Publications by authors named "Jiann-Torng Chen"

90 Publications

Glycemic Gap as a Useful Surrogate Marker for Glucose Variability and Progression of Diabetic Retinopathy.

J Pers Med 2021 Aug 16;11(8). Epub 2021 Aug 16.

National Defense Medical Center, Department of Family and Community Medicine, Tri-Service General Hospital, No.161, Min-Chun E. Rd., Sec. 6, Neihu, Taipei 11490, Taiwan.

(1) Background: Recent studies have reported that the glucose variability (GV), irrespective of glycosylated hemoglobin (HbA1c), could be an additional risk factor for the development of diabetic retinopathy (DR). However, measurements for GV, such as continuous glucose monitoring (CGM) and fasting plasma glucose (FPG) variability, are expensive and time consuming. (2) Methods: This present study aims to explore the correlation between the glycemic gap as a measurement of GV, and DR. In total, 2565 patients were included in this study. We evaluated the effect of the different types of glycemic gaps on DR progression. (3) Results: We found that the area under the curve (AUC) values of both the glycemic gap and negative glycemic gap showed an association with DR progression. (4) Conclusions: On eliminating the possible influences of chronic blood glucose controls, the results show that GV has deleterious effects that are associated with the progression of DR. The glycemic gap is a simple measurement of GV, and the predictive value of the negative glycemic gap in DR progression shows that GV and treatment-related hypoglycemia may cause the development of DR. Individual treatment goals with a reasonable HbA1c and minimal glucose fluctuations may help in preventing DR.
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http://dx.doi.org/10.3390/jpm11080799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401120PMC
August 2021

Repression of Smad4 by MicroRNA-1285 moderates TGF-β-induced epithelial-mesenchymal transition in proliferative vitreoretinopathy.

PLoS One 2021 12;16(8):e0254873. Epub 2021 Aug 12.

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.

The purpose of this study was to assess whether microRNA (miR)-1285 can suppress the epithelial-mesenchymal transition (EMT) in retinal pigment epithelial cells. Expression of miR-1285 was evaluated using quantitative real-time polymerase chain reaction (RT-qPCR). The features of EMT were assessed using Western blotting, immunocytochemical staining, scratch wound healing tests, modified Boyden chamber assay, and collagen gel contraction assay. A rabbit model of proliferative vitreoretinopathy (PVR) was used for in vivo testing, which involved the induction of PVR by injection of transfected ARPE cells into the vitreous chamber. Luciferase reporter assay was performed to identify the putative target of miR-1285. The expression of miR-1285 was downregulated in ARPE-19 cells treated with transforming growth factor (TGF)-β. Overexpression of miR-1285 led to upregulation of zonula occludens-1, downregulation of α-smooth muscle actin and vimentin, cell migration and cell contractility-all EMT features-in the TGF-β2-treated ARPE-19 cells. The reporter assay indicated that the 3' untranslated region of Smad4 was the direct target of miR1285. PVR progression was alleviated in the miR-1285 transfected rabbits. In conclusion, overexpression of miR-1285 attenuates TGF-β2-induced EMT in a rabbit model of PVR, and the effect of miR-1285 in PVR is dependent on Smad4. Further research is warranted to develop a feasible therapeutic approach for the prevention and treatment of PVR.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254873PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360606PMC
August 2021

Predisposing Factors for Severe Complications after Cataract Surgery: A Nationwide Population-Based Study.

J Clin Med 2021 Jul 28;10(15). Epub 2021 Jul 28.

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 11490, Taiwan.

We conducted a retrospective group study to evaluate the potential systemic risk factors for major postoperative complications of cataract surgery. Individuals diagnosed with ( = 2046) and without ( = 8184) serious complications after cataract surgery were matched 1:4 for age, sex, and index date obtained using Taiwan's National Health Insurance Research Database. The outcome was defined as at least one new inpatient or outpatient diagnosis of systemic disease one year before the index date. The effect of demographic data on postoperative complications was also analyzed in the multivariable model. Data were analyzed using univariate and multivariate conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals of the risk of developing serious complications. After the entire study interval, the major postoperative complications of cataract surgery were associated with the following systemic diseases: hypertension (adjusted OR (aOR) = 2.329, < 0.001), diabetes mellitus (aOR = 2.818, < 0.001), hyperlipidemia (aOR = 1.702, < 0.001), congestive heart failure (aOR = 2.891, < 0.001), rheumatic disease (aOR = 1.965, < 0.001), and kidney disease needing hemodialysis (aOR = 2.942, < 0.001). Additionally, demographic data including old age, higher urbanization level, higher level of care, and more frequent inpatient department visits were associated with a higher rate of postoperative complications. In conclusion, metabolic syndrome, chronic heart failure, end-stage renal disease, rheumatic disease, older age, and frequent inpatient department visits are correlated with the development of severe postoperative complications of cataract surgery. Therefore, cataract surgery patients should be informed about a higher possibility of postoperative complications.
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http://dx.doi.org/10.3390/jcm10153336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347944PMC
July 2021

Increased risk for central serous chorioretinopathy in nephrotic syndrome patients: A population-based cohort study.

J Chin Med Assoc 2021 Jul 26. Epub 2021 Jul 26.

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC Department of Nephrology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Taipei, Taiwan, ROC Department of Ophthalmology, Songshan Branch of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan, ROC Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.

Background: Nephrotic syndrome (NS) is characterized by various etiologies that damage the glomerulus. Central serous chorioretinopathy (CSCR) is a retinal disease characterized by neurosensory detachment of the retina. Several case reports have described the relationship between both. Therefore, we try to analyze the epidemiological associations between NS and CSCR using the National Health Insurance Research Database (NHIRD) in Taiwan.

