Comparing two mucin secretagogues for the treatment of dry eye disease: a prospective randomized crossover trial.

This study aimed to compare the clinical efficacy and investigate patients' preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty patients with DED were randomly treated with either 3% diquafosol or 2% rebamipide ophthalmic solution for 4 weeks, followed by an additional 4-week treatment using the other eye drop after a 2-week washout period. Objective and subjective assessments, including the corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer 1 test, tear osmolarity, tear matrix metalloproteinase-9 (MMP-9), lipid layer thickness (LLT) and ocular surface disease index (OSDI), were performed at baseline, 4 weeks, 6 weeks, and 10 weeks. Patient preferences were assessed based on four categories (comfort, efficacy, convenience, willingness to continue) using a questionnaire and the overall subjective satisfaction score for each drug was obtained at the end of the trial. In total, 28 eyes from 28 patients were included in the analysis. Both diquafosol and rebamipide significantly improved the OSDI (p = 0.033 and 0.034, respectively), TBUT (p < 0.001 and 0.026, respectively), and corneal (p < 0.001 and 0.001, respectively) and conjunctival (p = 0.017 and 0.042, respectively) staining after 4 weeks of treatment. An increase in Schirmer test scores was observed only after rebamipide treatment (p = 0.007). No significant changes were detected in tear osmolarity, MMP-9, and LLT following both treatments. The patients' preference was slightly greater for diquafosol (46.4%) than rebamipide (36.7%), presumably due to rebamipide's bitter taste. The self-efficacy of both drugs and overall satisfaction scores were comparable. These findings indicate that two mucin secretagogues showed comparable effects in ameliorating symptoms and improving signs (TBUT, corneal and conjunctival staining) in patients with DED.

Re-Esterified Triglyceride ω-3 Fatty Acids in Dry Eye Disease With Meibomian Gland Dysfunction: A Randomized Clinical Trial.

Importance: Taking ω-3 supplements has been associated with a reduction in symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). However, a recent relatively large clinical trial concluded that treating DED with ω-3 consumption was ineffective, potentially warranting additional investigations. Objectives: To investigate the effect of re-esterified triglyceride (rTG) ω-3 fatty acid supplementation on DED associated with MGD. Design, Setting, and Participants: This double-masked, parallel-group, randomized clinical trial was conducted at 7 institutions from September 2020 to January 2023. Patients with DED associated with MGD were included and randomly assigned to the ω-3 group (received 1680 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid), whereas those in the grape-seed group received 3000 mg of grape-seed oil daily. Interventions: rTG ω-3 Fatty acid supplementation vs grape-seed oil. Main Outcome Measures: The primary end point was the Ocular Surface Disease Index (OSDI) from baseline to 6 and 12 weeks. The safety parameters were visual acuity and intraocular pressure change. Results: A total of 132 patients (mean [SD] age, 50.6 [13.8] years; 103 female [78.0%]) were included in this study. The mean (SD) baseline OSDI scores of the ω-3 and grape-seed groups were 43.5 (16.5) and 44.1 (16.6), respectively. A total of 58 patients (87.9%) and 57 patients (86.4%) in the ω-3 and grape-seed groups, respectively, completed 12 weeks of follow-up. There were no differences in compliance with the dietary supplement intake between groups (ω-3, 95.8% and grape-seed, 95.4%). The OSDI (SD) change from baseline to 6 and 12 weeks was -20.5 (16.0) and -22.7 (15.7), respectively, in the ω-3 group and -15.1 (20.2) and -18.8 (21.7), respectively, in the grape-seed control group (difference at 6 weeks = -5.4; 95% CI, -12.15 to 1.33; P = .12 and at 12 weeks = -3.9; 95% CI, -10.90 to 3.13; P = .28). There were no changes in safety parameters or adverse events related to taking the dietary supplement in either group. Conclusions and Relevance: This randomized clinical trial did not show a benefit of the rTG form of ω-3 for ameliorating symptoms of DED associated with MGD, although fewer than 60 participants were evaluated in each group. Any secondary outcomes from this study should be considered for hypothesis generation of future evaluations of the effect of the rTG form of ω-3 on DED associated with MGD. Trial Registration: CRIS Identifier: KCT0004927.

Efficacy of a new refractive multifocal contact lens for presbyopia.

