Effect of spectacle correction on hyperopic children.

Background: Hyperopia is a significant refractive error in children, often leading to vision impairment. This study aimed to investigate whether partial or full spectacle correction is benefit for hyperopia in preschool-aged children. Methods: A retrospective study was conducted on hyperopic children visited to teaching medical center outpatient clinic between October 2011 and October 2018, and were categorized into three groups: full correction, overcorrection, and undercorrection. The study was approved by the institutional ethical committee of Tri-Service General Hospital. Results: Following a minimum of one-year follow-up period, no statistically significant differences were observed in best-corrected visual acuity (BCVA) among children receiving full, over, or under spectacle correction. Notably, the overcorrection group exhibited a significant reduction in spherical equivalent (SE) compared to both the full and under correction groups, indicating a better SE with spectacle overcorrection. Conclusions: Spectacle overcorrection may offer potential benefits for enhancing SE in preschool children with hyperopia. Nevertheless, further investigation through randomized controlled trials is warranted to establish the validity of this approach and its impact on visual outcomes in this hyperopic pediatric population.

Femtosecond laser-assisted astigmatic keratotomy versus toric IOL implantation for correcting astigmatism in cataract patients: a systematic review and meta-analysis with trial sequential analysis.

AIMS: To compare the refractive and visual outcomes of femtosecond laser-assisted astigmatic keratotomy (FSAK) and toric intraocular lens (IOL) implantation for correcting astigmatism in cataract patients. METHODS: Studies were retrieved from the Ovid-Medline, EMBASE, Cochrane Central Register of Controlled Trials and Scopus which compared FSAK and toric IOL for astigmatism correction in cataract patients. Outcome measures included postoperative refractive cylinder, correction index, uncorrected distance visual acuity (UDVA), the proportion of patients achieving a residual refractive cylinder of 1.00 dioptre or less, target-induced astigmatism (TIA) and surgically induced astigmatism (SIA). The trial sequential analysis (TSA) was used to collect firm evidence supporting our conclusion. RESULTS: 9 studies encompassing 590 participants were analysed. The meta-analysis revealed that toric IOLs could result in less postoperative refractive cylinder and provide better UDVA compared with FSAK. The TSA disclosed strong evidence of lower postoperative refractive cylinder in the toric IOL group compared with that of the FSAK group. FSAK showed a smaller correction index and lower mean TIA and SIA compared with toric IOLs. CONCLUSIONS: For cataract patients, both FSAK and toric IOLs are effective methods for correcting astigmatism. However, toric IOLs offer less postoperative astigmatism and result in better postoperative UDVA compared with FSAK. In vector analysis of astigmatism, toric IOLs can also produce higher TIA and SIA. Additionally, neither method is associated with severe untreatable complications. Therefore, the conclusion is that toric IOLs are the preferred choice for astigmatism correction in cataract patients and FSAK serves as a viable alternative when toric IOLs are contraindicated.

A meta-analysis of sutureless scleral-fixated intraocular lens versus retropupillary iris claw intraocular lens for the management of aphakia.

This study compared the visual outcomes and complications between sutureless scleral-fixated intraocular lens and iris claw intraocular lens implantation in aphakia without adequate capsule and/or zonule support. Studies comparing the clinical outcomes of scleral-fixated intraocular lens and iris claw intraocular lens implantation published until April 2022 were retrieved from the PubMed, EMBASE, Cochrane Library, and Google Scholar databases. The outcomes included postoperative final visual acuity, surgical time, surgery-induced astigmatism, and complications. The weighted mean difference and odds ratio were calculated. Two randomized controlled trials and five cohort studies, including 244 and 290 eyes in the scleral-fixated intraocular lens group and iris claw group, respectively, were included. Scleral-fixated intraocular lens implantation results in a better postoperative final corrected distance visual acuity compared with iris claw intraocular lens implantation; however, it is more time-consuming. Scleral-fixated intraocular lens implantation seems to have lesser incidences of surgery-induced astigmatism. Furthermore, both procedures have a similar complication rate. Therefore, based on current best evidence, these two procedures should be considered according to patient's conditions.

