Purpose
To assess potential associations between the prevalence of age-related macular degeneration (AMD) and systemic parameters in a Chinese population.
Design
Cross-sectional study.
Methods
The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital from 2017 to 2019. Detailed medical examinations and ophthalmic examinations were applied, including fundus photography. AMD was evaluated according to the Beckman Initiative guidelines.
Results
The study included 7,719 participants (mean age: 60.5 ± 8.1 years; range: 50-97 years). The prevalence of any, early, intermediate, and late AMD was 1,607 of 7,719 (20.8%; 95% confidence interval [CI]: 20.1%, 21.9%), 832 of 7,719 (10.8%; 95% CI: 10.1%, 11.5%), 733 of 7,719 (9.5%; 95% CI: 8.9%, 10.2%), and 42 of 7,719 (0.50%; 95% CI: 0.40%, 0.70%), respectively. In multivariate analysis, the prevalence of any AMD increased with higher blood monocyte count (odds ratio [OR]:3.49; 95% CI: 2.26, 5.38; P < .001), after adjusting for older age (OR: 1.06; 95% CI: 1.05, 1.07; P < .001), higher serum concentration of calcium (OR: 2.52; 95% CI: 1.32, 4.84; P = .005), high-density lipoproteins (OR: 1.39; 95% CI: 1.19, 1.61; P < .001), and lower lipoprotein a (OR: 0.99; 95% CI: 0.98, 0.99; P = .02). Similar findings were obtained for the prevalence of intermediate and late AMD combined. The association between higher monocyte count and higher AMD prevalence showed the highest odds ratio for the age group of 50-59 years (any AMD: OR: 4.35, P < .001; intermediate and late AMD: OR: 6.14, P < .001). Individuals with a monocyte count of ≥0.5 × 10 9 /L as compared to participants with a monocyte of 0.1-0.4 × 10 9 /L had a 1.45-fold increased risk for any AMD (OR: 1.45; 95% CI: 1.27, 1.64; P < .001) and 1.58 fold increase risk for intermediate/late AMD (OR: 1.58; 95% CI: 1.33, 1.87; P < .001).
Conclusion
A higher prevalence of early AMD, intermediate AMD, late AMD, and any AMD was associated with a higher peripheral monocyte count. In agreement with previous studies, the observation suggests monocytes playing a role in the pathogenesis of AMD.
A ge-related macular degeneration (AMD) is one of the most common causes of irreversible vision impairment and blindness in the elderly population. Its risk factors include higher age, shorter axial length or hyperopia, smoking and the ethnic background, to mention a few. In addition, investigations have examined the potential role the immune system may play in the AMD pathogenesis. , It has been discussed that there is a breakdown of the physiological immunosuppressive subretinal environment in eyes with AMD, associated with an accumulation debris and of mononuclear phagocytes in and around the AMD lesions and with an increase in the intraocular concentrations of inflammation-related cytokines. , It has also been reported about a systemic overactivation of the innate immune system in AMD patients, with peripheral blood monocytes expressing proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6, interleukin-8, monocyte chemoattractant protein 1 (MCP-1), and CD11b+, in patients with AMD. , , Monocytes form an essential component of the innate immune system and are involved in systemic inflammatory processes. Most of the previous investigations on a potential association between AMD and monocytes were conducted in clinical settings with a relatively small number of study participants, in particular patients with early or intermediate AMD. We therefore conducted the present study to examine a relationship between the prevalence of AMD and peripheral blood monocyte count, after adjusting for other known factors associated with AMD, in a relatively large study population recruited on a community basis.
Methods
The cross-sectional Tongren Health Care Study included individuals who attended regular health care check-up examinations in the Beijing Tongren Hospital from July 2017 to December 2019. Most of the study participants were employees or retirees from enterprises (34.9%), government offices (24.8%), hospitals (16.7%), academic institutes (3.6%), and churches (0.7%), and had free health care in association with their employment. About 19.2% of the study participants were self-payers. The population of the Tongren Health Care Study consisted of 22,945 individuals. Out of these, those with an age of 50+ years were included in the present study. The study protocol was approved by the Medical Ethics Committee of the participating centers and it was confirmed that it was in adherence with the Declaration of Helsinki.
