The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron

Introduction

We read with interest the article by Wang et al. ¹ in the February issue, in which they used self-reported glaucoma in the National Health and Nutrition Examination Survey (NHANES) population to find an association between the prevalence of glaucoma and the highest quintiles of the intake of calcium and iron supplementation. When we tried to replicate their analysis using the same NHANES 2007 and 2008 data, we noticed that there might be typos in quintiles of supplemental calcium and iron intake in their report, as shown in Table 1. 

Table 1. 

 

Quintiles of Supplemental Calcium and Iron Intake in the 2007 and 2008 NHANES Data

Quintiles of Supplemental Calcium and Iron Intake Reported in Wang et al.1	Quintiles of Supplemental Calcium and Iron Intake Used to Replicate Results in Wang et al.1
Calcium	Calcium
No intake	No intake
1st Quintile, >0 and  <100 mg/day	1st Quintile, >0 and  ≤100 mg/day
2nd Quintile, ≥100 and  <200 mg/day	2nd Quintile, >100 and  ≤200 mg/day
3rd Quintile, ≥200 and  <375 mg/day	3rd Quintile, >200 and  ≤375 mg/day
4th Quintile, ≥375 and  <800 mg/day	4th Quintile, >375 and  ≤800 mg/day
5th Quintile,  ≥800 mg/day	5th Quintile,  >800 mg/day
Iron	Iron
No intake	No intake
1st Quintile, >0 and  <6 mg/day	1st Quintile, >0 and  ≤6 mg/day
2nd Quintile, ≥6 and  <15 mg/day	2nd Quintile, >6 and  ≤15 mg/day
3rd Quintile, ≥15 and  <18 mg/day	3rd Quintile, >15 and  ≤18 mg/day
4th and 5th Quintiles,  ≥18 mg/da	4th and 5th Quintiles,  >18 mg/day

 NHANES, the National Health and Nutrition Examination Survey.

In addition, our analyses of the same NHANES data do not support the statement by the authors that “there is no compelling reason to believe that individuals taking a high level of supplementary oxidants would be systematically more or less likely to accurately recall a glaucoma diagnosis than would those taking lower levels of such supplementation.” In our analyses, a clinical diagnosis of glaucoma was defined as (1) having either two or more abnormal points in at least one eye on the frequency doubling threshold tests (N30-5 FDT) on two tests in the same eye ^2,3 along with a cup-to-disc ratio (CDR) in at least one eye on the optic disc photographs or CDR asymmetry between eyes of the same subject of ≥97.5th percentile of the normal NHANES population, or (2) having a CDR or CDR asymmetry between eyes of the same subject of ≥99.5th percentile of the normal NHANES population among subjects who did not have complete FDT results, ⁴ after excluding subjects who had a documented alternative explanation for CDR findings (dysplastic disc or marked anisometropia) or for the visual field defect (retinal vascular disease, macular degeneration, or cerebrovascular disease). ⁴ Based on this definition, 36% of 72 subjects who self-reported having glaucoma had a clinical diagnosis of glaucoma. Interestingly, individuals who did not report themselves as having glaucoma were less likely to report the supplemental intake of calcium and iron whether or not they had a clinical diagnosis of glaucoma. For example, 27.5% and 28.3% of those without self-reported glaucoma and with and without a clinical diagnosis of glaucoma, respectively, took calcium supplementation >200 mg/day versus 39.0% and 43.8% of those with self-reported glaucoma and with and without a clinical diagnosis of glaucoma, respectively, who took calcium supplementation >200 mg/day. The same trends were seen with supplemental iron intake (Table 2). 

Table 2. 

 

Percentages of Supplemental Nutrient Intake among Participants in NHANES 2007 and 2008 with and without Self-Reported Glaucoma and Clinical Diagnosis of Glaucoma*

Supplemental Calcium and Iron Intake	Self-Reported Glaucoma with Clinical Diagnosis of Glaucoma (n = 31)	Self-Reported Glaucoma without Clinical Diagnosis of Glaucoma (n = 41)	No Self-Reported Glaucoma with Clinical Diagnosis of Glaucoma (n = 111)	No Self-Reported Glaucoma without Clinical Diagnosis of Glaucoma (n = 1857)
Calcium
No intake	49.9	25.9	50.5	48.3
1st Quintile, >0 and ≤100 mg/day	4.5	27.7	7.9	12.0
2nd Quintile, >100 and ≤200 mg/day	6.6	2.6	14.1	11.5
≥3rd Quintile, >200 mg/day	39.0	43.8	27.5	28.3
Iron
No intake	74.4	76.3	83.4	78.7
1st Quintile, >0 and ≤6 mg/day	0	3.3	1.2	4.5
2nd Quintile, >6 and ≤15 mg/day	3.8	1.5	5.1	5.2
≥3rd Quintile, >15 mg/day	21.7	18.9	10.3	11.7

 NHANES, the National Health and Nutrition Examination Survey.

*  All percentages are weighted estimates of the US population characteristics, after accounting for the NHANES' complex sampling design.

Furthermore, in our evaluation of the serum levels of calcium and iron instead of the self-report of supplemental calcium and iron intake, there were no statistically significant associations between self-reported glaucoma and highest quintiles of albumin-corrected serum calcium (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.7–1.7), serum iron (OR 1.6, 95% CI 0.9–2.7), or serum ferritin (OR 2.0, 95% CI 0.1–31.6) in the fully adjusted (age, sex, ethnicity, socioeconomic status, comorbidities, and general health condition) logistic regression models. Similarly, there were no statistically significant associations between clinical diagnosis of glaucoma and highest quintiles of albumin-corrected serum calcium (OR 1.0, 95% CI 0.4–2.2), serum iron (OR 0.7, 95% CI 0.4–1.5), or serum ferritin (OR 0.1, 95% CI 0.005–1.8) in the fully adjusted logistic regression models. 

The above findings suggest that the knowledge of a glaucoma diagnosis may drive supplement use, as is found in other diseases, ^5–7 and that the use of self-report for a diagnosis of glaucoma as an outcome should be done cautiously. In addition, there was no statistically significant association between the serum levels of calcium, iron, or ferritin and the clinical diagnosis of glaucoma.