Effect of myopia on the progression of normal tension glaucoma.

PURPOSE: Identify risk factors of progression in treated normal-tension glaucoma (NTG) in highly myopic and non-highly myopic eyes. METHODS: This retrospective, observational case series study included 42 highly myopic glaucoma (HMG, <-6D) eyes and 39 non-highly myopic glaucoma (NHG,≧-6D) eyes. Glaucoma progression was determined by serial visual field data. Univariate and multivariate logistic regression method were used to detect associations between potential risk factors and glaucoma progression. RESULTS: Among 81 eyes from 81 normal-tension glaucoma patients (mean follow-up, 3.10 years), 20 of 42 eye (45.24%) in the HMG and 14 of 39 eyes (35.90%) in the NHG showed progression. The HMG group had larger optic disc tilt ratio (p = 0.007) and thinner inferior macular thickness (P = 0.03) than the NHG group. Changes in the linear regression values for MD for each group were as follows: -0.652 dB/year for the HMG and -0.717 dB/year for the NHG (P = 0.298). Basal pattern standard deviation (PSD) (OR: 1.55, p = 0.016) and post treatment IOP (OR = 1.54, p = 0.043) were risk factors for visual field progression in normal tension glaucoma patients. In subgroup analysis of HMG patients, PSD (OR: 2.77, p = 0.017) was a risk factor for visual field progression. CONCLUSION: Reduction IOP was postulated to be contributing in the prevention of visual field progression, especially in highly myopic NTG patients with large basal pattern standard deviation.

Retinal protection by fungal product theissenolactone B in a sodium iodate-induced AMD model through targeting retinal pigment epithelial matrix metalloproteinase-9 and microglia activity.

Age-related macular degeneration (AMD) is the leading cause of low vision and blindness for which there is currently no cure. Increased matrix metalloproteinase-9 (MMP-9) was found in AMD and potently contributes to its pathogenesis. Resident microglia also promote the processes of chronic neuroinflammation, accelerating the progression of AMD. The present study investigates the effects and mechanisms of the natural compound theissenolactone B (LB53), isolated from Theissenia cinerea, on the effects of RPE dysregulation and microglia hyperactivation and its retinal protective ability in a sodium iodate (NaIO3)-induced retinal degeneration model of AMD. The fungal component LB53 significantly reduces MMP-9 gelatinolysis in TNF-α-stimulated human RPE cells (ARPE-19). Similarly, LB53 abolishes MMP-9 protein and mRNA expression in ARPE-19 cells. Moreover, LB53 efficiently suppresses nitric oxide (NO) production, iNOS expression, and intracellular ROS levels in LPS-stimulated TLR 4-activated microglial BV-2 cells. According to signaling studies, LB53 specifically targets canonical NF-κB signaling in both ARPE-19 and BV-2 microglia. In an RPE-BV-2 interaction assay, LB53 ameliorates LPS-activated BV-2 conditioned medium-induced MMP-9 activation and expression in the RPE. In NaIO3-induced AMD mouse model, LB53 restores photoreceptor and bipolar cell dysfunction as assessed by electroretinography (ERG). Additionally, LB53 prevents retinal thinning, primarily the photoreceptor, and reduces retinal blood flow from NaIO3 damage evaluated by optic coherence tomography (OCT) and laser speckle flowgraphy (LSFG), respectively. Our results demonstrate that LB53 exerts neuroprotection in a mouse model of AMD, which can be attributed to its anti-retinal inflammatory effects by impeding RPE-mediated MMP-9 activation and anti-microglia.

Association of neovascular age-related macular degeneration with migraine.

