Prevalence of Age--related Maculopathy The Beaver Dam Eye Study Ronald Klein, MD, MPH, Barbara E. K. Klein, MD, MPH, Kathryn L. P. Linton, MS Purpose: The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study. Methods: The presence and severity of various characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. Results: One or more drusen were present in the macular area of at least 1 eye in 95.5% of the population. People 75 years of age or older had significantly higher frequencies (P < 0.01) of the following characteristics than people 43 to 54 years of age: larger sized drusen (;;::: 125 ttm. 24.0% versus 1.9%), soft indistinct drusen (23.0% versus 2.1%), retinal pigment abnormalities (26.6% versus 7.3%), exudative macular degeneration (5.2% versus 0.1 %), and geographic atrophy (2.0% versus 0%). Conclusion: These data indicate signs of age-related maculopathy are common in people 75 years of age or older and may pose a substantial public health pr~blem. Ophthalmology 1992;99: 933-943
There are few population-based data describing the prevalence and severity of age-related maculopathy in older people in the United States. 1- 5 Accurate prevalence rates of this disease are important for estimating needs for services and associated costs in terms of dollars and quality oflife. Such data also are of importance in planning future studies such as controlled clinical trials of prevention and treatment of age-related maculopathy. 6 The purpose of this report is to describe the prevalence of lesions asso-
Originally received: November 18, 1991. Revision accepted: January 27, 1992. From the Department of Ophthalmology, University of Wisconsin, Madison. Presented in part at the National Eye Institute Symposium on Eye Disease Epidemiology, Bethesda, March 1991. Supported by National Eye Institute/NIH grant EY06594 (R. Klein and B. E. K. Klein), Bethesda, Maryland. Reprint request to Ronald Klein, MD, MPH, Department of Ophthalmology, University of Wisconsin-Madison, 600 Highland Ave, ES/353 CSC, Madison, WI 53792.
ciated with age-related maculopathy in the large population-based Beaver Dam Eye Study.
Methods The Population Methods used to identify the population and descriptions of it appear in previous reports. 7•8 Briefly, a private census of the population of Beaver Dam, Wisconsin was performed from September 15, 1987 to May 4, 1988. Eligibility requirements for entry into the study included living in the city or township of Beaver Dam and being 43 to 84 years of age at the time of the census. In 3715 of the 6612 households identified by the census, there was at least 1 person who satisfied the age criteria. In these households, there were a total of 5833 individuals between the ages of 43 and 84 years at the time of the census. After completion of the census, 76 additional households with a total of 92 eligible people were identified, and these people were included in the population.
933
Ophthalmology
Volume 99, Number 6, June 1992
For reasons of efficiency in recruitment and examination, those who were eligible were divided into 10 groups by a random selection process. The population was examined over a 30-month period beginning March 1, 1988. Ofthe 5925 eligible people, 4926 (83.1%) participated in the study. Two hundred twenty-five people (3.8%) died before the examination, 91 people (1.5%) moved out of the area, and 23 people (0.4%) could not be located. Two hundred sixty-nine people (4.5%) permitted an interview only, and 391 (6.6%) refused to participate. Comparisons between participants and nonparticipants have been presented elsewhere. 8 Nonparticipants were significantly older (63.5 versus 60.6 years of age) (P < 0.05) and had a higher self-reported frequency of poorer near vision (4.0 versus 2.4%) than did participants. The frequencies of self-reported histories of poor distance vision, presence of age-related macular degeneration, diabetes, or hypertension did not differ. Figure 1. Clear plastic grid used to define subfields in macula.
