Screening for diabetic retinopathy and reduced vision among Indigenous Australians in Top End primary care health services: a TEAMSnet sub-study.

BACKGROUND: Diabetic retinopathy (DR) prevalence is higher in Indigenous Australians than in other Australians and is a major cause of vision loss. Consequently, timely screening and treatment is paramount, and annual eye screening is recommended for Indigenous Australians. AIMS: To assess the prevalence of DR, reduced vision and DR treatment coverage among Indigenous Australian adults with diabetes attending Top End indigenous primary care health services. METHODS: A cross-sectional DR screening study conducted from November 2013 to December 2015 in two very remote Northern Territory Aboriginal primary healthcare services. RESULTS: In 287 subjects, the prevalence of non-proliferative DR, proliferative DR and clinically significant diabetic macular oedema was 37.3%, 5.4% and 9.0% respectively. Treatment coverage for PDR was 60% (of 10 patients) and for CSMO was 17% (of 23 patients). Vision data were available from 122 participants at one site. The proportion with normal vision, reduced vision, impaired vision and blindness was 31.1%, 52.5%, 15.6% and 0.8% respectively. Overall, ungradable monocular image sets (46%) were associated with poorer quality images and missing protocol images (both P < 0.001). Ungradable images for DR were associated with presence of small pupils/media opacities (P < 0.001). Ungradable images for diabetic macular oedema were associated with poorer image quality (P < 0.001), cataracts (P < 0.001) and small pupils (P = 0.04). CONCLUSIONS: A high prevalence of DR, CSMO and impaired vision was noted in Indigenous Australians with diabetes. Screening in primary care is feasible, but more effective screening methods are needed.

The Indian Health Service Primary Care-Based Teleophthalmology Program for Diabetic Eye Disease Surveillance and Management.

Background: Historically, fewer than half of American Indians and Alaska Natives (AI/AN) with diabetes received the annual diabetic retinopathy (DR) examination that is considered the minimum standard of care; this rate is similar to that of the general United States (U.S.) population with diabetes. Solution: The Indian Health Service-Joslin Vision Network (IHS-JVN) Teleophthalmology Program in 2000 to increase compliance with DR standards of care among AI/AN through validated, primary care-based telemedicine. The IHS-JVN provides remote diagnosis of DR severity, with a report including management recommendations that is returned to the patient's primary care provider. The program conforms with the American Telemedicine Association (ATA) Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy. Outcomes: The IHS-JVN has been expanding incrementally since the first patients were recruited in 2000; this expansion coincides with large improvements in the annual DR examination rates reported as part of local, regional, and national regulatory compliance under the Government Performance and Results Act (GPRA). Currently, with 99 clinical implementations in 23 states, IHS-JVN is the largest primary care-based ATA validation category three telemedicine program in the U.S. Summary: This article describes the program's workflow, imaging and reading technologies, diagnostic protocols, reports to providers, training, quality assurance processes, and geographical distribution. In addition to its clinical use, the program has been utilized in research on utilization of diabetic eye care, cost-effectiveness, technology development, and DR epidemiology of the AI/AN population. Potential next steps for this program are discussed.

An evaluation of the telehealth facilitation of diabetes and cardiovascular care in remote Australian Indigenous communities: - protocol for the telehealth eye and associated medical services network [TEAMSnet] project, a pre-post study design.

BACKGROUND: Despite substantial investment in detection, early intervention and evidence-based treatments, current management strategies for diabetes-associated retinopathy and cardiovascular disease are largely based on real-time and face-to-face approaches. There are limited data re telehealth facilitation in type 2 diabetes management. Therefore, we aim to investigate efficacy of telehealth facilitation of diabetes and cardiovascular disease care in high-risk vulnerable Aboriginal and Torres Strait Islanders in remote/very remote Australia. METHODS: Using a pre-post intervention design, 600 Indigenous Australians with type 2 diabetes will be recruited from three primary-care health-services in the Northern Territory. Diabetes status will be based on clinical records. There will be four technological interventions: 1. Baseline retinal imaging [as a real-time patient education/engagement tool and telehealth screening strategy]. 2. A lifestyle survey tool administered at ≈ 6-months. 3. At ≈ 6- and 18-months, an electronic cardiovascular disease and diabetes decision-support tool based on current guidelines in the Standard Treatment Manual of the Central Australian Rural Practitioner's Association to generate clinical recommendations. 4. Mobile tablet technology developed to enhance participant engagement in self-management. Data will include: Pre-intervention clinical and encounter-history data, baseline retinopathy status, decision-support and survey data/opportunistic mobile tablet encounter data. The primary outcome is increased participant adherence to clinical appointments, a marker of engagement and self-management. A cost-benefit analysis will be performed. DISCUSSION: Remoteness is a major barrier to provision and uptake of best-practice chronic disease management. Telehealth, beyond videoconferencing of consultations, could facilitate evidence-based management of diabetes and cardiovascular disease in Indigenous Australians and serve as a model for other conditions. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN 12616000370404 was retrospectively registered on 22/03/2016.

Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation.

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy-based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I-induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I-induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema.

Incidence and Progression of Diabetic Retinopathy in American Indian and Alaska Native Individuals Served by the Indian Health Service, 2015-2019.

Importance: Estimates of diabetic retinopathy (DR) incidence and progression in American Indian and Alaska Native individuals are based on data from before 1992 and may not be informative for strategizing resources and practice patterns. Objective: To examine incidence and progression of DR in American Indian and Alaska Native individuals. Design, Setting, and Participants: This was a retrospective cohort study conducted from January 1, 2015, to December 31, 2019, and included adults with diabetes and no evidence of DR or mild nonproliferative DR (NPDR) in 2015 who were reexamined at least 1 time during the 2016 to 2019 period. The study setting was the Indian Health Service (IHS) teleophthalmology program for diabetic eye disease. Exposure: Development of new DR or worsening of mild NPDR in American Indian and Alaska Native individuals with diabetes. Main Outcomes and Measures: Outcomes were any increase in DR, 2 or more (2+) step increases, and overall change in DR severity. Patients were evaluated with nonmydriatic ultra-widefield imaging (UWFI) or nonmydriatic fundus photography (NMFP). Standard risk factors were included. Results: The total cohort of 8374 individuals had a mean (SD) age of 53.2 (12.2) years and a mean (SD) hemoglobin A1c level of 8.3% (2.2%) in 2015, and 4775 were female (57.0%). Of patients with no DR in 2015, 18.0% (1280 of 7097) had mild NPDR or worse in 2016 to 2019, and 0.1% (10 of 7097) had PDR. The incidence rate from no DR to any DR was 69.6 cases per 1000 person-years at risk. A total of 6.2% of participants (441 of 7097) progressed from no DR to moderate NPDR or worse (ie, 2+ step increase; 24.0 cases per 1000 person-years at risk). Of patients with mild NPDR in 2015, 27.2% (347 of 1277) progressed to moderate NPDR or worse in 2016 to 2019, and 2.3% (30 of 1277) progressed to severe NPDR or worse (ie, 2+ step progression). Incidence and progression were associated with expected risk factors and evaluation with UWFI. Conclusions and Relevance: In this cohort study, the estimates of DR incidence and progression were lower than those previously reported for American Indian and Alaska Native individuals. The results suggest extending the time between DR re-evaluations for certain patients in this population, if follow-up compliance and visual acuity outcomes are not jeopardized.

Comparison of low-light nonmydriatic digital imaging with 35-mm ETDRS seven-standard field stereo color fundus photographs and clinical examination.

PURPOSE: To compare agreement between diagnosis of clinical level of diabetic retinopathy (DR) and diabetic macular edema (DME) derived from nonmydriatic fundus images using a digital camera back optimized for low-flash image capture (MegaVision) compared with standard seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and dilated clinical examination. Subject comfort and image acquisition time were also evaluated. SUBJECTS AND METHODS: In total, 126 eyes from 67 subjects with diabetes underwent Joslin Vision Network nonmydriatic retinal imaging. ETDRS photographs were obtained after pupillary dilation, and fundus examination was performed by a retina specialist. RESULTS: There was near-perfect agreement between MegaVision and ETDRS photographs (κ=0.81, 95% confidence interval [CI] 0.73-0.89) for clinical DR severity levels. Substantial agreement was observed with clinical examination (κ=0.71, 95% CI 0.62-0.80). For DME severity level there was near-perfect agreement with ETDRS photographs (κ=0.92, 95% CI 0.87-0.98) and moderate agreement with clinical examination (κ=0.58, 95% CI 0.46-0.71). The wider MegaVision 45° field led to identification of nonproliferative changes in areas not imaged by the 30° field of ETDRS photos. Field area unique to ETDRS photographs identified proliferative changes not visualized with MegaVision. Mean MegaVision acquisition time was 9:52 min. After imaging, 60% of subjects preferred the MegaVision lower flash settings. CONCLUSIONS: When evaluated using a rigorous protocol, images captured using a low-light digital camera compared favorably with ETDRS photography and clinical examination for grading level of DR and DME. Furthermore, these data suggest the importance of more extensive peripheral images and suggest that utilization of wide-field retinal imaging may further improve accuracy of DR assessment.

