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An incomplete dislocated intraocular lens (IOL) is often treated with IOL exchange because the IOL subluxates posteriorly during surgery and makes it difficult to fixate the IOL in situ. A trocar blade used for 23-gauge vitrectomy was used to lift and stabilize the IOL-capsular complex. The IOL can then be fixated using a suture loop fixation technique, which was originally limited to patients with decentered IOL. The advantage of this technique is that it allows the remaining zonular fibers and IOL to be preserved. The modified technique using a trocar blade to assist scleral fixation allows the incomplete dislocated IOL to be retrieved and fixated with a simplified surgical procedure.

Background To investigate and compare the cytotoxicity of indocyanine green (ICG), brilliant blue G (BBG) and trypan blue (TB) using ARPE-19 cells that have been pre-treated/post-treated with balanced salt solution (BSS) or foetal bovine serum (FBS). Methods The cultured human retina pigment epithelium ARPE-19 cells were pre-treated/post-treated with BSS or FBS (represent the autologous serum in clinic) in parallel with cells being soaked with various concentrations of ICG, BBG and TB. The cells were then assessed for viability, growth rate, reactive oxygen species (ROS) level, mitochondrial membrane potential (Δψ) and mitochondrial mass as cytotoxic indices. For the FBS pre-treated cells, only ROS was examined. Results Using the MTT assay, cytotoxicity seemed to appear when the dye concentration was above 2.5 mg/mL for ICG but no cytotoxicity for BBG and TB at the concentrations used. Cell growth was arrested at a concentration 1 mg/mL when ICG or BBG were present but no arrest at any of the tested concentrations was found for TB with the cell-growth curve was slowest for ICG. Cellular ROS levels increased at all concentrations of all dyes, but the increasing slopes were decreased after FBS post-treatment washout. Conclusions As a rinse buffer FBS performs much better than BSS in terms of cell rescue, which agrees with a clinical report when autologous whole blood was applied to macular hole surgery. However, FBS pre-treatment seems to be much better than FBS use as washout buffer in post-treatment.

For age-related macular degeneration examination, imaging techniques of confocal scanning laser ophthalmoscopy (cSLO), indocyanine green angiography, and fluorescein angiography have been used for studying the fundus, but in a monochromatic manner. When an autofluorescence image is required to be added on a gray-scale reflection image, the software plays a key role to form the colored image. In this study, we develop a hardware plug-in device for traditional cSLO to upgrade it so that it will show an overlapped color image containing both the reflection and autofluorescence images. We only use the laser (488/514 nm) within cSLO to incorporate with the hardware image overlapping system (HIOS) developed herein to real-time detect and convert both the monochromatic reflection and autofluorescence signals into a colored image. A model-retina and fluorescein isothiocyanate (FITC) dye with different concentrations is painted on the “retina” to simulate the drusen in real retina. System validation and sensitivity are evaluated by examining the “retina” image, while the observance of fluorescence results from various concentrations of FITC. The reflection and autofluorescence images are successfully separated by the optic system, further overlapped through the HIOS, and real-time displayed on a color monitor. The system sensitivity to detect fluorescence of FITC is as low as 5 × 10−10 mol. The results of this study suggest that this type of hardware add-on technology can help upgradation of traditional cSLO to the level of autofluorescence fundus imaging economically and with a broadening of the diagnostic capability of cSLO.

Additional file 2: Supplementary Material 2. Animal number

Additional file 3. Cover letter. Inside were included responses to the Editor, Professor Haoyu Chen as well as the Reviewers, Professor Peiquan Zhao and Professor Stanley Chang.

Additional file 3: Supplementary Material 3. ARRIVE Guidelines

Additional file 4: Supplementary Material 4. Emodin blot

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.

