronate (Group S) or 0.05% CsA (Group C) plus IPL therapy. Before the first treatment (baseline), and at 12, 16, and 20 weeks after treatment commencement, we assessed the best corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI) score, the Schirmer I test (SIT), noninvasive tear breakup time (NBUT), corneal fluorescein staining (CFS), meibomian gland (MG) dropout, lid margin abnormality, MG expressibility, and meibum quality. RESULTS: Both groups showed significant improvements in the OSDI, NBUT, CFS, MG expressibility, and meibum quality (all p < 0.05). Group C showed a greater increase in OSDI, NBUT, MG expressibility, and meibum quality (all p < 0.05). Moreover, SIT and lid margin abnormalities significantly improved in Group C (both p < 0.05), but not in Group S. CONCLUSION: Treatment with 0.05% CsA eyedrops plus IPL therapy could significantly reduce the issues and physical discomfort of patients with SS-DE. CLINICAL TRIAL: Registered on 20 July 2021, with the registration number ChiCTR2100049059.

One step synthesis of highly photoluminescent red light-emitting carbon dots from O-phenylenediamine and 2,4-diaminophenol as fluorescent probes for the detection of pH and Cr(VI).

In this study, new red light-emitting carbon dots (R-CDs) that can selectively recognize Cr(VI) were prepared using a strategy that utilizes 2,4-diaminophenol to enhance the fluorescence of O-phenylenediamine based carbon dots. The results showed that 2,4-diaminophenol increased the quantum yield (QY) of the carbon quantum dots (CDs), and that the QY of the CDs increased from their original value of 8.7% to 20.1% (R-CDs). The R-CDs show sensitivity to acidic conditions and maintain good linearity between pH = 1.00-4.00, making them useful as pH probes. Furthermore, the prepared R-CDs possess good solubility in water and are responsive to changes in Cr(VI) concentrations in aqueous environments. The quenching of the R-CDs fluorescence was linearly correlated with the Cr(VI) concentration within a range of 0-20 µM, with a lower detection limit of 66 nM. The detection mechanism is attributed to the formation of hydrogen bonds between Cr(VI) and the R-CDs, resulting in the fluorescence quenching of the R-CDs. The R-CDs can be considered effective multifunctional fluorescent probes for both pH and Cr(VI) in aqueous environments. This study will provide new R-CD design strategies for probes that selectively identify specific target substances.

Cystathionine ß-Synthase Suppresses NLRP3 Inflammasome Activation via Redox Regulation in Microglia.

Aims: Cystathionine ß-synthase (CBS) is essential for homocysteine (Hcy) transsulfuration, yielding cysteine as a common precursor of hydrogen sulfide (H2S), glutathione (GSH), and other sulfur molecules, which produce neuroprotective effects in neurological conditions. We previously reported a disruption of microglial CBS/H2S signaling in a Parkinson's disease (PD) mouse model. Yet, it remains unclear whether CBS affects nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome activity and other pathologies in PD. Results: Microglial CBS expression decreased after lipopolysaccharide (LPS) stimulation. Elevated GSSG (the oxidized GSH) content and decreased H2S generation were found in the brains of microglial cbs conditional-knockout (cbscKO) mice, whereas serum and brain Hcy levels remained unaltered. Moreover, microglial cbscKO mice were susceptible to NLRP3 inflammasome activation and dopaminergic neuron losses caused by LPS injection into the substantia nigra, whereas cbs overexpression or activation produced opposite effects. In vitro studies showed that cbs overexpression or activation suppressed microglial NLRP3 inflammasome activation and interleukin (IL)-1ß secretion by reducing mitochondrial reactive oxygen species (mitoROS) level. Conversely, ablation of cbs enhanced NLRP3 expression and mitoROS generation and augmented microglial NLRP3 inflammasome activity in response to adenosine triphosphate challenge, which was blocked by the mitoROS scavenger. Innovation and Conclusion: The study demonstrated an elevated GSSG level and reduced H2S generation, which correlated with a susceptible status of microglia in the brain of cbscKO mice. Our findings reveal a critical role of CBS in restraining the microglial NLRP3 inflammasome by controlling redox homeostasis and highlight that activation or upregulation of CBS may become a potential strategy for PD treatment.

High-Intensity Use of Smartphone Can Significantly Increase the Diagnostic Rate and Severity of Dry Eye.

