Macular Degeneration: Xu X

Xu X, Li ZP. · Department of Ophthalmology, The First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China. · Zhonghua Yan Ke Za Zhi. · Pubmed #15840330 No free full text.

Abstract: The visual loss caused by fundus diseases such as age related macular degeneration and inherited retinal diseases is one of the toughest subjects in preventing blindness. The level of basic researches determines the progress of diagnosis and treatment for them. Although some fruits have been got these years in the fields of stem cell identification, transplantation and differentiation, local environment of survival cells and replacement of retinal pigment epithelium by iris pigment epithelium, many questions still remain to be elucidated about the regulation of gene expression and developmental environment. These answers will benefit the development of novel therapeutic approaches for refractory fundus dysfunctions finally.

Jiang H, Qu Y, Dang G, Zhang X, Yin N, Zhang Y, Bi H, Pan X, Xu X, Zhou F, Dai H. · Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, China. · Retina. · Pubmed #19491722 No free full text.

Abstract: PURPOSE: To investigate the effect of single nucleotide polymorphisms (SNPs) and haplotypes in the genes encoding age-related maculopathy susceptibility 2 (LOC387715/ARMS2) and high-temperature requirement A-1 (HTRA1) in a case-control study in a Chinese cohort of individuals with exudative age-related macular degeneration (AMD). METHODS: We genotyped 2 SNPs, namely, LOC387715 rs10490924 and HTRA1 rs11200638, in 159 exudative AMD patients and 140 age- and sex-matched control subjects. All the four possible haplotypes of these two SNPs were detected. Comparisons of the risk genotypes and risk or protective haplotypes across multiple populations were performed. RESULTS: Allelic or genotype association tests yielded significant results at P < 0.001. We observed that homozygous risk genotypes (TT in rs10490924 and AA in rs11200638) were more strongly associated with AMD than the heterozygous genotypes (GT in rs10490924 and geographic atrophy in rs11200638) for both SNPs. Comparisons of the odds ratios for genotypes revealed that there is ethnic disparity in AMD prevalence, even within the Chinese population. The haplotype TA, comprising both the SNPs, was identified as an at-risk factor and was significantly associated with AMD, whereas the protective haplotype GG was significantly overrepresented in the controls (P < 0.001). The frequency of the TA haplotype was relatively higher in the Chinese population than in the white population in both groups, whereas the frequency of the GG haplotype was relatively lower in the Chinese controls than in the white and Japanese controls. CONCLUSION: Both SNPs are significantly associated with exudative AMD in the Chinese cohort and seem to contribute equally to the disease status. A higher frequency of homozygous risk genotypes and risk haplotype and a lower frequency of protective haplotype in the Chinese may be the cause of higher prevalence of exudative AMD in the Chinese than in the whites.

SanGiovanni JP, Arking DE, Iyengar SK, Elashoff M, Clemons TE, Reed GF, Henning AK, Sivakumaran TA, Xu X, DeWan A, Agrón E, Rochtchina E, Sue CM, Wang JJ, Mitchell P, Hoh J, Francis PJ, Klein ML, Chew EY, Chakravarti A. · National Eye Institute (NEI)/National Institutes of Health (NIH), Bethesda, Maryland, United States of America. · PLoS One. · Pubmed #19434233 links to  free full text

Abstract: BACKGROUND: Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been reported in large prospective cohorts. METHODOLOGY/PRINICIPAL FINDINGS: We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease. In Stage I we resequenced the entire genome in 99 elderly AMD-free controls and 215 people with advanced AMD from the 12-year study. A consistent association with AMD in 14 of 17 SNPs characterizing the mtDNA T haplogroup emerged. Further analysis revealed these associations were driven entirely by the T2 haplogroup, and characterized by two variants in Complex I genes (A11812G of MT-ND4 and A14233G of MT-ND6). We genotyped T haplogroups in an independent sample of 490 cases and 61 controls from the same study (Stage II) and in 56 cases and 246 controls from the 10-year study (Stage III). People in the T2 haplogroup were approximately 2.5 times more likely to have advanced AMD than their peers (odds ratio [OR] = 2.54, 95%CI 1.36-4.80, P<or=0.004) after considering the totality of evidence. Findings persisted after considering the impact of AMD-associated variants A69S and Y402H (OR = 5.19, 95%CI 1.19-22.69, P<or=0.029). CONCLUSION: Loci defining the mtDNA T2 haplogroup and Complex I are reasonable targets for novel functional analyses and therapeutic research in AMD.

