Lin-Chung Woung

Risk of Alzheimer’s Disease in Relation to Diabetes: A Population-Based Cohort Study

Background/Aims: Detailed information on the age- and sex-specific relationships between diabetes and Alzheimer’s disease (AD) is scarce. This study aims to prospectively investigate the age- and sex-specific incidence density and relative hazards of AD in relation to diabetes. Methods: A total of 615,529 diabetic patients and 614,871 age- and sex-matched random controls were linked to the claim data from 2000–2008 to identify the first occurrence of a primary or secondary diagnosis of AD. Incidence density was calculated under the Poisson assumption. We also assessed the age- and sex-specific risk of AD in relation to diabetes with the Cox proportional hazards regression model. Results: Over nearly 9 years of follow-up, a total of 4,615 diabetic subjects developed AD, representing a cumulative incidence rate of 0.75% (n = 3,873; 0.63% in controls). The overall incidence densities of AD for diabetic men and women, respectively, were 0.82 and 1.15 per 1,000 person-years, which were higher than those for control men and women (0.63 and 0.89 per 1,000 person-years, respectively). Diabetic patients had a significantly higher hazard ratio (HR) of AD [1.45, 95% confidence interval (CI) 1.38–1.52]. Diabetic women ≥65 years had a higher HR (1.52, 95% CI 1.42–1.62) than diabetic women <65 years (1.34, 95% CI 1.15–1.56). Conclusion: Diabetes may increase the risk of AD in both sexes and in all ages. A higher HR of AD was especially notable in older diabetic women.

A Clinical Study of Acupuncture and SSP (Silver Spike Point) Electro-therapy for Dry Eye Syndrome

The present study was designed as a clinical trial to assess the efficacy of acupuncture and silver spike point (SSP) electro-therapy on dry eye syndrome. A total of 43 dry eye syndrome patients participated in the present study. Subjects were divided into control, acupuncture and SSP electro-therapy groups. The three groups were all given artificial tears treatment. Patients in the treatment groups were given two 20-minute treatments of either acupuncture or SSP. Assessment was carried out using the Basal Schirmer test, tear break-up time (BUT), visual analog scale (VAS) and an overall score of eye condition. After four weeks of treatment, both the acupuncture and SSP treatment groups showed improvements over the control group, in Schirmer tests of the left eye and average tearing of both eyes. After 8 weeks of treatment, both treatment groups showed improvements over the control group both in Schirmer tests and VAS. For the right eye, treatment groups showed significant improvements in Schirmer test and VAS versus the control group averages for both eyes. There was no significant difference in BUT at any time. Comparing scores before and after treatment, the acupuncture and SSP groups showed a significant improvement compared to the control group. The acupuncture group showed a greater 8-week improvement in Schirmer tests scores compared to the SSP group. However, the SSP group patients used fewer applications of artificial tears. Acupuncture and SSP electro-therapy were effective in increasing tear secretion in patients with dry eye syndrome. The SSP electro-therapy not only alleviated dry eye syndrome, but also reduced the number of applications of artificial tears necessary.

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

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.

Digital retroilluminated photography to analyze posterior capsule opacification in eyes with intraocular lenses.

PURPOSE To compare the formation and rates of posterior capsule opacification (PCO) in eyes with poly(methyl methacrylate) (PMMA) versus silicone intraocular lenses (IOLs) using an in vivo objective method. SETTING Taipei Municipal Yang-Ming Hospital, Taipei, Taiwan, Republic of China. METHODS This prospective study comprised 40 eyes with senile cataract receiving phacoemulsification with capsular implantation of an IOL from March to April 1997. The uneventful surgeries were performed using the stop and chop method by the same surgeon. Twenty eyes received a PMMA IOL (Pharmacia 812A) and 20, a silicone IOL (AMO SI-30NB). One year later, digital retroillumination images taken with the EAS-1000 anterior segment analysis system (Nidek) were used to analyze posterior capsule transparency over the central 3.0 and 5.0 mm optic zones and evaluate the degree of PCO over the central and peripheral zones. RESULTS Over the central 5.0 mm optic zone, mean transparency of the capsule was 87.71% +/- 11.35% (SD) in the silicone group and 79.22% +/- 21.10% in the PMMA group (P = .17). Over the central 3.0 mm optic zone, the means were 97.17% +/- 5.96% and 86.32% +/- 19.60%, respectively (P = .048). Mean opacity in the central zone was 75.18 +/- 13.22 digital opacity units (OUs) in the silicone group and 80.24 +/- 7.93 OUs in the PMMA group (P = .18). The means in the peripheral zone were 88.49 +/- 18.47 OUs and 90.35 +/- 9.98 OUs, respectively (P = .71). CONCLUSION The posterior capsule in the silicone IOL group was more transparent than in the PMMA IOL group over the central 3.0 mm optic zone after 1 year follow-up.

