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1.  New Systematic Review Methodology for Visual Impairment and Blindness for the 2010 Global Burden of Disease Study 
Ophthalmic epidemiology  2013;20(1):33-39.
To describe a systematic review of population-based prevalence studies of visual impairment (VI) and blindness worldwide over the past 32 years that informs the Global Burden of Diseases, Injuries and Risk Factors Study.
A systematic review (Stage 1) of medical literature from 1 January 1980 to 31 January 2012 identified indexed articles containing data on incidence, prevalence and causes of blindness and VI. Only cross-sectional population-based representative studies were selected from which to extract data for a database of age- and sex-specific data of prevalence of 4 distance and one near visual loss categories (presenting and best-corrected). Unpublished data and data from studies using ‘rapid assessment’ methodology were later added (Stage 2).
Stage 1 identified 14,908 references, of which 204 articles met the inclusion criteria. Stage 2 added unpublished data from 44 ‘rapid assessment studies’ and 4 other surveys. This resulted in a final dataset of 252 articles of 243 studies, of which 238 (98%) reported distance vision loss categories. Thirty-seven studies of the final dataset reported prevalence of mild VI and 4 reported near vision impairment.
We report a comprehensive systematic review of over 30 years of VI/blindness studies. While there has been an increase in population-based studies conducted in the 2000’s compared to previous decades; there is limited information from certain regions (eg. Central Africa and Central and Eastern Europe, and the Caribbean and Latin America), younger age groups and minimal data regarding prevalence of near vision and mild distance visual impairment.
PMCID: PMC3962016  PMID: 23350553
2.  Foveal Morphology Affects Self-Perceived Visual Function and Treatment Response in Neovascular Age-Related Macular Degeneration: A Cohort Study 
PLoS ONE  2014;9(3):e91227.
To investigate the relationship between foveal morphology and self-perceived visual function in patients with neovascular age-related macular degeneration (AMD) and whether foveal characteristics are associated with Ranibizumab treatment response on the self-perceived visual function.
This prospective cohort study included patients with newly diagnosed neovascular AMD found eligible for treatment with Ranibizumab. Foveal morphology of both eyes was assessed using spectral-domain optical coherence tomography and all patients were interviewed using the 39-item National Eye Institute Visual Function Questionnaire (VFQ). Patients were re-interviewed 3 and 12 months after initiation of treatment with Ranibizumab. We evaluated foveal morphology at baseline in relation to VFQ scores at baseline and clinically meaningful changes in VFQ after 3 and 12 months.
VFQ scores correlated with central foveal thickness, central foveal thickness of neuroretina (CFN), foveal RPE elevation, foveal integrity of the photoreceptor inner segment/outer segment junction (IS/OS), and external limiting membrane. In a multiple linear regression model, only best-corrected visual acuity of the better eye (p<0.001) and the IS/OS status in the better eye (p = 0.012) remained significant (Adjusted R2 = 0.418). Lower baseline VFQ and a baseline CFN within 170–270 µm in the better eye were both associated with a clinically meaningful increase in the VFQ scores after 3 and 12 months. An absent foveal IS/OS band in the better eye was associated with a clinically meaningful decrease in the VFQ scores at 12 months.
Foveal morphology in the better eye influences the self-perceived visual function in patients with neovascular AMD and possesses a predictive value for change in the self-perceived visual function at 3 and 12 months after initiation of treatment. These findings may help clinicians provide patients more individualized information of their disease and treatment prognosis from a patient-perceived point-of-view.
PMCID: PMC3949984  PMID: 24618706
3.  Spectacle Design Preferences among Chinese Primary and Secondary Students and Their Parents: A Qualitative and Quantitative Study 
PLoS ONE  2014;9(3):e88857.
To identify the specific characteristics making glasses designs, particularly those compatible with adjustable glasses, more or less appealing to Chinese children and their parents.
Patients and Methods
Primary and secondary school children from urban and rural China with < = −1.00 diopters of bilateral myopia and their parents ranked four conventional-style frames identified by local optical shops as popular versus four child-specific frames compatible with adjustable spectacles. Scores based on the proportion of maximum possible ranking were computed for each style. Selected children and their parents also participated in Focus Groups (FGs) discussing spectacle design preference. Recordings were transcribed and coded by two independents reviewers using NVivo software.
Among 136 urban primary school children (age range 9–11 years), 290 rural secondary school children (11–17 years) and 16 parents, all adjustable-style frames (scores on 0–100 scale 25.7–62.4) were ranked behind all conventional frames (63.0–87.5). For eight FGs including 12 primary children, 26 secondary children and 16 parents, average kappa values for NVivo coding were 0.81 (students) and 0.70 (parents). All groups agreed that the key changes to make adjustable designs more attractive were altering the round lenses to rectangular or oval shapes and adding curved earpieces for more stable wear. The thick frames of the adjustable designs were considered stylish, and children indicated they would wear them if the lens shape were modified.
Current adjustable lens designs are unattractive to Chinese children and their parents, though this study identified specific modifications which would make them more appealing.
PMCID: PMC3940429  PMID: 24594799
4.  Visual Difficulty and Employment Status in the World 
PLoS ONE  2014;9(2):e88306.