Procedures Letters from their primary care physicians, or from the principal investigators if no primary care physician was identified in the census, were sent to those who were eligible. These letters described the study and invited eligible people to participate. This was followed by a call from the study coordinator, who provided further information about the study and made an appointment for the examination. People who were not interested in participating in the examination were asked to respond by telephone to the same questionnaire that was administered at the time of the examination. During the examination, informed consent was obtained from each participant. Stereoscopic 30° color fundus photographs centered on the disc (Diabetic Retinopathy Study [DRS] standard field 1), macula (DRS standard field 2), and a nonstereoscopic color fundus photograph temporal to but including the fovea of each eye were taken. 9 •10 The slide transparencies were mounted in clear plastic sheets. Before grading, a grid consisting of three circles concentric with the center of the macula and four radial lines was superimposed over one member of the stereoscopic pair of field 2 (Fig 1). 11 The radius of the innermost circle corresponded to 500 ~m in the fundus of an average eye, and the radii of the middle and outer circles corresponded to 1500 and 3000 J.Lm, respectively. Nine subfields were defined by the grid: the central subfield (within the inner circle); the inner superior, nasal, inferior, and temporal subfields (between the inner and middle circles); and the outer superior, nasal, inferior, and temporal subfields (between the middle and outer circles). Some lesions were graded in each subfield, others in DRS field 2 as a whole, and others in other fields. For the purpose of this report, measurements made only within the nine subfields defined by the grid are presented. Three sets of circles (designated as C0 , Ct. C2, It. h, and Ot. 02) printed on clear plastic were used to estimate size of drusen, area involved by drusen, and area involved by increased retinal pigmentation. 11
934
Two levels of grading were carried out on the fundus photographs. First, a preliminary grading was performed by one of two senior graders. 10 After examining all of the photographic fields for the entire eye, the grader recorded determinations for various lesions associated with agerelated maculopathy and other abnormalities involving the retina and optic nerve head. This review was used to prepare a report for the primary care physician and the participant. Second, detailed grading was performed by one of three other graders. While preliminary grading involved concurrent examination of both right and left eyes, detailed grading involved separate gradings of the eyes. This assessment consisted of a subfield-by-subfield, lesion-by-lesion evaluation of each photograph set for each eye using the Wisconsin Age-Related Maculopathy Grading System.11·12 The detailed gradings were subjected to a computerized edit for internal consistency. When inconsistencies were found, forms accompanied by photographs were returned to the grader for correction. Next, the presence and severity of specific lesions (predominant drusen size, drusen area, retinal pigment epithelial [RPE] degeneration, retinal pigment and/or neurosensory retinal detachment, subretinal hemorrhage, subretinal fibrosis, or geographic atrophy), as determined by detailed grading for each eye, were compared with the presence and severity as determined by preliminary grading. Edit rules were used to define significant disagreements. When the two determinations disagreed, the eye was regraded for the specific lesion by another grader. If that grader agreed with either of the first two determinations, that result was accepted. If a discrepancy remained, the fundus photograph was referred to the most senior grader for adjudication. Of the 4926 participants, 4843 (98.3%) had fundus photographs of both eyes, 42 (0.9%) had them of 1 eye only, and 41 people (0.8%) did not have fundus photographs taken (Fig 2). Eyes were not photographed because
Klein et al · Prevalence of Age-related Maculopathy 4, 926 people examined 1988-1990
4, 885 people with fundus photographs of at least one eye (4,843 both eyes, 42 one eye)
I
I 41 - no photographs of either eye
lll
I 0 ungradab1e eyes
I j
4, 775 people with gradable fundus photographs in at least one eye
(4, 514 both eyes, 261 at least one eye)
Figure 2. Schematic diagram shows participant selection and inclusion in study analyses.
of inability to dilate the pupil, significant lens or corneal opacities, enucleation, or refusal of the participant. Eyes were considered gradable if field 2 was present and 5 or more subfields could be graded for drusen, if fewer than 5 subfields could be graded but at least 1 drusen was 125 ~-tm or greater in size, or if other signs of agerelated maculopathy (RPE abnormalities, exudative macular degeneration or geographic atrophy) were present. The degree of exact agreement achieved between the
graders ranged from 66% to 73% for each ofthe drusen characteristics and 88% or more for the other maculopathy characteristics. The Kappa scores were generally in the moderate to substantial agreement categories. 11 Of the 4885 people with fundus photographs of at least 1 eye, photographs were judged to be gradable in at least 1 eye for 4775 (97.7%) (Fig 2). Four people with gradable photographs were excluded from the analyses, one because of pigmentary abnormalities in the macular areas of both eyes, believed to be unrelated to age-related maculopathy, one who had one eye with pigmentary abnormalities and the other which could not be graded, and two who had signs of maculopathy which were believed to be secondary to other conditions that affected the macular area. In addition, there were 58 people in whom one eye was excluded from the analyses because ofthe presence of non age-related maculopathy (n = 35) or because of pigmentary abnormalities unrelated to age-related maculopathy (n = 23). For purposes of this report, only the 4771 people (96.8%) with at least one eye with gradable fundus photographs without an excluded lesion are included in the analyses. Comparisons between people who had at least one eye included in the analyses and those who had neither eye included are found in Table 1. People with neither eye included were significantly older (P < 0.05), had a greater body mass index, lower diastolic blood pressure, a higher blood glucose level, poorer visual acuity, and were more likely to be female and to have never had smoked than those who had at least one eye included.
Table 1. Comparisons between Participants Included and Those Excluded in the Analyses of Age-related Maculopathy (Beaver Dam Eye Study, 1988-1990) Included (n = 4771)
Excluded* (n = 155)
p
Characteristic
No.