Pauleikhoff D, Scheider A, Wiedmann P, Gelisken F, Scholl HP, Roider I, Mohr A, Zlateva G, Xu X. · Augenabteilung am St. Franziskus-Hospital, Münster, Deutschland. · Ophthalmologe. · Pubmed #18709375 No free full text.

Abstract: BACKGROUND: Approximately 35,000 cases of neovascular age-related macular degeneration (AMD) occur annually in Germany. The neovascular form of AMD (NV-AMD) is responsible for severe vision loss associated with the disease in 90% of the cases. This study was conducted to assess the humanistic and economic burden of NV-AMD in the German population. METHODS: A cross-sectional, observational study of subject self-reported functional health, well-being, and disease burden among elderly subjects with (n=83) and without (n=93) NV-AMD in Germany was conducted. Patients participated in telephone surveys involving the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and also reported history of falls, fractures, and healthcare resource utilization. Furthermore, the healthcare utilization and unit costs for the NV-AMD patients were calculated. RESULTS: The mean age of NV-AMD patients was 77.2 years and 64% were female. NV-AMD patients reported significantly worse vision-related function and overall well-being than controls (adjusted mean scores: NEI-VFQ-25 overall scale: 51.3 vs 96.3; p<0.0001) and significantly more depression symptoms than controls (HADS depression: 6.2 vs. 2.7; p<0.0001). NV-AMD patients also reported that the need for assistance with daily activities was more than 10 times greater compared to controls (26.5% vs. 2.2%; p<0.0001) and the prevalence of falls was 3 times that of the control group (13.3% vs 4.3%; p=0.031). Annual NV-AMD costs per patient were <euro> 9871, 6 times that of elderly patients without NV-AMD (<euro> 1559). Of the NV-AMD costs one-half were direct non-medical-related costs (assistance of ADL or social benefit) and one-third were direct medical costs. CONCLUSIONS: NV-AMD is associated with decreased functional abilities and quality of life, which result in an increase in healthcare resource utilization. Consequently, costs were higher for NV-AMD patients compared to controls. These findings emphasize the need for new NV-AMD treatments that will prevent vision loss and progression to blindness, and lessen the ensuing economic burden. Sponsored by Pfizer Inc. New York, US.

Zhu Q, Ziemssen F, Henke-Fahle S, Tatar O, Szurman P, Aisenbrey S, Schneiderhan-Marra N, Xu X, Anonymous00470, Grisanti S. · Centre for Ophthalmology, Eberhard-Karls University, University Eye Hospital, Tübingen, Germany. · Ophthalmology. · Pubmed #18708261 No free full text.

Abstract: PURPOSE: To investigate the vitreous levels of bevacizumab and vascular endothelial growth factor-A (VEGF-A) after intravitreal injection of the drug in patients with choroidal neovascularization (CNV). DESIGN: Interventional case series. PARTICIPANTS: Eleven eyes of 11 patients with submacular hemorrhage and CNV due to age-related macular degeneration (n = 10) or angioid streaks (n = 1). METHODS: All patients were treatment naïve except for a single dose of intravitreal injection of bevacizumab (1.25 mg/50 muL dose) and subsequent vitrectomy after various intervals (1-101 days) because of active and progressive lesion. Intravitreal free bevacizumab and VEGF-A levels were measured using enzyme-linked immunosorbent assay and microsphere-based immunoassay, respectively. Vitreous VEGF-A isoforms were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. MAIN OUTCOME MEASURES: Intravitreal bevacizumab and VEGF-A levels were measured and pharmacokinetic parameters were calculated. RESULTS: Pharmacokinetics of intravitreal bevacizumab followed a 2-compartment model with initial and terminal half-lives of 0.5 and 6.7 days, respectively. Bevacizumab could be detected in all cases, ranging from 2.63 ng/ml to 165 microg/ml. The peak concentration was observed on the second day after intravitreal bevacizumab injection. Vitreous free VEGF-A levels ranged from 0.2 to 33.9 pg/ml and showed a negative correlation with the bevacizumab concentration (P<0.001; r = -0.955) and a positive correlation with time (P<0.001; r = 0.964). However, the percentage expression of VEGF-A(165) exhibited a positive correlation with the bevacizumab concentration (P = 0.032, r = 0.645) and a negative correlation with time (P = 0.007, r = -0.755). A time-dependent increase was found for the percentage expression of VEGF-A(189) (P = 0.023, r = 0.673). Neither bevacizumab- nor time-related alterations were found for VEGF-A(121). CONCLUSIONS: Based on pharmacokinetics, the interval of 6-7 weeks would be appropriate for efficacy, although clinical trials should guide dosing recommendations. Vitreous levels of free VEGF-A showed a negative correlation with the bevacizumab concentration, which confirmed the in vivo binding affinity of bevacizumab to VEGF-A. The analysis of the VEGF-A isoforms suggests differences of interaction between bevacizumab and individual VEGF-A isoforms.

