Genome-wide association studies identify two novel loci conferring susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes.

Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (P < 1.0 × 10-4) in an independent case-control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stages 1 and 2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, P = 1.62 × 10-9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11-1.23, and rs140508424 within PALM2 on chromosome 9, P = 4.19 × 10-8, OR = 1.61, 95% CI 1.36-1.91. However, the association of these two loci was not replicated in Korean, European or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (P = 2.17 × 10-6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.

Do Black and Asian individuals wait longer for treatment? A survival analysis investigating the effect of ethnicity on time-to-clinic and time-to-treatment for diabetic eye disease.

AIMS/HYPOTHESIS: This study explored the impact of ethnicity on time-to-clinic, time-to-treatment and rates of vision loss in people referred to hospital with diabetic eye disease. METHODS: A survival analysis was performed on all referrals from an inner-city diabetic eye screening programme to a tertiary hospital eye service between 1 October 2013 and 31 December 2017. Exclusion criteria were failure to attend hospital, distance visual acuity in both eyes too low to quantify with the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart and treatment received prior to referral. Demographic and screening grade data were collected at the point of referral. Small-area statistics and census data were used to calculate indices of multiple deprivation. The main outcome measures were time taken from the date of referral for an individual to achieve the following: (1) attend the first hospital clinic appointment; (2) receive the first macular laser, intravitreal anti-vascular endothelial growth factor injection or pan-retinal photocoagulation treatment, in either eye; and (3) lose at least ten ETDRS letters of distance visual acuity, in either eye. RESULTS: Of 2062 referrals, 1676 individuals were included. Mean age (± SD) was 57.6 ± 14.7 years, with 52% male sex and 86% with type 2 diabetes. The ethnicity profile was 52% Black, 30% White, 10% Asian and 9% mixed/other, with similar disease severity at the time of referral. Time-to-clinic was significantly longer for Asian people than for Black people (p = 0.03) or White people (p = 0.001). Time-to-treatment was significantly longer for Black people than for White people (p = 0.02). Social deprivation did not significantly influence time-to-treatment. There were no significant differences in the rates of vision loss between ethnic groups. CONCLUSIONS/INTERPRETATION: Black people wait longer for hospital eye treatment compared with their White counterparts. The reasons for this delay in treatment warrant further investigation.

Racial, Ethnic, and Insurance-Based Disparities Upon Initiation of Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema in the US.

PURPOSE: This study characterizes the association of risk factors including race, ethnicity, and insurance status with presenting visual acuity (VA) and diabetic retinopathy (DR) severity in patients initiating treatment with anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME). DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: The Academy Intelligent Research in Sight (IRIS) Registry database was queried for patients who initiated anti-VEGF injection treatment for DME between 2012 and 2020 (n = 203 707). METHODS: Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features. MAIN OUTCOME MEASURES: Visual acuity and DR severity. RESULTS: Patients on Medicare and private insurance presented with higher baseline VA compared with patients on Medicaid (median of 2.31 and 4.17 greater Early Treatment Diabetic Retinopathy Scale [ETDRS] letters, respectively P < 0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P < 0.01). Black and Hispanic patients presented with a worse baseline DR severity compared with White and non-Hispanic patients (odds ratio, 1.23 and 1.71, respectively; P < 0.01). CONCLUSIONS: There are ethnic and insurance-based disparities in VA and disease severity upon initiation of anti-VEGF therapy for DME treatment. Public health initiatives could improve timely initiation of treatment.

Barriers to and enablers of attendance at diabetic retinopathy screening experienced by immigrants to Canada from multiple cultural and linguistic minority groups.

