Tsung-Jen Wang

Comorbidities of dry eye disease: a nationwide population‐based study

Purpose: To investigate the comorbidities of dry eye disease in a nationwide population‐based data in Taiwan.

Glaucoma, Alzheimer's Disease, and Parkinson's Disease: An 8-Year Population-Based Follow-Up Study

Background Glaucoma is the leading cause of irreversible blindness worldwide and primary open-angle glaucoma (POAG) is the most common type of glaucoma. An association between POAG and the subsequent risk of Alzheimers disease (AD) and Parkinsons disease (PD) was unclear. Objective To investigate the association between POAG (including normal-tension glaucoma) and the subsequent risk of AD or PD 8 years following a diagnosis of POAG. Methods We performed a retrospective, propensity-score-matched analysis of a population-based cohort consisting of patients with and without POAG aged 60 years and older. Control patients without POAG were propensity-score matched to POAG patients based on their baseline characteristics. Results The incidence rates and confidence intervals (CIs) of AD among the patients with and without POAG were 2.85 (95% CI: 2.19–3.70) and 1.98 (95% CI: 1.68–2.31) per 1000 person-years, respectively. The incidence rates of PD among the POAG and non-POAG cohorts were 4.36 (95% CI: 3.52–5.39) and 4.37 (95% CI: 3.92–4.86) per 1000 person-years, respectively. Kaplan-Meier failure curves showed that the POAG patients had a higher risk of AD than the control patients did (log-rank test, P = .0189). However, the cumulative PD hazard ratios for the POAG and non-POAG patients did not differ significantly (log-rank test, P = .9953). Conclusion In elderly patients, POAG is a significant predictor of AD, but POAG is not a predictor of PD.

Fabrication of a bioengineered corneal endothelial cell sheet using chitosan/polycaprolactone blend membranes

Our previous study has demonstrated cultivation of bovine corneal endothelial cells (BCECs) on the chitosan-polycaprolactone (PCL) blends. BCECs could grow well and express physiological phenotypes after PCL was introduced into chitosan by means of blending. The feasibility of using chitosan-PCL-blended membranes as scaffold and carrier for corneal endothelial cell (CEC) transplantation is worthy of more investigation. In this work, we attempt to manufacture various blended membranes to bring BCEC cultivation into harmony by hybridizing two polymers with fine adjustment. Therefore, chitosan, which does not promote BCECs maturation, and PCL, which supports, BCEC proliferation, are combined to prepare the blends. Analyses of transmittance, proliferative, abilities, phenotypic expressions, extracellular matrix (ECM) protein production, and hemotoxylin and eosin (H&E) staining were executed step-by-step. From our observations, the blended membranes united respective characteristics. The cultured BCECs on the blends illustrated normal appearance and good proliferative abilities. Immunohistochemical staining verified physiologically phenotypic expressions of ZO-1 and Na-K ATPase. Western blot analysis also confirmed the existence of collagen type IV proteins. Furthermore, the formation of a continuous monolayer of cells attached on the blended membrane was confirmed by H&E staining. These results suggested that chitosan-PCL blended membranes may be an optimized biomaterial to fabricate bioengineered corneal endothelium and show potential to facilitate CEC transplantation in the future.

The phenotypic response of bovine corneal endothelial cells on chitosan/polycaprolactone blends

Although various behaviors of corneal endothelial cells (CECs) have been investigated, the interaction of CECs with different biodegradable biomaterials has not been systematically well explored. Thus, two common biodegradable biomaterials with dissimilar characteristics, chitosan and polycaprolactone (PCL), were examined in bovine CEC (BCEC) culture systems to elucidate their possible impact on clinical demand and scientific interest. The interaction between cells and matrices was also surveyed. Pure PCL could not be used for observation because of its opacity. Nevertheless, BCECs did not adhere and proliferate well on chitosan. To overcome this drawback, we developed blends using various proportions of chitosan and PCL: PCL 25, PCL 50, and PCL 75. As the content of PCL increased in the blends, BCECs showed greater degrees of adhesion and proliferation. Furthermore, cells reached confluence and maintained their typical hexagonal shape at day 7 on blends PCL 50 and PCL 75. In addition, when BCECs were cultured on the blends, the expressions of the differentiation marker N-cadherin and tight junction marker ZO-1 were well developed, resembling the physiological phenotypes. A possible explanation for the increased proliferation and preservation of BCECs on the blends is that blending chitosan and PCL could create a bioactive substratum. This method could regulate gene expression to synthesize more extracellular matrix type IV collagen, paving an important way to provide a favorable environment for BCEC cultures. Accordingly, promoting CEC growth effects by blending may be applied to the tissue engineering of corneal endothelium.