Patients with early onset vascular pathology have been reported to manifest neovascular age-related macular degeneration (AMD). While the blood vessels involved in pathogenesis of migraine remains controversial, it is generally accepted that a major contributor is blood vessel pathology. This study aimed to examine the association between migraine and AMD using a nationwide population-based dataset. Retrospective claims data were collected from the Taiwan National Health Insurance Research Database. We identified 20,333 patients diagnosed with neovascular AMD (cases), and we selected 81,332 propensity score-matched controls from the remaining beneficiaries in Taiwan's National Health Insurance system. We used Chi-square tests to explore differences in the prevalence of migraine prior to the index date between cases and controls. We performed multiple logistic regressions to estimate the odds of prior migraine among neovascular AMD patients vs. controls after adjusting for age, sex, monthly income, geographic location, residential urbanization level, hyperlipidemia, diabetes, coronary heart disease, hypertension, and previous cataract surgery. A total of 5184 of sample patients (5.1%) had a migraine claim before the index date; 1215 (6.1%) among cases and 3969 (4.9%) among controls (p < 0.001), with an unadjusted OR of 1.239 (95% CI 1.160~1.324, p < 0.001) for prior migraine among cases relative to controls. Furthermore, the adjusted OR was 1.201 (95% CI 1.123~1.284; p < 0.001) for AMD cases relative to controls. The study offers population-based evidence that persons with migraine have 20% higher risk of subsequently being diagnosed with neovascular AMD.

Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation.

BACKGROUND: Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions. RESULTS: TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes. CONCLUSIONS: Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.

Associations between Attention-Deficit/Hyperactivity Disorder and Ocular Abnormalities in Children: A Population-based Study.

Purpose: Attention-deficit/hyperactivity disorder (ADHD) was reported to be associated with disturbances in the prefrontal circuitry and seems to be associated with dysfunctions of eye motility. This study aimed to explore associations between ADHD and ocular abnormalities, including amblyopia, hypermetropia, astigmatism, and heterotropia, using a large, nationwide population-based dataset in Taiwan.Methods: We retrieved our sample for this cross-sectional study from the Taiwan National Health Insurance Research Database. In total, 116,308 children with ADHD were selected as the study group and 116,308 randomly selected children without ADHD as the comparison group. We used conditional logistic regression analyses to examine the odds ratios (ORs) of amblyopia, hypermetropia, astigmatism, and heterotropia between children with and those without ADHD.Results: We found that children with ADHD had significantly higher prevalences of amblyopia (1.6% vs. 0.9%, p< .001), hypermetropia (2.4% vs. 1.3%, p < .001), astigmatism (0.2% vs. 0.1%, p < .001), and heterotropia (1.1% vs. 0.5%, p < .001) than children without ADHD. The ORs of amblyopia, hypermetropia, astigmatism and heterotropia for children with ADHD were 1.89 (95% confidence interval (CI) = 1.76 ~ 2.05), 1.82 (95% CI = 1.68 ~ 1.92), 1.73 (95% CI = 1.34 ~ 2.16), and 2.01 (95% CI = 1.82 ~ 2.21) compared to children without ADHD.Conclusions: The findings suggest that ADHD is associated with ocular abnormalities, including amblyopia, hypermetropia, astigmatism, and heterotropia.

The fungus-derived retinoprotectant theissenolactone C improves glaucoma-like injury mediated by MMP-9 inhibition.