Ruiz-Moreno JM, Coco RM, García-Arumí J, Xu X, Zlateva G. · University of Castilla La Mancha, Albacete, Spain. · Curr Med Res Opin. · Pubmed #18547463 No free full text.

Abstract: BACKGROUND: The burden of illness, including health resource utilization and costs associated with bilateral neovascular age-related macular degeneration (Nv-AMD), was assessed in Spain. PATIENTS AND METHODS: As part of an international prospective, case-controlled study, 89 Spanish patients with bilateral Nv-AMD were recruited by retina specialists and 96 Spanish control subjects were recruited by general practitioners and ophthalmologists. Physicians recorded clinical data and visual acuity (VA). In a subsequent telephone interview, Nv-AMD patients and controls completed the National Eye Institute Visual Function Questionnaire (NEI VFQ)-25, the EuroQol (EQ-5D), and the Hospital Anxiety and Depression Scale (HADS) questionnaire. Annual vision-related and non-vision-related medical costs and non-medical-related costs were calculated from study-specific questions. RESULTS: The mean age was 76.2 years for Nv-AMD patients and 61.9 years for control subjects. The adjusted mean (95% CI) NEI VFQ-25 summary score was 51.9 (48.5; 55.4) for Nv-AMD patients and 87.7 (85.5; 89.9) for control subjects (p<0.05). The summary score of Nv-AMD patients decreased significantly with VA declination. Mean direct vision-related medical and non-medical-related costs were significantly greater for Nv-AMD patients than the control subjects, whereas non-vision-related medical costs were similar between groups. The total mean annual resource utilization cost was euro5733 for Nv-AMD patients compared to euro1070 for control subjects (p<0.0001). CONCLUSIONS: Although the study design is subject to a number of limitations, patients with Nv-AMD in Spain have worse quality of life outcomes, greater depression, and higher healthcare costs as compared with similarly-aged individuals who are not affected by this disease.

Soubrane G, Zlateva G, Xu X, Buggage R, Kosa M. · Département d'Ophtalmologie, Université Paris XII Créteil, Centre Hospitalier Intercommunal de Créteil, France. · J Fr Ophtalmol. · Pubmed #18401314 links to  free full text

Abstract: OBJECTIVE: To assess the impact of bilateral neovascular age-related macula degeneration (NV-AMD) on function and health resource utilization (HRU) in France. PATIENTS AND METHODS: Cross-sectional study including 401 NV-AMD patients and 471 controls conducted in five countries in 2006. In both groups, demographic and clinical data were collected and the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQoL (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and questionnaires on HRU were administered. RESULTS: Eighty-seven NV-AMD patients and 92 controls were recruited in France. The mean age of the NV-AMD patients was 79 (range, 65-95), and 64% were female. After adjusting for age, gender, and co-morbidities, compared to controls, NV-AMD patients reported substantially worse vision-related quality of life on the NEI-VFQ (adjusted mean, 44.4 [36.2-52.7] versus 91.8 [86.2-97.5], p<0.0001). HADS anxiety and depression scores were significantly worse in NV-AMD patients (anxiety score, 8.5 [6.3-10.8] versus 5.1 [3.5-6.7] p=0.0005; depression score: 7.1 [5.1-9.1] versus 2.9 [1.5-4.4] p<0.0001). Per patient yearly cost analysis showed significantly higher direct medical costs: 3396 euro versus 85 euro (p<0.0001), and indirect nonmedical-related costs (mainly for assistance with activities of daily living): 2985 euro versus 494 euro (p=0.014). CONCLUSIONS: NV-AMD patients in France reported substantially worse QoL and more anxiety and depression symptoms. The functional impact of blindness led to significantly higher health resource utilization in the AMD patients, resulting in higher total health costs compared to a similarly aged control group.