To assess the efficacy of combined intravitreal bevacizumab (IVB) and macular grid and scatter laser photocoagulation in the treatment of macular edema secondary to branch retinal vein occlusion (BRVO) over a 12-month period.A prospective, interventional case series study was conducted in 20 patients. Patients were treated with 3 monthly IVB injections, followed by macular grid laser and scatter laser photocoagulation to nonperfused ischemic retina. Repeated IVB injections were performed on an as-needed basis when patients had recurrent macular edema.The best-corrected visual acuity of 20/40 or better was achieved in 17 eyes (85%) and a vision gain of 3 lines or more was noted in 12/20 eyes (60%). Mean visual acuity improved from 0.68 logMAR at baseline to 0.28 logMAR at 3 months, 0.26 logMAR at 6 months, and 0.26 logMAR at 12 months (P0.01). The mean central macular thickness (CMT) was 442 μm at baseline and decreased to 266, 264, 300, and 294 μm at 1, 3, 6, and 12 months' follow-up, respectively (P0.01). A mild rebound CMT increase was noted at 6 months, which was reduced after bevacizumab reinjection. Ten patients (50%) required repeated IVB injections. Fifteen eyes (75%) have complete edema resolution on optical coherence tomography scan at the 12-month return visit. Overall, patients received an average of 4 injections during the 12-month period. No adverse ocular or systemic events were observed following injections.Early IVB injections in combination with subsequent macular grid and scatter laser photocoagulation treatment significantly improved vision and reduced macular edema secondary to BRVO. Further studies are warranted to evaluate the long-term outcomes and safety.

Diabetic retinopathy (DR) is a well-characterized chronic ocular disorder that developed in nearly all diabetic patients in the long run. The knowledge of DR is crucial to manage this disorder when planning screening and preventive programs and identifying the appropriated therapeutic strategies among. Expectant management may represent a valid therapeutic approach depending upon the clinical manifestations of the disease and, in particular, on the changes over time. If early treatment of DR reduces the probability of severe stage or slows the progression of blindness, it might sufficiently reduce treatment costs in later years to offset the costs of screening and early treatment. In addition, whether screening for DR is worthwhile is contingent on whether subjects are willing to pay the eye screening program that would decrease the risk of photocoagulation. In this review we discuss epidemiology, management, and economic evaluation of screening of DR among type 2 diabetes.

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%, n=20) or ranibizumab plus PDT (45%, n=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, P=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, P=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.

To investigate and compare the cytotoxicity of indocyanine green (ICG), brilliant blue G (BBG) and trypan blue (TB) using ARPE-19 cells that have been pre-treated/post-treated with balanced salt solution (BSS) or foetal bovine serum (FBS).The cultured human retina pigment epithelium ARPE-19 cells were pre-treated/post-treated with BSS or FBS (represent the autologous serum in clinic) in parallel with cells being soaked with various concentrations of ICG, BBG and TB. The cells were then assessed for viability, growth rate, reactive oxygen species (ROS) level, mitochondrial membrane potential (Δψ) and mitochondrial mass as cytotoxic indices. For the FBS pre-treated cells, only ROS was examined.Using the MTT assay, cytotoxicity seemed to appear when the dye concentration was above 2.5 mg/mL for ICG but no cytotoxicity for BBG and TB at the concentrations used. Cell growth was arrested at a concentration 1 mg/mL when ICG or BBG were present but no arrest at any of the tested concentrations was found for TB with the cell-growth curve was slowest for ICG. Cellular ROS levels increased at all concentrations of all dyes, but the increasing slopes were decreased after FBS post-treatment washout.As a rinse buffer FBS performs much better than BSS in terms of cell rescue, which agrees with a clinical report when autologous whole blood was applied to macular hole surgery. However, FBS pre-treatment seems to be much better than FBS use as washout buffer in post-treatment.

Background: To investigate the clinical manifestations and imaging features of near-infrared autofluorescence (NIA), infrared reflectance (IR), fundus autofluorescence (FAF), indocyanine green angiography (ICGA) and fluorescein angiography (FAG) in the detection of patients with focal choroidal excavation (FCE) identified by cross-sectional spectral-domain optical coherence tomography (SD-OCT). Methods: This retrospective cross-sectional study included 12 eyes of 10 Taiwanese patients with FCE diagnosed by SD-OCT. The areas and depths of FCE in serial cross-sectional and en-face OCT were compared in different imaging modalities. NIA, IR, FAF, ICGA and FAG images were obtained. Best corrected visual acuity, subjective distortion area in the Amsler grid and history of maculopathies were also recorded. Results: In areas where the choroid started to excavate as shown in SD-OCT, hypo-autofluorescence in NIA was noted. The area of hypo-fluorescence in NIA of all the FCE lesions showed good correlation with the size. The area of FCE was associated with complications such as choroidal neovascularization and central serous chorioretinopathy (p = 0.014, d.f = 1) and the volume (NIA area × Depth measured by SD-OCT × 1/3) was associated with subjective distortion strongly (p = 0.051, Spearman's correlation = 0.600). Conclusion: Among all image modalities, NIA was the most sensitive tool in area measurement of FCE and peripheral lesion detection. Also, the volume of FCE was associated with subjective distortion and the area was related to complications. Recording the area and volume of FCE could play an important role in monitoring complications. Keywords: Choroid-retina disease, Focal choroidal excavation, Near-infrared autofluorescence, Spectral-domain optical coherence tomography