Investigation of corneal epithelial thickness and irregularity by optical coherence tomography after transepithelial photorefractive keratectomy.

CLINICAL RELEVANCE: Corneal epithelial healing after refractive surgery is a clinically significant issue, especially for surface ablation procedures, and this can be monitored using optical coherence tomography (OCT). BACKGROUND: The aim of this work is to investigate the corneal epithelial thickness and irregularity by OCT after transepithelial photorefractive keratectomy (t-PRK) and analyse its correlation with visual and refractive outcomes. METHODS: Patients aged ≥18 years with myopia, with or without astigmatism, who underwent t-PRK between May 2020 and August 2021 were included. All participants were subjected to complete ophthalmic examinations and OCT pachymetry at every follow-up visit. Patients were followed up at 1 week and 1, 3, and 6 months postoperatively. RESULTS: A total of 67 patients (126 eyes) were enrolled in this study. One month postoperatively, spherical equivalent refraction and visual acuity achieved preliminary stability. However, central corneal epithelial thickness (CCET) and standard deviation of the corneal epithelial thickness (SDcet) took 3-6 months to progressive recovery. Patients with higher baseline spherical equivalent refraction were associated with slower epithelial recovery. At every follow-up time point, a significant superior-inferior difference in the minimum corneal epithelial thickness area was observed. Higher stromal haze was correlated with higher spherical equivalent refraction (both baseline and residual) but had no relation with visual outcomes. There was a significant correlation between higher CCET with a better uncorrected distance visual acuity and lower corneal epithelial thickness irregularity. CONCLUSIONS: CCET and SDcet measured by OCT seem to be a good auxiliary indicator for reflecting the status of corneal wound recovery after t-PRK surgery. However, a well-designed randomised control study is needed to confirm the study results.

Prevalence of meibomian gland dysfunction at a tertiary centre in Taiwan.

CLINICAL RELEVANCE: Meibomian gland dysfunction and dry eye disease are closely related conditions that often coexist and can contribute to the development of each other. Understanding the similarities and differences between these diseases can assist clinicians in implementing effective treatments for both conditions in a clinical setting. BACKGROUND: Dry eye disease is a multifactorial disease of the tears and ocular surface. This study aimed to evaluate the demographic characteristics of patients with meibomian gland dysfunction in Taiwan, investigate the association between meibomian gland dysfunction and dry eye parameters, and estimate the prevalence of meibomian gland dysfunction among patients with dry eye symptoms at a tertiary referral centre. METHODS: This cross-sectional study enrolled patients aged ≥20 years who complained of dry eye symptoms and visited a tertiary centre between September 2019 and March 2020. The patients completed the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires before undergoing ocular examination. The lipid layer thickness and meiboscale scores were recorded. In addition, the study measured tear film break-up time, examined corneal staining, and evaluated the number of meibomian glands yielding liquid secretions using a slit lamp. RESULTS: The study evaluated 202 eyes of 202 patients with a mean age of 58.05 ± 13.34 years. The prevalence of meibomian gland dysfunction was 93%. Mean meiboscale score and age were negatively associated, and tear film break-up time was positively associated with the mean number of meibomian glands yielding liquid secretions. Hyperlipidaemia and smoking were the main risk factors for Meibomian gland dysfunction. CONCLUSIONS: The prevalence of meibomian gland dysfunction among patients with dry eye symptoms was extremely high at the tertiary centre, highlighting the strong relationship between Meibomian gland dysfunction and dry eye disease. Clinicians should consider meibomian gland dysfunction as a possible cause of dry eye.

Corneal topographic changes in patients with thyroid eye disease: A retrospective cross-sectional study.

