Lloyd Paul Aiello

OBJECTIVE: To assess self-reported awareness of diabetic retinopathy (DR) and concordance of eye examination follow-up compared with findings from concurrent retinal images. RESEARCH DESIGN AND METHODS: We conducted a prospective observational 10-year study of 26,876 consecutive patients with diabetes who underwent retinal imaging during an endocrinology visit. Awareness and concordance were evaluated using questionnaires and retinal imaging. RESULTS: Awareness information and gradable images were available in 25,360 patients (94.3%). Severity of DR by imaging was as follows: no DR (n = 14,317; 56.5%), mild DR (n = 6,805; 26.8%), or vision-threatening DR (vtDR; n = 4,238; 16.7%). In the no, mild, and vtDR groups, 96.7%, 88.5%, and 54.9% of patients, respectively, reported being unaware of any prior DR. When DR was present, reporting no prior DR was associated with shorter diabetes duration, milder DR, last eye examination >1 year before, no dilation, no scheduled appointment, and less specialized provider (all P < 0.001). Among patients with vtDR, 41.2%, 58.1%, and 64.2% did not report being aware of any DR and follow-up was concordant with current DR severity in 66.7%, 41.3%, and 25.4% (P < 0.001) of patients when prior examination was performed by a retinal specialist, nonretinal ophthalmologist, or optometrist (P < 0.001), respectively. CONCLUSIONS: Substantial discrepancies exist between DR presence, patient awareness, and concordance of follow-up across all DR severity levels. These discrepancies are present across all eye care provider types, with the magnitude influenced by provider type. Therefore, patient self-report should not be relied upon to reflect DR status. Modification of medical care and education models may be necessary to enhance retention of ophthalmic knowledge in patients with diabetes and ensure accurate communication between all health care providers.

Aims To compare microaneurysm (MA) counts using ultrawide field colour images (UWF-CI) and ultrawide field fluorescein angiography (UWF-FA). Methods Retrospective study including patients with type 1 or 2 diabetes mellitus receiving UWF-FA and UWF-CI within 2 weeks. MAs were manually counted in individual Early Treatment Diabetic Retinopathy Study (ETDRS) and extended UWF zones. Fields with MAs ≥20 determined diabetic retinopathy (DR) severity (0 fields=mild, 1–3=moderate, ≥4=severe). UWF-FA and UWF-CI agreement was determined and UWF-CI DR severity sensitivity analysis adjusting for UWF-FA MA counts performed. Results In 193 patients (288 eyes), 2.4% had no DR, 29.9% mild non-proliferative DR (NPDR), 32.6% moderate (NPDR), 22.9% severe NPDR and 12.2% proliferative DR. UWF-FA MA counts were 3.5-fold higher (pConclusions UWF-FA detects threefold to fivefold more MAs than UWF-CI and identifies 1.6–3.5-fold more fields affecting DR severity. Differences exist at all DR severity levels, thus limiting direct comparison between the modalities. However, correcting UWF-FA MA counts substantially improves DR severity agreement between the modalities. Trial registration number NCT03531294.

OBJECTIVE: To evaluate whether intensive treatment (INT) with the goal of achieving blood glucose levels as close to the nondiabetic range as safely possible reduced the risk of onset and progression of diabetic retinopathy (DR) in subjects with type 1 diabetes (T1D) compared with conventional therapy (CON). RESEARCH DESIGN AND METHODS: The Diabetes Control and Complications Trial (DCCT) (1982–1993) was a multicenter, controlled clinical trial comparing INT with CON for onset and progression of DR. The Epidemiology of Diabetes Interventions and Complications (EDIC) study (1994–present) is an observational follow-up of the DCCT cohort. RESULTS: Of the 1,441 DCCT subjects, 726 had no DR (primary prevention cohort) and 715 had mild DR (secondary intervention cohort) at baseline. Subjects were followed for a mean of 6.5 years. INT median HbA1c was 7% compared with CON median of 9%. INT reduced the adjusted mean risk for the development of DR by 76% and slowed progression of DR by 54% compared with CON. Following DCCT, the HbA1c levels in the original INT and CON groups converged (year 8, INT 7.98%; CON 8.07%); nevertheless, the groups continued to have a durable effect of initial assigned therapy with significantly lower incidence of further DR progression in the INT group (hazard reduction 53–56%). Severe retinal outcomes and procedures to treat them were reduced by 50% in the original INT group. CONCLUSIONS: INT delays the onset and slows the progression of DR. Furthermore, the early effects of metabolic control continue to accrue over many years despite subsequent comparable glycemic control (metabolic memory). These results emphasize the need for optimizing glycemic control as early as possible in patients with diabetes.

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.

Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases.

To evaluate efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with moderately severe to very severe nonproliferative diabetic retinopathy from the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2 ruboxistaurin (RBX) protein kinase C β inhibitor trials. Patients in these 3-year, randomized, placebo-controlled, double-masked, Phase 3 trials had best-corrected Early Treatment Diabetic Retinopathy Study visual acuity ≥45 letters (∼20/125 Snellen), Early Treatment Diabetic Retinopathy Study retinopathy level 47A/B-53E, and no previous panretinal photocoagulation in ≥1 eye. Patients received placebo (N = 401) or RBX 32 mg/day (N = 412). Data from the 2 studies were combined and masked evaluation of retinal photographs was performed for cause of visual decline in all patients experiencing sustained moderate visual loss (≥15-letter loss sustained for the last 6 months of study). In the studies combined, sustained moderate visual loss occurred in 10.2% of placebo-treated patients versus 6.1% of RBX-treated patients (P = 0.011). A ≥15-letter gain occurred in 2.4% of placebo versus 4.7% of RBX eyes (P = 0.021) and a ≥15-letter loss occurred in 11.4% versus 7.4%, respectively (P = 0.012). Diabetic macular edema was the probable primary cause of vision loss. Among eyes without focal/grid photocoagulation at baseline, fewer RBX group eyes (26.7%) required initial focal/grid photocoagulation versus placebo (35.6%; P = 0.008). No safety concerns were identified. Analysis of data combined from two similar studies adds further statistical significance to RBX's beneficial effects on visual loss, need for focal laser, and vision gain, most likely through effects on macular edema.

Current projections estimate that diabetes mellitus will afflict over 439 million individuals worldwide by 2030. The task of detecting and evaluating for the presence and severity of retinopathy in the populations with diabetes mellitus is enormous. Although current methods of treatment are effective in reducing the risk for vision loss, a substantial proportion of patients still do not receive appropriate eye care. The use of an ocular telemedicine–based approach has the potential to expand the reach of these highly effective treatments to virtually any location. Novel methods of image acquisition and analysis, as well as the identification of predictive biomarkers, will need to be developed to further enhance this approach of eye care delivery. In addition, such programs will allow the rapid transfer of clinically relevant discoveries and will allow a considerably larger benefit to a broader patient population.

Research from JAMA Ophthalmology — Rosiglitazone and Delayed Onset of Proliferative Diabetic Retinopathy