Publications by authors named "Lin-Chung Woung"

58 Publications

PLGA nanoparticles containing Lingzhi extracts rescue corneal epithelial cells from oxidative damage.

Exp Eye Res 2021 May 17;206:108539. Epub 2021 Mar 17.

Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan. Electronic address:

Oxidative stress-related ocular surface epithelial damage can be initiated by ambient oxygen, UV radiation, and chemical burns. The oxidative damage to cornea can lead to inflammation and even vision loss. Lingzhi (Ganoderma lucidum) is a Chinese herbal drug and has been shown to prevent chronic diseases in clinical practices and has been proven to possess anti-oxidative and anti-inflammatory properties. In the study, we prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as a sustained drug release system of Lingzhi (LZH) to improve bioavailability. The particle size of developed NPs containing LZH (LZH-NPs) was ~184 nm with narrow size distribution. The results of cellular uptake revealed that using NPs as a drug delivery system could significantly increases the intracellular retention time. The results of the cell viability and chemiluminescence assay revealed that 5 μg/ml of LZH-NPs might be the threshold concentration for cultivation of corneal epithelial cells. After treating LZH-NPs in oxidative damaged cells, the results showed that the inflammation-related gene expression and DNA fragmentation level were both significantly decreased. Post-treatment of LZH-NPs in damaged corneal epithelial cells could increase the cell survival rate. In the rabbit corneal alkali burn model, topical instillation of LZH-NPs could promote corneal wound healing and decrease the inflammation. These results suggest that LZH-NPs may have the potential to treat ocular surface diseases caused by oxidative stress.
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http://dx.doi.org/10.1016/j.exer.2021.108539DOI Listing
May 2021

Use and Cost-Effectiveness of a Telehealth Service at a Centralized COVID-19 Quarantine Center in Taiwan: Cohort Study.

J Med Internet Res 2020 12 11;22(12):e22703. Epub 2020 Dec 11.

Department of Neurosurgery, Taipei City Hospital, Taipei, Taiwan.

Background: Telehealth is a recommended method for monitoring the progression of nonsevere infections in patients with COVID-19. However, telehealth has not been widely implemented to monitor SARS-CoV-2 infection in quarantined individuals. Moreover, studies on the cost-effectiveness of quarantine measures during the COVID-19 pandemic are scarce.

Objective: In this cohort study, we aimed to use telehealth to monitor COVID-19 infections in 217 quarantined Taiwanese travelers and to analyze the cost-effectiveness of the quarantine program.

Methods: Travelers were quarantined for 14 days at the Taiwan Yangmingshan quarantine center and monitored until they were discharged. The travelers' clinical symptoms were evaluated twice daily. A multidisciplinary medical team used the telehealth system to provide timely assistance for ill travelers. The cost of the mandatory quarantine was calculated according to data from the Ministry of Health and Welfare of Taiwan.

Results: All 217 quarantined travelers tested negative for SARS-CoV-2 upon admission to the quarantine center. During the quarantine, 28/217 travelers (12.9%) became ill and were evaluated via telehealth. Three travelers with fever were hospitalized after telehealth assessment, and subsequent tests for COVID-19 were negative for all three patients. The total cost incurred during the quarantine was US $193,938, which equated to US $894 per individual.

Conclusions: Telehealth is an effective instrument for monitoring COVID-19 infection in quarantined travelers and could help provide timely disease management for people who are ill. It is imperative to screen and quarantine international travelers for SARS-CoV-2 infection to reduce the nationwide spread of COVID-19.
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http://dx.doi.org/10.2196/22703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735809PMC
December 2020

Trends of Utilization of Palliative Care and Aggressive End-of-Life Care for Patients Who Died of Cancers and Those Who Died of Noncancer Diseases in Hospitals.

J Pain Symptom Manage 2020 12 30;60(6):1136-1143. Epub 2020 Jun 30.

Taipei City Hospital, Taipei City, Taiwan; School of Medicine, National Taiwan University, Taipei City, Taiwan. Electronic address:

Context: Patients who died of cancers and those who died of noncancer diseases may receive different end-of-life care.

Objectives: This study aimed to evaluate the trends of utilization of palliative care and aggressive end-of-life care for patients who died of cancers and those who died of noncancer diseases in hospitals.

Methods: The medical records of patients who died in a public hospital because of cancer or other diseases were reviewed. The proportion of those who received palliative care, admitted to intensive care unit (ICU) within 30 days of death, died in ICU, and received cardiopulmonary resuscitation (CPR) within three days of death in 2013-2014, 2015-2016, and 2017-2018, respectively, was investigated. Multivariate logistic regression was applied to evaluate the independent effects of various factors on the risk of receiving aggressive end-of-life care.

Results: Significant trends of increase in receiving palliative care were found. The proportion of patients who died of noncancer diseases and received palliative care was lower than that of those who died of cancers. Palliative care was associated with a reduced risk of ICU admission within 30 days of death (adjusted odds ratio [AOR] 0.361), death in ICU (AOR 0.208), and receiving CPR within three days of death (AOR 0.057). Patients who died of noncancer diseases had a higher risk of ICU admission within 30 days of death (AOR 5.016), death in ICU (AOR 5.086), and receiving CPR within three days of death (AOR 3.274).

