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Members of the highly conserved homeobox (HOX) gene family encode transcription factors that confer cellular and tissue identities along the antero-posterior axis of mice and humans. We have identified a founder homozygous missense mutation in HOXB1 in two families from a conservative German American population. The resulting phenotype includes bilateral facial palsy, hearing loss, and strabismus and correlates extensively with the previously reported Hoxb1(-/-) mouse phenotype. The missense variant is predicted to result in the substitution of a cysteine for an arginine at amino acid residue 207 (Arg207Cys), which corresponds to the highly conserved Arg5 of the homeodomain. Arg5 interacts with thymine in the minor groove of DNA through hydrogen bonding and electrostatic attraction. Molecular modeling and an in vitro DNA-protein binding assay predict that the mutation would disrupt these interactions, destabilize the HOXB1:PBX1:DNA complex, and alter HOXB1 transcriptional activity.

The extent of damage following spinal cord injury (SCI) can be reduced by various neuroprotective regimens that include maintaining levels of cyclic adenosine monophosphate (cyclic AMP), via administration of the phosphodiesterase 4 (PDE4) inhibitor Rolipram. The current study sought to determine the optimal neuroprotective dose, route and therapeutic window for Rolipram following contusive SCI in rat as well as its prominent PDE target and putative mechanism of protection. Rolipram or vehicle control (10% ethanol) was given subcutaneously (s.c.) daily for 2 wk post-injury (PI) after which the preservation of oligodendrocytes, neurons and central myelinated axons was stereologically assessed. Doses of 0.1 mg/kg to 1.0 mg/kg (given at 1 h PI) increased neuronal survival; 0.5 mg to 1.0 mg/kg protected oligodendrocytes and 1.0 mg/kg produced optimal preservation of central myelinated axons. Ethanol also demonstrated significant neuronal and oligo-protection; though the preservation provided was significantly less than Rolipram. Subsequent use of this optimal Rolipram dose, 1.0 mg/kg, via different routes (i.v., s.c. or oral, 1 h PI), demonstrated that i.v. administration produced the most significant and consistent cyto- and axo- protection, although all routes were effective. Examination of the therapeutic window for i.v. Rolipram (1.0 mg/kg), when initiated between 1 and 48 h after SCI, revealed maximal neuroprotection at 2 h post-SCI, although the protective efficacy of Rolipram could still be observed when administration was delayed for up to 48 h PI. Importantly, use of the optimal Rolipram regimen significantly improved locomotor function after SCI as measured by the BBB score. Lastly we show SCI-induced changes in PDE4A, B and D expression and phosphorylation as well as cytokine expression and immune cell infiltration. We demonstrate that Rolipram abrogates SCI-induced PDE4B1 and PDE4A5 production, PDE4A5 phosphorylation, MCP-1 expression and immune cell infiltration, while preventing post-injury reductions in IL-10. This work supports the use of Rolipram as an acute neuroprotectant following SCI and defines an optimal administration protocol and target for its therapeutic application.

Background: Walking is a preferred, prevalent and recommended activity for aging populations and is influenced by the neighborhood built environment. To study this influence it is necessary to differentiate whether walking occurs within or outside of the neighborhood. The Neighborhood Physical Activity Questionnaire (NPAQ) collects information on setting-specific physical activity, including walking, inside and outside one's neighborhood. While the NPAQ has shown to be a reliable measure in adults, its reliability in older adults is unknown. Additionally its validity and the influence of type of neighborhood on reliability and validity have yet to be explored. Methods. The NPAQ walking component was adapted for Chinese speaking elders (NWQ-CS). Ninety-six Chinese elders, stratified by social economic status and neighborhood walkability, wore an accelerometer and completed a log of walks for 7 days. Following the collection of valid data the NWQ-CS was interviewer-administered. Fourteen to 20 days (average of 17 days) later the NWQ-CS was re-administered. Test-retest reliability and validity of the NWQ-CS were assessed. Results: Reliability and validity estimates did not differ with type of neighborhood. NWQ-CS measures of walking showed moderate to excellent reliability. Reliability was generally higher for estimates of weekly frequency than minutes of walking. Total weekly minutes of walking were moderately related to all accelerometry measures. Moderate-to-strong associations were found between the NWQ-CS and log-of-walks variables. The NWQ-CS yielded statistically significantly lower mean values of total walking, weekly minutes of walking for transportation and weekly frequency of walking for transportation outside the neighborhood than the log-of-walks. Conclusions: The NWQ-CS showed measurement invariance across types of neighborhoods. It is a valid measure of walking for recreation and frequency of walking for transport. However, it may systematically underestimate the duration of walking for transport in samples that engage in high levels of this type of walking. © 2011 Ester Cerin et al.; licensee BioMed Central Ltd., published_or_final_version

To evaluate retinal functional changes by multifocal electroretinography (mfERG) after photodynamic therapy with half-dose verteporfin in patients with acute central serous chorioretinopathy. Thirty-four patients with acute central serous chorioretinopathy were randomly assigned to receive photodynamic therapy with half-dose verteporfin (n = 24) or placebo (n = 10). Multifocal electroretinography was performed at baseline and at 12 months, and serial changes in response amplitudes were expressed as amplitude ratios. The mfERG amplitude ratios, best-corrected visual acuity, and optical coherence tomography central foveal thickness were compared between the verteporfin and placebo groups. Correlation analysis between the mfERG response amplitude ratios and the best-corrected visual acuity changes and reduction in optical coherence tomography central foveal thickness were also performed. At 12 months, the mean visual improvement was 1.8 line and 0.1 line for the verteporfin and placebo groups, respectively (P = 0.003). Eyes in the verteporfin group had significantly lower central foveal thickness (P = 0.028) and higher P1 mfERG response ratios for Rings 1 and 2 at 12 months compared with the eyes in the placebo group (P = 0.030 and P = 0.018, respectively). Significant correlations between mfERG N1 and P1 amplitude ratios at the central rings were observed with both changes in best-corrected visual acuity and reductions in optical coherence tomography central foveal thickness (P < 0.05). Multifocal electroretinography demonstrated higher retinal function at the central macula objectively in central serous chorioretinopathy patients treated with half-dose verteporfin photodynamic therapy. Changes in best-corrected visual acuity and optical coherence tomography central foveal thickness findings also correlated with mfERG responses of the central macula, confirming the usefulness of mfERG as an objective investigation to evaluate the functional changes in central serous chorioretinopathy.