Prevalence of Diabetic Eye Diseases in American Indians and Alaska Natives (AI/AN) as Identified by the Indian Health Service's National Teleophthalmology Program Using Ultrawide Field Imaging (UWFI).

PURPOSE: Estimates of diabetic eye disease in American Indian and Alaska Natives (AI/AN) vary over time, region, and methods. This article reports recent prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME) in AI/AN served by the Indian Health Services' (IHS) teleophthalmology program, as identified using ultrawide field imaging (UWFI). METHODS: This was a retrospective analysis of 2016-2019 clinical data (n = 53,900). UWF images were acquired by certified imagers using a validated protocol, and graded by licensed, certified optometrists supervised by an ophthalmologist. Graders evaluated the extent/severity of retinal lesions in comparison to standard photographs. DR lesions predominantly in any peripheral field were considered "predominantly peripheral lesions" (PPL). The analyses calculated prevalence of any DR, any DME, DR and DME severity, sight-threatening disease, and PPL. RESULTS: Patients averaged 56 years of age with a 68 mmol/mol A1c and 55% had had diabetes for 5+ years. Prevalence of any DR, any DME, and sight-threatening disease was 28.6%, 3.0%, and 3.0%. In patients with mild nonproliferative DR, PPL was seen in 25.3%. PPL suggested a more severe level of DR in 8.7% of patients. DR increased with age. DME decreased with age. Males and patients in the Nashville IHS area had more diabetic eye disease. CONCLUSION: AI/AN have a high burden of diabetes and its complications. The IHS is resource-constrained, making accurate disease estimates necessary for resource allocation and budget justifications to Congress. These data update the estimates of diabetic eye disease in Indian Country and suggest that UWFI identifies early DR.

Telehealth practice recommendations for diabetic retinopathy, second edition.

Ocular telemedicine and telehealth have the potential to decrease vision loss from DR. Planning, execution, and follow-up are key factors for success. Telemedicine is complex, requiring the services of expert teams working collaboratively to provide care matching the quality of conventional clinical settings. Improving access and outcomes, however, makes telemedicine a valuable tool for our diabetic patients. Programs that focus on patient needs, consider available resources, define clear goals, promote informed expectations, appropriately train personnel, and adhere to regulatory and statutory requirements have the highest chance of achieving success.

Associations with sight-threatening diabetic macular oedema among Indigenous adults with type 2 diabetes attending an Indigenous primary care clinic in remote Australia: a Centre of Research Excellence in Diabetic Retinopathy and Telehealth Eye and Associated Medical Services Network study.

OBJECTIVE: To identify factors associated with sight-threatening diabetic macular oedema (STDM) in Indigenous Australians attending an Indigenous primary care clinic in remote Australia. METHODS AND ANALYSIS: A cross-sectional study design of retinopathy screening data and routinely-collected clinical data among 236 adult Indigenous participants with type 2 diabetes (35.6% men) set in one Indigenous primary care clinic in remote Australia. The primary outcome variable was STDM assessed from retinal images. RESULTS: Age (median (range)) was 48 (21-86) years, and known diabetes duration (median (range)) was 8.0 (0-24) years. Prevalence of STDM was high (14.8%) and similar in men and women. STDM was associated with longer diabetes duration (11.7 vs 7.9 years, respectively; p<0.001) and markers of renal impairment: abnormal estimated Glomerular Filtration Rate (eGFR) (62.9 vs 38.3%, respectively; p=0.007), severe macroalbuminuria (>300 mg/mmol) (20.6 vs 5.7%, respectively; p=0.014) and chronic kidney disease (25.7 vs 12.2%, respectively; p=0.035). Some clinical factors differed by sex: anaemia was more prevalent in women. A higher proportion of men were smokers, prescribed statins and had increased albuminuria. Men had higher blood pressure, but lower glycated Haemoglobin A1c (HbA1c) levels and body mass index, than women. CONCLUSION: STDM prevalence was high and similar in men and women. Markers of renal impairment and longer diabetes duration were associated with STDM in this Indigenous primary care population. Embedded teleretinal screening, known diabetes duration-based risk stratification and targeted interventions may lower the prevalence of STDM in remote Indigenous primary care services. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trials Register: ACTRN 12616000370404.

