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Purpose: Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness. Design: We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system. Participants: Not applicable. Methods: The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these. Main Outcome Measures: Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD. Results: A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome. Conclusion: Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Objective: To report on the implementation and initial pilot data of diabetic retinopathy (DR) identified using a validated telemedicine program for DR in a multispecialty primary care clinic. Methods: This was a retrospective, cross-sectional pilot survey of diabetic patients imaged for the first time at the telemedicine program of The Medical City from November 26, 2012 to August 31, 2013. The retinal images were obtained following the validated program of the Joslin Vision Network nonmydriatic fundus photography for DR evaluation. These were evaluated by 4 retina specialists using a standardized protocol to assess for diabetic retinal disease and the presence of other retinal findings. The findings were recorded on customized electronic templates. Results: Seven hundred seventy-six (776) eyes of 388 patients were evaluated using the telemedicine program. The prevalence of DR was 28.2% (219 eyes), with 25.1% (195 eyes) having nonproliferative DR (NPDR). 14.2% [110 eyes] had mild, 8.2% [64 eyes] moderate, 2.2% [17 eyes] severe, and 0.5% [4 eyes] very severe NPDR. 3.1% (24 eyes) had proliferative DR (PDR), of which 45.8% (11 eyes) had high-risk characteristics. The ungradable rate with selective mydriasis was 1.80% (14 eyes). The rate of referable DR (moderate NPDR or worse, any level of diabetic macular edema, or ungradable images) was 21.90% (170 eyes). Conclusion: In the primary care setting, teleophthalmology can effectively identify patients with diabetic retinal complications and potentially refer these patients to appropriate levels of eye care. Retinopathy was present in over 28% of patients evaluated and over 21% had referable disease that may potentially progress to vision loss. Teleophthalmology for DR in this setting allows early detection of potentially sight threatening disease and may prevent visual loss and complications.