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Abstract In this single-center study, 62 eyes of 41 patients with regular astigmatism, who received cataract surgery with TECNIS Eyhance Toric II intraocular lens (IOL) insertion between January 1, 2022, and June 30, 2023, were retrospectively investigated. At 3 months postoperatively, there were significant improvements in the mean logMAR uncorrected distance visual acuity (VA) (from 0.64 ± 0.42 to 0.11 ± 0.13, p

Abstract The involvement of the mechanistic targets of rapamycin (mTOR) pathway in lipid metabolism has been recently elucidated. However, its specific role in the Meibomian gland, where lipid metabolism is significant, remains not fully understood. We investigated the role of mTOR signaling system in the lipogenesis and differentiation of human meibomian gland epithelial cells (HMGECs). Treatment of HMGECs with rapamycin resulted in a reduction in lipid synthesis and the expression of PPARγ and SREBP-1, the major regulators of lipid synthesis. The phosphorylation of p70S6kinase and AKT, which are downstream signals of mTOR complexes 1 and 2, respectively, decreased following rapamycin treatment. In addition, when both mTOR complex 1 and 2 were suppressed using siRNA, there was a significant reduction in the expression of PPARγ and SREBP-1, along with a decrease in lipid synthesis in HMGECs. Our findings suggest that inhibiting the mTOR pathway diminishes the differentiation and adipogenesis of meibomian gland epithelial cells, and both mTOR complexes 1 and 2 appear to play a role in this activity.

Abstract Background To investigate the influence of femtosecond laser-assisted cataract surgery (FLACS) on macula by examining changes in retinal layers after FLACS and to compare these changes with those after conventional cataract surgery (CCS). Methods This study included 113 unrelated Korean patients with age-related cataract who underwent CCS or FLACS in Severance Hospital between September 2019 and July 2021. Optical coherence tomography was performed before and 1 month after surgery. The total retinal layer (TRL) was separated into the inner retinal layer (IRL) and outer retinal layer (ORL); moreover, the IRL was subdivided into the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), outer plexiform layer, and outer nuclear layer. We performed between-group comparisons of the postoperative thickness in each retinal layer and the postoperative differences in retinal thickness. The average retinal thickness of the four inner macular ring quadrants was used for comparative analysis. Results Compared with the CCS group, the FLACS group exhibited a thicker ORL (P = 0.004) and a thinner INL (P = 0.007) after surgery. All retinal layer thickness values showed significant postoperative changes regardless of the type of surgery (P

Abstract 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

Abstract 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

Abstract 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.

Abstract 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

Abstract 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

Abstract This study was to analyze the clinical outcomes of immediate reapplication of small-incision lenticule extraction (SMILE) without adjusting the surgical parameters after suction loss and to compare the outcomes with contralateral eyes that underwent uneventful SMILE. A total of 74 patients who underwent uneventful SMILE in one eye (Uneventful group) and immediate reapplication of SMILE without adjusting the surgical parameters after suction loss in the contralateral eye (Suction loss group) were included. Suction loss occurred during the posterior lenticule surface cut in 39 eyes (53%) and the cap cut in 35 eyes (47%). Surgical outcomes, including visual acuity, manifest refraction, keratometry, and corneal wavefront aberrations, were evaluated at 6 months postoperatively. The mean uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalent were − 0.02 ± 0.07, − 0.04 ± 0.04, and − 0.10 ± 0.46 diopters (D), respectively, in the Suction loss group and − 0.02 ± 0.07, − 0.04 ± 0.05, and − 0.19 ± 0.53 D, respectively (P = 0.965, 0.519, and 0.265, respectively), in the Uneventful group. Changes between the preoperative and 6-month postoperative total corneal aberrations, spherical aberrations, and horizontal and vertical coma did not significantly differ between the Suction loss and Uneventful groups. Immediate reapplication of SMILE without adjusting the surgical parameters after suction loss resulted in good surgical outcomes that were comparable with those of uneventful SMILE.

Abstract This study investigated the reliability and correlation of two contrast sensitivity test (CST) devices in young adults with normal visual acuity, with or without refractive surgery. 57 patients aged 20–39 years who received both manual (OPTEC-6500) and automated CST (CGT-2000) examinations from June 19 to July 24, 2021 were retrospectively enrolled. Patients with corrected visual acuity under 20/20 or history of ocular surgery other than refractive surgery were excluded. 82 eyes of 41 patients (40 eyes with and 42 without history of refractive surgery) were enrolled. Mean time taken to complete each examination was 396.4 ± 20.4 and 286.8 ± 2.3 s using manual and automated CST, respectively (P

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.

Abstract Cataract is the leading cause of blindness worldwide, and advanced cataract techniques such as femtosecond laser-assisted cataract surgery (FLACS) have been commercially available. Corneal refractive surgery (CRS) is one of the most popular surgeries for the correction of refractive errors. CRS changes the cornea not only anatomically but also pathophysiologically. However, there has been no clinical research analyzing the refractive and safety outcomes of FLACS after CRS. The aim of this retrospective chart review and comparative study is to evaluate the effect and safety of FLACS after CRS comparing with conventional PCS. Participants with a previous CRS history who underwent FLACS or conventional PCS were included in this study. The visual outcomes and the refractive outcomes including refractive, corneal, and ocular residual astigmatism were compared. The safety outcomes were then studied intraoperatively and postoperatively. A total of 102 patients with age-related cataract were enrolled. At 3 months postoperatively, UCVA, BCVA, and predictive error were not significantly different between the FLACS and conventional PCS groups. Reduction of refractive astigmatism was higher in FLACS. Postoperative ORA was significant lower in FLACS. Reduction of ORA was higher in FLACS. The intraoperative and postoperative complications were also not significantly different between the two groups. FLACS could effectively change refractive astigmatism and ORA; without more complications than conventional PCS. FLACS’ competitive edge in postoperative ORA may provide better visual quality than conventional PCS in patients with a previous history of CRS.