Evolution of a web-based, prototype Personal Health Application for diabetes self-management.

Behaviors carried out by the person with diabetes (e.g., healthy eating, physical activity, judicious use of medication, glucose monitoring, coping and problem-solving, regular clinic visits, etc.) are of central importance in diabetes management. To assist with these behaviors, we developed a prototype PHA for diabetes self-management that was based on User-Centered Design principles and congruent with the anticipatory vision of Project Health Design (PHD). This article presents aspects of the prototype PHA's functionality as conceived under PHD and describes modifications to the PHA now being undertaken under new sponsorship, in response to user feedback and timing tests we have performed. In brief, the prototype Personal Health Application (PHA) receives data on the major diabetes management domains from a Personal Health Record (PHR) and analyzes and provides feedback based on clinically vetted educational content. The information is presented within "gadgets" within a portal-based website. The PHR used for the first implementation was the Common Platform developed by PHD. Key changes include a re-conceptualization of the gadgets by topic areas originally defined by the American Association of Diabetes Educators, a refocusing on low-cost approaches to diabetes monitoring and data entry, and synchronization with a new PHR, Microsoft® HealthVault™.

Combining iGoogle and personal health records to create a prototype personal health application for diabetes self-management.

OBJECTIVE: The aim of this project is to create a prototype for a personal health application (PHA) for patients (i.e., consumers) with diabetes by employing a user-centered design process. This article describes the design process for and resulting architecture, workflow, and functionality of such a PHA. MATERIALS AND METHODS: For the design process, we conducted focus groups with people who have diabetes (n = 21) to ascertain their needs for a PHA. We then developed a prototype in response to these needs, and through additional focus groups and step-by-step demonstrations for people with diabetes as well as healthcare providers, we obtained feedback about the prototype. The feedback led to changes in the PHA's presentation and function. RESULTS: Focus group participants said they wanted a tool that could give them timely, readily available information on how diabetes-related domains interact, how their behaviors affect them, and what to do next. Thus, the prototype PHA is Internet-based, retrieves data for diabetes self-management from a personal health record, displays those data using gadgets in the consumer's iGoogle page, and makes the data available to a decision-support component that provides lifestyle-oriented advice. Manipulation of the data enables consumers to anticipate the results of future actions and to see interrelationships. CONCLUSIONS: A user-centered design process resulted in a PHA that uses technology that is publicly available, employs a personal health record, and is Internet based. This PHA can provide the backbone for a decision support system that can bring together the cornerstones of diabetes self-management and integrate them into the life of the person with diabetes.

Usability test of an internet-based informatics tool for diabetes care providers: the comprehensive diabetes management program.

BACKGROUND: Research suggests Internet-based care management tools are associated with improvements in care and patient outcomes. However, although such tools change workflow, rarely is their usability addressed and reported. This article presents a usability study of an Internet-based informatics application called the Comprehensive Diabetes Management Program (CDMP), developed by content experts and technologists. Our aim is to demonstrate a process for conducting a usability study of such a tool and to report results. METHODS: We conducted the usability test with six diabetes care providers under controlled conditions. Each provider worked with the CDMP in a single session using a "think aloud" process. Providers performed standardized tasks with fictitious patient data, and we observed how they approached these tasks, documenting verbalizations and subjective ratings. The providers then completed a usability questionnaire and interviews. RESULTS: Overall, the scores on the usability questionnaire were neutral to favorable. For specific subdomains of the questionnaire, the providers' reported problems with the application's ease of use, performance, and support features, but were satisfied with its visual appeal and content. The results from the observational and interview data indicated areas for improvement, particularly in navigation and terminology. CONCLUSIONS: The usability study identified several issues for improvement, confirming the need for usability testing of Internet-based informatics applications, even those developed by experts. To our knowledge, there have been no other usability studies of an Internet-based informatics application with the functionality of the CDMP. Such studies can form the foundation for translation of Internet-based medical informatics tools into clinical practice.