Conclusion: Utilization of palliative care is increasing. Patients who died of noncancer diseases received less palliative care but more aggressive end-of-life care than those who died of cancers.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.06.037DOI Listing
December 2020

The 2020 Taipei Declaration for Universal Palliative Care.

J Palliat Med 2020 06;23(6):747-748

Cambia Palliative Care Center of Excellence, UW Medicine, Seattle, Washington, USA.

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http://dx.doi.org/10.1089/jpm.2020.0026DOI Listing
June 2020

The presence and impact of herpes virus DNA in recipient cornea and aqueous humor on graft survival following penetrating keratoplasty.

J Formos Med Assoc 2020 Nov 13;119(11):1650-1657. Epub 2020 Jan 13.

Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan. Electronic address:

Background/purpose: Reactivation of herpes viruses poses threat to corneal graft survival. This study evaluated the presence of herpes simplex virus type 1 (HSV-1), HSV type 2 (HSV-2), and cytomegalovirus (CMV) DNA in recipient corneas and the aqueous humor of patients undergoing penetrating keratoplasty (PKP), and the impact on graft survival.

Methods: This retrospective study reviewed 90 eyes of 71 patients underwent PKP between 2008 and 2016. Cornea and aqueous humor samples were sent for polymerase chain reaction (PCR) testing for viral DNA. The main outcomes were PCR results and graft survival.

Results: Recipient corneas tested positive for HSV-1 in 47 eyes (52.2%), for HSV-2 in 24 eyes (26.7%), and for CMV in seven eyes (7.8%). Aqueous humor tested positive for HSV-1 in 44 eyes (48.9%), for HSV-2 in 25 eyes (27.8%), and for CMV in eight eyes (8.9%). The presence of aqueous HSV-1 DNA was associated with higher risk of graft failure (p = 0.005), whereas corneal HSV-1 DNA was not. The presence of HSV-2 DNA had no significant impact on graft survival. Aqueous CMV DNA was associated with higher risk of graft failure in univariate model, but not in multivariate model.

Conclusion: There were high positive rates of HSV-1, HSV-2, and CMV DNA in recipient corneas and aqueous humor at the time of PKP, even among patients not suspected of latent viral infection. The presence of aqueous HSV-1 DNA was associated with higher risk of graft failure.
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http://dx.doi.org/10.1016/j.jfma.2019.12.009DOI Listing
November 2020

Expression Profiling of Exosomal miRNAs Derived from the Aqueous Humor of Myopia Patients.

Tohoku J Exp Med 2019 11;249(3):213-221

Department of Ophthalmology, Taipei City Hospital.

Myopia is the most common refractive disorder in Eastern Asia. The development of myopia is associated with the cooperation of various ocular tissues. Exosomes in the aqueous humor (AH) have been implicated to modulate intracellular communications by transferring exosomal miRNAs and proteins between cells. These exosomal miRNAs and proteins are likely involved in the pathogenesis of various eye diseases. In this study, we aimed to explore human exosomal miRNA profiles and their roles in myopia development. AH samples were collected from 16 patients (8 myopia and 8 control) undergoing routine cataract surgeries. Exosomes were isolated from AH of each individual using the ExoQuick solution. The numbers and sizes of exosomes were not significantly different between the myopia and control groups. The individual exosomes of the same group were pooled to purify RNA. Unexpectedly, the myopia group contained 2.78-fold total RNA amount than that in the control group. Thereafter, miRNA profiles were analyzed using the OpenArray system. We thus found 15 myopia-specific miRNAs and four myopia-absent miRNAs. By using bioinformatics analysis, we identified six well-known myopia-associated genes that are potential targets of five myopia-specific miRNAs (has-miR-582-3p, has-miR-17-5p, has-miR-885-3p, has-miR-19b-3p, and has-miR-450b-5p). These genes are cholinergic receptor muscarinic 2 (CHRM2), cyclic nucleotide-gated channel beta 3 (CNGB3), vascular endothelial growth factor A (VEGFA), adenosine A2a receptor (ADORA2A), insulin-like growth factor 1 (IGF1), and lumican (LUM). Moreover, CHRM2 may be a target of myopia-absent miRNA (has-miR-378a-5p). In conclusion, we show the expression profiles of AH-derived exosomal miRNAs and their potential roles in myopia development.
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http://dx.doi.org/10.1620/tjem.249.213DOI Listing
November 2019

A Worldwide Bibliometric Analysis of Publications on Advance Care Planning in the Past 3 Decades.

Am J Hosp Palliat Care 2020 Jun 21;37(6):474-480. Epub 2019 Nov 21.

Academy of Humanities and Innovation, Taipei City Hospital, Taipei City.

Background: In recent decades, issues related to end-of-life care and advance care planning (ACP) have attracted popular attention. Advance care planning has been broadly discussed as one of the potential solutions to protect a patient's rights, autonomy, and dignity at the end of life. To better understand publishing on this topic, we conducted this study to demonstrate the worldwide research productivity, trends, and citations of ACP in the past 3 decades by bibliometric analysis.