The examinations included an interview in which general demographic data and information about the medical history and other health-related events were obtained. To assess the smoking status, we differentiated between “ever smokers” and “never smokers” and calculated the smoking package-years by multiplying the mean daily number of cigarette packages smoked times the number of years of smoking. The physical examinations consisted of the measurement of anthropometric parameters such as body height and weight and circumferences of the waist and hip, measurement of blood pressure and heart rate, and electrocardiography.
The biochemical examinations of blood samples taken under fasting conditions included the differentiated blood cell count and the measurement of the serum concentrations of glucose, urea nitrogen, creatinine, uric acid, highly sensitive C-reactive protein, and blood lipids (triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, lipoprotein a). A complete blood cell count was performed using the Hematology Analyzer Coulter LH 780 (Beckman Coulter Inc, Miami, Florida, USA), within 4 hours after blood sample collection.
We calculated the body mass index and the waist-to-hip circumference ratio. Arterial hypertension was defined as a systolic blood pressure of ≥140 mm Hg, a diastolic blood pressure of ≥90 mm Hg, or history of a physician-based diagnosis of hypertension or use of antihypertensive medication. Diabetes mellitus was defined based on the history of a previously diagnosed diabetes or receiving a glucose-lowering therapy and/or fasting blood glucose concentration of ≥7.0 mmol/L. We calculated the estimated glomerular filtration rate based on the serum creatinine concentration and using the Chronic Kidney Disease Epidemiology Collaboration equation, and participants with estimated glomerular filtration rate of less than 60 mL/min/1.73 m 2 were defined as having chronic kidney disease.
The ophthalmologic examinations, performed by experienced technicians and ophthalmologists, consisted of the measurement of best-corrected visual acuity, noncontact tonometry, slit lamp–based biomorphometry of the anterior and posterior segment of the eye, and fundus photography (nonmydriatic 45-degree fundus camera; Topcon TRG-NW7SF; Topcon, Tokyo, Japan; or Canon CR6-45N; Canoon, Tokyo, Japan). AMD was defined and graded according to the guidelines of the Beckman Initiative. In contrast to the Beckman guidelines, we used a minimum age of 50 years for the definition of AMD. Fundus lesions within a circle with a diameter of 6 mm and centered on the fovea were assessed for the diagnosis of AMD.
Fundus photographs were considered evaluable if two-thirds of the foveal area was visible or with definitely detected AMD lesions despite the relatively poor quality of the fundus photograph. Early AMD was characterized by medium-sized drusen (diameter 63-125 µm), but without pigmentary abnormalities of the retinal pigment epithelium (RPE) or signs of late AMD. Intermediate AMD was defined by large drusen (diameter >125 µm) or pigmentary RPE abnormalities associated with at least medium-sized drusen (63-125 µm). Eyes with geographic atrophy or lesions associated with exudative AMD were classified as late AMD. Geographic atrophy was defined as a discrete circular area (at least 175 μm in diameter) of depigmentation of the RPE and showing visible choroidal vessels. Wet AMD was characterized by the presence of an RPE detachment or a serous detachment of the sensory retina, subretinal or sub-RPE hemorrhages, and subretinal fibrous scars. The final diagnosis of an individual was based on the eye with the more severe stage of AMD.
After a learning phase in which photographs of 800 eyes were assessed, all fundus images were reviewed and measured by an experienced ophthalmologist (C.C.X.), supervised by 2 senior retinal specialists (H.L.D., L.Q.G.). For the diagnosis of late AMD and in case of doubt, the images were reassessed by 2 senior retinal specialists (H.L.D., L.Q.G.). Randomly selected photographs of 100 participants were used to assess the interobserver variability.
