Developing a bioink for single-step deposition and maturation of human epidermis.

Patients with severe burns, which cause extensive damage to their skin, require rapid intervention to prevent life-threatening hypothermia, infection, and fluid loss. Current treatments typically involve surgical excision of the burned skin and reconstruction of the wound with the aid of skin autografts. However, there is a lack of donor site in the most severe cases. While alternative treatments such as cultured epithelial autografts and "spray-on" skin can allow much smaller donor tissues to be used (and hence reduce donor site morbidity), they present their own challenges in terms of fragility of the tissues and control of the cell deposition, respectively. Recent advances in bioprinting technology have led researchers to explore its use to fabricate skin grafts, which depend on several factors, including appropriate bioinks, cell types, and printability. In this work, we describe a collagen-based bioink that allows the deposition of a contiguous layer of the keratinocytes directly onto the wound. Special attention was given to the intended clinical workflow. For example, since media changes are not feasible once the bioink is deposited onto the patient, we first developed a media formulation designed to permit a single deposition step and promote self-organization of the cells into the epidermis. Using a collagen-based dermal template populated with dermal fibroblasts, we demonstrated by immunofluorescence staining that the resulting epidermis recapitulates the features of natural skin in expressing p63 (stem cell marker), Ki67 and keratin 14 (proliferation markers), filaggrin and keratin 10 (keratinocyte differentiation and barrier function markers), and collagen type IV (basement membrane protein involved in adherence of the epidermis to the dermis). While further tests are still required to verify its utility as a burn treatment, based on the results we have achieved thus far, we believe that our current protocol can already produce donor-specific model for testing purposes.

Prevalence of Microvascular Complications in Newly Diagnosed Type 2 Diabetes Mellitus in Primary Healthcare Clinics

@#Introduction: Delayed diagnosis of type 2 diabetes mellitus (T2D) increases the risk of presenting late with microvascular complications due to untreated long-standing hyperglycaemia. This study aimed to determine the prevalence of microvascular complications in newly diagnosed T2D patients in primary healthcare clinics. Methods: This was a cross-sectional study carried out in three government primary healthcare clinics in the state of Selangor, Malaysia. Malaysian aged 18 years and above with newly diagnosed T2D (≤ 6 months of diagnosis) were invited to participate in the study. Data collected included the sociodemographic characteristic and the clinical profile (weight, height, waist circumference, blood pressure, lipid, glycaemic, urine albumin, microalbuminuria and renal profile). The assessment of nephropathy, peripheral neuropathy and retinopathy were performed using standard protocol. Multivariate logistic regression analysis was used to identify the significant factors that contribute to the presence of microvascular complications. Results: A total of 162 newly diagnosed patients were recruited. The majority was women (64%). The mean age was 51 (SD 11) years. About one-third of the patients (27.7%) had developed at least one microvascular complication. Nephropathy was the commonest microvascular complication (19.2%), followed by peripheral neuropathy (8.6%) and retinopathy (6.5%). Poor glycaemic control was found to be a significant factor contributing to the presence of microvascular complications (OR 5.8, 95%CI:1.466, 23.288). Conclusion: There is a high prevalence of microvascular complications among the newly diagnosed T2D. There is a need to develop appropriate strategies to increase the awareness and early detection of T2D.

Scalable Geometrically Designed Protein Cages Assembled via Genetically Encoded Split Inteins.

Engineering proteins to assemble into user-defined structures is key in their development for biotechnological applications. However, designing generic rather than bespoke solutions is challenging. Here we describe an expandable recombinant assembly system that produces scalable protein cages via split intein-mediated native chemical ligation. Three types of component are used: two complementary oligomeric "half-cage" protein fusions and an extendable monomeric "linker" fusion. All are composed of modular protein domains chosen to fulfill the required geometries, with two orthogonal pairs of split intein halves to drive assembly when mixed. This combination enables both one-pot construction of two-component cages and stepwise assembly of larger three-component scalable cages. To illustrate the system's versatility, trimeric half-cages and linker constructs comprising consensus-designed repeat proteins were ligated in one-pot and stepwise reactions. Under mild conditions, rapid high-yielding ligations were obtained, from which discrete proteins cages were easily purified and shown to form the desired trigonal bipyramidal structures.

Quantitative assessment of changes in anterior segment morphology after argon laser peripheral iridoplasty: findings from the EARL study group.