Abstract To investigate keratometric measurements according to axial length in an aged population. Patients requiring cataract surgery with keratometric measurements from four different ophthalmic devices (autorefractor/keratometer, Scheimpflug imaging, corneal topography/ray-tracing aberrometry, and partial coherence interferometry) between January 2016 and March 2021 were reviewed retrospectively. Cases for which four ophthalmic devices were deployed in the same order a day were included in this investigation. The corneal curvature of the flattest and steepest meridian, mean corneal curvature, corneal astigmatism, steepest axis location, and axial length were evaluated. In total, 250 eyes (137 patients) were included in the analysis. A negative correlation was found between mean corneal curvature and axial length, with correlation coefficients of 0.587, 0.592, 0.588, 0.591, 0.588, and 0.562 for autorefractor/keratometer, Scheimpflug imaging, corneal topography/ray-tracing aberrometry, partial coherence interferometry, total corneal refractive power of Scheimpflug imaging, and simulated keratometry of corneal topography/ray-tracing aberrometry measurements, respectively. No statistically significant differences were found for corneal astigmatism according to axial length. In axial length group of less than 26.0 mm, negative correlation was found between axial length and mean frontal corneal curvature while no correlation was found between axial length and corneal astigmatism. All four ophthalmic devices showed good inter-device reliability for mean corneal curvature but not corneal astigmatism.

Abstract Background To investigate the surgical outcomes of implantable collamer lens (ICL) implantation in eyes with residual myopia after primary laser vision correction (LVC) surgeries. Methods This study included patients who underwent ICL implantation and had a history of LVC surgery, including photorefractive keratectomy (PRK) or laser-assisted in situ keratomileusis (LASIK). Visual acuity and refractive error were assessed pre and 3-months postoperatively and the efficacy and safety indices calculated accordingly. Results A total of 30 eyes of 17 patients were included in this study. At 3 months, the mean logMAR uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalent were − 0.03 ± 0.11 (include logMAR), − 0.04 ± 0.09 (include logMAR), and − 0.06 ± 0.33 diopters (D), respectively. The 3-month Snellen UDVA was better than 20/20 for 83% of eyes, and 97% of eyes showed an unchanged or improved CDVA after surgery. The mean efficacy and safety indices were 1.11 ± 0.22 and 1.13 ± 0.20, respectively. Further, 93 and 100% of eyes were within ±0.5 and ± 1.0 D of the attempted spherical equivalent refraction, respectively. Conclusions ICL implantation in eyes with myopic regression after previous LVC surgery showed safe, effective, and predictable outcomes. Trial registration retrospectively registered.

PurposeTo evaluate the value of artificial intelligence (AI) for recommendation of pupil dilation test using medical interview and basic ophthalmologic examinations.DesignRetrospective, cross-sectional study.SubjectsMedical records of 56,811 patients who visited our outpatient clinic for the first time between 2017 and 2020 were included in the training dataset. Patients who visited the clinic in 2021 were included in the test dataset. Among these, 3,885 asymptomatic patients, including eye check-up patients, were initially included in test dataset I. Subsequently, 14,199 symptomatic patients who visited the clinic in 2021 were included in test dataset II.MethodsAll patients underwent a medical interview and basic ophthalmologic examinations such as uncorrected distance visual acuity, corrected distance visual acuity, non-contact tonometry, auto-keratometry, slit-lamp examination, dilated pupil test, and fundus examination. A clinically significant lesion in the lens, vitreous, and fundus was defined by subspecialists, and the need for a pupil dilation test was determined when the participants had one or more clinically significant lesions in any eye. Input variables of AI consisted of a medical interview and basic ophthalmologic examinations, and the AI was evaluated with predictive performance for the need of a pupil dilation test.Main outcome measuresAccuracy, sensitivity, specificity, and positive predictive value.ResultsClinically significant lesions were present in 26.5 and 59.1% of patients in test datasets I and II, respectively. In test dataset I, the model performances were as follows: accuracy, 0.908 (95% confidence interval (CI): 0.880–0.936); sensitivity, 0.757 (95% CI: 0.713–0.801); specificity, 0.962 (95% CI: 0.947–0.977); positive predictive value, 0.878 (95% CI: 0.834–0.922); and F1 score, 0.813. In test dataset II, the model had an accuracy of 0.949 (95% CI: 0.934–0.964), a sensitivity of 0.942 (95% CI: 0.928–956), a specificity of 0.960 (95% CI: 0.927–0.993), a positive predictive value of 0.971 (95% CI: 0.957–0.985), and a F1 score of 0.956.ConclusionThe AI model performing a medical interview and basic ophthalmologic examinations to determine the need for a pupil dilation test had good sensitivity and specificity for symptomatic patients, although there was a limitation in identifying asymptomatic patients.

BackgroundCorneal topography is a clinically validated examination method for keratoconus. However, there is no clear guideline regarding patient selection for corneal topography. We developed and validated a novel artificial intelligence (AI) model to identify patients who would benefit from corneal topography based on basic ophthalmologic examinations, including a survey of visual impairment, best-corrected visual acuity (BCVA) measurement, intraocular pressure (IOP) measurement, and autokeratometry.MethodsA total of five AI models (three individual models with fully connected neural network including the XGBoost, and the TabNet models, and two ensemble models with hard and soft voting methods) were trained and validated. We used three datasets collected from the records of 2,613 patients' basic ophthalmologic examinations from two institutions to train and validate the AI models. We trained the AI models using a dataset from a third medical institution to determine whether corneal topography was needed to detect keratoconus. Finally, prospective intra-validation dataset (internal test dataset) and extra-validation dataset from a different medical institution (external test dataset) were used to assess the performance of the AI models.ResultsThe ensemble model with soft voting method outperformed all other AI models in sensitivity when predicting which patients needed corneal topography (90.5% in internal test dataset and 96.4% in external test dataset). In the error analysis, most of the predicting error occurred within the range of the subclinical keratoconus and the suspicious D-score in the Belin-Ambrósio enhanced ectasia display. In the feature importance analysis, out of 18 features, IOP was the highest ranked feature when comparing the average value of the relative attributions of three individual AI models, followed by the difference in the value of mean corneal power.ConclusionAn AI model using the results of basic ophthalmologic examination has the potential to recommend corneal topography for keratoconus. In this AI algorithm, IOP and the difference between the two eyes, which may be undervalued clinical information, were important factors in the success of the AI model, and may be worth further reviewing in research and clinical practice for keratoconus screening.

