Diabetic macular edema (DME) is a consequence of microvascular changes in the retina that develop as a result of the progression of diabetic retinopathy (Romero-Aroca, 2010, 2011). In DME, weakened capillaries in the eye allow fluid to cross the blood-retinal barrier, which in turn results in retinal thickening and an accumulation of fluid in the retinal tissue of the macula. Patients suffering from DME typically experience blurred vision, floaters and dark areas in the visual field, and/or poor night vision. Untreated, DME causes moderate vision loss in 25-30% of patients, and severe vision loss and blindness in many of these individuals (ETDRS, 1985; Morello, 2007; Wong, 2009; Romero-Aroca, 2010).
Diabetic retinopathy impacts approximately 2 million adults age .65 years in the U.S. (The Eye Diseases Prevalence Research Group, 2004). Of these, approximately 15% are estimated to have DME (Lee, 2008; Wong, 2006), and one-half of DME patients may have "clinically significant" disease. Clinically significant macular edema is characterized by retinal thickening or hard exudates close to the macula center, the area most critical for preserving vision, or particularly large zones of retinal thickening within range of the macula center (ETDRS, 1985). DME may also be characterized as "focal", in which disease is caused primarily by microaneurysms and other foci of vascular abnormalities, or "diffuse", in which widespread dilated retinal capillaries are the primary manifestation (Ali, 1997).
Several studies have found that levels of independence and ability to perform activities of daily living such as shopping, meal preparation, and using the telephone decreases as visual acuity worsens (Hazel, 2000; Haymes, 2002; Bibby, 2007). Worsening DME may also affect diabetes selfcare,
as patients report difficulties with reading nutrition and medication labels, testing blood sugar, and checking feet for wounds or sores (James, 2012). In these studies and others (Brown, 2002), overall quality of life measures have been highly correlated with visual acuity irrespective of disease etiology. For example, studies that employ the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), a vision-specific measure of quality of life and functional ability, have found that improvements in visual acuity correspond to significantly improved perceptions of quality of life (Suner, 2009; Cahill, 2005; Miskala, 2003; Miskala, 2004).
Beyond decrements in daily functioning and quality of life, clinically significant macular edema has been associated with poorer survival in patients with adult-onset diabetes (Hirai, 2008). Over a 20-year period, the risk of death from all causes among patients with clinically significant macular edema was estimated to be 40%, a rate twice that of patients without the condition (Hirai, 2008).
The economic impact of DME and its treatment is also substantial. Findings from a recent study indicate that patients with DME consume more resources overall than patients with diabetes who do not have DME, resulting in significantly higher direct medical costs to Medicare (Shea, 2008). A diagnosis of DME resulted in expenditures of $11,290 and $33,620 at 1 and 3 years, respectively, a 30% increase over patients without DME when controlling for other factors. Importantly, these data were collected prior to the introduction of expensive biologic agents to treat DME and other ocular disorders (see Section 2). The impact on overall utilization and costs of the introduction of these new agents is unknown.