Systemic Medical Management of Diabetic Retinopathy
Good glycemic control is by far the most important factor in the medical management of diabetic retinopathy, as demonstrated by both the Diabetes Control and Complications Trial (DCCT; Clinical Trial 5-1) and the United Kingdom Prospective Diabetes Study (UKPDS; Clinical Trial 5-2). In these studies, intensive glycemic control was associated with a reduced risk of a new onset of retinopathy and with reduced progression of existing retinopathy in people with diabetes mellitus (type 1 in the DCCT and type 2 in the UKPDS). In addition, the DCCT demonstrated that intensive glycemic control (compared with conventional treatment) was associated with reductions in progression to severe NPDR and PDR, incidence of DME, and need for panretinal and focal photocoagulation. Even small changes in sustained hemoglobin A1c (HbA1c) levels were found to have a large impact on diabetic retinopathy progression. Indeed, when compared to standard glycemic control, intensive glycemic control was associated with decreases in retinopathy onset, progression of retinopathy, and need for ocular surgery over at least 2 subsequent decades, even after the DCCT study ended and the HbA1c levels between the original randomization groups converged. This “metabolic memory” phenomenon implies sustained benefit from early intensive glycemic control. Based on the DCCT and UKPDS results, most patients with diabetes are now recommended to achieve an HbA1c level of <7.0%. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and its follow-up (ACCORDION) study demonstrated a benefit for further reduction in HbA1c levels down to <6.0% for slowed diabetic retinopathy progression in patients with type 2 diabetes mellitus; however, this intensive regimen is not generally recommended because it was also associated with greater mortality rate.
Hypertension, when poorly controlled over many years, is associated with a higher risk of progression of diabetic retinopathy and DME. The UKPDS showed that control of hypertension was also beneficial in reducing progression of retinopathy and vision loss. Severe carotid artery occlusive disease may result in advanced PDR as part of ocular ischemic syndrome. Advanced diabetic nephropathy and anemia may also exacerbate diabetic retinopathy. Abnormally high lipid levels are associated with greater risk of vision loss from DME-associated hard exudates.
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Aiello LP, Sun W, Das A, Gangaputra S, et al; DCCT/EDIC Research Group. Intensive diabetes therapy and ocular surgery in type 1 diabetes. N Engl J Med. 2015;372(18):1722–1733.
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Chew EY, Ambrosius WT, Davis MD, et al; ACCORD Study Group; ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363(3):233–244.
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Chew EY, Mills JL, Metzger BE, et al. Metabolic control and progression of retinopathy: The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study. Diabetes Care. 1995;18(5):631–637.
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Diabetes Control and Complications Trial Research Group. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology. 1995;102(4):647–661.
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Nathan DM, Genuth S, Lachin J, et al; Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329(14):977–986.
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UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837–853.
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UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–713.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.