IMPORTANCE: Argon laser peripheral iridoplasty (ALPI) could be effective in widening residual angle closure following laser peripheral iridotomy (LPI). BACKGROUND: We investigated changes in angle parameters following ALPI and its safety profile in this study. DESIGN: Retrospective, observational case series. PARTICIPANTS: The records from a single centre, of 36 patients (60 eyes) who underwent ALPI, for residual angle closure following LPI, were reviewed. METHODS: We analysed anterior chamber parameters in anterior segment optical coherence tomography (ASOCT) images using customized software pre- and post-ALPI. Paired t-test was used to compare changes. MAIN OUTCOME MEASURES: ASOCT parameters analysed included angle opening distance (AOD 500 and 750), trabecular iris surface area (TISA 500 and 750), anterior chamber width (ACW), anterior chamber volume (ACV), angle recess area (ARA), anterior chamber area (ACA), anterior chamber depth (ACD) and lens vault (LV). RESULTS: There was a mean increase in AOD 500 (0.05 vs. 0.16 mm, P < 0.001), AOD 750 (0.15 vs. 0.27 mm, P < 0.001), TISA 500 (0.010 vs. 0.038 mm2 , P < 0.001), TISA 750 (0.039 vs. 0.102 mm2 , P < 0.001), ACV (89.76 vs. 102.25 mm3 , P = 0.01), ARA 500 (0.015 vs. 0.033 mm2 , P < 0.001) and ARA 750 (0.044 vs. 0.088 mm2 , P < 0.001). There was no significant change in ACW, ACD, ACA and LV. Mean intraocular pressure (IOP) decreased post-ALPI (17.2 vs. 15.7 mmHg, P = 0.002). The mean follow-up duration was 2.1 years (range 0.5-5 years). CONCLUSIONS AND RELEVANCE: ALPI results in changes to the angle morphology and lowered IOP in eyes with residual angle closure. Our findings suggest a possible role for ALPI in eyes with residual angle closure following peripheral iridotomy.

Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis.

BACKGROUND: Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies. METHODS: We did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013. Only studies using retinal photographs and standardised grading classifications (the Wisconsin age-related maculopathy grading system, the international classification for age-related macular degeneration, or the Rotterdam staging system) were included. Hierarchical Bayesian approaches were used to estimate the pooled prevalence, the 95% credible intervals (CrI), and to examine the difference in prevalence by ethnicity (European, African, Hispanic, Asian) and region (Africa, Asia, Europe, Latin America and the Caribbean, North America, and Oceania). UN World Population Prospects were used to project the number of people affected in 2014 and 2040. Bayes factor was calculated as a measure of statistical evidence, with a score above three indicating substantial evidence. FINDINGS: Analysis of 129,664 individuals (aged 30-97 years), with 12,727 cases from 39 studies, showed the pooled prevalence (mapped to an age range of 45-85 years) of early, late, and any age-related macular degeneration to be 8.01% (95% CrI 3.98-15.49), 0.37% (0.18-0.77), and 8.69% (4.26-17.40), respectively. We found a higher prevalence of early and any age-related macular degeneration in Europeans than in Asians (early: 11.2% vs 6.8%, Bayes factor 3.9; any: 12.3% vs 7.4%, Bayes factor 4.3), and early, late, and any age-related macular degeneration to be more prevalent in Europeans than in Africans (early: 11.2% vs 7.1%, Bayes factor 12.2; late: 0.5% vs 0.3%, 3.7; any: 12.3% vs 7.5%, 31.3). There was no difference in prevalence between Asians and Africans (all Bayes factors <1). Europeans had a higher prevalence of geographic atrophy subtype (1.11%, 95% CrI 0.53-2.08) than Africans (0.14%, 0.04-0.45), Asians (0.21%, 0.04-0.87), and Hispanics (0.16%, 0.05-0.46). Between geographical regions, cases of early and any age-related macular degeneration were less prevalent in Asia than in Europe and North America (early: 6.3% vs 14.3% and 12.8% [Bayes factor 2.3 and 7.6]; any: 6.9% vs 18.3% and 14.3% [3.0 and 3.8]). No significant gender effect was noted in prevalence (Bayes factor <1.0). The projected number of people with age-related macular degeneration in 2020 is 196 million (95% CrI 140-261), increasing to 288 million in 2040 (205-399). INTERPRETATION: These estimates indicate the substantial global burden of age-related macular degeneration. Summarised data provide information for understanding the effect of the condition and provide data towards designing eye-care strategies and health services around the world. FUNDING: National Medical Research Council, Singapore.