Methods: Articles published on ACP were retrieved from the Web of Science Core Collection database, and the subject terms included "advance directive," or "advance care planning."

Results: Overall, 2126 publications on ACP were retrieved until January 22, 2019. North America, Western Europe, and Australia were the most productive regions. The top 15 countries published 95.9% of the total number of articles. The United States accounted for approximately three-fifths (61.0%) of all publications. When adjusted for population size, Australia had the highest number of articles per million persons (6.64), followed by the Netherlands (6.14) and Belgium (4.61). The most productive authors were Sudore (n = 37), Deliens (n = 29), and Green (n = 24).

Conclusions: The current study revealed that research in terms of publications on ACP has rapidly increased over the past 3 decades. Developed countries, especially the United States, were more concerned with the ACP research field than developing countries were.
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http://dx.doi.org/10.1177/1049909119886305DOI Listing
June 2020

The 2018 Taipei Declaration for Ultimate Integration of Palliative Care.

J Palliat Med 2019 May;22(5):476-477

6 Cambia Palliative Care Center of Excellence, UW Medicine, Seattle, Washington.

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http://dx.doi.org/10.1089/jpm.2019.0055DOI Listing
May 2019

Difference in frequency and outcome of geriatric emergency department utilization between urban and rural areas.

J Chin Med Assoc 2019 Apr;82(4):282-288

Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan, ROC.

Background: Elderly people are susceptible to develop multiple chronic diseases and are thus likely to utilize the emergency department (ED). Access to health care and health outcomes may differ between rural and urban areas. This study aims to compare the frequency and outcome of geriatric ED utilization between urban and rural areas.

Methods: This population-based study obtained information from the health insurance database. The frequency and outcome of ED utilization in 2013 were compared among people aged ≥65 years living in urban and rural areas. The independent effect of various characteristics on the frequency and outcome of ED utilization was evaluated using multivariate logistic regression analysis.

Results: Of the 6695 people living in urban areas, 1879 (28.07%) utilized the ED and accounted for 3859 ED visits. Meanwhile, 908 (29.75%) of the 3052 people living in rural areas utilized the ED and accounted for 1820 ED visits. No difference in the prevalence of ED utilization was found between the urban and rural areas. Urbanization did not affect the risk of frequent ED utilization among ED users. People living in rural areas had an increased risk of ED visits with a high acuity (adjusted odds ratio: 1.40, 95% CI: 1.12-1.75). Urbanization did not affect the risk of hospitalization or immediate death after ED visits.

Conclusion: The frequency of ED utilization showed no urban-rural difference. Elderly people living in rural areas had an increased risk of visiting the ED with a high acuity.
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http://dx.doi.org/10.1097/JCMA.0000000000000053DOI Listing
April 2019

Artificial intelligence-based decision-making for age-related macular degeneration.

Theranostics 2019 1;9(1):232-245. Epub 2019 Jan 1.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.

Artificial intelligence (AI) based on convolutional neural networks (CNNs) has a great potential to enhance medical workflow and improve health care quality. Of particular interest is practical implementation of such AI-based software as a cloud-based tool aimed for telemedicine, the practice of providing medical care from a distance using electronic interfaces. In this study, we used a dataset of labeled 35,900 optical coherence tomography (OCT) images obtained from age-related macular degeneration (AMD) patients and used them to train three types of CNNs to perform AMD diagnosis. Here, we present an AI- and cloud-based telemedicine interaction tool for diagnosis and proposed treatment of AMD. Through deep learning process based on the analysis of preprocessed optical coherence tomography (OCT) imaging data, our AI-based system achieved the same image discrimination rate as that of retinal specialists in our hospital. The AI platform's detection accuracy was generally higher than 90% and was significantly superior (p < 0.001) to that of medical students (69.4% and 68.9%) and equal (p = 0.99) to that of retinal specialists (92.73% and 91.90%). Furthermore, it provided appropriate treatment recommendations comparable to those of retinal specialists. We therefore developed a website for realistic cloud computing based on this AI platform, available at https://www.ym.edu.tw/~AI-OCT/. Patients can upload their OCT images to the website to verify whether they have AMD and require treatment. Using an AI-based cloud service represents a real solution for medical imaging diagnostics and telemedicine.
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http://dx.doi.org/10.7150/thno.28447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332801PMC
December 2019

A Novel Machine Learning Algorithm to Automatically Predict Visual Outcomes in Intravitreal Ranibizumab-Treated Patients with Diabetic Macular Edema.

J Clin Med 2018 Nov 24;7(12). Epub 2018 Nov 24.

Department of Ophthalmology, Taipei City Hospital, Taipei 10632, Taiwan.

Purpose: Artificial neural networks (ANNs) are one type of artificial intelligence. Here, we use an ANN-based machine learning algorithm to automatically predict visual outcomes after ranibizumab treatment in diabetic macular edema.

Methods: Patient data were used to optimize ANNs for regression calculation. The target was established as the final visual acuity at 52, 78, or 104 weeks. The input baseline variables were sex, age, diabetes type or condition, systemic diseases, eye status and treatment time tables. Three groups were randomly devised to build, test and demonstrate the accuracy of the algorithms.