Mean
Standard Deviation
No.
Mean
Standard Deviation
Value
Age (yrs) Body mass index (kg/m2) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Blood glucose (mg/dl) Visual acuity (number of letters read correctly, left eye)
4771 4740 4769 4769 4758
61.7 4.0 132.0 77.5 106.3
11.0 0.75 20.5 11.0 38.9
155 138 154 154 150
73.2 3.8 134.3 72.2 119.2
11.0 0.9 1.8 11.2 50.6
There are few population-based data describing the prevalence and severity of age-related maculopathy in older people in the United States. 1- 5 Accurate prevalence rates of this disease are important for estimating needs for services and associated costs in terms of dollars and quality oflife. Such data also are of importance in planning future studies such as controlled clinical trials of prevention and treatment of age-related maculopathy. 6 The purpose of this report is to describe the prevalence of lesions asso-
Originally received: November 18, 1991. Revision accepted: January 27, 1992. From the Department of Ophthalmology, University of Wisconsin, Madison. Presented in part at the National Eye Institute Symposium on Eye Disease Epidemiology, Bethesda, March 1991. Supported by National Eye Institute/NIH grant EY06594 (R. Klein and B. E. K. Klein), Bethesda, Maryland. Reprint request to Ronald Klein, MD, MPH, Department of Ophthalmology, University of Wisconsin-Madison, 600 Highland Ave, ES/353 CSC, Madison, WI 53792.
ciated with age-related maculopathy in the large population-based Beaver Dam Eye Study.
Methods The Population Methods used to identify the population and descriptions of it appear in previous reports. 7•8 Briefly, a private census of the population of Beaver Dam, Wisconsin was performed from September 15, 1987 to May 4, 1988. Eligibility requirements for entry into the study included living in the city or township of Beaver Dam and being 43 to 84 years of age at the time of the census. In 3715 of the 6612 households identified by the census, there was at least 1 person who satisfied the age criteria. In these households, there were a total of 5833 individuals between the ages of 43 and 84 years at the time of the census. After completion of the census, 76 additional households with a total of 92 eligible people were identified, and these people were included in the population.
933
Ophthalmology
Volume 99, Number 6, June 1992
For reasons of efficiency in recruitment and examination, those who were eligible were divided into 10 groups by a random selection process. The population was examined over a 30-month period beginning March 1, 1988. Ofthe 5925 eligible people, 4926 (83.1%) participated in the study. Two hundred twenty-five people (3.8%) died before the examination, 91 people (1.5%) moved out of the area, and 23 people (0.4%) could not be located. Two hundred sixty-nine people (4.5%) permitted an interview only, and 391 (6.6%) refused to participate. Comparisons between participants and nonparticipants have been presented elsewhere. 8 Nonparticipants were significantly older (63.5 versus 60.6 years of age) (P < 0.05) and had a higher self-reported frequency of poorer near vision (4.0 versus 2.4%) than did participants. The frequencies of self-reported histories of poor distance vision, presence of age-related macular degeneration, diabetes, or hypertension did not differ. Figure 1. Clear plastic grid used to define subfields in macula.
Procedures Letters from their primary care physicians, or from the principal investigators if no primary care physician was identified in the census, were sent to those who were eligible. These letters described the study and invited eligible people to participate. This was followed by a call from the study coordinator, who provided further information about the study and made an appointment for the examination. People who were not interested in participating in the examination were asked to respond by telephone to the same questionnaire that was administered at the time of the examination. During the examination, informed consent was obtained from each participant. Stereoscopic 30° color fundus photographs centered on the disc (Diabetic Retinopathy Study [DRS] standard field 1), macula (DRS standard field 2), and a nonstereoscopic color fundus photograph temporal to but including the fovea of each eye were taken. 9 •10 The slide transparencies were mounted in clear plastic sheets. Before grading, a grid consisting of three circles concentric with the center of the macula and four radial lines was superimposed over one member of the stereoscopic pair of field 2 (Fig 1). 11 The radius of the innermost circle corresponded to 500 ~m in the fundus of an average eye, and the radii of the middle and outer circles corresponded to 1500 and 3000 J.Lm, respectively. Nine subfields were defined by the grid: the central subfield (within the inner circle); the inner superior, nasal, inferior, and temporal subfields (between the inner and middle circles); and the outer superior, nasal, inferior, and temporal subfields (between the middle and outer circles). Some lesions were graded in each subfield, others in DRS field 2 as a whole, and others in other fields. For the purpose of this report, measurements made only within the nine subfields defined by the grid are presented. Three sets of circles (designated as C0 , Ct. C2, It. h, and Ot. 02) printed on clear plastic were used to estimate size of drusen, area involved by drusen, and area involved by increased retinal pigmentation. 11