Methods: Data spanning 14 years were extracted from the NHIRD and sub-grouped. The variables were analyzed using Pearson's chi-squared test and Fisher's exact test. The risk factors for disease development with or without co-morbidities were examined using an adjusted hazard ratio (aHR). Kaplan-Meier analysis was performed to evaluate the cumulative incidence of CSCR with or without NS.

Results: A total of 14,794 patients with NS and 14,794 matched controls without NS were enrolled in this cohort study. The incidence rate of CSCR was higher in the study cohort than in the control cohort (aHR = 3.349, p <0.001). The overall incidence of CSCR was 44.51 per 100,000 person-years in the study cohort and 33.39 per 100,000 person-years in the control cohort. In both groups, CSCR occurred more frequently in males than in females. Patients aged 40-49, 50-59, and ≥ 60 years in the study cohort had a significantly higher risk of developing CSCR than those in the control cohort (aHR = 3.445, 5.421, and 4.957, all p < 0.001). NS patient with a 4-week history of steroid usage has a higher risk of developing CSCR (aHR = 2.010, p < 0.001).

Conclusion: Our data showed that patients with NS have an increased risk of developing subsequent CSCR. Physician should routinely refer their NS patients to ophthalmologist for ophthalmic evaluation. This is the first nationwide epidemiological study reporting the association between these two diseases. Further studies are needed to clarify this relationship.
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http://dx.doi.org/10.1097/JCMA.0000000000000591DOI Listing
July 2021

Ultra-widefield retinal imaging for adjunctive resident training in retinal break detection.

PLoS One 2021 23;16(6):e0253227. Epub 2021 Jun 23.

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

We evaluated the clinical utility of ultra-widefield imaging as an adjunctive tool for training resident ophthalmologists in the detection of retinal breaks. This was a prospective study conducted at a secondary health care center (Tri-Service General Hospital) in Taiwan. Participants were 44 patients (53 eyes) who were referred to our hospital after being diagnosed with retinal breaks. Patients first underwent an indirect ophthalmoscopy examination of the total fundus without scleral depression by our junior (first and second year) or senior (third and fourth year) resident ophthalmologist and then underwent an ultra-widefield imaging examination with a central image and four gaze-steered (up, down, nasal, and temporal) images to determine the number of retinal breaks in the total fundus and the four quadrants. Of the total 53 eyes, 31 were examined by junior residents and 22 were examined by senior residents. In the group of junior residents, ultra-widefield imaging was significantly better at detecting retinal breaks of the total fundus (49 vs. 33 retinal breaks, p < 0.001) and the temporal quadrant (17 vs. 10 retinal breaks, p = 0.018) than indirect ophthalmoscopy. In the group of senior residents, there was no significant difference in the ability to detect retinal breaks in the total fundus or each of the four quadrants with ultra-widefield imaging or indirect ophthalmoscopy. Our results indicate that, compared to indirect ophthalmoscopy, ultra-widefield imaging with a central image and four gaze-steered images has a better performance and is a useful adjunct tool for the detection of retinal breaks in junior resident training. Additionally, it could be a useful method for teaching indirect ophthalmoscopy examination to junior residents.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253227PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221479PMC
June 2021

A Pulmonary Pleomorphic Carcinoma Patient with Exudative Retinal Detachment Secondary to Choroid Metastasis as Initial Presentation-A Case Report.

Medicina (Kaunas) 2021 May 28;57(6). Epub 2021 May 28.

National Defense Medical Center, Department of Ophthalmology, Tri-Service General Hospital, Taipei City 114, Taiwan.

Choroid metastasis is the initial presentation of pleomorphic carcinoma (PC) of the lung. PC is classified as poorly differentiated non-small cell lung carcinoma. It has a tendency to metastasize early and has a poor response to chemotherapy, which often results in poor prognosis. We report the case of a 63-year-old woman with a one-month history of deteriorating vision in the left eye. Fundus examination, fluorescein angiography, indocyanine green angiography, and B-scan sonography demonstrated choroidal metastasis of the left eye. Positron emission tomography/computed tomography (PET/CT) revealed a tumor with increased uptake in the left upper lung. Subsequent bronchoscopic biopsy confirmed a pleomorphic carcinoma of the lungs. Choroid metastasis as an initial presentation of PC in the lung is rare. Usually, it represents the late course of disseminated disease with hematogenous spread. Prompt diagnosis is imperative for patients to immediately initiate treatment.
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http://dx.doi.org/10.3390/medicina57060539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226557PMC
May 2021

The impact of glucosamine on age-related macular degeneration in patients: A nationwide, population-based cohort study.

PLoS One 2021 19;16(5):e0251925. Epub 2021 May 19.

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Purpose: To analyze the association between glucosamine (GlcN) use and the risk of age-related macular degeneration (AMD) using claims data from the National Health Insurance Research Database (NHIRD).

Methods: A retrospective, population-based study was conducted with NHIRD data from a 14-year period (2000-2013). Chi-squared and Student's t-tests were used to evaluate differences between the study and comparison cohorts for categorical and continuous variables, respectively. Risk factors for disease development were examined by the adjusted hazard ratio (aHR) with 95% confidence interval. Kaplan-Meier analysis was performed to compare the cumulative risk of AMD between the two cohorts.

Results: In total, 1,344 patients with GlcN treatment were enrolled in the study cohort and 5,376 patients without GlcN use were enrolled in the comparison cohort. The incidence rate of AMD was lower with GlcN use (3.65%) than without GlcN use (5.26%) (P = 0.014). GlcN use was associated with a lower risk of developing AMD among patients with hyperlipidemia, coronary artery disease, chronic obstructive pulmonary disease, stroke, other neurological disorders, or degenerative arthritis. Although the incidence of wet type AMD did not significantly differ (P = 0.91), the incidence of dry type AMD was lower in patients with GlcN use (2.9%) than those without GlcN use (4.84%) (P = 0.003). Kaplan-Meier analysis similarly revealed a lower rate of dry type AMD in patients with GlcN use compared to those without GlcN use (log-rank P = 0.004).