AIM: To identify barriers to/enablers of attendance at eye screening among three groups of immigrantsto Canada from cultural/linguistic minority groups living with diabetes. METHODS: Using a patient-oriented research approach leveraging Diabetes Action Canada's patient engagement platform, we interviewed a purposeful sample of people with type 2 diabetes who had immigrated to Canada from: Pakistan (interviews in Urdu), China (interviews in Mandarin) and French-speaking African and Caribbean nations (interviews in French). We collected and analysed data based on the Theoretical Domains Framework covering key modifiable factors that may operate as barriers to or enablers of attending eye screening. We used directed content analysis to code barrier/enabler domains. Barriers/enablers were mapped to behaviour change techniques to inform future intervention development. RESULTS: We interviewed 39 people (13 per group). Many barriers/enablers were consistent across groups, including views about harms caused by screening itself, practical appointment issues including forgetting, screening costs, wait times and making/getting to an appointment, lack of awareness about retinopathy screening, language barriers, and family and clinical support. Group-specific barriers/enablers included a preference to return to one's country of birth for screening, the impact of winter, and preferences for alternative medicine. CONCLUSION: Our results can inform linguistic and culturally competent interventions to support immigrants living with diabetes in attending eye screening to prevent avoidable blindness.

Retinopathy develops at similar glucose levels but higher HbA1c levels in people with black African ancestry compared to white European ancestry: evidence for the need to individualize HbA1c interpretation.

AIMS: To examine the association of HbA1c and glucose levels with incident diabetic retinopathy according to black African or white European ancestry. METHODS: In this retrospective cohort study of 202 500 US Veterans with diabetes (2000-2014), measures included HbA1c , outpatient random serum/plasma glucose, and incident retinopathy [conversion from negative to ≥2 positive evaluations (ICD-9 codes), without a subsequent negative]. RESULTS: At baseline, the study population had a mean age of 59.3 years, their mean BMI was 31.9 kg/m2 , HbA1c level was 57 mmol/mol (7.4%) and glucose level was 8.8 mmol/l, and 77% were of white European ancestry (white individuals) and 21% of black African ancestry (black individuals). HbA1c was 0.3% higher in black vs white individuals (P < 0.001), adjusting for baseline age, sex, BMI, estimated glomerular filtration rate (eGFR), haemoglobin, and average systolic blood pressure and glucose. Over 11 years, incident retinopathy occurred in 9% of black and 7% of white individuals, but black individuals had higher HbA1c , glucose, and systolic blood pressure (all P < 0.001); adjusted for these factors, incident retinopathy was reduced in black vs white individuals (P < 0.001). The population incidence of retinopathy (7%) was associated with higher mean baseline HbA1c in individuals with black vs white ancestry [63 mmol/mol (7.9%) vs 58 mmol/mol (7.5%); P < 0.001)], but with similar baseline glucose levels (9.0 vs 9.0 mmol/l; P = 0.660, all adjusted for baseline age, sex and BMI). CONCLUSIONS: Since retinopathy occurs at higher HbA1c levels in black people for a given level of average plasma glucose, strategies may be needed to individualize the interpretation of HbA1c measurements.

The increased risk of microvascular complications in South Asians with type 1 diabetes is influenced by migration.

AIM: We aimed to explore the association between South Asian ethnicity and complications of type 1 diabetes, and whether this is affected by migration. METHODS: In this retrospective cohort study, data on diabetes control and complications were obtained for South Asians in India (South AsiansIndia , n = 2592) and the UK (South AsiansUK , n = 221) and white Europeans in the UK (n = 1431). Multivariable logistic regression was used to identify associations between ethnicity and diabetic kidney disease, retinopathy and neuropathy adjusting for age, sex, BMI, disease duration, HbA1c , blood pressure (BP) and cholesterol. RESULTS: South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease [odds ratio (OR) 5.0, 95% confidence intervals (CI) 3.6-7.1] and retinopathy (OR 1.8, 95% CI 1.2-2.5), but lower odds of neuropathy (OR 0.5, 95% CI 0.4-0.6) than white Europeans. South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease (OR 3.0, 95% 1.8-5.3) than South AsiansUK , but there was no significant difference in the odds of other complications. CONCLUSIONS: In this hypothesis-generating study, we report that South Asian ethnicity is associated with greater risk of diabetic kidney disease and retinopathy, and lower risk of neuropathy than white European ethnicity. Part of the excess diabetic kidney disease risk is reduced in South AsiansUK . These associations cannot be accounted for by differences in vascular risk factors. Our findings in South Asians with type 1 diabetes mirror previous findings in type 2 diabetes and now need to be validated in a study of the effect of ethnicity on type 1 diabetes complications where healthcare is provided in the same setting.

