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related macular degeneration
Smoking and age related macular degeneration: a review of association
J Thornton1, R Edwards1, P Mitchell2, R A Harrison3, I Buchan1 and S P Kelly4
1Evidence for Population Health Unit, Division of Epidemiology and Health Sciences, University of Manchester, Manchester, UK2University of Sydney Department of Ophthalmology, Centre for Vision Research, Westmead Hospital, Westmead, Australia3Bolton Primary Care Trust, St Peter's House, Bolton, UK4Bolton Eye Unit. Bolton Hospitals NHS Trust, Bolton, UKCorrespondence: SP Kelly, Bolton Hospitals NHS Trust, Minerva Road, Bolton BL4 0JR, UK. Tel: +44 1204 390694; Fax: +44 1204 390554.
Top of pageAbstractPurpose Age related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss in the Western world. As there is no effective treatment for all types of AMD, identifying modifiable risk factors is of great importance. This review evaluates the epidemiological evidence associating smoking with AMD.
Methods Systematic review of published epidemiological studies evaluated against established criteria for evidence of a causal relationship.
Results In total, 17 studies (cross sectional studies, prospective cohort studies, and case studies) were included in the review. A total of 13 studies found a statistically significant association between smoking and AMD with increased risk of AMD of two to three fold in current smokers compared with never smokers. Five studies found no association between smoking and AMD. There was also evidence of dose response, a temporal relationship and reversibility of effect.
Conclusion The literature review confirmed a strong association between current smoking and AMD, which fulfilled established causality criteria. Cigarette smoking is likely to have toxic effects on the retina. This paper evaluates the evidence for a causal association between smoking and AMD.
Top of pageMethodsSearching and review of studiesMEDLINE (1966 to July 2003) and EMBASE (1980 to July 2003) were searched using combinations of the key words of 'smoking', 'macular degeneration', and 'age related maculopathy'. Bibliographies were checked for further relevant studies.
Studies were included if they were epidemiological studies (case cohort or cross sectional studies) published in English, assessed the relationship between tobacco smoking and AMD or ARM, and included an estimate of the degree of association (odds ratio (OR) or relative risk (RR)). The outcome measure was the presence of ARM or AMD fake van cleef bracelet as defined by the investigators of each study. The evidence was reviewed against a framework for assessing the evidence for causality derived from Hill10 and subsequently modified by Susser11 (see box).
Top of pageResultsDesign of studiesIn total, 23 studies examined the link between smoking and AMD. Two studies were excluded from the review as they were not published in the English language.12, 13 One study was excluded because it was a case series.14 Three studies did not report an OR or RR.15, 16, 17 We attempted to calculate crude ORs for these studies using the available data. Pauleikhoff et al15 did not contain sufficient data to allow calculation of an OR. In the study by Hirvela et al,16 there were very large differences in smoking between men and women but there were insufficient data to calculate a sex specific OR. The fourth study was a very small (30 cases) individually matched case study. For the cross sectional and prospective cohort studies, subjects were recruited from the general population or through selected occupations such as watermen,18 physicians19 and nurses.20 For the case studies, cases were recruited through knock off van cleef & arpels bangle eye clinics, and hospital controls were recruited through eye clinics21, 22, 23, 24 or general medicine clinics.25
The age range for subjects in most studies was 40 years. The sex of subjects was not always reported, but approximately equal numbers of males and females were included in studies where data were available. In total, 10 studies evaluated neovascular AMD and six of these found a positive association;22, 24, 25, 28, 29, 30 five studies evaluated atrophic AMD and four found a positive association.24, 30, 33, 34 In van cleef bracelets knock off addition, some studies found the association was different for men or women. These variations could have been caused by random fluctuation because of relatively small numbers after stratifying by lesion type.