Prevalence of diabetic retinopathy and diabetic macular edema in a primary care-based teleophthalmology program for American Indians and Alaskan Natives.

BACKGROUND: Diabetes and its complications are more common in American Indians and Alaska Natives (AI/AN) than other US racial/ethnic populations. Prior reports of diabetic retinopathy (DR) prevalence in AI/AN are dated, and research on diabetic macular edema (DME) is limited. This study characterizes the recent prevalence of DR and DME in AI/AN using primary care-based teleophthalmology surveillance. METHODS: This is a multi-site, clinic-based, cross-sectional study of DR and DME. The sample is composed of AI /AN patients with diabetes (n = 53,998), served by the nationally distributed Indian Health Service-Joslin Vision Network Teleophthalmology Program (IHS-JVN) in primary care clinics of US Indian Health Service (IHS), Tribal, and Urban Indian health care facilities (I/T/U) from 1 November 2011 to 31 October 2016. Patients were recruited opportunistically for a retinal examination using the IHS-JVN during their regular diabetes care. The IHS-JVN used clinically validated, non-mydriatic, retinal imaging and retinopathy assessment protocols to identify the severity levels of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), DME, and sight threatening retinopathy (STR; a composite measure). Key social-demographic (age, gender, IHS area), diabetes-related health (diabetes therapy, duration of diabetes, A1c), and imaging technology variables were examined. The analysis calculated frequencies and percentages of severity levels of disease. RESULTS: Prevalence of any NPDR, PDR, DME, and STR among AI/AN patients undergoing DR teleophthalmology surveillance by IHS-JVN was 17.7%, 2.3%, 2.3%, and 4.2%, respectively. Prevalence was lowest in Alaska and highest among patients with A1c >/ = 8%, duration of diabetes > 10 years, or using insulin. CONCLUSIONS: Prevalence of DR in this cohort was approximately half that in previous reports for AI/AN, and prevalence of DME was less than that reported in non-AI/AN populations. A similar reduction in diabetes related end-stage renal disease in the same population and time period has been reported by other researchers. Since these two diabetic complications share a common microvasculopathic mechanism, this coincident change in prevalence may also share a common basis, possibly related to improved diabetes management.

The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients.

We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (NID; endothelium independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin. Left ventricular function was evaluated using transthoracic echocardiogram. At the end of the 6-month period, a worsening in endothelium-dependent skin vasodilation (P = 0.02) and rise in endothelin levels (P = 0.01) were found in the vitamin E compared with the placebo group. At the end of the 12-month period, a worsening was observed in NID (P = 0.02) and a marginal worsening was seen in systolic blood pressure (P = 0.04) and FMD (P = 0.04) in the vitamin E compared with the placebo group. In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group (P = 0.05). No changes were observed in left ventricular function. We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients. Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects, the use of high dosages of vitamin E cannot be recommended.

Noninvasive volumetric imaging and morphometry of the rodent retina with high-speed, ultrahigh-resolution optical coherence tomography.

PURPOSE: To demonstrate high-speed, ultrahigh-resolution optical coherence tomography (OCT) for noninvasive, in vivo, three-dimensional imaging of the retina in rat and mouse models. METHODS: A high-speed, ultrahigh-resolution OCT system using spectral, or Fourier domain, detection has been developed for small animal retinal imaging. Imaging is performed with a contact lens and postobjective scanning. An axial image resolution of 2.8 mum is achieved with a spectrally broadband superluminescent diode light source with a bandwidth of approximately 150 nm at approximately 900-nm center wavelength. Imaging can be performed at 24,000 axial scans per second, which is approximately 100 times faster than previous ultrahigh-resolution OCT systems. High-definition and three-dimensional retinal imaging is performed in vivo in mouse and rat models. RESULTS: High-speed, ultrahigh-resolution OCT enabled high-definition, high transverse pixel density imaging of the murine retina and visualization of all major intraretinal layers. Raster scan protocols enabled three-dimensional volumetric imagingand comprehensive retinal segmentation algorithms allowed measurement of retinal layers. An OCT fundus image, akin to a fundus photograph was generated by axial summation of three-dimensional OCT data, thus enabling precise registration of OCT measurements to retinal fundus features. CONCLUSIONS: High-speed, ultrahigh-resolution OCT enables imaging of retinal architectural morphology in small animal models. OCT fundus images allow precise registration of OCT images and repeated measurements with respect to retinal fundus features. Three-dimensional OCT imaging enables visualization and quantification of retinal structure, which promises to allow repeated, noninvasive measurements to track disease progression, thereby reducing the need for killing the animal for histology. This capability can accelerate basic research studies in rats and mice and their translation into clinical patient care.

