Transpalpebral electrical stimulation for the treatment of retinitis pigmentosa: study protocol for a series of N-of-1 single-blind, randomized controlled trial.

BACKGROUND: Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive loss of rod photoreceptors of the eye, leading to irreversible blindness. To date, to our knowledge, no clinical prospective studies have been undertaken that could document the effect of interventions that could reverse or reduce the progression of this disease. The application of microcurrent stimulation (ES) of the eye in the treatment of chronic eye diseases such as glaucoma and age-related macular degeneration has been used over several decades and has been reported to have beneficial effects to reduce the progression of these blinding diseases and has been supported by animal studies and smaller clinical studies, but to date, no large randomized clinical trials on the use of microcurrent therapy have been published. More recent clinical reports have also shown beneficial effects of ES on slowing the progression of RP but also lacks data from robust prospective clinical outcome studies. To our knowledge, this is the first prospective randomized study to evaluate the safety and clinical effectiveness of transpalpebral electrical stimulation (TpES) on the progression of RP. METHODS: Randomized prospective study using N-of-1 trial 3 single-blind, crossover comparisons. The intervention period of each comparison is divided into treatment period and control period which are randomized arranged. Twelve participants will be strictly recruited in N-of-1 trial by the researcher in accordance with the inclusion and exclusion criteria. The main outcome of interest examined after each cycle of the 8-week intervention period is the assessment of the visual field (VF). Other variables of interest are best corrected visual acuity (BCVA), retinal function using electroretinogram (ERG), and visual function using NEI VFQ-25 questionnaire. Objective assessments of retinal changes will be undertaken using optical coherence tomography (OCT) and fundus autofluorescence (FAF). DISCUSSION: The trial will evaluate the efficacy and safety of microcurrent stimulation on RP and provide high-quality evidence for clinical application through N-of-1 trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry; ChiCTR2300067357; https://www.chictr.org.cn/showproj.html?proj=174635 . Registered on 5 January 2023.

Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial.

BACKGROUND: Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. METHODS/DESIGN: This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. DISCUSSION: Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR2000035990 . Registered on 21 August 2020.

The relationship between insulin resistance/ß-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study.

AIM: To investigate the relationship between insulin resistance (IR)/ß-cell dysfunction and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes mellitus (T2DM), and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index (BMI). METHODS: Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment (HOMA) method was employed for IR and ß-cell function assessment. RESULTS: After excluding those participants who were treated with insulin (n=352) or had missing data of fasting insulin (n=96), and further excluding those with poor quality of retinal photographs (n=10), a total of 1008 subjects were included for the final analysis, 406 (40.3%) were men and 602 (59.7%) were women, age ranging from 34 to 86 (64.87±8.28)y. Any DR (levels 14 and above) was present in 278 (27.6%) subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio (OR) 1.51, 95% confidence interval (CI) 0.87-2.61, P=0.14] or HOMA ß-cell (OR 0.71, 95%CI 0.40-1.26, P=0.25). After stratification by BMI, the presence of any DR was associated positively with HOMA IR (OR 2.46, 95%CI: 1.18-5.12, P=0.016), and negatively with HOMA ß-cell (OR 0.40, 95%CI: 0.19-0.87, P=0.021) in the group of patients with higher BMI (≥25 kg/m2). In the group of patients with lower BMI (<25 kg/m2), the presence of any DR was not associated with HOMA IR (OR 1.00, 95%CI: 0.43-2.33, P=1.00) or HOMA ß-cell (OR 1.41, 95%CI: 0.60-3.32, P=0.43). CONCLUSION: The data suggest that higher IR and lower ß-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

The Beijing Desheng Diabetic Eye Study: rationale, design, methodology and baseline data.

