A Simplified Severity Scale for Age-Related Macular Degeneration: AREDS Report No. 18
Open accessAbstract
OBJECTIVE: To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). METHODS: Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. RESULTS: The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. CONCLUSION: This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.
AI snapshot
Written from the paper’s full text.
TL;DR
This AREDS report developed a simplified 5-step (0–4) clinical severity scale for age-related macular degeneration based on large drusen and pigment abnormalities in each eye. The scale estimates 5-year risk of advanced AMD in at least one eye as approximately 0.5%, 3%, 12%, 25%, and 50% for 0, 1, 2, 3, and 4 risk factors.
Key findings
- The simplified scale assigns 1 risk factor per eye for 1 or more large drusen (≥125 µm, width of a large vein at the disc margin) and 1 risk factor per eye for any pigment abnormality; bilateral intermediate drusen with no large drusen counts as 1 risk factor.
- Approximate 5-year risk of advanced AMD in at least one eye rises from 0.5% (0 factors) to 3% (1), 12% (2), 25% (3), and 50% (4); in the scale-building data, exact rates were 0.4%, 3.1%, 11.8%, 25.9%, and 47.3%.
- For patients with advanced AMD in one eye, 2 risk factors are assigned for that eye plus additional factors for large drusen and/or pigment abnormalities in the at-risk eye; 3 risk factors carried a 35.4% 5-year risk versus 25.9% in patients without advanced AMD in either eye.
- Noncentral geographic atrophy was a strong predictor: 39 of 56 patients (69.6%; 95% CI, 57.6%–81.7%) with noncentral GA in one or both eyes developed advanced AMD.
Methods
- Using AREDS stereoscopic color fundus photographs, the study cross-classified 3211 persons free of advanced AMD in both eyes at baseline with complete baseline and 5-year information as of May 2001 by maximum drusen size and presence/absence of any pigmentary abnormality in each eye, then calculated 5-year rates of advanced AMD.
- The scale was also applied to left eyes and to 600 participants with advanced AMD in one eye at baseline; repeated-measures logistic regression estimated progression risk through 10 years for all participants and separately for placebo versus antioxidants plus zinc.
- Main analyses were cross-tabulations compared by inspection without formal statistical testing, with consideration of subgroup sizes and confidence intervals.
Limitations
- The paper states the patient group was not population based; many subgroups combined into scale steps were small with low outcome rates; treatment, age, sex, race, and drusen “softness” were not considered in scale building; and predictive power has not yet been examined in population-based cohorts or other large groups with nonadvanced AMD.
- The paper also notes clinical use requires estimating the largest druse size, which may be difficult in borderline cases or with atypical retinal vessel/optic disc sizes, and that pigment abnormalities can relate to diseases other than AMD, with possible judgment errors.
- Evident from the text: the cross-tabulations were not formally statistically tested, and the reported risks are global estimates that other factors such as smoking, family history, or supplement use may modify.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 5 cited sources checked · 0 supported · 0 flagged
- Findingown data
Large drusen and any pigment changes were particularly predictive of developing advanced AMD.
“Large drusen and any pigment changes were particularly predictive of developing advanced AMD.”
Quote in the paperSubstantial claim - Findingown data
For persons who already have advanced AMD in one eye, within each risk factor category, risks of advanced AMD in the contralateral eye are similar to those in the first section of Table 2 but somewhat higher.
“Within each risk factor category, risks are similar to those in the first section of the table, but somewhat higher.”
Quote in the paperSubstantial claim - Findingown data
The event rate estimates using the simplified risk factor scale for all AREDS participants through 10 years of follow-up are consistent with those seen using the scale-building data set.
“These results are consistent with those seen using the scale building data set”
Quote in the paperSubstantial claim - Findingown data
The 57 persons with GA involving the center of the macula in one eye at baseline had approximately the same 40% to 50% 5-year risk of developing advanced AMD in the second eye, whether large drusen were present in it or not.
“In addition, the 57 persons with GA involving the center of the macula in one eye at baseline had approximately the same 40% to 50% 5-year risk of developing advanced AMD in the second eye, whether large drusen were present in it or not.”
Quote in the paperSubstantial claim - Findingown data
The use of AREDS supplements can modify the risks somewhat.
“and also indicate how some risk factors, in this case the use of AREDS supplements, can modify the risks somewhat.”
Quote in the paperNot a substantial claim
- Findingown data
The presence of noncentral GA is a strong predictor of advanced AMD.
“For example, the presence of noncentral GA is a strong predictor of advanced AMD.”
Quote in the paperSubstantial claim - Findingown data
The simplified 5-step scale (0-4) yields approximate 5-year risks of advanced AMD in at least one eye of 0.5%, 3%, 12%, 25%, and 50% for 0-4 risk factors.
“Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%.”
- Also stated in: § RESULTS · plain
“Estimates of 5-year risks for the development of advanced AMD for each of the steps from 0 to 4 are 0.4%, 3.1%, 11.8%, 25.9%, and 47.3%, respectively.”
