Barriers and enablers to diabetic eye screening attendance: An interview study with young adults with type 1 diabetes.

AIM: The aim of this study was to identify barriers and enablers of diabetic eye screening (DES) attendance amongst young adults with diabetes living in the United Kingdom. METHODS: Semistructured qualitative interviews with adults aged 18-34 years with diabetes. Participants were purposively sampled to aim for representation across gender, geographical locations, diabetes type, years since diabetes diagnosis and patterns of attendance (i.e. regular attenders, occasional non-attenders, regular non-attenders). Data were collected and analysed using the Theoretical Domains Framework (TDF) to explore potential individual, sociocultural and environmental influences on attendance. Data were analysed using a combined deductive and inductive thematic analysis approach. Barriers/enablers were mapped to behaviour change techniques (BCTs) to identify potential strategies to increase attendance. RESULTS: Key barriers to attendance reported by the sample of 29 study participants with type 1 diabetes, fell within the TDF domains: [Knowledge] (e.g. not understanding reasons for attending DES or treatments available if diabetic retinopathy is detected), [Social Influences] (e.g. lack of support following DES results), [Social role and Identity] (e.g. not knowing other people their age with diabetes, feeling 'isolated' and being reluctant to disclose their diabetes) and [Environmental Context and Resources] (e.g. lack of appointment flexibility and options for rescheduling). Enablers included: [Social Influences] (e.g. support of family/diabetes team), [Goals] (e.g. DES regarded as 'high priority'). Many of the reported barriers/enablers were consistent across groups. Potential BCTs to support attendance include Instructions on how to perform the behaviour; Information about health consequences; Social support (practical) and Social comparison. CONCLUSIONS: Attendance to diabetic eye screening in young adults is influenced by a complex set of interacting factors. Identification of potentially modifiable target behaviours provides a basis for designing more effective, tailored interventions to help young adults regularly attend eye screening and prevent avoidable vision loss.

Circulating microRNAs as novel biomarkers for platelet activation.

RATIONALE: MicroRNA (miRNA) biomarkers are attracting considerable interest. Effects of medication, however, have not been investigated thus far. OBJECTIVE: To analyze changes in plasma miRNAs in response to antiplatelet therapy. METHODS AND RESULTS: Profiling for 377 miRNAs was performed in platelets, platelet microparticles, platelet-rich plasma, platelet-poor plasma, and serum. Platelet-rich plasma showed markedly higher levels of miRNAs than serum and platelet-poor plasma. Few abundant platelet miRNAs, such as miR-24, miR-197, miR-191, and miR-223, were also increased in serum compared with platelet-poor plasma. In contrast, antiplatelet therapy significantly reduced miRNA levels. Using custom-made quantitative real-time polymerase chain reaction plates, 92 miRNAs were assessed in a dose-escalation study in healthy volunteers at 4 different time points: at baseline without therapy, at 1 week with 10 mg prasugrel, at 2 weeks with 10 mg prasugrel plus 75 mg aspirin, and at 3 weeks with 10 mg prasugrel plus 300 mg aspirin. Findings in healthy volunteers were confirmed by individual TaqMan quantitative real-time polymerase chain reaction assays (n=9). Validation was performed in an independent cohort of patients with symptomatic atherosclerosis (n=33), who received low-dose aspirin at baseline. Plasma levels of platelet miRNAs, such as miR-223, miR-191, and others, that is, miR-126 and miR-150, decreased on further platelet inhibition. CONCLUSIONS: Our study demonstrated a substantial platelet contribution to the circulating miRNA pool and identified miRNAs responsive to antiplatelet therapy. It also highlights that antiplatelet therapy and preparation of blood samples could be confounding factors in case-control studies relating plasma miRNAs to cardiovascular disease.

Non-steroidal anti-inflammatory agents for treating cystoid macular oedema following cataract surgery.