AIM: To present the rationale, design, methodology, and the baseline data of the Beijing Desheng Diabetic Eye Study (BDDES), and to determine the prevalence of diabetic retinopathy (DR) and possible risk factors in patients with type 2 diabetes mellitus (T2DM) in an urban community of Beijing, China. METHODS: Community-based prospective cohort study of persons diagnosed with T2DM aged 30y or older. The main variables of interest are the presence and progression of DR as determined by the standardized ETDRS grading of seven fields fundus photographs. The presence and severity of DR were analyzed for possible correlations to non-genetic and genetic dispositions. RESULTS: A total of 1438 participants with data available for analysis, the prevalence of any DR was 35.4%. The prevalence of mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy was 27.7%, 2.6%, 0.5% and 4.5%, respectively. By multiple logistic regression analysis, risk factors for the presence of any DR included male (P=0.031), lower income level (P=0.011), lower education background (P=0.022), longer duration of diabetes (P=0.001), younger age at diabetic onset (P=0.001), higher systolic blood pressure (P=0.007), higher glycosylated hemoglobin A1c levels (P=0.001), high albuminuria (P=0.03), and use of insulin (P<0.001). For vision-threatening DR, four factors were significant: younger age at diabetic onset (P<0.001), higher systolic blood pressure (P=0.042), high albuminuria (P<0.001), and use of insulin (P<0.001). CONCLUSION: The BDDES is the first large-scale ongoing cohort study of a Chinese urban population of persons with type 2 diabetes. Using standardized grading system comparable to large cohort studies from western populations, our baseline data shows that the prevalence of DR and major risk factors in this Chinese ethnic population are comparable to that found in the western population studies.

Predictors for attending annual eye screening for diabetic retinopathy amongst patients with diabetes in an urban community of Beijing.

AIM: To gain a better understanding of possible factors that may influence the decision of diabetes persons to participate in annual eye screening in an urban community setting of China. METHODS: A structured interview including questions on attendance of eye screening, knowledge and awareness of diabetic retinopathy was conducted. The presence and degree of retinopathy were assessed using two field non-mydriatic retinal photography. RESULTS: Totally 720 diabetes persons were recruited and 519 were enrolled in this cross-sectional study. In this urban setting of Beijing, among diabetes patients of average of 10y duration, 77% confirmed having undergone at least one eye examination and 61% reported having at least one eye examination with dilated pupil. As for the last 12mo, the number decreased to 210 (47%) and 131 (30%) separately. Most of the participants (95%) were aware that diabetes could affect their vision and that regular eye examination was necessary. Very few of them (12%) however were aware that the early stages of diabetic retinopathy presented without symptoms of vision loss. Having attended patient education on diabetes was effective in building awareness about diabetic eye disease and was a significant positive predictor for attending eye screening [education in a year, Adj. OR=0.47 (0.29-0.74), P<0.001, education years ago, Adj. OR=0.56 (0.33-0.96), P=0.036]. The duration of disease also increased the likelihood of having undergone eye screening (Adj. OR=0.96, P<0.05). CONCLUSION: Being exposed to education about the complications of diabetes increases the probability of attending diabetic eye screening. An appropriate patient knowledge building strategy should be made available to patients from the time of diagnosis.

The diurnal variation pattern of choroidal thickness in macular region of young healthy female individuals using spectral domain optical coherence tomography.

AIM: To investigate the pattern of diurnal variations of choroidal thickness of macular region of healthyindividuals. METHODS: A prospective study of 32 healthy female subjects was conducted. Each subject underwent 1) a questionnaire on daily schedule, 2) the Pittsburgh Sleep Quality Index questionnaire (PSQI), and 3) ocular examinations including an eye dominance test, fundus photography, and sequential optical coherence tomography (OCT) imaging, on two separate days at five fixed 3h time intervals. Choroidal thickness was measured by two masked graders. RESULTS: A significant diurnal variation of choriodal thickness at fovea (P<0.001), at 500 µm nasal (P<0.001), temporal to fovea (P=0.01) or 1500 µm nasal to fovea (P=0.001) was observed. The median choroidal thickness peaked at 11:00 at fovea (P=0.01), at 500 µm nasal (P=0.009) and temporal (P=0.03) to fovea. The median amplitude of foveal choroidal thickness was 20.5 µm (13, 31) and 20.0 µm (12.5, 28.2) for the first and second series of measurements, respectively. The greater amplitude of foveal choroidal thickness was associated with thickner initial foveal choroidal thickness [0.05 (0.03, 0.08), P=0.01], dominant eye [10.51 (4.02, 14.60), P=0.04] in the multivariate linear regression. CONCLUSION: Our data show a significant diurnal variation of the choroidal thickness at fovea, at 500 µm nasal and temporal to fovea and 1500 µm nasal to fovea. Thicker initial foveal choroidal thickness and being dominant eye may influence the amplitude of foveal choroidal thickness.