Discordance of two interferon-γ release assays and tuberculin skin test in patients with uveitis.

AIMS: To describe interferon-γ release assay (IGRA) and IGRA/tuberculin skin test (TST) discordance and their associated factors in patients with uveitis. METHODS: Prospective study of 102 consecutive new patients presenting with uveitis to a tertiary referral centre. All patients underwent a complete ocular and systemic examination at presentation, with QuantiFERON-Gold in-tube (QFT), T-SPOT.TB and TST performed. Discordant results of TST/QFT, TST/T-SPOT.TB and QFT/T-SPOT.TB were analysed. Binary logistic regression was used to identify factors associated with discordant results. RESULTS: There was fair agreement between TST and T-SPOT.TB (κ=0.371, p<0.001); moderate agreement between TST and QFT (κ=0.471, p<0.001). Both IGRAs showed good agreement (κ=0.668, p<0.001). The discordance rate between the TST/QFT was 26.5%, while TST/T-SPOT.TB was 31.4%. The discordance rate between the IGRAs was 16.7%. There was a significant association between TST/IGRA discordance with increasing age (OR 0.95, 95% CI 0.92 to 0.99; p=0.022), less likely with panuveitis (OR 0.18, 95% CI 0.04 to 0.86; p=0.032), and with Indian ethnicity (OR 14.07, 95% CI 1.45 to 137.03; p=0.023). CONCLUSIONS: Discordance of IGRA and TST results is common and requires further study. In our study in patients with uveitis, we found that ethnicity, age, and type of uveitis were some significant factors associated with TST/IGRA discordance, which may need to be taken into consideration when interpreting these results.

Accounting for standard errors of vision-specific latent trait in regression models.

PURPOSE: To demonstrate the effectiveness of Hierarchical Bayesian (HB) approach in a modeling framework for association effects that accounts for SEs of vision-specific latent traits assessed using Rasch analysis. METHODS: A systematic literature review was conducted in four major ophthalmic journals to evaluate Rasch analysis performed on vision-specific instruments. The HB approach was used to synthesize the Rasch model and multiple linear regression model for the assessment of the association effects related to vision-specific latent traits. The effectiveness of this novel HB one-stage "joint-analysis" approach allows all model parameters to be estimated simultaneously and was compared with the frequently used two-stage "separate-analysis" approach in our simulation study (Rasch analysis followed by traditional statistical analyses without adjustment for SE of latent trait). RESULTS: Sixty-six reviewed articles performed evaluation and validation of vision-specific instruments using Rasch analysis, and 86.4% (n = 57) performed further statistical analyses on the Rasch-scaled data using traditional statistical methods; none took into consideration SEs of the estimated Rasch-scaled scores. The two models on real data differed for effect size estimations and the identification of "independent risk factors." Simulation results showed that our proposed HB one-stage "joint-analysis" approach produces greater accuracy (average of 5-fold decrease in bias) with comparable power and precision in estimation of associations when compared with the frequently used two-stage "separate-analysis" procedure despite accounting for greater uncertainty due to the latent trait. CONCLUSIONS: Patient-reported data, using Rasch analysis techniques, do not take into account the SE of latent trait in association analyses. The HB one-stage "joint-analysis" is a better approach, producing accurate effect size estimations and information about the independent association of exposure variables with vision-specific latent traits.

Can an inexperienced observer accurately plot disc contours using Heidelberg retinal Tomograph?

OBJECTIVE: To examine the reliability of inexperienced observers in plotting optic disc contours on Heidelberg retinal tomography images before and after training. DESIGN: Observational study. PARTICIPANTS: One hundred eyes that were randomly selected from the Singapore Indian Eye Study. METHODS: Both eyes of subjects were imaged with Heidelberg Retina Tomograph 3 (HRT-3; Heidelberg Engineering, Heidelberg, Germany). Optic disc contours were plotted on the same images by 2 new observers on 2 separate occasions, before and after 2-hour standardized training on the skills and tools available to accurately identify and delineate optic disc contours. These plottings were compared with an experienced, trained glaucoma expert (gold standard). Agreement and variability were analyzed by interclass correlation tests and Bland-Altman plots. RESULTS: A total of 182 images (18 excluded because of poor quality) from 89 Indian subjects were included. The mean age was 53.27 ± 7.25 years and 54.8% were male. There was moderate-to-high agreement between pretraining (both new observers) and experienced observer's results (interclass correlation values range, 0.76-0.99). The interclass correlation improved for all the HRT-3 parameters after the 2 new observers were adequately trained. Comparing the interclass correlation values before and after training, the differences for mean retinal nerve fibre layer thickness for Observer 1 and all the HRT-3 parameters for Observer 2 were statistically significant. CONCLUSIONS: This study shows that it is easy to train a new inexperienced observer to plot optic disc contours on HRT images, which translates into improved and acceptable interobserver variability and agreement.