BACKGROUND: Cystoid macular oedema (CMO) is the accumulation of fluid in the central retina (the macula) due to leakage from dilated capillaries. It is the most common cause of poor visual outcome following cataract surgery. The exact cause is unclear. Acute CMO, defined as oedema of less than four months duration, often resolve spontaneously. CMO that persists for four months or more is termed chronic CMO. Different types of non-steroidal anti-inflammatory agents (NSAIDs) are used in the treatment of CMO which may be delivered topically or systemically. OBJECTIVES: To examine the effectiveness of NSAIDs in the treatment of CMO following cataract surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 7), MEDLINE (January 1950 to August 2011), EMBASE (January 1980 to August 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (August 2011) and ClinicalTrials.gov (www.clinicaltrials.gov) (August 2011). We searched the reference lists of identified trials. We searched conference abstracts (sessions related to cataract) in The Association for Research in Vision and Ophthalmology (ARVO) 1975 to 2011. We contacted experts in the field and NSAIDs manufacturers for details on published and unpublished trials.There were no language or date restrictions in the search for trials. The electronic databases were last searched on 5 August 2011. SELECTION CRITERIA: We included randomised controlled trials evaluating the effects of NSAIDs in the treatment of CMO following cataract surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. Since considerable heterogeneity was observed between studies we did not conduct meta-analyses. MAIN RESULTS: Seven trials involving a total of 266 participants were included. Four trials studied the effects of NSAIDs in chronic CMO while the other three examined the effect of NSAIDs in acute CMO. Of the studies examining chronic CMO, one study enrolled 120 participants, but the remainder had 34 or fewer participants. Four different NSAIDs were used and administered in different ways. Indomethacin was used orally and was found to be ineffective for chronic CMO in one trial. Topical fenoprofen appeared effective but not statistically significantly so for chronic CMO in another small trial. Treatment with topical 0.5% ketorolac for chronic CMO was found to be effective in two trials. Three trials examined the effect of topical NSAIDs on acute CMO. The comparisons among these studies were of an NSAID to placebo, prednisolone or another NSAID. The study design differed between the studies in other important aspects thus they could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: This review found two trials which showed that topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) has a positive effect on chronic CMO and two trials which revealed no significant difference between comparative groups. As such, the effects of NSAIDs in acute and chronic CMO remain unclear and needs further investigation.

Retinal vascular calibre, geometry and progression of diabetic retinopathy in type 2 diabetes mellitus.

PURPOSE: To determine whether changes in retinal vascular calibre and geometry are associated with progression of diabetic retinopathy in type 2 diabetes (T2D). PROCEDURES: The retinal vascular calibre and geometry of 30 subjects with more than 20 years of diagnosed T2D with no retinopathy (NR) were compared to 30 subjects that progressed to proliferative diabetic retinopathy (PDR). The images of PDR subjects included in this study were those obtained before the onset of retinopathy. The diameter of retinal arterioles (CRAE), retinal venules (CRVE), tortuosity of retinal vessels, junctional exponent deviation (JE(a)) and fractal dimension (D(f)) were measured using Singapore I Vessel Assessment (SIVA 3.0) software and compared using Mann-Whitney U test. RESULTS: The median CRAE and the median CRVE were significantly wider in PDR subjects compared to NR subjects (p = 0.014 and 0.016), respectively. Curvature tortuosity of the retinal arteries and veins and D(f) were significantly decreased in the PDR subjects compared to NR subjects (p = 0.015, 0.016 and 0.03, respectively). The JE(a) was significantly increased in PDR subjects (p = 0.01). CONCLUSIONS: Retinal vessel calibre and geometry of the retinal vasculature may be important risk factors for the progression to PDR. More longitudinal prospective studies will be needed to further explore the findings of this study.

Mechanistic Evaluation of Panretinal Photocoagulation Versus Aflibercept in Proliferative Diabetic Retinopathy: CLARITY Substudy.