Conclusions: GlcN treatment can decrease the risk of developing dry type AMD. Further prospective controlled studies are needed to determine the effectiveness of GlcN treatment in patients with AMD and the associated mechanism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251925PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133402PMC
May 2021

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

J Clin Med 2021 Apr 23;10(9). Epub 2021 Apr 23.

Department of Ophthalmology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 114, Taiwan.

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 β 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.
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http://dx.doi.org/10.3390/jcm10091839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122949PMC
April 2021

Detecting Digoxin Toxicity by Artificial Intelligence-Assisted Electrocardiography.

Int J Environ Res Public Health 2021 04 6;18(7). Epub 2021 Apr 6.

School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan.

Although digoxin is important in heart rate control, the utilization of digoxin is declining due to its narrow therapeutic window. Misdiagnosis or delayed diagnosis of digoxin toxicity is common due to the lack of awareness and the time-consuming laboratory work that is involved. Electrocardiography (ECG) may be able to detect potential digoxin toxicity based on characteristic presentations. Our study attempted to develop a deep learning model to detect digoxin toxicity based on ECG manifestations. This study included 61 ECGs from patients with digoxin toxicity and 177,066 ECGs from patients in the emergency room from November 2011 to February 2019. The deep learning algorithm was trained using approximately 80% of ECGs. The other 20% of ECGs were used to validate the performance of the Artificial Intelligence (AI) system and to conduct a human-machine competition. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of ECG interpretation between humans and our deep learning system. The AUCs of our deep learning system for identifying digoxin toxicity were 0.912 and 0.929 in the validation cohort and the human-machine competition, respectively, which reached 84.6% of sensitivity and 94.6% of specificity. Interestingly, the deep learning system using only lead I (AUC = 0.960) was not worse than using complete 12 leads (0.912). Stratified analysis showed that our deep learning system was more applicable to patients with heart failure (HF) and without atrial fibrillation (AF) than those without HF and with AF. Our ECG-based deep learning system provides a high-accuracy, economical, rapid, and accessible way to detect digoxin toxicity, which can be applied as a promising decision supportive system for diagnosing digoxin toxicity in clinical practice.
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http://dx.doi.org/10.3390/ijerph18073839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038815PMC
April 2021

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

Sci Rep 2021 Apr 14;11(1):8195. Epub 2021 Apr 14.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 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.
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http://dx.doi.org/10.1038/s41598-021-87499-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046800PMC
April 2021

Outcomes of Small Size Ahmed Glaucoma Valve Implantation in Asian Chronic Angle-Closure Glaucoma.

J Clin Med 2021 Feb 17;10(4). Epub 2021 Feb 17.

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.

For chronic angle-closure glaucoma (ACG), Ahmed glaucoma valve (AGV) is a useful drainage device for intraocular pressure (IOP) control but there are few reports discussing the outcomes of small size AGV in adult patients. This retrospective study involved 43 Asian adult patients (43 eyes) with chronic ACG. All patients had undergone small size AGV insertion and were divided into anterior chamber (AC) group and posterior chamber (PC) group. In the AC group, tube was inserted through sclerectomy gap into the anterior chamber. In the PC group, tube was inserted into posterior chamber through a needling tract. Outcome measures were intraocular pressure (IOP), visual acuity, number of antiglaucoma medications, survival curve and incidence of complications. In total, 43 eyes of 43 patients, 24 in the AC group and 19 in the PC group, were reviewed. The mean follow-up period was 28.5 months (95% confidence interval: 25.5-31.4). Mean IOP had significantly decreased following AGV insertion. The Kaplan-Meier survival analysis demonstrated a probability of success at 24 months of 67.4% for qualified success and 39.5% for complete success. There were no significant differences between the AC and PC groups in terms of the mean IOP, cumulative probability of success, visual acuity change or antiglaucoma medication change, except IOP at 1-day and 1-month mean IOP. The most common complications noted was hyphema in the PC group. For adult chronic ACG patients, small size AGV insertion could be effective at lowering IOP. Besides, tube insertion into AC with sclerectomy may prevent the hypertensive phase in the early postoperative period.
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http://dx.doi.org/10.3390/jcm10040813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922335PMC
February 2021

Association between Optic Neuritis and Inflammatory Bowel Disease: A Population-Based Study.

J Clin Med 2021 Feb 10;10(4). Epub 2021 Feb 10.

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 11490, Taiwan.

Extraintestinal manifestations are common in patients with inflammatory bowel disease (IBD), and optic neuritis (ON) is a rare but severe one. This study aimed to evaluate possible factors associated with ON in patients with IBD. Adult patients with IBD who were not with concomitant ON on the index date identified from the Taiwan National Health Insurance Research Database (NHIRD) from the years 2000 to 2013 were included. A four-fold matched group was selected using age, sex and year of index date for comparison. All the patients were followed up until the development of ON or the end of the study period. Data of included patients were extracted and analyzed statistically. The mean follow-up time for all patients was 7.13 ± 5.21 years. At the study period conclusion, eight (0.18%) and five (0.003%) patients with and without IBD, respectively, had developed ON ( = 0.001). Adjusted HRs showed that patients with IBD aged between 30 and 39 years, with comorbidities including neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM), systemic lupus erythematosus (SLE) and with a higher Charlson Comorbidity Index, had a significantly higher risk of developing ON (all < 0.005). Among the eight IBD patients who developed ON, only one patient was diagnosed with Crohn's disease, the male gender was slightly dominant, and two (25%) patients received antitumor necrosis factor α (anti-TNF α) treatment for IBD. Patients with IBD have a higher risk of developing ON compared to patients without IBD. ON occurs more frequently in IBD patients aged between 30 and 39 years, with comorbidities including NMO, ADEM and SLE. Other factors besides anti-TNF α treatment for IBD are more likely associated with the development of ON.
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http://dx.doi.org/10.3390/jcm10040688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916645PMC
February 2021

The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy.