PURPOSE: This study aimed to evaluate corneal topographic findings in patients with thyroid eye disease (TED) using a Galilei camera and compare their corneal topographic parameters with those of control patients. METHODS: This retrospective cross-sectional study included 52 eyes of 26 patients with TED (study group) and 40 eyes of 20 controls treated at a tertiary medical center in Taiwan between January and December 2021. All participants underwent basic ophthalmological examinations, corneal topography examination using a Galilei dual Scheimpflug camera, thyroid function examination, and orbital computed tomography. The corneal topographic parameters and cross-sectional area of the extraocular muscles were compared between the TED and control groups. RESULTS: Several corneal topographic parameters, including the Inferior-Superior Index, Keratoconus Prediction Index, Surface Asymmetry Index, Surface Regularity Index, simulated keratometry astigmatism, and anterior instantaneous astigmatism axis, differed significantly between the groups (P ≤ 0.05). The anterior instantaneous astigmatism axis was more oblique in the TED group than in the control group. A scatter plot revealed a more scattered distribution in the anterior instantaneous astigmatism axis in the TED group than in the control group. However, the corneal topographic parameters did not differ significantly among the different thyroid dysfunction groups. CONCLUSIONS: The corneas of patients with TED are suspicious and keratoconus-like, and TED can increase anterior corneal astigmatism in the oblique axis, albeit with large variations in the extent of change. These TED-related corneal changes may aid in the early diagnosis of TED, especially "silent" TED.

Dental caries and periodontitis and the risk of myopia in young adults: CHIEF oral health study.

AIM: Oral health and ocular diseases may be associated with collagen defects and inflammation status. However, the results from prior studies are conflicting. The aim of this study was to explore the association of dental caries and periodontitis with myopia in young adults. MATERIALS AND METHODS: A total of 938 military personnel aged 19-39 years receiving both oral and eye examinations from 2018 through 2020 were included in this study in Taiwan. The severity of myopia was graded as no myopia (diopters > - 0.5, N = 459), low myopia (diopters: - 0.5 to -5.9, N = 225) and high myopia (diopters ≤ - 6.0, N = 254). A multiple logistic regression analysis with adjustments for age, body mass index, systolic blood pressure, smoking, alcohol consumption, missing teeth numbers, blood leucocyte counts, triglycerides, high-density lipoprotein, and uric acid were used to determine the associations of actively dental caries, filled teeth and stage II/III periodontitis with myopia. RESULTS: The presence of any actively dental caries was significantly associated with a higher risk of any myopia (low or high) (odds ratio [OR] and 95% confidence intervals [95% CI] 1.42 [1.04-1.94]), whereas there was no association for filled teeth. Moreover, the association for stage II/III periodontitis was only observed with high myopia (OR: 1.52 [1.07-2.15]) and was not observed with low myopia. CONCLUSIONS: Our findings suggest that only actively dental caries and a higher severity of periodontitis were associated with myopia among young adults, thus highlighting the dental inflammation status in the oral cavity as a potential link to ocular diseases.

Acellular Porcine Cornea Produced by Supercritical Carbon Dioxide Extraction: A Potential Substitute for Human Corneal Regeneration.

PURPOSE: The aim of this study was to develop a non-cytotoxic, biocompatible innovative acellular porcine cornea (APC) for corneal wound healing and corneal blindness treatment. METHODS: APC was produced by using supercritical carbon dioxide (SCCO2) to decellularize the porcine cornea. Decellularization of the porcine cornea was examined by hematoxylin and eosin staining and 4,6-diamidino-2-phenylindole, dihydrochloride staining. The residual DNA content of APC was analyzed in comparison with the native porcine cornea. Virus inactivation up to at least 6 log10 was confirmed for the stepwise process of APC for 4 different model viruses. In addition, a series of in vitro and in vivo tests in accordance with ISO-10993 biocompatibility assay and animal performance tests were performed. RESULTS: APC produced by the SCCO2 process revealed complete decellularization, without any residual non-collagenous proteins. The scanning electron microscopy structural features of the decellularized cornea were similar to those of human. APC was found to be nontoxic and exhibited excellent biocompatibility in both in vitro and in vivo studies. The animal performance test proved that APC exerted excellent adaptability on the cornea and no sign of irritation and good compatibility in lamellar corneal transplantation. CONCLUSIONS: APC manufactured by SCCO2 technology revealed complete cells and non-collagenous protein removal compared with the Triton-sodium dodecyl sulfate decellularization process. APC showed excellent biocompatibility in rabbit lamellar corneal transplantation with a follow-up to 1 year. APC can be a potential substitute for human-donated cornea for corneal transplantation in the near future.