We herein report the current status of ophthalmology in Taiwan. There are 1667 ophthalmologists in Taiwan (up to the year 2011), with an average of 7.22 eye specialists/100,000 people. The ophthalmology residency program is a 4-year course in Taiwan, and around 40–44 new residents pass out each year. The Ophthalmological Society of Taiwan and many other professional ophthalmological organizations, and 30 teaching hospitals provide continuing education for practicing ophthalmologists and hospital staff. From 2002 to 2010, the average yearly cataract surgery rate in Taiwan was 5350/million people. Taiwan has held many international congresses. The major areas of biomedical research in ophthalmology in Taiwan are ophthalmic epidemiology, glaucoma, vitreoretinal diseases, cornea, and stem cells. From 1990 to 2010, Taiwan ophthalmologists have published 15 monographs, 15 textbooks, and 2184 scientific articles. The future objectives of Taiwanese ophthalmologists are to promote preventive ophthalmology, to expand efforts in basic research, to establish a national eye-diseases registry, and to support the Taiwan Journal of Ophthalmology in becoming a Science Citation Index journal.

Summary Purpose This study was conducted to explore the incidence of and risk factors for gallstone disease (GSD) among elderly type 2 diabetic patients (aged 60 years or older) in Kinmen, Taiwan. Methods In 2001, a panel of specialists performed ultrasound sonography screening on 594 elderly type 2 diabetic patients who were diagnosed in 1991–1993. The screening program involved 298 elderly type 2 diabetic patients. After excluding 51 participants with prevalent GSD, 247 participants without GSD were invited for a second round of screening in 2002. A total of 192 (77.7%) elderly participants were re-examined. Results Among the 192 elderly type 2 diabetic patients who had no GSD at the first round screening, eight patients had developed GSD by 2002, which is an incidence of 4.17% per year [95% confidence interval (CI) = 2.22–7.05% per year]. Using a stepwise Cox regression model, the waist circumference [relative risk (RR) =1.07; 95%CI = 1.01–1.18] and the alanine transaminase (ALT) level (RR = 1.10; 95%CI = 1.05–1.16) appeared to be significantly related to the development of GSD. Conclusion Elderly type 2 diabetic patients had a slightly higher annual incidence of GSD, compared to the general population; however, the difference was not statistically significant. A greater waist circumference and high normal ALT levels were also associated with the development of GSD among this screened subpopulation.

Purpose: To discuss the prevalence and associated factors related to visual impairment and blindness amongst the elderly agricultural and fishing population. Methods: A total of 6542 healthy elderly adults voluntarily admitted to a teaching hospital for a physical check-up and eye disease in Taipei, Taiwan. Results: The overall prevalence of visual disability (the better eye visual acuity

Excitotoxicity has been proposed to play a pivotal role in retinal ischemia. Retinal ischemia-associated ocular disorders are vision threatening. The aim was to also examine whether and how S-allyl L-cysteine (SAC) can protect the retina against kainate excitotoxicity. In vivo retinal excitotoxicity was induced by an intravitreous injection of 100 μM kainate into a Wistar rat eye for 1 day. The management and mechanisms involved in the processes were evaluated by electrophysiology, immunohistochemistry, histopathology, and various biochemical approaches. In the present study, the cultured retinal cells were shown to possess kainate receptors. The defined retinal excitotoxic changes were characterized by a decrease in electroretinogram (ERG) b-wave amplitudes, a loss of the fluorogold retrograde labeled retinal ganglion cells (RGCs), an increase in the apoptotic cells in the RGC layer, and an increase in vimentin or glial fibrillary acidic protein (GFAP) immunoreactivity, a marker for Müller cells. An up-regulation in the mRNA levels of inducible nitric oxide synthase (iNOS) and matrix metalloproteinases-9 (MMPs-9) was also detected in the retina subjected to kainate excitoxicity. Importantly, the excitotoxicity-induced alterations were significantly blunted when 100 μM SAC and/or the kainate receptor antagonist CNQX was applied. Conclusively, SAC would seem to protect the retina against kainate excitotoxicity via an inhibition of the up-regulation of iNOS and MMP-9 as well as a modulation of glial activation and apoptosis.