Using a world-wide, population-based dataset, we sought to examine the relationship between visual difficulty and employment status.
The World Health Survey was conducted in 70 countries throughout the world in 2003 using a random, multi-stage, stratified, cluster sampling design. Far vision was assessed by asking about the level of difficulty in seeing and recognizing a person you know across the road (i.e. from a distance of about 20 meters). Responses included none, mild, moderate, severe, or extreme/unable. Participants were asked about their current job, and if they were not working, the reason why (unable to find job, ill health, homemaker, studies, unpaid work, other). The occupation in the last 12 months was obtained. Multinomial regression was used accounting for the complex survey design.
Of those who wanted to work, 79% of those with severe visual difficulty and 64% of those with extreme visual difficulty were actually working. People who had moderate, severe, or extreme visual difficulty had a higher odds of not working due to an inability to find a job and of not working due to ill health after adjusting for demographic and health factors (P<0.05).
As the major causes of visual impairment in the world are uncorrected refractive error and cataract, countries are losing a great deal of labor productivity by failing to provide for the vision health needs of their citizens and failing to help them integrate into the workforce.
PMCID: PMC3917855  PMID: 24516632
5.  Body Height, Estimated Cerebrospinal Fluid Pressure and Open-Angle Glaucoma. The Beijing Eye Study 2011 
PLoS ONE  2014;9(1):e86678.
To examine potential associations between body height, cerebrospinal fluid pressure (CSFP), trans-lamina cribrosa pressure difference (TLCPD) and prevalence of open-angle glaucoma (OAG) in a population-based setting.
The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range:50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44×Body Mass Index[kg/m2]+0.16×Diastolic Blood Pressure[mmHg]-0.18×Age[Years]-1.91
Data of IOP and CSFP were available for 3353 (96.7%) subjects. Taller body height was associated with higher CSFP (P<0.001; standardized correlation coefficient beta:0.13; regression coefficient B:0.29; 95% confidence interval (CI):0.25,0.33) after adjusting for male gender, urban region of habitation, higher educational level, and pulse rate. If TLCPD instead of CSFP was added, taller body height was associated with lower TLCPD (P<0.001;beta:−0.10;B:−0.20;95%CI:−0.25,−0.15). Correspondingly, higher CSFP was associated with taller body height (P = 0.003;beta:0.02;B:0.01;95%CI:0.00,0.02), after adjusting for age, gender, body mass index, pulse, systolic blood pressure, and blood concentration of cholesterol. If IOP was added to the model, higher CSFP was associated with higher IOP (P<0.001;beta:0.02;B:0.02;95%CI:0.01,0.03). TLCPD was associated with lower body height (P = 0.003;beta:−0.04;B −0.02,95%CI:−0.04,−0.01) after adjusting for age, body mass index, systolic blood pressure, pulse, blood concentrations of triglycerides, axial length, central corneal thickness, corneal curvature radius, and anterior chamber depth. Adding the prevalence of OAG to the multivariate analysis revealed, that taller body height was associated with a lower OAG prevalence (P = 0.03;beta:−0.03;B:−1.20;95%CI:−2.28,−0.12) after adjusting for educational level and gender.
Taller body height was associated with higher CSFP and lower TLCPD (and vice versa), after adjusting for systemic and ocular parameters. Parallel to the associations between a higher prevalence of glaucoma with a lower CSFP or higher TLCPD, taller body height was associated with a lower prevalence of OAG.
PMCID: PMC3906067  PMID: 24489767
6.  Ologen Implant versus Mitomycin C for Trabeculectomy: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(1):e85782.
To evaluate the application of the Ologen implant compared to mitomycin C (MMC) on the outcome of trabeculectomy and to examine the balance of risks and benefits.
A systematic literature search (Pubmed, Embase, the Cochrane Library, and the Chinese Biomedicine Database) was performed. Randomized controlled trials comparing the Ologen implant with MMC in trabeculectomy were selected. The efficacy measures were the weighted mean differences (WMDs) for the intraocular pressure reduction (IOPR), the reduction in glaucoma medications, and the relative risks (RRs) for success rates. The tolerability measures were RRs for adverse events. The pooled effects were calculated using the random-effects model.
Seven randomized controlled trials including 227 eyes were included in this meta-analysis. The WMDs of the IOPR comparing the Ologen group with the MMC group were −2.98 (95% Cl: −5.07 to −0.89) at one month, −1.41 (−3.72 to 0.91) at three months, −1.69 (−3.68 to 0.30) at six months, −1.94 (−3.88 to 0.01) at 12 months, and 0.65 (−2.17 to 0.47) at 24 months. There was no statistically significance except at one and 12 months after surgery. No significant difference in the reduction in glaucoma medications or complete and qualified success rates were found. The rates of adverse events also did not differ significantly between Ologen and MMC.
The Ologen implant is comparable with MMC for trabeculectomy in IOP-lowering efficacy, reduction in the number of glaucoma medications, success rates, and tolerability. However, the results should be interpreted cautiously since relevant evidence is still limited, although it is accumulating. Further large-scale, well-designed randomized controlled trials are urgently needed.
PMCID: PMC3896400  PMID: 24465704
7.  Gender Difference in the Association of Metabolic Syndrome and Its Components with Age-Related Cataract: The Korea National Health and Nutrition Examination Survey 2008-2010 
PLoS ONE  2014;9(1):e85068.