Purpose: The purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy. Methods: This is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks. Retinal oximetry and ultra-widefield angiography were performed at baseline and week 52. Ultra-widefield color fundus imaging was performed at baseline, week 12, and week 52. The outcomes were retinal arterio-venous oximetry differences (AVD), area of retinal nonperfusion, and area of neovascularization in disc areas (DA). Results: The AVD in the PRP group increased from 36.7% at baseline to 39.7%, whereas it decreased from 33.4% to 32.5% in the aflibercept group. The difference in AVD between groups at week 52 was 4.0% (95% confidence interval, -0.08, 8.8; P = 0.10). The baseline mean area of retinal nonperfusion of 125.1 DA and 131.2 DA in the PRP and aflibercept groups increased to 156.1 DA and 158.4 DA, respectively, at week 52 (P = 0.46). The median baseline area of neovascularization decreased from 0.98 DA to 0.68 DA in the PRP group and from 0.70 DA to 0 DA in the aflibercept group at week 12 (P = 0.019). At week 52, this measured 0.24 DA in the PRP group and 0 DA in the aflibercept group (P = 0.45). Conclusions: Intravitreal aflibercept achieved an earlier and complete regression of neovascularization in proliferative diabetic retinopathy compared with PRP. There were no significant differences in global change in intravascular oxygen saturation or areas of retinal nonperfusion between the two groups by 52 weeks.

Model for Risk-Based Screening of Diabetic Retinopathy in People With Newly-Diagnosed Type 2 Diabetes Mellitus.

Purpose: The purpose of this study was to evaluate the role of inflammatory/lipid markers and potential risk factors for diabetic retinopathy (DR) development in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Methods: Participants in this study were 1062 patients with newly diagnosed T2DM. Demographic and clinical data of patients were collected. Assessment of DR status was performed using digital two-field photography. In addition, HbA1c (%), lipid profile, and urinary albumin were measured at recruitment. The following inflammatory markers were also measured: serum C-reactive protein, white blood cells, platelet, adiponectin, IL-4, IL-6, IL-10, vascular endothelial growth factor, tumor necrosis factor-α (TNF-α), IL-1b, IL-1 receptor antagonist (IL-1RA), and monocyte chemotactic protein-1. Univariate and multivariate analyses of the association of various potential risk factors and DR were conducted. Results: Univariate analysis showed that male sex, any cardiovascular event, and HbA1c were positively associated with DR, while IL-1RA, IL-1b, IL-6, and TNF-α were significantly negatively associated with presence of DR in the cohort. Risk factors that remained significantly associated with DR presence at the multivariate analysis were male sex, any cardiovascular event, HbA1c, and IL-1RA. Conclusions: Our study demonstrated that HbA1c levels, male sex, and previous cardiovascular events were risk factors for presence of DR in people with newly diagnosed T2DM, while IL-1RA seemed to have a protective role. The prevalence of DR in our population was 20.2%, reflecting current practice. Our findings may contribute to future risk-based modelling of screening for DR.

Long-Term Outcomes of Aflibercept Treatment for Neovascular Age-Related Macular Degeneration in a Clinical Setting.

PURPOSE: To report 2-year treatment outcomes with intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) in routine clinical practice. DESIGN: Retrospective, nonrandomized, interventional case series. METHODS: Retrospective analysis of electronic medical record (EMR) notes (OpenEyes) and paper case notes and review of spectral-domain optical coherence tomography (SDOCT) imaging of patients with consecutively treated eyes with previously untreated nAMD. Patients were commenced on aflibercept injections in 1 or both eyes from October 1, 2013 to December 31, 2013. Data including age, sex, visual acuity (VA) measured on Early Treatment Diabetic Retinopathy Study charts, injection episodes, and complications were recorded. Additionally, SDOCT data, including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1 and 2, were recorded. RESULTS: Of the 109 eyes of 102 patients treated, data from 94 eyes of 88 patients were available at 2-year follow-up (86% of patients). In the analysis of 2-year outcomes, there were 58 women (65.9%); the mean (± standard deviation) age was 77.5 ± 8 years. Over the 2 years, these eyes received a median of 12 (mean, 11.4 ± 4) injections at a median of 100 (mean, 99.3 ± 5.3) weeks of follow-up. The mean VA changed from 55.9 ± 15 letters at baseline to 61.3 ± 16.9 letters (VA gain 5.4 letters) at 1 year and to 61 ± 17.1 letters (VA gain 5.1 ± 14.9 letters) at 2 years. The reduction in CSMT was 79 µm with absence of macular fluid in 72.7% of the 88 eyes with SDOCT data available at 2-year follow-up. CONCLUSIONS: The VA and SDOCT results compare favorably with outcomes seen in randomized controlled trials. The results suggest that good long-term outcomes can be achieved using aflibercept for nAMD in clinical settings.