This prospective single-arm study aimed to evaluate the clinical efficacy and safety of a refractive multifocal contact lens for the correction of presbyopia in 22 patients. The participants underwent clinical examinations before and 1 week after wearing a refractive multifocal contact lens (OptaCon ZOOM). The primary endpoints were the corrected distance visual acuity (CDVA) and distance-corrected near visual acuity (DCNVA). Defocus curve, contrast sensitivity, and ocular surface disease index (OSDI) were analyzed. A slit-lamp examination was performed for safety analysis. Contact lens comfort and patient satisfaction were assessed using a questionnaire. No significant difference in CDVA was observed before and 1 week after refractive multifocal contact lens use (p = 0.127), whereas DCNVA was significantly improved after 1 week (p < 0.001). The contrast sensitivity was not significantly affected at any spatial frequency under mesopic or photopic conditions. OSDI was significantly increased (p = 0.023). The patient-reported satisfaction scores were 96.2, 91.9, and 85.0 out of 100 at far, intermediate, and near distances, respectively. No significant adverse events were observed. Refractive multifocal contact lenses improved near vision while maintaining distance vision in presbyopic patients, without compromising contrast sensitivity. The study results suggest that OptaCon ZOOM can be considered safe and effective for the correction of presbyopia.

New Korean Guidelines for the Diagnosis and Management of Dry Eye Disease.

New Korean guidelines for the diagnosis and management of dry eye disease were developed based on literature reviews by the Korean Dry Eye Guideline Establishment Committee, a previous dry eye guideline by Korean Corneal Disease Study Group, a survey of Korean Dry Eye Society (KDES) members, and KDES consensus meetings. The new definition of dry eye was also proposed by KDES regular members. The new definition by the regular members of the KDES is as follows: "Dry eye is a disease of the ocular surface characterized by tear film abnormalities and ocular symptoms." The combination of ocular symptoms and an unstable tear film (tear breakup time <7 seconds) was considered as essential components for the diagnosis of dry eye. Schirmer test and ocular surface staining were considered adjunctive diagnostic criteria. The treatment guidelines consisted of a simplified stepwise approach according to aqueous deficiency dominant, evaporation dominant, and altered tear distribution subtypes. New Korean guidelines can be used as a simple, valid, and accessible tool for the diagnosis and management of dry eye disease in clinical practice.

A comparative study of two presbyopia-correcting intraocular lenses combining bifocal and extended depth-of-focus profiles.

OBJECTIVE: To compare the visual performance of two presbyopia-correcting intraocular lenses (IOLs) that combine both bifocal and extended depth-of-focus profiles, Artis® Symbiose® Plus (Symbiose Plus; Cristalens Industrie, Lannion, France) and Tecnis® Synergy® (Synergy; Johnson & Johnson Vision, Santa Ana, CA, USA). METHODS: The medical records of patients with cataract bilaterally implanted with either Symbiose Plus or Synergy between January 2022 and January 2023 were assessed. The principal measures of postoperative findings included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near (40 and 33 cm) visual acuity (UNVA), objective optical quality (OOQ) parameters, distance-corrected defocus curve analysis, and surveys of subjective satisfaction. RESULTS: Total of 96 eyes from 48 patients were enrolled. Each group was equally composed of 24 patients, 48 eyes. There were no significant differences between the two groups on baseline characteristics. Both IOLs displayed excellent binocular UDVA, CDVA, and UNVA (40 and 33 cm) with no statistical difference (p = 0.467(UDVA), p = 0.584(CDVA), p = 0.096(40-cm UNVA), and p = 0.621(33-cm UNVA)). However, with regard to UIVA, the Synergy group showed significantly superior results (p < 0.001). In contrast, the Symbiose Plus group showed significantly better results on OOQ parameters and patient-reported quality of vision survey outcomes (both p < 0.001). CONCLUSIONS: Both IOLs provided a decent continuous range of vision from near to far distance.

Clinical Evaluation of a Hydrophobic Intraocular Lens Using a Preloaded Automated Injector in a Korean Population.