Results: At 52, 78 and 104 weeks, 512, 483 and 464 eyes were included, respectively. For the training group, testing group and validation group, the respective correlation coefficients were 0.75, 0.77 and 0.70 (52 weeks); 0.79, 0.80 and 0.55 (78 weeks); and 0.83, 0.47 and 0.81 (104 weeks), while the mean standard errors of final visual acuity were 6.50, 6.11 and 6.40 (52 weeks); 5.91, 5.83 and 7.59; (78 weeks); and 5.39, 8.70 and 6.81 (104 weeks).

Conclusions: Machine learning had good correlation coefficients for predicating prognosis with ranibizumab with just baseline characteristics. These models could be the useful clinical tools for prediction of success of the treatments.
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http://dx.doi.org/10.3390/jcm7120475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306861PMC
November 2018

Clinical Course and Treatment Response of Neuromyelitis Optica Spectrum Disease: An 8-Year Experience.

Asia Pac J Ophthalmol (Phila) 2019 May-Jun;8(3):206-210. Epub 2018 Nov 13.

Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan.

Purpose: To report the clinical course and treatment response in a cohort of patients with neuromyelitis optica spectrum disorder (NMOSD) from a single referral center in Taiwan.

Design: Case series.

Methods: All NMOSD patients who received treatment and follow-up checks at National Taiwan University Hospital for at least 2 years between January 2008 and December 2016 were recruited. Demographic data and detailed characteristics of clinical course including acute episodes, maintenance therapies, and visual outcome were collected. Patients were examined every 6 months and during each episode of relapse.

Results: A total of 96 patients were identified; of them, 68 (70.8%) had optic neuritis. Optic neuritis was the initial presentation of NMOSD in 44 patients. Among the patients with optic neuritis, 32.4% had recurrent optic neuritis within 1 year from the first episode. Compared with the group without optic neuritis, the group with optic neuritis had a younger age of presentation (34.4 ± 15.9 vs 42.4 ± 14.8 years, = 0.02) and a higher 1-year recurrence rate (64.7% vs 17.9%, < 0.001). Among the patients with optic neuritis, 51.5% had a final visual acuity of worse than 20/200. Multiple regression analysis showed that the presence of aquaporin-4-IgG antibodies and poor initial visual acuity were the risk factors for worse visual outcome.

Conclusions: In this study, patients with optic neuritis were younger and had a higher 1-year recurrence rate. Despite using steroid therapy during the acute phase and immunosuppressive agents as long-term treatment, visual prognosis was poor. Aquaporin-4-IgG antibodies and initial visual acuity were associated with final visual outcome.
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http://dx.doi.org/10.22608/APO.2018247DOI Listing
June 2019

Elevation of serum oxidative stress in patients with retina vein occlusions.

Acta Ophthalmol 2019 Mar 26;97(2):e290-e295. Epub 2018 Sep 26.

School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Purpose: Retina vein occlusion (RVO) is a visual-threatening retinal disease that causes irreversible impaired quality of life. The contribution of oxidative stress behind clinical course of RVO was rarely investigated. The study aimed to measure the serum oxidative biomarker in patients with RVO to investigate further physical response.

Methods: We measured the serum levels of malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8OHdG), Sirutin 1 (SIRT1), peroxisome proliferator- activated receptor gamma (PPAR-r), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), orkhead box protein O1 (FOXO1), orkhead box protein O3 (FOXO3), catalase, (SOD) and hydrogen peroxide (H O ) among 19 patients with cataract as control group and 36 patients with RVO, respectively.

Results: The mean MDA, 8OHdG and hydrogen peroxide in the serum were significantly higher in patients with RVO compared with the results in control group subjects. Whereas SIRT1, PPAR-r, PGC-1, FOXO1, FOXO3, catalase and SOD levels in serum were significantly decreased in patients with RVO compared with control group.

Conclusion: We demonstrated that the serum level of MDA, 8OHdG and hydrogen peroxide is increased in patients with RVO. Among these, the elevation of MDA, 8OHdG and hydrogen peroxide suggests the increasing of serum oxidative stress in RVO patients. All enzymes related reactive oxygen species scavenge were decreased. Thus, focal RVO may increase systemic oxidative stress within serum.
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http://dx.doi.org/10.1111/aos.13892DOI Listing
March 2019

Update on ocular myasthenia gravis in Taiwan.

Taiwan J Ophthalmol 2018 Apr-Jun;8(2):67-73

National Taiwan University Hospital, Taipei City, Taiwan.