The Polymorphism at PLCB4 Promoter (rs6086746) Changes the Binding Affinity of RUNX2 and Affects Osteoporosis Susceptibility: An Analysis of Bioinformatics-Based Case-Control Study and Functional Validation.

Purpose: Genome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP). Methods: We performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment. Results: Through candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23-21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen's q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05). Conclusions: Our results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.

Prevalence and risk factors for myopia in Taiwanese diabetes mellitus patients: a multicenter case-control study in Taiwan.

This population-based retrospective cohort study investigated the prevalence of myopia among patients with Type 1 and Type 2 diabetes mellitus (DM) and evaluate risk factors for myopia in these groups. Records from 2000 to 2012 with at least one year of follow-up from the Taiwan National Health Insurance Research Database were included. This study included 35,538 patients with DM and 71,076 patients without DM. Patients with DM had a significantly higher adjusted hazard ratio for myopia in all age groups and both sexes compared with patients without DM. The subgroup analysis results revealed that the rates of myopia and astigmatism were significantly higher among patients with DM compared with patients without DM aged < 60 years. However, the rates of high myopia or myopia progression to high myopia did not differ significantly between the two groups. These findings indicate that DM is a critical risk factor for myopia and astigmatism among patients aged < 60 years. Therefore, active surveillance and earlier treatment of myopia are critical for patients with DM.

Serum Calcium Level as a Useful Surrogate for Risk of Elevated Intraocular Pressure.

BACKGROUND: Uncontrolled intraocular pressure (IOP) plays a principal role in the deterioration of glaucoma, and the intraocular pressure is also accepted as the most important modifiable factor. Calcium ion has been found to play a vital role in regulating the resistance of the trabecular meshwork in humans. However, the relationship between serum total calcium and IOP has not been well-established. METHODS: We investigated the association between serum total calcium and the IOP in a large population (14,037 eligible participants, consisting of 7712 men and 6325 women, were included) at the Tri-Service General Hospital from 2010 to 2016. Several models of covariate adjustments associated with IOP were designed. Univariate and multivariate regression analysis was performed for gender differences in the association between the serum total calcium level and IOP. RESULTS: There was a significant relationship between serum total calcium levels and IOP in women and men with a ß coefficient of 0.050 (95% confidence interval (CI), 0.030-0.069) and 0.025 (95%CI, 0.007-0.043). Notably, participants in the highest tertiles of serum total calcium levels had significantly higher IOP, in both the male and female participants. CONCLUSIONS: Our study shows that IOP is significantly associated with serum total calcium levels in a large Asian population. This study supports the notion that serum total calcium may play an important role in groups at high risk for elevated IOP.

Polymorphism of rs6426749 at 1p36.12 is associated with the risk of osteoarthritis in Taiwanese female population.

BACKGROUND: Osteoarthritis (OA) is a multifactorial disease that is associated with several genetic factors. TFAP2A with a motif of C allele at rs6426749 demonstrates a higher binding ability, thereby increasing CDC42 expression, potentially affecting OA occurrence. In this study, we evaluated the role of rs6426749 polymorphisms on knee OA in a female Taiwanese population. METHODS: We performed a case-control study of 368 OA cases and 379 controls between March 2017 and October 2018. Knee OA was defined using the Kellgren-Lawrence grading system, and genotypes were determined using the Sequenom MassArray iPLEX Gold assay. Stratified sex and body mass index (BMI) analyses were performed using logistic regression to explore interactions between genes and the environment. We also used expression quantitative trait loci data from the genotype-tissue expression project to conduct functional analyses. RESULTS: The C allele of rs6426749 was associated with the risk of knee OA (odds ratio [OR] = 1.31, 95% confidence interval [CI], 1.01-1.71; p = 0.042), after adjusting for gender, age, and BMI. In addition, subgroup analyses indicated that females expressing C alleles showed an increased risk for knee OA (OR = 1.56; 95% CI, 1.12-2.18; p = 0.009). Females with a normal BMI and the C allele had the highest OA risk (OR = 1.73; 95% CI, 1.08-2.76; p = 0.022). CONCLUSION: Our findings indicated that rs6426749 may be related to OA susceptibility in the Taiwanese population. This was particularly true for women with normal BMI.

