Glaucoma is a chronic neuropathy that leads to progressive atrophy in the optic nerve head, degeneration in retinal ganglion cells, and visual field losses and causes visual loss due to optic atrophy when not treated. These changes usually exist together with intraocular pressure elevation (IOP) [
Anemia is clinically defined as a blood hemoglobin or hematocrit value under the valid reference range for the patient [
The aim of this study was to determine the IDA frequency in glaucoma patients which is a neurodegenerative disease. We compared the IDA incidence in the normal population and the glaucoma patients to evaluate whether detecting and treating the anemia could slow down or stop the progress of the disorder.
A total of 131 glaucoma patients who were being followed up at our Glaucoma Unit and met the study inclusion criteria and 130 healthy individuals were included in the study. The healthy individuals were included in Group 1 and the patients with glaucoma in Group 2.
The study was conducted in accordance with the ethical standards stated in the Declaration of Helsinki and approved by our institutional ethics board. The patients were informed on the purpose of the study and the procedures to be performed in detail and consent was obtained.
Each subject underwent a full ophthalmic examination, including best-corrected visual acuity, IOP measurement with a Goldmann applanation tonometry, slit-lamp biomicroscopy, gonioscopy, stereoscopic fundus evaluation on the slit lamp using a 90-diopter lens, and visual field examination with Humphrey Field Analyzer (HFA) (Humphrey-Zeiss Systems, Dublin, CA, USA) Swedish Interactive Threshold Algorithm (SITA) 30–2 test. Each test was performed on the same machine with the same technician. The tests were repeated in the same week if an abnormality was found in the reliability indexes (fixation loss >20%, false positive response >25%, false negative response >25%). Both test strategies were investigated in terms of test duration and mean deviation (MD).
Inclusion criteria in normal subjects were IOP under 21 mmHg, normal optic disc, and visual field examination and the lack of any systemic disease or systemic drug use. Inclusion criteria in glaucoma patients were a minimum of one-year follow-up at our clinic, the presence of glaucomatous damage in the optic disc (glaucomatous cupping and/or glaucomatous optic nerve head changes), the use of at least one antiglaucomatous agent, and presence of glaucomatous visual field changes in a minimum of two computerized visual field examinations (30-2 SITA). History of laser treatment or trauma, presence of cornea or lens pathology, presence of uveitis, posterior segment pathology, neurodegenerative diseases of the central nervous system, and systemic diseases such as diabetes that can predispose to such disorders were accepted as exclusion criteria for both groups.
Erythrocyte parameters were studied with the Beckman Coulter LH 780, biochemical data, Fe and IBC with the
Quantitative data were presented as mean ± standard deviation (SD) or median (min-max). Compliance with a normal distribution was determined with the Shapiro-Wilk test. The homogeneity of the variances was evaluated with the Levene test. One-way variance analysis and the Kruskal-Wallis test were used for statistical analyses and the
Patients who fulfilled the entry criteria were enrolled in this prospective, controlled study. There were 130 normal subjects (63 females, 67 males) in control group and 131 glaucoma patients (74 females, 57 males). The mean age of the normal subjects was 50,
There were no statistically significant differences in the erythrocytes parameters and the iron status indicator values between the groups. (Table
Comparisonof Fe, TIBC and ferritin valuesbetween Group 1 and Group 2.
| | | |
---|---|---|---|
| 13.73±1.8 | 13.48±1.7 | 0.21 |
| 4.75±0.80 | 4.68±0.79 | 0.51 |
| 40.94±5.29 | 40.41±4.93 | 0.40 |
| 87.20±7.87 | 87.62±7.19 | 0.62 |
| 33.13±2.12 | 32.90±1.40 | 0.30 |
| 29.35±3.26 | 28.97±3.52 | 0.35 |
| 14.29±1.81 | 13.81±2.28 | 0.06 |
| 74.38±36.2 | 71.82±33.89 | 0.55 |
| 269.67±64.15 | 273.12±66.26 | 0.69 |
| 70.60 (1-240) | 70.07(2-294)) | 0.95 |
| 241.22±80.82 | 268.39±72.00 | |
We detected 26 IDA patients in normal subjects and 24 patients with IDA in glaucoma group. No statistically significant difference was observed between the groups in terms of the number of patients with IDA (p=0.48, p>0.05, respectively).
The glaucoma group was consisting of primer open angle patients glaucoma (POAG) (n=57), pseudoexfoliation glaucoma (PEXG) patients (n=43), and normotensive glaucoma (NTG) patients (n=31). The number of patients with IDA was fourteen in POAG, five in PEXG, and seven in NTG patients. No statistically significant difference was found between the glaucoma subgroups regarding the IDA incidence (p=0.251, p>0.05).
