Macular Degeneration: Wang Y

Zhang P, Wang Y, Hui Y, Hu D, Wang H, Zhou J, Du H. · Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China. · Ophthalmologica. · Pubmed #17947829 No free full text.

Abstract: BACKGROUND: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for choroidal neovascularization. The upregulation of VEGF expression in response to hypoxia occurs through hypoxia-inducible factor 1 (HIF-1), which is a transcription factor that regulates genes involved in the response to hypoxia. HIF-1 alpha is the inducible subunit of the HIF-1. AIMS: To further define HIF-1 function in angiogenesis and to explore novel approaches to modulate choroidal neovascularization in age-related macular degeneration. METHODS: In this study, we examined the response of human retinal pigment epithelium (RPE) cells to hypoxia and employed the small interference RNA technique to knock down gene expression of HIF-1 alpha in RPE cells. Results: We found that both the mRNA and protein levels of HIF-1 alpha in the RPE cells increased in response to hypoxia, followed by increasing expression of VEGF. Both the mRNA and protein levels of HIF-1 alpha and VEGF in the RPE cells were decreased dramatically after transfection with a HIF-1 alpha-specific small interference RNA vector. CONCLUSION: Our results suggest that HIF-1 may be involved in angiogenesis by controlling the expression of VEGF in vivo and provide a possible strategy for the treatment of angiogenesis by targeting the HIF-1 alpha in ischemic retinopathies.

Xu J, Wang Y, Yang X, Zhang P, Chen L. · Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. · Yan Ke Xue Bao. · Pubmed #17162902 No free full text.

Abstract: PURPOSE: Choroidal neovascularization (CNV) plays an important role in pathogenesis of age-related macular degeneration (AMD), ocular histoplasmosis syndrome (OHS) and so on. However, mechanisms of CNV formation are not fully understood. The aim of this study is to investigate the correlation between expressions of CD105 and vascular endothelial growth factor (VEGF) in experimental laser-induced CNV in rats. METHODS: CNV model was established by 532 nm laser photocoagulation in Brown-Norway rats. The expression of CD105 and VEGF in CNV was observed by immunohistochemistry at 3, 7, 14, 21, 28 and 56 days after laser photocoagulation. The image analysis was performed with the professional software of Image-Pro Plus. RESULTS: Fluorescein angiography showed fluorescein leakage in CNV from days 7 to 56 after photocoagulation. VEGF expression was mainly observed in vascular endothelial cells, ganglion cells, inner nuclear layers and retinal pigment epithelial cells in normal retina and vascular endothelial cells in normal choroid of the rats. On day 3 after photocoagulation, VEGF began to express in laser-induced lesions. VEGF was strongly expressed in CNV after 7 days (P < 0.05) and decreased after 14 days (P > 0.05). CD105 was initially presented in CNV at 7 days and obviously expressed at 14 days after photocoagulation (P < 0.05). Four weeks later, when angiogenesis tended toward inactive status, expression of CD105 was markedly decreased (P>0.05). There was notablely direct correlation between CD105-positive-microvessel density and positively semiquantitative scoring of VEGF in the CNV (r = 0.989, P < 0.01). CONCLUSIONS: There is direct correlation between the expression of CD105 and VEGF in the laser-induced CNV in rat. It suggests that CD105 and VEGF might participate in the new blood vessel formation and promote the growth of CNV.

Xu L, Li Y, Wang S, Wang Y, Wang Y, Jonas JB. · Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China. · Ophthalmology. · Pubmed #17070594 No free full text.