Leveraging Multimodal Deep Learning Architecture with Retina Lesion Information to Detect Diabetic Retinopathy.

Purpose: To improve disease severity classification from fundus images using a hybrid architecture with symptom awareness for diabetic retinopathy (DR). Methods: We used 26,699 fundus images of 17,834 diabetic patients from three Taiwanese hospitals collected in 2007 to 2018 for DR severity classification. Thirty-seven ophthalmologists verified the images using lesion annotation and severity classification as the ground truth. Two deep learning fusion architectures were proposed: late fusion, which combines lesion and severity classification models in parallel using a postprocessing procedure, and two-stage early fusion, which combines lesion detection and classification models sequentially and mimics the decision-making process of ophthalmologists. Messidor-2 was used with 1748 images to evaluate and benchmark the performance of the architecture. The primary evaluation metrics were classification accuracy, weighted κ statistic, and area under the receiver operating characteristic curve (AUC). Results: For hospital data, a hybrid architecture achieved a good detection rate, with accuracy and weighted κ of 84.29% and 84.01%, respectively, for five-class DR grading. It also classified the images of early stage DR more accurately than conventional algorithms. The Messidor-2 model achieved an AUC of 97.09% in referral DR detection compared to AUC of 85% to 99% for state-of-the-art algorithms that learned from a larger database. Conclusions: Our hybrid architectures strengthened and extracted characteristics from DR images, while improving the performance of DR grading, thereby increasing the robustness and confidence of the architectures for general use. Translational Relevance: The proposed fusion architectures can enable faster and more accurate diagnosis of various DR pathologies than that obtained in current manual clinical practice.

Risk of Mitral Valve Prolapse in Patients with Keratoconus in Taiwan: A Population-Based Cohort Study.

This retrospective, nationwide, matched-cohort study included 4488 new-onset keratoconus (KCN) patients, ≥12 years old, recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The control group included 26,928 non-KCN patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence rate of mitral valve prolapse (MVP) was 1.77 times (95% confidence interval (CI) = 1.09-2.88; p = 0.0206) higher in KCN patients ≥40 years old and 1.49 times (95% CI = 1.12-1.98; p = 0.0060) higher in female KCN patients than in controls. After using the Cox proportional hazard regression analysis to adjust for potential confounders, including hypertension, hyperlipidemia, and congestive heart failure, KCN maintained an independent risk factor, MVP being 1.77 times (adjusted hazard ratio (HR) = 1.77, 95% CI = 1.09-2.88) and 1.48 times (adjusted HR = 1.48, 95% CI = 1.11-1.97) more likely to develop in patients ≥40 years old and female patients in the study cohort, respectively. We found that KCN patients ≥40 years of age and female KCN patients have increased risks of MVP. Therefore, it is recommended that KCN patients should be alerted to MVP.

Serum Iron and Risk of Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is indicated as a major cause of blindness in the world. Emerging evidence supports the interaction of iron metabolism with diabetes. However, little research is available concerning the relationship between iron metabolism and DR. The intent of this paper is to describe the correlation between serum iron and the occurrence of DR. METHODS: A total of 5321 participants who underwent related examinations as part of the National Health and Nutrition Examination Survey (2005-2008) were included. DR was defined by the criteria of the Early Treatment for Diabetic Retinopathy Study based on nonmydriatic fundus photography. The cutoff point of serum iron for DR was explored by the receiver operating characteristics curve. The relationship of serum iron with the occurrence of DR was explored by multivariate logistic regression models. RESULTS: Participants with DR had significantly lower serum iron than the control group. Serum iron was negatively correlated with the occurrence of DR after the adjustment of pertinent variables (an odds ratio (OR) of 0.995 (95% CI: 0.992-0.999)). After dividing serum iron into quartiles, the third quartile was associated with DR with an OR of 0.601 (95% CI: 0.418-0.863). Furthermore, the cutoff point of serum iron had an inverse relationship for the occurrence of DR with an OR of 0.766 (95% CI: 0.597-0.984). CONCLUSION: Serum iron has an inverse association with the occurrence of DR in diabetic adults. The assessment of serum iron levels might be a part of follow-up visits with diabetic patients.