C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus.

AIM: To investigate the relationship between C-reactive protein (CRP) and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: Community-based observational cohort study. There were 1131 participants recruited from November 2009 to September 2011 in Desheng community in urban Beijing. Patients diagnosed T2DM were recruited and underwent a standardized evaluation consisting of a questionnaire, ocular and anthropometric examinations and laboratory investigation. The presence and severity of DR were assessed by seven fields 30° color fundus photographs. Subjects were then classified into groups with no DR, any DR, or vision-threatening DR. CRP was analyzed from serum of study subjects. RESULTS: A total of 1007 patients with T2DM were included for analysis, including 408 (40.5%) men and 599 (59.5%) women. The median CRP level was 1.5 mg/L for women and 1.1 mg/L for men (P=0.004, OR 0.37, 95% CI 0.18-0.74). After adjusting for possible covariates, higher levels of CRP were associated with lower prevalence of any DR (P=0.02, OR 0.55, 95% CI 0.35-0.89), but not associated with vision-threatening DR (P=0.62, OR 0.78, 95% CI 0.28-2.14). After stratification by sex, the inverse association between CRP and DR was found to be statistically significant in men (P=0.006, OR 0.35, 95% CI 0.16-0.73), but not in women (P=0.58, OR 0.88, 95% CI 0.29-1.16). CONCLUSION: The data drawn from a Chinese population with T2DM suggest that increasing CRP levels may be inversely associated with development of DR.

Relationship of retinal vascular calibre and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study.

AIMS: To describe the relationship of retinal arteriolar and venular calibre with diabetic retinopathy (DR) and related risk factors, including glucose levels and other biomarkers in a Chinese population with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study. Patients with T2DM were recruited from a local community in urban Beijing. Seven fields 30° colour fundus photographs were taken and examined for the presence and severity of DR using a standardised grading system. Retinal vascular calibres were measured and expressed as average central retinal arteriolar and venular equivalent using a computer-based program. RESULTS: A total of 1340 patients with T2DM were included for analysis. Of these, 472 (35.22%) had DR. Wider retinal venular calibre, but not arteriolar calibre, was associated with increasing glucose and glycosylated haemoglobin A1c levels (p<0.006) and dyslipidaemia (p for trend <0.05). After adjusting for possible covariates, the higher quartile of retinal venular calibre was associated with higher prevalence of any DR (OR 2, 95% CI 1.36 to 2.95). Venular calibre increased from 224.33 µm in those without retinopathy to 231.21 µm in those with mild, 241.01 µm in those with moderate and 235.65 µm in those with severe retinopathy (p for trend <0.001). Arteriolar calibre was not associated with DR. CONCLUSIONS: In the current study, wider venular calibre, but not arteriolar calibre, was shown to be associated with development and increased severity of DR independently from other risk factors in a Chinese diabetic population.

Measurement of macular pigment optical density among healthy Chinese people and patients with early-stage age-related macular degeneration.

AIM: To measure the macular pigment optical density (MPOD) in healthy Chinese people and patients with early age-related macular degeneration (AMD). METHODS: Cross-sectional population based study. Demographic and lifestyle characteristics were ascertained by questionnaire. A food frequency questionnaire was completed for all participants. Participants underwent general physical and ophthalmic examinations and MPOD was measured by heterochromatic flicker photometry. Foveal architecture was measured by optical coherence tomography. RESULTS: MPOD of 225 participants (122 healthy and 103 early AMD) was 0.48±0.18. Patients with early AMD (0.52±0.19) tended to have higher MPOD levels than healthy people (0.47±0.17), but the difference was not statistically significant (P=0.06). Participants with carrot or corn oil intake every week tended to have higher levels of MPOD (P=0.002 and 0.008 respectively) while those with corn intake had relatively lower level of MPOD (P=0.01). MPOD increased with the center foveal thickness (P=0.01). CONCLUSION: Our findings show that there is no statistically significant association between MPOD and early AMD in the studied population. MPOD is related to center foveal thickness and diets would influence MPOD levels.