An exploratory study evaluating the effects of macular carotenoid supplementation in various retinal diseases.

PURPOSE: The aim of this study was to assess the impact of daily oral supplementation with Macushield (10 mg/d meso-zeaxanthin, 10 mg/d lutein, and 2 mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. METHODS: Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6 months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute- Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. RESULTS: A statistically significant increase in the MP optical density was observed using the dual-wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P<0.05) improvements in glare sensitivity in low and medium spatial frequencies were observed at 3 months and 6 months. Ceiling effects confounded other visual function tests and quality of life changes. CONCLUSION: Supplementation with the three carotenoids enhances certain aspects of visual performance in retinal diseases.

Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting.

CONTEXT: Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD) remains unclear. AIMS: The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting. SETTINGS AND DESIGN: A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact. MATERIALS AND METHODS: A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8) and the patients' demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined. RESULTS: The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8), health-related quality of life (EQ-5D-3L), and duration of AMD. Visual acuity changes were rated as less important than one would have expected. CONCLUSION: The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment.

Associations between Retinal Markers of Microvascular Disease and Cognitive Impairment in Newly Diagnosed Type 2 Diabetes Mellitus: A Case Control Study.

OBJECTIVE: To investigate associations between retinal microvascular changes and cognitive impairment in newly diagnosed type 2 diabetes mellitus. DESIGN: Case control study. SETTING: A primary care cohort with newly diagnosed type 2 diabetes mellitus. METHODS: For this analysis, we compared 69 cases with lowest decile scores (for the cohort) on the Modified Telephone Interview for Cognitive Status and 68 controls randomly selected from the remainder of the cohort. Retinal images were rated and the following measures compared between cases and controls: retinal vessel calibre, arterio-venous ratio, retinal fractal dimension, and simple and curvature retinal vessel tortuosity. RESULTS: Total and venular (but not arteriolar) simple retinal vessel tortuosity levels were significantly higher in cases than controls (t = 2.45, p = 0.015; t = 2.53, p = 0.013 respectively). The associations persisted after adjustment for demographic factors, retinopathy, neuropathy, obesity and blood pressure. There were no other significant differences between cases and controls in retinal measures. CONCLUSIONS: A novel association was found between higher venular tortuosity and cognitive impairment in newly diagnosed type 2 diabetes mellitus. This might be accounted for by factors such as hypoxia, thrombus formation, increased vasoendothelial growth factor release and inflammation affecting both the visible retinal and the unobserved cerebral microvasculature.

A prospective randomised controlled clinical trial comparing a combination of repeated intravitreal Ozurdex and macular laser therapy versus macular laser only in centre-involving diabetic macular oedema (OZLASE study).

BACKGROUND/AIMS: To evaluate the clinical efficacy and safety of combined repeated Ozurdex and macular laser therapy (MLT) compared with MLT monotherapy in participants with visual impairment due to centre-involving diabetic macular oedema (DMO). METHODS: 80 patients with best corrected visual acuity (BCVA) between 54 and 78 ETDRS letters due to centre-involving DMO were randomised to combination therapy with Ozurdex and MLT or MLT only. The combination arm received mandated Ozurdex injections at baseline and 16 weeks followed by retreatment criteria-guided pro-re-nata therapy at 32 and 48 weeks. Patients randomised to MLT only were treated every 16 weeks if clinically significant macular oedema was present. The primary outcome was the mean change from baseline in BCVA between arms at 56 weeks. RESULTS: The mean change in BCVA at 56 weeks was -0.3 (SD 11.4) ETDRS letters in the combination arm versus +0.4 (SD 9.6) ETDRS (Early Treatment Diabetic Retinopathy study) letters in the MLT arm (effect estimate 1.15 (95% CI -3.32 to 5.61)). However, at 56 weeks, a post hoc comparison of central subfield thickness (CST) showed a decrease of -113 µm (IQR -218, -64) (combination) versus -17 µm (-128, 12) (MLT arm) (p<0.001). Elevated intraocular pressure requiring topical therapy was observed in 8 (20%) eyes in the combination versus 1 (2.5%) in the MLT arm. 33% (9/27) of phakic patients in the combination arm underwent cataract surgery. CONCLUSIONS: Visual outcome following combination therapy did not differ from MLT alone in the centre-involving DMO despite a significant decrease in CST likely due to an entry visual acuity-related ceiling effect and cataract development. TRIAL REGISTRATION NUMBER: EudraCT 2011-003339-74.