J Clin Med 2020 Dec 22;10(1). Epub 2020 Dec 22.

Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City 11490, Taiwan.

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.
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http://dx.doi.org/10.3390/jcm10010003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792601PMC
December 2020

A 12-month, prospective, observational study of ranibizumab in treatment-naïve Taiwanese patients with neovascular age-related macular degeneration: the RACER study.

BMC Ophthalmol 2020 Nov 25;20(1):462. Epub 2020 Nov 25.

Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Dapi Road, Niaosong District, Kaohsiung City, Taiwan.

Background: The current National Health Insurance scheme in Taiwan reimburses 3 initial plus 4 additional injections of ranibizumab 0.5 mg for eligible patients with neovascular age-related macular degeneration (nAMD). The Ranibizumab AMD Clinical Efficacy in Real-world practice (RACER) study aimed to observe the effectiveness of ranibizumab injections under this reimbursement system.

Methods: RACER was a 12-month, prospective, observational study conducted in treatment-naïve, adult Taiwanese patients with nAMD. Patients received intravitreal ranibizumab 0.5 mg injections in adherence with local prescribing information.

Results: Of 161 patients enrolled, 114 (70.8%) completed the 12-month study. Overall, patients received a mean (standard deviation [SD]) of 4.3 (1.7) ranibizumab injections. The mean (SD, [95% confidence interval], P value) gain in best-corrected visual acuity (BCVA) from baseline at Month 3 was 5.2 (12.2, [3.1, 7.3] letters, P < 0.0001) and at Month 12 was 3.4 (15.4, [0.2-6.6] letters, P = 0.0352). Mean central retinal thickness also decreased from baseline at Months 3 and 12 (both P < 0.001). In subgroup analyses, better treatment outcomes at Months 3 and 12 were observed among patients who received a loading dose and those who had a shorter duration of nAMD at baseline. Adverse events were reported in 58.4% of patients; most (94.4%) were mild-to-moderate in severity and 98.8% were deemed unrelated to study treatment.

Conclusions: Treatment with ranibizumab 0.5 mg resulted in significant improvements in visual outcomes among treatment-naïve Taiwanese patients with nAMD. Early treatment and frequent dosing in the real-world setting may be the key to achieving better outcomes.
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http://dx.doi.org/10.1186/s12886-020-01715-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687747PMC
November 2020

AR12286 Alleviates TGF-β-Related Myofibroblast Transdifferentiation and Reduces Fibrosis after Glaucoma Filtration Surgery.

Molecules 2020 Sep 26;25(19). Epub 2020 Sep 26.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.

Scar formation can cause the failure of glaucoma filtration surgery. We investigated the effect of AR12286, a selective Rho-associated kinase inhibitor, on myofibroblast transdifferentiation and intraocular pressure assessment in rabbit glaucoma filtration surgery models. Cell migration and collagen contraction were used to demonstrate the functionality of AR12286-modulated human conjunctival fibroblasts (HConFs). Polymerase chain reaction quantitative analysis was used to determine the effect of AR12286 on the production of collagen Type 1A1 and fibronectin 1. Cell migration and collagen contraction in HConFs were activated by TGF-β1. However, compared with the control group, rabbit models treated with AR12286 exhibited higher reduction in intraocular pressure after filtration surgery, and decreased collagen levels at the wound site in vivo. Therefore, increased α-SMA expression in HConFs induced by TGF-β1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-β1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-β1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-β receptor-related SMAD signaling pathways. In vivo results indicated that AR12286 thus improves the outcome of filtration surgery as a result of its antifibrotic action in the bleb tissue because AR12286 inhibited the TGF-β receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.
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http://dx.doi.org/10.3390/molecules25194422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583051PMC
September 2020

Serum Iron and Risk of Diabetic Retinopathy.

Nutrients 2020 Jul 31;12(8). Epub 2020 Jul 31.

Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei 114, Taiwan.

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.
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http://dx.doi.org/10.3390/nu12082297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469039PMC
July 2020

Detection of Diabetic Retinopathy Using Bichannel Convolutional Neural Network.

J Ophthalmol 2020 19;2020:9139713. Epub 2020 Jun 19.

Department of Medicine, Hualien Armed Forces General Hospital, Hualien 971, Taiwan.

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.
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http://dx.doi.org/10.1155/2020/9139713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322591PMC
June 2020

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

PLoS One 2020 23;15(6):e0234706. Epub 2020 Jun 23.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.

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 β-galactosidase (SA-β-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-β-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-β-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-β1-induced stress fibers were passivated in senescent HTFs. In addition, cellular migration enhanced by TGF-β1was inactivated. In vivo, histological examination indicated increased SA-β-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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234706PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310836PMC
September 2020

Management of diabetic macular edema: experts' consensus in Taiwan.

Jpn J Ophthalmol 2020 May 28;64(3):235-242. Epub 2020 Apr 28.