Accommodative adaptation and age of onset of myopia

Tonic accommodation in an empty field and accommodative adaptation, defined as accommodation shift after 2 min viewing of a 4 D near task, were measured using an infrared optometer. Subjects were classified into three types: emmetropes (n= 18). early onset myopes (n= 18) and late onset myopes (n= 15). The relationship between accommodative adaptation and the onset age of myopia were compared. There was no statistical difference in the pre‐task ionic accommodation among the three subject groups. However, the accommodative adaptation differed in the three groups during the 5 min post‐task period. The average accommodative adaptation of emmetropia. early onset myopia and late onset myopia were 0.66. 0.27 and 1.19 D. respectively. Accommodative adaptation in the late onset myopia group was significantly higher than in the emmetropia group. Furthermore, the accommodative adaptation in the early onset myopia group was significantly lower than in the emmetropia group. Two possible aetiologies of myopia are discussed: one for the group which shows low accommodative adaptation that has no relationship with the age of onset and another for the group which shows high accommodative adaptation that has a relationship to an onset age of 15 years or later. The aetiology is also considered with regard to a potentiating chemical effect on the synapses of the ciliary muscle.

Position of poly(methyl methacrylate) and silicone intraocular lenses after phacoemulsificaxion

Purpose: To compare the positional change of poly(methyl methacrylate) (PMMA) and silicone intraocular lenses (IOLs) in vivo after phacoemulsification. Setting: Taipei Municipal Yang‐Ming Hospital, Taipei, Taiwan. Methods: A prospective study of 70 cataractous eyes treated by phacoemulsification with IOL implantation was carried out. The eyes were randomized into 2 groups based on IOL type: 1‐piece PMMA IOL; 3‐piece silicone IOL. The amount of IOL tilt and decentration was measured and anterior chamber depth (ACID) determined by Scheimpflug photography using an anterior eye segment analysis system (EAS‐1000, Nidek). All eyes were examined 1 week and 1 to 6 months after surgery. Results: No statistically significant differences were found in the amount of tilt and decentration between 2 IOL types throughout the study. The ACDs were relatively constant in both groups through the early postoperative periods. Conclusion: The stability of PMMA and silicone IOLs were the same after phacoemulsification.

Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells.

IntroductionCD133 (PROM1) is a potential marker for cancer stem cells (CSCs), including those found in brain tumors. Recently, medulloblastoma (MB)-derived CD133-positive cells were found to have CSC-like properties and were proposed to be important contributors to tumorigenicity, cancer progression, and chemoradioresistance. However, the biomolecular pathways and therapeutic targets specific to MB-derived CSCs remain unresolved.Materials and methodsIn the present study, we isolated CD133+ cells from MB cell lines and determined that they showed increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared to CD133− cells. Bioinformatics analysis suggested that the STAT3 pathway might be important in MB and CD133+ cells. To evaluate the effects of inhibiting the STAT3 pathway, MB-derived CD133+/− cells were treated with the potent STAT3 inhibitor, cucurbitacin I. Treatment with cucurbitacin I significantly suppressed the CSC-like properties and stemness gene signature of MB-derived CD133+ cells. Furthermore, cucurbitacin I treatment increased the apoptotic sensitivity of MB-derived CD133+ cells to radiation and chemotherapeutic drugs. Notably, cucurbitacin I demonstrated synergistic effects with ionizing radiation to inhibit tumorigenicity in MB-CD133+-inoculated mice.ResultsThese results indicate that the STAT3 pathway plays a key role in mediating CSC properties in MB-derived CD133+ cells. Targeting STAT3 with cucurbitacin I may therefore represent a novel therapeutic approach for treating malignant brain tumors.