Purpose: This study assessed post-market clinical outcomes of the Clareon monofocal intraocular lens (IOL) preloaded in the AutonoMe Delivery System in a real-world setting of Korean patients. Methods: This prospective, multicenter, single-arm study in Korea was conducted from July 2020 to December 2021. Patients were ≥20 years old with unilateral or bilateral cataracts who received Clareon IOLs (CNA0T0) preloaded in an automated injector system. Best corrected distance visual acuity (BCDVA) and uncorrected distance visual acuity (UCDVA) were evaluated under photopic conditions. Surgeon delivery system preference was assessed using a survey questionnaire. Glistenings, surface haze, adverse events, posterior capsule opacification (PCO), and Nd:YAG capsulotomy rates were also assessed during the 12-month postoperative follow-up. Results: Mean ± SD monocular BCDVA was 0.02 ± 0.11 and 0.00 ± 0.10 logMAR at 1 month and 12 months, respectively. BCDVA of 0.2 logMAR or better was achieved by 94.4% and 99.1% of eyes at 1 month and 12 months after implantation, respectively. Mean monocular UCDVA was 0.11 ± 0.14 and 0.07 ± 0.13 logMAR at 1 month and 12 months, respectively. UCDVA of 0.3 logMAR or better was achieved by 97.4% of eyes at 12 months after implantation. Preparation of the automated injector system was rated as "very easy" or "easy" and CNA0T0 IOL delivery was rated as "very controllable" or "controllable" by all surgeons. Only grade 0 glistenings and no surface haze were observed during the 12-month follow-up. No clinically significant PCO or Nd:YAG capsulotomy were reported throughout the study; clinically nonsignificant PCO was reported in 23% of eyes. Conclusion: This 12-month real-world study of the CNA0T0 IOL and the automated injector system demonstrated excellent visual outcomes and high surgeon satisfaction.

Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction.

Earlier studies have reported that elevated protein levels in the aqueous humor (AH) are associated with corneal endothelial cell dysfunction (CECD), but the details of the underlying mechanism as well as specific biomarkers for CECD remain elusive. In the present study, we aimed to identify protein markers in AH directly associated with changes to corneal endothelial cells (CECs), as AH can be easily obtained for analysis. We carried out an in-depth proteomic analysis of patient-derived AH as well as transcriptomic analysis of CECs from the same patients with bullous keratopathy (BK) resulting from CECD. We first determined differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) from CECs and AH in CECD, respectively. By combining transcriptomic and proteomic analyses, 13 shared upregulated markers and 22 shared downregulated markers were observed between DEGs and DEPs. Among these 35 candidates from biomarker profiling, three upregulated markers were finally verified via data-independent acquisition (DIA) proteomic analysis using additional individual AH samples, namely metallopeptidase inhibitor 1 (TIMP1), Fc fragment of IgG binding protein (FCGBP), and angiopoietin-related protein 7 (ANGPTL7). Furthermore, we confirmed these AH biomarkers for CECD using individual immunoassay validation. Conclusively, our findings may provide valuable insights into the disease process and identify biofluid markers for the assessment of CEC function during BK development.

Oral Porphyromonas gingivalis infection affects intestinal microbiota and promotes atherosclerosis.

AIM: The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis. MATERIALS AND METHODS: ApoE-/- mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 109 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces. RESULTS: En face bloc preparation of the aortae showed that the PG group had a 1.7-fold increase in atherosclerotic lesions compared with the WD group (p < .01). Serum analyses showed that oral PG infection induced a significant decrease in high-density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR-B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD-fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator. CONCLUSIONS: Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR-B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis.

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial.

BACKGROUND: To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). METHODS: Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. RESULTS: The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (- 3.15±2.00) at 12 weeks from baseline than the placebo group (- 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. CONCLUSIONS: 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway.

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.

Effect and Safety of Pressure Sensor-equipped Handpiece in Phacoemulsification System.

PURPOSE: To evaluate the effect of the Active Sentry handpiece of the Centurion Vision System compared to the Centurion Ozil handpiece for phacoemulsification in cataract surgery. METHODS: A retrospective study was conducted on 281 patients (449 eyes) who underwent cataract surgery between August 2020 and June 2021. Preoperative measurements, intraoperative parameters, complication rate, and postoperative outcomes were compared between the Active Sentry handpiece and the Centurion Ozil handpiece groups. Additionally, the parameters were compared in different cataract severity groups and multiple predictive factors for the number of active surge mitigation (ASM) actuations were assessed with the Active Sentry handpiece. RESULTS: There were 198 eyes in the Active Sentry group and 251 eyes in the Centurion Ozil group. There were no statistically significant differences between the two groups, as the cumulative dissipated energy in the Active Sentry and Centurion Ozil groups were 8.32 ± 7.74 and 7.87 ± 9.25 µJ, respectively (p = 0.576). Total surgery time, ultrasound usage time, aspiration time, amount of fluid aspirated, postoperative corrected distant visual acuity, and postoperative decrease in corneal endothelial cell density were comparable between the two groups. The significant contributors to the number of ASM actuations were age, preoperative corrected distant visual acuity, axial length, and total ultrasound time. CONCLUSIONS: There was no clear advantage of the Active Sentry handpiece compared to the Centurion Ozil handpiece. ASM actuation increases with age, poor visual acuity before surgery, short axial length, and prolonged ultrasound usage time. It is expected that in more severe and high-risk cataract surgery, the Active Sentry handpiece functions more effectively, possibly affecting the safety and prognosis.