Objective: To examine dose-response associations between depressive symptoms and suicide and modification effects of sex, age and health status in older Chinese. Methods: We used the Chinese version of the 15-item Geriatric Depression Scale (GDS) to measure depressive symptoms (GDS score ≥ 8) and Cox regression to examine association with suicide mortality in a population-based cohort of 55,946 individuals, aged 65 years or above, enrolled from July 1998 to December 2000 at one of 18 Elderly Health Centres of Hong Kong Department of Health. The cohort was followed up for suicide mortality till 31 March 2009 (mean follow-up 8.7 years). Results: Depressive symptoms were associated with suicide in men [hazard ratio (HR) 2.03, 95% confidence interval (CI) 0.96-4.29] and women (HR = 2.36, 95% CI 1.31-4.24) after adjusting for age, education, monthly expenditure, smoking, alcohol drinking, physical activity, body mass index, health status, and self-rated health. There was no threshold for GDS score and suicide in either sex. Age, sex and health status did not modify the association. Conclusions: Depressive symptoms predict higher suicide risk in older Chinese in a dose-response pattern. These associations were not attenuated by adjustment for health status, suggesting that depressive symptoms in older people are likely to be an independent causal factor for suicide. The GDS score showed no threshold in predicting suicide risk, suggesting that older people with low GDS scores deserve further attention and those with very high scores need urgent intervention. © 2011 The Author(s)., published_or_final_version, Springer Open Choice, 21 Feb 2012

Free radical copolymerization in high-pressure autoclave reactors is studied by developing a mathematical model. Kinetic mechanisms to describe the polymerization rate, molecular weight averages, branching frequencies, as well as copolymer composition are presented. Two phase kinetics due to polymer-monomer solubilities in the reaction mixture are taken into account. Gel formation from cross-linking reactions is also analyzed. A mixing model is developed to represent the stirring effect inside the reactor. The mathematical model is implemented as a computer program to simulate commercial autoclave reactors. PID control equations are used to maintain operation at the unstable steady state. A sensitivity study is performed on the mixing model parameters and on some of the kinetic parameters and the model is compared to rate data from commercial reactors.

AIM—To determine the pattern of rhodopsin mutations in Chinese retinitis pigmentosa (RP) patients. METHODS—The rhodopsin gene was examined in 101 RP patients and 190 controls from Hong Kong. RESULTS—Three coding changes were identified: Pro347Leu, Ala299Ser, and 5211delC. Each protein sequence alteration was found in one patient. Ala299Ser also existed in two controls. CONCLUSION—The C-terminal nonsense mutation may cause mis-sorting of rhodopsin protein. The finding of controls with Ala299Ser suggests this is only the third missense alteration reported that does not cause RP. The expected frequency of rhodopsin mutations in RP is

Background: studies have suggested that neuropsychiatric (NP) symptoms influence the development of dementia among older adults. But, the results are inconsistent and there is limited information about NP symptoms in population-based samples. Objective: to explore the association between NP symptoms and risk of cognitive decline in Chinese older persons residing in the community. Design: prospective study. Setting: community sample. Subjects: a total of 321 community-dwelling Chinese older persons aged 60 or over with mild cognitive impairment participated in the study. Methods: at baseline, each subject was assessed with Clinical Dementia Rating (CDR), Mini-Mental State Examination, list learning and delayed recall, and Category Verbal Fluency Test. Severity of NP symptoms was evaluated with Neuropsychiatric Inventory (NPI). Global cognitive status at the end of 2-year study period was determined by CDR. Results: at baseline, 40.5% of participants exhibited one or more NP symptoms (NPI total score ≥1). Night-time behaviours (22.1%), depression (16.8%), apathy (14.0%) and anxiety (12.8%) were the most common NP symptoms. At the end of 2-year follow-up, 27.5% of participants with depression at baseline developed dementia, compared with 14.8% of those without depression (χ 2 = 4.90, P= 0.03). Aberrant motor behaviour was also significantly associated with deterioration in cognition (χ 2 = 5.84, P= 0.02), although it was an infrequent occurrence. On logistic regression analysis, only depression at baseline was shown to be a risk factor for progression to dementia (OR= 2.40, 95% CI 1.05–5.46, P= 0.04). Conclusion: depression in non-demented older persons may represent an independent dimension reflecting early neuronal degeneration. Further studies should be conducted to assess whether effective management of NP symptoms exerts beneficial effects on cognitive function.

The effects of the built environment on walking in seniors have not been studied in an Asian context. To examine these effects, valid and reliable measures are needed. The aim of this study was to develop and validate a questionnaire of perceived neighborhood characteristics related to walking appropriate for Chinese seniors (Neighborhood Environment Walkability Scale for Chinese Seniors, NEWS-CS). It was based on the Neighborhood Environment Walkability Scale - Abbreviated (NEWS-A), a validated measure of perceived built environment developed in the USA for adults. A secondary study aim was to establish the generalizability of the NEWS-A to an Asian high-density urban context and a different age group.Methods: A multidisciplinary panel of experts adapted the original NEWS-A to reflect the built environment of Hong Kong and needs of seniors. The translated instrument was pre-tested on a sample of 50 Chinese-speaking senior residents (65+ years). The final version of the NEWS-CS was interviewer-administered to 484 seniors residing in four selected Hong Kong districts varying in walkability and socio-economic status. Ninety-two participants completed the questionnaire on two separate occasions, 2-3 weeks apart. Test-rest reliability indices were estimated for each item and subscale of the NEWS-CS. Confirmatory factor analysis was used to develop the measurement model of the NEWS-CS and cross-validate that of the NEWS-A.Results: The final version of the NEWS-CS consisted of 14 subscales and four single items (76 items). Test-retest reliability was moderate to good (ICC > 50 or % agreement > 60) except for four items measuring distance to destinations. The originally-proposed measurement models of the NEWS-A and NEWS-CS required 2-3 theoretically-justifiable modifications to fit the data well.Conclusions: The NEWS-CS possesses sufficient levels of reliability and factorial validity to be used for measuring perceived neighborhood environment in Chinese seniors. Further work is needed to assess its construct validity and generalizability to other Asian locations. In general, the measurement model of the original NEWS-A was generalizable to this study context, supporting the feasibility of cross-country and age-group comparisons of the effect of the neighborhood environment on walking using the NEWS-A as a tool to measure the perceived built environment. © 2010 Cerin et al; licensee BioMed Central Ltd., published_or_final_version