- Also stated in: § CONCLUSIONS · plain
“The 5-year risk of advanced AMD using this scale increases in the approximate sequence of: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Eye care professionals can more effectively assess maximum drusen size than drusen area.
- Rests on an assumption: Other risk factors, such as smoking, family history, or supplement use, have relatively small effects compared with the 100-fold change in risk between those with a score of 0 and those with a score of 4 based on fundus characteristics.
- Also stated in: § RESULTS · plain
- Interpretationown data
The classification scheme seems quite robust for identifying persons at small (≤12%), medium (approximately 25%), and large (approximately 50%) risk.
“In general, if one takes the perspective that this system is identifying persons at small (Յ12%), medium (approximately 25%), and large (approximately 50%) risk, the classification scheme seems quite robust.”
Quote in the paperSubstantial claim - Premisecitation
Drusen size and area are closely associated.
“As is well known and demonstrated in Table 2 of the companion report, drusen size and area are closely associated.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1]
Not checked in the free run.
- Premisecitation
The presence of large drusen in both eyes is a stronger risk factor for progression to advanced AMD than presence in only one eye.
“the finding in a previous AREDS report that the presence of large drusen in both eyes was a stronger risk factor for progression to advanced AMD than presence in only one eye.6”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Not checked in the free run.
- Study design and conductreasoning
The simplified scale shares the limitation that many of the subgroups combined to produce the steps in the scale were small and outcome rates low.
“many of the subgroups that were combined to produce the steps in the scale were small and outcome rates low”
Quote in the paperNot a substantial claim - Premiseown data
The format of the simplified clinical scale was suggested by the low frequency of retinal pigment epithelial depigmentation and/or GA in the absence of increased retinal pigment (Table 4 of the companion report).
“(2) the low frequency of retinal pigment epithelial depigmentation and/or GA in the absence of increased retinal pigment (Table 4 of the companion report)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1]
Not checked in the free run.
- Study design and conductreasoning
The simplified scale shares the limitation that the patient group studied was not population based.
“The simplified scale shares the limitations of the more complex scale described in the companion report: the patient group studied was not population based”
Quote in the paperNot a substantial claim - Interpretationreasoning
For the medium- and high-risk levels (approximately 25% and 50% 5-year risk), the risk is cut in half for each decrease in the number of risk factors.
“For the medium-and high-risk levels (approximately 25% and 50% 5-year risk), the risk is cut in half for each decrease in the number of risk factors.”
Quote in the paperSubstantial claim - Study design and conductreasoning
The simplified scale shares the limitation that age, sex, race, or softness of drusen were not considered in scale building.
“nor was age, sex, race, or”
Quote in the paperNot a substantial claim - Interpretationown data
The simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in AREDS.
“This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Eye care professionals can more effectively assess maximum drusen size than drusen area.
- May combine two claims. 7
- Classified as probably not a substantial claim. 7
May combine two claims.
Findingown dataWhen at least 1 large druse was present in each eye, drusen area was ≥0.5 disc area in at least one eye in 71% of AREDS participants; when large drusen were present in only one eye, drusen area was ≥0.5 disc area in that eye in only 10%.
“When at least 1 large druse was present in each eye, drusen area was greater than or equal to 0.5 disc area in at least one eye in 71% of AREDS participants, while in participants with large drusen in only one eye, drusen area was greater than or equal to 0.5 disc area in that eye in only 10%.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe simplified scale was developed based on the presence or absence of 2 features characteristic of AMD (drusen size and pigment abnormalities) that were easily identified clinically and highly associated with the development of advanced AMD, especially when the status of both eyes was considered.
“A simplified scale was developed based on the presence or absence of 2 features characteristic of AMD that were easily identified clinically (drusen size and pigment abnormalities) and highly associated with the development of advanced AMD, especially when the status of both eyes was considered.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAmong persons with 3 risk factors, those with advanced AMD in one eye have a 35.4% 5-year risk for developing advanced AMD in the second eye, compared with a 25.9% risk of advanced AMD in one or both eyes for persons without advanced AMD in either eye.
“For example, among persons with 3 risk factors, those with advanced AMD in one eye have a 35.4% 5-year risk for developing advanced AMD in the second eye, compared with a 25.9% risk of advanced AMD in one or both eyes for persons without advanced AMD in either eye.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningThe simplified scale shares the limitation that treatment was not considered in scale building.
“and treatment was not considered in scale building”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationLarge drusen, presence of pigmentary abnormalities, presence of noncentral GA, and presence of advanced AMD in the fellow eye are all well-recognized risk factors for progression to advanced AMD.
“Large drusen, presence of pigmentary abnormalities, presence of noncentral GA, and presence of advanced AMD in the fellow eye are all well-recognized risk factors for progression to advanced AMD. [7][8][9][10][11][12][13]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7][8][9]
Not checked in the free run.
Classified as probably not a substantial claim.
Premiseown dataThe format of the simplified clinical scale was suggested by the strong association of maximum drusen size and drusen area shown in Table 2 of the companion report.
“(1) the strong association of maximum drusen size and drusen area shown in Table 2 of the companion report”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1]
Not checked in the free run.