Cross Talk between Lipid Metabolism and Inflammatory Markers in Patients with Diabetic Retinopathy.

PURPOSE: The purpose of this study was to examine the relationship between metabolic and inflammatory markers in patients with diabetic retinopathy (DR). METHODS: 208 adult patients with type 2 diabetes participated in this study and were categorized into (1) mild nonproliferative diabetic retinopathy (NPDR) without clinically significant macular edema (CSME), (2) NPDR with CSME, (3) proliferative diabetic retinopathy (PDR) without CSME, and (4) PDR with CSME. Variable serum metabolic markers were assessed using immunoassays. Multinomial logistic regression analysis was performed. RESULTS: Diabetes duration and hypertension are the most significant risk factors for DR. Serum Apo-B and Apo-B/Apo-A ratio were the most significant metabolic risk factors for PDR and CSME. For every 0.1 g/L increase in Apo-B concentration, the risk of PDR and CSME increased by about 1.20 times. We also found that 10 pg/mL increase in serum TNF-α was associated with approximately 2-fold risk of PDR/CSME while an increase by 100 pg/mL in serum VEGF concentration correlated with CSME. CONCLUSIONS: In conclusion, it seems that there is a link between metabolic and inflammatory markers. Apo-B/Apo-A ratio should be evaluated as a reliable risk factor for PDR and CSME, while the role of increased systemic TNF-α and VEGF should be explored in CSME.

Caregiver Burden in Patients Receiving Ranibizumab Therapy for Neovascular Age Related Macular Degeneration.

PURPOSE: To assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD). METHODS: This is a cross-sectional questionnaire survey of 250 matched patient caregiver dyads across three large ophthalmic treatment centres in United Kingdom. The primary outcome was the subjective caregiver burden measured using caregiver reaction assessment scale (CRA). Objective caregiver burden was determined by the caregiver tasks and level of care provided. The factors that may predict the caregiver burden such as the patient's visual acuity of the better eye and vision related quality of life, demographics, satisfaction and support provided by the healthcare and the health status of the dyads were also collected and assessed in a hierarchical regression model. RESULTS: The mean CRA score was 3.2±0.5, similar to the score reported by caregivers for atrial fibrillation who require regular hospital appointments for monitoring their thromboprophylaxis. Caregiver tasks including accompanying for hospital appointments for eye treatment and patient's visual acuity in the better eye were the biggest contributors to the caregiver burden hierarchical model explaining 18% and 11% of the variance respectively. CONCLUSION: Ranibizumab therapy for nAMD is associated with significant caregiver burden. Both disease impact and treatment frequency contributed to the overall burden.

Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy.

