|Year : 2021 | Volume
| Issue : 2 | Page : 113-125
Risk Factors for Age-related Macular Degeneration in Benin City, Southern Nigeria
Osayem J Otabor-Olubor1, L. O. Ekechukwu2, O. M. Uhumwangho1, A.. E Omoti1
1 Department of Ophthalmology, University of Benin Teaching Hospital, Benin City, Nigeria
2 MedricVision, 9 Kudirat Salami Street, Agungi, Lekk, Lagos, Nigeria
|Date of Submission||05-Feb-2020|
|Date of Decision||01-Feb-2021|
|Date of Acceptance||28-May-2021|
|Date of Web Publication||18-Jan-2022|
Dr. Osayem J Otabor-Olubor
Department of Ophthalmology, University of Benin Teaching Hospital, Benin City-310101
Source of Support: None, Conflict of Interest: None
Objectives: Various risk factors for age-related macular degeneration (ARMD) have been postulated and identified. This study seeks to identify risk factors for cases with ARMD in our environment and proffer appropriate recommendations on ways to reduce the risk of its development and progression. Methods: This was a case–control hospital-based study conducted in the out-patient eye clinic of the Department of Ophthalmology, University of Benin Teaching Hospital, Benin City, Nigeria. The cases were patients attending the eye clinic, with a diagnosis of ARMD and the controls were patients without a diagnosis of ARMD for a period of 7 months, all 50 years and above. Chi-squared and Fisher exact analyses were used to explore variables. Logistic regression (unadjusted and adjusted) were used to determine possible risk factors and their interactions. Results: A total of 240 respondents made of 120 cases and 120 controls participated in the study. A higher proportion of the respondents in both study groups was in the age group 60 to 69 years; cases 48 (40.0%) and controls 49 (40.8%) years. Adjusted odds ratio (OR) for risk factors for ARMD includes male sex [OR: 3.07; 95% confidence interval (CI): 0.92–10.23], those who resided in urban areas (OR: 3.08; 95% CI: 0.13–73.14), those who were employed (OR: 1.45; 95% CI: 0.46–4.54), alcohol use (OR: 1.86; 95% CI: 0.21–16.61), regular consumption of fast foods (OR: 1.43; 95% CI: 0.00–2355.87), obesity (OR: 1.39; 95% CI: 0.46–4.16), use of nontinted glasses (OR: 0.43; 95% CI: 0.14–1.35), and diabetes (OR: 1.31; 95% CI: 0.30–5.63). Conclusion: In this study, increasing age, the female gender, increasing body weight, and myopia were positively associated with ARMD. Tertiary education, weekly consumption of fruits, and the use of tinted spectacles were protective against ARMD. Identifying these risk factors in our environment will be a major step in planning health awareness programs geared toward management of progression of ARMD.
Keywords: Age-related macular degeneration, increased age, risk factors
|How to cite this article:|
Otabor-Olubor OJ, Ekechukwu LO, Uhumwangho OM, Omoti AE. Risk Factors for Age-related Macular Degeneration in Benin City, Southern Nigeria. Niger J Ophthalmol 2021;29:113-25
| Introduction|| |
Age-related macular degeneration (ARMD) is one of the age-related eye diseases in relation to low vision and blindness of great concern globally. It is a progressive neuroretinal degenerative disease in which patients advance from early and intermediate stages, and characterized by changes in pigment and drusen deposits to more advanced pathology, such as geographic atrophy and choroidal neovascularization. It ranks third among the global causes of visual impairment with a blindness prevalence of 8.7%. It commonly occurs in the sixth decade of life and it is generally bilateral. ARMD increases with age in men and women; however, no significant sex differences in rates have been found. It is the leading cause of visual loss and blindness in western countries.,, In developing countries, there is paucity of data on the prevalence of this disease, possibly due to the nonavailability of equipment needed to make accurate diagnosis of this important cause of low vision and blindness in the aging population.
Various risk factors for ARMD have been postulated and identified.,, It is also possible that the risk factors in western countries may differ slightly from that in the Nigerian elderly patients. These may affect the prevalence and characteristics of ARMD in sub-Saharan Africa when compared with western countries. This study seeks to identify risk factors for cases with ARMD in our environment and proffer appropriate recommendations on ways to reduce the risk of its development and progression.