To characterize and grade the spectrum of foveal hypoplasia based on different stages of arrested development of the fovea. Grading was performed using morphologic findings obtained by ultra high-resolution spectral-domain optical coherence tomography. Best-corrected visual acuity (BCVA) was calculated for different grades.Observational case series.Sixty-nine patients with foveal hypoplasia (albinism, n = 34; PAX6 mutations, n = 10; isolated cases, n = 14; achromatopsia, n = 11) and 65 control subjects were examined.A 7×7-mm retinal area was sampled using a 3-dimensional scanning protocol (743×75, A scans×B scans) with ultra high-resolution spectral-domain optical coherence tomography (SOCT Copernicus HR; 3-μm axial resolution). Gross morphologic abnormalities were documented. B-scans at the fovea were segmented using a longitudinal reflectivity profile. Logarithm of the minimum angle of resolution BCVA was obtained.Grading was based on presence or absence of foveal pit and widening of the outer nuclear layer (ONL) and outer segment (OS) at the fovea. Quantitative measurements were obtained for comparing atypical foveal hypoplasia in achromatopsia. Best-corrected visual acuity was compared with the grade of foveal hypoplasia.Four grades of foveal hypoplasia were distinguished: grade 1, shallow foveal pit, presence of ONL widening, presence of OS lengthening; grade 2, grade 1 but absence of foveal pit; grade 3, grade 2 but absence of OS lengthening; grade 4, grade 3 but absence of ONL widening. There was significant difference in visual acuity (VA) associated with each grade (P0.0001). Grade 1 was associated with the best VA (median VA, 0.2), whereas grades 2, 3, and 4 were associated with progressively poorer VA with a median VA of 0.44, 0.60, and 0.78, respectively. The atypical features seen with foveal hypoplasia associated with achromatopsia were characterized by decreased retinal and ONL thickness and deeper foveal depth.A structural grading system for foveal hypoplasia was developed based on the stage at which foveal development was arrested, which helps to provide a prognostic indicator for VA and is applicable in a range of disorders associated with foveal hypoplasia. Atypical foveal hypoplasia in achromatopsia shows different characteristics.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objectives We reported the interim findings of a randomized controlled trial (RCT) to examine the effects of a mind body physical exercise (Tai Chi) on cognitive function in Chinese subjects at risk of cognitive decline. Subjects 389 Chinese older persons with either a Clinical Dementia Rating (CDR 0.5) or amnestic-MCI participated in an exercise program. The exercise intervention lasted for 1 year; 171 subjects were trained with 24 forms simplified Tai Chi (Intervention, I) and 218 were trained with stretching and toning exercise (Control, C). The exercise comprised of advised exercise sessions of at least three times per week. Results At 5th months (2 months after completion of training), both I and C subjects showed an improvement in global cognitive function, delayed recall and subjective cognitive complaints (paired t-tests, p

To evaluate the outcome of verteporfin photodynamic therapy (PDT) with or without intravitreal triamcinolone acetonide (IVTA) for the treatment of symptomatic polypoidal choroidal vasculopathy (PCV).Retrospective analysis of PCV patients who underwent PDT with or without IVTA with follow-up of 2 or more years. Changes in best-corrected visual acuity (BCVA), proportion of eyes with moderate visual loss (3 or more lines), and complications were compared between patients with or without IVTA.Twenty-seven eyes of 27 patients were analyzed, with 12 eyes treated by PDT monotherapy and 15 eyes treated by combined PDT with IVTA. The baseline characteristics of both groups were similar. At 1 year, the mean logMAR BCVA for the PDT monotherapy group improved from 0.74 to 0.58 (P = 0.011), whereas the combined PDT and IVTA group improved from 0.84 to 0.74 (P = 0.17). At 2 years, the mean logMAR BCVA for the monotherapy and combined treatment groups were 0.62 and 0.84, respectively, and the changes compared with baseline were not statistically significant. No significant difference was found in the mean logMAR BCVA, the mean line of visual changes, and the mean number of PDT treatments between the 2 groups at 1 and 2 years. One (8.3%) and 4 (26.7%) eyes in the monotherapy and the combined groups lost 3 or more lines at 2 years, respectively. Patients who had combined PDT with IVTA were more likely to develop cataract requiring surgery and ocular hypertension (P = 0.043 and 0.046, respectively).PDT reduced the risks of visual loss in patients with symptomatic PCV in the short term but the effect might not be sustained after 1 year. The adjunctive use of IVTA during PDT did not appear to result in additional benefit for treating PCV.

The HOXA1-related syndromes result from autosomal-recessive truncating mutations in the homeobox transcription factor, HOXA1. Limited horizontal gaze and sensorineural deafness are the most common features; affected individuals can also have facial weakness, mental retardation, autism, motor disabilities, central hypoventilation, carotid artery, and/or conotruncal heart defects. Mobius syndrome is also phenotypically heterogeneous, with minimal diagnostic criteria of nonprogressive facial weakness and impaired ocular abduction; mental retardation, autism, motor disabilities, additional eye movements restrictions, hearing loss, hypoventilation, and craniofacial, lingual, and limb abnormalities also occur. We asked, given the phenotypic overlap between these syndromes and the variable expressivity of both disorders, whether individuals with Mobius syndrome might harbor mutations in HOXA1. Our results suggest that HOXA1 mutations are not a common cause of sporadic Mobius syndrome in the general population.

A 45-year-old woman, originally scheduled for cataract surgery in the left eye, was referred for management of a globe perforation noticed after the retrobulbar injection of an anesthetic solution. There was a moderate degree of vitreous hemorrhage, and initial visual acuity was hand movement. A submacular blood clot of about 4-disc diameter was detected when the vitreous hemorrhage gradually cleared. One week after the incident, combined phacoemulsification, intraocular lens implantation, pars plana vitrectomy, and submacular clot removal using tissue plasminogen activator (tPA) as an adjunct were performed. Recovery was uneventful. At the last follow-up 6 months after surgery, best corrected visual acuity was 20/30.

A 73-year-old woman presented to our institution with an abnormal shadow on chest radiography. The patient was a nonsmoker and enjoyed good past health. There were no constitutional symptoms. She was completely asymptomatic during exercise and at rest. An ECG (Figure 1) showed normal sinus rhythm. A posteroanterior view of the chest radiograph (Figure 2) showed a well-circumscribed roundish mass at the left heart border. A lateral chest radiograph (Figure 3) suggested a more anterior-located abnormality. Figure 1. ECG showing normal sinus rhythm with normal cardiac axis. Figure 2. Posteroanterior view of chest radiograph showing a mass at the left heart border. Figure 3. Lateral chest radiograph showing an anteriorly located mass. An echocardiogram was performed to delineate the relationship of the mass and the adjacent cardiac structure. It showed a large vascular structure anterior to the main pulmonary artery and continuous …

Purpose To assess the long-term role of bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in inflammatory ocular neovascularization. Design Retrospective multicenter consecutive case series of inflammatory ocular neovascularization. Methods settings: Multicenter institutional and private practices. study population: Patients with inflammatory ocular neovascularization in one or both eyes of varying etiologies who failed standard therapy. intervention: Intravitreal injection of bevacizumab. main outcome measures: Improvement of best-corrected visual acuity (BCVA) expressed as logarithm of minimal angle of resolution (logMAR), and decrease in central foveal thickness as measured by optical coherence tomography at 6, 12, 18, and 24 months of follow-up. Results Mean logMAR BCVA (central foveal thickness) following intravitreal bevacizumab was as follows: baseline, 0.65 (6/27 or 20/90) (338 μm; 99 eyes of 96 patients); 6 months, 0.42 (6/16 or 20/53) (239 μm; 2.0 injections; 81 eyes); 12 months, 0.39 (6/15 or 20/49) (241 μm; 2.3 injections; 95 eyes); 18 months, 0.40 (6/15 or 20/50) (261 μm; 3.0 injections; 46 eyes); and 24 months, 0.34 (6/13 or 20/44) (265 μm; 3.6 injections; 27 eyes). Paired comparisons revealed significant visual improvement at 6 months of 2.4 lines ( P = .000), at 12 months of 2.5 lines ( P = .000), at 18 months of 2.5 lines ( P = .001), and at 24 months of 2.2 lines ( P = .013). Paired comparisons revealed significant central foveal flattening at 6 months of 78 μm ( P = .000), at 12 months of 85 μm ( P = .000), at 18 months of 90 μm ( P = .003), and at 24 months of 77 μm ( P = .022). Three eyes developed submacular fibrosis and 1 eye submacular hemorrhage. Conclusion Intravitreal bevacizumab led in the long-term to significant mean visual improvement of ≥2.2 lines and significant foveal flattening in a wide variety of inflammatory ocular diseases without major complications.