The results were not completely consistent and five studies found no association or only a very weak link between smoking and AMD.18, 23, 35, 36, 37 Of these, West et al18 found a nonsignificant decreased risk of AMD in ever smokers in a small cross sectional study, and Blumenkranz et al35 found a small nonsignificant increase among current smokers in a small case study. More importantly, a generally well conducted large French case study found only a weak and nonsignificant association between previous and current smoking with AMD after adjustment for confounding factors.23 Finally, although the Beaver Dam Eye Study found a strong association between smoking and neovascular AMD at baseline,28 the association at the 5 and 10 year follow up examinations was weaker.36, 37
Findings from the three large well executed cross sectional studies from Europe, Australia, and the USA demonstrate a consistent association between smoking and AMD.28, 29, 30 The populations from these three key studies were combined giving a pooled population of 12 468 subjects.26 Apart from age, smoking was the only factor that retained a clear (three fold) association with AMD (Table 4). The association with current smoking was stronger for neovascular AMD compared with atrophic AMD.
Is there a temporal relationship? The prospective cohort study design is best for demonstrating that smoking preceded the development of AMD. The three key cross sectional studies (the Beaver Dam Eye Study, the Rotterdam Study, and the Blue Mountains Eye Study) were subsequently extended into longitudinal studies; two studies reported results from further analysis of smoking and the risk of AMD after 533, 36 and 10 years37 follow up. In the Blue Mountains Eye Study, the association between all ARM and atrophic AMD (but not neovascular AMD) was still present 5 years from baseline.33 A further pooled analysis of the 5 year results from these three studies found a continued three fold association of current smoking with development of AMD (Table 4).27 The Physicians' Health Study19 and the Nurses' Health Study20 also observed positive associations between smoking and AMD after 7 years of follow up.
Is there a dose effect? Eight studies investigated a dose by comparing different levels of smoking, classified using pack years (Table 5).19, 20, 25, 29, 31, 32, 36, 37 All except the 10 year follow up of the Beaver Dam cohort study identified a dose effect. In the 5 year follow up results from the Beaver Dam study, the relative risk of early ARM increased as the amount smoked (measured in cigarette pack years) increased.36 However, there appeared to be a negative association between the incidence of late ARM and the amount smoked in the 10 year follow up.37 In female current smokers and ex smokers, an increasing number of cigarettes smoked was associated with an increased risk of developing AMD.20 In men, current smokers of 20 cigarettes per day.19 When the length and duration of smoking were combined as pack years, compared with never smokers, there was an increasing risk of AMD as the number of pack years increased from 0.25 to >40 (P for trend 19
Smoking and age related macular degeneration: a review of association
J Thornton1, R Edwards1, P Mitchell2, R A Harrison3, I Buchan1 and S P Kelly4
1Evidence for Population Health Unit, Division of Epidemiology and Health Sciences, University of Manchester, Manchester, UK2University of Sydney Department of Ophthalmology, Centre for Vision Research, Westmead Hospital, Westmead, Australia3Bolton Primary Care Trust, St Peter's House, Bolton, UK4Bolton Eye Unit. Bolton Hospitals NHS Trust, Bolton, UKCorrespondence: SP Kelly, Bolton Hospitals NHS Trust, Minerva Road, Bolton BL4 0JR, UK. Tel: +44 1204 390694; Fax: +44 1204 390554.
Top of pageAbstractPurpose Age related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss in the Western world. As there is no effective treatment for all types of AMD, identifying modifiable risk factors is of great importance. This review evaluates the epidemiological evidence associating smoking with AMD.
Methods Systematic review of published epidemiological studies evaluated against established criteria for evidence of a causal relationship.
Results In total, 17 studies (cross sectional studies, prospective cohort studies, and case studies) were included in the review. A total of 13 studies found a statistically significant association between smoking and AMD with increased risk of AMD of two to three fold in current smokers compared with never smokers. Five studies found no association between smoking and AMD. There was also evidence of dose response, a temporal relationship and reversibility of effect.
Conclusion The literature review confirmed a strong association between current smoking and AMD, which fulfilled established causality criteria. Cigarette smoking is likely to have toxic effects on the retina. This paper evaluates the evidence for a causal association between smoking and AMD.
Top of pageMethodsSearching and review of studiesMEDLINE (1966 to July 2003) and EMBASE (1980 to July 2003) were searched using combinations of the key words of 'smoking', 'macular degeneration', and 'age related maculopathy'. Bibliographies were checked for further relevant studies.