This was a case–control hospital-based study conducted in the out-patient eye clinic of the Department of Ophthalmology, University of Benin Teaching Hospital, Benin City, Nigeria within a period of 7 months from December 2015 to June 2016.
From every new consenting consecutive patient aged 50 years and above attending the eye clinic during the period of the study, all those diagnosed with ARMD were recruited as cases. Those without ARMD were recruited as controls. In addition to age 50 years or more, cases and controls were patients who did not have significant media opacities obscuring visualization of the fundus, those who did not have a prior history of eye trauma, and those without macular pathologies such as retinal vascular occlusions, proliferative diabetic retinopathy, and diabetic macular edema. This was carried out to exclude bias in the study.
Ethical clearance to conduct this research was sought and obtained from the Ethics and Research Committee of the University of Benin Teaching Hospital, Benin City, Nigeria, before commencement of this study. Written informed consent was obtained from each respondent before the conduct of interviews. Confidentiality and privacy was respected during the course of the interviews. Participants were treated with dignity and respect.
Basic demographic data were collected using structured interviewer-administered questionnaires. The accurate age of nonliterate participants was determined using landmark historical events. The blood pressure was measured with mercury sphygmomanometer and a stethoscope and anthropometric measurements (weight and height) using a weighing scale and a standometer, respectively.
Visual acuity was performed using an illuminated Snellen chart or an illiterate E chart where applicable. Near vision was tested using a new version near chart held at 33 cm from the patient. Refraction was carried out to obtain the best corrected visual acuity of patients who showed improvement in their visual acuity using a pin-hole disc. Anterior segment and dilated retinal examination was performed using a bright pen torch, Carl Zeiss slit lamp biomicroscope, and +78D Volk lens, Carl Zeiss Meditec AG SL 115 Classic. Photographs taken were compared using standard photographs from the International ARM Epidemiological Study Group to help to get an objective assessment of the lesion and classification. Measurements of the size of the lesion were taken using the optic disc as a scale (assuming that a disc diameter is 1500 μm). Fundus fluorescein angiography and/or optical coherence tomography were performed when indicated in cases suspected to have neovascular ARMD. Registered participants had their fasting blood glucose and fasting serum lipid profiles checked. The collected data were entered into a database, cleaned, and analyzed using the International Business Machine Statistical Product for Scientific Solutions version 20 software (IBM SPSS Inc, Chicago, Illinois, USA). Variables such as sociodemographic characteristics, chronic medical conditions, and lifestyle, and biochemical parameters were explored for the cases and controls using Chi-squared and Fisher exact where applicable. Logistic regression (unadjusted and adjusted) was carried out with independent variables such as age, sex, smoking, body mass index (BMI), etc., and possible confounding factors to determine possible risk factors for ARMD and statistical interactions with each other.
| Results|| |
A total of 240 respondents made of 120 cases and 120 controls participated in the study. There were 97 males (40.4%) and 143 females (59.6%), giving a male to female ratio of 1:1.5. The mean age was 66.7 ± 8.0 years (range 50–88 years). A higher proportion of the respondents in both study groups were in the age group 60 to 69 years; cases 48 (40.0%), controls 49 (40.8%) years, as shown in [Table 1]. The mean ages of the respondents were cases; 67.8 ± 8.1 years, control; 65.5 ± 7.8 years (P = 0.514).
|Table 1 Sociodemographic characteristics of cases with age-related macular degeneration and controls|
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[Table 2] summarizes that weekly consumption of fruits was significantly more common among the controls than in the cases with ARMD (P = 0.005). There was no significant relationship between the presence of chronic medical conditions such as diabetes mellitus, hypertension, dyslipidemia, and risk of having ARMD in both cases and controls. Majority of the respondents in both study groups obtained animal protein predominantly through eating of fish; cases 118 (98.3%), controls 114 (95.0%) (P = 0.407). In the control group, 53.3% used prescribed spectacles; 38.3% of the study group used spectacles (P = 0.026). Ninety-three (77.5%) of the cases had hypermetropia compared to 108 (90.0%) of the control group. However, a significant portion of the cases (20.8%) was myopic compared to controls where only 6.7% were myopic (P = 0.03). The mean weight for the cases and the control groups were 74.4 ± 7.6 and 78.0 ± 11.5 kg, respectively (P = 0.004); the mean height for the cases and the control groups were 1.61 ± 0.06 and 1.64 ± 0.10 m, respectively (P = 0.001); the mean BMI of the cases and the control groups were 28.9 ± 2.9 and 29.3 ± 5.7 kg/m2, respectively (P = 0.493).