Diabetic eye disease and screening attendance by ethnicity in New Zealand: A systematic review.

To examine differences in incidence, prevalence and screening for diabetic retinopathy in New Zealand, we searched MEDLINE, EMBASE and CINAHL up to 6 December 2018 for observational studies reporting diabetic eye disease or attendance at retinal screening, disaggregated by ethnicity. Two authors separately screened and selected studies, and extracted data. None of the 11 included studies reported data on visual impairment from diabetic retinopathy. All nine studies reporting diabetic eye disease by ethnicity found Pacific people and Maori had higher rates of sight-threatening disease and lower rates of screening attendance compared to Europeans. Data for Asian people were infrequently reported, but when they were, they also fared worse than Europeans. This review highlights that equity-focused strategies are needed to address ethnic disparities in eye health among New Zealanders with diabetes. The review also identifies how research methods can be strengthened to enable future calculation of robust disease prevalence estimates.

Presence of diabetic retinopathy is associated with worse 10-year mortality among Indigenous Australians in Central Australia: The Central Australian ocular health study.

IMPORTANCE: Diabetes mellitus (DM) is highly prevalent among Indigenous Australians and contributes greatly to premature death. The association of diabetic retinopathy (DR) with early mortality, however, has not previously been reported among Indigenous Australians. BACKGROUND: To investigate associations between 10-y mortality and the presence of DR among Indigenous Australians living in Central Australia. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 1257 individuals aged 40 y or older, living in one of 30 remote communities within Central Australia were recruited through outreach clinics. METHODS: Fundus examination was performed on all patients at recruitment. The presence of any DR was recorded. MAIN OUTCOME MEASURES: Mortality rate and cause were obtained at 10 y, and their association with any DR was determined. RESULTS: Ten-year all-cause mortality was found to be 29.3%. Of those with DM but no DR, 24.0% died during the 10 y after recruitment, compared with 40.1% for those with any DR (P < 0.0001). Those who had any DR were 75% more likely to die (hazard ratio [HR] 1.75; P < 0.0001) and were more likely to die from renal failure (HR 2.71; P = 0.004) or stroke (HR 5.91; P = 0.026). CONCLUSION AND RELEVANCE: The presence of any DR among those with DM, was associated with a 75% greater 10-y all-cause mortality rate and were more likely to die from renal failure or stroke. We recommend that whenever DR is noted among Indigenous Australians with DM, that they be immediately referred for investigation and management of risk factors, which might predispose to renal failure and stroke.

Automated Reminders Improve Retinal Screening Rates in Low Income, Minority Patients with Diabetes and Correct the African American Disparity.

Diabetic retinopathy (DR) is a major cause of blindness in the United States. Prevention relies on periodic DR screening, yet overall national screening rates are not optimal, especially in low-income, minority patients. We prospectively evaluated show rates for prescheduled teleretinal DR screening appointments in diabetic patients (n = 301) in a large safety-net clinic in South Central Los Angeles. Patients were predominately African American (n = 88) and Latino (n = 200). Patients received either usual care telephone reminders or automated reminder calls in addition to usual care. The overall mean (SEM) show rate for DR screening, irrespective of reminder method, was low: 54 + 1.03%. Show rates with usual care alone were 46.3 + 2.6%, and with automated reminders added, 59.9 + 1.47% (p = 0.036). Show rate with usual care amongst African Americans was 23.6 + 6.46% compared with 53.2 + 3.41% for Latinos (p = 0.025). When automated calling was added, the show rate doubled amongst African Americans, to 51.6 + 3.96% (p = 0.002) with a slightly higher, non-significant show rate in Latinos. In summary, show rates for pre-scheduled teleretinal DR screening appointments were low with usual care alone in a safety-net clinic, with evidence for a racial disparity amongst low-income, minority patients with diabetes. Addition of a pre-recorded automated reminder call improved show rates, and corrected much of the racial disparity observed. Greater focus on failed appointments as an explanation for low DR screening rates and racial disparities, and as a potentially remediable target with automated reminders, may improve DR screening rates and reduce blindness in low-income minority patients with diabetes.