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

Diabetic macular edema (DME) is the most common cause of vision loss among patients with diabetes mellitus (DM), rendering it an important growing challenge in ophthalmology. In the past decades, the management strategies for DME had a few paradigm shifts, and the advent of an expanding number of anti-vascular endothelial growth factor (VEGF) agents also calls for an in-depth examination of the currently available evidence. This article was composed with the intention to provide recommendations for practicing clinicians to improve the management and, through it the outcomes of DME. Drawing from current guideline recommendations, clinical trial findings and local clinical experiences, these consensus recommendations for the management of DME were formed by an expert panel through iterations of discussion and voting. First, the treatment goal of DME is to achieve best visual outcome with edema improvement while minimizing treatment burden. Second, anti-VEGF therapy should be considered as the first-line treatment for patients with center-involving DME causing vision loss. Baseline visual acuity (VA) and central subfield thickness (CST) should be taken into consideration when choosing anti-VEGF agents. Third, early intensive anti-VEGF therapy (at least 3 monthly doses) is important for better patients' VA and anatomical improvement. In non-responders who have already been treated with 3-5 injections of anti-VEGF agents, it is reasonable to switch to other modalities, such as steroids. Finally, for the follow-up phase, fixed or individualized dosing should be considered based on VA and OCT.
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http://dx.doi.org/10.1007/s10384-020-00741-4DOI Listing
May 2020

The anti-fibrotic and anti-inflammatory effects of 2,4-diamino-5-(1-hydroxynaphthalen-2-yl)-5H-chromeno[2,3-b] pyriine-3-carbonitrile in corneal fibroblasts.

Pharmacol Rep 2020 Feb 19;72(1):115-125. Epub 2019 Dec 19.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Background: Although several studies had addressed the anti-inflammatory effects of derivatives of 4H-chromene and chromeno[2,3-b]pyridine in the different types of cells, whether these derivatives would exert beneficial anti-fibrotic effects during corneal fibrotic scar formation was unclear.

Methods: We examined the cyclooxygenase-2 (COX-2) expression of 2,4-diamino-5-(1-hydroxynaphthalen-2-yl)-5H-chromeno[2,3-b]pyridine-3-carbonitrile (N1) in the human corneal fibroblasts (HCFs) under the treatment TGF-β1. Signaling pathways underlying the mechanism of the N1 effect on the HCFs were determined.

Results: Application of N1 significantly decreased COX-2 expression after 2 h and 4 h in the HCFs stimulated with TGF-β1. Notably, reduced production of extracellular matrix proteins under N1 treatment was found, including fibronectin, collagen I, and matrix metallopeptidase 9. Immunoblot analysis showed that treatment with N1 significantly attenuated phosphorylation of both STAT3 and Smad 2 in the TGF-β1-stimulated HCFs. Upregulated mRNA of Smad2 and downregulated mRNA of Smad3 were observed using the quantitative real-time polymerase chain reaction. In addition, N1 induced significant increases in HO-1 and Nrf2 expression, but inhibited phosphorylation of NF-κB in the HCFs treated with TGF-β1.

Conclusions: Our findings show for the first time that N1 exerts anti-fibrotic and anti-inflammatory effects through suppression of COX-2, Smad2, STAT3, iNOS and NF-κB expressions as well as upregulation of Nrf2 and HO-1 expressions, which suggests they are potential therapeutic targets in the treatment of corneal fibrosis.
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http://dx.doi.org/10.1007/s43440-019-00026-9DOI Listing
February 2020

Relationship between heart failure and central serous chorioretinopathy: A cohort study in Taiwan.

J Chin Med Assoc 2019 Dec;82(12):941-947

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

Background: Both central serous chorioretinopathy (CSCR) and heart failure (HF) are disorders with a complex pathogenesis, whereas the two diseases might share similar pathogenesis. This study aimed to evaluate whether patients with HF are exposed to potential risk of CSCR by using the National Health Insurance Research Database (NHIRD).

Methods: Data were collected from the NHIRD over a 14-year period. Variables were analyzed with the Pearson chi-square test and Fisher's exact test. The risk factors for disease development were examined by adjusted hazard ratio (aHR). Kaplan-Meier analysis was performed to compare the cumulative incidence of CSCR.

Results: A total of 24 426 patients with HF were enrolled in the study cohort, and there were 24 426 patients without HF in the control cohort. The incidence rate of CSCR was higher in the study cohort than in the control cohort (aHR = 4.572, p < 0.001). CSCR occurred more commonly in males than in females. The overall incidence of CSCR was 30.07 per 100 000 person-years in the study cohort and 23.06 per 100 000 person-years in the control cohort. Besides, subgroup analysis revealed that no matter in gender or age group, HF patients were in an increased risk of CSCR diagnosis (male/female, aHR = 3.268/7.701; 20-59 years/≥60 years, aHR = 3.405/5.501, p < 0.001).

Conclusion: HF is a significant indicator for CSCR. Patients with HF should stay alert for potential disorder of visual impairment. Further prospective studies to investigate the relationship between HF and CSCR could provide more information.
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http://dx.doi.org/10.1097/JCMA.0000000000000207DOI Listing
December 2019

Examining the associations among intraocular pressure, hepatic steatosis, and anthropometric parameters.

Medicine (Baltimore) 2019 Oct;98(43):e17598

Division of Family Medicine.

Emerging evidences had reported the positive relationship between obesity and intraocular pressure (IOP). The aim of the present study was to investigate the association between hepatic steatosis and IOP in an adult Taiwanese population.Seven thousand seven hundred twelve males and 6325 females who received a health examination at the Tri-Service General Hospital during the period from 2010 to 2016 were included in this study.IOP was measured by noncontact tonometry. Hepatic steatosis was diagnosed by abdominal ultrasound examination. Multivariate regression analyses were used to assess the associations among various anthropometric parameters and IOP.After adjusting for pertinent covariables, hepatic steatosis had a closer association with increased IOP than percentage body fat, body mass index, or waist circumference (β = 0.017, 95% confidence interval [CI] = 0.006, 0.028). This relationship remained significant among males in the study population (β = 0.015, 95% CI = 0.001, 0.029). Furthermore, hepatic steatosis was significantly correlated with increased risk of high IOP (odd ratios = 1.235, 95% CI = 1.041-1.465).Our study highlights that hepatic steatosis is a better index for assessing the relationship with increased IOP than other anthropometric parameters. Underlying pathophysiological mechanisms regulating the association between hepatic steatosis and increasing IOP and even the risk of glaucoma should be examined in further studies.
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http://dx.doi.org/10.1097/MD.0000000000017598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824641PMC
October 2019

Quantitative Physical Fitness Measures Inversely Associated With Myopia Severity in Military Males: The CHIEF Study.