Myasthenia gravis (MG) is an autoimmune disease involving the neuromuscular junction. Autoantibodies to the acetylcholine receptor or, less frequently, to muscle-specific kinase, attack against the postsynaptic junctional proteins, resulting in fluctuating and variable weakness of muscles. Extraocular, levator palpebrae superioris, and orbicularis oculi muscles are particularly susceptible. The majority of patients with MG present with purely ocular symptoms including ptosis and diplopia initially. About half of these patients progress to generalized disease within 2 years. The prevalence of MG in Taiwan is 140 per million with male to female ratio of 0.7. The incidence rate is higher in the elderly. Several immune-related diseases such as lymphoid malignancy, diabetes, and thyroid diseases are associated with MG in the national population-based studies in Taiwan. Ice pack test, rest test, Tensilon/neostigmine test, circulating antibody measurement, and electrophysiological studies are useful diagnostic tools with variable sensitivity and specificity. For the patients with ocular MG, acetylcholinesterase inhibitors are usually the first-line treatment. Corticosteroids and immunosuppressant could provide better disease control and may reduce the risk of conversion to generalized form although there is still some controversy. A thymectomy is also beneficial for ocular MG, especially in refractory cases. The correction of ptosis and strabismus surgery could improve the visual outcome but should be performed only in stable disease.
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http://dx.doi.org/10.4103/tjo.tjo_39_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055315PMC
July 2018

The 2017 Taipei Declaration for Health-Promoting Palliative Care.

J Palliat Med 2018 05;21(5):581-582

7 Cambia Palliative Care Center of Excellence, University of Washington , Seattle, Washington.

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http://dx.doi.org/10.1089/jpm.2017.0708DOI Listing
May 2018

Intraocular lens opacification after Descemet's stripping automated endothelial keratoplasty.

Taiwan J Ophthalmol 2017 Jul-Sep;7(3):160-163

Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan.

Compared with conventional penetrating keratoplasty, Descemet's stripping automated endothelial keratoplasty (DSAEK) more effectively maintain global integrity and rapid vision rehabilitation with less ocular surface disorders in patients with endothelial dysfunction. Here, we report a case of a 76-year-old woman who experienced opacification of a hydrophilic intraocular lens (IOL) approximately 10 months after DSAEK. The patient with no history of systemic disease developed pseudophakic bullous keratopathy in the right eye 2 years after undergoing cataract surgery. The best-corrected visual acuity (BCVA) of the right eye was Snellen 0.01 when presented to our hospital. DSAEK was arranged and performed smoothly. However, the graft detached over the upper part of the cornea on postoperative day 1. Thus, rebubbling was performed immediately. After the procedure, the graft was well attached, and the cornea became clear gradually. The BCVA returned to Snellen 0.6. However, progressive opacification over the anterior surface of the IOL was observed 10 months postoperatively. Vision deteriorated to 0.5 with various refractive errors during 2-year follow-up. IOL exchange may be considered if the vision is getting worse. IOL opacification may result from a direct contact between the IOL surface and exogenous air, particularly in a hydrophilic IOL, and can be a rare but significant complication after DSAEK. Clinicians planning to perform DSAEK should consider the composition of the IOL, the amount of intracameral air, duration of air filling, and high intraocular pressure.
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http://dx.doi.org/10.4103/tjo.tjo_54_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637382PMC
October 2017

Intraocular pressure monitoring by rebound tonometry in children with myopia.

Taiwan J Ophthalmol 2017 Jul-Sep;7(3):149-154

Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan.

Background/purpose: Topical atropine treatment is generally accepted to retard the progression of myopia, but it is associated with side effects such as photophobia and elevation of intraocular pressure (IOP). IOP measurements in children are challenging. The traditional applanation tonometry by direct contact with the cornea will require patient's cooperation. The rebound tonometer, using a dynamic electromechanical method for measuring IOP, shows good correlation with traditional tonometry. The purpose of this study is to evaluate the IOP of myopic children under atropine treatment using rebound tonometer and to compare the characteristics between rebound tonometry and applanation tonometry.

Methods: This study is a prospective study measuring IOP by rebound tonometer in myopic children under regular low-dose atropine treatment. We recruited children with refraction error showing myopia over -0.5 D with 0.15%, 0.3%, or 0.5% atropine eye drops use every night or every other night for myopia control. Children with treatment duration of atropine <1 month were excluded from the study. IOP measurements were performed by applanation tonometer (Tono-Pen XL, Reichert) and rebound tonometer (ICARE). The reliability of rebound tonometer was analyzed with percentage. Comparison of IOP between rebound tonometer and applanation tonometry was presented.

Results: The rebound tonometry was well tolerated by all participants and caused no complaints, discomfort, or adverse events. Totally 42 myopic eyes of 42 subjects were included in the study. The average age of these participants was 10 years old, range from 5 to 16. Median = 10 years old. The average IOP of the right eye by rebound tonometer was 17.4 ± 3 mmHg, and 17.1 ± 3 mmHg by applanation tonometry. Nearly 19%, 33%, and 24% of difference of IOP readings between rebound tonometer and Tono-Pen applanation are within 0 mmHg, 1 mmHg, and 1-2 mmHg, respectively.

Conclusions: Rebound tonometry has good correlation with applanation tonometry and 76.1% of differences between two tonometers are <2 mmHg. The advantage of drop-free rebound tonometry has made it easier to obtain IOP readings in myopia children under atropine treatment.
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http://dx.doi.org/10.4103/tjo.tjo_45_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637380PMC
October 2017

Factors predicting a home death among home palliative care recipients.