The statistical analyses were performed using a software program (SPSS 26.0; SPSS Inc, Chicago, Illinois, USA). The data were presented as mean ± standard deviation for continuous variables and as frequency and percentages for categorical variables. The prevalence of AMD was presented as percentage and with the 95% confidence interval (CI). To determine the factors associated with the AMD prevalence, binary logistic regression analyses were performed with the presence of AMD as the dependent variable and adjusting for age. Odds ratios (OR) and their 95% CI were calculated. The univariate analyses were followed by a multivariable analysis, which included the AMD prevalence as the dependent variable and as independent parameters all those variables for which the P value in the univariate analysis (with adjustment for age) was ≤.10. For the assessment of the association between the blood monocyte count and the AMD prevalence, we reassessed the association after stratification of the study population by age. In a further step, the blood monocyte count was taken as a categorical variable after stratification of the study population by the monocyte count. We used the linear-by-linear association χ 2 test to examine the linear association between the blood monocyte count and the prevalence of AMD. Spline curves were created to fit the impact of age and blood monocyte count on the AMD prevalence. For all multivariable analyses, the variance inflation factor was calculated to estimate the collinearity, and collinearity was considered to be significant when the variance inflation factor was higher than 5. A 2-tailed P value of <.05 was considered to be statistically significant. For multiple comparisons, the AMD prevalence among different monocyte cell count levels (0.1-0.4 × 10 9 /L, 0.5 × 10 9 /L, ≥0.6 × 10 9 /L) was compared using the χ 2 test. We applied Bonferroni’s method to control for a statistical type I error, so that the difference between subgroups was considered statistically significant with a P value of <.017 (3 pairs).
Results
After exclusion of 195 individuals with unevaluable fundus photographs, the study eventually included 7,719 individuals (3,544 men, 45.9%) with a mean age of 60.5 ± 8.1 years (range: 50-97 years). The mean uncorrected visual acuity and best-corrected visual acuity were 0.30 ± 0.33 logMAR and 0.03 ± 0.13 logMAR, respectively. The mean intraocular pressure was 14.2 ± 3.1 mm Hg in the right eyes and 14.5 ± 3.2 mm Hg in the left eyes.
AMD was detected in 1,607 of 7,719 participants (749 men, 46.6%) with an overall prevalence of 20.8% ± 0.5% (95% CI: 20.1%, 21.9%). Early AMD, intermediate AMD, and late AMD were found in 832 individuals (10.8% ± 0.4%; 95% CI: 10.1%, 11.5%), 733 individuals (9.5% ± 0.3%; 95% CI: 8.9%, 10.2%), and 42 individuals (0.5% ± 0.1%; 95% CI: 0.4%, 0.7%), respectively ( Figure 1 ). Bilateral AMD was present in 468 (29.1%) patients while AMD was unilateral in 1,139 (71.9%) patients. The data on age and sex distribution in the subgroups of any AMD, early AMD, intermediate AMD, and late AMD, as well as subgroups with specific AMD-related lesions, including the presence of large drusen, pigmentary abnormalities, geographic atrophy, and exudative AMD, are presented in Table 1. The prevalence of AMD