Friedenwald Lecture recognizes epidemiological research in eye diseases

May 4

- Fort Lauderdale, FL - Ronald Klein, MD, MPH, and his wife Barbara E. K. Klein, MD, MPH, received the Friedenwald Award at the Association for Research in Vision and Ophthalmology annual meeting for their contributions in the area of ophthalmic epidemiological research in studies of diabetes, glaucoma, age-related eye diseases and eye diseases in systemic disorders.

In their lecture, "The Epidemiology of Eye Disease: Glycemia to Genetics," Dr. Ronald Klein described their landmark investigation, the Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR), which provided significantly to the understanding of diabetes in general and of diabetic eye disease.

"In 1979 when we began our research, diabetic retinopathy was considered the leading cause of legal blindness in persons 25 to 74 years of age," noted Dr. Ronald Klein.

The aims of the study undertaken in 1979 were to:

• Describe the prevalence and severity of retinopathy and vision loss in persons with diabetes;

• Describe the relationship of retinopathy and clinical complications;

• Understand the risk factors associated with retinopathy;

• Derive information about healthcare delivery.

In Wisconsin, 452 physicians participated in the study with 10,135 diabetic patients identified, and 2,990 patients were selected for examination. Of these examinations, 1,210 individuals were in the young onset group (less than 30 years old at diagnosis and insulin dependent) and 1,780 were in the older onset group (30 years or older at diagnosis). From 1980 to 1982, 996 in the younger onset group and 1,370 in the older onset group were examined.

In the baseline characteristics, the researchers observed poor glycemic control and a high frequency of complications, such as hypertension, diabetic retinopathy, diabetic neuropathy, and cardiovascular disease in both cohorts.

"Based on the study data, we estimated 400,000 of 5.8 million persons with known diabetes have either severe proliferative retinopathy or clinically significant macular edema," he said. "We also demonstrated that in this population the prevalence of any retinopathy by duration of diabetes."

Other findings showed only 67% of persons with diabetic retinopathy and high-risk factors for severe vision loss or clinically significant macular edema had been seen by an ophthalmologist within 2 years of the study exam. Reasons why individuals had not undergone an ophthalmic examination included lack of insurance with eye care coverage. Those in the younger eye set who had not sought an exam cited different reasons, such the thought that they had no problems with their eyes (80%), they were too busy (30%), or they were told no exams were needed.

"This demonstrated the need for education in physicians and diabetic patients," Dr. Ronald Klein said. "The National Eye Institute responded with the development of the National Eye Health Education Program."

Another important finding from WESDR is that the type of diabetes does not determine whether a patient develops proliferative diabetic retinopathy, but the level of glycemic control.

Drs. Ronald and Barbara Klein are continuing to follow the young cohort and report on the 25-year follow-up.

Dr. Barbara Klein explained how they looked at the epidemiology of diabetic retinopathy, vascular diseases in age-related eye problems, retinal vascular changes as a reflection of systemic disease, and systemic and environmental correlates of ocular traits that are associated with disease.

She described the findings of one of the population-based studies, the Beaver Dam Eye Study. In this study, 4,926 patients, ranging in age from 46 to 86 years, were identified from the Beaver Dam population. The prevalence of disease in this study was as follows:

• 17% had nuclear cataract;

• 16% had cortical cataract;

• 6% had posterior subcapsular cataract;

• 16% had early lesions related to AMD or maculopathy;

• 2% had late lesions related to AMD or maculopathy;

• 2% had glaucoma;

• 5% had visual impairment (greater than 20/40 in the better eye).

"Common risk factors for cataracts, macular degeneration, and impaired vision were age, gender, smoking, and family history," Dr. Barbara Klein said.

Additional risk factors for some of the conditions were also described. In patients with cataract, diabetes and UVB exposure also played a role in the disease. In individuals with AMD, hypertension or elevated blood pressure also was involved.

An exciting new direction in this study was the identification of siblings and parents of patients in the Beaver Dam Eye Study who also presented with disease. "There were sibling correlations in cataract and macular degeneration or maculopathy, which were all statistically significant," she added.

Then Dr. Barbara Klein explained that they applied to the National Institutes of Health to conduct genotyping for siblings with more severe levels of age-related maculopathy or AMD and cortical opacities.

"From that first genotype scan, we found there were several areas of linkage for cortical cataract," she said. And they were able to identify "a novel region on the six chromosome and it was a relatively large link," she said. They also identified linkage for macular degeneration.

"Further genetic studies are ongoing," she noted.