Prospective head-to-head study comparing 2 commercial interferon gamma release assays for the diagnosis of tuberculous uveitis.

PURPOSE: To perform a head-to-head comparison of 2 commercially available interferon-gamma release assays, QuantiFERON-TB Gold In-Tube (Cellestis, Chadstone, Victoria, Australia) and T-SPOT.TB (Oxford Immunotech, Abingdon, Oxfordshire, UK), in the diagnosis of tuberculous uveitis. DESIGN: Prospective cohort to study diagnostic accuracy. METHODS: We recruited consecutive new patients who presented with uveitis to a tertiary institution over a 2-year period. All patients underwent complete ocular examination and systemic evaluation, including T-SPOT.TB, QuantiFERON-TB Gold In-Tube, and tuberculin skin test. Patients were followed-up for a minimum of 1 year after completion of antituberculous therapy where indicated. The main outcome measures were the sensitivity, specificity and accuracy of each test, estimated using Bayesian latent class analysis (presented with 95% Bayesian credible intervals) (Crl). Prior information was obtained from published meta-analyses for diagnostic tests: QuantiFERON Gold In-Tube sensitivity (0.64, 0.59-0.69) and specificity (0.99, 0.99-1.00); T-SPOT. tuberculosis sensitivity (0.50, 0.33-0.67) and specificity (0.91, 0.88-0.93). RESULTS: From our study in patients with uveitis, QuantiFERON-TB Gold In-Tube was more specific but slightly less sensitive (sensitivity: 0.64, 0.60-0.69; specificity: 0.995, 0.988-0.999) than T-SPOT.TB (sensitivity: 0.67, 0.60-0.74; specificity: 0.91, 0.88-0.93). However, QuantiFERON Gold In-Tube was significantly more accurate in identifying true-positive tuberculous uveitis cases than was T-SPOT.TB among discordant cases (QuantiFERON Gold In-Tube positive 98% vs T-SPOT.TB positive 76%; ratio 1.28, 95% Crl: 1.11-1.72, ie, 95% Crl >1.0, statistically significant). CONCLUSION: Based on statistical decision theory, our head-to-head study suggests that QuantiFERON-TB Gold In-Tube is the first-line test that should be performed in preference to T-SPOT.TB (and the tuberculin skin test) for diagnosing tuberculous uveitis.

Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion.

PURPOSE: To assess the efficacy of intravitreal 0.5 mg ranibizumab for the treatment of center-involving macular edema secondary to branch retinal vein occlusion (BRVO) over 1 year compared with standard-of-care grid laser. DESIGN: A prospective randomized controlled clinical trial. METHODS: A total of 36 patients with vision loss in 1 eye attributable to macular edema following BRVO were recruited from 5 institutions. Patients were randomized 1:1 to a treatment group that received 6 monthly injections of 0.5 mg ranibizumab and thereafter monthly as needed based on best-corrected visual acuity (BCVA) and central foveal thickness (CFT) assessments on optical coherence tomography scans, or a standard-of-care group that received monthly sham injections for the 1-year duration of the study. Grid laser was administered at 13 and 25 weeks in both groups if criteria for laser treatment were met. Main outcome measures included mean change in BCVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores from baseline to month 12. Secondary outcomes included anatomic outcomes and the percentage of patients requiring grid laser in both groups. RESULTS: Mean BCVA change from baseline was significantly greater in the treatment compared with the standard-of-care group at 12 months (12.5 ETDRS letters vs -1.6 ETDRS letters, P = .032). The mean CFT was significantly reduced in the treatment compared with standard-of-care group (361.7 µm vs 175.6 µm, P = .025). At 13 and 25 weeks, more patients in the standard-of-care group (68.4%, 50.0%) received grid laser than in the treatment group (6.7%, 8.3%). No new ocular or systemic adverse events were observed. CONCLUSIONS: Compared with standard grid laser, intravitreal ranibizumab provided significant and sustained benefits in visual acuity gain and anatomic improvement in eyes with macular edema secondary to BRVO.