To evaluate the changes in aqueous vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) following intravitreal bevacizumab injections for choroidal neovascularization (CNV) secondary to age-related macular degeneration or pathologic myopia.Aqueous samples were obtained at the time of injection from 51 eyes of 51 patients who underwent three monthly intravitreal bevacizumab (Avastin) injections at baseline, 1, and 2 months. Concentrations of VEGF and PEDF in the aqueous were evaluated using enzyme-linked immunosorbent assay and compared.For the 34 eyes with age-related macular degeneration CNV, the mean +/- standard deviation aqueous VEGF level reduced from 102.6 pg/mL +/- 90.6 pg/mL at baseline to 18.3 pg/mL +/- 22.5 pg/mL at 2 months (P0.001), whereas the mean PEDF level increased from 11.2 ng/mL +/- 10.4 ng/mL at baseline to 38.7 ng/mL +/- 47.9 ng/mL at 2 months (P = 0.001). For the 17 eyes with myopic CNV, the mean +/- standard deviation aqueous VEGF level reduced from 20.1 pg/mL +/- 28.9 pg/mL at baseline to 3.8 pg/mL +/- 5.3 pg/mL at 2 months (P = 0.016), whereas the mean PEDF level increased from 20.0 ng/mL +/- 16.3 ng/mL at baseline to 126.0 ng/mL +/- 152.0 ng/mL at 2 months (P = 0.016).Intravitreal bevacizumab injections resulted in reduced aqueous VEGF and increased PEDF levels in patients with CNV secondary to age-related macular degeneration or pathologic myopia. These changes may be favorable for the inhibition of CNV angiogenesis.

Background: Moderate alcohol use is generally associated with lower ischaemic heart disease (IHD) mortality but it is difficult to ascertain whether this is due to attributes of moderate alcohol users or the properties of alcohol itself. Evidence from populations with different patterns of alcohol use and IHD can provide crucial evidence. We assessed the association of moderate alcohol use with IHD mortality in older Chinese people from Hong Kong. Methodology: We used Cox regression to determine whether moderate alcohol use was associated with IHD mortality in a prospective, population-based cohort study of all 56167 attendees, aged 65 years or over, from July 1998 to December 2000 at all 18 Elderly Health Centers operated by the Department of Health in Hong Kong. Principal Findings: After a median follow-up of 4.2 years, there were 406 (188 in men, 218 in women) deaths from IHD in 54,090 subjects (96.3% successful follow-up). Moderate alcohol use in men was not associated with IHD mortality adjusted only for age [Hazard Ratio, HR 1.01 (95% Cl 0.55 to 1.84) compared with never drinkers] or additionally adjusted for socio-economic status and lifestyle. Almost all women were occasional drinkers and their current alcohol use was not significantly associated with IHD mortality [HR 0.88, (95% Cl 0.51 to 1.53)] Conclusions: Moderate alcohol use had no effect on IHD mortality in older Chinese men. Lack of replication of the usual protective effect of moderate alcohol use in a setting with a different pattern of alcohol use and IHD could be due to chance or could suggest that the protective effect of alcohol on IHD does not extend to all populations. © 2008 Schooling et al., published_or_final_version

Purpose We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR). Methods A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1–80C>A, IVS1–206G>C, IVS1–252A>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited. Results A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms. Conclusions The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes.

Age-related macular degeneration (AMD) is a leading cause of severe visual impairment in most developed countries, affecting more than 10 million people worldwide.1,2 Exudative AMD is an advanced form of the disease that poses a serious threat of vision loss. It is characterized by the formation of new blood vessels beneath the retina. Leakage of blood and fluid from the choroidal neovascular membrane causes scarring that leads to permanent damage from the surrounding retinal tissue, destroying central vision. Nearly 90% of severe cases of AMD are exudative. Population-based association studies have consistently shown that, among the various environmental factors, smoking is associated with a higher risk of advanced AMD.3–9 The population attributable risk (PAR) of AMD in former and current smokers has been reported to be from 20% to 68%.10 Smoking may affect metabolic processes in the retinal pigment epithelium (RPE) by depressing the release of antioxidants and altering the choroidal blood flow. The retina is thus subjected to oxidative stress due to a high consumption of oxygen. The free radicals, the extracellular matrix along Bruch’s membrane, and the increased levels of the angiogenic factors in RPE cells from the insult of oxidative stress then promote neovascularization.11 First-degree relatives of patients with advanced AMD have a higher incidence and earlier age of disease manifestation according to familial aggregation analysis studies.12,13 Twin studies have revealed a higher incidence of of AMD manifestation in monozygotic than in dizygotic twin pairs, which further reinforces the importance of genetic factors in AMD risk.14–16 Genome-wide linkage studies of AMD in large pedigrees, affected sib pairs, and discordant sib pairs have mapped susceptible genetic loci to 1q, 2q, 3p, 6q, 9q, 10q, 16q, 17q, and 22q.17–25 Associations of AMD risk with most loci have been inconsistent in various reports, but the two loci on 1q31 and 10q26 have frequently been implicated in AMD in different studies. A meta-analysis of six independent studies has provided further evidence of linkage on 10q26 and 1q.26 This meta-analysis also showed weak linkage to 2p, 3p, 4q, 12q, and 16q. Yet no AMD-causing gene has been identified, with subsequent traditional positional cloning. After a genome-wide scan, candidate gene screening of extended families and sib pairs was performed on exon 104 of hemicentin-1 and the 11 exons of EFEMP1 residing on 1q31 and 2p16, respectively. No disease-causing allele was identified.21 In 2005, a genome-wide association study revealed the single-nucleotide polymorphism (SNP) Tyr402His in the complement factor H (CFH) gene on 1q32 as an AMD-related variant, but no association was found between CFH Tyr402His and AMD in Chinese and Japanese populations.27–32 We have shown that some sequence variants in CFH, including rs3753394 (P = 0.003), rs800292 (Val62Ile, P = 0.00053), and rs1329428 (P = 0.00092), but not rs1061170 (Tyr402His), have significant associations with exudative AMD in Chinese.32 Recently, we reported the SNP rs11200638, residing in the promoter of HTRA1, to be associated with exudative AMD in a cohort of Chinese patients.33 It was also found to have a PAR of 49.3% of AMD in Caucasians.34 In this study, the whole sequence of HTRA1 was examined to characterize further the critical genetic factors linked to AMD. The effect of smoking was also investigated. Because the CFH SNP rs800292 was found to be significantly associated with exudative AMD in our previous study in a Chinese cohort,32 its interactions with HTRA1 SNPs were examined in this study.