PurposeTo assess the effects of femtosecond laser arcuate keratotomy with femtosecond laser-assisted cataract surgery in the management of corneal astigmatism, compared with conventional phacoemulsification cataract surgery.DesignRetrospective comparative interventional case series.MethodsA total of 2,498 eyes of consecutive patients who presented with 3.00 diopters (D) or under of astigmatism were included. The patients were treated with conventional phacoemulsification cataract surgery (conventional group) and femtosecond laser arcuate keratotomy with femtosecond laser-assisted cataract surgery (femtosecond group).ResultsSurgically induced astigmatism (SIA) was higher in the femtosecond group than the conventional group (0.215, p < 0.001). Difference vector (DV) was lower in the femtosecond group (-0.136, p < 0.001). The cut-off value of the overcorrection in the femtosecond group was 0.752 D of target induced astigmatism (TIA). For patients with TIA 0.75 D or under, DV and the value of index of success (TIA into DV) were significantly higher in the femtosecond group (p = 0.022 and < 0.001). The overcorrection ratios were 48.8% in the conventional and 58.9% in the femtosecond group. (p < 0.001). For patients with TIA over 0.75 D, SIA and correction index (TIA into SIA) was higher in femtosecond group (0.310 and 0.250, p < 0.001 and < 0.001, respectively). Absolute angle of error was 20.612 ± 18.497 in the femtosecond group and higher than the conventional group (2.778, p = 0.010).ConclusionFemtosecond laser arcuate keratotomy in cataract surgery was effective in SIA between 0.75 to 3.00 D of corneal astigmatism. However, the overcorrection in the lower astigmatism and angle of error in the higher astigmatism were due to the postoperative corneal astigmatism not decreasing as much as SIA. Overcoming these challenges will lead to better management of corneal astigmatism.

Abstract Background No studies have been reported on the efficacy and safety of long-term (≥12 months) use of topical tacrolimus for refractory ocular surface inflammation in pediatric patients. Methods Medical records of pediatric patients who were prescribed topical 0.02% tacrolimus ointment for refractory ocular surface inflammation between January of 2010 and March of 2018 were reviewed retrospectively. Changes in ocular surface signs during slit-lamp examination, clinical symptoms and concurrent steroid use were graded with a scoring system. The presence of side effects was also assessed. The changes in disease severity and patient symptoms were compared between baseline and after the treatment. Results Among 72 patients (55% males, mean age 10.8 ± 3.9 years, range 3 to 17 years), 25 patients (48% males, mean age 11.4 ± 3.9 years) fully recovered, resulting in discontinuance of the ointment treatment before 12 months. Six patients experienced intolerable burning sensation, which required treatment cessation. Cessation days of those who quit were 1,5,14,20,26, and 35 days. Seven patients were lost during follow-up. Thirty-four patients (56% males, mean age 11.2 ± 4.2 years, range 3 to 17 years) were treated with tacrolimus ointment for over 12 months (average 23.1 ± 19.1 months, range 12 to 98 months). During the follow-up period, all patients showed improved clinical signs and symptoms, and no adverse reaction was noted. Conclusions Long-term maintenance of topical tacrolimus 0.02% ointment is safe and effective in improving refractory ocular surface inflammation in pediatric patients.

Abstract This study evaluated the accuracy of total keratometry (TK) and standard keratometry (K) for intraocular lens (IOL) power calculation in eyes treated with femtosecond laser-assisted cataract surgery. The retrospective study included a retrospective analysis of data from 62 patients (91 eyes) who underwent uneventful femtosecond laser-assisted cataract surgery with Artis PL E (Cristalens Industrie, Lannion, France) IOL implantation by a single surgeon between May 2020 and December 2020 in Severance Hospital, Seoul, South Korea. The new IOLMaster 700 biometry device (Carl Zeiss Meditec, Jena, Germany) was used to calculate TK and K. The mean absolute error (MAE), median absolute error (MedAE), and the percentages of eyes within prediction errors of ± 0.25 D, ± 0.50 D, and ± 1.00 D were calculated for all IOL formulas (SRK/T, Hoffer-Q, Haigis, Holladay 1, Holladay 2, and Barrett Universal II). There was strong agreement between K and TK (intraclass correlation coefficient = 0.99), with a mean difference of 0.04 D. For all formulas, MAE tended to be lower for TK than for K, and relatively lower MAE and MedAE values were observed for SRK/T and Holladay 1. Furthermore, for all formulas, a greater proportion of eyes fell within ± 0.25 D of the predicted postoperative spherical equivalent range in the TK group than in the K group. However, differences in MAEs, MedAEs, and percentages of eyes within the above prediction errors were not statistically significant. In conclusion, TK and K exhibit comparable performance for refractive prediction in eyes undergoing femtosecond laser-assisted cataract surgery.