Severe ocular complications of SJS/TEN and associations among pre-onset, acute, and chronic factors: a report from the international ophthalmology collaborative group.

We formed an international research collaboration that included Japan, South Korea, Brazil, Thailand, Taiwan, the UK, and the US (682 patients from 13 hospitals between 2005 and 2020), to better evaluate the role of race, ethnicity, and other risk factors in the pathophysiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Ophthalmologists often see SJS/TEN patients with severe ocular complications (SOC; frequency 50% SJS/TEN patients) when the patients are referred to them in the chronic stage after the acute stage has passed. Global data were collected using a Clinical Report Form, capturing pre-onset factors, as well as acute and chronic ocular findings. Key conclusions of this retrospective observational cohort study were as follows: (1) Ingestion of cold medications [acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs)] was significantly and positively correlated with trichiasis, symblepharon, and/or conjunctivalization of the cornea in the chronic stage; (2) common cold symptoms prior to onset of SJS/TEN were significantly and positively correlated with acute conjunctivitis and ocular surface erosions in the acute stage and with trichiasis and symblepharon and/or conjunctivalization of the cornea in the chronic stage; (3) patients with SJS/TEN who presented with SOC tended to be female; (4) patients less than 30 years of age are more likely to develop SOC in the acute and chronic stages of SJS/TEN; (5) patients with acute severe conjunctivitis with ocular surface erosion and pseudomembrane formation in the acute stage are more likely to develop ocular sequelae in the chronic stage; and (6) onychopathy in the acute stage was positively correlated with ocular sequelae in the chronic stage. Our findings show that the ingestion of cold medications, common cold symptoms prior to the onset of SJS/TEN, and a young age might strongly contribute to developing the SOC of SJS/TEN.

Causes of Punctal Plug Loss in Sjögren's Syndrome.

PURPOSE: To evaluate the long-term maintenance rate and associated factors of silicone punctal plugs in patients with Sjögren's syndrome (SS). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 163 patients with SS who underwent silicone punctal plug insertion between December 2013 and July 2021 at Severance Hospital. The status of punctal plug insertions was classified into the following three categories by the clinician: maintenance, spontaneous loss, and intended removal. Cox proportional hazards model was used to evaluate the risk factors for spontaneous loss. RESULTS: The mean maintenance period was 12.8±15.3 (median 7.07) months. The rate of spontaneous loss was 58%, and the rate of punctal plug removal by the clinician was 14%. The number of prior plug insertions was a risk factor for spontaneous loss [hazard ratio (HR) 1.055, p=0.035]. The upper eyelid punctum was at a higher risk than the lower one (p=0.042). Small-sized plugs showed a significantly higher risk for spontaneous loss than large-sized ones (HR 1.287, p=0.035). Flow-controller type plugs were more vulnerable to spontaneous loss than complete occluders [Micro Flow™ vs. EagleFlex® (HR 2.707, p=0.008) and Micro Flow™ vs. Ultraplug™ (HR 3.402, p=0.005)]. The most common reason for removal was tear overflow (5.6%). CONCLUSION: In repeated insertion, characteristics of the punctal plug, including the type and size, and location of plug insertion, influenced the spontaneous loss of plugs. The management of punctal plugs, including insertion, maintenance, and removal, requires personalized strategies for versatile situations.

Comparison of the Predictive Accuracy of Intraocular Lens Power Calculations after Phototherapeutic Keratectomy in Granular Corneal Dystrophy Type 2.

Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease affecting vision. Phototherapeutic keratectomy (PTK) is advantageous in removing vision-threatening corneal opacities and postponing keratoplasty; however, it potentially disturbs accurate intraocular lens (IOL) power calculation in cataract surgery. The myopic/hyperopic Haigis-L method with or without the central island has been reported; nevertheless, an optimal method has not yet been established. To compare the predictive accuracy of post-PTK IOL power calculations in GCD2, the retrospective data of 30 eyes from July 2017 to December 2020 were analyzed. All GCD2-affected eyes underwent post-PTK standard cataract surgery using the WaveLight EX500 platform (Alcon Laboratories, Inc., Fort Worth, TX, USA) under a single surgeon. The mean prediction error (MPE) and absolute error (MAE) with the myopic/hyperopic Haigis-L, Barrett Universal II, Barrett True-K, Haigis, and SRK/T by standard keratometry (K) and total keratometry (TK), where possible, were analyzed. Barrett Universal II and SRK/T showed significantly superior MPE, and MAE compared with the myopic/hyperopic Haigis-L method. TK was not significantly superior to K in the same formula. In conclusion, this study suggests that these biometries and formulas, especially Barrett Universal II and SRK/T, are potentially useful in IOL power calculation in GCD2 after PTK.

Automatic measurement of mouse visual acuity based on optomotor response: SKY optomotry.

In the field of visual science study using rodents, several assessment methods have been developed for measuring visual function. However, methods such as electroretinograms tests, visual evoked potentials tests and maze tests have limitations in that they measure function of only a specific type of cells, are difficult to quantify or require sufficient training time. The method which uses an optokinetic reflex and optomotor response, a compensatory eye and head movement in response to changes in the visual scene, became the most widely used method. However, this method requires highly trained experimenters and is time consuming. We showed that measured visual acuity values are significantly different between beginner and expert. Here we suggest an automated optometry program, 'SKY optomotry', which automatically tracks rodents' optomotor response to overcome subjectivity and the lengthy scoring procedure of the existing method. To evaluate the performance of SKY optomotry using 8-12-week-old C57BL/6 mice we compared the binomial decision of SKY optomotry with a skilled expert, and the area under the curve of SKY optomotry was 0.845. Comparing the final visual acuity, the intraclass correlation coefficient value between SKY optomotry and an expert was 0.860 (95% confidence interval (CI) 0.709-0.928), whereas that between an expert and a beginner was 0.642 (95% CI 0.292-0.811). SKY optomotry showed an excellent level of performance with good inter-rater agreements based on the visual acuity measured by an expert. With the use of our application, researchers will be able to test an experimental animal's eyesight more accurately while saving time on specialized training.

Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5-a]pyrimidine CFTR Activator That Ameliorates Dry Eye Disease.

Dry eye disease (DED) is one of the most prevalent ocular diseases but has limited treatment options. Cystic fibrosis transmembrane conductance regulator (CFTR), a major chloride channel that stimulates fluid secretion in the ocular surface, may pave the way for new therapeutic strategies for DED. Herein, we report the optimization of Cact-3, a potent CFTR activator with poor solubility, to 16d, a potent CFTR activator with suitable solubility for eye drop formulation. Notably, 16d was well distributed in target tissues including cornea and conjunctiva with minimal systemic exposure in rabbit. Topical ocular instillation of 16d significantly enhanced tear secretion and improved corneal erosion in a mouse model of DED. In addition, 16d significantly reduced mRNA expression of pro-inflammatory cytokines including IL-1ß, IL-17, and TNF-α and MMP2 in cornea and conjunctiva of DED mice.

Effects of Y-27632, a Rho-associated Kinase Inhibitor, on Human Corneal Endothelial Cells Cultured by Isolating Human Corneal Endothelial Progenitor Cells.

CONCLUSIONS: Y-27632 enabled the isolation and expansion of HCEPs. It also enhanced the proliferation, viability, and migration of differentiated HCEPs. METHODS: HCEPs were isolated and expanded in a medium with and without 10µM Y-27632, and then differentiated into HCECs in a medium with fetal bovine serum. The characteristics of HCEPs and differentiated HCEPs were confirmed by immunofluorescence staining. The proliferation, viability, morphology, and wound-healing ability of differentiated HCEPs were assessed in the presence of different concentrations of Y-27632. PURPOSE: Human corneal endothelial progenitor cells (HCEPs), which has been selectively isolated and differentiated into human corneal endothelial cells (HCECs), are crucial for repairing corneal endothelial damage. In this study, we evaluated the roles of a Rho-assisted kinase (ROCK) inhibitor, Y-27632, on the isolation and expansion of HCEPs, and assessed the in vitro effects of different concentrations of Y-27632 on the differentiated HCEPs. RESULTS: Y-27632 enabled the isolation and expansion of HCEPs from the corneal endothelium. The differentiated HCEPs showed an optimal increase in proliferation and survival in the presence of 10µM Y-27632. As the concentration of Y-27632 increased, differentiated HCEPs became elongated, and actin filaments were redistributed to the periphery of cells. Y-27632 also caused a concentration-dependent enhancement in the wound-healing ability of differentiated HCEPs.