To evaluate the efficacy of photodynamic therapy (PDT) with half-dose verteporfin for treating acute central serous chorioretinopathy (CSC).Prospective, double-masked, placebo-controlled, randomized clinical trial.Sixty-three eyes of 63 patients with acute symptomatic CSC of 3 months' duration or less were recruited. Forty-three eyes were randomized to indocyanine green angiography (ICGA)-guided PDT with half-dose (3 mg/m(2)) verteporfin and 21 eyes were randomized to placebo.Patients in the verteporfin group received an infusion of half-dose verteporfin over 8 minutes, followed by ICGA-guided PDT 10 minutes from the start of infusion. Laser was applied for 83 seconds covering the choroidal abnormalities observed in ICGA, with a maximum laser spot size of 4500 mum.The primary outcome measure was the proportion of eyes with absence of subretinal fluid at the macula at 12 months. Secondary outcome measures included changes in mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), subjective symptoms, optical coherence tomography (OCT) results, central foveal thickness (CFT), and angiographic findings during the 12-month study period.Thirty-nine patients in the verteporfin group and 19 patients in the placebo group completed 12 months of follow-up. Thirty-seven (94.9%) eyes in the verteporfin group compared with 11 (57.9%) eyes in the placebo group showed absence of subretinal fluid at the macula at 12 months (P = 0.001). The mean logMAR BCVA at 12 months was significantly better in the verteporfin group compared with the placebo group: -0.05 and 0.05, respectively (P = 0.008). All 39 (100%) verteporfin-treated eyes had stable or improved vision, compared with 15 (78.9%) eyes in the placebo group (P = 0.009). The mean OCT CFT for the verteporfin group also was significantly lower compared with the placebo group at 12 months (P = 0.001). No ocular or systemic adverse event was encountered in the study.Photodynamic therapy with half-dose verteporfin is effective in treating acute symptomatic CSC, resulting in a higher proportion of patients with absence of exudative macular detachment and better visual acuity compared with placebo.

To evaluate the efficacy of a safety enhanced photodynamic therapy (PDT) protocol with half-dose verteporfin for treating chronic central serous chorioretinopathy (CSC).Forty-eight eyes of 48 patients with symptomatic chronic CSC underwent indocyanine green angiography guided PDT with half dose (3 mg/m) verteporfin. Outcome measures included logMAR best-corrected visual acuity (BCVA), central retinal thickness, and angiographic changes during the 12-month study period.The mean CSC duration was 8.2 months (range, 3-40 months). At 12 months after PDT, the mean logMAR BCVA improved from 0.31 to 0.15 (P0.001). The mean improvement was 1.6 lines and 45 (95.8%) eyes had stable or improved vision. Eyes without pigment epithelial detachment (PED) had significantly greater visual improvement compared with eyes with PED (P = 0.031). Patients with CSC of 6 months or less or younger than 45 years were more likely to gain vision by two or more lines after treatment (P = 0.007 and P = 0.018, respectively). Forty (83.3%) eyes had complete resolution of serous detachment at 3 months, with 43 (89.6%) eyes at 12 months.The safety enhanced PDT protocol appeared to be beneficial for patients with chronic CSC. Further controlled study is warranted to evaluate the safety and efficacy of this treatment option.

Dengue fever is a viral disease transmitted by Aedes mosquitoes and is endemic in the tropics.1 The severity of dengue fever varies from mild non-specific febrile illness to potentially fatal dengue haemorrhagic fever causing thrombocytopenia and shock. Patients with dengue fever may develop various ophthalmic manifestations causing visual loss, including macular oedema, macular haemorrhage, retinal vasculitis, “cotton-wool” spots and optic disc swelling.2–8 We report the use of multifocal electroretinography (mfERG) in the assessment of a patient with dengue fever-associated maculopathy in whom there were no clinical or angiographic abnormalities. A 16-year-old girl with serologically confirmed dengue fever presented with left relative scotoma and reduced vision 7 days after the onset of fever. Her visual acuity was 20/20 …

Background Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A. Results Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands. Conclusion Analysis of sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.

Background: To assess the efficacy and safety of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of choroidal neovascularisation (CNV) secondary to pathological myopia. Methods: 22 eyes of 22 patients with subfoveal or juxtafoveal CNV due to pathological myopia were prospectively recruited for combined PDT with IVTA. The treatment outcomes at 1 year were compared with those in a control group of 22 eyes that received PDT monotherapy. Results: At 1 year, the logMAR best-corrected visual acuity (BCVA) for the combined PDT with IVTA group changed from 0.62 to 0.61 (p = 0.74), whereas that for the monotherapy group changed from 0.61 to 0.67 (p = 0.33). The mean logMAR BCVA and proportions of patients without losing ⩾3 lines at 1 year were similar between the two groups (p = 0.68 and 0.74, respectively). Subgroup analyses showed that eyes with baseline logMAR BCVA worse than 0.6 (Snellen equivalent 20/80) or CNV with greatest linear dimension ⩾750 μm which received combined therapy had better mean logMAR BCVA at 1 year (p = 0.023 and 0.041, respectively), with a higher proportion of eyes gaining ⩾2 lines of BCVA (p = 0.027 and 0.017, respectively) compared with PDT monotherapy. Conclusions: Combined PDT with IVTA did not seem to result in significantly better visual outcome compared with PDT monotherapy. However, combined therapy might result in better visual outcome in selected patients with worse initial visual acuity or larger myopic CNV. Further studies are warranted to investigate the role of combined PDT with IVTA in the treatment of myopic CNV, especially in patients with worse prognostic factors.

Multifocal electroretinography (mfERG) is an investigation that can simultaneously measure multiple electroretinographic responses at different retinal locations by cross-correlation techniques. mfERG therefore allows topographic mapping of retinal function in the central 40-50 degrees of the retina. The strength of mfERG lies in its ability to provide objective assessment of the central retinal function at different retinal areas within a short duration of time. Since the introduction of mfERG in 1992, mfERG has been applied in a large variety of clinical settings. This article reviews the clinical applications of mfERG based on the currently available evidence. mfERG has been found to be useful in the assessment of localized retinal dysfunction caused by various acquired or hereditary retinal disorders. The use of mfERG also enabled clinicians to objectively monitor the treatment outcomes as the changes in visual functions might not be reflected by subjective methods of assessment. By changing the stimulus, recording, and analysis parameters, investigation of specific retinal electrophysiological components can be performed topographically. Further developments and consolidations of these parameters will likely broaden the use of mfERG in the clinical setting.