Studies were included if they were epidemiological studies (case cohort or cross sectional studies) published in English, assessed the relationship between tobacco smoking and AMD or ARM, and included an estimate of the degree of association (odds ratio (OR) or relative risk (RR)). The outcome measure was the presence of ARM or AMD fake van cleef bracelet as defined by the investigators of each study. The evidence was reviewed against a framework for assessing the evidence for causality derived from Hill10 and subsequently modified by Susser11 (see box).
Top of pageResultsDesign of studiesIn total, 23 studies examined the link between smoking and AMD. Two studies were excluded from the review as they were not published in the English language.12, 13 One study was excluded because it was a case series.14 Three studies did not report an OR or RR.15, 16, 17 We attempted to calculate crude ORs for these studies using the available data. Pauleikhoff et al15 did not contain sufficient data to allow calculation of an OR. In the study by Hirvela et al,16 there were very large differences in smoking between men and women but there were insufficient data to calculate a sex specific OR. The fourth study was a very small (30 cases) individually matched case study. For the cross sectional and prospective cohort studies, subjects were recruited from the general population or through selected occupations such as watermen,18 physicians19 and nurses.20 For the case studies, cases were recruited through knock off van cleef & arpels bangle eye clinics, and hospital controls were recruited through eye clinics21, 22, 23, 24 or general medicine clinics.25
The age range for subjects in most studies was 40 years. The sex of subjects was not always reported, but approximately equal numbers of males and females were included in studies where data were available. In total, 10 studies evaluated neovascular AMD and six of these found a positive association;22, 24, 25, 28, 29, 30 five studies evaluated atrophic AMD and four found a positive association.24, 30, 33, 34 In van cleef bracelets knock off addition, some studies found the association was different for men or women. These variations could have been caused by random fluctuation because of relatively small numbers after stratifying by lesion type.
The results were not completely consistent and five studies found no association or only a very weak link between smoking and AMD.18, 23, 35, 36, 37 Of these, West et al18 found a nonsignificant decreased risk of AMD in ever smokers in a small cross sectional study, and Blumenkranz et al35 found a small nonsignificant increase among current smokers in a small case study. More importantly, a generally well conducted large French case study found only a weak and nonsignificant association between previous and current smoking with AMD after adjustment for confounding factors.23 Finally, although the Beaver Dam Eye Study found a strong association between smoking and neovascular AMD at baseline,28 the association at the 5 and 10 year follow up examinations was weaker.36, 37
Findings from the three large well executed cross sectional studies from Europe, Australia, and the USA demonstrate a consistent association between smoking and AMD.28, 29, 30 The populations from these three key studies were combined giving a pooled population of 12 468 subjects.26 Apart from age, smoking was the only factor that retained a clear (three fold) association with AMD (Table 4). The association with current smoking was stronger for neovascular AMD compared with atrophic AMD.
Is there a temporal relationship? The prospective cohort study design is best for demonstrating that smoking preceded the development of AMD. The three key cross sectional studies (the Beaver Dam Eye Study, the Rotterdam Study, and the Blue Mountains Eye Study) were subsequently extended into longitudinal studies; two studies reported results from further analysis of smoking and the risk of AMD after 533, 36 and 10 years37 follow up. In the Blue Mountains Eye Study, the association between all ARM and atrophic AMD (but not neovascular AMD) was still present 5 years from baseline.33 A further pooled analysis of the 5 year results from these three studies found a continued three fold association of current smoking with development of AMD (Table 4).27 The Physicians' Health Study19 and the Nurses' Health Study20 also observed positive associations between smoking and AMD after 7 years of follow up.
Is there a dose effect? Eight studies investigated a dose by comparing different levels of smoking, classified using pack years (Table 5).19, 20, 25, 29, 31, 32, 36, 37 All except the 10 year follow up of the Beaver Dam cohort study identified a dose effect. In the 5 year follow up results from the Beaver Dam study, the relative risk of early ARM increased as the amount smoked (measured in cigarette pack years) increased.36 However, there appeared to be a negative association between the incidence of late ARM and the amount smoked in the 10 year follow up.37 In female current smokers and ex smokers, an increasing number of cigarettes smoked was associated with an increased risk of developing AMD.20 In men, current smokers of 20 cigarettes per day.19 When the length and duration of smoking were combined as pack years, compared with never smokers, there was an increasing risk of AMD as the number of pack years increased from 0.25 to >40 (P for trend 19
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