Medicine (Baltimore) 2017 Oct;96(41):e8210

Department of Urology, Taipei City Hospital, Taipei City Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei City School of Medicine, Fu-Jen Catholic University, New Taipei City Superintendent Office, Taipei City Hospital, Taipei City Department of Surgery, National Taiwan University, Taipei City Center of Quality Management, Taipei City Hospital, Taipei City Cross-Strait Medical and Management Communication Center, Taipei City Hospital, Taipei City Administrative Center, Ministry of Health and Welfare Taipei Hospital, New Taipei City Department of Cardiology, Taipei City Hospital, Taipei City, Taiwan.

Awareness of factors affecting the place of death could improve communication between healthcare providers and patients and their families regarding patient preferences and the feasibility of dying in the preferred place.This study aimed to evaluate factors predicting home death among home palliative care recipients.This is a population-based study using a national representative sample retrieved from the National Health Insurance Research Database. Subjects receiving home palliative care, from 2010 to 2012, were analyzed to evaluate the association between a home death and various characteristics related to illness, individual, and health care utilization. A multiple-logistic regression model was used to assess the independent effect of various characteristics on the likelihood of a home death.The overall rate of a home death for home palliative care recipients was 43.6%. Age; gender; urbanization of the area where the patients lived; illness; the total number of home visits by all health care professionals; the number of home visits by nurses; utilization of nasogastric tube, endotracheal tube, or indwelling urinary catheter; the number of emergency department visits; and admission to intensive care unit in previous 1 year were not significantly associated with the risk of a home death. Physician home visits increased the likelihood of a home death. Compared with subjects without physician home visits (31.4%) those with 1 physician home visit (53.0%, adjusted odds ratio [AOR]: 3.23, 95% confidence interval [CI]: 1.93-5.42) and those with ≥2 physician home visits (43.9%, AOR: 2.23, 95% CI: 1.06-4.70) had higher likelihood of a home death. Compared with subjects with hospitalization 0 to 6 times in previous 1 year, those with hospitalization ≥7 times in previous 1 year (AOR: 0.57, 95% CI: 0.34-0.95) had lower likelihood of a home death.Among home palliative care recipients, physician home visits increased the likelihood of a home death. Hospitalizations ≥7 times in previous 1 year decreased the likelihood of a home death.
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http://dx.doi.org/10.1097/MD.0000000000008210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662310PMC
October 2017

Risk factors for myopia progression in second-grade primary school children in Taipei: a population-based cohort study.

Br J Ophthalmol 2017 12 18;101(12):1611-1617. Epub 2017 Mar 18.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.

Purpose: To evaluate the 1-year progression of myopia and associated risk factors in second-grade primary school children.

Methods: The myopia investigation study in Taipei provided semiannual visual acuity testing and cycloplegic refraction for all second-grade primary school children (mean age: 7.49 years) in Taipei who provided parental consent. A questionnaire was distributed to the participants' parents before the first and third examinations. We evaluated 1-year follow-up data for children noted to have myopia on the first examination. Multinomial logistic regression models were applied to assess risk factors associated with myopia progression. Myopia progression was categorised, based on the change in spherical equivalent (ΔSE) over 1 year, as slow (ΔSE>-0.5 dioptres (D)), moderate (-1.0 D<ΔSE≤-0.5 D) or fast (ΔSE≤-1.0 D). Of the 4214 myopic children, data were analysed for 3256 (77.3%) who completed the 1-year follow-up evaluation.

Results: The baseline SE was -1.43±1.1 D. The average ΔSE was -0.42±0.85 D, with 46.96%, 28.50% and 24.54% of the study subjects showing slow, moderate and fast myopia progression, respectively. When compared with slow myopia progression, fast myopia progression was associated with a greater myopic SE at baseline (OR: 0.67, 95% CI: 0.61 to 0.72) and a shorter eye-object distance when doing near work (OR: 1.45, 95% CI: 1.18 to 1.78). More outdoor activity time and self-reported cycloplegic treatment were not associated with slow myopia progression.

Conclusions: Children with fast annual myopia progression were more myopic at baseline and had a shorter reading distance. Our study results highlight the importance of having children keep a proper reading distance.
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http://dx.doi.org/10.1136/bjophthalmol-2016-309299DOI Listing
December 2017

Summary of the Neuro-Ophthalmology Symposium in the 31st Asia-Pacific Academy of Ophthalmology Congress (APAO 2016).

Neuroophthalmology 2016 Oct 15;40(5):251-253. Epub 2016 Jul 15.

Department of Ophthalmology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.

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http://dx.doi.org/10.1080/01658107.2016.1201520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122963PMC
October 2016

Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors.

Int J Med Sci 2016 12;13(9):717-23. Epub 2016 Sep 12.

Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan;; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.

Objectives: Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR.

Methods: At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs.

Results: We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines.

Conclusion: Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally.
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http://dx.doi.org/10.7150/ijms.16345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027191PMC
March 2017

Prevalence and risk factors for myopia in second-grade primary school children in Taipei: A population-based study.