Am J Mens Health 2019 Sep-Oct;13(5):1557988319883766

Department of Medicine, Hualien Armed Forces General Hospital, Hualien.

Myopia has been linked to body weight and sedentary status, but the association with quantitatively measured physical fitness in adults has not been examined. Cross-sectional analyses were performed to investigate the association between physical fitness and myopia in 3,669 military men (aged 29.4 years) in Taiwan. The severity of myopia obtained from the left eye was classified as mild (-0.5 to -3.0 diopters; = 544), moderate -3.1 to -6.0 diopters; = 563), and high (<-6.0 diopters; =150); others were defined as nonmyopia ( = 2,412). Aerobic fitness was evaluated by time for a 3000-meter run test, and muscular endurance was evaluated by numbers of 2-min sit-ups and 2-min push-ups. A value of < .0125 was considered significant. A multiple linear regression analysis was used to determine the relationship. Individuals who were less physically fit had higher risk of myopia. The associations were dose-dependently significant with mild, moderate, and high myopia for 3000-meter running time (β = 9.64; 95% confidence intervals [3.22, 16.05], β = 12.41; 95% CI [6.05, 18.76], and β = 20.87; 95% CI [9.22, 32.51], respectively) after controlling for the potential covariates. There tended to be an inverse association with moderate and high myopia for numbers of 2-min push-ups (β = -1.38; 95% CI [-2.43, -0.34] and β = -2.10; 95% CI [- 3.97, -0.22], respectively) and 2-min sit-ups (β = -0.83; 95% CI [-1.54, -0.12] and β = -1.29; 95% CI [-2.56, -0.02], respectively), respectively. This study suggested that physical fitness, particularly aerobic fitness of the military males who received regular training, is inversely associated with myopia severity, independent of service specialty, body mass index, and educational level.
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http://dx.doi.org/10.1177/1557988319883766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820180PMC
September 2020

Glucosamine impedes transforming growth factor β1-mediated corneal fibroblast differentiation by targeting Krüppel-like factor 4.

J Biomed Sci 2019 Oct 9;26(1):72. Epub 2019 Oct 9.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Background: Transforming growth factor (TGF) family members play important roles in the regulation of corneal integrity, and the pathogenesis of corneal fibrosis. Currently, there are no effective agents targeting TGF-β signaling to diminish corneal fibrosis. Glucosamine (GlcN), which is widely used in the treatment of osteoarthritis, abrogates the morphologic effects of TGF-β2 on retinal pigmented epithelial cells in a mouse disease model. Here, we sought to determine whether GlcN would exert beneficial effects against TGF-β1-induced corneal fibrosis.

Methods: In human corneal fibroblasts (HCFs) treated with GlcN, the expression of Krüppel-like factor 4 (KLF4) and its downstream signaling effects were determined in the presence and absence of TGF-β1 using immunoblot analysis. We further explored GlcN inhibition of fibroblast-to-myofibroblast differentiation via KLF4 siRNA. The effect of cycloheximide on KLF4 protein levels with or without GlcN administration was assessed to determine whether GlcN affects the stability of the KLF4 protein.

Results: In HCFs, GlcN induced the expression of KLF4, which regulated the maturation and maintenance of the ocular surface. GlcN partially suppressed the TGF-β1-induced expression of alpha-smooth muscle actin (α-SMA) and reduced the collagen contraction capacity in HCFs, suggesting a decrease in fibroblast-to-myofibroblast differentiation. This effect appeared to be mediated through suppression of Smad2 phosphorylation and ERK-dependent signaling. The levels of KLF4 mRNA were increased by GlcN and decreased by TGF-β1 and the TGF-β1-induced α-SMA mRNA expression was upregulated when the KLF4 gene was silenced. GlcN also appeared to stabilize the KLF4 protein, reducing its turnover in corneal fibroblasts.

Conclusion: These findings shed light on a novel mechanism by which GlcN suppresses TGF-β1-induced fibroblast-to-myofibroblast differentiation through the upregulation of KLF4 expression. Current strategies for treating corneal fibrosis were not effective. Elevating KLF4 levels through the use of GlcN might provide an effective alternative to alleviate the development and progression of corneal fibrosis.
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http://dx.doi.org/10.1186/s12929-019-0566-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784344PMC
October 2019

Modulation of osmotic stress-induced TRPV1 expression rescues human iPSC-derived retinal ganglion cells through PKA.

Stem Cell Res Ther 2019 09 23;10(1):284. Epub 2019 Sep 23.

Institute of Pharmacology, National Yang-Ming University, Taipei, 112, Taiwan.

Background: Transient receptor potential vanilloid 1 (TRPV1), recognized as a hyperosmolarity sensor, is a crucial ion channel involved in the pathogenesis of neural and glial signaling. Recently, TRPV1 was determined to play a role in retinal physiology and visual transmission. In this study, we sought to clarify the role of TRPV1 and the downstream pathway in the osmotic stress-related retina ganglion cell (RGC) damage.

Methods: First, we modified the RGC differentiation protocol to obtain a homogeneous RGC population from human induced pluripotent stem cells (hiPSCs). Subsequently, we induced high osmotic pressure in the hiPSC-derived RGCs by administering NaCl solution and observed the behavior of the TRPV1 channel and its downstream cascade.

