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Introduction Artificial lighting is a basic element in modern society; however, the potential health risks caused by light pollution have increased with the development of more sophisticated lighting technology (Chepesiuk [...], BACKGROUND: Light-emitting diodes (LEDs) deliver higher levels of blue light to the retina than do conventional domestic light sources. Chronic exposure to high-intensity light (2,000-10,000 lux) has previously been found to result in light-induced retinal injury, but chronic exposure to relatively low-intensity (750 lux) light has not been previously assessed with LEDs in a rodent model. OBJECTIVE: We examined LED-induced retinal neuronal cell damage in the Sprague-Dawley rat using functional, histological, and biochemical measurements. METHODS: We used blue LEDs (460 nm) and full-spectrum white LEDs, coupled with matching compact fluorescent lights, for exposures. Pathological examinations included electroretinogram, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and transmission electron microscopy (TEM). We also measured free radical production in the retina to determine the oxidative stress level. RESULTS: H&E staining and TEM revealed apoptosis and necrosis of photoreceptors, which indicated blue-light induced photochemical injury of the retina. Free radical production in the retina was increased in LED-exposed groups. IHC staining demonstrated that oxidative stress was associated with retinal injury. Although we found serious retinal light injury in LED groups, the compact fluorescent lamp (CFL) groups showed moderate to mild injury. CONCLUSION: Our results raise questions about adverse effects on the retina from chronic exposure to LED light compared with other light sources that have less blue light. Thus, we suggest a precautionary approach with regard to the use of blue-rich 'white' LEDs for general lighting. 10.1289/ehp.1307294

Purpose: To investigate the antioxidative properties of Lycium barbarum (LB) fruits in the eyes and to study whether LB fruits prepared with new nanotechnology have stronger antioxidative effects. Methods: Fourteen days post-supplementation with milled or blended LB fruits, intravitreal paraquat (PQ) was injected into Wistar rats to create oxidative stress. After an additional 14-day supplementation with LB fruits, the rats were sacrificed. An electroretinogram (ERG) was performed to evaluate retinal function before and after the PQ injection. Expression levels of antioxidative responders' mRNA in retina were detected by reverse transcription-polymerase chain reaction. Superoxide dismutase (SOD) and glutathione reductase activity in the aqueous humor (AqH) were analyzed by ELISA. Immunohistochemistry was conducted to evaluate the morphological changes of retina and the levels of oxidative biomarkers. The levels of cell apoptosis were assessed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The reactive oxygen species (ROS) levels in AqH were measured by chemiluminescence methods. Results: The murine eyes supplemented with LB fruits exhibited several changes compared with the control group. The ERGs revealed significant improvement in retinal function. The mRNA expression levels of oxidative responders were downregulated in the retinas. The ROS was significantly reduced in the retinas, but the SOD meaningfully increased in the AqH. Immunohistochemistry staining and TUNEL assays showed decreased incidences of oxidative biomarkers and apoptosis in the retinas. Milled LB fruits exhibited better antioxidative effects than blended fruits. Conclusions: Milled LB fruits demonstrated superior protection against oxidative threats than blended fruits. Thus, these fruits could be an inexpensive supplement for many oxidative stress-related ocular diseases. [ABSTRACT FROM AUTHOR]

Purpose: To describe the optical coherence tomographic findings of hyperreflective foci (HF) in neovascular age-related macular degeneration and evaluate the use of HF to predict visual outcome after antivascular endothelium growth factor (anti-VEGF) therapy. Methods: This was a post-hoc analysis of a retrospective cohort study. Hyperreflective foci were localized in the inner retina, outer retina, or subretinal fluid (SRF) layer. The treatment response of HF was recorded. The association between HF and visual outcome was analyzed. Results: We enrolled 126 eyes. Hyperreflective foci involving more than one layer were associated with poor initial visual acuity (P < 0.001). Hyperreflective foci in each layer at baseline were negatively correlated with baseline visual acuity. At 3 months posttreatment, HF in the SRF layer had decreased significantly (P = 0.003), which was faster compared with HF in other layers. Baseline HF status at each layer was not associated with final visual outcome. The eyes with reduced HF in the SRF at 3 months had better visual improvement at 12 months (P = 0.038). Conclusion: Hyperreflective foci involving multiple layers were associated with poor initial visual acuity but not with final visual outcome. With anti-VEGF treatment, HF in the SRF layer resolved faster, which may predict better visual outcome. [ABSTRACT FROM AUTHOR]

Polypoidal choroidal vasculopathy (PCV) is a prevalent retinal disease predominantly occurs in Asians that shares some similarities seen in neovascular age-related macular degeneration. Recent large multicenter clinical trials on intravitreal anti-vascular endothelial growth factor (VEGF) agents and photodynamic therapy (PDT) have shed lights on the management of PCV. The Taiwan National Health Insurance had granted limited anti-VEGF agents and PDT for patients with PCV after the approval of required data submission, especially fundus angiography, optical coherence tomography, and visual acuity. In order to best utilize these limited resources for the patients, an expert meeting was held to provide updated Taiwan consensus recommendations for the management of PCV, including initial therapy selection, assessment of treatment response, re-treatment/rescue treatment, and determination of treatment extension/follow-up schedule. An algorithm for treatment allocation under both initial and re-treatment setting was proposed. Further mechanistic and clinical studies are required to investigate the prognostic factors and optimal treatment protocols that will improve healthcare quality and reduce burden of disease and treatment for patients with PCV. [ABSTRACT FROM AUTHOR]