To explore the relationship of the metabolic syndrome (MetS) and its components with age-related cataract in a representative Korean population.
We analyzed the data from the Korea National Health and Nutrition Examination Surveys (2008–2010). A total of 11,076 adults (4,811 men and 6,265 women) aged 40 and over who completed ophthalmologic examination were evaluated. Cataract was defined as the presence of cortical, nuclear, anterior (sub)capsular or posterior subcapsular cataract, from slit-lamp examination or previous cataract surgery. MetS was defined according to the Joint Interim Statement proposed in 2009 from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute.
The prevalence of cataract and MetS in this population was 39.4% (37.1% for men and 41.6% for women) and 38.5% (37.6% for men and 39.4% for women), respectively. Cataract prevalence tended to increase with the number of MetS components in both genders (both P< 0.001). After being controlled for confounders, however, MetS was significantly associated with cataract only in women (adjusted odds ratio (aOR), 1.24; 95% confidence interval (CI), 1.02–1.50]. Reduced HDL cholesterol, elevated fasting glucose, and elevated triglycerides were also significantly associated with cataract in women (aOR, 95% CI; 1.27 (1.07–1.50), 1.23 (1.01–1.50), and 1.26 (1.04–1.52), respectively). In the subgroup analysis for cataract subtype, MetS and reduced HDL cholesterol were significantly associated with nuclear cataract in women (aOR, 95% CI; 1.25 (1.07–1.55) and 1.25 (1.03–1.52), respectively). However, such associations were not found in men.
Our results suggest that MetS and its components appear to be associated with age-related cataract only among Korean women, especially in nuclear cataract.
PMCID: PMC3885677  PMID: 24416342
8.  Imaging Evidence of Diabetic Choroidopathy In Vivo: Angiographic Pathoanatomy and Choroidal-Enhanced Depth Imaging 
PLoS ONE  2013;8(12):e83494.
To describe the pathoanatomy of diabetic choroidopathy (DC) in pre-diagnosed diabetic retinopathy (DR) cases and to provide angiographic and optical evidence for DC using indocyanine green angiography (ICGA) and enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT).
A retrospective analysis of 80 eyes from 40 DR patients was conducted. In Group One, choroidal vascular abnormalities were evaluated by comparing angiographic findings from simultaneous ICGA with those from fundus fluorescein angiography (FFA). In Group Two, EDI SD-OCT was used to evaluate the subfoveal choroidal thickness (SFCT) and define the choroid boundary in order to acquire the bilateral and symmetric choroidal area (CA). Data were then analyzed by Image Pro Plus 6.0.
In Group One, choroidal abnormalities that were evident using ICGA but not FFA included early hypofluorescent spots in 47 eyes (75.81%), late hyperfluorescent spots in 37 eyes (59.68%), and late choroidal non-perfusion regions in 32 eyes (51.61%). In particular, a significant difference between proliferative DR (PDR) in 17 of 23 eyes (73.91%) and non-PDR in 16 of 39 eyes (41.03%) was observed in late choroidal non-perfusion regions. Eighteen of 31 eyes (58.06%) also exhibited “inverted inflow phenomena.” In Group Two, both the SFCT and CA of eyes with diabetic macular edema and serous macular detachment were significantly greater than those in the other eyes. The CA in panretinal photocoagulation (PRP) treated cases was also greater than that in non-PRP treated cases.
Early hypofluorescent spots, late choroidal non-perfusion regions, inverted inflow phenomena, higher SFCT, and larger CA are qualitative and quantitative indexes for DC. Moreover, the late choroidal non-perfusion region is a risk factor for DC with DR. Our study suggests that the supplemental use of ICGA and EDI SD-OCT with FFA is a better choice for DR patients.
PMCID: PMC3862692  PMID: 24349522
9.  Trans-Lamina Cribrosa Pressure Difference and Open-Angle Glaucoma. The Central India Eye and Medical Study 
PLoS ONE  2013;8(12):e82284.
To assess associations of the trans-lamina cribrosa pressure difference (TLCPD) with glaucomatous optic neuropathy.
The population-based Central India Eye and Medical Study included 4711 subjects. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44 Body Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]−0.18×Age[Years] −1.91. TLCPD was IOP–CSFP.
