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DIABETIC RETINOPATHY
Stanley Chang, M.D.
(Presented at The CAMS 2000 Semi- Annual Scientific Meeting)
The pathogenesis of diabetic retinopathy begins with prolonged hyperglycemia, which results in expression of factors which activates the ß2 isoform of protein kinase C and stimulate vascular endothelial proliferation and increased capillary permeability. Other mechanisms may also be involved such as increased glucose metabolism via the polyol pathway (aldose reductase), or the accumulation of advanced glycation endproducts. The early changes of diabetic retinopathy are intrinsic changes within the retinal capillary bed such as microaneurysms, dot hemorrhages, flame hemorrhages and hard and soft exudates (non proliferative or background retinopathy). More advanced stages (proliferative diabetic retinopathy) lead to the proliferation of new blood vessels (neovascularization), and fibrous proliferation on the retina which result in vitreous hemorrhage and traction retinal detachment.
The incidence of diabetic retinopathy (DR) increases with the duration of diabetes. Of insulin-dependent
diabetics with more than 30 years of the disease, 12% are blind. Other factors which affect the progression of
diabetic retinopathy are the age of onset of diabetes, the level of glycemic control,
C-peptide level, blood pressure, proteinuria, and pregnancy. In younger-onset patients taking insulin, the
incidence and progression of retinopathy increases with age. Patients developing diabetes postmenarche were
found to have a 3.2 times greater risk of having DR as those who were premenarchal. Insulin-dependent patients with undetectable or
low plasma levels of C-peptide were found to have the highest frequencies and most severe
retinopathy. It is recommended all
patients between ages 10-30 with diabetes duration of 5 or more years be examined
annually. Patients who have had diabetes
diagnosed at 30 or more years of age should be examined at the time of diagnosis or
shortly thereafter.
Many studies now confirm the importance of glucose control on the development and progression of DR. The most prominent study was the Diabetes Control and Complications Trial (DCCT)1. This study enrolled 726 type 1 diabetics with no DR (primary intervention cohort) and 715 with mild-to-moderate DR (secondary-intervention cohort), randomly assigning them to intensive glucose management or to conventional therapy. The intensive therapy group achieved a median Hgb A1C of 7.1% vs. 9.1% in the conventional group. Mean blood glucose was 155 mg/dL in the intensive therapy group and 230 mg/dL in the conventional therapy group. A 3-step change in the degree of retinopathy was measured using a standard fundus grading system. Cumulative 8.5 year rates for the progression of retinopathy were 54.1% for the conventional therapy group compared to 11.5% in the intensive therapy group in the primary intervention cohort, and 49.2% with conventional treatment and 17.1 with intensive therapy in the secondary intervention cohort. In some patients there was an unanticipated and paradoxical worsening of retinopathy during the induction of intensive therapy. These changes had no effect on the long term outcome of DR and vision.
The results of several other multicenter controlled clinical trials concerning diabetic retinopathy are notable. The Diabetic Retinopathy Study2 (DRS) defined the high risk characteristics for visual loss and indications for panretinal photocoagulation. In eyes with neovascularization of the optic disk, or retinal neovascularization associated with vitreous or preretinal hemorrhage, argon laser reduced the rate of sever visual loss by 50%. The Early Treatment Diabetic Retinopathy Study3 (ETDRS) found that aspirin use did not affect the progression of mild-to-moderate diabetic retinopathy. Another part of the study standardized the indications for focal laser photocoagulation of diabetic macular edema. For clinically significant macular edema (CSME) focal photocoagulation decreased the risk of moderate visual loss (doubling of the visual angle). Focal photocoagulation increased the chance of moderate visual gain (halving of the visual angle) and reduced retinal thickening.
New advances in the care of patients with DR are directed toward early detection and prevention. It is estimated that 30-50% of diabetics do not receive the appropriate eye care. Thus screening programs using telemedicine technology are being developed. Clinical trials with the systemic administration of protein-kinase C inhibitors, ACE-inhibitors and somatostatin analogs are being evaluated for their effects on DR. New therapies directed toward the inhibition of ocular neovascularization are also being developed.
(Dr. Chang is the Edward S. Harkness Professor and Chairman of Ophthalmology, Columbia University)
3. Early Treatment Diabetic Retinopathy Study Research Group: Photocoagulation for diabetic macular edema: ETDRS Report Number 1. Arch Ophthalmol 1985; 103:1796-1806
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