Leung KW, Liu M, Xu X, Seiler MJ, Barnstable CJ, Tombran-Tink J. · Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18326752 links to  free full text

Abstract: PURPOSE: Zinc is an essential cofactor for normal cell function. Altered expression and function of zinc transporters may contribute to the pathogenesis of neurodegenerative disorders including macular degeneration. The expression and regulation of zinc transporters in the RPE and the toxicity of zinc to these cells were examined. METHODS: Zinc transporters were identified in a human RPE cell line, ARPE19, using a 28K human array, and their expression was confirmed by PCR, immunocytochemistry, and Western blot analysis in primary human RPE cultures and ARPE19. Zinc toxicity to ARPE19 was determined using monotetrazolium, propidium iodide, and TUNEL assays, and Zn(2+) uptake was visualized with Zinquin ethyl ester. The effect of various growth factors on zinc transporter expression also was examined. RESULTS: Transcripts for 20 of 23 zinc transporters are expressed in fetal human RPE, 16 of 23 in adult human RPE, and 21 of 23 in ARPE19. Zn transporter proteins were also detected in ARPE19. ZnT5 expression was not observed, whereas ZnT6, ZIP1, and ZIP13 were the most abundantly expressed in all RPE samples. The addition of low concentrations of Zn(2+) to cultures resulted in a dose-dependent increase in intracellular Zn(2+) content in ARPE19, and >30 nM Zn(2+) induced necrosis with an LC(50) of 117.4 nM. Brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor (GDNF), and pigment epithelial-derived neurotrophic factor (PEDF) increased ZIP2 expression, GDNF and PEDF increased ZnT2 expression, and PEDF increased ZnT3 and ZnT8 expression. These neurotrophic factors also promoted Zn(2+) uptake in the RPE. CONCLUSIONS: The array of zinc transporters expressed by the RPE may play a key role in zinc homeostasis in the retina and in ocular health and diseases.

Wang N, Xu X, Zou H, Zhu J, Wang W, Ho PC. · Department of Ophthalmology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China. · Ophthalmologica. · Pubmed #18097178 No free full text.

Abstract: Diabetic macular edema (DME) is the major cause of vision loss in patients with diabetic retinopathy (DR). The purpose of this study was to assess the prevalence of DR and DME in a community in China and to analyze the characteristics of their optical coherence tomography (OCT) images. This study was an incidence survey based on data from 108,132 residents living in the Beixinjing District, Shanghai, China. Patients with DME came from the local health network. OCT was performed in 151 eyes of 100 type 2 diabetes patients with DR and 102 eyes of normal control subjects. Totally 795 cases were examined, and 215 of them were diagnosed to have DR. The average thickness of the macular fovea was 195.56 microm in 151 eyes from 100 random samples. Forty-six eyes had macular thickening. The statistical analysis showed that there was a positive correlation between the thickness of the macular fovea and -log of best-corrected visual acuity (r = 0.2869, p = 0.0004) as well as the severity of DR (p = 0.0003). However, there was no statistical significance between DME and posterior vitreous detachment. The images of OCT in DME included 3 types. Best-corrected visual acuity moderately correlated with retinal thickness. The macular thickness correlated with the severity of DR but not with posterior vitreous detachment.

Cruess AF, Zlateva G, Xu X, Soubrane G, Pauleikhoff D, Lotery A, Mones J, Buggage R, Schaefer C, Knight T, Goss TF. · Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada. <> · Pharmacoeconomics. · Pubmed #18088159 No free full text.