Abstract: OBJECTIVE: To evaluate factors associated with high myopia (defined as a myopic refractive error exceeding -8 diopters) in a population-based study. DESIGN: Population-based prevalence study. PARTICIPANTS: The Beijing Eye Study included 4439 participants from among 5324 individuals from a rural area and an urban region of Greater Beijing, > or =40 years old and invited to participate (response rate, 83.4%). METHODS: Interview and detailed ophthalmic examination. MAIN OUTCOME MEASURES: Refractive error, microvascular retinal abnormalities, optic disc morphometry, amount of cataract, and age-related macular changes. RESULTS: Fundus photographs and data for refractive error were available for 4319 participants (97.3%; 8484 eyes). In binary logistic regression analysis, prevalence of high myopia was significantly associated with low best-corrected visual acuity (P<0.001; 95% confidence interval [CI], 0.15-0.40), large optic disc size (P<0.001; 95% CI, 1.64-2.25), large size of beta zone (P = 0.31; 95% CI, 1.45-1.75) and alpha zone of peripapillary atrophy (P<0.001; 95% CI, 1.20-1.58), and lower macular drusen count (P = 0.020; 95% CI, 0.81-0.98). The highly myopic group had a smaller mean size of macular drusen (P = 0.03; 95% CI, 0.02-0.26) and a smaller area covered by drusen (P = 0.01; 95% CI, 0.03-0.22). In the highly myopic group, the predominant drusen type was significantly (P = 0.01; 95% CI, 0.05-0.41) more often the hard distinct drusen type than the soft drusen type, and visual field defects were significantly more common (P<0.001; odds ratio [OR], 24.0; 95% CI, 13.9-41.4) and larger (P<0.001; 95% CI, -1.67 to -1.13). The frequencies of early macular degeneration (P = 0.03; OR, 3.0; 95% CI, 1.21-7.51) and late macular degeneration (P<0.001; OR, 6.33) were significantly lower in the highly myopic group than in the non-highly myopic group. High myopia was not significantly associated with gender (P = 0.18; 95% CI, 0.76-1.05), focal arteriolar thinning (P>0.35), arteriolar sheathing (P>0.45), arteriovenous crossing abnormalities (P>0.20), self-reported diagnosis of diabetes mellitus (P = 0.54; OR, 1.36; 95% CI, 0.48-3.80), or arterial hypertension (P = 0.34; OR, 0.66; 95% CI, 0.32-1.34). CONCLUSIONS: In the adult Chinese population, high myopia is associated with a lower number, smaller, size and less advanced type of macular drusen, a larger optic nerve head, and decreased best-corrected visual acuity. The risk of early and late macular degeneration was lower for highly myopic participants than for non-highly myopic participants.

Xu L, Li Y, Wang S, Wang Y, Wang Y, Jonas JB. · Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China. · Ophthalmology. · Pubmed #17070594 No free full text.

Abstract: OBJECTIVE: To evaluate factors associated with high myopia (defined as a myopic refractive error exceeding -8 diopters) in a population-based study. DESIGN: Population-based prevalence study. PARTICIPANTS: The Beijing Eye Study included 4439 participants from among 5324 individuals from a rural area and an urban region of Greater Beijing, > or =40 years old and invited to participate (response rate, 83.4%). METHODS: Interview and detailed ophthalmic examination. MAIN OUTCOME MEASURES: Refractive error, microvascular retinal abnormalities, optic disc morphometry, amount of cataract, and age-related macular changes. RESULTS: Fundus photographs and data for refractive error were available for 4319 participants (97.3%; 8484 eyes). In binary logistic regression analysis, prevalence of high myopia was significantly associated with low best-corrected visual acuity (P<0.001; 95% confidence interval [CI], 0.15-0.40), large optic disc size (P<0.001; 95% CI, 1.64-2.25), large size of beta zone (P = 0.31; 95% CI, 1.45-1.75) and alpha zone of peripapillary atrophy (P<0.001; 95% CI, 1.20-1.58), and lower macular drusen count (P = 0.020; 95% CI, 0.81-0.98). The highly myopic group had a smaller mean size of macular drusen (P = 0.03; 95% CI, 0.02-0.26) and a smaller area covered by drusen (P = 0.01; 95% CI, 0.03-0.22). In the highly myopic group, the predominant drusen type was significantly (P = 0.01; 95% CI, 0.05-0.41) more often the hard distinct drusen type than the soft drusen type, and visual field defects were significantly more common (P<0.001; odds ratio [OR], 24.0; 95% CI, 13.9-41.4) and larger (P<0.001; 95% CI, -1.67 to -1.13). The frequencies of early macular degeneration (P = 0.03; OR, 3.0; 95% CI, 1.21-7.51) and late macular degeneration (P<0.001; OR, 6.33) were significantly lower in the highly myopic group than in the non-highly myopic group. High myopia was not significantly associated with gender (P = 0.18; 95% CI, 0.76-1.05), focal arteriolar thinning (P>0.35), arteriolar sheathing (P>0.45), arteriovenous crossing abnormalities (P>0.20), self-reported diagnosis of diabetes mellitus (P = 0.54; OR, 1.36; 95% CI, 0.48-3.80), or arterial hypertension (P = 0.34; OR, 0.66; 95% CI, 0.32-1.34). CONCLUSIONS: In the adult Chinese population, high myopia is associated with a lower number, smaller, size and less advanced type of macular drusen, a larger optic nerve head, and decreased best-corrected visual acuity. The risk of early and late macular degeneration was lower for highly myopic participants than for non-highly myopic participants.