Comparison of the clinical effects of carbomer-based lipid-containing gel and hydroxypropyl-guar gel artificial tear formulations in patients with dry eye syndrome: a 4-week, prospective, open-label, randomized, parallel-group, noninferiority study.

BACKGROUND Most marketed artificial tears are substitutes for the aqueous layers of the tear film; therefore, frequent instillation of artificial tears is necessary. Newer gel-, cellulose-, and mineral oil-based formulations have been designed to overcome the disadvantages of current aqueous tear substitutes by offering prolonged retention times. OBJECTIVES The aim of this study was to compare the efficacy, safety, and local tolerance of artificial tears containing carbomer-based lipids or hydroxypropyl (HP)-guar gel in patients with dry eye syndrome. METHODS A 4-week, prospective, randomized, parallel-group, comparative, noninferiority study was conducted at the Taipei Medical University Hospital (Taipei, Taiwan) in patients with dry eye syndrome who were randomly assigned to 1 of 2 treatment groups: the carbomer-based lipid-containing (CBLC) gel group and the HP-guar gel group. The primary end point was global assessment of study treatment by the patients at weeks 2 and 4. All patients met the diagnostic criteria of impaired tear function and ocular surface abnormalities. Outcomes measured at baseline and 2 and 4 weeks included Schirmers test values, tear breakup time (TBUT), and a patient subjective assessment of symptoms. Safety and tolerability were assessed by clinically significant changes in terms of incidence of adverse events and conducted by unmasked investigators. RESULTS A total of 30 Taiwanese patients with dry eye syndrome were included and randomly assigned to the 2 treatment groups: the mean (SD) age was 40.37 (14.96) years in the CBLC gel group and 49.49 (12.20) years in the HP-guar gel group. At baseline, the mean (SD) Schirmers test value was 4.53 (2.28) mm in the right eye and 5.13 (2.42) mm in the left eye in the CBLC gel group; 4.40 (2.16) mm in the right eye and 4.20 (1.78) mm in the left eye for the HP-guar gel group. The mean (SD) for both eyes was 4.83 (2.36) mm in the CBLC gel group and 4.30 (2.08) mm in the HP-guar gel group. There was no statistically significant difference between Schirmers scores at baseline. Patients in both treatment groups experienced an improvement from baseline in symptoms and signs, Schirmers test value, and TBUT at 2 and 4 weeks after treatment. The Schirmers test score increased to a mean of 8.20 (4.49) mm in the right eye and 9.33 (4.94) mm in the left eye in the CBLC gel group after 2 weeks, and increased to 10.07 (5.56) mm in the right eye and 10.86 (5.58) mm in the left eye after 4 weeks. The increases in Schirmers test score and TBUT were also observed in the HP-guar gel group. The Schirmers test score increased to 5.13 (2.18) mm in the right eye and 5.60 (2.74) mm in the left eye after 2 weeks, and increased to 6.93 (3.37) mm in the right eye and 6.53 (3.16) mm in the left eye after 4 weeks. The increase in Schirmers test values in both eyes was significantly greater at 2 and 4 weeks in the CBLC gel group than that in the HP-guar gel artificial tear group (all, P < 0.05). Subjective patient assessment was better with the CBLC group (excellent and good reported by 26.6% and 73.4%, respectively, of the CBLC gel group vs 13.4% and 33.4% of the HP-guar gel group at 4 weeks; both, P = 0.004). CONCLUSIONS Both artificial tear formulations were effective in relieving dry eye syndrome in these patients. The tolerance of CBLC gel artificial tears was comparable to that of HP-guar gel artificial tears.