MicroRNA 34a (miR-34a) is involved in regulating tissue senescence. However, the role of miR-34a in age-related cataracts is unclear. In this study, we evaluated the correlations among the severity of lens opacity, patient age, and miR-34a expression level in the lens epithelium of age-related cataracts for clarifying the role of miR-34a in the lens senescence. This study was carried as a case control study in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan. We recorded age of each patient at the time of their cataract surgery and information regarding lens opacity according to a modified version of the Lens Opacities Classification System III. Correlations among age, lens opacity, and miR-34a expression levels were evaluated. This study evaluated 110 patients with a mean age of 73.19 years (SD±10.2). Older patients had higher nuclear cataract (NC), cortical (C), and posterior subcapsular cataract (P) scores (one-way analysis of variance (ANOVA), P

XFZUD No. of rats. (PDF 158Â kb)

Retinal ischemia-associated ocular disorders, such as retinal occlusive disorders, neovascular age-related macular degeneration, proliferative diabetic retinopathy, and glaucoma are vision-threatening. In this study, we examined whether and by what mechanisms resveratrol, a polyphenol found in red wine, is able to protect against retinal ischemia/reperfusion injury.In vivo rat retinal ischemia was induced by high intraocular pressure (HIOP), namely, 120 mmHg for 60 min. The mechanism and management was evaluated by electroretinogram (ERG) b-wave amplitudes measurement, immunohistochemistry, and real-time polymerase chain reaction.The HIOP-induced retinal ischemic changes were characterized by a decrease in ERG b-wave amplitudes, a loss of choline acetyltransferase immunolabeling of amacrine cell bodies/neuronal processes, and increased vimentin immunoreactivity, which is a marker of Müller cells, together with upregulation of matrix metalloproteinase-9 (MMP-9), heme oxygenase-1 (HO-1), and inducible nitric oxide (iNOS), and downregulation of Thy-1, both at the mRNA level. The detrimental effects due to the ischemia were concentration-dependent (weaker effect at 0.05 nmole) and/or significantly (at 0.5 nmole) altered when resveratrol was applied 15 min before or after retina ischemia.This study supports the hypothesis that resveratrol may be able to protect the retina against ischemia by downregulation of MMP-9 and iNOS, and upregulation of HO-1.

Background Studies on vitrectomy with and without internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (ERM) have yielded uncertain results regarding clinical outcomes and recurrence rates. Objective To compare the clinical outcomes of vitrectomy with and without ILM peeling for idiopathic ERM. Methods Databases, including PubMed, Embase, Cochrane, Web of Science, Google Scholar, CNKI databases, FDA.gov, and ClinicalTrials.gov, published until July 2016, were searched to identify studies comparing the clinical outcomes following vitrectomy with ERM and ILM peeling and with only ERM peeling, for treating idiopathic ERM. Studies with sufficient data were selected. Pooled results were expressed as mean differences (MDs) and risk ratios (RRs) with corresponding 95% confidence intervals (CI) for vitrectomy with and without ILM peeling with regard to postoperative best corrected visual acuity (BCVA), central retinal thickness (CRT), and ERM recurrence rate. Results Eleven retrospective studies and one randomized controlled trial involving 756 eyes were identified. This demonstrated that the postoperative BCVA within 12 months was significantly better in the non-ILM peeling group (MD = 0.04, 95% CI: 0.00 to 0.08; P = 0.0460), but that the patients in the ILM peeling group had significantly better postoperative BCVA after 18 months (MD = −0.13, 95% CI: −0.23 to −0.04; P = 0.0049) than did those in the non-ILM peeling group. The non-ILM peeling group exhibited a higher reduction in postoperative CRT (MD = 51.55, 95% CI:−84.23 to −18.88; P = 0.0020) and a higher recurrence rate of ERM (RR = 0.34, 95% CI:0.16 to 0.72; P = 0.0048) than did the ILM peeling group. However, the improvement rates of BCVA (RR = 1.03, 95% CI:0.72 to 1.47; P = 0.8802) and postoperative CRTs (MD = 18.15, 95% CI:−2.29 to 38.60; P = 0.0818) were similar between the two groups. Conclusions Vitrectomy with ILM peeling results in better visual improvement in long-term follow-ups and lower ERM recurrence rates, and vitrectomy with only ERM peeling is more efficacious in reduction of CRT than is vitrectomy with ILM peeling.

