Despite numerous advances in medical options and ophthalmologic treatments, diabetic retinopathy (DR) remains the leading cause of irreversible blindness in working-age adults, and is an escalating concern for diabetic patients and their physicians. An estimated 24 million Americans, or 7.8% of the population, are diabetic, and of these, an estimated 5.7 million are undiagnosed.¹ The diabetes epidemic is underscored by a tripling in the number of diagnosed cases in the past 20 years, a trend expected to continue in step with an ageing population and the prevalence of obesity and metabolic syndrome.

DR is one of several microvascular complications of diabetes that adversely affect patients' quality of life and constitute a major societal burden due to health care costs, disability, lost productivity and income and long-term care.

Epidemiology

The major risk factor for DR is the duration of diabetes. Retinopathy is rare within five years of onset of diabetes, and increases steadily thereafter. For example, DR is present in 13% of juvenile-onset diabetics at five years after a diabetes diagnosis and in nearly 90% at 10 to 15 years.² A similar trend is found for type 2 diabetics, in which insulin-dependence is an additional risk factor. Five years after diagnosis DR prevalence is 40% and 24% in adults using or not using insulin, respectively. These numbers increase to 84% and 53% at 15 to 19 years after diagnosis.³ Because diagnosis of type 2 diabetes is sometimes delayed, vision loss may be a warning sign.

The prevalence of diabetes increases with age and rises to 23% for patients 60 years of age and older (CDCP National Diabetes Fact Sheet, 2007). By the year 2050, the number of patients in the United States over age 65 years with DR is projected to nearly quadruple from 2.5 million to 9.9 million and a similar increase (0.5 to 1.9 million) in visually-threatening DR is anticipated.⁴

Correlation of DR with duration of diabetes implicates chronic hyperglycemia as a critical risk factor for DR. The Diabetes Control and Complications Trial randomized 1441 patients with insulin-dependent diabetes mellitus (IDDM) without DR or with mild DR to receive either intensive or conventional insulin treatment. The efficacy of intensive treatment was confirmed by a significantly reduced HbA1c (7% vs 9.2%). Onset of DR was reduced by 75% and progression was reduced by 50% in patients receiving the intensive regimen.⁵

The United Kingdom Prospective Diabetes Study (UKPDS) extended these results to adult-onset non-insulin dependent diabetes mellitus (NIDDM); patients treated with oral antihyperglycemic agents exhibited a lower HbA1c level than those treated by diet alone, and a 25% reduction in DR progression and need for laser treatment.⁶ A target HbA1c below 7% is now recommended.

Two caveats emerge from these studies. First, excellent glycemic control does not entirely eliminate the risk for DR to develop or progress, so that vigilance to detect DR is required for all diabetic patients. Second, a paradoxical exacerbation of DR is occasionally seen following rapid normalization of blood glucose levels; thus glycemic control should be pursued more gradually in patients with especially elevated HbA1c.⁵

The UKPDS also showed that blood pressure control reduced the need for retinal laser treatment by approximately one-third.⁷ The beneficial effect of blood pressure reduction was independent of the use of angiotensin-converting enzyme inhibitors, which have been suggested to ameliorate retinal complications of diabetes. Additional systemic conditions correlated with DR include hyperlipidemia, anaemia, carotid stenosis, and diabetic nephropathy and neuropathy. Gestational diabetes poses no risk for retinopathy, but pre-existing DR may progress rapidly during pregnancy.

Several genetic loci appear to confer risk or protection for development and progression of DR. Native Americans exhibit the highest known prevalence of type 2 diabetes and develop more severe retinopathy.⁸ Latin Americans, perhaps because of gene sharing with Native Americans, may also be at risk for more severe retinopathy than other ethnic and racial groups, even when adjusting for diabetes and hypertension duration and control.⁷ Socioeconomic factors likely exacerbate these disparities.

In apparent contradiction with the above data, only 48% of patients with type 1 diabetes for 50 or more years reported DR and only 54% of this geriatric population had any microvascular complication. Moreover, retinopathy was least prevalent in the oldest patients and in those with greater duration of diabetes, and was not associated with glycemic control.⁹ These unexpected results point to unknown microvascular-protective factors in long-term survivors of diabetes.