AIMS: We previously showed that circulating mitochondrial DNA (MtDNA) levels are altered in diabetic nephropathy. The aim of the current study was to determine if circulating MtDNA levels are altered in patients with diabetic retinopathy. METHODS: Patients with diabetes (n=220) were studied in a clinical setting using a cross-sectional study design as the following groups: DR-0 (no retinopathy, n=53), DR-m (mild non-proliferative diabetic retinopathy NPDR, n=98) and DR-s (severe proliferative diabetic retinopathy, n=69). MtDNA content in peripheral blood DNA was measured as the mitochondrial to nuclear genome ratio using real time qPCR. Circulating cytokines were measured using the luminex assay and MtDNA damage was assessed using PCR. Differences were considered significant at P<0.05. RESULTS: Circulating MtDNA values were higher in DR-m compared to DR-0 (P=0.02) and decreased in DR-s compared to DR-m (P=0.001). These changes remained significant after adjusting for associated parameters. In parallel there were increased levels of circulating cytokines IL-4 (P=0.005) and TNF-α (P=0.02) in the DR-s group and increased MtDNA damage in DR-m patients compared to DR-0 (P=0.03). CONCLUSIONS: Our data show that circulating MtDNA levels are independently associated with diabetic retinopathy, showing an increase in DR-m and decrease in DR-s with a parallel increase in MtDNA damage and inflammation. Hyperglycemia-induced changes in MtDNA in early diabetes may contribute to inflammation and progression of diabetic retinopathy. Longitudinal studies should be carried out to determine a potential causality of MtDNA in diabetic retinopathy.

A multicentre phase III randomised controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark-adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomised controlled trial.

BACKGROUND: This study will evaluate hypoxia, as a novel concept in the pathogenesis of diabetic macular oedema (DMO). As the oxygen demand of the eye is maximum during dark-adaptation, we hypothesize that wearing light-masks during sleep will cause regression and prevent the development and progression of DMO. The study protocol comprises both an efficacy and mechanistic evaluation to test this hypothesis. METHOD/DESIGN: This is a phase III randomised controlled single-masked multicentre clinical trial to test the clinical efficacy of light-masks at preventing dark-adaptation in the treatment of non-central DMO. Three hundred patients with non-centre-involving DMO in at least one eye will be randomised 1:1 to light-masks and control masks (with no light) to be used during sleep at night for a period of 24 months. The primary outcome is regression of non-central oedema by assessing change in the zone of maximal retinal thickness at baseline on optical coherence tomography (SD-OCT). Secondary outcomes will evaluate the prevention of development and progression of DMO by assessing changes in retinal thickness in different regions of the macula, macular volume, refracted visual acuity and level of retinopathy. Safety parameters will include sleep disturbance. Adverse events and measures of compliance will be assessed over 24 months. Participants recruited to the mechanistic sub-study will have additional retinal oximetry, multifocal electroretinography (ERG) and microperimetry to evaluate the role of hypoxia by assessing and comparing changes induced by supplemental oxygen and the light-masks at 12 months. DISCUSSION: The outcomes of this study will provide insight into the pathogenesis of DMO and provide evidence on whether a simple, non-invasive device in the form of a light-mask can help prevent the progression to centre-involving DMO and visual impairment in people with diabetes.

The relationship between diabetic retinopathy and cognitive impairment.

OBJECTIVE: Recent studies have shown an increased risk for cognitive impairment and dementia in patients with diabetes. An association between diabetic retinopathy (DR) and retinal microvasculature disease and cognitive impairment has been reported as potential evidence for a microvascular component to the cognitive impairment. It was hypothesized that severity of DR would be associated with cognitive impairment in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Three hundred eighty patients with type 2 diabetes were recruited from a population-based eye screening program and grouped by severity of DR as follows: no/mild DR (n=252) and proliferative diabetic retinopathy (PDR) (n=128). Each participant underwent psychosocial assessment; depression screening; ophthalmic and physical examination, including blood assays; and cognitive assessment with the Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), and the Mini-Cog. General linear modeling was used to examine severity of DR and cognitive impairment, adjusting for confounders. RESULTS: Severity of DR demonstrated an inverse relationship with cognitive impairment (fully adjusted R2=0.415, P<0.001). Ethnicity contributed most to the variance observed (16%) followed by education (7.3%) and retinopathy status (6.8%). The no/mild DR group had lower cognitive impairment scores on ACE-R (adjusted mean±SE 77.0±1.9) compared with the PDR group (82.5±2.2, P<0.001). The MMSE cutoff scores showed that 12% of the no/mild DR group (n=31) had positive screening results for dementia or significant cognitive impairment compared with 5% in the PDR group (n=6). CONCLUSIONS: Patients with minimal DR demonstrated more cognitive impairment than those with advanced DR. Therefore, the increased prevalence of cognitive impairment in diabetes may be associated with factors other than evident retinal microvascular disease.