Abstract Background The aim of this study was to evaluate the effects of systemic parameters, laboratory findings, oral parameters, and other ocular surface parameters on ocular surface epithelial damage in patients with primary Sjögren’s syndrome (pSS). Methods A total of 82 dry eye disease (DED) patients with pSS were enrolled in this study. Ocular surface epithelial damage was measured by ocular staining score (OSS). Systemic parameters, laboratory findings including serologic markers, oral parameters, and other ocular surface parameters were collected. Other ocular surface parameter assessments such as the Schirmer’s test, fluorescein tear breakup time, meibomian gland examinations, noninvasive keratographic tear film break-up time measurements using the Keratograph® 5 M were performed, and the Ocular Surface Disease Index was determined. Results In a multivariate analysis, decreased age and increased duration of pSS were significantly related to increased logarithm-transformed OSS (β = -0.011, P = 0.043 and β = 0.003, P = 0.008). Among the ocular surface parameters, decreased fluorescein tear breakup time and increased MGD grade were significantly associated with increased logarithm-transformed OSS (β = -0.183, P

Abstract Background To acquire desirable outcomes of penetrating keratoplasty (PKP), various factors affecting graft survival, visual function, and subjective symptom should be considered. As ocular surface and meibomian gland function are associated with these factors, this study aims to investigate changes of ocular surface and meibomian gland parameters after PKP. Methods This retrospective case series study included 24 eyes of 24 patients who underwent penetrating keratoplasty. Examinations on lipid layer thickness (LLT), meiboscore, tear meniscus area (TMA), tear breakup time (TBUT), corneal fluorescein staining (CFS), Schirmer I test (SIT), Ocular Surface Disease Index (OSDI), and meibomian gland functions were performed before and at 1 week, 1 month, 6 months, and 12 months after surgery. Results Compared to baseline (2.9 ± 0.6 s), TBUTs were longer at 1 week (4.4 ± 0.5 s, P = 0.027) and 6 months (4.4 ± 0.5, P = 0.048) after surgery. CFS values improved from baseline (6.5 ± 1.1) to 6 months (3.5 ± 0.6, P = 0.023) and 12 months (3.3 ± 0.7, P = 0.001) after surgery. Meibum quality value worsened at 1 week and 12 months after surgery and meibomian gland expressibility value worsened at 1 week and 6 months after surgery compared to baseline. OSDI scores improved at 6 and 12 months after surgery. Meiboscore showed no change throughout the follow up period. The patients with high preoperative meiboscore had worse meibomian gland expressibility at 6 and 12 months and meibum quality at 6 months postoperatively compared to their baseline and to those of patients with low preoperative meiboscore. Conclusions After penetrating keratoplasty, ocular surface parameters including corneal staining, TBUT, and OSDI significantly improved whereas meibomian gland parameters showed deteriorations, which was marked in patients with high preoperative meiboscore. Thus, perioperative management of MGD is recommended for patients who undergo penetrating keratoplasty, especially in patients with advanced MGD.

Abstract We aimed to determine the clinical impact of conjunctivochalasis (CCh) and its correction using high-frequency radiowave electrosurgery (HFR-ES), for signs and symptoms of dry eye disease (DED). Forty patients diagnosed with symptomatic CCh were prospectively enrolled. As a result, patients with CCh had moderate to severe DED and most of them exhibited meibomian gland dysfunction (MGD). Corneo-conjunctival fluorescein staining score (CFS) and all lid-parallel-conjunctival-folds scores (LIPCOFs) were positively correlated. Nasal LIPCOF significantly correlated with symptoms and tear volume. Central, temporal, and total LIPCOF significantly correlated with MG loss, MGD stage, and lipid layer thickness. Independent significant factors associated with total LIPCOF included CFS, tear break-up time, and MGD stage. One month following HFR-ES, CCh was completely resolved in all cases. Patient age and preoperative nasal LIPCOF were determinants of outcomes associated with postoperative improvements in symptoms. Ocular surface parameters significantly improved, but MGD-related signs did not. Collectively, CCh associated with MGD severity deteriorates not only tear film stability and reservoir capacity, leading to DED exacerbation. Therefore, CCh should be corrected in patients with DED and MGD. Younger patients with nasal CCh are likely to experience more symptomatic relief after HFR-ES. Particularly, management for MGD should be maintained after CCh correction.

Abstract Visually impaired and blind people due to diabetic retinopathy were 2.6 million in 2015 and estimated to be 3.2 million in 2020 globally. Though the incidence of diabetic retinopathy is expected to decrease for high-income countries, detection and treatment of it in the early stages are crucial for low-income and middle-income countries. Due to the recent advancement of deep learning technologies, researchers showed that automated screening and grading of diabetic retinopathy are efficient in saving time and workforce. However, most automatic systems utilize conventional fundus photography, despite ultra-wide-field fundus photography provides up to 82% of the retinal surface. In this study, we present a diabetic retinopathy detection system based on ultra-wide-field fundus photography and deep learning. In experiments, we show that the use of early treatment diabetic retinopathy study 7-standard field image extracted from ultra-wide-field fundus photography outperforms that of the optic disc and macula centered image in a statistical sense.

PurposeTo investigate an artificial intelligence (AI) model performance using multi-source anterior segment optical coherence tomographic (OCT) images in estimating the preoperative best-corrected visual acuity (BCVA) in patients with senile cataract.DesignRetrospective, cross-instrument validation study.SubjectsA total of 2,332 anterior segment images obtained using swept-source OCT, optical biometry for intraocular lens calculation, and a femtosecond laser platform in patients with senile cataract and postoperative BCVA ≥ 0.0 logMAR were included in the training/validation dataset. A total of 1,002 images obtained using optical biometry and another femtosecond laser platform in patients who underwent cataract surgery in 2021 were used for the test dataset.MethodsAI modeling was based on an ensemble model of Inception-v4 and ResNet. The BCVA training/validation dataset was used for model training. The model performance was evaluated using the test dataset. Analysis of absolute error (AE) was performed by comparing the difference between true preoperative BCVA and estimated preoperative BCVA, as ≥0.1 logMAR (AE≥0.1) or 0.1 was 21.4% in the AE≥0.1 group, of which 88.9% were in the underestimation group. The incidence of vision-impairing disease in the underestimation group was 95.7%. Preoperative corneal astigmatism and lens thickness were higher, and nucleus cataract was more severe (p < 0.001, 0.007, and 0.024, respectively) in AE≥0.1 than that in AE