|Table 2 Chronic medical conditions and lifestyle in cases with age-related macular degeneration and controls|
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[Table 3] summarizes that 117 (97.5%) of the respondents in the cases compared to 114 (95.0%) in the control group had normal fasting blood glucose (P = 0.120). There was no statistically significant relationship in the lipid profile in both groups.
|Table 3 Biochemical parameters of cases with age-related macular degeneration and controls|
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[Table 4] summarizes that the variables in the regression model represented between 60.1% and 80.1% of the variation observed in the outcome variable (ARMD). Adjusting for other covariables in the regression model, a year increase in the age of the respondents leads to 1.13 increase in the odds of developing ARMD. Female respondents were 3.07 [95% confidence interval (CI): 0.92–10.23] times more likely to develop ARMD compared to males. Respondents who resided in rural areas were 3.08 (95% CI: 0.13–73.14) times more likely to develop ARMD compared to those who resided in urban areas. Respondents who had no formal education, primary education, and secondary education were 0.67, 1.98, and 2.67 times more likely to develop ARMD compared to those with tertiary education. The respondents who were employed were 1.45 (95% CI: 0.46–4.54) times more likely to develop ARMD compared to those who were unemployed. The respondents who smoked cigarettes were 0.76 (95% CI: 0.46–4.54) times more likely to develop ARMD compared to those who did not smoke cigarettes. The respondents who took alcohol were 1.86 (95% CI: 0.21–16.61) times more likely to develop ARMD compared to those who did not take alcohol. The respondents who ate fast food were 1.43 (95% CI: 0.00–2355.87) times more likely to develop ARMD compared to those who did not eat fast foods. The respondents who were obese were 1.39 (95% CI: 0.46–4.16) times more likely to develop ARMD compared to those who were not obese. The respondents whose glasses were not tinted were 0.43 (95% CI: 0.14–1.35) times more likely to develop ARMD compared to those who used tinted glasses. The respondents who were hypertensives were 0.99 (95% CI: 0.35–2.79) times more likely to develop ARMD compared to those who were not hypertensives. Those who were diabetic were 1.31 (95% CI: 0.30–5.63) times more likely to develop ARMD compared to those who were not diabetic, whereas those who had hyperlipidemia were 0.43 (95% CI: 0.00–446.71) times more likely to develop ARMD compared to those who did not have hyperlipidemia. Only the age of respondents showed statistically significant association with ARMD.
|Table 4 Risk factors for age-related macular degeneration among the cases|
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| Discussion|| |
A higher proportion of respondents were aged 60 to 69 years. This is in agreement with the fact that ARMD becomes more clinically apparent as age increases, especially after the age of 50 years. This finding was similar to data from the United Kingdom, where it was shown that individuals aged 65 to 75 years had ARMD.,. Similar findings were shown by Nwosu and Omoti in Nigeria. In this study, the greater proportion of individuals with ARMD was females (60.0%). Such was the case in the Nigerian hospital studies by Onakpoya et al., Nwosu and Omoti, where there was a female preponderance of cases with ARMD. This was also the case in the Blue Mountains Eye Study, a population-based study conducted in Sydney, Australia, where the higher prevalence of ARMD was reported in females compared to males. In a study by Klein et al., increased longevity in females was attributed to the higher prevalence observed in the female group. Of note however is the fact that this study was a hospital-based study when compared with the Blue Mountains Eye Study which was a population-based study.