Purpose: To investigate the effects of high-intensity use of smartphones on ocular surface homeostasis and to explore whether high-intensity use of handheld digital devices can cause false increase of dry eye diagnostic rate. Methods: In this prospective self-control study, 60 subjects (120 eyes) were recruited and asked to read on smartphones provided by the same manufacturer for two consecutive hours. This study was conducted during 8:00 - 10:00 AM to eliminate the influence of digital equipment used the previous day. Ophthalmological examinations [non-invasive tear breakup time (NIBUT), fluorescein breakup time (FBUT), Schirmer I test, corneal fluorescein staining (CFS), bulbar conjunctival redness and meibomian gland (MG) assessment] and a questionnaire survey were conducted before and after the reading test. Based on the collected data, the changes in ocular surface damage and subjective symptoms of the subjects were evaluated, and the differences in the diagnostic rate of dry eye before and after high-intensity use of smartphones were compared. Results: The diagnostic rate of dry eye was sharply increased (61.7% vs. 74.2%). The severity of dry eye also changed significantly, and the moderate and severe degree increased after reading (10% vs. 15%; 5% vs. 10.8%). The aggravated severity subjects had lower MG expressibility and more evident bulbar conjunctival redness compared to the non-aggravated severity subjects. After 2 h of continuous reading, NIBUT-First, NIBUT-Average and FBUT-Average were significantly decreased, while the proportion of BUT ≤ 5 s increased significantly. Non-invasive keratograph tear meniscus height(NIKTMH) decreased significantly compared to the baseline level, while the proportion of NIKTMH<0.20 mm increased significantly. No significant difference was observed in the Schirmer I test and CFS score between the two groups. Compared to the baseline, evident aggravation was observed in bulbar conjunctival redness. The Ocular Surface Disease Index (OSDI) was significantly higher than the baseline after the reading test. Conclusion: Diagnostic indicators related to dry eye are rapidly deteriorating after high-intensity smartphone use, especially those with lower MG expressibility and ocular redness. High-intensity smartphone use can increase the false positive rate of dry eye diagnosis by disturbing ocular surface homeostasis.

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.

Efficacy of Intense Pulsed Light Combined Blood Extract Eye Drops for Treatment of Nociceptive Pain in Dry Eye Patients.

PURPOSE: To investigate the efficacy of intense pulsed light (IPL) combined with deproteinized calf blood extract (DCBE) eye drops for dry eye disease (DED) patients with nociceptive ocular pain. METHODS: In this prospective, one-center, interventional study, 23 subjects with DED and ocular pain were treated with a combination of IPL and DCBE eye drops for four sessions at a four-week interval. Subjective and objective assessments on nociceptive pain and dry eye were examined and analyzed. RESULTS: The visual analog scale (VAS), ocular surface disease index, ocular pain assessment survey (OPAS), patient health questionnaire-9 items, generalized anxiety disorder (GAD-7), Athens insomnia scale, corneal fluorescein staining score, meibomian gland secretion quality, and expressibility scores were significantly reduced after the treatment. Tear break-up time and Schirmer I test increased significantly. The brand density of corneal nerves and neuropeptide substance P also significantly increased. OPAS, GAD-7, meibomian gland secretion quality, and expressibility scores were essential factors affecting the VAS changes. CONCLUSIONS: IPL combined with DCBE drop therapy was effective for DED patients with ocular pain. With such treatment, both DED symptoms and the sensation of ocular pain may be improved.

Risk factors and severity of keratoconus on the East Coast of China.

PURPOSE: This study aims to investigate the characteristics, potential risk factors and associated severity of keratoconus on the east coast of China. METHODS: In this case-control study, patients diagnosed with keratoconus were invited to fill in the online electronic questionnaire designed with the help of the App named WenJuanXing. Several questions like, sex, age of diagnosis and eye care habits were administered to each subject through this e-questionnaire. Corneal topographies at diagnosis taken from Pentacam were also collected. RESULTS: Totally 391 Chinese keratoconus outpatients were enrolled in this study, among which 159 patients were newly diagnosed. Only three patients (0.77%) had a positive family history of keratoconus. Atopy could be identified in 66.0% of our patients. A total of 357 patients (91.3%) mentioned the habit of eye rubbing, with 191 patients (48.8%) rubbing their eyes frequently. Patients with younger age at onset (p = 0.005), male sex (p = 0.042), frequent eye rubbing (p = 0.003) and smoke (p = 0.002) were found significantly associated with increased risk of acute hydrops. In newly diagnosed patients, 79.9% had the maximum keratometry (Kmax) more than 52D, with males and patients aged 21-30 being even more serious (p = 0.009; p = 0.005). Besides, in patients aged over 21, frequent eye rubbing was significantly associated with steeper Kmax and more severe astigmatism (all p < 0.05). CONCLUSION: Our results suggest that frequent eye rubbing is closely related to the severity of keratoconus in Chinese patients. Chinese keratoconus patients always had much serious disease condition at the time of diagnosis. Thus, increasing the publicity of keratoconus and advocating appropriate eye care habits are needed urgently in China. REGISTRATION: The research was retrospectively registered, and the trial registration number is ChiCTR1900021273, and the registration date is 2019/02/09.