Wang Y, Xu L, Jonas JB. · Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Capital University of Medical Science, China. · Am J Ophthalmol. · Pubmed #16765676 No free full text.

Abstract: PURPOSE: To determine prevalence and causes of visual field loss (VFL) as determined by frequency doubling perimetry in elderly Chinese individuals. DESIGN: Population-based, cross-sectional cohort study. METHODS: The Beijing Eye Study included 4439 of 5324 subjects (83.4%) who were invited to participate with an age of 40+ years. Visual field was assessed by frequency doubling threshold perimetry. Main outcome measure was an abnormal visual field defined as at least one test location of reduced sensitivity. RESULTS: Of the 4439 people who were examined, 4350 subjects (98.0%; 8617 eyes) provided measurement data by frequency doubling perimetry. In subjects aged 40 to 49 years, the most frequent cause for VFL was degenerative myopia followed by glaucoma, other optic nerve diseases, and cataract. In the subjects aged 60 to 69 years, the most frequent cause for VFL was cataract, followed by glaucoma and degenerative myopia. In the subjects aged 70+ years, the most frequent cause for VFL was glaucoma, followed by cataract and degenerative myopia. VFL was associated significantly with age (P < .001), myopic refractive error (P < .001), rural region (P = .001), low level of education (P = .01), degree of nuclear cataract (P < .001), and intraocular pressure (P < .001). CONCLUSION: In contrast to Western countries, age-related macular degeneration and diabetic retinopathy play a minor role as a cause for VFL in China.

Bora PS, Kaliappan S, Xu Q, Kumar S, Wang Y, Kaplan HJ, Bora NS. · Department of Ophthalmology and Visual Science, Kentucky Lions Eye Center, University of Louisville, KY, USA. · FEBS J. · Pubmed #16689928 No free full text.

Abstract: One of the pathologic complications of exudative (i.e. wet-type) age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The aim of this study was to investigate whether chronic and heavy alcohol consumption influenced the development of CNV in a rat model. The oxidative metabolism of alcohol is minimal or absent in the eye, so that ethanol is metabolized via a nonoxidative pathway to form fatty acid ethyl esters (FAEE). Fatty acid ethyl ester synthase (FAEES) was purified from the choroid of Brown Norway (BN) rats. The purified protein was 60 kDa in size and the antibody raised against this protein showed a single band on western blot. BN rats on a regular diet were fed alcohol for 10 weeks. Control rats were fed water with a regular diet and pair-fed control rats were fed regular diet, water and glucose. We found that FAEES activity was increased 4.0-fold in the choroid of alcohol-treated rats compared with controls. The amount of ethyl esters produced in the choroid of 10 week alcohol-fed rats was 7.4-fold more than rats fed alcohol for 1 week. The increased accumulation of ethyl esters was associated with a 3.0-fold increased expression of cyclin E and cyclin E/CDK2; however, the level of the cyclin kinase inhibitor, p27Kip, did not change. The increased accumulation of ethyl esters was also associated with 3.0-fold decreased expression of APN in the choroid. We also found that the size of CNV increased by 28% in alcohol-fed rats. Thus, our study showed that chronic, heavy alcohol intake was associated with both an increased accumulation of ethyl esters in the choroid and an exacerbation of the CNV induced by laser treatment. These results may provide insight into the link between heavy alcohol consumption and exudative AMD.

Xu L, Wang Y, Li Y, Wang Y, Cui T, Li J, Jonas JB. · Department of Ophthalmology and Eye Hospital, Tongren Hospital, Beijing, China. · Ophthalmology. · Pubmed #16647133 No free full text.