Significantly fewer cases with ARMD had tertiary level of education (P = 0.010), showing a reduction in the risk of having ARMD with increasing level of education. This is in keeping with earlier studies carried out which showed that the risk of having ARMD reduces with increasing level of education, though this has not been sufficiently proven., The role of education in influencing the social living standards of individuals, by creating better awareness on healthy lifestyle behaviors could be attributed to this. In Nigeria, there are five social class systems: upper-upper class (the presidency, top government officials, wealthy royal families, elders in council), lower-upper class (military officers, top entrepreneurs, top politicians, top professors), upper-middle class (professors, lecturers, public servants, teachers), lower-middle class (owners of small businesses, policemen), and the working class (petty traders, brick layers, temporary job workers). The greater percentage of the population was in social class V (53.3% cases, 46.7% controls). This difference was not statistically significant. This buttresses the unlikelihood of social class, impacting on the incidence of ARMD.,
About one-fifth (20%) of those with ARMD were diabetics, with a mean duration of 7.8 ± 6.5 years. The difference in proportions in both study groups was not statistically significant (P = 0.400). This was similar to the Blue Mountains Eye Study where no association was found between diabetes mellitus and early ARMD. However, the same study found a significant relationship with geographic atrophy. The difference in proportions between both study groups who were hypertensives was not statistically significant. This is in agreement with other population-based cross-sectional studies where no association was found between hypertension and ARMD., Other factors, probably genetic, are responsible for a hypertensive coming down with ARMD and not necessarily the hypertension itself.
Of the study population, four persons (one case, three controls) had hyperlipidemia and were on lipid-lowering medication. This did not reflect an association between the use of lipid-lowering medication and development of ARMD as shown by the Beaver Dam and Blue Mountains Eye studies which showed a relationship between them.
Only two (1.7%) individuals diagnosed with ARMD during the study period alluded to smoking cigarettes compared to one control. The difference was not statistically significant. This reduced number could be due to the fact that the study population do not smoke as much cigarettes when compared with those in the western world. An average of one packet of cigarettes was smoked per day, for up to 25 years (25 pack years). This finding was in agreement with studies conducted by Klein et al. and Evans which showed individuals who had smoked 11 pack years or more coming down with early ARMD, reflecting a dose–response relationship of cigarette smoking and development of ARMD. In contrast to this, West et al. and Blumenkranz et al. had findings which did not reflect this relationship. Though studies show an increased risk of neovascular ARMD in individuals who had smoked 10 or more pack years, this study revealed otherwise, as none of those identified with neovascular ARMD were smokers., However, since only two subjects in this study had neovascular ARMD, the number is too small to draw valuable conclusions. The possibility of genetics playing a more significant role in the development of late ARMD could be entertained. In addition, increasing western exposure and lifestyle could increase the risk of an individual coming down with ARMD.
Alcohol consumption, beer especially, in this study did not contribute significantly to the development of ARMD. This was similar to a study by Knudtson et al. where the amount of beer, wine, or liquor ingested did not affect the incidence or progression of ARMD. Similar findings were seen in the Rotterdam study. The Blue Mountains Eye Study associated early ARMD with ingestion of spirits, not beer consumption. The major form of alcohol ingested by participants in this study was beer.
Diet and nutrition was shown to significantly influence the development of ARMD in this study. Frequent consumption of fruits (predominantly watermelon and oranges) was significantly more common among controls than participants with ARMD (P < 0.005). This indicates a measure of protection from ARMD by these fruits. Although 44.2% of cases with ARMD attested to frequent weekly consumption of vegetables, there was no statistically significant difference between both study groups regarding intake of vegetables. This finding contrasts that by Amirul et al. where frequent intake of varied types of vegetables was associated with a lower prevalence of advanced ARMD. The reason for this disparity could possibly be due to the differences in the state of the vegetables at the point of consumption observed in the western continent and that reported here in sub-Saharan Africa. In the western world, vegetables are mostly eaten raw, whereas here in sub-Saharan Africa, the vegetables tend to be overcooked before they are consumed. The nutrients remain intact at the point of consumption when eaten raw, whereas they are destroyed when overcooked, losing the protection possibly offered by these vegetables. Another plausible reason could be the difference in the population studied, as the participants in this study majorly had features of early ARMD against advanced ARMD as was observed in the study by Amirul et al. Weekly consumption of junk food was not common among the study population. This was probably due to the prevailing economic situation of most families, making it difficult for individuals to indulge in fast food consumption. Of the few who took fast foods weekly (one case, two controls), no statistically significant difference in proportions was noticed. Despite this finding, Amirul et al. associated the risk of having