J Chin Med Assoc 2016 Nov 24;79(11):625-632. Epub 2016 Jun 24.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC. Electronic address:

Background: High myopia is associated with multiple ocular morbidities that may lead to irreversible blindness. Because high myopia in an adult is thought to be related to onset of myopia in very early childhood, detecting myopia early and working to improve modifiable risk factors may help reduce the development of high myopia. In this study, we tried to evaluate the prevalence of myopia and associated risk factors in second-grade primary school children in Taipei, Taiwan.

Methods: A questionnaire was distributed to the participants' parents, and their written informed consent was obtained before performing eye examinations that included visual acuity testing and cycloplegic autorefraction. Multiple logistic regression models were applied to assess possible risk factors associated with myopia. Myopia was defined as spherical equivalent of -0.50 D or less in either eye.

Results: The prevalence of myopia in the second graders was 36.4%. After adjustment for other characteristics, the following variables were significantly associated with a higher risk of myopia: male sex [odds ratio (OR)=1.24, p<0.001]; suburban residence (vs. urban; OR=1.10, p=0.02); lower maternal education level (OR=1.25, p<0.001); the presence of myopia in one parent (OR=1.66, p<0.001) or both parents (OR=2.82, p<0.001); time spent on near-work activity every day (OR=1.21, p<0.001); shorter visual distance when doing near-work activity (OR=1.17, p<0.001); and participation in an after-school tutorial program (OR=1.20, p<0.001). By contrast, resting after 30 minutes of near-work activity (OR=0.84, p<0.001) and spending more time participating in outdoor activities on weekends (OR=0.91, p=0.03) were significantly associated with a lower risk of myopia.

Conclusion: Our findings indicate that lifestyle and reading habits impact the development of myopia during early childhood. Behavior modification, such as more time spent outside during the day and limited near-work activity, may be a feasible strategy for curbing the increasingly high prevalence of myopia in Taipei.
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http://dx.doi.org/10.1016/j.jcma.2016.02.011DOI Listing
November 2016

Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing.

Carbohydr Polym 2016 Jan 3;135:308-15. Epub 2015 Sep 3.

Institute of Pharmacology, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 112, Taiwan, ROC; Department of Education and Research, Taipei City Hospital, No. 145, Zhengzhou Rd., Datong Dist., Taipei 103, Taiwan, ROC. Electronic address:

Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn.
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http://dx.doi.org/10.1016/j.carbpol.2015.08.098DOI Listing
January 2016

Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration.

J Chin Med Assoc 2015 Nov 14;78(11):635-41. Epub 2015 Sep 14.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address:

Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF) and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.
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http://dx.doi.org/10.1016/j.jcma.2015.07.008DOI Listing
November 2015

Subconjunctival Herniated Orbital Fat Mimicking Adipocytic Neoplasm.

Optom Vis Sci 2015 Oct;92(10):1021-6

*MD †PhD Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan (CCL, SWL, CCC, LCW); Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan (SLL); and Department of Pathology, Taipei City Hospital, Renai Branch, Taipei, Taiwan (YYW).

Purpose: To describe and discuss rare and benign conditions of subconjunctival orbital fat herniation that may mimic adipocytic neoplasm.

Methods: Sixteen eyes of 13 patients with subconjunctival orbital fat herniation were included. They all underwent transconjunctival excision owing to cosmesis, discomfort, or suspicion of malignancy. Histopathologic examination, postoperative complications, and recurrent conditions were analyzed.

Results: Eleven male and two female patients were included. The lesion was unilateral in 10 and bilateral in 3 cases. Excision was performed via conjunctival wound and removing the prolapsed orbital fat. The conjunctiva was then closed with two to three interrupted sutures. All the histopathologic specimens revealed Lochkern cells, floret cells, and mature adipocytes separated by fibrovascular septae without hyperchromatic cells, consistent with subconjunctival herniated orbital fat. All the patients were treated successfully with transconjunctival excision without recurrence at an average follow-up of 10.6 months (range, 6 to 16 months).

Conclusions: Prolapse of subconjunctival orbital fat is an uncommon entity of intraorbital masses and may mimic adipocytic neoplasm. It is usually associated with a dehiscence in the Tenon capsule. Surgical excision is indicated and pathologic evaluation is necessary if any malignancy is suspected.
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http://dx.doi.org/10.1097/OPX.0000000000000693DOI Listing
October 2015

Socioeconomic disparities in preventable hospitalization among adults with diabetes in Taiwan: a multilevel modelling approach.

Int J Equity Health 2015 Mar 21;14:31. Epub 2015 Mar 21.

Institute of Health and Welfare Policy, National Yang-Ming University, No.155, Sec. 2, Linong St, Beitou Dist, Taipei City, 112, Taiwan.

Introduction: Literature shows socioeconomic disparities are related to various aspects of diabetes care. However, few studies have explored the relationship between socioeconomics and healthcare outcomes, particularly with regard to preventable hospitalization. This cohort study employed hierarchical modelling to evaluate the role of socioeconomics at both the individual and regional levels in order to examine disparities associated with the preventable hospitalization of diabetes patients in Taiwan.