Mean TLCPD was 3.64±4.25 mm Hg in the non-glaucomatous population and 9.65±8.17 mmHg in the glaucomatous group. In multivariate analysis, TLCPD was associated with older age (P<0.001; standardized coefficient beta:0.53; regression coefficient B:0.18; 95% confidence interval (CI):0.17, 0.18), lower body mass index (P<0.001; beta: −0.28; B: −0.36; 95%CI: −0.38, −0.31), lower diastolic blood pressure (P<0.001; beta: −0.31; B: −0.12; 95%CI: −0.13, −0.11), higher pulse (P<0.001; beta:0.05; B:0.02; 95%CI:0.01,0.2), lower body height (P = 0.02; beta: −0.02; B: −0.01; 95%CI: −0.02,0.00), higher educational level (P<0.001; beta:0.04; B:0.15; 95%CI:0.09,0.22), higher cholesterol blood concentrations (P<0.001; beta:0.04; B:0.01; 95%CI:0.01,0.01), longer axial length (P = 0.006; beta:0.03; B:0.14; 95%CI:0.04,0.24), thicker central cornea (P<0.001; beta:0.15; B:0.02; 95%CI:0.02,0.02), higher corneal refractive power (P<0.001; beta:0.07; B:0.18; 95%CI:0.13,0.23) and presence of glaucomatous optic neuropathy (P<0.001; beta:0.11; B:3.43; 95%CI:2.96,3.99). Differences between glaucomatous subjects and non-glaucomatous subjects in CSFP were more pronounced for open-angle glaucoma (OAG) than for angle-closure glaucoma (ACG) (3.0 mmHg versus 1.8 mmHg), while differences between glaucomatous subjects and non-glaucomatous subjects in IOP were higher for ACG than for OAG (8.5 mmHg versus 3.0 mmHg). Presence of OAG was significantly associated with TLCPD (P<0.001; OR:1.24; 95%CI:1.19,1.29) but not with IOP (P = 0.08; OR:0.96; 95%CI:0.91,1.00). Prevalence of ACG was significantly associated with IOP (P = 0.04; OR:1.19; 95%CI:1.01,1.40) but not with TLCPD (P = 0.92).
In OAG, but not in ACG, calculated TLCPD versus IOP showed a better association with glaucoma presence and amount of glaucomatous optic neuropathy. It supports the notion of a potential role of low CSFP in the pathogenesis of open-angle glaucoma.
PMCID: PMC3855749  PMID: 24324767
10.  Visual Impairment as a Function of Visual Acuity in Both Eyes and Its Impact on Patient Reported Preferences 
PLoS ONE  2013;8(12):e81042.
To assess the impact of VA loss on patient reported utilities taking both eyes into account compared to taking only the better or the worse eye into account.
In this cross-sectional study 1085 patients and 254 controls rated preferences with the generic health-related (EQ-5D; n = 868) and vision-specific (Vision and Quality of Life Index (VisQoL); n = 837) multi-attribute utility instruments (MAUIs). Utilities were calculated for three levels of VA in the better and worse eyes, as well as for 6 different vision states based on combinations of the better and worse eye VA.
Using the VisQoL, utility scores decreased significantly with deteriorating vision in both the better and worse eyes when analysed separately. When stratified by the 6 vision states, VisQoL utilities decreased as VA declined in the worse eye despite stable VA in the better eye. Differences in VisQoL scores were statistically significant for cases where the better eye had no vision impairment and the worse seeing fellow eye had mild, moderate or severe vision impairment. In contrast, the EQ-5D failed to capture changes in better or worse eye VA, or any of the six vision states.
Calculating utilities based only on better eye VA or using a generic MAUI is likely to underestimate the impact of vision impairment, particularly when the better eye has no or little VA loss and the worse eye is moderately to severely visually impaired. These findings have considerable implications for the assessment of overall visual impairment as well as economic evaluations within eye health.
PMCID: PMC3855212  PMID: 24339893
11.  Prevalence and Associated Factors for Pterygium in Rural Agrarian Central India. The Central India Eye and Medical Study 
PLoS ONE  2013;8(12):e82439.
To evaluate the prevalence of pterygia and associated factors in a rural population in a mostly undeveloped agrarian region.
The Central India Eye and Medical Study is a population-based study performed in a rural region of Central India. The study comprised 4711 subjects (aged 30+ years). A detailed ophthalmic and medical examination was performed. A pterygium was diagnosed during the slit lamp examination and confirmed on corneal photographs. It was defined as a fleshy fibrovascular growth, crossing the limbus and typically seen on the nasal, and sometimes temporal, conjunctiva.
A pterygium was detected in 798 eyes (prevalence rate: 8.47±0.29%) of 608 (12.91±0.49%) subjects. Bilateral pterygia were present in 190 subjects (4.0% of study population). Pterygia prevalence increased from 6.7±0.8% in the age group 30-39 years, to 13.5±1.2% in the age group 50-59 years, to 25.3±2.1% in the age group 70-79 years. Prevalence of pterygia was associated with older age (P<0.001; regression coefficient B: 0.02; odds ratio (OR): 1.02; 95%CI: 1.01, 1.03), male gender (P<0.001;B:-0.73;OR: .48;95%CI:0.39,0.61), lower level of education (P<0.001;B:-0.30;OR:0.74;95%CI:0.69,0.80), lower body height (P=0.001;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.26;95%CI:1.18,1.34). If the education level was dropped, the number of hours spent with vigorous activity outdoors (P=0.001;B:0.001;OR:1.001;95%CI:1.000,1.0001) was significantly associated with the prevalence of pterygia, in addition to older age (P<0.001;B:0.03;OR:1.03;95%CI:1.03,1.04), male gender (P<0.001;B:-0.49;OR:0.62;95%CI:0.49,0.77), lower body height (P=0.005;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.25;95%CI:1.18,1.34).
Pterygium prevalence in rural Central India is about 13% among adult Indians aged 30+ years. Older age, male gender, lower educational level, lower body height and more time spent outdoors with vigorous work were associated factors. Since the living conditions in the study location were mostly untouched by modern developments, the results may show the prevalence and associations of pterygia without major medical or technologic influences.