May combine two claims.
Study design and conductown dataSimilar results were found when the scale was applied to the left eyes of the 3211 participants whose right eyes were used in developing it and to 600 different participants who had advanced AMD in one eye at baseline.
“although similar results were found when the scale was applied to the left eyes of the 3211 participants whose right eyes were used in developing it and to 600 different participants who had advanced AMD in one eye at baseline”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
InterpretationreasoningIn many cases these estimates will be easy, although in borderline cases or in eyes with retinal vessels or optic discs that are larger or smaller than average, they may not be.
“In many cases these estimates will be easy, although in borderline cases or in eyes with retinal vessels or optic discs that are larger or smaller than average, they may not be.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationnone givenUse of the simple scale clinically requires estimation of the size of the largest druse present in the posterior pole of each eye.
“In addition, use of the simple scale clinically requires estimation of the size of the largest druse present in the posterior pole of each eye.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Interpretationown dataThe sometimes difficult task of distinguishing between depigmentation and GA is avoided by defining pigmentary abnormalities as any of the 3 pigment disturbances characteristic of AMD and by the rarity of depigmentation and/or GA in the absence of increased pigment.
“Fortunately, the sometimes difficult task of distinguishing between depigmentation and GA is avoided by defining”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningThe simplified scale may be useful clinically, either with ophthalmoscopy or slitlamp biomicroscopy, or in less optimal photographs using less complex grading procedures than those used in AREDS.
“This scale may be useful clinically, either with ophthalmoscopy or slitlamp biomicroscopy, or in less optimal photographs using less complex grading procedures than those used in AREDS.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: Eye care professionals can more effectively assess maximum drusen size than drusen area.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningErrors in judging AMD-related pigment changes may have occurred.
“The rates published herein are related to pigment changes thought to be associated with AMD, but errors in making this judgment may have occurred.”
Quote in the paperNot a substantial claim
The authors state this as an assumption.
Eye care professionals can more effectively assess maximum drusen size than drusen area.
“Furthermore, we assumed that eye care professionals can more effectively assess maximum drusen size than drusen area.”
The paper relies on this without support.
Other risk factors, such as smoking, family history, or supplement use, have relatively small effects compared with the 100-fold change in risk between those with a score of 0 and those with a score of 4 based on fundus characteristics.
“However, these other factors have relatively small effects compared with the 100-fold change in risk between those with a score of 0 and those with a score of 4 based on fundus characteristics.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Soft drusen are associated with more extensive damage to the retina, RPE, and choroid, and predict more severe clinical outcomes such as geographic atrophy and choroidal neovascularization.
“Soft drusen are associated with more extensive damage to the retina, RPE, and choroid, and predict more severe clinical outcomes, such as GA and CNV (45).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [45]
Individuals with both large drusen and pigmentary changes in both eyes, or with these lesions in one eye and advanced age-related macular degeneration in the other, have about a 50% risk of developing advanced age-related macular degeneration in 5 years.
“For example, based on the simplified scale, individuals with both large drusen and the pigmentary changes in both eyes, or with these lesions in one eye and advanced age-related macular degeneration in the other, have about a 50% risk of developing advanced age-related macular degeneration in 5 years.8”
From Age-related macular degeneration (2008) · cites this paper as [8]
In both classification schemes, the risk of developing advanced age-related macular degeneration is directly associated with the extent of drusen and the amount of hypopigmentary or hyperpigmentary changes of the retinal pigment epithelial layer.
“In both schemes the risk of developing the advanced forms of age-related macular degeneration is directly associated with the extent of the drusen and the amount of hypopigmentary or hyperpigmentary changes of the retinal pigment epithelial layer.”
From Age-related macular degeneration (2008) · cites this paper as [8]
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- Authors
- Age-Related Eye Disease Study Research Group
- Affiliations
- Emmes (United States) (US)
- Corresponding author
- Age-Related Eye Disease Study Research Group
- Venue
- Archives of Ophthalmology
- Publisher
- American Medical Association (AMA)
- Published
- 2005-11-01
- Volume
- 123
- Issue
- 11
- Pages
- 1570
- ISSN
- 0003-9950 (ISSN-L)
- PMC
- PMC1473206
- OpenAlex
- W180947891
- Semantic Scholar
- 93834b247d86a1068671e4ce7df9e84f3f575257
- Cited by
- 807
- References
- 13
- Citations by year
- 2026: 34 · 2025: 38 · 2024: 44 · 2023: 52 · 2022: 69 · 2021: 61 · 2020: 60 · 2019: 37 · 2018: 45 · 2017: 38 · 2016: 31 · 2015: 51 · 2014: 39 · 2013: 51 · 2012: 36
- FWCI
- 15.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1z01ey000394-01, Z99 EY999999, Z01 EY000394)
- National Eye Institute (ZIAEY000489)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, severity scale, drusen, fundus photography grading, risk categories, AMD progression
- MeSH terms
- Humans, Macular Degeneration, Photography, Retinitis Pigmentosa, Risk Factors, Severity of Illness Index, Retinal Drusen, Disease Progression
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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