Effectiveness and safety of injectable human papilloma virus vaccine administered as eyedrops.

Mucosal vaccines have the advantages of ease of administration and the induction of strong mucosal immunity and a systemic immune response. Recently, the eye mucosa has been shown to be an effective and safe alternative vaccination route against influenza, Toxoplasma gondii infection, and hemolytic uremic syndrome in mice. In this study, we showed that the commercially available human papilloma virus (HPV) vaccine, Cervarix, induced significant immune reactions in terms of anti-HPV antigen (Ag)-specific immunoglobulin G (IgG) and IgA antibody production following eyedrop (ED) vaccination in mice. The HPV ED vaccines (EDV) provoked no signs of inflammation within 24 h, as indicated by the inflammatory cytokine mRNA levels and infiltration of mononuclear cells in inoculation sites. Moreover, the morphology of the cornea and retina and intraocular pressure of mice did not change after the HPV EDV. The functions of photoreceptor cells, including rod and cone cells, were normal following the HPV EDV inoculation in mice. These results suggest that Cervarix EDV could be a potent, safe, and effective mucosal vaccine against HPV-associated cancers.

Visual outcomes, spectacle independence, and patient satisfaction of pseudophakic mini-monovision using a new monofocal intraocular lens.

Modified monovision-or "mini-monovision"-is an alternative method to multifocal intraocular lenses (IOLs) for treating presbyopia. This study aimed to evaluate the clinical outcomes of patients bilaterally implanted with the new enhanced monofocal Tecnis Eyhance (ICB00) IOLs with the mini-monovision technique to improve near vision. In this retrospective case series, the medical records of 50 patients (100 eyes) who underwent bilateral cataract surgery were reviewed. Patients were divided into the Emmetropia and Mini-monovision groups based on the postoperative spherical equivalent and residual myopia. The binocular visual acuity for far (4 m), intermediate (66 cm), and near (40 cm) distances, binocular defocus curves, contrast sensitivity, visual symptoms, spectacle independence, and patient satisfaction rates were evaluated at 3 months postoperatively. The binocular uncorrected distance and intermediate visual acuities, contrast sensitivity, incidence of photic phenomena, and patient satisfaction were not significantly different between the two groups (p > 0.05). However, the binocular uncorrected near visual acuities and spectacle independence rates were significantly better in the Mini-monovision group (p < 0.001). Conclusively, the pseudophakic mini-monovision technique using enhanced monofocal IOLs may be a promising option for presbyopia correction in patients unsuitable for multifocal IOLs.

Gut microbiota of the young ameliorates physical fitness of the aged in mice.

BACKGROUND: Aging is a natural process that an organism gradually loses its physical fitness and functionality. Great efforts have been made to understand and intervene in this deteriorating process. The gut microbiota affects host physiology, and dysbiosis of the microbial community often underlies the pathogenesis of host disorders. The commensal microbiota also changes with aging; however, the interplay between the microbiota and host aging remains largely unexplored. Here, we systematically examined the ameliorating effects of the gut microbiota derived from the young on the physiology and phenotypes of the aged. RESULTS: As the fecal microbiota was transplanted from young mice at 5 weeks after birth into 12-month-old ones, the thickness of the muscle fiber and grip strength were increased, and the water retention ability of the skin was enhanced with thickened stratum corneum. Muscle thickness was also marginally increased in 25-month-old mice after transferring the gut microbiota from the young. Bacteria enriched in 12-month-old mice that received the young-derived microbiota significantly correlated with the improved host fitness and altered gene expression. In the dermis of these mice, transcription of Dbn1 was most upregulated and DBN1-expressing cells increased twice. Dbn1-heterozygous mice exhibited impaired skin barrier function and hydration. CONCLUSIONS: We revealed that the young-derived gut microbiota rejuvenates the physical fitness of the aged by altering the microbial composition of the gut and gene expression in muscle and skin. Dbn1, for the first time, was found to be induced by the young microbiota and to modulate skin hydration. Our results provide solid evidence that the gut microbiota from the young improves the vitality of the aged. Video Abstract.