Comparison of nonmydriatic digital retinal imaging versus dilated ophthalmic examination for nondiabetic eye disease in persons with diabetes.

OBJECTIVE: To evaluate the ability of stereoscopic nonmydriatic digital retinal imaging to detect ocular pathologic features other than diabetic retinopathy (DR) in patients with diabetes mellitus (DM) compared with dilated retinal examination by retinal specialist ophthalmologists. DESIGN: Clinic-based comparative instrument study and retrospective chart review. PARTICIPANTS: Two hundred eighty Joslin Diabetes Center outpatients (560 eyes) with type 1 or type 2 DM. METHODS: Nonsimultaneous stereoscopic nonmydriatic digital retinal images (640 x 480 pixels) of three 45 degrees retinal fields were acquired and graded for clinical level of DR and other ocular pathologic features by certified readers according to Joslin Vision Network (JVN) protocol. Retrospective chart review compared findings from JVN digital images with findings from dilated retinal examination by retinal specialists performed within an average of 39.6 days of digital imaging. An independent senior retinal specialist adjudicated disagreements by review of 7 standard field 35-mm Early Treatment Diabetic Retinopathy Study protocol fundus photographs and JVN images. MAIN OUTCOME MEASURES: Detection of non-DR ocular pathologic features by digital imaging as compared with clinical examination. RESULTS: Nonmydriatic digital evaluation identified at least 1 non-DR ocular finding in 40.7% of patients (114/280). Non-diabetes mellitus ocular pathologic features identified by digital images, clinical examination, or both included cataract (n = 100); age-related maculopathy (n = 52); suspicion of glaucoma (n = 18); choroidal lesions (n = 18); evidence of systemic disorder (e.g., hypertension or renal disease; n = 15); epiretinal membrane (n = 11); chorioretinal atrophy, scar, or both (n = 6); retinal emboli (n = 3); retinitis pigmentosa (n = 1); and asteroid hyalosis (n = 1). Agreement of nonmydriatic imaging with clinical examination for presence and absence of these findings was 95.4%, 91.3%, 98.2%, 98.6%, 98.2%, 99.6%, 100%, 100%, 100%, and 100%, respectively. Kappa values for all non-DR lesions demonstrated near perfect agreement (kappa> or =0.80) except for age-related maculopathy (kappa = 0.71) and choroidal lesions (kappa = 0.73), where agreement was substantial. Overall, only 55 eyes (9.8%) were ungradable for level of DR and 85 eyes (15.2%) were ungradable for macular edema. CONCLUSIONS: Joslin Vision Network nonmydriatic digital imaging demonstrated excellent agreement with dilated ophthalmic examination by retinal specialists in the detection of ocular disease other than DR, suggesting a potential role for this technology in evaluating non-DR disorders and highlighting the extent of findings other than retinopathy in patients with diabetes.

Role of the angiotensin II type 1 receptor in the pathogenesis of diabetic retinopathy: effects of blood pressure control and beyond.