Injection frequency and response to bevacizumab monotherapy for diabetic macular oedema (BOLT Report 5).

AIMS: To explore the parameters that influence injection frequency in patients treated with intravitreal bevacizumab (ivB) for diabetic macular oedema. Injection frequency was considered as a surrogate marker of persistent or recurrent oedema. METHODS: A post hoc analysis of the patients randomised to the ivB arm of a prospective, randomised controlled trial (A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study)) was done to assess the factors that may determine the injection frequency at 12 and 24 months. The injection response patterns were classified based on the specific time point at which the macula was first defined as 'dry'. RESULTS: Eyes with better baseline visual acuity less frequently had persistent oedema and had fewer recurrences in the second year. All eyes with baseline subretinal detachment showed persistent macular oedema at 24 months. None of the other factors assessed influenced injection frequency or response in the first or second year. CONCLUSIONS: Good long-term response is predicted by resolution of macular oedema by 4 months. However, approximately 20% of patients with persistent oedema at 12 months achieved a dry macula and 50% gained more than 15 letters at 24 months with sustained treatment, suggesting that oedema at 4 or 12 months should not be used as a stopping criterion for treatment.

Structural and functional measures of efficacy in response to bevacizumab monotherapy in diabetic macular oedema: exploratory analyses of the BOLT study (report 4).

BACKGROUND: To describe structural and functional changes associated with diabetic macular oedema (DMO) treated with intravitreal bevacizumab over 24 months. METHODS: A post-hoc analysis of the data of 34 patients that completed 24 months follow-up in the intravitreal bevacizumab arm of a prospective, randomized controlled trial (BOLT study) was performed. The outcome measures previously used in clinical trials of intravitreal ranibizumab in DMO were employed to describe the visual acuity and macular thickness changes at 12 and 24 months. RESULTS: The standard outcomes of mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) in participants treated with bevacizumab were comparable to those reported in association with ranibizumab. However, exploratory analyses showed that thick maculae at baseline defined as CMT of ≥ 400 µm, remained significantly thicker than those <400 µm with intensive bevacizumab therapy, despite a comparable gain in visual acuity at both 12 and 24 months. The proportion of subjects that attained a dry macula doubled in both CMT groups between the 12 and 24-month time-points. CONCLUSIONS: These findings provide valuable information both for clinical practice and trials. Further studies are required to investigate the impact of intravitreal bevacizumab on retinal thickness profiles in DMO.

Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective.

The alarming rise in diabetes prevalence is a global public health and economic problem. Diabetic retinopathy is the most common complication of diabetes and the leading cause of blindness among working-age populations in the Western world. Screening and prompt treatment of diabetic retinopathy are not top priorities in many regions of the world, because the impacts of other causes of preventable blindness remain an issue. Ethnicity is a complex, independent risk factor for diabetic retinopathy. Observations from white populations cannot be extrapolated fully to other ethnic groups. The prevalence of diabetic retinopathy, sight-threatening diabetic retinopathy, and clinically significant macular edema are higher in people of South Asian, African, Latin American, and indigenous tribal descent compared to the white population. Although all ethnic groups are susceptible to the established risk factors of diabetic retinopathy-such as length of exposure and severity of hyperglycemia, hypertension, and hyperlipidemia-ethnic-specific risk factors also may influence these rates. Such risk factors may include differential susceptibility to conventional risk factors, insulin resistance, differences in anthropometric measurements, truncal obesity, urbanization, variations in access to healthcare systems, genetic susceptibility, and epigenetics. The rates of nonproliferative diabetic retinopathy appear to be declining in the United States, supporting the observation that better medical management of diabetes and prompt treatment of sight-threatening diabetic retinopathy substantially improve the long-term diabetic retinopathy incidence; studies from other parts of the world are limited and do not mirror this finding, however. We examine the ethnicity and region-based prevalence of diabetic retinopathy around the world and highlight the need to reinforce ethnicity-based screening and treatment thresholds in diabetic retinopathy.