• Polypoidal choroidal vasculopathy may cause profound visual loss. • Ranibizumab and verteporfin photodynamic therapy can be the treatment of choice. • Outcomes of two loading doses ranibizumab is comparable to other regimens. • Recurrent hemorrhage is associated with poor visual improvement. • Complete polyp eradication is associated with a lower risk of recurrent hemorrhage. To investigate the prognostic factors for the combined therapy of ranibizumab and prompt verteporfin photodynamic therapy (vPDT) for eyes with polypoidal choroidal vasculopathy (PCV). Sixty-two PCV eyes of 62 patients that received the initial treatment of intravitreal ranibizumab followed by vPDT within 1 week plus a 2nd intravitreal ranibizumab 1 month later in one single medical center were retrospectively enrolled. Best-corrected visual acuity (BCVA) and parameters obtained from optical coherence tomography at baseline, 3 months, 6 months and 1 year were measured and compared. Factors associated with polyp regression, recurrent hemorrhage and visual improvement were analyzed. After the loading treatment, complete and partial polyp regression was achieved in 53.6% and 39.3% of cases, respectively at Month 3. The mean logarithm of the minimum angle of resolution of BCVA improved from 0.64 ± 0.38 to 0.55 ± 0.46 (P = 0.008) at Month 12. Recurrent hemorrhage (P = 0.001) and previous anti-vascular endothelial growth factor (VEGF) treatment (P = 0.017) were associated with poorer visual improvement at Month 12. Incomplete polyp regression (P = 0.038) and previous anti-VEGF treatment (P = 0.005) were associated with a higher risk of recurrent hemorrhage. Recurrent hemorrhage was associated with poor visual improvement after combined ranibizumab and vPDT for PCV. Complete polyp eradication was associated with a lower risk of recurrent hemorrhage. Patients who had previously received anti-VEGF were associated with recurrent hemorrhage and poor visual improvement; more frequent follow-ups and more aggressive subsequent treatments may be needed for these cases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the anatomic versus functional changes in diabetic retinopathy (DR) by studying the correlation of retinal vascular perfusion density and dark adaptation (DA). Methods: Optical coherence tomography angiography (OCTA) and DA tests were performed in diabetic patients and nondiabetic controls. DA was measured using AdaptDx dark adaptometer and the rod intercept was recorded. Macular OCTA images were acquired using the RTVue XR Avanti with AngioVue. Results: Eighty-six eyes from 57 patients with diabetes (19 with no DR, 19 with non-proliferative DR [NPDR], and 19 with proliferative DR [PDR] who had undergone photocoagulation) and 10 eyes from 10 patients without diabetes were recruited. A significant decrease in vascular density and a prolonged rod intercept were found as DR progressed (P <.01). A negative trend was found between vascular density and the rod intercept. The negative trend in the deep layer (R2 = 0.28) was more substantial than that in the superficial layer (R2 = 0.14). A prolonged rod intercept was associated with elevated HbA1c (R2 = 0.08). Conclusions: The vascular density of the macula could be assessed by OCTA and the functional change in the outer retina could be measured non-invasively by DA. The severity of decreasing vascular density and prolongation of DA are proportional to progression of DR. Decreased deep retinal vascular perfusion density and impaired DA response are correlated and show a negative trend according to the severity of DR. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anti-oxidative and anti-inflammatory effects of cilostazol in the ocular tissues of streptozotocin (STZ)-induced diabetic rats. Materials and methods: Diabetes was induced in 6-week-old Wistar rats via peritoneal injections of STZ. The treatment group received cilostazol 18 mg/kg/day for 8 weeks (n = 10), and the diabetic group received phosphate buffer solution (n = 20). The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by reverse-transcription polymerase chain reactions, immunohistochemical (IHC) staining, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Results: Reverse-transcription polymerase chain reactions, IHC staining, Western blot analysis, and ELISA showed that cilostazol inhibited mRNA and protein expressions of intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and fractalkine in the retina and aqueous humor (AqH). Consistent with these findings, cilostazol attenuated the activation of nuclear factor-κB (NF-κB) in the diabetic rats. The levels of oxidatively modified DNA (8-OHdG), nitrotyrosine and oxidative lipids (acrolein) were also diminished in the cilostazol-treated group. Chemiluminescence analysis showed that reactive oxygen species (ROS) levels in the AqH was significantly higher in the diabetic rats than in the non-diabetic rats. Treatment with cilostazol significantly reduced the ROS levels in the AqH compared to the diabetic rats. Conclusions: Our results indicated that cilostazol reduced inflammatory reactions and oxidative stress in diabetic eyes. The anti-inflammatory effects of cilostazol may be indirectly via reducing oxidative stress, inhibiting NF-κB activity, and subsequently decreasing inflammatory mediators. Cilostazol may be beneficial to prevent the progression of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background: To identify genotypes associated with neovascular age‐related macular degeneration (nAMD) and investigate the associations between genotype variations and anti‐vascular endothelial growth factor (VEGF) treatment response. Methods: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti‐VEGF treatment in National Taiwan University Hospital with at least one‐year follow‐up between 2012 and 2020. A genome‐wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. Results: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2‐DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). Conclusions: Among the 16 SNPs found in the GWAS, four loci—CFH, ARMS2/HTRA1, and two novel loci—were correlated with the susceptibility of nAMD and anatomical/functional responses after anti‐VEGF treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the associations between fluid accumulation at different levels in the retina and visual outcome in polypoidal choroidal vasculopathy (PCV). Design: A retrospective observational study. Institutional setting. Study Population: A total of 91 eyes from 91 patients of PCV were included, with 65 receiving intravitreal aflibercept monotherapy and 26 receiving combined intravitreal ranibizumab and photodynamic therapy (PDT). Observation Procedures: Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination results were recorded at baseline and 3, 6, and 12 months after treatment. Main Outcome Measures: The correlations between visual outcomes and fluid biomarkers including intraretinal fluid (IRF), subretinal fluid (SRF), serous pigment epithelium detachment (PED), and hemorrhage at fovea were analyzed. Results: No differences in treatment outcomes were noted between patients receiving aflibercept and those receiving combined ranibizumab and PDT. IRF and hemorrhage at baseline predicted poorer vision at 3, 6, and 12 months. The presence of IRF was associated with poorer vision at 6 months and 12 months (p < 0.05 for all). The presence of SRF or PED was not associated with better vision at any time point. No differences in the correlations between fluid markers and visual outcomes were noted between thin and thick subfoveal choroidal thickness groups. Conclusions: For PCV, IRF and hemorrhage at baseline served as surrogates for poor visual prognosis after treatment, and IRF was a biomarker for poor vision during the treatment course. No fluid markers predicted good visual prognosis or had a positive impact on vision at any time point. [ABSTRACT FROM AUTHOR]