Background Retinal ischemia is a retinal disorder related to retinal vascular occlusion, glaucoma, diabetic retinopathy and age-related macular degeneration. The study aimed to evaluate the protective effects and underlying mechanisms of Chi-Ju-Di-Huang-Wan (CJDHW) against retinal ischemia in rats. Methods High intraocular pressure (HIOP)-induced retinal ischemia was established in Wistar rats by raising their intraocular pressure to 120 mmHg for 60 min with in an eye whose anterior chamber was cannulated with a 30-guage needle adapted to a normal saline bottle through an intravenous line. This ischemic insult was followed by 1 or 7 days of reperfusion. The effects of CJDHW were studied by (i) electroretinogram (ERG); (ii) real-time polymerase chain reaction to determine the retinal mRNA levels of Thy-1 and matrix metalloproteinase-9 (MMP-9); (iii) Western blot analysis to determine the retinal protein levels of B cell lymphoma 2 (Bcl-2), heme oxygenase-1 (HO-1), phosphorylated-p38 mitogen-activated protein kinase (P-p38 MAPK) and MMP-9; (iv) hematoxylin and eosin (HE) staining; (v) fluorogold retrograde labeling; and (vi) terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) apoptosis assay. Moreover, after fixation with 4 % paraformaldehyde and 30 % sucrose, the isolated retinas were sectioned and immunolabeled with goat anti-choline acetyltransferase (ChAT) polyclonal antibody, mouse anti-vimentin monoclonal antibody and rabbit anti-glial fibrillary acidic protein (GFAP) polyclonal antibody. The retinal sections were then incubated with rhodamine-conjugated rabbit anti-goat antibody, fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse IgG or FITC-conjugated goat anti-rabbit IgG. A daily oral intake of 3 mL of water (vehicle; Group 2) or CJDHW (2.8 or 4.2 g/kg/day; CJDHW2.8 or CJDHW4.2; Group 3 or 4) was given for 7 consecutive days either before (preischemic drug administration) or after HIOP-induced retinal ischemic injury (postischemic drug administration). In Group 5, an intravitreal injection of 4 μL of 0.5 mM SB203580 (p38 MAPK inhibitor) was performed on the ischemic eye 15 min before retinal ischemia. The control rats received a sham procedure (Group 1) where the saline reservoir was not raised. Results The ischemia-induced changes (Group 2) were significantly modulated by pretreating the rats with 4.2 g/kg/day of CJDHW (Group 4; ERG: P

Hypoxia and light illumination can both decrease oxygen consumption in the photoreceptor layers. The purpose of the present study was to investigate whether the mutual effects of hypoxia and intense illumination to the photoreceptors are additive. The a-wave of flash electroretinogram (fERG) was recorded to indirectly measure the photoreceptors function under given conditions. Six normal healthy subjects, mean age 34.0 ± 3.8 years, all of whom had high-altitude (3,000 m) mountain hiking experience, were recruited for the study. Flash a-wave electroretinography was examined under four conditions: (1) normal (D/N); (2) systemic hypoxia induced by inhaling a mixture of O(2) and N(2) gases, which caused oxyhemoglobin saturation (SaO(2)) ≈ 80% (D/H); (3) intense light illumination, which resulted in photoreceptor bleaching (B/N); and (4) a combination of conditions b and c (B/H). Thirty light stimuli, each with a 20-ms ON and 1,980-ms OFF cycle, were given and ERG performed to probe the photoreceptor function. The results showed that a-wave at the various conditions did not respond to all stimuli. The average a-wave amplitudes were 91.4 ± 46.5, 22.8 ± 42.5, 15.5 ± 28.9, and 35.2 ± 41.1 μV for D/N, D/H, B/N, and B/H, respectively. Nonparametric Friedman test for a-wave amplitude indicated that significant differences occurred in D/N-D/H, D/N-B/N, D/N-B/H, D/H-B/H, and B/N-B/H (all p values were0.001, but D/H-B/N was 0.264). Thus, systemic hypoxia or strong illumination to the retina can cause an absence of the ERG a-wave or change its response, although individual differences were observed. In this study, systemic hypoxia appeared to reduce photoreceptor bleaching, an interesting finding in itself. The mechanisms underlying the disappearance of the ERG a-wave following hypoxia or intense illumination to the photoreceptors seem to differ.