Abstract: OBJECTIVE: To evaluate the causes of visual impairment and blindness in adult Chinese in an urban and rural region of Beijing, China. DESIGN: Population-based prevalence survey. PARTICIPANTS: From a rural region and an urban region of Greater Beijing, 4439 of 5324 > or=40-year-old invited subjects participated in the study (response rate, 83.4%). Using the World Health Organization (WHO) standard and the United States standard, blindness was defined as best-corrected visual acuity (BCVA) in the better-seeing eye of <20/400 and of <2/20, respectively, and visual impairment was defined as best-corrected vision of <20/60 and > or =20/400, and of <20/40 and > or =2/20, respectively. METHODS: Determination of BCVA, pneumotonometry, frequency doubling perimetry, evaluation of photographs of the fundus and lens, and clinical examination. MAIN OUTCOME MEASURE: Causes of visual impairment and blindness. RESULTS: Visual acuity measurements were available for 8816 eyes of 4409 subjects (99.3%). Using the WHO standard and the U.S. standard, 49 (1.1%) subjects and 95 (2.2%) subjects, respectively, had low vision, and 13 (0.3%) subjects and 15 (0.3%) subjects, respectively, were blind by definition. Taking the whole study population, the most frequent cause of low vision/blindness was cataract (36.7%/38.5%), followed by degenerative myopia (32.7%/7.7%), glaucoma (14.3%/7.7%), corneal opacity (6.1%/15.4%), and other optic nerve damage (2.0%/7.7%). Age-related macular degeneration (AMD) (2.0%/7.7%) and diabetic retinopathy (0%/7.7%) were responsible for a minority of cases. In subjects 40 to 49 years old, the most frequent cause of low vision and blindness was degenerative myopia. In the 50- to 59-year age group, the most frequent cause was cataract, followed by degenerative myopia. In the 60- to 69-year-old subjects and the > or =70-year group, the most frequent cause of low vision and blindness was cataract, followed by degenerative myopia and glaucoma. CONCLUSIONS: The most frequent cause of low vision and blindness in adult Chinese is cataract, followed by degenerative myopia and glaucomatous optic neuropathy, with degenerative myopia dominating in younger groups and cataract dominating in elder groups. In contrast to studies in Western countries, AMD and diabetic retinopathy appear to play a minor role as a cause of visual impairment in elderly Chinese.

Xu L, Wang Y, Li Y, Wang Y, Cui T, Li J, Jonas JB. · Department of Ophthalmology and Eye Hospital, Tongren Hospital, Beijing, China. · Ophthalmology. · Pubmed #16647133 No free full text.

Abstract: OBJECTIVE: To evaluate the causes of visual impairment and blindness in adult Chinese in an urban and rural region of Beijing, China. DESIGN: Population-based prevalence survey. PARTICIPANTS: From a rural region and an urban region of Greater Beijing, 4439 of 5324 > or=40-year-old invited subjects participated in the study (response rate, 83.4%). Using the World Health Organization (WHO) standard and the United States standard, blindness was defined as best-corrected visual acuity (BCVA) in the better-seeing eye of <20/400 and of <2/20, respectively, and visual impairment was defined as best-corrected vision of <20/60 and > or =20/400, and of <20/40 and > or =2/20, respectively. METHODS: Determination of BCVA, pneumotonometry, frequency doubling perimetry, evaluation of photographs of the fundus and lens, and clinical examination. MAIN OUTCOME MEASURE: Causes of visual impairment and blindness. RESULTS: Visual acuity measurements were available for 8816 eyes of 4409 subjects (99.3%). Using the WHO standard and the U.S. standard, 49 (1.1%) subjects and 95 (2.2%) subjects, respectively, had low vision, and 13 (0.3%) subjects and 15 (0.3%) subjects, respectively, were blind by definition. Taking the whole study population, the most frequent cause of low vision/blindness was cataract (36.7%/38.5%), followed by degenerative myopia (32.7%/7.7%), glaucoma (14.3%/7.7%), corneal opacity (6.1%/15.4%), and other optic nerve damage (2.0%/7.7%). Age-related macular degeneration (AMD) (2.0%/7.7%) and diabetic retinopathy (0%/7.7%) were responsible for a minority of cases. In subjects 40 to 49 years old, the most frequent cause of low vision and blindness was degenerative myopia. In the 50- to 59-year age group, the most frequent cause was cataract, followed by degenerative myopia. In the 60- to 69-year-old subjects and the > or =70-year group, the most frequent cause of low vision and blindness was cataract, followed by degenerative myopia and glaucoma. CONCLUSIONS: The most frequent cause of low vision and blindness in adult Chinese is cataract, followed by degenerative myopia and glaucomatous optic neuropathy, with degenerative myopia dominating in younger groups and cataract dominating in elder groups. In contrast to studies in Western countries, AMD and diabetic retinopathy appear to play a minor role as a cause of visual impairment in elderly Chinese.