Abstract To investigate conditions that cause temporal lens opacity, we tested chemical and physical factors, such as anaesthesia dose, ocular surface dryness, and infrared (IR) light exposure in anaesthetised C57BL/6 N mice. Mice were anaesthetised with a low (80%; tiletamine/zolazepam 32 mg/kg and xylazine 8 mg/kg, intraperitoneal injection) or high (120%; 48 mg/kg and 12 mg/kg) dose of anaesthetic and examined every 5 min from 10 to 30 min after anaesthesia was induced. Lens opacity levels were assessed and graded (1–6) using the standard classification system. Regardless of the anaesthetic dose, lens opacity grade was 1–2 in moisturised eyes with application of 0.5% carboxymethylcellulose, and 5–6 in dry ocular surface conditions. Lens opacity in mice with high-dose anaesthetic in the dry ocular surface condition was not different from that of mice with low-dose anaesthetic. Lens opacity grade 1–2 was noted in eyes in the wet ocular surface condition, regardless of IR light exposure. During IR light exposure in eyes in the dry ocular surface condition, lens opacity (grade 6) in mice with high-dose anaesthetic was not different from that (grade 6) in mice with low-dose anaesthetic. We demonstrated that ocular surface dryness might be a relevant factor for the formation and progression of lens opacity in anesthetized C57BL/6 N mice. Anaesthesia dose and IR light exposure did not strongly influence lens opacity formation. Furthermore, eyes with corneal dryness-induced lens opacity recovered to normal status without additional intervention.

Dendritic cells (DCs) are key antigen-presenting cells that prime naive T cells and initiate adaptive immunity. Although the genetic deficiency and transgenic overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) signaling were reported to influence the homeostasis of DCs, the in vivo development of DC subsets following injection of GM-CSF has not been analyzed in detail. Among the treatment of mice with different hematopoietic cytokines, only GM-CSF generates a distinct subset of XCR1-33D1- DCs which make up the majority of DCs in the spleen after three daily injections. These GM-CSF-induced DCs (GMiDCs) are distinguished from classical DCs (cDCs) in the spleen by their expression of CD115 and CD301b and by their superior ability to present blood-borne antigen and thus to stimulate CD4+ T cells. Unlike cDCs in the spleen, GMiDCs are exceptionally effective to polarize and expand T helper type 2 (Th2) cells and able to induce allergic sensitization in response to blood-borne antigen. Single-cell RNA sequencing analysis and adoptive cell transfer assay reveal the sequential differentiation of classical monocytes into pre-GMiDCs and GMiDCs. Interestingly, mixed bone marrow chimeric mice of Csf2rb+/+ and Csf2rb-/- demonstrate that the generation of GMiDCs necessitates the cis expression of GM-CSF receptor. Besides the spleen, GMiDCs are generated in the CCR7-independent resident DCs of the LNs and in some peripheral tissues with GM-CSF treatment. Also, small but significant numbers of GMiDCs are generated in the spleen and other tissues during chronic allergic inflammation. Collectively, our present study identifies a splenic subset of CD115hiCD301b+ GMiDCs that possess a strong capacity to promote Th2 polarization and allergic sensitization against blood-borne antigen.

BackgroundIn epidemiological studies, finding the best subset of factors is challenging when the number of explanatory variables is large. ObjectiveOur study had two aims. First, we aimed to identify essential depression-associated factors using the extreme gradient boosting (XGBoost) machine learning algorithm from big survey data (the Korea National Health and Nutrition Examination Survey, 2012-2016). Second, we aimed to achieve a comprehensive understanding of multifactorial features in depression using network analysis. MethodsAn XGBoost model was trained and tested to classify “current depression” and “no lifetime depression” for a data set of 120 variables for 12,596 cases. The optimal XGBoost hyperparameters were set by an automated machine learning tool (TPOT), and a high-performance sparse model was obtained by feature selection using the feature importance value of XGBoost. We performed statistical tests on the model and nonmodel factors using survey-weighted multiple logistic regression and drew a correlation network among factors. We also adopted statistical tests for the confounder or interaction effect of selected risk factors when it was suspected on the network. ResultsThe XGBoost-derived depression model consisted of 18 factors with an area under the weighted receiver operating characteristic curve of 0.86. Two nonmodel factors could be found using the model factors, and the factors were classified into direct (P

Background Porphyromonas gingivalis (Pg) is an oral anaerobe which damages teeth and periodontal tissues. Its body infection is known to cause chronic inflammation, thereby inducing an early stage of atherosclerosis through humoral immune actions. Hence, vaccination by immunizing the proteins of P. gingivalis (Pg) post sonication with heating may prevent atherosclerosis. This study aimed to compare the effect of its vaccination with statin, which effectively prevents atherosclerosis by lowering lipids. Methods The vaccine was produced by sonicating P. gingivalis through heating, and a total of 32 male APOE-/-mice (8-week old) were subjected Western diet for 8 weeks, in order to induce atherosclerosis in a physiological manner. Then, the mice were grouped to undergo four treatment conditions (i.e., no treatment, pitavastatin, vaccine, or pitavastatin with vaccine). Vaccination was conducted through nasal immunization and confirmed by a Pg-specific humoral immune reaction. Then, half of the mice in each group were orally injected with P. gingivalis for the next 5 weeks while the other half remained uninfected, generating a total of eight groups (n = 4/group). The mice were sacrificed at 3 weeks after the last injection. After harvesting the aorta, Oil Red O staining of en face was conducted with imaging and image analysis, and plaque formation was quantitatively determined. Results Compared to no treatment, the vaccination through nasal immunization significantly reduced the atherosclerotic plaque sizes in APOE -/- mice under Western diet to the comparable level of statin group. When both vaccine and statin were used, no clear synergistic effect was observed as opposed to expectation. Conclusions This study revealed that nasal immunization of heat shock P. gingivalis has a significant impact on the prevention of arteriosclerosis and acts as a potential comparator of statin.