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.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.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.Let-7b microRNA expression was demonstrated to be positively associated with patient age (R=0.472; p0.001). 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 (p0.001). 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.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.

Background: Visual disturbances after high-altitude exposure were first reported in 1969. Manifestations may include retinal hemorrhage, papilledema, and vitreous hemorrhage. Methods: We observed a group of 6 experienced climbers who ascended Mt Aconcagua to an altitude of 6,962 m in February 2007. Visual acuity study, intraocular pressure study, visual field study, nerve fiber layer analysis, eye Doppler, laboratory studies, fundus photography, and intravenous fluorescein angiography were performed on the climbers before and after their exposures to high altitude. Results: In all six study subjects, retinal vascular engorgement and tortuosity were present in varying degrees in both eyes. One of the climbers had both retinal hemorrhage and pulmonary edema. Of the two subjects who had visual field defects, one had severe nerve fiber layer defects of both eyes. Furthermore, laboratory studies of this climber showed a high level of antiphospholipid antibody. Significant reduction of the left ocular blood flow was also noted on this subject's eye Doppler examination after the Mt Aconcagua expedition. Conclusion: Various high-altitude retinopathies were observed in the experienced climbers of this study. As high-altitude pursuits become more popular, attention should be paid to the increasing prevalence of high-altitude retinopathy.

Retinal ischemia-induced neuronal death plays a crucial role in certain severe visual impairment diseases. The aims of this study were to investigate the effects of low dose cobalt protoporphyrin IX (CoPP), an inducer of heme oxygenase-1 (HO-1), on the retina of rats against ischemia-reperfusion (IR) injury.Retinal IR was achieved in rats by raising intraocular pressure for 60 min. CoPP (1 mg/ kg) was injected intraperitoneally 24 hr before IR. Retinal injury was assessed by the number of retinal ganglion cells (RGCs) seven days after reperfusion. TUNEL assay was used to detect the appearance of apoptotic cells 24 hr after reperfusion. The expressions of the HO-1 and Bax proteins were evaluated by Western blot.Both HO-1 expression, examined by Western blot, and enzyme activity were increased strongly after CoPP administration. Rats treated with CoPP before IR had more RGCs (p = 0.034) and less apoptotic cells (p = 0.04) together with downregulated Bax protein levels (p = 0.03) compared to ischemic rats without CoPP. The protective effects of CoPP were HO-1 dependent because the upregulation of HO-1 and the RGC protection were both abolished by the HO-1 inhibitor tin protoporphyrin (SnPP).In this study, we demonstrated that induction of HO-1 expression by low dose CoPP ameliorated retinal damage from IR injury. The favorable effect appears to be related with modulations of the apoptotic pathway.

Purpose: Age-related macular degeneration is a leading cause of blindness in the elderly. At a later stage, neovascular or exudative age-related macular degeneration can lead to severe central vision loss that is related to aging-associated cumulative oxidative stress of the human retinal pigment epithelium (hRPE) cells. Early prevention with antioxidants is mandatory. The aim of this study was to determine whether and how baicalein can act as an antioxidant. Methods: The methods used included lactate dehydrogenase, 2′,7′-dichloro-fluorescein diacetate, or enzyme-linked immunosorbent assay to measure cell viability, oxygen free radical levels, or the levels of vascular endothelial growth factor (VEGF)/matrix metalloproteinase-9 (MMP-9), respectively. Results: H2O2 dose-dependently reduced the cell viability of hRPE cells. This negative effect was dose-dependently (with a lower effect at 20 μM) and significantly counteracted by pretreatment with baicalein (50 μM). Treatment with H2O2 significantly...

Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1), a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H(2)O(2) treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H(2)O(2)-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1). SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. At a later stage, neovascular or exudative AMD can lead to severe central vision loss that is related to aging-associated cumulative oxidative stress of the human retinal pigment epithelium (hRPE) and choroid capillary. Early prevention with antioxidants is mandatory. The aim of this study was to determine whether and how mannitol can act as an antioxidant.The methods used included measurements of cell viability, oxygen free radical (OFR) levels, lipid peroxide (LP) levels, and OFR-related enzyme protein levels.H(2)O(2) dose-dependently reduced the cell viability of hRPE cells. This negative effect was significantly counteracted by pretreatment with mannitol (1 mM). H(2)O(2) significantly stimulated the formation of OFR and LP. These increases were dose-dependently and significantly blunted by mannitol. Furthermore, treatment with H(2)O(2) was associated with a reduction in the level of catalase, but not of manganese superoxide dismutase (MnSOD). In contrast, it was shown that mannitol protected hRPE cells against the H(2)O(2)-induced oxidative stress by increasing the level of catalase, but not the level of MnSOD.This study supports an antioxidative role for mannitol that acts through up-regulating the level of catalase, which is decreased by H(2)O(2).

The incidence of gallstone is higher in patients with diabetes mellitus than in general popula- tion. It is generally attributed to hypomotility and lowered emptying function of the gallblad- der. In this study, we investigate if chronic hy- perglycemia is correlated with reduced contrac- tile function of the bile ducts in rat. Hypergly- cemic rats were induced by streptozotocin-nic-otinamide treatment. Hyperglycemic rats were sacrificed eight months after induction and bile ducts were removed for the subsequent studies. The bile duct contractility of the normal rats is consistently higher than that of the hypergly- cemic rats. The contractities were measured to be 5.5 ± 0.2 mg vs. 4.2 ± 0.1 mg without CCK stimulation, and 5.5 ± 0.3 mg vs. 7.9 ± 0.4 mg with CCK stimulation, respectively for hypergly-cemic and normal rats. There was no significant difference in plasma CCK concentration in hy- perglycemic rats and normal rats. The expres- sion of CCK-A receptor protein in the bile duct tissue was decreased in hyperglycemic rats compared with that of the normal rats, and it may, at least in part, responsible for a reduced contractility. A reduced bile duct motility may cause bile retention, and may be one of the factors predispose to gallstone formation in type 2 diabetes patients, which is characterized with chronic hyperglycemia.

The purpose of this study is to explore whether it is worthwhile to launch a routine diabetic retinopathy (DR) screening for blindness pre-vention among Chinese type 2 diabetes from different perspective based on the popula-tion-based study in Kinmen, Taiwan. A total of 971 community dwelling adults previously di-agnosed with type 2 diabetes in 1991-1993 un-derwent DR screening in 1999-2002 by a panel of ophthalmologists using on-site indirect oph-thalmoscopy and 45-degree color fundus retinal photographs. The cost-benefit analysis is used to evaluate the DR screening. In terms of bene-fit-cost ratio, the different screening programs for DR could save New Taiwan Dollars (NTD) from 14.38 to 36.83 in discounted costs for each dollar incurred in different screening years from the societal viewpoint for Taiwan and save NTD from 0.81 to 1.80 in different screening years from health care payer’s perspective. The av-erage estimate of willingness-to-pay to translate into benefit yields NTD from 937.8 to 4,689 be- nefits per case due to DR screening in different screening years during 10-year follow-up. The net present value of the DR screening were NTD from -167,318 to -307,251.2 in different screening years. In conclusion, it is worthwhile to initial a routine DR screening of Chinese type 2 diabetes for blindness prevention from the societal per-spective but not from consumer decision based on the willingness-to-pay perspective.

Background This community-based study conducted in Kinmen aimed to discover whether screening for diabetic retinopathy (DR) among Chinese with type 2 diabetes was economically feasible and clinically effective. Methods A total of 971 community-dwelling adults previously diagnosed with type 2 diabetes in 1991-1993 underwent DR screening in 1999-2002 by a panel of ophthalmologists, who used on-site indirect ophthalmoscopy and 45-degree color fundus retinal photographs. Economic evaluation included estimates for cost effectiveness and the cost utility of screening for DR. Results For each DR case, screening efficacy and utility decreased, while cost increased with the length of the screening interval. The cost per sight year gained in the annual screening, biennial screening, 3-year screening, 4-year screening, 5-year screening, and control groups were New Taiwan dollars (NT dollars) 20962, NT dollars 24990, NT dollars 30847, NT dollars 37435, NT dollars 44449, and NT dollars 83411, respectively. The cost per quality-adjusted life year gained by the annual screening, biennial screening, 3-year screening, 4-year screening, 5-year screening, and control groups were NT dollars 21924, NT dollars 25319, NT dollars 30098, NT dollars 35106, NT dollars 40037, and NT dollars 61542, respectively. Threshold values indicate that the screening programs are highly sensitive to screening cost in the plausible range. Conclusion Screening for DR is both medically and economically worthwhile. Annual screening for DR among Chinese with type 2 diabetes should be conducted. Prevention programs aimed at improving eye care for patients with type 2 diabetes result in both substantial federal budgetary savings and highly cost-effective health care.