Trends and factors related to outcomes for primary rhegmatogenous retinal detachment surgery in a large asian tertiary eye center.

PURPOSE: To describe trends and outcomes of vitreoretinal surgery for primary rhegmatogenous retinal detachment in a large Asian tertiary eye center. METHODS: Retrospective review of 1,530 eyes with primary retinal detachment between 2005 and 2011 managed at the Singapore National Eye Center by one of the following: scleral buckling (SB), pars plana vitrectomy (PPV), and combined SB and PPV (SB + PPV). Anatomical and functional outcomes were assessed. RESULTS: There was a trend toward PPV and PPV + SB as the primary reattachment procedure from 2005 to 2011. The primary anatomical success rate for PPV (78.6%) was worse than that for SB (88.8%) or SB + PPV (89.0%, P = 0.000). Final anatomical success rates were similar for all 3 procedures: SB 97.7%, PPV 95.2%, and SB + PPV 96.4%. Better functional success was achieved in the SB group (86.1%) than both the PPV (72.5%) and SB + PPV groups (77.5%, P = 0.000), partly attributable to the less complex nature of retinal detachments in the SB group. Older age and proliferative vitreoretinopathy were related to the poor functional outcomes in both phakic and pseudophakic eyes. CONCLUSION: There was an increasing trend toward PPV and PPV + SB as the primary retinal reattachment surgery from 2005 through to 2011. High rates of anatomical and functional outcomes were achieved with SB, PPV, and SB + PPV, proliferative vitreoretinopathy and older age were negatively correlated with the functional success in both phakic and pseudophakic eyes.

Interferon γ release assay for the diagnosis of uveitis associated with tuberculosis: a Bayesian evaluation in the absence of a gold standard.

AIM: To evaluate an interferon γ release assay in the diagnosis of uveitis associated with tuberculosis (TB), in the absence of a gold standard. METHODS: We conducted a prospective 1-year study on consecutive patients with a new diagnosis of uveitis presenting with ocular signs suggestive of TB-associated uveitis (TAU). All subjects underwent ocular and systemic review with investigations, including T-SPOT.TB assay and tuberculin skin test (TST). The main outcome measures were sensitivity and specificity; positive and negative predictive values (PPV, NPV) of T-SPOT.TB were estimated using Bayesian statistics (presented with 95% Bayesian credible intervals (CrI)). RESULTS: Analysis after exclusion of patients with indeterminate results and other diseases included 191 patients, with mean age of 47.2±15.3 years. The majority were Chinese (n=110, 57.6%) and women (n=102, 53.4%). The TST (0.70, 0.65 to 0.75) was more sensitive compared to T-SPOT.TB (0.53, 0.42 to 0.66) but the T-SPOT.TB (0.91, 0.88 to 0.93) was more specific than TST (0.71, 0.58 to 0.83). The T-SPOT.TB had a higher PPV (0.88, 0.80 to 0.93) compared to the TST (0.76, 0.57 to 0.90), but a lower NPV (0.60, 0.38 to 0.78) than the TST (0.65, 0.46 to 0.78). Patients who are TST and T-SPOT.TB positive are very likely (95.1% likelihood) to have TAU (39/41 95% CrI 35 to 41). Based on statistical decision theory, in populations where the prevalence of TAU is high the TST should be the first-choice test; the T-SPOT.TB should be performed if the prevalence of TB is low. CONCLUSIONS: The T-SPOT.TB assay is more specific but less sensitive than the TST and should be used in preference to the TST in low-TB-prevalence populations. Used in conjunction, the likelihood of TAU is greatest if the T-SPOT.TB and TST are both positive.

The prevalence and types of glaucoma in an urban Indian population: the Singapore Indian Eye Study.

