What Does the Literature Indicate About Rates of Diabetic Retinopathy Progression?

The impact of treatments on outcomes of severe visual loss and development of proliferative diabetic retinopathy.

STEPHEN G. SCHWARTZ, MD, MBA ∙ HARRY W. FLYNN, Jr., MD ∙ BARBARA WIROSTKO, MD

Despite continuing advances in the care of diabetes mellitus and its ophthalmologic manifestations, diabetic retinopathy remains a major worldwide cause of preventable visual loss.¹ Among US patients with diabetes age 40 and older, the prevalence of DR is 40.3% and the prevalence of vision-threatening retinopathy is 8.2%.² In a US series of patients with type 1 diabetes, the reported 25-year cumulative incidence of visual impairment (20/40 or worse) was 13% and the incidence of severe visual impairment (20/200 or worse) was 3%.³ Similarly, in a Danish series of patients with type 1 diabetes, the reported 25-year cumulative incidence of blindness (defined as 20/200 or worse or visual field constriction worse than 10°) is 7.5%.⁴

WHAT HAS CHANGED OVER THE DECADES?

Intensive metabolic control has been shown to be effective in reducing disease burden in patients with both type 1⁵ and type 2⁶ diabetes mellitus. Tighter control of blood glucose, blood pressure, and serum cholesterol has translated to better outcomes. Although the prevalence of diabetes may have increased significantly in the last 30 years, a relative decline in rates of DR and other microvascular complications has been suggested by some studies over the last decade.^7-10

There is increased awareness among primary care providers that earlier ophthalmic examinations, better follow-up, and improved patient education all have an impact on disease progression. The greater medical community is also aware that photocoagulation is effective in the treatment of both diabetic macular edema¹¹ and proliferative diabetic retinopathy¹² (Figure 1). Pars plana vitrectomy is effective at treating vitreous hemorrhage¹³ and traction retinal detachment¹⁴ in many patients (Figure 2). Multiple pharmacologic therapies are being investigated as treatments for DR.¹⁵

Figure 1. Fresh panretinal photocoagulation.

Figure 2. Pars plana vitrectomy with small-gauge instrumentation and wide-field viewing.

HOW HAVE THESE ADVANCES IN MEDICAL AND OPHTHALMIC CARE AFFECTED OUR DIABETIC PATIENTS?

There is evidence to suggest that the clinical course and rate of progression for systemic diabetic complications have improved over the past 25 years, due to more intense and tighter systemic management, even though the incidence of diabetes mellitus continues to increase. It is unclear whether advances in systemic management over the last 30 years have had a similar effect on the rate of progression of DR.

HAVE THE MAJOR CLINICAL STUDIES HAD AN IMPACT ON THE INCIDENCE OF THIS DISEASE?

Contemporary estimates for DR progression are clearly needed. Because diabetes is becoming a global epidemic, DR will remain a vision-threatening disease that will only increase in prevalence, increasing the burden of disease and affecting health care expenditures.

A systematic review and meta-analysis was recently conducted to investigate the clinical course and to examine trends in the incidence of specific DR endpoints over the last 35 years (from 1975 to 2008) that could provide contemporary data to guide future research and assist in clinical trial design and public health planning.¹⁶ The two primary outcome measures were progression to PDR and progression to severe visual loss (SVL), defined as LogMAR visual acuity worse than 1.0 (the equivalent of Snellen visual acuity worse than 5/200 in some studies).¹⁷ The relevant peer-reviewed literature was reviewed, and studies were divided into the time periods 1975-1985 and 1986-2008, based on the fact that the Early Treatment Diabetic Retinopathy Study (ETDRS) report number 1 was published in 1985.

Twenty-eight primary studies met inclusion criteria for this review: 14 pre-ETDRS and 14 post-ETDRS. These 28 studies included 27,120 patients assessed at up to 10 years postenrollment. The incidence of PDR increased from four years (8.7%) to 10 years (17.6%), but the incidence of SVL decreased from four years (10.0%) to 10 years (2.5%).

How do we explain these inverse trends, with lower rates of SVL at 10 years? We know that the prevalence of PDR goes up with time, but the trend toward decreasing rates of SVL with time despite PDR may be explained in part by better treatment options (such as panretinal photocoagulation, focal laser, and pars plana vitrectomy), earlier laser intervention, and tighter metabolic control.

In Table 1 , the data are stratified by time period to attempt to determine if changes in systemic management (based on major clinical trials) have affected outcomes. For example, the use of photocoagulation was shown to be effective in 1985 in the ETDRS,¹⁷ and systemic control of both hyperglycemia and hypertension was shown to be important in the 1990s.^18,19

The rates of PDR and SVL appear to decline, at both the four-year and 10-year intervals, following publication of the ETDRS. In Table 2 , the data are stratified by presence or absence of any DR at the baseline examination. In patients with both pre-existing and no pre-existing DR, the four-year rates of PDR and SVL generally declined in the more recent time period. Hence, larger percentages of patients developed either PDR or SVL in the 1975-1985 time period than in the 1986-2008 period, regardless of the presence of baseline DR.

These results suggest that the progression of DR may be slowing, perhaps due to earlier detection and advances in treatment, as well as more aggressive medical management of hyperglycemia, hypertension, and other associated systemic factors.

The principal strength of this review is the use of systematic methods to minimize bias and error in the selection of studies, data extraction and analysis. Implications for future research include consideration of contemporary rates of progression to proliferative diabetic retinopathy and/or severe visual loss (rather than those observed pre-1985) in estimating sample sizes for clinical trials, as well as reporting common nomenclature for diabetic retinopathy and visual acuity outcomes, so that rates of DR progression can be estimated consistently.

As we continue to manage our patients clinically, understanding the impact on progression and outcomes is important not only from a research perspective, but also in terms of health economics and comparative effectiveness with other interventions.

CONCLUSION

In conclusion, understanding the natural history and the progression of diabetic retinopathy will help determine if various clinical interventions are having an impact on disease progression that is meaningful to our patients, is cost-effective, and provides the best outcomes. This literature review reminds us that DR is a manifestation of a systemic disease and that attention to the systematic management of associated comorbidities, in close partnership with our internal medical colleagues, can allow for the best outcomes for our patients. RP

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