and the proportion of early, intermediate, and late AMD did not differ significantly between male and female participants for the whole study population and for participants aged 60+ years (χ 2 test, all P > .05), while in the age group of 50-59 years, prevalence of any AMD and of intermediate and late AMD combined was significantly higher in male than in female participants (15.9% ± 0.8% vs 12.9% ± 0.7% for any AMD; P = .006; 6.1% ± 0.5% vs 4.3% ± 0.4% for intermediate/late AMD, P = .006; χ 2 test).
| Age (Years) | Total Participants | Any AMD | Early AMD | Intermediate AMD | Late AMD | Large Drusen a | Pigmentary Abnormalities a , b | Wet AMD c | Geographic Atrophy c | |
|---|---|---|---|---|---|---|---|---|---|---|
| Men | 50-59 | 1,898 | 15.9 (14.5, 18.2) | 9.8 (8.6, 11.3) | 6.0 (5.0, 7.3) | 0.1 (0.0, 0.3) | 4.5 (3.6, 5.5) | 1.5 (1.0, 2.2) | 0.05 (0.0, 0.2) | 0.05 (0.0, 0.2) |
| 60-69 | 1,211 | 23.7 (21.5, 27.1) | 11.3 (9.7, 13.6) | 11.6 (10.1, 13.8) | 0.8 (0.4, 1.4) | 8.2 (6.8, 10.1) | 3.4 (2.5, 4.6) | 0.7 (0.3, 1.2) | 0.2 (0.0, 0.4) | |
| 70+ | 435 | 36.8 (32.2, 46.5) | 12.2 (9.4, 18.1) | 21.6 (17.9, 29.9) | 3.0 (1.6, 5.2) | 14.3 (11.3, 21.4) | 7.4 (5.1, 11.9) | 2.3 (1.0, 4.1) | 0.7 (0.0, 1.6) | |
| Total | 3,544 | 21.1 (20.0, 22.9) | 10.6 (9.7, 11.8) | 9.8 (8.9, 11.1) | 0.7 (0.5, 1.0) | 6.9 (6.2, 7.8) | 2.9 (2.3, 3.5) | 0.5 (0.3, 0.8) | 0.2 (0.1, 0.3) | |
| Women | 50-59 | 2,168 | 12.9 (11.6, 14.5) | 8.6 (7.6, 10.0) | 4.2 (3.4, 5.1) | 0.05 (0.0, 0.1) | 3.2 (2.5, 4.1) | 1.0 (0.6, 1.5) | 0 (0, 0) | 0.05 (0.0, 0.1) |
| 60-69 | 1,489 | 24.2 (22.6, 27.2) | 12.2 (10.8, 14.3) | 11.7 (10.3, 13.9) | 0.4 (0.1, 0.8) | 9.7 (8.4, 11.6) | 2.0 (1.4, 2.9) | 0.3 (0.1, 0.6) | 0.1 (0.0, 0.4) | |
| 70+ | 518 | 42.1 (38.2, 51.7) | 17.2 (14.1, 21.8) | 23.0 (20.0, 31.0) | 1.9 (0.8, 3.5) | 17.6 (14.9, 22.4) | 5.4 (3.7, 8.1) | 1.9 (0.9, 3.5) | 0 (0, 0) | |
| Total | 4,175 | 20.6 (19.4, 21.9) | 10.9 (10.1, 12.0) | 9.2 (8.4, 10.2) | 0.4 (0.2, 0.6) | 7.3 (6.6, 8.2) | 1.9 (1.6, 2.4) | 0.3 (0.2, 0.5) | 0.1 (0.0, 0.2) | |
| Men + women | 50-59 | 4,066 | 14.3 (13.2, 15.5) | 9.1 (8.3, 10.1)) | 5.1 (4.5, 5.8) | 0.1 (0.0, 0.2) | 3.8 (3.3, 4.4) | 1.3 (0.9, 1.6) | 0.02 (0.0, 0.1) | 0.05 (0.0, 0.1) |
| 60-69 | 2,700 | 24.0 (22.7, 26.1) | 11.8 (10.7, 13.1) | 11.6 (10.4, 13.0) | 0.6 (0.3, 0.9) | 9.0 (8.0, 10.2) | 2.6 (2.1, 3.3) | 0.4 (0.2, 0.7) | 0.15 (0.0, 0.3) | |
| 70+ | 953 | 39.7 (36.9, 45.4) | 14.9 (13.1, 18.6) | 22.4 (19.8, 26.9) | 2.4 (1.6, 3.5) | 16.1 (14.1, 19.7) | 6.3 (4.8, 8.2) | 2.1 (1.3, 3.2) | 0.3 (0.0, 0.7) | |
| Total | 7,719 | 20.8 (20.1, 21.9) | 10.8 (10.1, 11.5) | 9.5 (8.9, 10.2) | 0.5 (0.4, 0.7) | 7.1 (6.6, 7.7) | 2.4 (2.0, 2.7) | 0.4 (0.3, 0.6) | 0.15 (0.05, 0.2) |
a Included in intermediate AMD.
b AMD pigmentary abnormalities: any definite hyperpigmentary or hypopigmentary abnormalities associated with medium (63-125 µm) or large drusen (>125 µm) but not associated with known disease entities.
A binary regression analysis between the AMD prevalence and systematic parameters was performed, after adjusting for age ( Table 2 ). A higher prevalence of AMD was related to a higher blood monocyte and lymphocyte count, higher serum concentrations of calcium and high-density lipoprotein, and lower serum concentrations of lipoprotein a ( P < .05) ( Table 2 ).