PURPOSE: To determine the prevalence and types of glaucoma in an urban Singaporean Indian population. METHODS: The Singapore Indian Eye Study (SINDI) was a population-based, cross-sectional survey that examined 3400 (75.6% response) persons aged 40 to 80 years. Participants underwent a standardized examination including slit-lamp biomicroscopy, Goldmann applanation tonometry, and dilated optic disc assessment. Participants suspected to have glaucoma also underwent visual field examination (24-2 SITA standard, Humphrey Visual Field Analyzer II), gonioscopy, and repeat applanation tonometry. Glaucoma was defined according to International Society for Geographical and Epidemiologic Ophthalmology criteria. RESULTS: Of the 3400 participants, 78 (2.29%) had diagnosed glaucoma, giving an age-standardized prevalence of 1.95% (95% confidence interval [CI], 1.5%-2.5%). The age-standardized prevalence of primary open-angle glaucoma (POAG) was 1.25% (95% CI, 0.89%-1.73%), primary angle-closure glaucoma (PACG) 0.12% (95% CI, 0.04%-0.33%), and secondary glaucoma 0.55% (95% CI, 0.35%-0.86%). The mean IOP among the participants in the normal group in the study population was 15.6 ± 2.6 mm Hg and 17.7 ± 6.1 mm Hg in subjects with glaucoma (P = 0.003). The mean central corneal thickness (CCT) in the normal study population was 540.31 ± 33.79; the mean CCT in subjects with POAG (529.8 ± 30.8 µm) was statistically different from the normal study group (P = 0.003). CONCLUSIONS: The prevalence of glaucoma among Singaporean Indians 40 years of age and older in Singapore was 1.95%, approximately half that of the Chinese and the Malay persons in Singapore. As in other Asian studies, POAG was the main form of glaucoma accounting for nearly 60% of cases.

Racial differences in retinal vessel geometric characteristics: a multiethnic study in healthy Asians.

PURPOSE: To investigate potential racial/ethnic differences in retinal vascular geometric parameters in a multiethnic Asian population (Chinese, Malay, and Indian) free of clinical diseases. METHODS: A series of retinal vascular parameters were measured from retinal photographs using a computer-assisted program following a standardized protocol. Healthy participants were defined as nonsmokers, the absence of diabetes mellitus, uncontrolled hypertension, obesity, stroke, heart disease, glaucoma, and retinopathy. RESULTS: THERE WERE SIGNIFICANT DIFFERENCES IN MEASUREMENTS OF RETINAL VASCULAR CALIBER, TORTUOSITY, AND FRACTAL DIMENSION AMONG THE THREE ETHNIC GROUPS. IN MULTIPLE LINEAR REGRESSION MODEL CONTROLLING FOR AGE, SEX, BODY MASS INDEX, SYSTOLIC BLOOD PRESSURE, CHOLESTEROL, AND GLUCOSE LEVELS, INDIANS HAD THE LARGEST ARTERIOLAR AND VENULAR CALIBERS (ARTERIOLES [SE]: 158.94 µm [1.00]; venules: 228.26 µm [1.53]), followed by Malays (arterioles: 138.31 µm [0.74]; venules: 204.26 µm [1.13]), and then Chinese (arterioles: 131.20 µm [0.84]; venules: 195.09 µm [1.28]). Chinese had the largest arteriolar and venular tortuosity (arterioles [× $${10}^{5}$$]: 7.20 [0.08] VENULES [ $${10}^{5}$$]: 9.09 [0.10]), and venular fractal dimension (1.244 [0.003]). There were no statistically significant differences in other retinal vascular parameters after correcting multiple comparisons by the method of modified false discovery rate. CONCLUSIONS: We found that among ethnic groups composed of healthy Chinese, Malay, and Indians, there were statistically significant differences in several retinal parameters. There exist racial influences in retinal vascular parameters and other yet unknown or unmeasured environmental factor or lifestyle habits and genetic variations not related to race that may also contribute to these differences.

A prospective comparison of chronic primary angle-closure glaucoma versus primary open-angle glaucoma in Singapore.

INTRODUCTION: To describe the optic disc, visual field and ocular characteristics of a consecutive cohort of Asian patients with chronic primary angle-closure glaucoma (CPACG), and compare them with those having primary open-angle glaucoma (POAG). METHODS: In a prospective comparative case series of new patients with POAG or CPACG in Singapore, all patients underwent visual acuity assessment, slit-lamp examination, tonometry, gonioscopy, refraction, Heidelberg Retina Tomograph (HRT) and Humphrey visual field (HVF) assessment. RESULTS: 98 patients were enrolled (POAG n = 48; CPACG n = 50). CPACG patients were significantly older (66.5 ± 9.2 years vs. 64.1 ± 13.5 years; p = 0.027) and mostly female (p = 0.004). CPACG eyes had significantly higher intraocular pressure (26.9 ± 6.9 mmHg vs. 24.5 ± 3.3 mmHg; p = 0.03), shorter axial length (22.89 ± 0.97 mm vs. 24.26 ± 1.79 mm; p < 0.001) and shallower anterior chamber depth (2.60 ± 0.25 mm vs. 3.16 ± 0.48 mm; p < 0.001). HVF mean deviation or pattern standard deviation (PSD) did not differ significantly between POAG and CPACG eyes, but the latter had a lower PSD for a given mean deviation. HRT parameters between the two groups were not significantly different. CONCLUSION: In this study, CPACG eyes had significantly higher presenting intraocular pressure than POAG eyes, but there were no significant differences in optic disc topography. A majority of the patients in both groups had moderate field defects at the time of presentation, followed by severe and then mild defects. The field loss in CPACG eyes was more diffuse than that in POAG eyes.