To investigate the relationship between myopia and macular thickness, as measured by optical coherence tomography.A total of 143 normal subjects comprising 80 eyes with high myopia (spherical equivalent [SE]-6.0 D), 37 eyes with low to moderate myopia (SE between -6.0 and -0.5 D), and 26 nonmyopic eyes (SE-0.5 D) were analyzed in this cross-sectional study. Total average, foveal, and inner and outer average macular thicknesses measured by the StratusOCT (Carl Zeiss Meditec Inc., Dublin, CA) were compared among the three diagnostic groups. Associations between macular thickness and refractive error/axial length were evaluated by linear regression analysis.The minimum foveal and average foveal (1-mm ring on the OCT retinal thickness map) thicknesses were significantly greater, and the outer ring macular (3-6-mm) thicknesses significantly lower in the high myopic eyes than in the low to moderate myopic and nonmyopic eyes. No significant difference was found in the inner ring (1-3-mm) macular thickness measurements among the groups. There was a positive correlation between the axial length and the average foveal thickness (r = 0.374, P0.001). Negative correlations were found between axial length and the average outer ring macular thickness (r= -0.471, P0.001) and total average macular thickness (r= -0.311, P0.001).Retinal thickness is related to refractive error/axial length in normal subjects with regional variations in correlation within the 6-mm macular region. Analysis of macular thickness in the evaluation of macular diseases and glaucoma should be interpreted only in the context of refractive errors and the location of measurement.

Background: Although the harms of smoking are well established, it is unclear how they extend into old age in the Chinese. Aim: To examine the relationship of smoking with all-cause and major cause-specific mortality in elderly Chinese men and women, respectively, in Hong Kong. Methods: Mortality by smoking status was examined in a prospective cohort study of 56 167 (18 749 men, 37 416 women) Chinese aged ≥65 years enrolled from 1998 to 2000 at all the 18 elderly health centres of the Hong Kong Government Department of Health. Results: After a mean follow-up of 4.1 years, 1848 male and 2035 female deaths occured among 54 214 subjects (96.5% successful follow-up). At baseline, more men than women were current smokers (20.3% vs 4.0%) and former smokers (40.8% vs 7.9%). The adjusted RRs (95% Cl) for all-cause mortality in former and current smokers, compared with never smokers, were 1.39 (1.23 to 1.56) and 1.75 (1.53 to 2.00) in men and 1.43 (1.25 to 1.64) and 1.38 (1.14 to 1.68) in women, respectively. For current smokers, the RRs (95% Cl) for all-cause mortality were 1.59 (1.39 to 1.82), 1.72 (1.48 to 2.00) and 1.84 (1.43 to 2.35) for daily consumption of 1-9, 10-20 and >21 cigarettes, respectively (p for trend, published_or_final_version

Background The Dietary Approaches to Stop Hypertension (DASH) diet has been found to effectively lower blood pressure in Western populations within controlled experimental settings, with an efficacy similar to that of antihypertensive drugs. Nevertheless, studies of the pragmatic effectiveness of DASH counselling in the Chinese population are scarce. The aim of this study was to test the a priori hypotheses that DASH dietary intervention by a single counselling session with a dietician in addition to standard care by physicians improved estimated 10-year cardiovascular risk to a greater extent than standard care given by physicians alone. We also assessed participants who were less likely to have their cardiovascular risk optimised. Methods This parallel-group, randomised controlled trial was done with enrolment at two General Outpatient Clinics and at community health seminars through a primary-care network in Hong Kong. Computer-generated numbers with a block size of six and an allocation ratio of 1:1 were used for group allocation. The research nurse opened the opaque envelope in which the randomised sequence was sealed. Patients were notified into either intervention or control group, whereas the outcome assessors were masked. We recruited male and female patients (aged 40–70 years) who were newly diagnosed with grade 1 hypertension. Standard care was offered by the attending physician that lasted for 3–5 minutes, resembling the routine clinic practice. Only patients in the intervention group received a further 25 min one-off dietary counselling, based on the DASH recipe tailored-made for Chinese patients with hypertension, offered by a registered dietitian. Individualised DASH diet goals were recommended and educational pamphlets on the DASH diet were given. 10-year cardiovascular risk was estimated by a recalibrated and validated Chinese version of the Framingham equation. Analysis of covariance was performed to compare between-group differences, with adjustment for the effects of other factors and baseline outcome measures. This trial is registered with the Chinese Clinical Trial Register, number ChiCTRTRC-13003014. The study was approved by the Joint CUHK-NTEC Clinical Research Ethics Committee, Hong Kong. Each trial participant provided written informed consent. Findings We recruited a total of 556 patients (273 males; 283 females) aged 40–70 years who were newly diagnosed with grade 1 hypertension. 275 patients were randomly assigned to receive standard care and 281 patients were assigned to receive standard care plus DASH-based dietary counselling. Outcome data were available for 504 (91%) patients at 6 months and 485 (87%) patients at 12 months. Between-group analyses showed no difference in the reduction of cardiovascular risk between the two groups at 6 months (–0·13% [95% CI –0·50% to 0·23%], p=0·477) and 12 months (–0·08% [–0·33% to 0·18%], p=0·568). Multivariate regression analyses showed that men (p=0·012), patients younger than 55 years (p=0·049), current smokers (p=0·007), patients with educational level of junior secondary or below (p=0·009), and those who dined out for main meals for four times or more in a typical week (p=0·038) were significantly associated with no improvement in cardiovascular risk. Interpretation We found that additional counselling with a dietitian for Chinese patients with grade 1 hypertension might not confer additional benefits to those achieved with standard care. This finding does not support routine referral of these patients to dietary counselling. Patients with risk factors identified in this study should receive more clinical attention and regular follow-up to reduce cardiovascular risk. Future research is still necessary to assess the effectiveness of other plausible DASH diet delivery models. Funding The Health and Medical Research Fund and the Food and Health Bureau of the Hong Kong Government.

To investigate whether triamcinolone acetonide (TA) affects the expression of vascular endothelial growth factor (VEGF) and pigment epithelial derived factor (PEDF) in human retinal pigment epithelium (ARPE19) and human umbilical vein endothelial (HUVE) cells. Study the time course of the effects of TA on VEGF and PEDF expressions in cultured cells.ARPE19 and HUVE cells were grown to subconfluence and treated with TA (0.1 mg/ml, 1 mg/ml). The mRNA expressions of VEGF and PEDF were determined from 10 min to three days using real-time RT-PCR. Concurrently, the protein levels of VEGF and PEDF in ARPE cells were detected with ELISA.Real-time RT-PCR showed TA affected a 0.5 fold decrease in VEGF(165) level and about a 2.5 fold increase in PEDF level at both TA concentrations. The effect was maintained at 12 h at 0.1 mg/ml TA and 24 h at 1 mg/ml TA. Similar changes were observed in the respective protein concentrations. The effects of TA on VEGF and PEDF transcript levels were similar in HUVE and ARPE19 cells. VEGF and PEDF protein productions in HUVE cells were too low for statistical analysis.TA reduces the expression of VEGF but increases the expression of PEDF in ARPE19 and HUVE cells. These observations suggest TA may influence the inhibition of neovascularization and macular edema through differential VEGF and PEDF expressions.