BACKGROUND: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that has been found to induce matrix metalloproteinase-9 (MMP-9) activation and result in eventual retinal dysfunction. Proinflammatory cytokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-1ß (IL-1ß) were also found to be involved in disease progression by mediating MMP-9 production. We previously reported that fungal derivative theissenolactone C (LC53) could exert ocular protective effects by suppressing neuroinflammation in experimental uveitis. PURPOSE: The aim of this study was to investigate the retinoprotective effects of natural compound LC53 on the high IOP-induced ischemia/reperfusion (I/R)-injury model of glaucoma and its cellular mechanisms. METHODS: A high IOP-induced I/R-injury model was manipulated by normal saline injection into the anterior chamber of the rat eye. MCP-1-stimulated monocytes and IL-1ß-activated primary astrocytes were used to investigate the cellular mechanisms of LC53. Retinal function was evaluated with the scotopic threshold response (STR) and combined rod-cone response by electroretinography (ERG). As a positive control, rats were treated with memantine. MMP-9 gelatinolysis, mRNA expression and protein expression were analyzed by gelatin zymography, RT-PCR, and Western Blot, respectively. The phosphorylation levels of MAPKs and NF-κB p65 were tested by Western Blot. Additionally, the levels of inflammatory MCP-1 and IL-1ß were determined by ELISA. RESULTS: The present study revealed that LC53 preserved the retina functional deficiency assessed by scotopic threshold response (STR) and combined rod-cone response of ERG after high IOP-induced I/R injury. These retinal protective effects of LC53 were positively correlated with inhibitory activities in I/R injury-elicited ocular MMP-9 activation and expression. The increased level of MCP-1 was not affected, and the enhanced IL-1ß production was partially reduced by LC53 in the retina after I/R injury. According to cellular studies, LC53 significantly and concentration-dependently abrogated MMP-9 activation and expression in MCP-1-stimulated THP-1 monocytes. We found the inhibitory activities of LC53 were through the ERK- and NF-κB-dependent pathways. In addition, LC53 dramatically suppressed IL-1ß-induced MMP-9 activation and expression in primary astrocytes. The phosphorylation of 65-kD protein (p65) of NF-κB was substantially blocked by LC53 in IL-1ß-stimulated primary astrocytes. CONCLUSION: LC53 exerted a retinal protective effect through NF-κB inhibition and was highly potent against MMP-9 activities after high IOP-induced I/R injury, suggesting that LC53 would be a promising drug lead for glaucoma or related medical conditions attributed to retinal ischemia.

Novel Protective Effects of Cistanche Tubulosa Extract Against Low-Luminance Blue Light-Induced Degenerative Retinopathy.

BACKGROUND/AIMS: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo. METHODS: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation. RESULTS: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model. CONCLUSION: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Theissenolactone C Exhibited Ocular Protection of Endotoxin-Induced Uveitis by Attenuating Ocular Inflammatory Responses and Glial Activation.

The aim of this study was to investigate the effects of a natural component, theissenolactone C (LC53), on the ocular inflammation of experimental endotoxin-induced uveitis (EIU) and its related mechanisms in microglia. Evaluation of the severity of anterior uveitis indicated that LC53 treatment significantly decreased iridal hyperemia and restored the clinical scores. Additionally, the deficient retina functions of electroretinography were improved by LC53. LC53 significantly reduced levels of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1, protein leakage and activation of matrix metalloproteinases in the anterior section during EIU. Moreover, LC53 treatment decreased the oxidative stress as well as neuroinflammatory reactivities of GFAP and Iba-1 in the posterior section. Furthermore, LC53 decreased the phosphorylation of p65, expression of HSP90, Bax, and cleaved-caspase-3 in EIU. According to the microglia studies, LC53 significantly abrogated the productions of TNF-α, PGE2, NO and ROS, as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-stimulated microglial BV2 cells. The microglial activation of IKKß, p65 phosphorylation and nuclear phosphorylated p65 translocation were strongly attenuated by LC53. On the other hand, LC53 exhibited the inhibitory effects on JNK and ERK MAPKs activation. Our findings indicated that LC53 exerted the ocular-protective effect through its inhibition on neuroinflammation, glial activation, and apoptosis in EIU, suggesting a therapeutic potential with down-regulation of the NF-κB signaling for uveitis and retinal inflammatory diseases.

Neovascular age-related macular degeneration is associated with cataract surgery.

PURPOSE: This retrospective cohort study examines the association between cataract surgery and neovascular age-related macular degeneration (AMD) during 5-year follow-up using population-based claims data. METHODS: We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study included 3465 patients who had undergone cataract operations and did not have a diagnosis of AMD before or on the surgery date (study group), and 10 395 age- and sex-matched comparison patients selected randomly from the remaining patients without an AMD diagnosis before the index date. We tracked the claims of each patient for a 5-year period to identify patients with a subsequent diagnosis of neovascular AMD. RESULTS: The incidence rate of neovascular AMD was 0.88 (95% confidence interval (CI): 0.66-1.14) per 1000 person-years among all sampled patients, 1.60 (95% CI: 1.04-2.36) among the cataract surgery patients and 0.64 (95% CI: 0.43-0.91) among comparison patients (p < 0.001). Stratified Cox proportional analysis showed that relative to the comparison cohort, the adjusted hazard ratio for neovascular AMD during 5-year follow-up was 2.68 (95% CI: 1.55-4.66) for patients who had undergone cataract operation. We censored those who died during follow-up period and adjusted for patients' monthly income, geographical location, urbanization level, diabetes, hypertension, cardiovascular disease and hyperlipidaemia. CONCLUSION: This study demonstrated epidemiological evidence of a link between cataract surgery and neovascular AMD during a 5-year follow-up period.

Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy.

Diabetic retinopathy (DR), a major microvascular complication of diabetes, leads to retinal vascular leakage, neuronal dysfunction, and apoptosis within the retina. In this study, we combined STZ with whole-body hypoxia (10% O2) for quicker induction of early-stage retinopathy in C57BL/6 mice. We also compared the effects of a high glucose condition combined with hypoxia (1% O2) to a low glucose condition by using retinal pigment epithelial (RPE) cells, which are a crucial component of the outer blood-retinal barrier and the damage is related to retinopathy. In the retina of DM/hypoxic C57BL/6 mice, abnormal a-wave and b-wave activity, yellowish-white spots, hyperfluorescence, and reduced retinal thickness were found using electroretinography (ERG), fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Shikonin dose-dependently (0.5-50 mg/kg, per os) prevented DM/hypoxia-induced lesions. In eye tissue, administration of shikonin also attenuated DM/hypoxia-induced pre-apoptotic protein BAX expression as well as the production of inflammatory proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). We also demonstrated that shikonin administration rescues high glucose/hypoxia (1% O2)-induced inflammation, decreased junction protein expression, and permeability in RPE cells. These results indicate that shikonin treatment may prevent the loss of vision associated with DR.

Editor's Highlight: Periodic Exposure to Smartphone-Mimic Low-Luminance Blue Light Induces Retina Damage Through Bcl-2/BAX-Dependent Apoptosis.

Blue light-induced phototoxicity plays an important role in retinal degeneration and might cause damage as a consequence of smartphone dependency. Here, we investigated the effects of periodic exposure to blue light-emitting diode in a cell model and a rat retinal damage model. Retinal pigment epithelium (RPE) cells were subjected to blue light in vitro and the effects of blue light on activation of key apoptotic pathways were examined by measuring the levels of Bcl-2, Bax, Fas ligand (FasL), Fas-associated protein with death domain (FADD), and caspase-3 protein. Blue light treatment of RPE cells increased Bax, cleaved caspase-3, FasL, and FADD expression, inhibited Bcl-2 and Bcl-xL accumulation, and inhibited Bcl-2/Bax association. A rat model of retinal damage was developed with or without continuous or periodic exposure to blue light for 28 days. In this rat model of retinal damage, periodic blue light exposure caused fundus damage, decreased total retinal thickness, caused atrophy of photoreceptors, and injured neuron transduction in the retina.

The natural retinoprotectant chrysophanol attenuated photoreceptor cell apoptosis in an N-methyl-N-nitrosourea-induced mouse model of retinal degenaration.

Retinitis pigmentosa (RP) is an inherited photoreceptor-degenerative disease, and neuronal degeneration in RP is exacerbated by glial activation. Cassia seed (Jue-ming-zi) is a traditional herbal medicine commonly used to treat ocular diseases in Asia. In this report, we investigated the retina-protective effect of chrysophanol, an active component of Cassia seed, in an N-methyl-N-nitrosourea (MNU)-induced mouse model of RP. We determined that chrysophanol inhibited the functional and morphological features of MNU-induced retinal degeneration using scotopic electroretinography (ERG), optical coherence tomography (OCT), and immunohistochemistry analysis of R/G opsin and rhodopsin. Furthermore, TUNEL assays revealed that chrysophanol attenuated MNU-induced photoreceptor cell apoptosis and inhibited the expression of the apoptosis-associated proteins PARP, Bax, and caspase-3. In addition, chrysophanol ameliorated reactive gliosis, as demonstrated by a decrease in GFAP immunolabeling, and suppressed the activation of matrix metalloproteinase (MMP)-9-mediated gelatinolysis. In vitro studies indicated that chrysophanol inhibited lipopolysaccharide (LPS)-induced iNOS and COX-2 expression in the BV2 mouse microglia cell line and inhibited MMP-9 activation in primary microglia. Our results demonstrate that chrysophanol provided neuroprotective effects and inhibited glial activation, suggesting that chrysophanol might have therapeutic value for the treatment of human RP and other retinopathies.