Use of cataract surgery in urban Beijing: a post screening follow-up of the elderly with visual impairment due to age-related cataract.

OBJECTIVE: To understand the perception for the use of cataract surgical services in a population of acceptors and non-acceptors of cataract surgery in urban Beijing. METHODS: From a community-based screening program a total of 158 patients with presenting visual acuity of less than 6/18 on either eye due to age-related cataract were informed about the possibility of surgical treatment. These patients were interviewed and re-examined 36 to 46 months after initial screening. The main reasons for not accepting surgery were obtained using a questionnaire. Vision function and vision-related quality of life scores were assessed in those who received and did not receive surgery. RESULTS: At the follow-up examination 116 of the 158 patients were available and 36 (31.0%) had undergone cataract surgery. Cases who chose surgery had higher education level than those who did not seek surgery (OR=2.64, 95% CI: 1.08-6.63, P=0.02). There were no significant differences in vision function (P=0.11) or quality of life scores (P=0.16) between the surgery group and the non-surgery group. Main reasons for not having surgery included no perceived need (50.0%), feeling of being "too old" (19.2%), and worry about the quality of surgery (9.6%). Cost was cited by 1 (1.9%) subject as the main reason for not seeking surgery. CONCLUSIONS: The data suggest that in China's capital urban center for patients with moderate visual impairment there is a relative low acceptance rate of cataract surgery, mainly due to people's perception of marginal benefits of surgery. Cost is not a determining factor as barrier to undergo surgery and patients with poorer education are less likely to undertake surgery.

Association of C(-106)T polymorphism in aldose reductase gene with diabetic retinopathy in Chinese patients with type 2 diabetes mellitus.

OBJECTIVE: To identify the possible association between C(-106)T polymorphism of the aldose reductase (ALR) gene and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy (DWR) group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C(-106)T polymorphism (rs759853) in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. RESULTS: A total of 268 T2DM patients (129 in the DR group and 139 in the DWR group) were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset (P=0.10) and gender (P=0.78). The success rate of genotyping for the study subjects was 99.6% (267/268), with one case of failure in the DR group. The frequencies of the T allele in the C(-106)T polymorphism were 16.0% (41/256) in the DR group and 19.4% (54/278) in the DWR group (P=0.36). There was no significant difference in the C(-106)T genotypes between the 2 groups (P=0.40). Compared with the wild-type genotype, odds ratio (OR) for the risk of DR was 0.7 (95% CI, 0.38-1.3) for the heterozygous CT genotype and 0.76 (95% CI, 0.18-3.25) for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria (OR=4.61; 95% CI, 2.34-9.05) and insulin therapy (OR=3.43; 95% CI, 1.94-6.09). CONCLUSIONS: Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C(-106)T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.

Candidate gene association study for diabetic retinopathy in Chinese patients with type 2 diabetes.

PURPOSE: To investigate whether variants in a set of eight candidate genes are associated with diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: Case-control study. Patients with T2DM were recruited from the Desheng community in urban Beijing and assigned into a DR group or diabetic without retinopathy (DWR) group, based on the duration of diabetes and grading of fundus images. Twenty-six single-nucleotide polymorphisms (SNPs) within eight candidate genes, including PPARγ, vascular endothelial growth factor (VEGF) and its receptor kinase insert domain receptor (KDR), erythropoietin, aldose reductase, protein kinase C-ß, angiotensin-converting enzyme, and intercellular adhesion molecule 1, were analyzed using the MassARRAY genotyping system. RESULTS: A total of 500 patients with T2DM (216 with DR and 284 with DWR) were enrolled in the study. Significant associations of DR were noted with genotypes of four SNPs-rs699947 (p<0.001), rs833061 (p = 0.001), rs13207351 (p<0.001), and rs2146323 (p=0.006)--in the VEGF gene and one variant, rs2071559, in the KDR gene (p=0.034). After adjustment for covariates, significant association of DR remained with the homozygous genotype of the minor allele for the SNPs rs699947 (odds ratio [OR] = 3.54, 95% confidence interval [CI]: 1.12-11.19), rs833061 (OR = 3.72, 95% CI: 1.17-11.85), rs13207351 (OR = 3.76, 95% CI: 1.21-11.71), and rs2146323 (OR = 2.8, 95% CI: 1.46-5.37) in the VEGF gene as well as the SNP rs2071559 (OR = 1.62, 95% CI: 1.08-2.41) in the KDR gene. However, only rs699947 and rs13207351 in the VEGF gene remained statistically significant after Bonferroni correction. No associations were found in other genes tested. CONCLUSIONS: These data expanded previous observations on the association of DR with variants in the VEGF gene in Chinese patients with T2DM. Moreover, a possible association between DR and KDR polymorphisms is suggested.