Trends and Racial/Ethnic Disparities in Diabetic Retinopathy Among Adults with Diagnosed Diabetes in North Carolina, 2000-2015.

BACKGROUND There is limited information available in North Carolina on the current burden of, and racial disparities in, diabetic retinopathy (DR), a major complication associated with diabetes mellitus (DM). This study aims to describe the overall trend of, and racial/ethnic disparities in, DR among adults with DM in North Carolina.METHODS Data were from 13 waves (2000, 2002-2010, 2012, 2013, and 2015) of the Behavioral Risk Factor Surveillance System. The study sample included 16,976 adults aged ≥ 40 years with DM in North Carolina. DR was identified by self-report by the question, "Has a doctor ever told you that diabetes has affected your eyes or that you had retinopathy?" The overall prevalence of DR was assessed during the time period, and was compared between whites and blacks. All analyses were conducted using Stata 13.0.RESULTS The prevalence of self-reported DR in North Carolina decreased from 27.2% in 2000 to 18.3% in 2015, a reduction of 33% (Trend P = .003). The age-adjusted DR prevalence in whites decreased from 21.7% to 17.6% (Trend P = .04), and in blacks from 39.4% to 20.2% (Trend P = .002). The declining rates in DR were not statistically different between whites and blacks (P = .06). Blacks were more likely to report DR (adjusted odds ratio = 1.20, 95% confidence interval, 1.03-1.40) during 2000-2015.CONCLUSION The prevalence of self-reported DR in adults with DM declined significantly in North Carolina in the past 15 years. While racial differences in some years appeared to be decreasing, the black-white disparity in DR prevalence during the entire period persisted. Focused efforts on reducing the gap are needed.

Association of plasma osteopontin with diabetic retinopathy in Asians with type 2 diabetes.

Purpose: Osteopontin (OPN) is a proinflammatory cytokine with diverse functions. Increased levels of OPN in vitreous fluid have been reported in patients with diabetic retinopathy (DR); however, studies on circulating OPN levels in DR are limited. We aim to examine the association of plasma OPN levels with the presence and severity of DR in a multiethnic cohort with type 2 diabetes mellitus (type 2 diabetes) in Singapore. Methods: Plasma levels of OPN were measured using enzyme-linked immunosorbent assay. Digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR). Gradable fundus photographs and OPN measurements for 443 patients were used for analysis. A logistic regression model was used to evaluate the association of OPN with DR. Results: DR was diagnosed in 174 (39.3%) patients, including 132 (75.9%) with NPDR and 42 (24.1%) with PDR. The median of OPN was higher in the patients with DR (64.7 [49.7-89.5] ng/ml) than in the patients without DR (51.7 [38.9-66.9] ng/ml; p<0.001). After adjustment for clinical and biochemical factors, a 1-unit increase in nature logarithm (ln)-transformed OPN was associated with the presence of DR (2.770 [1.599-3.800], p<0.001). The area under the curve (AUC) increased statistically significantly after the addition of OPN (0.805[0.763-0.846] versus 0.825 [0.785-0.865], p=0.011). In the severity analyses, the median of OPN was statistically significantly higher in the patients with PDR (76.8 [55.0-103.6] ng/ml) than in the patients with NPDR (61.7 [47.7-87.3] ng/ml; p=0.017). After adjustment, the 1-unit increase in lnOPN remained associated with NPDR (2.673 [1.519-4.704], p=0.001) and PDR (3.389 [1.254-9.226], p=0.017), respectively (p-trend=0.001). Conclusions: Plasma OPN levels were associated with the presence and severity of DR in patients with type 2 diabetes, suggesting OPN may be useful as a potential biomarker for DR.

Impact of Incidence and Progression of Diabetic Retinopathy on Vision-Specific Functioning.