Bora PS, Sohn JH, Cruz JM, Jha P, Nishihori H, Wang Y, Kaliappan S, Kaplan HJ, Bora NS. · Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, 301E Muhammad Ali Boulevard, Louisville, KY 40202, USA. · J Immunol. · Pubmed #15611275 links to  free full text

Abstract: Choroidal neovascularization (CNV), or choroidal angiogenesis, is the hallmark of age-related macular degeneration and a leading cause of visual loss after age 55. The pathogenesis of new choroidal vessel formation is poorly understood. Although inflammation has been implicated in the development of CNV, the role of complement in CNV has not been explored experimentally. A reliable way to produce CNV in animals is to rupture Bruch's membrane with laser photocoagulation. A murine model of laser-induced CNV in C57BL/6 mice revealed the deposition of C3 and membrane attack complex (MAC) in the neovascular complex. CNV was inhibited by complement depletion using cobra venom factor and did not develop in C3(-/-) mice. Anti-murine C6 Abs in C57BL/6 mice inhibited MAC formation and also resulted in the inhibition of CNV. Vascular endothelial growth factor, TGF-beta2, and beta-fibroblast growth factor were elevated in C57BL/6 mice after laser-induced CNV; complement depletion resulted in a marked reduction in the level of these angiogenic factors. Thus, activation of complement, specifically the formation of MAC, is essential for the development of laser- induced choroidal angiogenesis in mice. It is possible that a similar mechanism may be involved in the pathophysiology of other angiogenesis essential diseases.

Chen JH, Xu L, Hu AL, Sun BC, Li JJ, Ma K, Xia CR, Cui TT, Zheng YY, Li YB, Zhang RX, Yang H, Sun XY, Zou Y, Wang Y, Ma BR. · Beijing Institute of Ophthalmology, Tongren Hospital, Capital Medical University, Beijing 100730, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #14521745 No free full text.

Abstract: OBJECTIVE: To investigate the prevalence and causes of low vision and blindness in Beijing residents aged 40 and over. METHODS: 4,451 residents aged 40 and over in 3 rural communities and 5 urban communities in Beijing underwent eye examination, including examination of distant and near visual acuity (VA), best corrected distant and near VA, pinhole VA, and visual field, slit lamp biomicroscopy, and dilated ocular examination in the form of in-home survey by defined population-based sampling. The medical history was surveyed too. The data were analyzed based on the criteria of the World Health Organization. RESULTS: The general prevalence rates of low vision and blindness were 0.99% (95% CI: 0.70-1.28) and 0.39% (95% CI: 0.21-0.57) respectively. The prevalence rate of low vision in females was 1.45%, 2.23 times that of males (0.65%) (OR: 1.97, 95% CI: 1.00-3.95). The prevalence rate of low vision of rural residents was 1.76%, 2.89 times that of urban residents (0.61%) (OR: 2.93, 95% CI: 1.43-6.11). The prevalence rate of blindness in females was 0.64% and 0.37% in males. The prevalence rate of blindness of rural residents was 1.06%, 2.04 times that of the urban residents (0.52%) (OR: 3.77, 95% CI: 1.41-10.62). The 3 major causes of blindness were cataract (37.50%), glaucoma (29.20%), and high myopic macular degeneration (8.30%). The prevalence of blindness increased with age. CONCLUSION: The prevalence rates of low vision and blindness are higher in the rural areas. Cataract, glaucoma, and high myopic macular degeneration are the major causes of blindness. The prevalence of low vision and blindness are influenced by age, sex; area, health care level, educational level, and environmental factors.

Wang Y, Taylor JM. · Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, Michigan 48109-2029, USA. · Biometrics. · Pubmed #12495134 No free full text.

Abstract: Randomized clinical trials with rare primary endpoints or long duration times are costly. Because of this, there has been increasing interest in replacing the true endpoint with an earlier measured marker. However, surrogate markers must be appropriately validated. A quantitative measure for the proportion of treatment effect explained by the marker in a specific trial is a useful concept. Freedman, Graubard, and Schatzkin (1992, Statistics in Medicine 11, 167-178) suggested such a measure of surrogacy by the ratio of regression coefficients for the treatment indicator from two separate models with or without adjusting for the surrogate marker. However, it has been shown that this measure is very variable and there is no guarantee that the two models both fit. In this article, we propose alternative measures of the proportion explained that adapts an idea in Tsiatis, DeGruttola, and Wulfsohn (1995, Journal of the American Statistical Association 90, 27-37). The new measures require fewer assumptions in estimation and allow more flexibility in modeling. The estimates of these different measures are compared using data from an ophthalmology clinical trial and a series of simulation studies. The results suggest that the new measures are less variable.