PMCID: PMC3854013  PMID: 24324789
12.  Prevalence and Risk Factors for Refractive Errors: Korean National Health and Nutrition Examination Survey 2008-2011 
PLoS ONE  2013;8(11):e80361.
To examine the prevalence and risk factors of refractive errors in a representative Korean population aged 20 years old or older.
A total of 23,392 people aged 20+ years were selected for the Korean National Health and Nutrition Survey 2008–2011, using stratified, multistage, clustered sampling. Refractive error was measured by autorefraction without cycloplegia, and interviews were performed regarding associated risk factors including gender, age, height, education level, parent's education level, economic status, light exposure time, and current smoking history.
Of 23,392 participants, refractive errors were examined in 22,562 persons, including 21,356 subjects with phakic eyes. The overall prevalences of myopia (< -0.5 D), high myopia (< -6.0 D), and hyperopia (> 0.5 D) were 48.1% (95% confidence interval [CI], 47.4–48.8), 4.0% (CI, 3.7–4.3), and 24.2% (CI, 23.6–24.8), respectively. The prevalence of myopia sharply decreased from 78.9% (CI, 77.4–80.4) in 20–29 year olds to 16.1% (CI, 14.9–17.3) in 60–69 year olds. In multivariable logistic regression analyses restricted to subjects aged 40+ years, myopia was associated with younger age (odds ratio [OR], 0.94; 95% Confidence Interval [CI], 0.93-0.94, p < 0.001), education level of university or higher (OR, 2.31; CI, 1.97–2.71, p < 0.001), and shorter sunlight exposure time (OR, 0.84; CI, 0.76–0.93, p = 0.002).
This study provides the first representative population-based data on refractive error for Korean adults. The prevalence of myopia in Korean adults in 40+ years (34.7%) was comparable to that in other Asian countries. These results show that the younger generations in Korea are much more myopic than previous generations, and that important factors associated with this increase are increased education levels and reduced sunlight exposures.
PMCID: PMC3818255  PMID: 24224049
13.  Comparison of Dry Eye and Corneal Sensitivity between Small Incision Lenticule Extraction and Femtosecond LASIK for Myopia 
PLoS ONE  2013;8(10):e77797.
To investigate the changes in dry eye symptoms and clinical signs and corneal sensitivity after small incision lenticule extraction (SMILE) and femtosecond LASIK (femto-LASIK).
Prospective, non-randomized comparative study.
The study included a total of 71 eyes of 71 patients; the SMILE group comprised 38 eyes of 38 patients, and the femto-LASIK group comprised 33 eyes of 33 patients. Ocular Surface Disease Index (OSDI), Tear film breakup time (TBUT), the Schirmer test without anesthesia (S1T), corneal fluorescein staining, and central corneal sensation were evaluated before surgery and at 1 week, 1 month, 3 months, and 6 months after surgery.
OSDI scores in both groups were increased immediately and returned to preoperative level at 1 month after surgeries. The TBUT values in both groups were reduced after surgeries relative to their preoperative scores. Patients in SMILE group were less likely to have corneal staining compared with those in the femto-LASIK group ([odds ratio] OR = 0.50, 95% [confidence interval] CI 0.28 to 0.93, P = 0.03). Central corneal sensitivity was decreased at all postoperative time points in both groups. However, the central corneal sensation scores in the SMILE group were greater than that in the femto-LASIK group at all of the postoperative time points (all P<0.05).
SMILE surgeries resulted in a short-term increase in dry eye symptoms, tear film instability, and loss of corneal sensitivity. Furthermore, SMILE surgeries have superiority over femto-LASIK in lower risk of postoperative corneal staining and less reduction of corneal sensation.
PMCID: PMC3812215  PMID: 24204971
14.  Prevalence of Cataract Surgery and Visual Outcomes in Indian Immigrants in Singapore: The Singapore Indian Eye Study 
PLoS ONE  2013;8(10):e75584.
To determine the prevalence of cataract surgery and factors associated with post-surgical visual outcomes in migrant Indians living in Singapore.
Research Design and Methods
We conducted a population-based study in 3,400 Indian immigrants residing in Singapore−the Singapore Indian Eye Study (SINDI). All participants underwent comprehensive medical eye examination and a standardized interview. Post-operative visual impairment (VI) was defined as best-corrected or presenting visual acuity (BCVA or PVA) of 20/60 or worse.
The age- and gender-standardized prevalence of cataract surgery was 9.7% (95% confidence interval [CI]: 8.9%, 10.7%) in Singapore resident Indians. Post-operative VI defined by BCVA occurred in 10.9% eyes (87/795). The main causes of post-operative VI were diabetic retinopathy (20.7%), posterior capsular opacification (18.4%), and age-related macular degeneration (12.6%). Undercorrected refractive error doubled the prevalence of post-operative VI when PVA was used.
The rate of cataract surgery is about 10% in Indian residents in Singapore. Socioeconomic variables and migration had no significant impact on the prevalence of cataract surgery. Diabetic retinopathy was a major cause of post-operative VI in migrant Indians living in Singapore. Uncorrected postoperative refractive error remains an efficient way to improve vision.