This review describes the current knowledge regarding genetic susceptibilities and treatment strategies for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with ocular complications, in Korea. In a case-control study, the gene frequencies of both HLA-A*0206 (20.0%) and HLA-Cw*0304 (15.0%) increased but the gene frequency of HLA-Cw*0303 (1.3%) decreased with cold medicine (CM)-SJS/TEN with severe ocular complications (SOCs). In a case-series, positive genotyping of HLA-B*5801 was 80.0% in allopurinol-induced SJS/TEN without SOCs. In a genome-wide association study, HLA-A*0206 was substantially related to CM-SJS/TEN with SOCs. Both HLA-A*0206 and prostaglandin-E receptor 3 (PTGER3) single nucleotide polymorphism (SNP) rs1327464 exert a synergistic effect on SOCs in CM-SJS/TEN. In the acute stage, conventional procedures, amniotic membrane transplantation or suture-less amniotic contact lenses are applied. Applications of intravenous Immunoglobulin (IVIG) or mega-dose steroids are attempted in patients with high acute ocular and systemic involvement scores. In the chronic stage, keratolimbal transplantation and penetrating keratoplasty are the standard procedures. Either autologous nasal or oral mucosal grafts, or biomaterial-free cultured oral mucosal epithelial cell sheets are transplanted as alternative therapies. Deep anterior lamellar keratoplasty is attempted. Combined photodynamic therapy with intrastromal bevacizumab injection or intense pulse laser are used to resolve chronic ocular complication. Corneoscleral contact lenses are available for a visual rehabilitation. As a last resort, Seoul-type keratoprosthesis had been transplanted. There are unmet needs to standardize nationwide ocular grading system and to correct tarsal scarring using mucosal grafting. This review provides a perspective on the current practices to treat ocular complications in SJS/TEN.

Abstract Transplantation of cultivated limbal epithelial transplantation has been proven to restore the corneal surface in limbal stem cell deficiency (LSCD). Here we comparatively investigated the optimized conditions and the efficiency of limbal epithelial sheet growth in three media conditions as well as with substrate free (transwell), human amniotic membrane (HAM) sutured onto transwell inserts (HAMTW), and HAM slide scaffold (HAMS). Outcomes evaluated were outgrowth sheet size from limbal explants, expression of stem/progenitor cell markers p63α, ABCG2 and CK15, and colony formation efficiency (CFE). Additionally, limbal epithelial sheets on HAMS were transplanted into corneas of LSCD rabbit models. Limbal epithelial sheets with 5% human AB serum showed the greatest increase in ABCG2 efflux activity (JC1low), p63α expression, and CFE compared in both conditions without HAM and with HAM, respectively. The outgrowth sheet size, cell yield, and Ki67 expression were increased in limbal epithelial sheets on HAMS compared to transwell and HAMTW. ABCG2 efflux activity, p63α and CK15 expressions, and CFE were also increased in limbal epithelial sheets on HAMS as well. In corneas of transplanted rabbit LSCD models, p63α expressions were noted in the basal layers and CK12 expressions were observed in superficial layers. Cultivation of limbal epithelial sheet on HAMS with xeno-free medium enhances the growth and stemness of limbal epithelial sheets.

Abstract Background To evaluate clinical factors affecting postoperative vaulting in eyes that had achieved optimal vaulting within the range of 250–750 μm following implantation of 12.6-mm V4c implantable collamer lenses (ICL). Methods A total of 236 eyes of 236 patients that had achieved optimal vaulting following implantation of a 12.6-mm V4c ICL were retrospectively analyzed. Associations between postoperative vaulting and age, preoperative anterior chamber depth (ACD), preoperative axial length (AL), preoperative white-to-white diameter, preoperative pupil size, preoperative sulcus-to-sulcus diameter, and preoperative manifest refraction spherical equivalent were investigated using simple regression, stepwise multiple regression, and multinomial logistic regression analyses. Results Mean central vaulting at the 6-month follow-up was 519.0 ± 112.8 μm. Variables relevant to postoperative vaulting were, in order of influence, preoperative ACD (β = 0.305, p

Abstract Background To compare the clinical outcomes of wavefront-optimized (WFO) transepithelial photorefractive keratectomy (trans-PRK) and corneal wavefront-guided (CWFG) trans-PRK for myopic eyes with moderate to high astigmatism. Methods One hundred ninety-six eyes (196 patients) with moderate to high astigmatism (≥ 1.75 D) treated with WFO or CWFG trans-PRK (101 and 95 eyes, respectively) were retrospectively registered. Safety, efficacy, predictability, vector analysis, and corneal aberrations were compared between groups preoperatively and at 6 months postoperatively. Results At postoperative 6 months, the mean logMAR uncorrected distance visual acuity was similar in the WFO (− 0.07 ± 0.08) and CWFG (− 0.07 ± 0.07) groups. Safety, efficacy, and predictability of refractive and visual outcomes were also similar. The correction indices were 1.02 ± 0.14 and 1.03 ± 0.13 in the WFO and CWFG groups, respectively, with no significant difference. The absolute values of the angle of error were significantly higher in the WFO group (2.28 ± 2.44 vs. 1.40 ± 1.40; P = 0.002). Corneal total root mean square higher-order aberrations and corneal spherical aberrations increased postoperatively in both groups; however, the change was smaller in the CWFG group. Corneal coma showed a significant increase postoperatively only in the WFO group. Conclusions WFO and CWFG trans-PRK are safe and effective for correcting moderate to high astigmatism. However, CWFG trans-PRK provides a more predictable astigmatism correction axis and fewer induced corneal aberrations.