Cataract conversion assessment using lens opacity classification system III and Wisconsin cataract grading system.

PURPOSE: To propose a general conversion approximation algorithm and illustrate its application to two cataract classification systems, the Lens Opacity Classification System III (LOCS III) and Wisconsin Cataract Grading System (Wisconsin system). METHODS: Lens opacity of 3265 participants (78.7% response rate) aged 40 to 80 years from the Singapore Malay Eye study were assessed both clinically during slit-lamp examination using LOCS III, and via slit-lamp and retro-illumination photographic grading using the Wisconsin system. Collapsed contingency tables were used to convert between the LOCS III and Wisconsin System. RESULTS: The conversion between the two cataract classification systems is affected by the direction of transformation. The conversion algorithm was validated and explained with an application example. CONCLUSIONS: An approximate conversion algorithm for any two cataract grading systems was proposed and applied to the LOCS III and Wisconsin system. These findings provide general ways to pool and compare cataract prevalence using different grading systems in epidemiological studies.

Determinants of ganglion cell-inner plexiform layer thickness measured by high-definition optical coherence tomography.

PURPOSE: To determine the distribution, variation, and determinants of ganglion cell-inner plexiform layer (GC-IPL) thickness in nonglaucomatous eyes measured by high-definition optical coherence tomography (HD-OCT). METHODS: Six hundred twenty-three Chinese adults aged 40 to 80 years were consecutively recruited from a population-based study. All subjects underwent a standardized interview, ophthalmic examination, and automated perimetry. HD-OCT with macular cube protocol was used to measure the GC-IPL thickness. Univariate and multiple linear regression analyses were performed to examine the relationship between GC-IPL thickness with ocular and systemic factors. RESULTS: The mean (±SD) age of study subjects was 52.84 ± 6.14 years, 50.1% were male, and all subjects had normal visual fields with no signs of glaucoma or glaucoma suspect. The mean overall, minimum, superior, and inferior GC-IPL thicknesses were 82.78 ± 7.01 µm, 79.67 ± 9.17 µm, 83.30 ± 7.89 µm, and 80.16 ± 8.31 µm, respectively. In multiple linear regression analysis, GC-IPL thickness was significantly associated with age (ß = -0.202, P < 0.001), female sex (ß = -2.367, P < 0.001), axial length (ß = -1.279, P = 0.002), and mean peripapillary retinal nerve fiber layer (RNFL) thickness (ß = 0.337, P < 0.001). IOP, central corneal thickness, disc area, serum glucose level, and history of diabetes mellitus had no significant influence on GC-IPL thickness. CONCLUSIONS: Thinner GC-IPL was independently associated with older age, female sex, longer axial length, and thinner RNFL thickness. These factors should be taken into account when interpreting GC-IPL thickness measurements with HD-OCT for glaucoma assessment.

Prevalence and risk factors of epiretinal membrane in Asian Indians.