Abstract: BACKGROUND: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. OBJECTIVE: To document the economic burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a societal perspective. STUDY DESIGN, SETTING AND PARTICIPANTS: A cross-sectional, observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD subjects in Canada, France, Germany, Spain and the UK. Physicians' records and subjects' standardized telephone interviews were used to record medical resource utilization, assistance with daily living and social benefits. Annual bilateral NV-AMD-related socioeconomic costs were calculated in euro, year 2005 values. MAIN OUTCOME MEASURES: Societal costs including direct vision-related medical costs (e.g. treatment of AMD and vision-related equipment), direct non-vision-related medical costs (e.g. medications) and direct non-medical-related costs (e.g. home healthcare and social services) were the main outcome measures. RESULTS: The demographic profile of NV-AMD patients was similar across countries; however, co-morbid condition profiles varied. NV-AMD patients reported substantial health-related problems and associated health resource utilization (HRU). In the previous 12 months, 12-22% of patients fell, and half of these patients required medical treatments. More than 20% (range 21-59%) of patients were prescribed vision-enhancing equipment. More than half of the patients (54-81%) were living with a spouse or family member and 19-41% reported receiving assistance for activities of daily living.The average annual societal cost per bilateral NV-AMD patient treated was estimated to be euro 7879 in Canada, euro 7349 in France, euro 12 445 in Germany, euro 5732 in Spain and euro 5300 in the UK, and direct vision-related medical costs accounted for 23-63% of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for <1 year, with an average length of 5 months; there were no statistically significant differences in total annual costs per patient between these patients and those who were diagnosed with bilateral disease for > or =1 year. Estimated annual societal costs of bilateral NV-AMD patients in these countries ranged from euro 268 to euro 1311 million. Estimated annual societal costs of all NV-AMD patients in these countries ranged from euro 671 to euro 3278 million. CONCLUSIONS: Bilateral NV-AMD imposes significant functional impairment on patients, leading to increased HRU and a high societal cost burden. Differences in national healthcare systems and NV-AMD treatment patterns were reflected in the wide variation of NV-AMD costs across the five surveyed countries. Even though the prevalence rates and per-patient costs varied by country, the societal costs of NV-AMD patients were substantial in each country. Earlier intervention with effective therapies is expected to reduce disease burden and disability associated with NV-AMD and, thus, decrease the overall societal cost.

Cruess A, Zlateva G, Xu X, Rochon S. · Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, NS. · Can J Ophthalmol. · Pubmed #18026200 links to  free full text

Abstract: BACKGROUND: Age-related macular degeneration (AMD) is a retinal disease affecting more than 2 million Canadians over the age of 50. The neovascular form of AMD is responsible for 90% of severe vision loss associated with the disease. This study was conducted to assess the burden of neovascular AMD in the Canadian population. METHODS: A cross-sectional, observational study was conducted of self-reported functional health, well-being, and disease burden among elderly subjects in Canada with (n = 67) and without (n = 99) neovascular AMD. Subjects completed telephone surveys of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol questionnaire (EQ-5D), and the Hospital Anxiety and Depression Scale (HADS). Subjects also reported their history of falls and fractures and annual health care resource utilization. RESULTS: Subjects with neovascular AMD reported significantly worse vision-related functioning and overall well-being than controls (adjusted mean scores on the NEI-VFQ-25: 48.0 vs. 87.5; p < 0.0001) and significantly more depression symptoms than controls (HADS depression: 5.8 vs. 4.3; p = 0.037). Subjects with neovascular AMD also reported more than twice the need for assistance with daily activities compared with controls (19.4% vs. 9.1%; p = 0.013) and a nearly 3 times higher fall rate than the control group (22.4% vs. 8.1%; p = 0.014). The annual neovascular AMD cost per patient was Can dollars 11,334, which is over 8 times that of elderly subjects without neovascular AMD (Can dollars 1,412). Over half of the neovascular AMD costs were direct medical costs. INTERPRETATION: Neovascular AMD is associated with significant limitation in functional abilities and quality of life, resulting in increased health care resource utilization and high patient support costs. These findings emphasize the need for new treatments for neovascular AMD that will prevent vision loss and progression to blindness in order to lessen the ensuing economic burden.