Comparison of the influence of light between circularly polarized and linearly polarized smartphones on dry eye symptoms and asthenopia.

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.

Reliability and efficacy of maximum fluorescein tear break-up time in diagnosing dry eye disease.

This study aims to investigate the reliability and efficacy of maximum fluorescein tear break-up time (FTBUTmax) in diagnosing dry eye disease (DED). 147 participants were enrolled in this study. Ocular symptoms were assessed by Ocular Surface Disease Index (OSDI). The fluorescein tear break-up time (FTBUT) examination, corneal fluorescein staining (CFS), and Schirmer I test were performed on both eyes. Each participant underwent 3 consecutive FTBUT tests, and five types of FTBUT values including FTBUTmax, the minimum FTBUT (FTBUTmin), the first FTBUT (FTBUT1), the average of three FTBUTs (FTBUT123) and the average of the first and second FTBUT (FTBUT12) were recorded. FTBUTmax was larger than the other FTBUT values, but no differences were found among the values of FTBUT1, FTBUT123, FTBUT12 and FTBUTmin. In the ROC analysis, FTBUTmax had the largest or the second largest area under the ROC (AUROC) in all three DED diagnostic criteria, while FTBUTmin had the least AUROC of them. ROC efficacy of FTBUTmax was significantly higher than that of FTBUT123, FTBUT12, FTBUT1 and FTBUTmin in the OSDI criteria and higher than that of FTBUT1 and FTBUTmin in Schirmer I test and CFS tests. FTBUTmax has a close correlation with OSDI, Schirmer I test and CFS, and is an effective tool for the DED diagnosis.

A 4-week, randomized, double-masked study to evaluate efficacy of deproteinized calf blood extract eye drops versus sodium hyaluronate 0.3% eye drops in dry eye patients with ocular pain.

BACKGROUND: To evaluate the clinical efficiency of the treatment of dry eye disease (DED) with ocular pain using deproteinized calf blood extract (DCBE) eye drops as compared to 0.3% sodium hyaluronate (SH) eye drops. METHODS: This prospective, single-center, masked (double-blind), randomized controlled study included 53 patients divided into two groups: DCBE (n=22) and SH (n=31) group. The DCBE group received DCBE eye drops for 4 weeks, and the SH group received 0.3% SH eye drops for 4 weeks. Corneal fluorescein staining (CFS) scores, tear break up time (TBUT), Schirmer test and the ocular surface disease index (OSDI) scores were evaluated in all patients before treatment, 2 and 4 weeks post-treatment. RESULTS: The DCBE group showed better improvement in the OSDI light sensitivity scores and ocular pain scores compared with the SH group (P<0.05). At 2 and 4 weeks post-treatment, the DCBE group and the SH group showed significant improvement in TBUT, Schirmer test, CFS, OSDI score, light sensitivity score and ocular pain score (P<0.05) compared with the data from before treatment. CONCLUSIONS: This study indicates that DCBE eye drops can relieve ocular pain and light sensitivity in dry eye patients better than SH eye drops.

Advances in Dry Eye Disease Examination Techniques.

Dry eye-related ocular surface examination is very important in the diagnosis and treatment of dry eye disease. With the recent advances in science and technology, dry eye examination techniques have progressed rapidly, which has greatly improved dry eye diagnoses and treatment. However, clinically, confusion remains about which examination to choose, how to ensure the repeatability of the examination, and how to accurately interpret the examination results. In this review, we systematically evaluate previous examinations of dry eye, analyze the latest views and research hotspots, and provide a reference for the diagnosis and management of dry eye.

Effects on the Ocular Surface from Reading on Different Smartphone Screens: A Prospective Randomized Controlled Study.

The purpose of this study was to investigate the influence of smartphone reading on the ocular surface and to compare the various effects of different screens and light conditions on the ocular surface. One hundred nineteen volunteers were randomly divided into: light + organic light-emitting diode (OLED), light + electronic ink (eINK), dark + OLED, and dark + eINK. Ocular surface examinations, including noninvasive break-up time (NIBUT), noninvasive keratograph tear meniscus height (NIKTMH), ocular redness, fluorescein break-up time (FBUT), corneal fluorescein staining, meibomian gland assessment, Schirmer I Test, and blinking frequency, were performed before and after a reading task. Symptoms were evaluated using the Ocular Surface Disease Index (OSDI) and Computer Vision Syndrome Questionnaire (CVS-Q). NIBUT and FBUT were decreased statistically significantly after participants read on an OLED screen for 2 hours compared with the baseline in light and dark environments, whereas no statistically significant decrease was observed on an eINK screen. NIKTMH was statistically significantly decreased after reading on an OLED screen in light and dark settings, and the eINK screen had a lesser effect on NIKTMH. An obvious increase in the ocular redness, OSDI and CVS-Q scores was observed after reading on an OLED screen, whereas the eINK screen had a lesser effect on these indicators. Blink rate increased gradually in OLED subgroups during the reading task, whereas no statistically significant difference was observed in the eINK subgroups. Our research suggested that reading on an OLED screen can cause ocular surface disorder and obvious subjective discomfort, whereas reading on an eINK screen can minimize ocular surface disorder in both dark and light environments.

