Asst. Professor of Ophthalmology, Thomas Jefferson University, Retina Service at Wills Eye Hospital
Director of Retina Research of Wills Eye Hospital, Professor of Ophthalmology
Currently affecting more than 425 million people worldwide, and projected to drastically rise in the coming decades, diabetes is a worldwide problem on both an individual and population level.1 Diabetic retinopathy (DR) is the most common cause of preventable vision loss in working aged adults in many countries.2 In the United States, 86% of those with type 1 diabetes (T1D) have diabetic retinopathy, with 42% having vision-threatening retinopathy. In cases of type 2 diabetes (T2D), 40% of people have diabetic retinopathy, with 8% vision-threatening.3,4 These rates are relatively consistent in similarly developed countries. Although T2D is more prevalent than T1D, the incidence of DR in T1D patients is substantially higher, with studies suggesting that over a 25-year period, almost all patients (97%) with T1D will develop DR, with one-third to one-half of those patients developing vision-threatening disease.5,6,7,8
There are numerous pathophysiologic mechanisms and pathways that help explain the anatomic and functional changes from DR. Our understanding of these concepts continues to evolve alongside our research in the field. The cornerstone of dysregulation is believed to be secondary to chronic levels of hyperglycemia combined with alterations in cellular metabolism, signaling, and growth factors that initiate a deluge of physiologic and biochemical alterations leading to damage of the retinal microvasculature and resultant dysfunction.9 Some of these implicated pathways include the well-known upregulation of vascular endothelial growth factor (VEGF), inflammatory mediators released in response to hyperglycemic stress, accumulation of sorbitol and other advanced glycation end-products, oxidative stress, and activation of protein kinase C.9,10,11
Nonproliferative DR (NPDR) is characterized by levels of microvascular changes and ischemia – microaneurysms, hemorrhages (flame and dot blot), lipid deposits, venous dilation and beading, intraretinal microvascular abnormalities (dilated pre-existing capillaries), and cotton wool spots. Retinal neovascularization signifies the presence of proliferative DR (PDR), which carries significantly more risk of progression of severe vision loss from vitreous hemorrhage and/or tractional retinal detachment from fibrovascular proliferation.12 Diabetic macular edema (DME) can develop at any stage of DR, and can wax and wane independently from other features of DR. Loss of vision can ultimately result from iris neovascularization (and secondary neovascular glaucoma), retinal neovascularization, and secondary fibrovascular proliferation (leading to vitreous hemorrhage and/or tractional retinal detachment) or macular dysfunction (retinal ischemia or DME).
Management and treatment of DR had progressed rapidly over the last two decades, with intravitreal anti-VEGF therapy targeted towards the treatment of DME, PDR, and NPDR leading the charge.13,14,15 Vitreoretinal specialists also rely on intravitreal corticosteroids and focal laser photocoagulation to help manage DME, whereas panretinal photocoagulation remains a timeless treatment for PDR.16,17,18 Ultimately, pars plana vitrectomy remains the most invasive tool for management and treatment of non-clearing vitreous hemorrhage and/or tractional retinal detachment. Even though meticulous blood sugar control combined with careful management of other systemic vascular risk factors (blood pressure, serum lipids, smoking) have been proven to slow the advancement of DR, some patients require medical or surgical intervention despite optimal disease management.19,20,21
Screening for DR is essential, as a large number of patients with diabetes can have advanced and severe diabetic retinopathy without any visual impairment or change in visual acuity. This also represents one of the biggest challenges in managing diabetic patients, as vision-threatening disease can already exist before patients carry any previous ocular diagnoses (and often can pre-date his/her diagnosis of diabetes). Diabetic patients who had never received a retinal assessment had a four-fold increase in the risk to develop sight-threatening complications from DR, and screening helps to ameliorate that, aiming to identify all cases of retinopathy and prevent progression to sight-threatening disease by early intervention.22,23 Although careful retinal evaluation by an ophthalmologist or optometrist remain the gold standard for diagnosing, and even screening for, DR, limited access to these professionals and other restraints on the medical system has led to the development and research of other screening tools (telescreening, automated detection by artificial intelligence, smartphone-based systems, etc.).1 The research focus on the field of DR screening remains focused on accuracy, effectiveness, and resource allocation, as the importance and necessity have been well documented. Screening for DR should be as vital as A1c levels, blood pressure and lipid control, foot examinations, and urinalysis – fundamental tenants of complete care of the diabetic patient.
The incredible advances in treatment and management of DR have preserved sight and prevented vision loss in an immeasurable number of patients. To have access to these treatment tools, it is essential that diabetic patients undergo appropriate DR screening to help mitigate, or prevent, the development of sight-threatening complications.
Michael N. Cohen is a member of the Retina Service at Wills Eye Hospital, an associate at Mid Atlantic Retina, and an Assistant Professor of Ophthalmology at the Kimmel School of Medicine at Thomas Jefferson University.
Allen C. Ho, MD is the Director of Retina Research of Wills Eye Hospital a partner at Mid Atlantic Retina and a Professor of Ophthalmology at the Kimmel School of Medicine at Thomas Jefferson University.
References
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