PURPOSE: To describe the prevalence of epiretinal membrane (ERM) and its risk factors in an Indian population and compare the findings with other populations. METHODS: The Singapore Indian Eye Study is a population-based survey of 3400 Asian Indians aged between 40 and 80 years. A comprehensive ophthalmic examination, standardized interviews, and laboratory blood tests were performed. Digital retinal fundus photographs were assessed for the presence of ERM following the definitions used in the Blue Mountains Eye Study (BMES). ERM was classified into a less severe form termed "cellophane macular reflex" (CMR) and a more severe form termed "preretinal macular fibrosis" (PMF) and also as primary and secondary (if it was associated with retinal pathology or cataract surgery). RESULTS: A total of 3328 persons (mean age 57.8 ± [SD] 10.1 years, and 50.2% male) provided data in this study. The age-standardized prevalence of ERM was 7.6% (95% confidence interval [CI], 6.8-8.6), CMR 4.1% (95% CI, 3.5-4.9), and PMF 3.5% (95% CI, 2.9-4.2). Older age (odds ratio [OR], 1.09; 95% CI, 1.07-1.11, per year increase), increasing myopic refraction (OR, 1.14; 95% CI, 1.07-1.22, per diopter decrease), and narrower retinal arteriolar diameter (OR, 1.02; 95% CI, 1.00-1.03, per µm decrease) were significantly associated with primary ERM. CONCLUSIONS: The age-standardized prevalence of ERM in the Indian population in Singapore was 7.6%. This is similar to Malays in Singapore (8.0%) and higher than the prevalence in whites in Australia (4.7%). Significant factors associated with primary ERM were older age, myopia, and narrower retinal arteriolar diameter.

Prevalence and risk factors of meibomian gland dysfunction: the Singapore Malay eye study.

PURPOSE: To describe the prevalence and associations of meibomian gland dysfunction (MGD) in an urban Malay population in Singapore. METHODS: Population-based cross-sectional study of 3280 (78.7% response rate) Malay persons aged 40 to 80 years, living in Singapore. MGD was defined by a slit-lamp clinical examination as either lid margin telangiectasia or meibomian gland orifice plugging in at least one eye. Participants underwent a standardized questionnaire and clinical examination, including laboratory investigations. Data were analyzed for 3271 persons. RESULTS: The age-standardized prevalence of MGD was 56.3% [95% confidence interval (CI), 53.3-59.4]. A higher MGD prevalence was found in male participants across all age groups [odds ratio (OR), 1.30; 95% CI, 1.35-1.79], postmenopausal women (OR, 1.64; 95% CI, 1.19-2.33), and all participants with pinguecula (OR, 2.43; 95% CI, 2.08-2.85), high diastolic blood pressure (OR, 1.32; 95% CI, 1.08-1.62), and use of angiotensin II receptor blockers (OR, 4.02; 95% CI, 1.74-9.27). CONCLUSIONS: MGD was highly prevalent in this Asian population and associated with various systemic and ocular conditions.

Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2).

PURPOSE: Our previous study, Atropine for the Treatment of Myopia 1 (ATOM1), showed that atropine 1% eyedrops were effective in controlling myopic progression but with visual side effects resulting from cycloplegia and mydriasis. The aim of this study was to compare efficacy and visual side effects of 3 lower doses of atropine: 0.5%, 0.1%, and 0.01%. DESIGN: Single-center, double-masked, randomized study. PARTICIPANTS: A total of 400 children aged 6-12 years with myopia of at least -2.0 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION: Children were randomly assigned in a 2:2:1 ratio to 0.5%, 0.1%, and 0.01% atropine to be administered once nightly to both eyes for 2 years. Cycloplegic refraction, axial length, accommodation amplitude, pupil diameter, and visual acuity were noted at baseline, 2 weeks, and then every 4 months for 2 years. MAIN OUTCOME MEASURES: Myopia progression at 2 years. Changes were noted and differences between groups were compared using the Huber-White robust standard error to allow for data clustering of 2 eyes per person. RESULTS: The mean myopia progression at 2 years was -0.30±0.60, -0.38±0.60, and -0.49±0.63 D in the atropine 0.5%, 0.1%, and 0.01% groups, respectively (P=0.02 between the 0.01% and 0.5% groups; between other concentrations P > 0.05). In comparison, myopia progression in ATOM1 was -1.20±0.69 D in the placebo group and -0.28±0.92 D in the atropine 1% group. The mean increase in axial length was 0.27±0.25, 0.28±0.28, and 0.41±0.32 mm in the 0.5%, 0.1%, and 0.01% groups, respectively (P < 0.01 between the 0.01% and 0.1% groups and between the 0.01% and 0.5% groups). However, differences in myopia progression (0.19 D) and axial length change (0.14 mm) between groups were small and clinically insignificant. Atropine 0.01% had a negligible effect on accommodation and pupil size, and no effect on near visual acuity. Allergic conjunctivitis and dermatitis were the most common adverse effect noted, with 16 cases in the 0.1% and 0.5% atropine groups, and no cases in the 0.01% group. CONCLUSIONS: Atropine 0.01% has minimal side effects compared with atropine at 0.1% and 0.5%, and retains comparable efficacy in controlling myopia progression.