Detection of Diabetic Retinopathy Using Bichannel Convolutional Neural Network.

Deep learning of fundus photograph has emerged as a practical and cost-effective technique for automatic screening and diagnosis of severer diabetic retinopathy (DR). The entropy image of luminance of fundus photograph has been demonstrated to increase the detection performance for referable DR using a convolutional neural network- (CNN-) based system. In this paper, the entropy image computed by using the green component of fundus photograph is proposed. In addition, image enhancement by unsharp masking (UM) is utilized for preprocessing before calculating the entropy images. The bichannel CNN incorporating the features of both the entropy images of the gray level and the green component preprocessed by UM is also proposed to improve the detection performance of referable DR by deep learning.

Decisive evidence corroborates a null relationship between MTHFR C677T and chronic kidney disease: A case-control study and a meta-analysis.

BACKGROUND: Previous meta-analyses have explored the association between the C677T polymorphism of methyltetrahydrofolate reductase (MTHFR) and chronic kidney disease (CKD) but there were no studies with a decisive conclusion. Furthermore, the high heterogeneity among different populations is not yet interpreted. OBJECTIVES: This study used trial sequential analysis (TSA) to evaluate whether the nowadays conclusion supported by current cumulative samples. We also applied case-weighted meta-regression to explore the potential gene-environment interactions. METHODS: For the first stage of this study we conducted a case-control study involving 847 dialysis patients from 7 hemodialysis centers in Taipei during 2015 to 2018 and 755 normal controls from a health center in the Tri-Service General Hospital. The second stage combined the results from the first stage with previous studies. The previous studies were collected from PubMed, EMBASE, and Web of Science databases before January 2018. RESULTS: From the case-control study, the T allele of MTHFR C677T appeared to have a protective effect on end-stage renal disease compared with the C allele [odds ratio (OR): 0.80, 95% CI (confidence interval) = 0.69-0.93]. However, the meta-analysis contradicted the results in Asian (OR = 1.12, 95% CI = 0.96-1.30). The same analysis was also applied in Caucasian and presented similar results from Asian (OR = 1.18, 95% CI = 0.98-1.42). The TSA showed our case-control study to be the decisive sample leading to a null association among Asian population. The high heterogeneity (I = 75%) could explain the contradictory results between the case-control study and the meta-analysis. However, further case-weighted meta-regression did not find any significant interaction between measured factors and MTHFR C677T on CKD. CONCLUSIONS: High heterogeneities were found in both Caucasian and Asian, which caused the null relationship in meta-analysis while there were significant effects in individual studies. Future studies should further explore the high heterogeneity that might be hidden in unmeasured gene-environment interactions, to explain the diverse findings among different populations.

Risk of recurrent corneal erosion in patients with diabetes mellitus in Taiwan: a population-based cohort study.