Methods: This study employed the Longitudinal Health Insurance Database 2010, which provided a representative cohort comprising one million people enrolled in Taiwan's National Health Insurance in 2010. All diabetes patients aged 18 and older who received regular care in 2010 were included in this study. The outcome examined in this study was diabetes-related preventable hospitalization during the period of 2010 to 2011. Socioeconomic status at the individual level was measured according to income and at the regional level according to level of urbanization and the proportion of residents who had completed college education. Control variables included age, gender, comorbidities, time of diabetes diagnosis, participated in the pay-for-performance program status, and the characteristics of regular sources of care, including the level of the facility (i.e., medical centre, regional hospital, local hospital, outpatient clinic) and ownership. Statistical analysis was performed using generalized linear mixed models.

Results: A total of 57,791 patients from 25 regions diagnosed with type-2 diabetes mellitus were identified in the National Health Insurance claim data for the year 2010. 1040 of these patients (1.8%) had at least one diabetes-related preventable hospitalization event during the period of 2010-2011. After controlling for the characteristics of patients and health care providers, our results show that dependents and patients in low and middle income brackets (OR = 2.48, 2.44, and 2.08 respectively) as well as those living in regions with a low, median, or high education bracket (OR = 1.32, 1.38, and 1.46 respectively) face a higher probability of preventable hospitalization.

Conclusions: Our results demonstrate that the socioeconomic effects of higher education at the regional level as well as income at the individual level are important factors which affect disparities in diabetes-related preventable hospitalization.
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http://dx.doi.org/10.1186/s12939-015-0160-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377057PMC
March 2015

Herpetic keratouveitis mixed with bilateral Pseudomonas corneal ulcers in vitamin A deficiency.

J Formos Med Assoc 2015 Feb 30;114(2):184-7. Epub 2012 Apr 30.

Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.

A 56-year-old woman complained of blurred vision and pain in her right eye for several days. Slit lamp examination revealed a large epithelial defect and disciform stromal edema with ring infiltration in her right cornea. Unfortunately, hypopyon and purulent discharge subsequently developed in both eyes. Herpetic keratouveitis and a superimposed pseudomonas infection were diagnosed. A systemic review on the patient showed malnutrition due to her dietary preference and vegetarianism. After the infection was controlled, bilateral epithelial defects persisted for a long time. We performed amniotic membrane transplantation on both eyes and the clinical status improved with administration of vitamin and protein supplements. Although rare in Taiwan, vitamin A deficiency should be kept in mind when conjunctival and corneal xerosis occurred. Vitamin A supplements are suggested because of the increased susceptibility to infection in patients with this clinical status.
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http://dx.doi.org/10.1016/j.jfma.2011.07.018DOI Listing
February 2015

Stem Cell Therapy for Corneal Regeneration Medicine and Contemporary Nanomedicine for Corneal Disorders.

Cell Transplant 2015 12;24(10):1915-30. Epub 2014 Dec 12.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

The ocular surface is the outermost part of the visual system that faces many extrinsic or intrinsic threats, such as chemical burn, infectious pathogens, thermal injury, Stevens-Johnson syndrome, ocular pemphegoid, and other autoimmune diseases. The cornea plays an important role in conducting light into the eyes and protecting intraocular structures. Several ocular surface diseases will lead to the neovascularization or conjunctivalization of corneal epithelium, leaving opacified optical media. It is believed that some corneal limbal cells may present stem cell-like properties and are capable of regenerating corneal epithelium. Therefore, cultivation of limbal cells and reconstruction of the ocular surface with these limbal cell grafts have attracted tremendous interest in the past few years. Currently, stem cells are found to potentiate regenerative medicine by their capability of differentiation into multiple lineage cells. Among these, the most common cell sources for clinical use are embryonic, adult, and induced stem cells. Different stem cells have varied specific advantages and limitations for in vivo and in vitro expansion. Other than ocular surface diseases, culture and transplantation of corneal endothelial cells is another major issue for corneal decompensation and awaits further studies to find out comprehensive solutions dealing with nonregenerative corneal endothelium. Recently, studies of in vitro endothelium culture and ρ-associated kinase (ROCK) inhibitor have gained encouraging results. Some clinical trials have already been finished and achieved remarkable vision recovery. Finally, nanotechnology has shown great improvement in ocular drug delivery systems during the past two decades. Strategies to reconstruct the ocular surface could combine with nanoparticles to facilitate wound healing, drug delivery, and even neovascularization inhibition. In this review article, we summarized the major advances of corneal limbal stem cells, limbal stem cell deficiency, corneal endothelial cell culture/transplantation, and application of nanotechnology on ocular surface reconstruction. We also illustrated potential applications of current knowledge for the future treatment of ocular surface diseases.
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http://dx.doi.org/10.3727/096368914X685744DOI Listing
August 2016

The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress.

Front Aging Neurosci 2014 1;6:191. Epub 2014 Aug 1.

Department of Medical Research and Education, Taipei Veterans General Hospital Taipei, Taiwan ; Department of Ophthalmology, Taipei Veterans General Hospital Taipei, Taiwan.

Age-related macular degeneration (AMD) is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE) cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs) via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2, and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient-derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress.
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http://dx.doi.org/10.3389/fnagi.2014.00191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117985PMC
August 2014
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