Polyvinylidene fluoride for proliferation and preservation of bovine corneal endothelial cells by enhancing type IV collagen production and deposition

In this study, biomaterials with different hydrophobic properties including polyvinyl alcohol (PVA), poly(ethylene-co-vinyl alcohol) (EVAL), tissue culture polystyrene (TCPS), and polyvinylidene fluoride (PVDF) were examined in the bovine corneal endothelial cells (BCECs) culture system to elucidate their possible impact on clinical demand and scientific interest. It was found that BCECs were inhibited to attach onto the PVA surface. Conversely, relatively more hydrophobic biomaterials EVAL, TCPS, and PVDF successfully initiate BCEC adhesion. Compared to EVAL, cultured BCECs on TCPS and PVDF exhibited higher viability. Furthermore, fibroblastic transformation on EVAL and TCPS was observed at day 17, but BCECs maintained typical hexagonal shape on the PVDF surface at day 21. This phenomenon can be rescued by previously coating type IV collagen on TCPS but not on EVAL. In addition, when BCECs were cultured on PVDF, the expressions of gap junction connexin-43, differentiation marker N-cadherin, and tight junction ZO-1 were well-developed, resembling the physiological phenotypes. After examining the type IV collagen expression by Western blot analysis and protein absorption test, a possible explanation for the better proliferation and preservation of BCECs on the PVDF substrate is that PVDF is a bioactive substratum which enables BCECs to synthesize and reserve more extracellular matrix type IV collagen, paving an important way to provide a more preferential environment for BCEC cultures. Accordingly, promoting CEC growth effects after cell-biomaterial association may be applied to the tissue engineering of corneal endothelium.

Cell fractionation on pH-responsive chitosan surface

The purpose of this study is to demonstrate pH-responsive chitosan is able to be used for cell fractionation under precise adjustment of medium pH. Cells were first seeded to attach on chitosan surface at medium pH 7.20 for 24 h. After raising medium pH to 7.65 for 1 h, cells with elongated morphology possessed rapider detachment rate and cells with round shape detached at a lesser rate. Therefore, successful cell separation has been achieved by choosing appropriate cell combination with different detachment rates without additional antibody or enzyme treatment and extensive washing steps. Furthermore, the method also could be applied to specific manipulation of viable cell populations from tissue specimen. Most importantly and interestingly, the efficiency of cell fractionation of our system could be theoretically predicted according to the individual cell detachment rate on pH-responsive chitosan surface, without considering the presence of heterotypic cells.

Comparison of the effects of cylindrical correction with and without iris recognition technology in wavefront laser-assisted in situ keratomileusis.

Background:  To analyse the magnitude of cylindrical corrections over which cyclotorsion compensation with iris recognition (IR) technology is beneficial during wavefront laser‐assisted in situ keratomileusis.

Correction: Glaucoma, Alzheimer's Disease, and Parkinson's Disease: An 8-Year Population-Based Follow-Up Study.

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Applications of biomaterials in corneal endothelial tissue engineering

Abstract: When corneal endothelial cells (CECs) are diseased or injured, corneal endothelium can be surgically removed and tissue from a deceased donor can replace the original endothelium. Recent major innovations in corneal endothelial transplantation include replacement of diseased corneal endothelium with a thin lamellar posterior donor comprising a tissue-engineered endothelium carried or cultured on a thin substratum with an organized monolayer of cells. Repairing CECs is challenging because they have restricted proliferative ability in vivo. CECs can be cultivated in vitro and seeded successfully onto natural tissue materials or synthetic polymeric materials as grafts for transplantation. The optimal biomaterials for substrata of CEC growth are being investigated. Establishing a CEC culture system by tissue engineering might require multiple biomaterials to create a new scaffold that overcomes the disadvantages of single biomaterials. Chitosan and polycaprolactone are biodegradable biomaterials approved by the Food and Drug Administration that have superior biological, degradable, and mechanical properties for culturing substratum. We successfully hybridized chitosan and polycaprolactone into blended membranes, and demonstrated that CECs proliferated, developed normal morphology, and maintained their physiological phenotypes. The interaction between cells and biomaterials is important in tissue engineering of CECs. We are still optimizing culture methods for the maintenance and differentiation of CECs on biomaterials.