Purpose: To report the one-year outcomes of diabetic macular edema (DME) treated with ranibizumab under a real-life setting in Taiwan, and to identify the prognostic factors.Methods: Between July 2013 and January 2015, 119 eyes receiving intravitreal ranibizumab for DME were retrospectively recruited. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) measured with optical coherence tomography were collected at baseline and at Month 3, 6, and 12. Linear regression was used to identify the predicting factors for changes in BCVA and CFT at Month 12.Results: The average number of ranibizumab given within one year was 4.36 ± 1.87. The BCVA (logMAR) improved from 0.74 ± 0.30 at baseline to 0.64 ± 0.37 at Month 12 (p = 0.002). A better improvement in BCVA at Month 3 was significantly correlated with a better visual improvement at Month 12 (p < 0.001). The existence of subretinal fluid at baseline (p = 0.02) and a greater reduction in CFT at Month 3 (p < 0.001) were both correlated with a greater reduction in CFT at Month 12. Previous subtenon injection of triamcinolone acetonide was associated with fewer additional IVR after Month 3 (odds ratio = 0.35, 95% CI = 0.14-0.89).Conclusion: Compared with existing prospective studies, the one-year real-life data in Taiwan showed fewer ranibizumab injections for DME and a less prominent yet still significant visual improvement. Both visual and anatomical improvements at Month 3 were correlated with the level of improvements at Month 12. Previous subtenon steroid injection might reduce the need of additional ranibizumab injections. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Retinal pigment epithelial cell apoptosis increase with longer blue light exposure. • Chitosan oligosaccharides reduce cell apoptosis in a dose-dependent manner. • Chitosan oligosaccharides decrease oxidative stress and inflammation-related proteins. • Chitosan oligosaccharides stabilize mitochondrial function and inhibit NF-κB pathway. Abstract Excessive blue light light-emitting diode (LED) exposure and consequent oxidative stress causes damage to retinal pigment epithelial (RPE) cells. Chitosan oligosaccharides (COSs) are the hydrolyzed products of chitin, which is abundant in the exoskeleton of crustaceans and cell walls of fungi. We investigated the protective effect of COSs on blue light LED-induced RPE cell damage. These cells were treated with various concentrations of COSs and then exposed to blue light LED. Our results confirmed that RPE cell apoptosis increased significantly with longer light exposure. Treatment with COSs significantly reduced apoptosis in a dose-dependent manner. These molecules also suppressed the production of reactive oxygen species and the expression of inflammation- and apoptosis-related proteins. Moreover, COSs stabilized the mitochondrial membrane potential of cells and down-regulated the NF-κB pathway. In this study, the protective effects of COSs on blue light LED-induced RPE cell damage, as well as the associated mechanisms, were demonstrated. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance (p < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR. [ABSTRACT FROM AUTHOR]