AIM: To compare characteristics of preloaded and non-preloaded intraocular lens (IOL) delivery systems during IOL delivery procedures. METHODS: Total 101 human eyes were included in this prospective observational case series. Delivery characteristics of 5 types of IOLs including iSert250 NC60 (NC60), EnVista MX60 (MX60), AcrySof IQ SN60WF (SN60WF), TECNIS ZCB00 (ZCB00), and TECNIS PCB00 (PCB00) were investigated. NC60 and PCB00 were injected via preloaded delivery systems and other IOLs were injected via non-preloaded systems. In the human trial, time taken from IOL loading to completion of implantation was measured in all eyes undergoing conventional cataract surgery. Using 4 excised porcine eyes, dynamics of ophthalmic viscosurgical device (OVD) between an IOL injector and a porcine eye was analyzed using fluorescein sodium-stained OVD. RESULTS: The average time for IOL implantation was 22.0s for NC60, 43.2s for MX60, 32.3s for SN60WF, 41.4s for ZCB00, and 14.6s for PCB00 respectively. The number of cases with IOL manipulation with a second instrument was 6 for MX60, 2 for ZCB00, 0 for SN60WF, NC60, and PCB00. Amount of OVD pushed into a porcine eye was smaller with a preloaded system than with non-preloaded systems. CONCLUSION: IOL delivery with preloaded systems is faster and more predictable. Moreover, a preloaded delivery system shows relatively less OVD pushed into a porcine eye than non-preloaded systems.

Abstract Background To investigate the effects of combined corneal wavefront-guided transepithelial photorefractive keratectomy (tPRK) and accelerated corneal collagen cross-linking (CXL) after intracorneal ring segment (ICRS) implantation in patients with moderate keratoconus. Methods Medical records of 23 eyes of 23 patients undergoing combined tPRK and CXL after ICRS implantation were retrospectively analyzed. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent (MRSE), corneal indices based on Scheimpflug tomography, higher-order aberrations (HOAs), and corneal biomechanical properties were evaluated before and after ICRS implantation, and at 1, 3, and 6 months after combined tPRK and CXL. Results There were significant improvements in final logMAR UDVA and logMAR CDVA, and reductions in sphere, MRSE, and all corneal indices from baseline. Significant improvements in logMAR UDVA and reductions in sphere, MRSE, maximal keratometry, keratometry at the apex, mean keratometry, and keratoconus index were noted after ICRS implantation. After tPRK and CXL, significant improvements in logMAR UDVA and logMAR CDVA, and reductions in cylinder and all corneal indices were observed. There were significant improvements in final root mean square HOAs and coma aberrations from baseline, but no changes from baseline after ICRS implantation. Significant reductions in final radius and deformation amplitude from baseline were noted. Conclusions Combined tPRK and accelerated CXL after ICRS implantation in moderate keratoconus appears to be a safe and effective treatment, providing an improvement in visual acuity, corneal indices, and HOAs. Trial registration retrospectively registered (identification no. NCT03355430 ). Date registered: 28/11/2017.

An amendment to this paper has been published and can be accessed via the original article.

Ex vivo culture of human limbal epithelial cells (LECs) is used to treat limbal stem cell (LSC) deficiency, a vision loss condition, and suitable culture systems using feeder cells or serum without animal elements have been developed. This study evaluated the use of human umbilical cord or placenta mesenchymal stem cells (C-MSCs or P-MSCs, resp.) as feeder cells in an animal/serum-free coculture system with human LECs. C-/P-MSCs stimulated LEC colony formation of the stem cell markers (p63, ABCG2) and secreted known LEC clonal growth factors (keratinocyte growth factor, β-nerve growth factor). Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix (ECM) protein, was produced by C-/P-MSCs and resulted in an increase in p63+ ABCG2+ LEC colonies. TGFBIp-activated integrin signaling molecules (FAK, Src, and ERK) were expressed in LECs, and TGFBIp-induced LEC proliferation was effectively blocked by a FAK inhibitor. In conclusion, C-/P-MSCs enhanced LEC culture by increasing growth of the LSC population by secreting growth factors and the ECM protein TGFBIp, which is suggested to be a novel factor for promoting the growth of LECs in culture. C-/P-MSCs may be useful for the generation of animal-free culture systems for the treatment of LSC deficiency.

Although numerous population-based studies have reported the prevalences and risk factors for pterygium, information regarding the incidence of pterygium is scarce. This population-based cohort study aimed to evaluate the South Korean incidence and prevalence of pterygium. We retrospectively obtained data from a nationally representative sample of 1,116,364 South Koreans in the Korea National Health Insurance Service National Sample Cohort (NHIS-NSC). The associated sociodemographic factors were evaluated using multivariable Cox regression analysis, and the hazard ratios and confidence intervals were calculated. Pterygium was defined based on the Korean Classification of Diseases code, and surgically removed pterygium was defined as cases that required surgical removal. We identified 21,465 pterygium cases and 8,338 surgically removed pterygium cases during the study period. The overall incidences were 2.1 per 1,000 person-years for pterygium and 0.8 per 1,000 person-years for surgically removed pterygium. Among subjects who were ≥40 years old, the incidences were 4.3 per 1,000 person-years for pterygium and 1.7 per 1,000 person-years for surgically removed pterygium. The overall prevalences were 1.9% for pterygium and 0.6% for surgically removed pterygium, and the prevalences increased to 3.8% for pterygium and 1.4% for surgically removed pterygium among subjects who were ≥40 years old. The incidences of pterygium decreased according to year. The incidence and prevalence of pterygium were highest among 60-79-year-old individuals. Increasing age, female sex, and living in a relatively rural area were associated with increased risks of pterygium and surgically removed pterygium in the multivariable Cox regression analysis. Our analyses of South Korean national insurance claims data revealed a decreasing trend in the incidence of pterygium during the study period.