Variants in the complement factor H (CFH) gene have been reported to be associated with age-related macular degeneration (AMD). We conducted a case-control association study to investigate the association of 6 single nucleotide polymorphisms (SNPs) in CFH with exudative AMD in the Chinese population.We recruited 163 cases and 244 controls, all ethnic Chinese, with complete ophthalmic examination including fundus investigation. Cigarette smoking was recorded. Six SNPs (dbSNP ID: rs3753394, rs800292, rs1061147, rs1061170, rs380390, and rs1329428) in the CFH gene were genotyped by Taqman assays.Y402H (1277 TC) has low frequencies in our study population, 5.8% in patients and 3.9% in controls. It was not associated with exudative AMD adjusted for age, gender and smoking. Significant associations were detected for AMD with rs3753394 (p=0.003, p(corr)=0.018), rs800292 (p=0.00053, p(corr)=0.0032), and rs1329428 (p=0.00092, p(corr)=0.0028), p(corr) values obtained after adjustment for multicomparison. A haplotype containing these four SNPs (TGTC) was found to confer a significantly increased likelihood of exudative AMD with an odds ratio of 1.68 (95% CI: 1.26-2.23) p=0.0003 (p(corr)=0.0026 after correction by permutation test). Logistic regression analysis detected no interactions between the SNPs and age, gender or smoking.We have found differences in the association between the CFH gene and exudative AMD in Chinese from Caucasians and Japanese. We detected SNP rs3753394 in the CFH promoter carrying a significantly increased risk for exudative AMD.

To report the development of retinal pigment epithelial (RPE) tear after intravitreal injection of ranibizumab (Lucentis, Novartis, Basel, Switzerland). Case report with presentation of the fundus photography, fluorescein angiography (FA) and optical coherence tomography (OCT) findings. A 70-year-old man received intravitreal injections of ranibizumab for the treatment of occult choroidal neovascularisation (CNV) with fibrovascular pigment epithelial detachment due to age-related macular degeneration. One day after the third intravitreal ranibizumab injection, fundus examination showed a RPE defect at the foveal region. FA and OCT confirmed the presence of RPE tear sparing the fovea. No further progression of the RPE tear was observed after withholding subsequent ranibizumab injection and his right eye visual acuity remained at 20/100 at 3 months from the last injection. As with other anti-vascular endothelial growth factor treatment for CNV, RPE tear might occur after intravitreal ranibizumab injection even after previous uneventful intravitreal injections.

Age-related macular degeneration (AMD), the most common cause of irreversible vision loss in individuals aged older than 50 years, is classified as either wet (neovascular) or dry (nonneovascular). Inherited variation in the complement factor H gene is a major risk factor for drusen in dry AMD. Here we report that a single-nucleotide polymorphism in the promoter region of HTRA1 , a serine protease gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A whole-genome association mapping strategy was applied to a Chinese population, yielding a P value of –11 . Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype.

Objective To describe a novel approach to measuring anterior chamber angle dimensions and configurations. Methods Sixty-nine images were selected randomly from the ultrasound biomicroscopic image database to develop the algorithm. Thirty images were selected for further analyses. The value of each pixel of the 8-bit grayscale ultrasound biomicroscopic images was quantized into 0 (black) or 1 (white), and the edge points outlining the angle were detected and fitted with straight lines. The dimensions and profiles of anterior chamber angles were then measured. Results The algorithm failed to identify the edge points correctly in 8 (11.6%) of 69 images because of strong background noise. Three basic types of angle configuration were identified based on the derived angle profiles: constant, increasing, and decreasing, which corresponded to flat, bowed forward, and bowed backward iris contours, respectively. The angle measurements demonstrated high correlation with trabecular-iris angle and angle opening distance 500 (calculated as the distance from the corneal endothelium to the anterior iris surface perpendicular to a line drawn at 500 μm from the scleral spur). The strongest association was found between the averaged angle derived from the angle profile and the angle opening distance 500 ( r = 0.91). Conclusion The proposed algorithm has high correlations with angle opening distance and trabecular-iris angle with the added advantages of being fully automated, reproducible, and able to capture the characteristic angle configurations. However, good-quality ultrasound biomicroscopic images with high signal-to-noise ratio are required to identify the edge points correctly.

Objective A community-based programme for chronic obstructive pulmonary disease (COPD) patients in group sessions is designed, and the feasibility, acceptability and physical and psychosocial outcomes evaluated. Methods Patients with COPD discharged from hospital, or those attending specialist outpatient clinic, with a history of hospital admission owing to COPD in the preceding 12 months were recruited. Those who had malignancy or were housebound were excluded. Group sessions were arranged once a week in a Community Centre, and consisted of two hourly sessions. The components of each session consist of education regarding the disease, breathing techniques, use of oxygen and other medication, smoking cessation, nutrition, dyspnoea management skills, relaxation and energy conservation techniques, introduction of social and community support, and strengthening as well as aerobic exercises. Assessments before and after intervention include lung function, 6 minutes walk test (6MWT), general Health Questionnaire (GHQ), the St. George’s Respiratory Questionnaire (SGRQ), and a COPD knowledge Questionnaire. A programme evaluation was carried out using questionnaire and group discussions. Results Fortyfour subjects were recruited, with 75% completing the programme, and 20% with drawing for unavoidable reasons. Statistically significant improvement was noted in all domains of the GHQ, SGRQ, and knowledge test, while the mean 6MWT improved, although statistical significance was not reached. Subjects were enthusiastic about the provision of this service in helping them cope with the disease through empowerment and mutual support. Conclusion A group community intervention programme for COPD patients is feasible and acceptable, with positive psychosocial outcomes. Such a model could be further developed and cost-effectiveness evaluated as a model of chronic disease management in the community.

To evaluate the safety and efficacy of intravitreal bevacizumab in the treatment of idiopathic choroidal neovascularization (CNV) and CNV secondary to central serous chorioretinopathy (CSC) or punctate inner choroidopathy (PIC).Prospective, nonrandomized, interventional case series.In an institutional clinical practice, 15 patients were recruited; nine had idiopathic CNV, two had CNV secondary to CSC, and four had CNV attributable to PIC. Patients received three monthly 1.25-mg intravitreal bevacizumab injections for three months. Patients were followed for six months, and the best-corrected visual acuity (BCVA), fluorescein angiography (FA) findings, and optical coherence tomography (OCT) central foveal thickness (CFT) were assessed.At baseline, the mean logMAR BCVA was 0.48 (Snellen equivalent = 20/60). The mean logMAR BCVA improved significantly to 0.25 (Snellen equivalent = 20/36) and 0.17 (Snellen equivalent = 20/30) at one and six months, respectively (both P = .001). The mean OCT CFT reduced from 306 microm at baseline to 201 microm at six months (P.001). All eyes (100%) had visual improvement of 1 line or more at six months, and 11 (73.3%) improved by 2 or more lines. FA showed absence of CNV leakage, the angiographic end point, at three months, and no recurrence was observed at six months in all eyes. No systemic or ocular adverse events were encountered.Intravitreal bevacizumab injections resulted in visual and anatomic improvements in eyes with idiopathic CNV and CNV attributable to CSC or PIC. Further studies are warranted to assess the long-term safety and the regimen for optimal efficacy of intravitreal bevacizumab.

