Overview

Series editors: Susan Lightman and Peter McCluskey

Lead clinician, Building 31, Room 6A52, 31 Center Drive, MSC 2510, Bethesda, MD 20892-2510, USA; echew@nei.nih.gov

Keywords: diabetic retinopathy; macular oedema; vision loss; vitrectomy

This patient has both medical and ocular conditions that need to be addressed. It is important to emphasise the need to improve his glycaemic control. This information should be communicated to his primary care physician to initiate tighter control of his glycaemia. In the UK Prospective Diabetes Study (UKPDS), the largest and longest randomised study of intensive v conventional glucose control in patients with type 2 diabetes, there was a 25% reduction in the risk of the "any diabetes related microvascular end point," including the need for retinal photocoagulation in the intensive treatment group compared with the conventional treatment group.1 After 6 years of follow up, a smaller proportion of patients in the intensive treatment group than in the conventional group had a two step progression (worsening) in diabetic retinopathy (p<0.01). Epidemiological analysis of the UKPDS data showed a continuous relation between the risk of microvascular complications and glycaemia, such that for every percentage point decrease in HbA1c (for example, 9% to 8%), there was a 35% reduction in the risk of microvascular complications.

Although the data from the Diabetes Control and Complications Trial (DCCT) are from patients with type 1 diabetes, the results showed the importance as well as the persistent effects of glucose control in preventing the progression of the severity of diabetic retinopathy and the development of macular oedema.2 Following the completion of the controlled clinical trial of glycaemic control, the DCCT study was then extended as a follow up study, the Epidemiologic Study of Diabetes Intervention and Complications (EDIC).3,4 Patients enrolled into both arms of the study were informed of the beneficial results of tight glycaemic control and the patients in the conventional treatment group were offered intensive therapy. The care of all the patients was then transferred to their own physicians. At 4 years and again at 6 years of follow up, the difference of the HbA1c values narrowed. The proportion of patients who had worsening of retinopathy, including proliferative diabetic retinopathy, macular oedema, and the need for laser therapy, was still statistically significantly reduced in the intensive treatment group compared with the conventional treatment group. It appears that a period of good glycaemic control results in the decrease in the progression of both diabetic retinopathy and nephropathy, despite increasing hyperglycaemia.

The blood pressure in this patient, fortunately, is good. It is important to note that a controlled clinical trial of blood pressure lowering in the UKPDS patients with hypertension also showed a clinically important effect on the progression of retinopathy and the development of moderate vision loss.5

Although clinical trials are crucial in assessing the effects of treatments, secondary analyses of risk factors such as elevated serum cholesterol levels provide important information. In the ETDRS, the observational data showed that the risk of developing retinal hard exudate and the severity of retinal hard exudate were associated with elevated serum cholesterol levels.6 The risk of moderate vision loss at 5 years (decrease of three or more lines of vision compared to the baseline vision on the logarithmic visual acuity chart) was also doubled with elevated serum cholesterol levels. Although these are observational data, the results are compelling for recommending the reduction of elevated serum cholesterol levels in such patients. Furthermore, a similar association of increasing retinal hard exudate with elevated serum cholesterol levels was found in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population based study.7 This patient should be treated medically to reduce these elevated levels of cholesterol. Patients with diabetes have a threefold to fourfold increased risk of cardiovascular disease and one of the major associated risk factor is elevated level of serum cholesterol. This indication alone may be sufficient to recommend the treatment of elevated serum cholesterol levels but the risk of potential losing vision may motivate such patients to be compliant with their medical treatment.

In addition to the intensive medical treatment, it would be reasonable to recommend that this patient be considered for focal laser photocoagulation for diabetic macular oedema, which may be present, to be followed by scatter (panretinal) photocoagulation. This patient with type 2 diabetes has the ocular features of very severe non-proliferative diabetic retinopathy, as defined by the so called "4-2-1 rule" which is dependent on the following ocular features found in the four peripheral quadrants, as indicated by Dowler. In 1 year, 50% of these patients will develop any proliferative disease and 17% will develop high risk proliferative retinopathy.8 The main ETDRS data showed that early laser photocoagulation results in a statistically significant benefit of early photocoagulation in preventing severe vision loss. Other secondary analyses in the ETDRS also suggest that there is an interaction of diabetes type with scatter photocoagulation. It appears that the risk of severe vision loss can be reduced by 50% if early scatter photocoagulation is administered in patients with type 2 diabetes and severe non-proliferative diabetic retinopathy or worse (figs 1 and 2).9 Such a treatment effect was not found in patients with type 1 diabetes. This interaction was also seen in the Diabetic Retinopathy Study, adding further evidence that this is not a chance finding. Often patients with type 2 diabetes and this level of severity of diabetic retinopathy may present with vitreous haemorrhage, thus making it difficult to administer scatter photocoagulation in a timely fashion. Based on the ETDRS data and personal experience, I would recommend that focal laser photocoagulation be followed by the administration of the scatter photocoagulation.

 Figure 1 The rates of severe vision loss or vitrectomy in types 1 and 2 diabetes were not statistically different in patients with mild to moderate non-proliferative diabetic retinopathy (NPDR).

Figure 2 The rates of severe vision loss or vitrectomy were reduced in patients with type 2 diabetes and severe non-proliferative diabetic retinopathy (SNPDR) or worse by as much as 50% at 5 years (p<0.01). There were no statistically significant differences among the patients with type 1 diabetes.

In summary, patients with severe non-proliferative diabetic retinopathy (SNPDR) should have their macular oedema treatment performed as soon as possible. A scatter (panretinal) photocoagulation will be considered in patients with type 2 diabetes and severe NPDR because of the likelihood of reducing severe vision loss is greater with early laser photocoagulation. Although vigilant follow up is a potential option there is a high risk that the patient may present at the next visit with a preretinal or vitreous haemorrhage, which may make the treatment difficult.
Laser photocoagulation should also be considered in those patients with pending cataract extraction, pregnancy, and renal disease. These are all guidelines which obviously have to be evaluated in the context of each patient with his or her set of risk factors. The medical management is also an important part of the treatment. We need to communicate with our medical colleagues on this need. Together, we can hope to bring effective therapy to our patients with diabetic retinopathy.

REFERENCES

UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–53.

The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86.

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000;342:381–9.

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563–9.

UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703–13.

Chew EY, Klein ML, Ferris FL III, et al. for the ETDRS Research Group. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Arch Ophthalmol 1996;114:1079.

Klein BEK, Moss SE, Klein R, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: X. Relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology 1991;98:1261.

Early Treatment Diabetic Retinopathy Study (ETDRS) Research Group. Early photocoagulation for diabetic retinopathy: ETDRS report number 9. Ophthalmology 1991;98(Suppl):767.

Ferris FL III. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc 1996;94:505–37.