Soubrane G, Cruess A, Lotery A, Pauleikhoff D, Monès J, Xu X, Zlateva G, Buggage R, Conlon J, Goss TF. · Department of Ophthalmology, University Paris XII, Centre Hospitalier Intercommunal de Créteil, 40 Avenue de Verdun, Créteil, France. · Arch Ophthalmol. · Pubmed #17846366 links to  free full text

Abstract: OBJECTIVE: To describe the burden of bilateral neovascular age-related macular degeneration (NV-AMD) on patient-reported functioning and health resource utilization. METHODS: A cross-sectional study of 401 patients with bilateral NV-AMD and 471 elderly control subjects without AMD was conducted in 5 countries. Subjects completed a telephone survey, including the National Eye Institute 25-Item Visual Function Questionnaire, the EuroQol instrument, the Hospital Anxiety and Depression Scale, and history of falls, fractures, and health care resource utilization. RESULTS: The mean age for patients with NV-AMD was 78.1 years, and 65% were women. The patients reported 45% worse vision-related functioning, 13% worse overall well-being, and 30% more anxiety and 42% more depression symptoms than controls after adjusting for covariates (all, P < .001). The effect of NV-AMD was also observed as a doubled fall rate (16% vs 8% [P < .001]) and a quadrupled need for assistance with daily activities (29% vs 7% [P < .001]) in the patients compared with controls. CONCLUSIONS: The evidence of extensive decline in quality of life and increased need of daily living assistance for patients with NV-AMD compared with a control population substantiates the need for new treatments that prevent vision loss and progression to blindness.

Lotery A, Xu X, Zlatava G, Loftus J. · University of Southampton, Southampton Eye Unit, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. · Br J Ophthalmol. · Pubmed #17504847 No free full text.

Abstract: BACKGROUND/AIMS: Quantitative data regarding the impact of neovascular age-related macular degeneration (NV-AMD) on individuals and society is a prerequisite for rational decision-making processes when evaluating alternative treatments for the disease. METHODS: 75 bilateral NV-AMD (patients) and 91 elderly non-AMD (controls) subjects forming the UK cohort of an international cross-sectional, observational study were independently analysed. Subjects completed a telephone survey including the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), history of falls and health resource utilisation. RESULTS: Patients with NV-AMD reported substantially worse vision-related functioning and overall well-being, including higher depression scores, than controls after adjusting for age, gender and co-morbidities (adjusted mean scores: NEI-VFQ-25 overall 52.7 vs 90.7, p<0.0001; EQ-5D 0.67 vs 0.77, p = 0.0273; HADS depression 6.8 vs 4.0, p = 0.0026). Significantly more patients reported a need for assistance with daily activities compared with controls (25.3% vs 6.6%, p = 0.003). Total annual healthcare utilisation costs were more than sevenfold higher for patients with AMD compared with controls ( pound 3,823.89 vs pound 517.05, respectively; p<0.0001) CONCLUSIONS: Patients with NV-AMD show a significant decline in quality of life and increased need for daily living assistance compared to a control population without AMD. With the availability of effective new therapies there is a need for improved early access to treatment.

Zou Y, Xu X, Chiou GC. · Institute of Ocular Pharmacology, Medical Pharmacology & Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843, USA. · J Ocul Pharmacol Ther. · Pubmed #16503771 No free full text.