Prospective registration, bias risk and outcome-reporting bias in randomised clinical trials of traditional Chinese medicine: an empirical methodological study.

BACKGROUND: Clinical trials on Traditional Chinese Medicine (TCM) should be registered in a publicly accessible international trial register and report on all outcomes. We systematically assessed and evaluated TCM trials in registries with their subsequent publications. OBJECTIVE: To describe the characteristics of TCM trials, estimate bias risk and outcome-reporting bias in clinical trials. DATA SOURCES AND STUDY SELECTION: Fifteen trial registries were searched from their inception to July 2012 to identify randomised trials on TCM including Chinese herbs, acupuncture and/or moxibustion, cupping, tuina, qigong, etc. DATA EXTRACTION: We extracted data including TCM specialty and treated disease/conditions from the registries and searched for subsequent publications in PubMed and Chinese databases. We compared information in the registries of completed trials with any publications focusing on study design, sample size, randomisation, bias risk including reporting bias from the register protocol. RESULTS: 1096 registered randomised trials were identified evaluating TCM, of which 505 were completed studies (46.1%). The most frequent conditions were pain (13.3%), musculoskeletal (11.7%), nervous (8.7%), digestive (7.1%), circulatory (6.5%), respiratory (6.3%), mental and behavioural disorders (6.2%) and cancer (6.0%). The trial register data identified parallel, phase II/III randomised trials with sample size estimations and blinding, but limited information about randomisation (sequence generation and allocation concealment). Comparing trial registration data of 115 completed trials (22.8%) with their subsequent 136 publications, inconsistencies were identified in one or more of the following: sample size (11%), outcome assessor blinding (37.5%), primary outcomes (29%) and safety (28%) reporting. CONCLUSIONS: Increasing numbers of clinical trials investigating a variety of TCM interventions have been registered in international trial registries. The study design of registered TCM trials has improved in estimating sample size, use of blinding and placebos. However, selective outcome reporting is widespread and similar to conventional medicine and therefore study conclusions should be interpreted with caution.

Strategies of digital fundus photography for screening diabetic retinopathy in a diabetic population in urban China.

PURPOSE: To evaluate the effect of mydriasis and different field strategies on technical failure, probability to refer diabetic retinopathy (DR, sensitivity) and probability not to refer patients without DR (specificity) of digital photography in screening with a fundus camera. METHODS: A total of 531 patients with diabetes underwent fundus photography with cross-combinations of mydriasis/nonmydriasis and single-field/two-field strategies, followed by slit lamp biomicroscopic examination by a trained ophthalmologist. Fundus photographs were graded independently by another experienced ophthalmologist. Calculations were first based on cases with non-gradable images treated as being referred and then with them excluded. RESULTS: Percentages of DR and referable DR in this patient cohort were 22.4% and 7.7%, respectively, based on slit lamp biomicroscopic examination. Mydriasis significantly reduced the technical failure rate from 27.1% to 8.3% under a single-field strategy, and from 28.2% to 8.9% under a two-field strategy. As compared to the single-field strategy, the two-field strategy increased sensitivity from 75.6% to 87.8% without mydriasis and from 73.2% to 90.2% with mydriasis. Mydriasis increased specificity from 68.8% to 84.3% in the single-field strategy and from 64.7% to 81.6% in the two-field strategy. Had the subjects with non-gradable images been excluded, the two-field strategy without mydriasis reported sensitivity of 85.7% and specificity of 91.6%. CONCLUSIONS: Both mydriasis and the two-field strategy are useful in photographic screening tests. Technical failure should be taken into consideration when screening strategies for DR are determined.