ARMD with consumption of high fat diet. Compared to red meat and white meat, it was found that the greater proportion of the study population (98.3% cases and 95% controls) consumed fish (majorly crayfish, Titus). The majority of the respondents in both study groups obtained proteins predominantly through eating fish. This could be attributed to the low purchasing power of the participants and the relatively low cost of procurement of fish in the Nigerian markets and yet benefitting from the high nutritional value. Though higher intake of fish rich in omega-3 fatty acids (salmon, tuna, mackerel) has been associated with a lower risk of development of ARMD as shown by Tan et al. and Swenor et al., this study did not show any statistically significant difference between the two study population regarding intake of fish. It was observed in this study that despite the high proportion of fish consumption among the cases (98.3%), the risk of ARMD was still high. Studies carried out have shown inconsistent associations between intake of fish and the risk of developing ARMD.,,
Majority of those who used glasses were the control group. The difference in proportion was statistically significant. Of these, 6.8% of them had their glasses tinted or wore photochromic lenses. It has been hypothesized that exposure to sunlight is a plausible risk factor for ARMD. The possibility of the tint offering some form of protection from bright sunlight could be attributed to the controls not coming down with ARMD earlier. In this study, myopia was found to be significantly more common among cases with ARMD than in the controls. This is in contrast to findings from North India, Australia, and a case–control study carried out in Baltimore, United States of America, where statistically significant associations were demonstrated between ARMD and hypermetropia.,,, This finding needs to be evaluated further before valuable conclusions can be drawn, as the number of cases and controls with myopia were small.
In this study, it was found that there was a statistically significant difference in the weight and height of the controls compared to the cases with ARMD (P < 0.05). The cases in this study were more overweight. This shows that weight, the modifiable aspect of BMI, is an important predictor in an individual coming down with ARMD, though it was not singularly assessed as a risk factor for ARMD in other studies reviewed. Documented findings in literature show an increased risk of ARMD with increasing BMI.,, This study however did not show any statistically significant relationship between BMI and the risk of having ARMD. It has been postulated that BMI does not take into account the body composition of an individual (lean muscle mass and fat mass). Hence, an individual can be said to have a high BMI and be tagged as being overweight or obese, whereas the body fat constituent is low. This drawback could possibly explain the finding in this study.
A greater proportion of the cases with ARMD had lens opacities compared to the controls and this was statistically significant (P < 0.001). This agrees with the study by Fletcher where a link was shown in the pathogenesis of ARMD and cataract, both resulting from accumulation of reactive oxygen species from the mitochondria and from sunlight exposure.
Though studies reviewed did not single out a relationship between Amsler grid findings and the pattern of ARMD observed, this study showed that Amsler grid was normal in the majority of cases with ARMD (>75%) and this was statistically significant (P < 0.001). This could be due to the fact that the majority of cases had features suggestive of early ARMD, in which case image distortions noticeable on Amsler grid would not have become prominent enough to be noticed on examination.
The increase in age of the respondents by a year gave rise to a 1.13 increase in the odds of developing ARMD. This correlates with the already established fact that age is the strongest risk factor for ARMD and is comparable with other research findings from studies carried out in western nations,,, and in Nigeria., This strongly corroborates the widely accepted notion that the focal accumulation of extracellular deposits beneath the retinal pigment epithelium (RPE) gives rise to the formation of age-dependent macular drusen, which precedes the age-dependent formation of macular degeneration.
This study showed that the risk of ARMD increases with age, with a greater preponderance among females (60%). The risk of having ARMD was shown to be reduced with increasing level of education and social class was not a significant risk factor for ARMD. The use of tinted or photochromic lenses was shown to offer some form of protection from direct sunlight, reducing the risk of ARMD. The presence of lens opacities was associated with an increased risk of having ARMD, and Amsler grid was normal in patients with early ARMD.
Health education to elderly patients on the importance of frequent consumption of fruits which is likely to reduce the burden of this disease or retard its progression. Health education on measures to avoid overweight such as exercise and dietary control, which would help reduce the risk of developing ARMD. Government to promulgate policies to improve the level of education of the population, as it has been shown that increasing level of education reduces the risk of having ARMD. Routine examination of individuals aged 50 years and above to recognize features of early ARMD. Lenses of individuals should preferably be tinted/photochromic as this has been shown to offer some form of protection or retard the onset of ARMD. More multicenter hospital-based and population-based studies to be conducted to characterize the pattern and risk factors of ARMD in sub-Saharan Africa, as the disease is increasingly becoming a major cause of blindness.
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Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4]