PMCID: PMC3792142  PMID: 24116058
15.  How Often Are Major Blood-Borne Pathogens Found in Eye Patients? A Serosurvey at an Eye Hospital in Southern China 
PLoS ONE  2013;8(9):e73994.
The hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and treponema pallidum (TP) are blood-borne pathogens. They can lead to nosocomial and occupational infections in health care settings. We aimed to identify the prevalence of and risk factors associated with HBV, HCV, HIV and TP infections among patients with eye diseases at a tertiary eye hospital in Southern China.
From July 2011 to June 2012, a total of 26,386 blood units were collected from eye patients, including inpatients and the day surgery patients at Zhongshan Ophthalmic Center, one of the biggest eye hospitals in China. Based on the primary diagnoses from this period, the subjects were classified into different ocular disease groups. All blood samples were tested for HBsAg, anti-HCV, anti-HIV and anti-TP.
The overall prevalence of HBV, HCV, TP and HIV was 9.79%, 0.99%, 2.43% and 0.11%, respectively. The prevalence of HBsAg was much lower among patients younger than 20 years compared to other age groups. In addition, the risk of HBsAg was associated with the male gender, ocular trauma and glaucoma. The prevalence of TP increased with age and the prevalence among patients older than 30 was higher than that in patients younger than 20 years.
The prevalence of HBV, HCV, HIV and TP in patients with eye diseases was identified. This information can be utilised to strengthen the health education and implementation of universal safety precautions to prevent the spread of blood-borne pathogens in health care settings.
PMCID: PMC3762772  PMID: 24023922
16.  Prevalence, Awareness, Medication, Control, and Risk Factors Associated with Hypertension in Bai Ethnic Group in Rural China: The Yunnan Minority Eye Study 
PLoS ONE  2013;8(8):e70886.
This study aimed to assess the prevalence, awareness, treatment, and control of hypertension and their associated factors among Bai ethnic population in the rural China.
A population-based survey was conducted in 2010 with a randomly cluster sampling in rural communities in Dali, southwest China. A total of 2133 adults aged 50 or above were interviewed, and their blood pressure, height, weight and waist circumference were measured. Hypertension was defined as a mean SBP≥140 mmHg and/or DBP≥90 mmHg, and/or current use of antihypertensive medications.
The prevalence of hypertension was 42.1% (899/2133), and the age- and gender-adjusted prevalence was 40.0%. Among the hypertensive participants, 28.4% (255/899)were aware of their condition, while 24.6% (221/899) took antihypertensive medications, with only 7.5% (67/899) of those achieving blood pressure control (<140/90 mmHg). Risk factors for hypertension were older age, smoking, alcohol drinking, family history of HBP, overweight, and obesity, while protective factors included being lean, and having finished senior high school or above.
Hypertension prevalence is high among the population of Bai ethnic group in China, while the associated risk factors of hypertension include overweight/obesity, cigarette smoking, history of hypertension, and older age. The percentages of hypertensive participants aware of their hypertension and those taking antihypertensive medications were low with an incredibly low proportion of hypertensive patients who kept their hypertension under control. It is suggested that health education and hypertension screening programs be carried out in the area for the high blood pressure prevention and control.
PMCID: PMC3741331  PMID: 23951030
17.  Posttranslational Modifications of HIV-1 Integrase by Various Cellular Proteins during Viral Replication 
Viruses  2013;5(7):1787-1801.
HIV-1 integrase (IN) is a key viral enzyme during HIV-1 replication that catalyzes the insertion of viral DNA into the host genome. Recent studies have provided important insights into the multiple posttranslational modifications (PTMs) of IN (e.g., ubiquitination, SUMOylation, acetylation and phosphorylation), which regulate its multifaceted functions. A number of host cellular proteins, including Lens Epithelium‑derived Growth factor (LEDGF/p75), p300 and Ku70 have been shown to interact with IN and be involved in the PTM process of IN, either facilitating or counteracting the IN PTMs. Although previous studies have revealed much about the important roles of IN PTMs, how IN functions are fine-tuned by these PTMs under the physiological setting still needs to be determined. Here, we review the advances in the understanding of the mechanisms and roles of multiple IN PTMs.
PMCID: PMC3738961  PMID: 23863879
HIV; integrase; posttranslational modification; ubiquitination; SUMOylation; acetylation; phosphorylation
18.  Comparison of Visual Performance of Multifocal Intraocular Lenses with Same Material Monofocal Intraocular Lenses 
PLoS ONE  2013;8(6):e68236.
To compare the visual performance of multifocal intraocular lenses (IOLs) and monofocal IOLs made of the same material.
The subjects included patients implanted with either Tecnis® monofocal IOLs (ZA9003 or ZCB00) or Tecnis® multifocal IOLs (ZMA00 or ZMB00) bilaterally. We conducted a retrospective study comparing the two types of IOLs. The multifocal group included 46 patients who were implanted with Tecnis® multifocal IOLs bilaterally. The monofocal group was an age- and sex-matched control group, and included 85 patients who were implanted with Tecnis® monofocal IOLs bilaterally. Lens opacity grading, the radius of corneal curvature, corneal astigmatism, axial length and the refractive status were measured preoperatively. Pupil size, ocular aberrometry, distance, intermediate and near visual acuity, contrast sensitivity with and without glare and the responses to a quality-of-vision questionnaire were evaluated pre- and postoperatively.