Association of glutathione S-transferase pi isoform single-nucleotide polymorphisms with exudative age-related macular degeneration in a Chinese population.

PURPOSE: To investigate the association between single-nucleotide polymorphisms in the pi isoform of glutathione S-transferase (GSTP1) gene and the risk of exudative age-related macular degeneration (AMD) in a Chinese case-control cohort. METHODS: A total of 131 Chinese patients with exudative AMD and 138 control individuals were recruited. Genomic DNA was extracted from venous blood leukocytes. Two common nonsynonymous single-nucleotide polymorphisms in GSTP1 (rs1695 and rs1138272) were genotyped by polymerase chain reaction followed by allele-specific restriction enzyme digestion and direct sequencing. RESULTS: Significant association with exudative AMD was detected for single-nucleotide polymorphism, rs1695 (P = 0.019). The risk G allele frequencies were 21.8% in AMD patients and 12.7% in control subjects (P = 0.007). Compared with the wild-type AA genotype, odds ratio for the risk of AMD was 1.91 (95% confidence interval, 1.09-3.35) for the heterozygous AG genotype and 2.52 (95% confidence interval, 0.6-10.61) for the homozygous GG genotype. In contrast, rs1138272 was not associated with exudative AMD (P = 1.00). The risk G allele frequencies of rs1138272 were 0.4% in AMD patients and 0.4% in control subjects (P = 1.00). CONCLUSION: Our data suggest that the GSTP1 variant rs1695 moderately increases the risk of exudative AMD. The variant rs1138272 was rare and was not associated with exudative AMD in this Chinese cohort.

Measurement of macular pigment optical density in a healthy Chinese population sample.

PURPOSE: Macular pigment may protect against age-related macular degeneration (AMD) by its capacity to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasian populations. The purpose of this study was to assess macular pigment density and its determinant factors in a Chinese population sample. METHODS: Macular pigment optical density (MPOD) was measured in a healthy Chinese population using heterochromatic flicker photometry (HFP). Participants received a standard ophthalmic examination, and only subjects who were confirmed not to have any eye diseases except mild age-related cataract were included in the study. Demographic and lifestyle data and general health status were recorded by questionnaire. RESULTS: A total of 281 unrelated healthy Chinese individuals, including 96 males and 185 females, with ages ranging from 17 to 85 years, participated in the study. The mean and standard deviation of MPOD levels were 0.56 ± 0.19, 0.49 ± 0.18, 0.36 ± 0.15, and 0.19 ± 0.12, respectively, at 0.25°, 0.5°, 1.0°, and 1.75° eccentricity points. A significant age-related decline in MPOD was observed at 0.25° (P = 0.014). Females tended to have relatively lower levels of MPOD than males at 0.25° (P = 0.21), 0.5° (P = 0.025), and 1.0° (P = 0.16). No statistically significant association of MPOD was observed with body mass index or smoking status. CONCLUSIONS: Macular pigment density measured by HFP tended to decline with aging in this healthy Chinese population sample. Females may have lower levels of MPOD than males.

Polymorphisms in the vascular endothelial growth factor gene and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes.

PURPOSE: To investigate whether single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene are associated with diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 268 patients with T2DM (129 with DR and 139 without DR) were recruited and enrolled in the study. Patients with T2DM were assigned to a DR group or a diabetic-without-retinopathy group, based on the duration of diabetes and grading of fundus images. Genotypes of eight SNPs in the VEGF gene (rs699947, rs833061, rs13207351, rs2010963, rs833069, rs2146323, rs3025021, and rs3025039) were analyzed using a mass-array genotyping system, and an association study was performed. RESULTS: After adjusting for covariates, a significant association of DR was observed with the homozygous genotype of the minor allele for promoter SNPs rs699947 (odds ratio (OR)=3.54, 95% confidence interval (CI): 1.12-11.19), rs833061 (OR=3.72, 95% CI: 1.17-11.85) and rs13207351 (OR=3.76, 95% CI: 1.21-11.71). A significant association of DR was also observed with haplotype ACA, as defined by minor alleles of promoter SNPs rs699947, rs833061, and rs13207351 (OR=1.52, 95% CI: 1.03-2.24), and haplotype GAA, as defined by SNPs rs2010963, rs833069, and rs2146323 (OR=1.62, 95% CI: 1.08-2.41). CONCLUSIONS: Our data suggest that polymorphisms in the promoter region of the VEGF gene increase the risk of DR in Chinese patients with T2DM.