Acetylsalicylic Acid Promotes Corneal Epithelium Migration by Regulating Neutrophil Extracellular Traps in Alkali Burn.

Neutrophils are the first cells to migrate into the cornea in response to alkali burns, and excessive neutrophil infiltration is associated with inflammatory injury and a poorer prognosis. In an effort to understand the mechanisms underlying the inflammation mediated by neutrophils after alkali burns, we examined the role of alkali-activated neutrophils on human corneal epithelial cells (HCEs) proliferation and migration, as well as the effects of acetylsalicylic acid (ASA) and dexamethasone (DXM) on NETosis. We stimulated human neutrophils with sodium hydroxide (NaOH) and observed dose- and time-dependent neutrophil extracellular traps (NETs) formation. We also observed that ASA, but not DXM, significantly inhibited NaOH-induced NETosis. Furthermore, the activation of nuclear factor (NF)-κB, but not the production of reactive oxygen species, was involved in ASA-regulated NETosis. Moreover, NETs were found to be involved in alkali-activated neutrophils (ANs) induced neutrophil-HCE adhesion. ANs enhanced HCEs proliferation via phagocytosis. Meanwhile, ANs inhibited HCEs migration through the release of NETs, which was partially rescued by 5 mM ASA. In conclusion, ANs may interfere with HCEs proliferation and migration by phagocytosis and NETs formation, respectively. ASA may enhance HCEs migration by decreasing NETs formation through inhibition of NF-κB activation and could be a promising strategy for improving the prognosis of corneal alkali burns.

Insights into the Mechanism of Thiol-Triggered COS/H2S Release from N-Dithiasuccinoyl Amines.

The hydrolysis of carbonyl sulfide (COS) to form H2S by carbonic anhydrase has been demonstrated to be a viable strategy to deliver H2S in a biological system. Herein, we describe N-dithiasuccinoyl amines as thiol-triggered COS/H2S donors. Notably, thiol species especially GSH and homocysteine can trigger the release of both COS and H2S directly from several specific analogues via an unexpected mechanism. Importantly, two representative analogues Dts-1 and Dts-5 show intracellular H2S release, and Dts-1 imparts potent anti-inflammatory effects in LPS-challenged microglia cells. In conclusion, N-dithiasuccinoyl amine could serve as promising COS/H2S donors for either H2S biological studies or H2S-based therapeutics development.

Clinical efficacy comparison of low-temperature plasma radiofrequency ablation and Nd:YAG laser in treating recurrent acquired nasolacrimal duct obstruction.

To evaluate the effectiveness and safety of low-temperature plasma radiofrequency ablation (coblation) and Nd:YAG laser in treating recurrent nasolacrimal duct obstruction. A prospective study was performed on patients who agreed to be treated with coblation or Nd:YAG laser for recurrent nasolacrimal duct obstruction after failed lacrimal Nd:YAG laser combined with silicone intubation. The visual analogue scale (VAS) pain grade was assessed at baseline, immediately, and 3 and 7 days after surgery. The degree of watering, lacrimal passage irrigation, and complications were also evaluated 1 week and 1, 3, and 6 months after surgery. Ninety-five patients who met the criteria for recurrent nasolacrimal duct obstruction from February 2018 to February 2019 were included in this study, with 46 patients receiving coblation and 49 patients Nd:YAG laser. The intraoperative and postoperative (3 days after surgery) VAS pain grades of the patients who received coblation were significantly lower than those who received Nd:YAG laser (P < 0.001). The number of patients in the coblation group who achieved complete clinical relief (no epiphora symptoms with fluent lacrimal passage irrigation) was significantly larger than that in the lacrimal Nd:YAG laser group at 1, 3, and 6 months after surgery (P = 0.033, P = 0.006, P = 0.003, respectively). During the follow-up period, there were no unexpected complications in either group. Compared with Nd:YAG laser, coblation performed well in alleviating pain and maintaining sustained disease relief and may therefore be an alternative to conventional laser or dacryocystorhinostomy surgery in the management of recurrent nasolacrimal duct obstruction.