The uncorrected near visual acuity was significantly better in the multifocal group, whereas both the corrected intermediate and near visual acuity were better in the monofocal group. Contrast sensitivity (with and without glare) was significantly better in the monofocal group. The rate of spectacle dependency was significantly lower in the multifocal group. There were no significant differences between the two groups regarding most items of the postoperative quality-of-vision questionnaire (VFQ-25), with the exception that the patients in the monofocal group reported fewer problems with nighttime driving.
The multifocal IOLs used in this study reduced spectacle dependency more so than monofocal IOLs and did not compromise the subjective visual function, with the exception of nighttime driving.
PMCID: PMC3695892  PMID: 23840836
19.  In Vivo 3D Meibography of the Human Eyelid Using Real Time Imaging Fourier-Domain OCT 
PLoS ONE  2013;8(6):e67143.
Recently, we reported obtaining tomograms of meibomian glands from healthy volunteers using commercial anterior segment optical coherence tomography (AS-OCT), which is widely employed in clinics for examination of the anterior segment. However, we could not create 3D images of the meibomian glands, because the commercial OCT does not have a 3D reconstruction function. In this study we report the creation of 3D images of the meibomian glands by reconstructing the tomograms of these glands using high speed Fourier-Domain OCT (FD-OCT) developed in our laboratory. This research was jointly undertaken at the Department of Ophthalmology, Seoul St. Mary's Hospital (Seoul, Korea) and the Advanced Photonics Research Institute of Gwangju Institute of Science and Technology (Gwangju, Korea) with two healthy volunteers and seven patients with meibomian gland dysfunction. A real time imaging FD-OCT system based on a high-speed wavelength swept laser was developed that had a spectral bandwidth of 100 nm at the 1310 nm center wavelength. The axial resolution was 5 µm and the lateral resolution was 13 µm in air. Using this device, the meibomian glands of nine subjects were examined. A series of tomograms from the upper eyelid measuring 5 mm (from left to right, B-scan) × 2 mm (from upper part to lower part, C-scan) were collected. Three-D images of the meibomian glands were then reconstructed using 3D “data visualization, analysis, and modeling software”. Established infrared meibography was also performed for comparison. The 3D images of healthy subjects clearly showed the meibomian glands, which looked similar to bunches of grapes. These results were consistent with previous infrared meibography results. The meibomian glands were parallel to each other, and the saccular acini were clearly visible. Here we report the successful production of 3D images of human meibomian glands by reconstructing tomograms of these glands with high speed FD-OCT.
PMCID: PMC3689717  PMID: 23805297
20.  Ex-PRESS Implantation Versus Trabeculectomy in Uncontrolled Glaucoma: A Meta-Analysis 
PLoS ONE  2013;8(5):e63591.
To evaluate the efficacy and tolerability of Ex-PRESS implantation (Ex-Press) compared with trabeculectomy (Trab) in the treatment of patients with uncontrolled glaucoma.
A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify controlled clinical trials comparing Ex-Press with Trab. Efficacy estimates were measured by weight mean difference (WMD) for the percentage intraocular pressure (IOP) reduction from baseline to end-point, odds ratio (OR) for complete success, and qualified success rates. Tolerability estimates were measured by OR for adverse events. All outcomes were reported with a 95% confidence interval (CI). Data were synthesized by Stata 11.0 SE for Windows.
Eight controlled clinical trials meeting the predefined criteria were included in the meta-analysis. A total of 605 eyes from 559 patients with medically uncontrolled glaucoma were included. The weighted mean difference of the percentage IOP reduction from baseline was 2.33 (95% confidence interval: −2.59–7.24) when comparing Ex-Press with Trab. Ex-Press was associated with numerically greater, but nonsignificant, IOP lowering efficacy than Trab. The pooled odds ratio comparing Ex-Press with Trab were 0.93 (0.39, 2.23) for the complete success rate and 1.00 (0.39, 2.56) for the qualified success rate. Ex-Press was associated with a significantly lower frequency of hypotony and hyphema than Trab, with pooled ORs of 0.29 (0.13, 0.65) and 0.36 (0.13, 0.97), respectively.
Ex-Press was associated with equivalent efficacy to Trab in lowering IOP. Comparable proportions of patients reached the IOP target with Ex-Press and Trab. Ex-Press was better tolerated than Trab.
PMCID: PMC3669314  PMID: 23741296
21.  Retinal Vascular Geometry in Asian Persons with Diabetes and Retinopathy 
Our purpose was to examine the relationship of retinal vascular parameters with diabetes and retinopathy in an older Asian population.
Retinal photographs from participants of a population-based survey of Asian Malay persons aged 40–80 years were analyzed. Specific retinal vascular parameters (tortuosity, branching angle, fractal dimension, and caliber) were measured using a semiautomated computer-based program. Diabetes was defined as random plasma glucose ≥ 11.1 mmol/liter, the use of diabetes medication, or physician-diagnosed diabetes. Retinopathy signs were graded from photographs using the modified Airlie House classification system.
