The appearance of retinopathy and progression to proliferative retinopathy: the WHO multinational study of vascular disease in diabetes

Abstract

Aims/hypothesis. We aimed to estimate incidences of any retinopathy and proliferative diabetic retinopathy (PDR) by direct ophthalmoscopy and relate them to baseline risk factors in re-examined diabetic survivors from 10 centres of the WHO Multinational Study of Vascular Disease in Diabetes. Methods. After a mean follow-up of 8.4 years (11.7 years in Oklahoma), 2877 (71.6 %) survivors were resubmitted to standardised direct ophthalmoscopy as at baseline. The presence of any retinopathy and PDR were recorded at each centre and their incidence estimated in those without retinopathy and PDR at baseline. The independent associations of these incidences with baseline risk factors are expressed as odds ratios derived from multiple logistic regression analyses, within individual centres (which included fasting plasma glucose in 8 and triglyceride in 5) and in pooled data. Results. Of the 4662 original patients, 465 (10.4 %) of those without and 77 (43.0 %) of those with baseline PDR had died (p < 0.001). Any retinopathy was newly reported at follow-up in 47.7 % and PDR in 9.7 % of those free of them at baseline, with reported incidences varying substantially among centres. Incident retinopathy appeared earlier in the known course of diabetes but incidence rates rose more slowly with duration in patients with Type II (non-insulin-dependent) diabetes mellitus than in those with Type I (insulin-dependent) diabetes mellitus. In pooled data and in some individual centres, any retinopathy incidence gave significantly positive odds ratios with age, diabetes duration, systolic pressure, plasma cholesterol, BMI, insulin treatment and proteinuria, and with fasting plasma glucose in the centres where it was measured. Positive odds ratios for PDR were similarly obtained for age, duration, insulin treatment, cholesterol, proteinuria and fasting glycaemia. Smoking status odds ratios were negative for both outcomes. Conclusion/interpretation. Incidence of ophthalmoscopically ascertained any retinopathy varied about twofold and of PDR about threefold among centres. Although, in part attributable to differences between observers, variation in incidence in all centres and in some cases within centres was associated with a number of baseline risk factors. Such associations are not likely due to observer variation or selection biases and emerged despite the imprecision of clinical ophthalmoscopy. Improved detection and control of these risk factors should reduce the impact of diabetic retinopathy and its consequences. [Diabetologia (2001)

Longitudinal study examining the risk factors for proliferative retinopathy and maculopathy in type-I diabetes: The Royal College of Physicians of Edinburgh Diabetes Register Group

“…In the DCCT, HbA1c was also an important risk factor for the development and progression towards proliferative disease and maculopathy, with intensive control of blood glucose lowering the incidence of both. 3 Our study helps confirm the association of raised blood pressure as a risk factor for retinopathy in type-I diabetes which has been demonstrated elsewhere, 8,18 but an interventional study to demonstrate the benefits of blood pressure lowering is required.…”

“…However, in univariate analysis, high cholesterol concentrations were associated with maculopathy, but not with proliferative eye disease. Some longitudinal studies have established an association between serum cholesterol and triglycerides with the development of any retinopathy, 7,8,10 and some have associated serum cholesterol concentrations with visual loss 9,18 in a small number of individuals with diabetes. Cholesterol concentrations are also associated with the development of hard exudates.…”

“…2,3 Hypertension is also a risk factor in observational studies, 4,5 although there is no evidence that aggressive blood pressurelowering therapy reduces the incidence of retinopathy in type-I diabetes. Observational data have also identified the duration of diabetes, 6 raised cholesterol, [7][8][9] raised triglycerides, 9,10 and proteinuria 11 as risk factors. Smoking has previously been of borderline significance in type-I diabetes, 12,13 but may be of significance for patients who have had diabetes for less than 5 years.…”

The incidence of visual impairment and its determinants in the WHO multinational study of vascular disease in diabetes

“…Patients with baseline nonproliferative retinopathy were 3 times more likely to develop SVI and those with proliferative retinopathy 16 times, than those free of retinopathy at baseline. Systolic blood pressure, associated with baseline retinopathy [28,34] and retinopathy progression [6], was also a powerful independent predictor of SVI. The relation between arterial pressure, retinopathy and the potential for visual impairment has been noted in many other studies [22,31,35,36].…”

A hemochromatosis-causing mutation C282Y is a risk factor for proliferative diabetic retinopathy in Caucasians with type 2 diabetes

“…Although several risk factors for progression of diabetic retinopathy to PDR have been identified (Porta et al 2001, Keen et al 2001, the underlying pathogenesis is still not known. PDR is characterized by active angiogenesis and the formation of fibrovascular tissue at the vitreoretinal interface.…”