Apolipoprotein E gene and age-related macular degeneration in a Chinese population.

PURPOSE: To examine the association between apolipoprotein E (APOE) polymorphisms and age-related macular degeneration (AMD) in a Chinese population. METHODS: The study consisted of 712 subjects, including 201 controls, 363 cases with early AMD, and 148 cases with exudative AMD. Genomic DNA was extracted from venous blood leukocytes. Common allelic variants of APOE (ε2, ε3, and ε4) were analyzed by PCR and direct sequencing. RESULTS: APOE ε3ε3 was the most frequent genotype, with a frequency of 72.6% in controls, 72.5% in early AMD, and 70.3% in exudative AMD. Frequency of the ε2 allele was 6.7% in controls, 7.4% in early AMD, and 8.8% in exudative AMD. Frequency of the ε4 allele was 8.7% in controls, 7.7% in early AMD, and 7.8% in exudative AMD. No statistically significant difference in APOE genotype and allele frequency distribution was observed among controls, cases with early AMD, and cases with exudative AMD. For ε2 allele carriers, the odds ratio was 1.12 (95% confidence interval [CI], 0.65-1.93) for early AMD and 1.06 (95% CI, 0.53-2.10) for exudative AMD. For ε4 allele carriers, the odds ratio was 1.04 (95% CI, 0.61-1.75) for early AMD and 0.83 (95% CI, 0.42-1.62) for exudative AMD. CONCLUSIONS: Our data provide no evidence to support an association of APOE polymorphisms with early or exudative AMD, suggesting that APOE is less likely to be a major AMD susceptibility gene in the Chinese population.

Serum carotenoids and risk of age-related macular degeneration in a chinese population sample.

PURPOSE: It has been hypothesized that the macular carotenoids protect against age-related macular degeneration (AMD). In this study, the association between serum concentrations of carotenoids and the presence of AMD was evaluated in a case-control sample of elderly Chinese subjects. METHODS: Two hundred sixty-three individuals aged between 50 and 88 years enrolled in the study. Subjects included 82 cases with exudative AMD, 92 cases with early AMD, and 89 control individuals. Serum carotenoids (lutein, zeaxanthin, lycopene, α- and ß-carotenes, and ß-cryptoxanthin) and retinol were measured with reversed-phase high-performance liquid chromatography (HPLC). RESULTS: Serum levels of carotenoids and retinol were significantly lower in the cases with exudative AMD than in the controls. Median levels of lutein and zeaxanthin were 0.538 and 0.101 µM, respectively, in the control subjects, and 0.488 and 0.076 µM, respectively, in cases with exudative AMD. After adjustment for age, sex, smoking status, and body mass index (BMI), a significant inverse association was observed for exudative AMD with serum zeaxanthin (relative risk ratio [RRR], 0.04; 95% confidence interval [CI], 0-0.35), lycopene (RRR, 0.22; 95% CI, 0.1-0.48), and α-carotene (RRR, 0.24; 95% CI, 0.12-0.51). Early AMD was inversely associated only with lycopene (RRR, 0.49; 95% CI, 0.28-0.86) but was positively associated with α-carotene (RRR, 2.22; 95% CI, 1.37-3.58). No significant associations were observed between serum lutein and cases with early or exudative AMD. CONCLUSIONS: The data suggest that higher levels of serum carotenoids, in particular zeaxanthin and lycopene, are associated with a lower likelihood of having exudative AMD. Serum levels of carotenoids were relatively higher in this Chinese cohort than in samples of other ethnicities in previous reports.