OBJECTIVE: To investigate the risk of recurrent corneal erosion (RCE) in patients with diabetes mellitus (DM). DESIGN, SETTING AND PARTICIPANTS: This retrospective, nationwide, matched cohort study included 239 854 patients with DM recruited between 2003 and 2005 from the Longitudinal Cohort of Diabetes Patients database. The control group included the same number of age-matched and sex-matched patients without DM selected from the Taiwan Longitudinal Health Insurance Database, 2000. Data for each patient were collected from the index date until December 2013. MAIN OUTCOMES AND MEASURES: The incidence and risk of RCE were compared between the two groups. Cox proportional hazards regression was used to calculate the HR for RCE after adjustment for potential confounders. The cumulative RCE incidence rate was calculated using Kaplan-Meier analysis. RESULTS: In total, 1236 patients with DM and 884 controls developed RCE during the follow-up period, resulting in an incidence rate of RCE in patients with DM (5.87/10 000 person-years (PY)) higher than that in the controls (4.23/10 000 PY). After adjustment for potential confounders, including hypertension, hyperlipidaemia, chronic renal disease and keratoconjunctivitis sicca, patients with DM were 1.35 times (95% CI, 1.24 to 1.48) more likely to develop RCE than the total sample cohort. CONCLUSIONS: DM increases the risk of RCE, which is an interdisciplinary issue. Therefore, close collaboration between endocrinologists and ophthalmologists is important in managing RCE following DM.

Antifibrotic role of low-dose mitomycin-c-induced cellular senescence in trabeculectomy models.

PURPOSE: We assessed whether mitomycin-C (MMC) has different antifibrotic mechanisms in trabeculectomy wound healing. METHODS: We identified 2 concentrations of MMC as "low-dose" by using WST-1 assay, Lactic dehydrogenase assay, and fluorescence-activated cell sorting flow cytometry. Senescence-associated ß-galactosidase (SA-ß-gal) and fibrotic gene expression was examined through immunocytochemistry, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, Western blotting, zymography, and modified scratch assay in vitro. In vivo, 0.1 mL of MMC or normal saline was injected to Tenon's capsule before trabeculectomy in a rabbit model. SA-ß-gal expression, apoptotic cell death, and collagen deposition in sites treated and not treated with MMC were evaluated using terminal dUTP nick end labeling assay and histochemical staining. Bleb function and intraocular pressure (IOP) levels were examined 3, 7, 14, 21, 28, and 35 days after trabeculectomy. RESULTS: In vitro, human Tenon's fibroblast (HTF) senescence was confirmed by observing cell morphologic change, SA-ß-gal accumulation, formation of senescence-associated heterochromatin, increased p16INK4a and p21CIP1/WAF1 expression, lower percentage of Ki-67-positive cells, and decreased COL1A1 release. Increased expression of α-SMA, COL1A1, and Smad2 signaling in TGF-ß1-induced stress fibers were passivated in senescent HTFs. In addition, cellular migration enhanced by TGF-ß1was inactivated. In vivo, histological examination indicated increased SA-ß-gal accumulation, lower apoptosis ratios, and looser collagen deposition in sites treated with 0.2 µM MMC. Low-dose MMC-induced cellular senescence prolonged trabeculectomy bleb survival and reduced IOP levels in a rabbit model. CONCLUSION: Low-dose MMC-induced cellular senescence is involved in the antifibrotic mechanism of trabeculectomy wound healing.

Risk of Corneal Ulcer in Patients with Diabetes Mellitus: A Retrospective Large-Scale Cohort Study.

This nationwide, retrospective, matched cohort study was designed to investigate the risk of corneal ulcer in patients with diabetes mellitus (DM). It included 238,701 patients with DM, recruited between 2003 and 2005 from the Longitudinal Cohort of Diabetes Patients database. The control group included the same number of age- and sex-matched non-DM patients selected from the Taiwan Longitudinal Health Insurance Database, 2000. The data of each patient were collected from the index date until December 2013. The incidence of corneal ulcer was compared between the two groups. In total, 2,549 patients with DM and 1,988 controls developed corneal ulcer during the follow-up period, resulting in an incidence rate for corneal ulcers that was 1.27 times (95% confidence interval [CI] = 1.20-1.35; P < 0.001) higher in patients with DM than in controls. After adjustment for potential confounders, including hyperlipidemia, hypertension, congestive heart failure, coronary artery disease, and chronic renal disease, patients with DM were 1.31 times (95% CI, 1.24-1.40; P < 0.05) more likely than the cohort to develop corneal ulcers. In conclusion, this study shows that DM increases the risk of corneal ulcer. Therefore, close collaboration between ophthalmologists and endocrinologists is important to ensure timely ophthalmology visits.