Long-term Fluorometholone Topical Use Induces Ganglion Cell Damage in Rats Analyzed With Optical Coherence Tomography.

To determine the toxic effects of long-term topical usage of fluorometholone (FLM) on ganglion cells using a direct in vivo retinopathological Brown Norway (BN) rat model. The BN rat retinal model was investigated with a minimum of 3 rats and a maximum of 4 rats per group. Rats received vehicle and 0.02% FLM suspension via topical administration 3 times a day for 28 days. The fundus images and retinal vessels were detected on days 1, 14, and 28 using Micron III retinal imaging microscope and fundus fluorescein angiography (FFA). For retinal structures, spectral-domain optical coherence tomography (SD-OCT) images were taken after FFA on days 1, 14, and 28 using an SD-OCT Imaging System. For retinal function, electrical signal transduction of photoreceptors and bipolar cells was determined by electroretinographic (ERG) recording on days 1 and 28 and IOP detection. At the end of the experiment on day 28, immunohistochemistry and TUNEL assay were performed to investigate apoptosis in ganglion cells. Total retina and nerve fiber layer (NFL) to the inner plexiform layer (IPL) were significantly thinner following 28 days of FLM treatment. Hematoxylin and eosin stain showed that there were NFL and ganglion cell layer deformations in the FLM group. With FLM treatment, TUNEL assay showed approximately a 4.68-fold increase in apoptotic cells. Moreover, FLM decreased ERG b-wave amplitude by about 56%. Using ophthalmofundoscopy devices, after 28 days of topical administration, FLM decreased NFL-IPL and total retina thickness. This suggests that long-term FLM induces adverse effects with respect to ganglion cell apoptosis.

Incremental Healthcare Service Utilization for Open-angle Glaucoma: A Population-Based Study.

PURPOSE: To investigate differences in the utilization of healthcare services between subjects with open-angle glaucoma (OAG) and comparison subjects without OAG using Taiwan's National Health Insurance population-based database. PATIENTS AND METHODS: The study comprised 2204 subjects with OAG and 2204 sex-matched and age-matched subjects without OAG. We individually followed each subject for a 1-year period to evaluate their healthcare resource utilization. Outcome variables of the healthcare resource utilization were as follows: numbers of outpatient visits and inpatient days and the mean costs of outpatient and inpatient treatment. In addition, we divided healthcare resource utilization into ophthalmologic and nonophthalmologic services. RESULTS: As for the utilization of ophthalmologic services, OAG subjects had significantly more outpatient visits (7.4 vs. 1.3, P<0.001) and significantly higher outpatient costs (US$272 vs. US$39, P<0.001) than comparison subjects. For nonophthalmologic services, OAG subjects also had significantly more outpatient visits (29.4 vs. 21.8, P<0.001) and significantly higher outpatient costs (US$1263 vs. US$847, P<0.001) than comparison subjects. Furthermore, OAG subjects incurred significantly higher inpatient costs compared with comparison subjects (US$434 vs. US$234, P<0.001). For all healthcare services, OAG subjects had significantly more outpatient visits (36.8 vs. 23.1, P<0.001) and significantly higher outpatient (US$1535 vs. US$887, P<0.001) and total (US$2245 vs. US$1122, P<0.001) costs than comparison subjects. In other words, the total cost was about 2-fold greater for OAG subjects than comparison subjects. CONCLUSIONS: We concluded that subjects with OAG had significantly higher utilization of all healthcare services than comparison subjects.

Increased incidence of peptic ulcer disease in central serous chorioretinopathy patients: a population-based retrospective cohort study.