Diabetic retinopathy is characterized by both functional and morphological changes in the retinal microvessels that can lead to macular edema, neovascularization, and vision loss. Hypertension has been identified as a major risk factor for diabetic retinopathy and randomized clinical trials have shown that reduction of blood pressure using angiotensin converting enzyme (ACE) inhibitors reduces the progression of diabetic retinopathy. The major components of the renin-angiotensin system have been identified in ocular tissues. Activation of angiotensin II type 1 (AT1) receptors expressed on retinal endothelial cells and pericytes has been implicated in contributing to the microvascular abnormalities in diabetic retinopathy. We have examined the experimental and clinical evidence for the role of the renin-angiotensin system in the pathogenesis of diabetic retinopathy, including the effects of ACE inhibition and AT1-receptor antagonism on diabetes-induced abnormalities in retinal hemodynamics, vascular permeability, and leukostasis; retinal neovascularization in rodent models of oxygen-induced retinopathy; and results from randomized clinical trials that have investigated the effects of ACE inhibitors on the progression of diabetic retinopathy in diabetic patients in the absence or presence of hypertension. The effects of AT1-receptor antagonism on the retina have been attributed to decreases in systemic blood pressure and the concomitant reduction in mechanical vascular stretch, in addition to the intraocular effects blocking AT1-receptor stimulation of retinal endothelial cells and pericytes. Results from the current DIabetic REtinopathy Candesartan Trials program will evaluate the potential of the AT1-receptor as a therapeutic target for diabetic retinopathy.

Characterization of retinal leukostasis and hemodynamics in insulin resistance and diabetes: role of oxidants and protein kinase-C activation.

Increases in leukostasis/monocyte adhesion to the capillary endothelium (leukostasis) and decreases in retinal blood flow may be causally associated and are implicated in the pathogenesis of diabetic retinopathy. In this study, we demonstrate that increases in leukostasis are observed in insulin-resistant states without diabetes, whereas decreases in retinal blood flow require diabetes and hyperglycemia. Microimpaction studies using beads mimicking retinal capillary obstruction by leukocytes did not affect retinal blood flow. In diabetic rats, treatment with the antioxidant alpha-lipoic acid normalized the amount of leukostasis but not retinal blood flow. In contrast, treatment with D-alpha-tocopherol and protein kinase-C beta-isoform inhibition (LY333531) prevented the increases in leukostasis and decreases in retinal blood flow in diabetic rats. Serum hydroxyperoxide, a marker of oxidative stress, was increased in diabetic rats, but normalized by treatment with antioxidants alpha-lipoic acid and D-alpha-tocopherol and, surprisingly, PKC beta-isoform inhibition. These findings suggest that leukostasis is associated with endothelial dysfunction, insulin resistance, and oxidative stress but is not related to retinal blood flow and is not sufficient to cause diabetic-like retinopathy. Moreover, treatment with PKC beta inhibition is effective to normalize diabetes or hyperglycemia-induced PKC beta-isoform activation and oxidative stress.

An internet-based diabetes management platform improves team care and outcomes in an urban Latino population.

OBJECTIVE: To compare usual diabetes care (UDC) to a comprehensive diabetes care intervention condition (IC) involving an Internet-based "diabetes dashboard" management tool used by clinicians. RESEARCH DESIGN AND METHODS: We used a parallel-group randomized design. Diabetes nurses, diabetes dietitians, and providers used the diabetes dashboard as a clinical decision support system to deliver a five-visit, 6-month intervention to 199 poorly controlled (HbA1c >7.5% [58 mmol/mol]) Latino type 2 diabetic (T2D) patients (mean age 55 years, 60% female) at urban community health centers. We compared this intervention to an established, in-house UDC program (n = 200) for its impact on blood glucose control and psychosocial outcomes. RESULTS: Recruitment and retention rates were 79.0 and 88.5%, respectively. Compared with UDC, more IC patients reached HbA1c targets of <7% (53 mmol/mol; 15.8 vs. 7.0%, respectively, P < 0.01) and <8% (64 mmol/mol; 45.2 vs. 25.3%, respectively, P < 0.001). In multiple linear regression adjusting for baseline HbA1c, adjusted mean ± SE HbA1c at follow-up was significantly lower in the IC compared with the UDC group (P < 0.001; IC 8.4 ± 0.10%; UDC 9.2 ± 0.10%). The results showed lower diabetes distress at follow-up for IC patients (40.4 ± 2.1) as compared with UDC patients (48.3 ± 2.0) (P < 0.01), and also lower social distress (32.2 ± 1.3 vs. 27.2 ± 1.4, P < 0.01). There was a similar, statistically significant (P < 0.01) improvement for both groups in the proportion of patients moving from depressed status at baseline to nondepressed at follow-up (41.8 vs. 40%; no significance between groups). CONCLUSIONS: The diabetes dashboard intervention significantly improved diabetes-related outcomes among Latinos with poorly controlled T2D compared with a similar diabetes team condition without access to the diabetes dashboard.