Additional file 1. The ARRIVE guidelines.

BACKGROUND: In Taiwan, there were few population-based studies of WTP values related to DR screening among persons with type 2 diabetes. This community-based study was to explore the willingness- to-pay (WTP) values for screening for diabetic retinopathy (DR) associated with varying degrees of DR among persons with type 2 diabetes in Kinmen, Taiwan.METHODS: A total of 725 eligible community-dwelling adults diagnosed with type 2 diabetes received DR screening during 1999-2002 and then evaluated WTP values in 2003. Diagnosis of DR was performed by a panel of ophthalmologists using ophthalmoscopy and a 45-degree color retinal photographs to examine fundus after dilating pupils. WTP values were measured by discrete-choice method.RESULTS: The 406 adults with type 2 diabetes participating in the WTP survey had a 56% response rate. Of 406 subjects, 265 (65.3%) said they would be willing to pay for DR screening to reduce blindness. The overall mean WTP value was New Taiwan Dollars 468.9±327.7 (US dollars 14.3±10.0). Age was borderline significant (p=0.07) related to WTP values. Those with severe stage DR had higher WTP values for screening than subjects with mild stage.CONCLUSIONS: Degree of DR was the independent factor affecting WTP values in DR screening among community-dwelling adults with type 2 diabetes.J Epidemiol 2007; 17: 186-193.

Background: The purpose of this study was to assess the prevalence and associated factors of cataract surgery among patients with type 2 diabetes in Kinmen, Taiwan. Methods: A community-based population survey between 1991 and 1993 identified 971 patients over the age of 30 years with type 2 diabetes. In 1999, a total of 578 patients (59.5%) with type 2 diabetes from the population were examined in an ophthalmic screening study. Two senior ophthalmologists employed slit-lamp biomicroscopy, indirect ophthalmoscopy, and retinal photographs with pupil dilatation to examine the patients' lenticular and retinal status. Results: The prevalence of cataract surgery in one eye, both eyes, and any cataract surgery among patients with type 2 diabetes was 4.5%, 5.4%, and 9.9%, respectively. The prevalence of cataract surgery in women (11.3%) was not significantly higher than in men (7.7%), but there was a statistical increase with age ( p = 0.001, χ 2 trend test). Multiple logistic regression showed that age (OR 1.13,95% CI 1.07–1.19) and diabetic retinopathy (OR 4.68,95% CI 1.94–11.33) were independent factors associated with cataract surgery. Interpretation: Age and diabetic retinopathy were associated with prevalence of cataract surgery among persons with type 2 diabetes.

Familial exudative vitreoretinopathy (FEVR) belongs to a group of genetically and clinically heterogeneous disorders in retinal vascular development. To date, in approximately 50% of patients with FEVR, pathogenic mutations have been detected in FZD4, LRP5, TSPAN12, NDP and ZNF408. In this study, we identified two heterozygous frameshift mutations in RCBTB1 from three Taiwanese cases through exome sequencing. In patient-derived lymphoblastoid cell lines (LCLs), the protein level of RCBTB1 is approximately half that of unaffected control LCLs, which is indicative of a haploinsufficiency mechanism. By employing transient transfection and reporter assays for the transcriptional activity of β-catenin, we demonstrated that RCBTB1 participates in the Norrin/FZD4 signaling pathway and that knockdown of RCBTB1 by shRNA significantly reduced nuclear accumulation of β-catenin under Norrin and Wnt3a treatments. Furthermore, transgenic fli1:EGFP zebrafish with rcbtb1 knockdown exhibited anomalies in intersegmental and intraocular vessels. These results strongly support that reduced RCBTB1 expression may lead to defects in angiogenesis through the Norrin-dependent Wnt pathway, and that RCBTB1 is a putative genetic cause of vitreoretinopathies.