PURPOSE:To calculate actual corneal astigmatism using the total corneal refractive astigmatism for the 4-mm apex zone of the Pentacam (TCRP4astig) and keratometric astigmatism (Kastig) before and after photorefractive keratectomy or laser in situ keratomileusis. METHODS:Uncomplicated 56 eyes after more than 6 months from the surgery were recruited by chart review. Various corneal astigmatisms were measured using the Pentacam and autokeratometer before and after surgery. Three eyes were excluded and 53 eyes of 38 subjects with with-the-rule astigmatism (WTR) were finally included. The astigmatisms were investigated using polar value analysis. When TCRP4astig was set as an actual astigmatism, the efficacy of arithmetic or coefficient adjustment of Kastig was evaluated using bivariate analysis. RESULTS:The difference between the simulated keratometer astigmatism of the Pentacam (SimKastig) and Kastig was strongly correlated with the difference between TCRP4astig and Kastig. TCRP4astig was different from Kastig in magnitude rather than meridian before and after surgery; the preoperative difference was due to the posterior cornea only; however, the postoperative difference was observed in both anterior and posterior parts. For arithmetic adjustment, 0.28 D and 0.27 D were subtracted from the preoperative and postoperative magnitudes of Kastig, respectively. For coefficient adjustment, the preoperative and postoperative magnitudes of Kastig were multiplied by 0.80 and 0.66, respectively. By arithmetic or coefficient adjustment, the difference between TCRP4astig and adjusted Kastig would be less than 0.75 D in magnitude for 95% of cases. CONCLUSIONS:Kastig was successfully adjusted to TCPR4astig before and after myopic keratorefractive surgery in cases of WTR. For use of TCRP4astig directly, SimKastig and Kastig should be matched.

We investigated eyedrop vaccination (EDV) in pre-clinical development for immunological protection against influenza and for potential side effects involving ocular inflammation and the central nervous system (CNS). Live attenuated influenza EDV, CA07 (H1N1), PZ-4 (H1N2) and Uruguay (H3N2), induced both systemic and mucosal virus-specific antibody responses in ferrets. In addition, EDV resulted in a clinically significant protection against viral challenge, and suppression of viral replication in nasal secretion and lung tissue. Regarding safety, we found that administered EDV flow through the tear duct to reach the base of nasal cavity, and thus do not contact the olfactory bulb. All analyses for potential adverse effects due to EDV, including histological and functional examinations, did not reveal significant side effects. On the basis of these findings, we propose that EDV as effective, while being a safe administration route with minimum local side effects, CNS invasion, or visual function disturbance.

Previous research has suggested that immunoglobulin E (IgE)-mediated events lead to several chronic diseases. We investigated the association between allergic conditions and age-related cataracts in the South Korean adult population.A cross-sectional study was performed using data obtained from 1,170 participants aged 40 years or older who were enrolled in the Korean National Health and Nutrition Examination Survey 2010. Multivariable logistic regression was used to examine the relationship between age-related cataracts and allergic conditions, including total serum IgE and allergen-specific serum IgE levels, after adjustment for potential confounders (age, sex, alcohol consumption, smoking, sun exposure, blood pressure, plasma glucose and cholesterol levels, as well as histories of asthma, atopic dermatitis, and rheumatoid arthritis).After adjusting for potential confounders, the odds ratio (OR) for age-related cataract was greater in participants with higher total serum IgE levels (OR = 1.37; P = 0.044). In particular, increased IgE levels were significantly associated with nuclear cataract (OR = 1.42; P = 0.032). However, allergen-specific serum IgE levels did not differ significantly between groups. In the trend analysis, no significant relationship was observed between serum IgE and any type of age-related cataract.Increased total serum IgE level is independently associated with age-related cataracts after adjustment for confounding factors.

The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C) showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT) after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C) showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1) virus challenge. Additionally, ocular inoculation with poly(I:C) plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C) is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.

We investigated whether eyedrop vaccination using modified outer membrane vesicles (mOMVs) is effective for protecting against hemolytic uremic syndrome (HUS) caused by enterohemorrhagic E. coli (EHEC) O157:H7 infection. Modified OMVs and waaJ-mOMVs were prepared from cultures of MsbB- and Shiga toxin A subunit (STxA)-deficient EHEC O157:H7 bacteria with or without an additional waaJ mutation. BALB/c mice were immunized by eyedrop mOMVs, waaJ-mOMVs, and mOMVs plus polymyxin B (PMB). Mice were boosted at 2 weeks, and challenged peritoneally with wild-type OMVs (wtOMVs) at 4 weeks. As parameters for evaluation of the OMV-mediated immune protection, serum and mucosal immunoglobulins, body weight change and blood urea nitrogen (BUN)/Creatinin (Cr) were tested, as well as histopathology of renal tissue. In order to confirm the safety of mOMVs for eyedrop use, body weight and ocular histopathological changes were monitored in mice. Modified OMVs having penta-acylated lipid A moiety did not contain STxA subunit proteins but retained non-toxic Shiga toxin B (STxB) subunit. Removal of the polymeric O-antigen of O157 LPS was confirmed in waaJ-mOMVs. The mice group vaccinated with mOMVs elicited greater humoral and mucosal immune responses than did the waaJ-mOMVs and PBS-treated groups. Eyedrop vaccination of mOMVs plus PMB reduced the level of humoral and mucosal immune responses, suggesting that intact O157 LPS antigen can be a critical component for enhancing the immunogenicity of the mOMVs. After challenge, mice vaccinated with mOMVs were protected from a lethal dose of wtOMVs administered intraperitoneally, conversely mice in the PBS control group were not. Collectively, for the first time, EHEC O157-derived mOMV eyedrop vaccine was experimentally evaluated as an efficient and safe means of vaccine development against EHEC O157:H7 infection-associated HUS.

BackgroundVitamin D(3), the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3) ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE); however, the direct effect of vitamin D(3) on T cells is largely unknown.Methodology/principal findingsIn an in vitro system using cells from mice, the active form of vitamin D(3) (1,25-dihydroxyvitamin D(3)) suppresses both interleukin (IL)-17-producing T cells (T(H)17) and regulatory T cells (Treg) differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H)17 cells. Under T(H)17-polarizing conditions, 1,25(OH)(2)D(3) helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)(2)D(3)'s negative regulation of T(H)17 development is still defined in the IL-10(-/-) T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH)(2)D(3) inhibits IL-17 production in STAT1(-/-) T cells. Most interestingly, 1,25(OH)(2)D(3) negatively regulates CCR6 expression which might be essential for T(H)17 cells to enter the central nervous system and initiate EAE.Conclusions/significanceOur present results in an experimental murine model suggest that 1,25(OH)(2)D(3) can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H)17-mediated autoimmune diseases.