934
Two levels of grading were carried out on the fundus photographs. First, a preliminary grading was performed by one of two senior graders. 10 After examining all of the photographic fields for the entire eye, the grader recorded determinations for various lesions associated with agerelated maculopathy and other abnormalities involving the retina and optic nerve head. This review was used to prepare a report for the primary care physician and the participant. Second, detailed grading was performed by one of three other graders. While preliminary grading involved concurrent examination of both right and left eyes, detailed grading involved separate gradings of the eyes. This assessment consisted of a subfield-by-subfield, lesion-by-lesion evaluation of each photograph set for each eye using the Wisconsin Age-Related Maculopathy Grading System.11·12 The detailed gradings were subjected to a computerized edit for internal consistency. When inconsistencies were found, forms accompanied by photographs were returned to the grader for correction. Next, the presence and severity of specific lesions (predominant drusen size, drusen area, retinal pigment epithelial [RPE] degeneration, retinal pigment and/or neurosensory retinal detachment, subretinal hemorrhage, subretinal fibrosis, or geographic atrophy), as determined by detailed grading for each eye, were compared with the presence and severity as determined by preliminary grading. Edit rules were used to define significant disagreements. When the two determinations disagreed, the eye was regraded for the specific lesion by another grader. If that grader agreed with either of the first two determinations, that result was accepted. If a discrepancy remained, the fundus photograph was referred to the most senior grader for adjudication. Of the 4926 participants, 4843 (98.3%) had fundus photographs of both eyes, 42 (0.9%) had them of 1 eye only, and 41 people (0.8%) did not have fundus photographs taken (Fig 2). Eyes were not photographed because
Klein et al · Prevalence of Age-related Maculopathy 4, 926 people examined 1988-1990
4, 885 people with fundus photographs of at least one eye (4,843 both eyes, 42 one eye)
I
I 41 - no photographs of either eye
lll
I 0 ungradab1e eyes
I j
4, 775 people with gradable fundus photographs in at least one eye
(4, 514 both eyes, 261 at least one eye)
Figure 2. Schematic diagram shows participant selection and inclusion in study analyses.
of inability to dilate the pupil, significant lens or corneal opacities, enucleation, or refusal of the participant. Eyes were considered gradable if field 2 was present and 5 or more subfields could be graded for drusen, if fewer than 5 subfields could be graded but at least 1 drusen was 125 ~-tm or greater in size, or if other signs of agerelated maculopathy (RPE abnormalities, exudative macular degeneration or geographic atrophy) were present. The degree of exact agreement achieved between the
graders ranged from 66% to 73% for each ofthe drusen characteristics and 88% or more for the other maculopathy characteristics. The Kappa scores were generally in the moderate to substantial agreement categories. 11 Of the 4885 people with fundus photographs of at least 1 eye, photographs were judged to be gradable in at least 1 eye for 4775 (97.7%) (Fig 2). Four people with gradable photographs were excluded from the analyses, one because of pigmentary abnormalities in the macular areas of both eyes, believed to be unrelated to age-related maculopathy, one who had one eye with pigmentary abnormalities and the other which could not be graded, and two who had signs of maculopathy which were believed to be secondary to other conditions that affected the macular area. In addition, there were 58 people in whom one eye was excluded from the analyses because ofthe presence of non age-related maculopathy (n = 35) or because of pigmentary abnormalities unrelated to age-related maculopathy (n = 23). For purposes of this report, only the 4771 people (96.8%) with at least one eye with gradable fundus photographs without an excluded lesion are included in the analyses. Comparisons between people who had at least one eye included in the analyses and those who had neither eye included are found in Table 1. People with neither eye included were significantly older (P < 0.05), had a greater body mass index, lower diastolic blood pressure, a higher blood glucose level, poorer visual acuity, and were more likely to be female and to have never had smoked than those who had at least one eye included.
Table 1. Comparisons between Participants Included and Those Excluded in the Analyses of Age-related Maculopathy (Beaver Dam Eye Study, 1988-1990) Included (n = 4771)
Excluded* (n = 155)
p
Characteristic
No.
Mean
Standard Deviation
No.
Mean
Standard Deviation
Value
Age (yrs) Body mass index (kg/m2) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Blood glucose (mg/dl) Visual acuity (number of letters read correctly, left eye)
4771 4740 4769 4769 4758
61.7 4.0 132.0 77.5 106.3
11.0 0.75 20.5 11.0 38.9
155 138 154 154 150
73.2 3.8 134.3 72.2 119.2
11.0 0.9 1.8 11.2 50.6