The current status of visual disability in the elderly population of Taiwan

PurposeThis study was conducted to explore the prevalence and the associated factors of visual impairment and blindness among the elderly Taiwanese population.MethodsA nationwide population-based visual health care screening program of elderly people aged 65 years or older was conducted between 1 July 2002 and 31 December 2002 in Taiwan. Based on the same standardized protocol used by the Bureau of Health Promotion, Department of Health, and a stratified random sampling design, 3160 out of 5000 elderly subjects were selected by a two-stage visual care screening method. The overall response rate was 63.2%.ResultsThe mean age of the elderly participants was 72.4 ± 5.1 years. The overall prevalence of glaucoma, corneal diseases, trauma, cataracts, myopic or diabetic retinopathy, and age-related macular degeneration among the elderly population was 2.1%, 6.3%, 0.9%, 60.2%, 7.5%, and 2.9%, respectively. The overall prevalence of visual disability (visual acuity of the better eye <0.5) was 17.7%, including 17.1% with visual impairment and 0.6% with blindness. Based on logistic regression, the significant independent factors of visual disability (visual impairment plus blindness) were sex (male vs. female, odds ratio (OR) = 0.62, 95% confidence interval (CI), 0.51–0.76), age (70–74 years vs. 65–69 years, OR = 1.60, 95% CI, 1.24–2.06; 75–79 years vs. 65–69 years, OR = 2.52, 95% CI, 1.92–3.32, ≥80 yrs vs. 65–69 yrs, OR = 4.86, 95% CI, 3.52–6.70), corneal diseases (OR = 2.26, 95% CI, 1.61–3.16), myopic or diabetic retinopathy (OR = 1.69, 95% CI, 1.20–2.39), age-related macular degeneration (OR = 4.96, 95% CI, 3.16–7.78), and cataract (OR = 3.40, 95% CI, 2.67–4.33).ConclusionsThe geographic difference in the prevalence of vision-related eye disease, visual impairment, and blindness point to the importance of taking actions that suit local circumstances. Our results also revealed that visual impairment and blindness are important visual health problems in the elderly Taiwanese population. Age-related macular degeneration, cataracts, corneal diseases, myopic or diabetic retinopathy, female sex, and aging were the leading causes of visual disability. Further organized preventive strategies for eye care are recommended in this population.

MicroRNAs and cataracts: correlation among let-7 expression, age and the severity of lens opacity

Background Let-7 microRNA is an important regulator of cellular ageing and tissue senescence. The objective of this study is to evaluate the expression of let-7a/let-7b/let-7c microRNAs in human age-related cataracts. Aim To evaluate the correlation among the severity of lens opacity, the level of let-7a/let-7b/let-7c microRNA expression and patient age in the context of age-related cataracts. Methods The authors evaluated the mRNA level of let-7a/let-7b/let-7c microRNA in lens epithelia obtained from 174 eyes with age-related cataracts. The authors also recorded the patient age and the severity of lens opacity as classified according to the modified version of the Lens Opacities Classification System version III. Results Let-7b microRNA expression was demonstrated to be positively associated with patient age (R=0.472; p<0.001). A positive correlation was also observed between higher N, C and P cataract scores and higher expression of let-7b microRNA in patients with age-related cataracts (p<0.001). However, no significant correlation was observed between the let-7a and let-7c microRNA expression levels and either the severity of lens opacity or the patient age. Conclusion These findings suggest that microRNAs play a role in age-related cataracts. A local let-7b microRNA increase may represent a risk factor in the formation of age-related cataracts.

Anterior Ischemic Optic Neuropathy Associated with Pegylated Interferon Therapy for Chronic Hepatitis C

Purpose: To report a case of anterior ischemic optic neuropathy (AION) associated with the combined therapy of pegylated interferon alpha (PEG-IFNα) and ribavirin. Methods: Case report. Results: A 57-year-old male with chronic hepatitis C, treated with PEG-IFNα -2b and ribavirin for 6 months, noted sudden onset of painless blurred vision in his right eye. The initial visual acuity decreased to 20/60 in the right eye. Fundoscopy of right eye revealed optic disc edema with disc hemorrhage. Visual field examination disclosed inferior altitudinal defect. Relative afferent pupillary defect with poor color vision function was also noted in the right eye. Visual evoked potential demonstrated decreased amplitude in the right eye. A marked resolution of disc edema and improvement of visual acuity to 20/20 were noted at 6 weeks follow-up. Conclusions: AION may occur in combined treatment of PEG-IFNα -2b and ribavirin for chronic hepatitis C. Patients who are candidates for this treatment should be informed about its possible occurrence.