Results: We obtained a purified RGC population from the heterogeneous retina cell population using our modified method. Our findings revealed that TRPV1 was activated after 24 h of NaCl treatment. Upregulation of TRPV1 was noted with autophagy and apoptosis induction. Downstream protein expression analysis indicated increased phosphorylation of CREB and downregulated brain-derived neurotrophic factor (BDNF). However, hyperosmolarity-mediated defective morphological change and apoptosis of RGCs, CREB phosphorylation, and BDNF downregulation were abrogated after concomitant treatment with the PKA inhibitor H89.

Conclusion: Collectively, our study results indicated that the TRPV1-PKA pathway contributed to cellular response under high levels of osmolarity stress; furthermore, the PKA inhibitor had a protective effect on RGCs exposed to this stress. Therefore, our findings may assist in the treatment of eye diseases involving RGC damage.
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http://dx.doi.org/10.1186/s13287-019-1363-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755708PMC
September 2019

Diabetic Retinopathy as a Risk Factor for Chronic Kidney Disease Progression: A Multicenter Case⁻Control Study in Taiwan.

Nutrients 2019 Feb 27;11(3). Epub 2019 Feb 27.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.

It has rarely been studied whether the presence and severity of diabetic retinopathy (DR) could influence the renal disease progression among all chronic kidney disease (CKD) diabetic patients. This study investigates the characteristics of diabetic patients, with different stages of chronic kidney disease (CKD), according to the occurrence of diabetic retinopathy and determines the influence of retinopathy in the deterioration of renal function. We conduct a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of the CKD project (2008⁻2013) and the National Health Insurance Research Database (NHIRD) (2001⁻2013). A total of 4050 diabetic patients with CKD, 20⁻85 years of age, from 14 hospitals and the community are included in this study. As compared to CKD patients without DR, CKD patients with DR have a lower baseline estimated glomerular filtration rate (eGFR) (39.17 ± 30.36 mL/min per 1.73 m² vs. 54.38 ± 33.67 mL/min per 1.73 m² ); poorer glycemic control (higher glycated hemoglobin (HbA1c) 7.85 ± 4.97 vs. 7.29 ± 4.02, < 0.01); higher proteinuria (urine protein-to-creatinine ratio (UPCR )1.94 ± 2.96 g/dL vs. 0.91 ± 2.11 g/dL, < 0.01); more anemia (Hb 11.22 ± 2.43 g/dL vs. 12.39 ± 3.85 g/dL, < 0.01), and more hypoalbuminemia (3.88 ± 0.95 g/dL vs. 4.16 ± 1.74 g/dL, < 0.01). Later stage (stage 3b⁻5) CKD patients with DR had significantly higher CKD progression compared with patients without DR (OR (odds ratio) 1.66 (1.36⁻2.02)). Patients with proliferative DR had significantly higher CKD progression events compared to patients with non-proliferative DR (OR 2.18 (1.71⁻2.78)). The presence and severity of DR is a risk factor for CKD progression among our Taiwanese CKD patients with diabetes. Prevention and early detection of DR are important and DR should be routinely screened as early as possible among diabetic CKD patients.
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http://dx.doi.org/10.3390/nu11030509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470494PMC
February 2019

Protective effects of hypercapnic acidosis on Ischemia-reperfusion-induced retinal injury.

PLoS One 2019 25;14(1):e0211185. Epub 2019 Jan 25.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Ischemia-reperfusion (I/R) injury is associated with numerous retinal diseases, such as diabetic retinopathy, acute glaucoma, and other vascular retinopathies. Hypercapnic acidosis (HCA) has a protective effect on lung, myocardial, and central nervous system ischemic injury models. However, no study has evaluated its protective effects in an experimental retinal I/R injury model. In this study, retinal I/R injury was induced in Sprague Dawley rats by elevating the intraocular pressure to 110 mmHg for 60 minutes. HCA was induced before and after the injury. After 24 hours, the terminal dUTP nick end labeling assay was performed. Moreover, the ratios of cleaved caspase-3/total caspase-3, phosphorylated IκB/IκB, and phosphorylated p38 were measured through Western blotting. After 7 days, the rats' aqueous humor was analyzed. In addition, electroretinography and retinal thickness measurement were performed in the rats. Moreover, the retinal neural cell line RGC-5 was exposed to 500 μM H2O2 for 24 hours to induce a sustained oxidative stress in vitro. The effects of HCA were evaluated by comparing oxidative stress, MAPK signals, NF-κB signals, survival rates, and apoptosis rates in the RGC-5 cells before and after H2O2 exposure. We further investigated whether the potent I/R-protective heat shock protein (HSP) 32 contribute to protective effects of HCA. Our results indicated that HCA has protective effects against retinal I/R injury both in vivo and in vitro, at multiple levels, including antiapoptotic, anti-inflammatory, antioxidative, and functional retinal cell protection. Further research clarifying the role of HCA in retinal I/R injury prevention and treatment is warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211185PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347245PMC
October 2019

Optical coherence tomography angiography in unilateral multifocal choroiditis and panuveitis: A case report.

Medicine (Baltimore) 2019 Jan;98(4):e14259

Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center.

Rationale: Optical coherence tomography angiography (OCT-A) has the advantage to visualize the microvascular structure of the retina in vivo and was utilized clinically in various neovascular retinal diseases. The OCT-A has also been used to examine the lesion in multifocal choroiditis and panuveitis (MCP). This study aimed to describe a case of MCP and present the disease process of a punched-out lesion in the chorioretina with neovascular activity using OCT-A.

Patients Concerns: A 32-year-old female Caucasian patient presented with a 2-week history of progressive blurred vision in her right eye with photophobia and a diminished temporal visual field. On presentation, her best corrected visual acuity was 6/60 in the right eye with a prominent anterior uveitis seen under slit lamp examination.

