Are Individuals With Diabetes Seeing Better?

Diabetic retinopathy (DR) was the leading cause of severe visual impairment (VI) in subjects 25–64 years of age in the U.S. 30 to 40 years ago (1,2). At that time, severe VI (best corrected visual acuity of 20/200 or worse in the better eye) was 25 times as common in subjects with diabetes compared with those without diabetes. VI in subjects with diabetes resulted mainly from vitreous hemorrhage, tractional detachment of the macula due to proliferative diabetic retinopathy (PDR), and from macular edema involving the foveal area due to leakage from the breakdown of the blood-retinal barrier. Cataract and glaucoma also contributed to VI in individuals with diabetes. Poor glycemic control was common in subjects with diabetes at that time (3,4). This was due, in part, to the fact that intensive appropriate insulin treatment was difficult to achieve. This was related to the technology that was available for monitoring glucose levels (self-monitoring of glycemic control was done by testing of spot urines; no glycosylated hemoglobin A1c was available) and to the way insulin was administered (no pump, treatment with one injection per day of a long-acting insulin). There was no definitive evidence that achieving good glycemic control would actually result in less DR; thus, there was a lack of consensus on optimal glucose levels among physicians caring for individuals with diabetes. Some clinicians believed that high blood glucose was less likely to result in the development of severe DR in subjects with type 2 diabetes than in those with type 1 diabetes (5). Blood pressure was also poorly controlled in individuals with diabetes at that time (3,4). In 1972, the efficacy of photocoagulation had not yet been demonstrated to prevent visual loss due to PDR or macular edema. Vitrectomy, a surgical intervention to restore vision in eyes with vitreous hemorrhage or tractional detachments of the macula, was in its developmental stages. The purpose of this article is to provide a historical epidemiological perspective showing the relation of changes in the management of diabetes and its retinal and visual complications to the changes in the incidence and progression of DR and VI over the past 30 years. Evidence of a relationship of hyperglycemia to DR. In 1979, the relationship between hyperglycemia and the development of DR had not been resolved. Kelly M. West, in his 1978 textbook, Epidemiology of Diabetes and Its Vascular Lesions, wrote, “The extent to which the level of hyperglycemia determines the risk of retinopathy is not at all clear. This is the most important issue at hand and deserves high priority in epidemiologic research” (6). Baseline data (1980–1982) from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a cohort study of both type 1 and type 2 diabetes showed that less than 10% of individuals with diabetes achieved levels of glycemia (glycosylated hemoglobin A1c 7%) and blood pressure ( 130/80 mmHg) considered adequate by today’s standards (Table 1) (3,4). Epidemiological data from the WESDR and other cohort studies showed that glycemic control was strongly related to the incidence and progression of DR and that achieving glycemic control was beneficial at any time during the course of diabetes and at any level of severity of DR prior to the onset of PDR (7). There was no threshold level above normal at which the lowering of glycosylated hemoglobin levels was not associated with the lowering of risk of incidence or progression of DR. Moreover, for a given level of glycemia, the risk of retinopathy progressing or developing into PDR or clinically significant macular edema (CSME) (the thickening of the retina involving the fovea or a certain area threatening the fovea) was similar for both individuals with type 1 and type 2 diabetes. This provided evidence that glycemic control and not the type of diabetes was important in determining risk of progression of DR. Two large randomized therapeutic trials of metabolic control, the Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) (for type 1 and type 2 diabetes, respectively), provided evidence of the efficacy of intensive glycemic control (8,9). DCCT showed an approximate 76% reduction in the progression of retinopathy in the primary prevention cohort (subjects without DR at baseline) and a 54% reduction in the progression of DR in the secondary prevention cohort (subjects with mild to moderate nonproliferative diabetic retinopathy [NPDR] at baseline) in the intensive therapy group compared with the conventional therapy group after five years of follow-up. DCCT data suggested that if intensive therapy for the 120,000 subjects with type 1 diabetes in the U.S. who met DCCT criteria could maintain a hemoglobin A1c level of 7.2% for life, 920,000 years of sight would be gained (10). The long-term benefits of intensive treatment went well beyond its implementation and led investigators to suggest that “intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes and maintained thereafter, aiming for a practicable target HbA1c level of 7.0% or less” (11). However, achieving intensive glycemic control in the From the Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Corresponding author: Ronald Klein, [email protected]. Received 29 December 2009 and accepted 19 May 2010. DOI: 10.2337/db09-1904 © 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by -nc-nd/3.0/ for details. PERSPECTIVES IN DIABETES