Objectives The main objectives were to examine the relation between age-comparative (self vs others of same age) self-rated health (SRH) and time-comparative (self this year vs last year) SRH, and to evaluate which was more strongly associated with specific physical health problems. Methods Cross-sectional data on two SRH measures and various physical health problems from 18749 male and 37413 female clients aged 65 or over from 18 Elderly Health Centres in Hong Kong were analysed using logistic regression with adjustment for potential confounders. Results Men were more likely to report ‘better’ and less likely to report ‘worse’ SRH than women. ‘Normal’ was the most common option but the proportions choosing this decreased with age on both SRH measures. There was a fairly weak but statistically significant correlation between these two measures, with Kappa coefficients of 0.125 and 0.167 for men and women, respectively. For both men and women, there were significantly positive linear trends between age-comparative SRH options from ‘better’ to ‘worse’ and physical health problems, such as respiratory diseases, musculoskeletal diseases, any active chronic diseases, functional disability, depressive symptoms, taking medication regularly, and admission to hospital last year. However, for time-comparative SRH, those who rated ‘normal’ had the smallest odds ratios in all of the physical health problems above than those who rated ‘better’ or ‘worse’. Conclusions The two SRH measures correlated with each other weakly but significantly. Age-comparative SRH was linearly, and time-comparative SRH was curvilinearly associated with physical health problems. Copyright © 2006 John Wiley & Sons, Ltd.

To detect the levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in aqueous humor of patients with active choroidal neovascularization (CNV).Aqueous humor samples were obtained from 32 patients with active CNV. The concentrations of VEGF and PEDF in aqueous humor were measured by enzyme linked immunosorbent assay (ELISA) for quantitative analysis. VEGF and PEDF in 10 samples of aqueous humor from patients with cataract were also detected by the same methods as control.The mean VEGF and PEDF concentrations in aqueous humor of active CNV patients were higher than those in the control group (P=0.000).The patients with active CNV exhibit significantly higher VEGF and PEDF levels than those in control, indicating that VEGF along with PEDF may modulate the formation of CNV.

To investigate the structure-function relationship in patients with retinal arterial occlusion by measuring the macular and the peripapillary retinal nerve fibre layer (RNFL) thickness and the visual sensitivity.This is an observational case series with three patients with central retinal arterial occlusion (CRAO) and two patients with branch retinal arterial occlusion (BRAO). The macular/peripapillary RNFL thickness and the visual field were measured with Stratus optical coherence tomography (OCT) and Humphrey visual field analyzer, respectively, at least 1 year after the diagnosis of CRAO or BRAO.The macular thickness, in particular the inner retinal layer, and the peripapillary RNFL thickness were reduced in patients with retinal arterial occlusion. The decrease in the macular and the peripapillary RNFL thickness corresponded to the sites of retinal arterial occlusion with diffuse and segmental thinning found in CRAO and BRAO, respectively. Visual field defects were found in the corresponding locations of macular and RNFL thinning, and closely correlated with the degree of the structural damage.Structural damages in terms of reduction in the macular and peripapillary RNFL thickness were evident in patients with retinal arterial occlusion. A close structure-function correlation was found and a worse functional outcome is associated with a more extensive thinning of the macula and RNFL. OCT measurements of the macular/peripapillary RNFL thickness provide useful indicators to reflect the severity of the disease in retinal arterial occlusion and serve as a new paradigm to study and monitor the disease longitudinally.

To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) caused by age related macular degeneration (AMD).48 eyes from 48 patients with subfoveal CNV caused by AMD were prospective recruited, with 24 eyes treated with combined PDT with IVTA and compared with a control group of 24 eyes which received PDT monotherapy. In the combined treatment group, IVTA was performed immediately after PDT as an outpatient procedure. The mean number of treatments, mean logMAR best corrected visual acuity (BCVA), mean line of visual acuity changes, and proportion of patients without moderate visual loss at 1 year were compared between the combined and monotherapy groups.At 1 year the logMAR BCVA for the PDT with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline), whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09 (p0.001 compared with baseline). A significantly higher proportion of patients who had PDT with IVTA did not develop moderate visual loss at 1 year compared with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which had combined treatment had significantly fewer lines lost compared with monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis showed that PDT with IVTA is effective in preventing visual loss in both predominately classic and occult CNV groups. The mean number of treatments for the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076).Combined PDT with IVTA appeared more effective statistically at 12 months for stabilisation of vision (3 logMAR lines change) compared with PDT monotherapy. Further randomised control trials might be justified to conclude the efficacy of PDT with IVTA.

Deferoxamine mesylate is a chelating agent used in the treatment of iron overload in patients requiring regular transfusions. Deferoxamine is most commonly administered as a slow subcutaneous infusion but continuous intravenous infusion may be required for treating life threatening cardiac complications due to iron overload.1 Toxic retinopathy is one of the complications associated with deferoxamine, in which different manifestations including pigmentary retinopathy, bull’s eye maculopathy, and vitelliform maculopathy have been described.2–,8 We report a patient who had rapid development of irreversible diffuse pigmentary retinopathy with severe visual loss while receiving continuous intravenous deferoxamine infusion. A 17 year old β thalassaemic patient was referred for ophthalmic assessment with recent onset of colour vision impairment 4 months after commencement of continuous intravenous deferoxamine infusion. He had been on subcutaneous deferoxamine for …

Background: Polypoidal choroidal vasculopathy (PCV) with peculiar vascular lesions presents frequently as recurrent submacular haemorrhage. The best treatment is still not certain. It is the authors’ objective to evaluate the 1-year safety and efficacy of photodynamic therapy (PDT) using verteporfin for persistent macular PCV after pneumatic displacement of the massive submacular haemorrhage with intravitreal perfluoropropane (C3F8). Methods: A prospective, non-comparative, interventional case series on patients with extensive and thick submacular haemorrhage secondary to PCV, which was displaced pneumatically with intravitreal pure 0.4 ml C3F8. Fluorescein angiography and indocyanine green angiography were repeated 1–2 weeks later to delineate any persistent active leaking polypoidal lesions, which were then treated with PDT. Retreatment might be considered in each follow up at every 3 months. Results: Six eyes of six patients with the mean age of 53.6 years had been recruited and completed 1-year follow up. The mean baseline Snellen equivalent best-corrected visual acuity (BCVA) was 6/92 and the mean final BCVA at 1 year was 6/17. The mean improvement in logMAR BCVA after the sequential treatments was seven lines (range +3 to +19 lines) (Wilcoxon signed-ranks test, P = 0.03). All patients had at least moderate visual gains. No patient suffered serious complications from PDT. Conclusions: This first report on combined treatment with intravitreal gas injection and sequential PDT on PCV seems to be a well-tolerated option. Further comparative studies with larger sample size and longer follow up are warranted.