PURPOSE: To investigate the independent impact of the incidence and progression of diabetic retinopathy (DR) on visual functioning (VF). DESIGN: Population-based cohort study. PARTICIPANTS: A total of 518 participants aged 40 to 80 years (baseline visit 2007-2009 and second visit 6 years later, 2013-2015), with diabetes, clinical data, and VF information at both visits. MAIN OUTCOME MEASURES: VF-7 scores, converted to interval-level person measures (in logits) using Rasch analysis. METHODS: Incident DR was defined using the Modified Airlie House classification as "none or minimal" DR at baseline and at least mild nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe nonproliferative DR, proliferative DR, and/or clinically significant macular edema) as no VTDR at baseline, and present at follow-up; and DR progression as at least a 1-step worsening in DR at follow-up from mild or worse status at baseline. The longitudinal associations between incident DR, VTDR, and DR progression, as well as change in composite and individual item scores of VF, were assessed using multivariable linear regression models. RESULTS: Of the 518 participants (mean age ± standard deviation [SD] 59.8±9.0 years; 47.7% female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and DR progression, respectively, at follow-up. In models adjusting for traditional confounders, persons with incident DR and VTDR had a 13.7% (ß = -0.60; 95% confidence interval [CI], -0.96 to -0.24; P = 0.001) and 23% (ß = -1.00; 95% CI, -1.61 to -0.38; P = 0.001) reduction in mean VF scores at follow-up. Furthermore, individuals with incident DR had similar independent reductions in scores for 7 individual items of the VF-7, whereas those with incident VTDR had the largest reductions for activities like cooking (31%; P = 0.003), reading the newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow-up. Progression of DR was not independently associated with change in overall VF (ß = -0.18; 95% CI, -1.00, 0.64; P = 0.660). CONCLUSIONS: Incident DR, particularly vision-threatening stages, has a substantial negative impact on people's overall vision-dependent functioning and specific activities such as cooking, seeing street signs, and reading the newspaper. Our findings reinforce the need for strategies to prevent or delay the development of DR.

Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To evaluate the prevalence and risk factors for diabetic retinopathy (DR) in the Singapore Epidemiology of Eye Diseases (SEED) Study. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Persons of Malay, Indian, and Chinese ethnicity aged 40+ years, living in Singapore. METHODS: Diabetes was defined as nonfasting plasma glucose ≥200 mg/dl (11.1 mmol/l), glycated hemoglobin A1c (HbA1c) >6.5%, self-reported physician-diagnosed diabetes, or the use of glucose-lowering medication. Retinal photographs, were graded for the presence and severity of DR using the modified Airlie House classification system. MAIN OUTCOME MEASURES: Diabetic retinopathy, diabetic macular edema (DME), vision-threatening diabetic retinopathy (VTDR), defined as the presence of severe nonproliferative or proliferative DR, or clinically significant macular edema (CSME). RESULTS: Of the 10 033 subjects, 2877 (28.7%) had diabetes and gradable photographs for analysis. The overall age-standardized prevalence (95% confidence interval [CI]) was 28.2% (25.9-30.6) for any DR, 7.6% (6.5-9.0) for DME, and 7.7% (6.6-9.0) for VTDR. Indians had a higher prevalence of any DR (30.7% vs. 26.2% in Chinese and 25.5% in Malays, P = 0.012); a similar trend was noted for any DME (P = 0.001) and CSME (P = 0.032). Independent risk factors for any DR were Indian ethnicity (odds ratio [OR], 1.41; 95% CI, 1.09-1.83, vs. Chinese), diabetes duration (OR, 1.10; 95% CI, 1.08-1.11, per year), HbA1c (OR, 1.25; 95% CI, 1.18-1.32, per %), serum glucose (OR, 1.03; 95% CI, 1.00-1.06, per mmol/l), and systolic blood pressure (OR, 1.14; 95% CI, 1.09-1.19, per 10 mmHg). Diastolic blood pressure (OR, 0.74; 95% CI, 0.65-0.84, per 10 mmHg increase), total cholesterol (OR, 0.87; 95% CI, 0.80-0.95, per mmol/l increase), and low-density lipoprotein (LDL) cholesterol (OR, 0.83; 95% CI, 0.74-0.92, per mmol/l increase) were associated with lower odds of any DR. Risk factors were largely similar across the 3 ethnic groups. CONCLUSIONS: Indian Singaporeans have a higher prevalence of DR and DME compared with Chinese and Malays. Major risk factors for DR in this study were similar across the 3 ethnic groups. Addressing these risk factors may reduce the impact of DR in Asia, regardless of ethnicity.

