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Diabetic Retinopathy as a Predictor of Systemic Micro and Macrovascular Complications

Op-Med is a collection of original articles contributed by Doximity members.

During the ASRS 2020 virtual meeting, Bobeck S Modjtahedi, and coworkers presented a retrospective study examining patients with type 2 DM for new incidents of CVA, MI, or all-cause mortality within five years of the retinal grading, excluding patients with previously diagnosed CHF, CVA and/or MI, but evaluating for the risk associated with the severity of retinopathy in addition to the known risk factors of age, gender, race, smoking status, HTN, body mass index, duration of diabetes, and hemoglobin A1c. Although the overall rates were relatively low with 2.5% suffering an MI, 3.3% a CVA, and 5.5% dying within 5 years, the severity of diabetic retinopathy was independently associated with increased risk hazards ratios ranging from 1.2 to 1.3 with mild retinopathy to 1.72 to 2.34 for the events occurring in the presence of severe retinopathy (Modjtahedi, 2020). 

This report is in line with the current recognition of diabetes as an autoimmune disorder producing system wide oxidative and inflammatory injury of organ tissues along with microvascular injury and exacerbations of macrovascular disease. Tissue apoptosis occurs of pancreas beta cells, the central and peripheral nervous system, cardiac muscle, and kidney in line with the recognition of retinal neuron injury that occurs long before the traditionally recognized microvascular lesions (Sinclair, 2020, Barber, 1998, Bui, 2009, Coughlin, 2017, Gastinger, 2008, Kern. 2008, Meshi, 2018). While AI programs assist in the photographic screening of retinopathy and monitoring progression, they rely upon detection of the traditional microaneurysm, and microvascular changes with hemorrhages, overwhelmingly only following vision loss and are poor at detecting ischemic defects of the inner retina, the exudative components of vascular leakage within the mid-retina, and the abnormalities of the retinal pigment epithelium (Duh, 2017, Gulshan, 2016, Simó, 2018, Sinclair, 2006). More recently we have come to realize that retinal neuronal injury actually precedes the microangiopathy (Araszkiewicz, 2016, Gardner, 2017, Lynch, 2017, Simo, 2018, Villarroel, 2010) paralleling similar disease processes occurring within the other organs (Sinclair 2020). 

Because of the delayed screening identification of the retinopathy and relative poor monitoring, the treatments have been focused by participating ophthalmologists solely on the treatment modalities for the end stages of the disease — intravitreal injections and laser photocoagulation for severe retinal ischemia, leakage producing edema, and neovascularization — but with poor resultant vision recovery. Among other organs the detection of the disease process and its progression are similarly delayed with the treatments directed primarily toward the end stages before organ failure (renal failure, congestive heart failure, peripheral neuropathy). Desperately needed are systemic measurements of the diabetic inflammatory process that can be used to screen in the early stages and predict the course for the individual patient. Examinations have demonstrated associations with serum C reactive protein, Cyclooxygenase 2 , ICAM-1, N-epsilon carboxymethyl lysin, AGE’s, pentraxin 3, Calgranulin C, among others (Pusparajah, 2016), and, since the photographed retina is the window to the soul, we desperately need imaging methods that will detect the process and its progression, such as with PSVue or Annexin (Mazzoni, 2019, Cordeiro, 2017). This should not only provide for the improved application of systemic treatments that will retard the process systemically, such as with minocycline, pentoxifylline, or Tie2 activator, to name a few (Suchitra, 2016, Lopes de Jesus, 2008, Rubsam, 2018) but also with localized retinal treatment, such as with super-dense micropulse laser (Luttrull, 2012). In addition, hopefully this will provide for improved warning communication from the generalist physician or endocrinologist to the ophthalmologist as well as the reverse. The specialties can no longer be focused on their own endpoints of treatment but must collaborate.


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