Ординатура / Офтальмология / Английские материалы / Diabetes and Ocular Disease Past, Present, and Future Therapies 2nd edition_Scott, Flynn, Smiddy_2009

174 Diabetes and Ocular Disease

Blood Pressure Lowering. A randomized clinical trial of lisinopril, an inhibitor of angiotensin-converting enzyme (ACE) suggested that ACE inhibitor or blood pressure lowering, even in normotensive persons, may slow the progression of diabetic retinopathy [65].

United Kingdom Prospective Diabetes Study 1981–1998. Date from another randomized clinical trial, the United Kingdom Prospective Diabetes Study (UKPDS), suggest that it may be the blood pressure lowering that is responsible for slowing the progression of retinopathy and not a specific retina-vascular response to ACE inhibitor [66,67]. The UKPDS showed that both captopril, an ACE inhibitor, and atenolol, a beta blocker, were effective in slowing the progression of retinopathy compared with the control group and that there was no statistically significant difference between the two treatment groups.

Patients allocated to tight BP control showed benefit in many different aspects of diabetic retinopathy. They were less likely to undergo photocoagulation (RR, 0.65; P = .03) and less likely to have their retinopathy progress. Macular edema was less likely in the tight BP group and these patients were less likely to need photocoagulation for macular edema (RR, 0.58; P = .02). Blindness (defined as 20/200 or worse) was also reduced by tight blood pressure when compared with the conventional blood pressure control (P = .046; RR, 0.76; 99% confidence interval, 0.29–1.99) [68].

ACCORD Study. An NIH sponsored trial will evaluate these three important medical factors. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) is a randomized clinical trial with three components, determining the cardiovascular disease (CVD) effects of blood glucose lowering, blood pressure lowering, and lowering of serum triglycerides plus raising serum high density lipoprotein cholesterol levels in patients with type 2 diabetes. 10,251 participants were randomly assigned in equal numbers to two glycemic management treatment arms, while 4733 of the 10,251 were also randomly assigned to the blood pressure management trial and the remainder, 5518, were randomly assigned to strategies of treatment dyslipidemia. Follow-up of at least 5 years is expected to be completed by May of 2009. An ACCORD Eye Substudy [69] was conducted on 3537 participants who had comprehensive eye exams with stereoscopic fundus photography of seven standard fields at baseline and at the 4 year follow-up visit. Study results will be available in fall of 2009 (http://www.accordtrial.org).

Aldose-Reductase Inhibitor. A medical approach for preventing the development of retinopathy that has been hypothesized for decades involves blocking the effects of aldose reductase [70]. This enzyme facilitates the conversion of glucose to sorbitol, which accumulates in cells during hyperglycemia and may result in cell death [71,72]. Animal experiments suggest that an aldose-reductase inhibitor could slow the development of diabetic retinopathy [73,74]. Clinical trials in patients with diabetes have not yet demonstrated any slowing of the progression of retinopathy.

Sorbinil Retinopathy Trial, 1983–1985. The Sorbinil Retinopathy Trial (SRT) enrolled 497 patients with type 1 diabetes and little or no retinopathy. After 3 to 4 years of follow-up, administration of the drug sorbinil showed no apparent effect on progression of diabetic retinopathy or neuropathy (Table 9.9 and Fig. 9.9) [75,76]. However, interest continues in developing more potent inhibitors, which may slow the progression of diabetic retinopathy or neuropathy.

Other Medical Investigations. Other medical approaches to reduce the secondary complications of diabetes are currently under evaluation. Drugs with antiangiogenic activity, such as inhibitors of vascular endothelial growth factor (VEGF), protein kinase C inhibitors, and growth hormone antagonists are in early clinical trials, as are inhibitors of advanced glycosylated end products [77–80]. Prevention will inevitably be more effective than treatment, and methods to prevent the development of diabetes and improved techniques for blood glucose control are also being tested.

Table 9.9. Sorbinil Retinopathy Study

Study Question

Does aldose-reductase inhibitor sorbinil reduce rate of progression of diabetic retinopathy?

Eligibility

Type 1 diabetes of 1–15 years’ duration and no more than 5 microaneurysms in either eye

Randomization

497 patients randomly assigned to sorbinil (250 mg/d) or placebo

Outcomes Variable

Progression of retinopathy

Result

No significant reduction in progression of retinopathy in treated eyes compared with placebo

Figure 9.9. Sorbinil Retinopathy Trial results: Cumulative incidence of sustained worsening of retinopathy (two steps on modified Airlie House scale for at least 6 months) in patients with type 1 diabetes with mild or no retinopathy at baseline receiving placebo or 250 mg/d sorbinil.

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The DRCR Network was established in 2003 for the purpose of conducting multicenter clinical research of diabetic retinopathy and associated disorders. The DRCR Network involves community-based practices as well as academic medical centers. This National Eye Institute sponsored cooperative agreement has conducted multiple studies (see Appendix) including laser photocoagulation, pharmacotherapy, and vitrectomy. The DRCR Network has industry collaboration as well as foundation support from the Juvenile Diabetes Research Foundation and the International Diabetes Foundation. DRCR Network clinical studies incorporate optical coherence tomography as well as both monotherapies and combined therapies for both diabetic macular edema and proliferative diabetic retinopathy.

CONCLUSION

The history of treatments for diabetic retinopathy is one of the best examples of the use of evidence-based patient care. From developing methods of preventing retinopathy to treatment with photocoagulation or vitrectomy, there are clinical trial results that reveal which treatments are more effective, who is most at risk, and who will benefit most from intervention.

Diabetic retinopathy is probably still the leading cause of visual loss in the United States among working-age Americans. This is surprising because, when retinopathy is properly treated, the 5-year risk of blindness for patients with PDR is reduced by 90% and the risk of visual loss from macular edema is reduced by 50%. Unfortunately, only 50% of patients with diabetes receive regular dilated eye examinations and many patients go blind without treatment [81–83], despite the fact that the value of screening eye examinations has been well documented [84].

Many professional groups, including the American Diabetes Association, the American College of Physicians, the American Academy of Ophthalmology, and the American Optometric Association, have provided guidelines for their members as to when eye examinations should be performed (Table 9.10). Emphasis on identifying patients at risk and new screening methods will, hopefully, reduce the number of patients who do not have regular eye examinations, appropriate medical care and careful follow-up.

Table 9.10. Recommended Eye Examination Schedule

Improved patient education programs, such as the National Eye Health Education Program, can motivate patients to take better care of themselves [85–87]. Access to the educational materials and facilities that will enable patients to improve the control of their diabetes will lead to fewer secondary complications.

Prevention is cost effective [88–91]. The record of carefully developing new treatments for diabetic retinopathy is a good one. With continued careful research, the risk of blindness from diabetic retinopathy can be further reduced and the lifelong preservation of vision a reality.

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