Evaluating the impact of optical coherence tomography in diabetic retinopathy screening for an Aboriginal population.

IMPORTANCE: Optical coherence tomography is used routinely in management of diabetic eye disease but has not been evaluated in Australian outreach settings for screening programmes. BACKGROUND: The study aims to evaluate the use of optical coherence tomography combined with a fundus camera compared with a fundus camera only in a telehealth diabetic retinopathy screening programme for Aboriginal Australians. DESIGN: Retrospective comparative study was used. PARTICIPANTS: The study included patients with diabetes at two Aboriginal Health Services. METHODS: An intervention group was studied in 2015 using a Topcon 3D optical coherence tomography-1 Maestro combined with optical coherence tomography/fundus camera. A control group was studied in 2014 using a DRS non-mydriatic fundus camera. Fundus photographs were emailed to trained retinal graders for review. Optical coherence tomography scans were graded by ophthalmologists via remote TeamViewer access. MAIN OUTCOME MEASURE: Referral rates to an eye health professional and the rate of inadequate photographs. RESULTS: Two hundred and twenty-two patients were included, with 80 in the control group and 142 in the intervention group. There was a significantly higher rate of inadequate fundus photographs in the intervention group (31.0% vs. 13.8%). Although there was a higher rate of referral to an eye health professional in the intervention group (39.6% vs. 30.0%), this was not significant. Diabetic retinopathy and maculopathy was evident in 32.3% and 12.0% of adequate fundus photographs, respectively. Diabetic macular oedema was present in 3.6% of optical coherence tomography scans. CONCLUSIONS AND RELEVANCE: The combined optical coherence tomography fundus camera provided no advantage for diabetic retinopathy screening compared with fundus photography in an Australian programme. The rate of referral to an eye health professional was not reduced with a higher rate of inadequate fundus photographs.

Visual outcomes following vitrectomy for diabetic retinopathy amongst Indigenous and non-Indigenous Australians in South Australia and the Northern Territory.

IMPORTANCE: Visual outcomes following diabetic vitrectomy have not previously been studied in an Australian population. BACKGROUND: This analysis aimed to determine the rate of, and factors associated with visual success following diabetic vitrectomy performed for Indigenous and non-Indigenous Australians, and investigate factors predisposing to early progression to diabetic retinopathy (DR) requiring vitrectomy. DESIGN: Retrospective, population-based audit. PARTICIPANTS: All patients undergoing vitrectomy for the complications of DR in South Australia (SA) and the Northern Territory (NT) between 2007 and 2011. METHODS: Medical records were audited and data collected, including demographics, diabetic history, past treatment for DR, indication for vitrectomy and visual acuity pre and postoperatively. MAIN OUTCOME MEASURES: Visual success (gain of ≥15 ETDRS letters) at 6 and 12 months, postoperatively. RESULTS: A total of 495 diabetic vitrectomies, for 404 eyes of 335 patients were performed in SA and NT between 2007 and 2011. 77 (23%) patients requiring diabetic vitrectomy were Indigenous Australians. 87% of patients undergoing diabetic vitrectomy had stable or improved vision at 1 year, postoperatively. There was no significant difference between indigenous and non-indigenous eyes achieving visual success (P = 0.929). Timely preoperative laser treatment (P = 0.03) and preoperative visual acuity (P = 0.01) were the predominant factors associated with visual success. CONCLUSIONS AND RELEVANCE: Indigenous patients are just as likely to have improved vision following diabetic vitrectomy as non-Indigenous Australians. However, the small subset of indigenous patients with blind eyes prior to vitrectomy are significantly less likely to improve from surgery. The underlying factors associated with poor outcomes in this group requires further exploration.

Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes.