Diagnoses: Dilated fundus examination of the right eye showed vitritis and multiple, punched-out yellowish-white lesions over the peripheral retina. Additional multimodal imaging (MMI) were done including fluorescein angiography (FA), indocyanine green angiography (ICGA) and fundus autofluorescence (FAF), which all revealed characteristic findings of MCP. In general, the diagnosis of unilateral MCP was made. Furthermore, one of the punched-out lesions in the right eye was particularly selected and examined under OCT and OCT-A, which revealed a subretinal elevated lesion with high flow signal under OCT-A.

Interventions: Treatment with oral prednisolone at 30 mg daily with topical prednisolone acetate 1% every 2 hours were prescribed, which were gradually tapered down within a 2-month course.

Outcomes: The patient's best corrected visual acuity of the right eye returned to 6/6 at 2 months after the diagnosis. The flow signal in the OCT-A study of the punched-out lesion had also resolved after steroid treatment.

Lessons: The MCP is an uncommon uveitis with multiple inflammatory chorioretinal lesions. Using multimodal imaging technique, physicians can better differentiate these lesions for diagnosis and for further monitoring. Our results demonstrated that these chorioretinal lesions in MCP may display neovascular activities that might not be seen easily using conventional FA or ICGA study. With OCT-A, ophthalmologists could identify and monitor subtle choroidal neovascularization (CNV) changes over these punched-out lesions.
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http://dx.doi.org/10.1097/MD.0000000000014259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358364PMC
January 2019

One-year real-world outcomes of ranibizumab 0.5 mg treatment in Taiwanese patients with polypoidal choroidal vasculopathy: a subgroup analysis of the REAL study.

Int J Ophthalmol 2018 18;11(11):1802-1808. Epub 2018 Nov 18.

Chang Gung Memorial Hospital-Linkou, Guishan District, Taoyuan City, Taiwan 333, China.

Aim: To assess the effectiveness and safety of ranibizumab 0.5 mg in Taiwanese patients with polypoidal choroidal vasculopathy (PCV) by performing a retrospective exploratory subgroup analysis of the REAL study.

Methods: REAL was a 12-month, observational, prospective, non-interventional phase IV post-marketing surveillance study conducted at 9 centers in Taiwan. The study collected data as part of the routine patient visits from the medical records of patients with neovascular age-related macular degeneration treated with ranibizumab 0.5 mg according to local standard medical practice and local label and/or reimbursement guidelines. The presence of PCV at baseline was determined using indocyanine green angiography.

Results: At baseline, PCV was diagnosed in 64 of the 303 enrolled patients (21.1%). Of these, 41 patients (64.1%) had received prior treatment; 15 (23.4%) patients had received ranibizumab. The intent-to-treat population included 58 patients; 47 (80%) who received ranibizumab and 11 (20%) who received ranibizumab plus photodynamic therapy (PDT; 9 patients received once, 2 patients received twice). Bevacizumab was used as a concomitant medication in a similar percentage of patients who received ranibizumab (43%, =20) or ranibizumab plus PDT (45%, =5). In patients who received ranibizumab, visual acuity (VA) at baseline was 50.1±12.9 Early Treatment Diabetic Retinopathy Study letters, and the gain at month 12 was 1.1±17.8 letters. In patients who received ranibizumab plus PDT, VA at baseline was 51.4±15.9 letters, and there was a marked gain in VA at month 12 (14.0±9.2 letters, =0.0009). In the intent-to-treat population, the reduction in central retinal subfield thickness from baseline at month 12 was 69.6±122.6 µm (baseline: 310.8±109.8 µm, =0.0004). The safety results were consistent with the well-characterized safety profile of ranibizumab.

Conclusion: In real-world settings, ranibizumab 0.5 mg treatment for 12mo results in maintenance of VA and reduction in central retinal subfield thickness in Taiwanese patients with PCV. Improvements in VA are observed in patients who received ranibizumab plus PDT. There are no new safety findings.
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http://dx.doi.org/10.18240/ijo.2018.11.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232327PMC
November 2018

Application of lateral tarsoconjunctival flap to correct ocular complications of Madelung's disease: A case report and literature review.

Medicine (Baltimore) 2018 Oct;97(42):e12864

Department of Ophthalmology, Tri-Service General Hospital.

Rationale: Madelung's disease is a specific type of benign symmetric lipomatosis, which is characterized by overgrowing fat distributed at the neck and shoulder. This excessive fat accumulation may occur in different regions, including vital organs, such as the larynx, trachea, or the orbits. Surgery is usually performed to correct the esthetic or functional concern of the affected area. There are only few case reports mentioned about the orbital involvement of this disease. This study aimed to describe a case of Madelung's disease with ocular complications and the successful treatment using tarsoconjunctival flap.

Patient Concerns: A 90-year-old obese male presented with decreased visual acuity accompanied with severe band form punctate epithelial erosions and ciliary injections in both eyes. Exophthalmos and ectropion of the lower eyelids were observed.

Diagnoses: Orbital computed tomography revealed a rare entity of Madelung's disease with significant massive deposits of lipomas located symmetrically around the orbit and neck region.

Interventions: Bilateral lateral tarsoconjunctival flaps with lateral tarsal strip procedures were performed to correct the lower eyelid ectropion-related exposure keratopathy.

Outcomes: The patient obtained improved visual acuity, intact and clear corneal surfaces, and perfect lower eyelid positions over both eyes.

Lessons: Madelung's disease is a rare condition. There are few reports to describe its ocular complications, due to lipoma overgrowing in the orbit. We shared our successful experience to correct ocular complications using tarsoconjunctival flap technique.
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http://dx.doi.org/10.1097/MD.0000000000012864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211917PMC
October 2018
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