Abstract: PURPOSE: The aim of this study was to investigate the effect of interleukin-1 blockers, CK112 and CK116, on laser-induced experimental choroidal neovascularization (CNV) in rat models in vivo and endothelial cell proliferation in vitro. METHODS: Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch's membrane. CK112, CK116, and prednisolone were given once-daily through intraperitoneal (i.p.) injection after laser treatment for 4 weeks. The development of CNV was determined by fluorescein angiography performed on weeks 2 and 4. Human umbilical vein endothelial cells (HUVEC) were tested with proliferation assay with CK112, CK116, and prednisolone at different concentrations. RESULTS: The intensity of fluorescein leakage from the photocoagulated lesions decreased significantly, compared to the control group (treated with dimethyl sulfoxide [DMSO] only), following CK112, CK116, and prednisolone treatment. Four (4) weeks after administration, CK112, at 10 mg/kg and 30 mg/kg, inhibited CNV development to 75% and 77% of the control group, respectively (P < 0.01). Both CK116, 10 mg/kg, and prednisolone, 5 mg/kg, inhibited the CNV development to 85% of the control group (P < 0.05). All three compounds interfered with the endothelial cell proliferation significantly. The reduction of the endothelial cells was 50.5% (P < 0.01), 28.5% (P < 0.05), and 23.1% (P < 0.05), respectively, in 500 microg/mL, 300 microg/mL, and 100 microg/mL of the CK112-treated group. CK116 inhibited the cell proliferation significantly to 77.2% of the control group at 500 microg/mL (P < 0.05). CONCLUSIONS: CK112 and CK116 inhibited the development of CNV in the rat model and interfered with vascular endothelial cell proliferation in vitro. Our results suggest that CK112 and CK116 may be good candidates to inhibit ocular neovascularization related to age-related macular degeneration (ARMD).

Zou HD, Zhang X, Xu X, Wang FH, Zhang SJ. · Department of Ophthalmology, First People's Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200080, China. · Zhonghua Yan Ke Za Zhi. · Pubmed #15774107 No free full text.

Abstract: OBJECTIVE: To investigate the prevalence of age-related maculopathy (AMD) in Shanghai residents older than 50 years. METHODS: 1023 individuals were examined in the years 2002 and 2003 for clinical and subjective signs of dry and exudative AMD. A interview concerning clinical symptoms of AMD as also a complete eye exam was performed. Non-mydriatic retinoscopy was done by use of a direct opthalmoscopy. Fundus photography was used to confirm and document the diagnosis. The diagnosis of both forms of AMD was made according to the criteria of the Sub-society of Fundus Disease, Chinese Ophthalmological Society. RESULTS: 15.5% of the included population had AMD and 19 of them were exudative AMD. The prevalences of AMD in the age groups of 50-59, 60-69, 70-79 and more than 80 were identified as 5.7%, 13.5%, 20.2% and 23.5%, respectively (chi(2) = 27.97, P < 0.01). No statistical differences were found concerning atrophic and exudative AMD related to gender, education, daily focus time, smoking, alcohol consumption and systematic diseases. In the AMD patients, 5.1% and 36.2% of the eyes were identified as blind or with low vision. In exudative AMD patients, 23.3% and 63.3% of the eyes were identified as blind or with low vision. The visual acuity of eyes with exudative AMD was significantly lower than the visual acuity of atrophic AMD eyes. (chi(2) = 15.4, P < 0.01). CONCLUSIONS: The prevalence of AMD is high, and increasing with aging. The AMD, especially the exudative AMD, leads to severe visual impairment.

Xu X, Quiambao AB, Roveri L, Pardue MT, Marx JL, Röhlich P, Peachey NS, Al-Ubaidi MR. · Research Service (151), Hines VA Hospital, Hines, Illinois 60141, USA. · Exp Neurol. · Pubmed #10785460 No free full text.

Abstract: Although transgenic expression of oncogenes typically leads to tumorigenesis, oncogene expression directed to the rod photoreceptors leads to cell death without tumor formation. To evaluate the cellular and functional changes induced in cone photoreceptors by an oncogene, the Mas1 protooncogene was targeted to the cones of transgenic mice by the human red/green opsin promoter. Mas1 was chosen because of its exclusive expression in the nervous system and its homology to opsin. The overall histologic appearance of the transgenic retina was normal and retinal tumors were never observed. While rod-mediated electroretinograms were normal in all respects, cone-mediated responses were diminished in direct relationship to the level of transgene expression as determined by Northern blot analysis. Responses of UV- and green-sensitive cones were reduced equivalently, and Northern analysis and immunocytochemistry indicated that cone photoreceptor densities were markedly diminished throughout transgenic retinas. These results indicate that oncogene expression in cones induces cell death without tumor formation and support the possibility that aberrant oncogene expression may underlie some forms of hereditary retinal diseases. The Mas1 transgenic mice may be useful in understanding the cone photoreceptor degeneration that occurs in cone dystrophies and age-related macular degeneration and in evaluating potential therapies for these disorders.