| Non-AMD (N = 6,112) | AMD (N = 1,607) | Age-Adjusted Univariate Analysis | ||
|---|---|---|---|---|
| P Value | OR (95% CI) | |||
| Age (years) | 59.6 ± 7.5 | 64.1 ± 9.4 | / | / |
| Male (%) | 45.7 | 46.6 | .432 | 0.96 (0.85, 1.07) |
| Arterial hypertension (%) | 12.9 | 17.9 | .229 | 1.10 (0.94, 1.29) |
| Diabetes mellitus (%) | 18.8 | 22.1 | .702 | 1.03 (0.89, 1.18) |
| Chronic kidney disease (%) | 2.2 | 5.9 | .288 | 1.17 (0.87, 1.58) |
| Ever smokers (%) | 19.4 | 18.8 | .70 | 1.11 (0.65, 1.88) |
| Smoking package-years | 7.3±16.1 | 7.8±17.3 | .581 | 1.00(0.99, 1.02) |
| Weight (kg) | 66.9 ± 11.6 | 66.0 ± 11.5 | .570 | 0.99 (0.99, 1.00) |
| Height (cm) | 164.8 ± 8.2 | 163.8 ± 9.4 | .258 | 0.99 (0.99, 1.00) |
| Body mass index (kg/m 2 ) | 24.5 ± 3.2 | 24.5 ± 3.3 | .870 | 0.99 (0.98, 1.02) |
| Heart rate | 74.0 ± 9.3 | 74.6 ± 10.3 | .128 | 1.01 (0.99, 1.01) |
| Waist circumference (cm) | 83.6 ± 9.9 | 84.2 ± 9.8 | .589 | 1.00 (0.99, 1.01) |
| Hip circumference (cm) | 93.9 ± 6.0 | 93.7 ± 5.8 | .377 | 1.00 (0.99, 1.01) |
| Waist-to-hip circumference ratio | 0.89 ± 0.15 | 0.90 ± 0.08 | .818 | 1.05 (0.71, 1.53) |
| Blood monocyte (10 9 /L) | 0.41 ± 0.13 | 0.43 ± 0.15 | <.001* | 2.72 (1.82, 4.07) |
| Blood lymphocyte (10 9 /L) | 2.01 ± 0.58 | 2.03 ± 0.62 | .025* | 1.11 (1.01, 1.22) |
| Serum sodium (mmol/L) | 140.2 ± 2.1 | 140.1 ± 2.2 | .096 | 0.98 (0.95, 1.00) |
| Serum potassium (mmol/L) | 4.21 ± 0.31 | 4.23 ± 0.34 | .677 | 1.04 (0.87, 1.25) |
| Serum chlorine (mmol/L) | 104.2 ± 2.3 | 104.2 ± 2.4 | .312 | 0.99 (0.96, 1.01) |
| Serum calcium (mmol/L) | 2.34 ± 0.09 | 2.34 ± 0.09 | .005* | 2.54 (1.33, 4.86) |
| Serum phosphonium (mmol/L) | 1.12 ± 0.16 | 1.12 ± 0.15 | .213 | 1.28 (0.87, 1.88) |
| Blood urea nitrogen (mmol/L) | 5.15 ± 1.34 | 5.37 ± 1.54 | .096 | 1.03 (0.99, 1.08) |
| Creatinine (umol/L) | 70.9 ± 21.8 | 72.1 ± 19.8 | .557 | 0.99 (0.99, 1.00) |
| Uric acid (umol/L) | 331.2 ± 79.1 | 329.4 ± 79.2 | .196 | 1.00 (0.99, 1.00) |
| Highly sensitive C-reactive protein (mg/L) | 1.75 ± 3.76 | 1.88 ± 3.54 | .792 | 1.00 (0.99, 1.02) |
| Blood glucose (mmol/L) | 5.82 ± 1.58 | 5.93 ± 1.64 | .516 | 1.01 (0.98, 1.05) |
| Lipoprotein a (mg/L) | 22.4 ± 23.9 | 21.4 ± 22.9 | .040* | 0.99 (0.99, 0.99) |
| Triglyceride (mmol/L) | 1.60 ± 1.16 | 1.49 ± 1.32 | .148 | 0.96 (0.91, 1.01) |
| Total cholesterol (mmol/L) | 5.16 ± 1.0 | 5.10 ± 1.10 | .686 | 1.01 (0.96, 1.07) |
| Low-density lipoprotein (mmol/L) | 3.10 ± 0.84 | 3.04 ± 0.87 | .783 | 0.99 (0.93, 1.06) |
| High-density lipoprotein (mmol/L) | 1.44 ± 0.40 | 1.48 ± 0.43 | .002* | 1.25 (1.09, 1.43) |
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