PURPOSE: Previous studies have yielded conflicting results regarding whether serum lipid levels are associated with retinal hard exudates in diabetic retinopathy. The majority of studies have assessed hard exudates only as a dichotomous trait (presence vs. absence) and included limited numbers of African Americans (AA). The purpose of this study was to determine if there are any associations between serum lipid levels and hard exudates in AA with type 2 diabetes (T2D). METHODS: 890 AA participants with T2D were enrolled from 5 sites. Macular fundus photographs were graded by masked ophthalmologist investigators. Hard exudate areas were measured using a semi-automated algorithm and ImageJ software. Multivariate regression models were used to determine the association between serum lipid levels and (1) presence of hard exudate and (2) area of hard exudate. RESULTS: Presence of hard exudates was associated with higher total cholesterol [(odds ratio (OR) = 1.08, 95 % confidence interval (CI) 1.03-1.13, P = 0.001)] and higher low-density lipoprotein (LDL) cholesterol (OR = 1.08, 95 % CI 1.03-1.14, P = 0.005) in models controlling for other risk factors. Hard exudate area was also associated with both higher total and LDL cholesterol levels (P = 0.04 and 0.01, respectively) in multivariate models controlling for other risk factors. CONCLUSIONS: Higher total and LDL cholesterol were associated with the presence of hard exudates and a greater hard exudate area in AA with T2D. This information can be used to counsel diabetic patients regarding the importance of lipid control to decrease the risk of macular hard exudates.

What do patients with diabetes and providers think of an innovative Australian model of remote diabetic retinopathy screening? A qualitative study.

BACKGROUND: Diabetic retinopathy (DR) is the commonest cause of preventable blindness in working age populations, but up to 98% of visual loss secondary to DR can be prevented with early detection and treatment. In 2012, an innovative outreach DR screening model was implemented in remote communities in a state of Australia. The aim of this study was to explore the acceptability of this unique DR screening model to patients, health professionals and other key stakeholders. METHODS: This descriptive qualitative study used semi-structured interviews with patients opportunistically recruited whilst attending DR screening, and purposefully selected health care professionals either working within or impacted by the programme. Interviews were audiotaped, transcribed and analysed using NVIVO. An iterative process of thematic analysis was used following the principles of grounded theory. RESULTS: Interviews were conducted with fourteen patients with diabetes living in three remote communities and nine health professionals or key stakeholders. Nine key themes emerged during interviews with health professionals, key stakeholders and patients: i) improved patient access to DR screening; ii) efficiency, financial implications and sustainability; iii) quality and safety; iv) multi-disciplinary diabetes care; v) training and education; vi) operational elements of service delivery; vii) communication, information sharing and linkages; viii) coordination and integration of the service and ix) suggested improvements to service delivery. CONCLUSIONS: The Remote Outreach DR Screening Service is highly acceptable to patients and health professionals. Challenges have primarily been encountered in communication and coordination of the service and further development in these areas could improve the programme's impact and sustainability in remote communities. The service is applicable to other remote communities nationally and potentially internationally.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

Association between LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms and diabetic retinopathy of type 2 diabetes mellitus in the Chinese Han population.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. The present study aimed to identify a possible connection between gene polymorphisms and the risk of developing DR. MATERIALS AND METHODS: A total of 319 patients with type 2 diabetes mellitus (T2DM) were selected. All patients underwent a complete eye examination. Based on this, the patients with T2DM were divided into two subgroups: 175 patients with retinopathy (DR) and 144 patients without retinopathy (NDR). We calculated the genotype frequencies of case and control subjects using the chi-squares test. The odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age and sex. RESULTS: The finding by analysis is that the mean of duration of diabetes, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), glomerular filtration rate and C-peptide were significantly different between DR and NDR. We found significant differences in cystatin-C concentrations with LEKR1-CCNL1 rs13064954 and NOS3 rs3918227 of different genotypes. Significant differences in serum TG levels were seen among the three genotypes of MTHFR rs1537516. Subjects carried the T allele of IGSF21-KLHDC7A rs3007729 had higher serum LDL concentrations (p = 0.015). In the allele model, LEKR1-CCNL1 rs13064954 decreased the risk of DR (OR =0.57, 95% CI = 0.34-0.96, p = 0.032). Under the dominant model, the IGSF21-KLHDC7A rs3007729 CT-TT genotype increased the risk of DR (OR =1.84, 95% CI = 1.14-2.99, p = 0.013). CONCLUSIONS: Our results suggest that LEKR1-CCNL1 and IGSF21-KLHDC7A influence the development of DR.