A total of 2735 persons were included in the study. Persons with diabetes (n = 594) were more likely to have straighter (less tortuous) arterioles and wider arteriolar and venular caliber than those without diabetes (n = 2141). Among subjects with diabetes, those with retinopathy had wider venular caliber than those without retinopathy (211.3 versus 204.9 mm, p = .001). Among nondiabetic subjects, however, those with retinopathy had more tortuous venules than those without retinopathy [5.19(×104) versus 4.27(×104), p < .001].
Retinal vascular parameters varied by diabetes and retinopathy status in this older Asian cohort. Our findings suggest that subtle alterations in retinal vascular architecture are influenced by diabetes.
PMCID: PMC3440033  PMID: 22768891
diabetes; epidemiology; imaging; retinopathy
22.  Prevalence and Outcomes of Cataract Surgery in Adult Rural Chinese Populations of the Bai Nationality in Dali: The Yunnan Minority Eye Study 
PLoS ONE  2013;8(4):e60236.
To investigate the prevalence and visual acuity (VA) outcomes of cataract surgery in adults of the Bai Nationality populations in rural China.
We conducted a population-based cross-sectional survey (from randomly selected block groups) of Chinese Bai Nationality aged ≥50 years in southwestern China. Presenting visual acuity (PVA), best corrected visual acuity (BCVA) were recorded and a detailed eye examination was carried out. For all aphakic and pseudophakic subjects identified, information on the date, setting, type, and complications of cataract surgery were recorded. In eyes with VA <20/63, the principal cause of visual impairment was identified.
Of 2133 (77.8% of 2742) subjects, 99 people (129 eyes) had undergone cataract surgery. The prevalence of cataract surgery was 4.6%. Surgical coverage among those with PVA <20/200 in both eyes because of cataract was 52.8%. Unoperated cataract was associated with older age. The main barrier to cataract surgery was lack of awareness and knowledge, cost, and fear. Among the 129 cataract-operated eyes, 22.5% had PVA of ≥20/32, 25.6% had PVA of 20/40 to 20/63, 23.3% had PVA <20/63 to 20/200, and 28.7% had PVA<20/200. With BCVA, the percentages were 42.6%, 23.3%, 10.9%, and 23.3%, respectively. Aphakia (odds ratio [OR], 8.49; P<0.001) and no education (OR, 10.18; P = 0.001) or less education (OR, 6.49; P = 0.014) were significantly associated with postoperative visual impairment defined by PVA, while aphakia (OR, 8.49; P<0.001) and female gender (OR, 4.19; P = 0.004) were significantly associated with postoperative visual impairment by BCVA. The main causes of postoperative visual impairment were refractive error, retinal disorders and glaucoma.
Half of those with bilateral visual impairment or blindness because of cataract remain in need of cataract surgery in Bai population. Surgical uptake and visual outcomes should be further improved in the future.
PMCID: PMC3618447  PMID: 23577095
23.  Corneal Endothelial Cells Provide Evidence of Accelerated Cellular Senescence Associated with HIV Infection: A Case-Control Study 
PLoS ONE  2013;8(2):e57422.
Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults.
Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma.
The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00–2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12–6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD.
The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.
PMCID: PMC3584030  PMID: 23460854
24.  Obesity and the Microvasculature: A Systematic Review and Meta-Analysis 
PLoS ONE  2013;8(2):e52708.
Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber.
Methods and Findings
Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m2 increase in BMI was associated with a difference of 0.07 μm [95% CI: −0.08; −0.06] in arteriolar caliber and 0.22 μm [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children.
Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists.
PMCID: PMC3566162  PMID: 23405065
25.  Association of Glutathione S transferases Polymorphisms with Glaucoma: A Meta-Analysis 
PLoS ONE  2013;8(1):e54037.
Glutathione S transferase (GST) polymorphisms have been considered risk factors for the development of glaucoma, including primary open angle glaucoma (POAG) and other types of glaucoma. However, the results remain controversial. In this study, we have conducted a meta-analysis to assess the association between polymorphisms of GSTM1, GSTT1 and GSTP1 and glaucoma risk.
Published literature from PubMed and other databases were retrieved. All studies evaluating the association between GSTM1, GSTT1 and GSTP1 polymorphisms and glaucoma risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.
Twelve studies on GSTM1 (1109 cases and 844 controls), ten studies on GSTT1 (709 cases and 664 controls) and four studies on GSTP1 (543 cases and 511 controls) were included. By pooling all the studies, either GSTM1 or GSTT1 null polymorphism was not associated with a POAG risk, and this negative association maintained in Caucasian. The GSTP1 Ile 105 Val polymorphism was significantly correlated with increased POAG risk among Caucasian in a recessive model (Val/Val vs. Ile/Ile+Ile/Val: OR, 1.62, 95%CI: 1.00–2.61). Interestingly, increased glaucoma risk was associated with the combined GSTM1 and GSTT1 null genotypes (OR, 2.20; 95% CI, 1.47–3.31), and with the combined GSTM1 null and GSTP1 Val genotypes (OR, 1.86; 95% CI, 1.15–3.01).
This meta-analysis suggests that combinations of GST polymorphisms are associated with glaucoma risk. Given the limited sample size, the associations between single GST polymorphism and glaucoma risk await further investigation.
PMCID: PMC3544666  PMID: 23342067

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