PURPOSE: To investigate peptic ulcer disease and other possible risk factors in patients with central serous chorioretinopathy (CSR) using a population-based database. METHODS: In this population-based retrospective cohort study, longitudinal data from the Taiwan National Health Insurance Research Database were analyzed. The study cohort comprised 835 patients with CSR and the control cohort comprised 4175 patients without CSR from January 2000 to December 2009. Conditional logistic regression was applied to examine the association of peptic ulcer disease and other possible risk factors for CSR, and stratified Cox regression models were applied to examine whether patients with CSR have an increased chance of peptic ulcer disease and hypertension development. RESULTS: The identifiable risk factors for CSR included peptic ulcer disease (adjusted odd ratio: 1.39, P = 0.001) and higher monthly income (adjusted odd ratio: 1.30, P = 0.006). Patients with CSR also had a significantly higher chance of developing peptic ulcer disease after the diagnosis of CSR (adjusted odd ratio: 1.43, P = 0.009). CONCLUSION: Peptic ulcer disease and higher monthly income are independent risk factors for CSR. Whereas, patients with CSR also had increased risk for peptic ulcer development.

Association of cataract with chronic rhinosinusitis: a population-based case-control study.

PURPOSE: To assess the association between cataract and chronic rhinosinusitis (CRS) using a population-based database. METHODS: The study sample for this case-control study was retrieved from Taiwan's Longitudinal Health Insurance Database 2000. The study included 3045 patients who had undergone cataract surgery as cases and 9135 subjects without cataract as controls. Conditional logistic regression was performed to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of having a prior diagnosis of CRS in cases versus controls. RESULTS: In the total study sample, the prevalence of prior CRS was 3.88%; 5.16% among cases and 3.45% among controls (p < 0.001). Conditional logistic regression suggested that the unadjusted OR for prior CRS among cases was 1.52 (95% CI 1.25-1.85, p < 0.001) compared to controls. After adjusting for monthly income, residential urbanization and geographic region, the OR for prior CRS among cases was 1.58 (95% CI 1.30-1.94, p < 0.001) compared to controls. Furthermore, the results consistently suggested that cases had higher adjusted ORs for prior CRS than controls across all age groups (40-59, 60-69, and >69 years). It is particularly noteworthy that younger groups demonstrated higher ORs for prior CRS among cases compared to controls. In particular, the adjusted OR for cases aged 40-50 years was 1.71 (95% CI 1.09∼2.66; p < 0.05) compared to controls. CONCLUSION: While the true relationship between CRS and cataract remains to be further investigated, the result of this present study demonstrated CRS may be associated with cataract.

Increased risk of Parkinson disease following a diagnosis of neovascular age-related macular degeneration: a retrospective cohort study.

PURPOSE: To investigate the risk for Parkinson disease during a 3-year follow-up period after a diagnosis of neovascular age-related macular degeneration (AMD) using a nationwide population-based dataset in Taiwan. DESIGN: A retrospective matched-cohort study. METHODS: We identified 877subjects with neovascular AMD as the study cohort and randomly selected 8770 subjects for a comparison cohort. Each subject was individually followed for a 3-year period to identify those who subsequently developed Parkinson disease. Stratified Cox proportional hazard regressions were performed as a means of comparing the 3-year risk of subsequent Parkinson disease between the study and comparison cohorts. RESULTS: The incidence rate of Parkinson disease was 5.32 (95% confidence interval [CI]: 3.03-8.72) per 1000 person-years in patients with neovascular AMD and 2.09 (95% CI: 1.59-2.70) per 1000 person-years in comparison patients. The log-rank test indicated that subjects with neovascular AMD had a significantly lower 3-year Parkinson disease-free survival rate than comparison subjects (P < .001). After censoring cases in which patients died during the follow-up period and adjusting for monthly income, geographic region, hypertension, diabetes, hyperlipidemia, and coronary heart disease, the hazard ratio of Parkinson disease during the 3-year follow-up period for subjects with neovascular AMD was 2.57 (95% CI: 1.42-4.64) that of comparison subjects. CONCLUSION: In this study, subjects with neovascular AMD were found to be at a significant risk of Parkinson disease during a 3-year follow-up period after their diagnosis among Taiwanese Chinese. Further study is needed to confirm our findings and explore the underlying pathomechanism.