No statistically significant difference was found regarding the number of antiglaucomatous agents used between the patients with and without IDA in glaucoma patients (p=0.68, p>0.05). Similarly, changes in the mean deviation (MD) in the right and left eye 30-2 computerized visual fields obtained at intervals of at least 6 months in these patients were not found to be statistically significant (p=0.44, p=0.21, p>0.05, respectively) (Table
Comparisonofthenumber of antiglaucomatous agents used and changes of visual fields patients in glaucoma patients according to presence of anemia.
| Patients With Anemia (Mean ± SD) | Patients Without Anemia (Mean ± SD) | P value |
---|---|---|---|
The number of antiglaucomatous agents used | 2.36±0.7 | 2.85±1.3 | 0.68 |
MD Right eye | 0.08±1.9 | -0.55±2.6 | 0.44 |
MD Left eye | -2.21±4.3 | -0.24±1.5 | 0.21 |
No statistically significant difference was found between the erythrocyte parameters and the iron status indicator values of the patients in glaucoma patients according to the number of antiglaucomatous agents used (Table
Comparisonthe hemogram, iron, TIBC, and ferritin valuesaccording to thenumber of antiglaucomatous agents used in Group 2.
| | | | | P value |
---|---|---|---|---|---|
| 13.48±1.50 | 12.85±1.90 | 13.45±2.04 | 14.11±1.54 | 0.14 |
| 4.87±0.55 | 4.46±0.45 | 5.00 ±1.73 | 4.83±0.46 | 0.28 |
| 39.66±4.48 | 38.71±5.67 | 39.68±6.43 | 42.11±3.25 | 0.16 |
| 83.69±4.53 | 86.66±6.84 | 88.07±10.27 | 88.04±6.56 | 0.34 |
| 33.25±2.09 | 32.77±1.00 | 32.56±1.76 | 32.87±1.32 | 0.65 |
| 28.40±2.15 | 28.85±2.40 | 29.52±3.87 | 27.48±6.02 | 0.69 |
| 13.38±1.33 | 14.02 ±1.60 | 13.72±1.43 | 13.39±1.06 | 0.39 |
| 69.69±31.24 | 74.42±32.25 | 75.44±42.62 | 84.00±41.39 | 0.71 |
| 293.07±65.82 | 284.95±80.11 | 261.22±66.25 | 253.81±52.5 | 0.25 |
| 69.90 | 67.46 | 67.58 | 70.88 | 0.93 |
| 230.77±50.99 | 287.79±85.93 | 257.11±38.90 | 264.67±55.28 | 0,07 |
There was no statistically significant difference between the erythrocytes parameters and the iron status indicator values according to the duration of glaucoma in glaucoma patients, but the difference in MCH values was statistically significant (p=0.03, p<0.05) (Table
Comparison of the hemogram, iron, TIBC, and ferritin values according to the duration of glaucoma in Group 2.
| | | | | |
---|---|---|---|---|---|
| 12.71±2.03 | 13.36±1.73 | 13.45±1.68 | 14.09±1.70 | 0.13 |
| 4.72±1.24 | 4.63±0.62 | 4.98±1.11 | 4.67±0.64 | 0.64 |
| 37.72±5.50 | 40.43±5.31 | 40.32±5.32 | 41.30±4.52 | 0.18 |
| 84.23±7.41 | 85.56±8.00 | 86.38±6.42 | 90.30±7.30 | 0.058 |
| 32.54±1.45 | 32.58±1.53 | 32.95±1.83 | 33.10±1.28 | 0.59 |
| 28.35±2.89 | 26.48±6.83 | 28.47±2.34 | 30.27±2.6 | |
| 14.29±1.90 | 13.69±1.40 | 13.56±1.18 | 13.27±0.86 | 0.14 |
| 75.45±31.34 | 71.07±30.93 | 76.05±36.65 | 81.32±45.97 | 0.87 |
| 277.88±59.48 | 286.86±47.19 | 281.86±73.99 | 247.86±77.68 | 0.25 |
| 21 (3-250) | 26 (3-250) | 58 (5-183) | 71 (13-254) | 0.14 |
This study was undertaken to determine whether the IDA frequency is higher in glaucoma patients than the normal population. We could not find any statistically significant difference between the groups according to the IDA frequency. Although ocular findings of severe anemia have been defined more commonly in recent years, we could not find any study investigating the relationship between glaucoma and IDA. The severity of retinal findings is consistent with the severity of the anemia. Retinal ischemia findings of optic disc edema, retinal hemorrhages, and soft exudes can be seen in certain patients with anemia [
Considering that IDA may accelerate the visual field loss in patients with glaucoma, we obtained two separate 30-2 visual field tests with an interval of six months in patients with and without iron deficiency anemia but the difference in mean deviations in visual field tests was not found to be statistically significant. We also showed that the need for antiglaucomatous agents also did not increase in glaucoma patients with IDA. A possible explanation can be the severity of anemia in our study. The range of hemoglobin level in anemia patients was 9-12 g/dl in normal group and 9.2-12 g/dl in glaucoma group. As shown in previous reports ocular side effects of anemia were seen in severe anemia cases. Retinal findings can be seen when the hemoglobin levels were less than 6 g/dl [
We also demonstrated that the anemia frequencies in POAG, NTG, and PEXG are the same. Goldberg et al. studied the systemic factors including hemoglobin concentration and hematocrit levels in NTG and ocular hypertension patients. Similar to our study they found out that the hemoglobin and hematocrit levels were the same in NTG and ocular hypertension patients [
Iron is an essential element for many functions in the cell like oxygen transport, myelin synthesis, and oxidative phosphorylation. On the other hand if the iron is found in excess amount it can cause reactive oxygen species formation that can cause cellular degeneration and damage [
However, the neuronal affinity of iron and ferritin may increase in glaucoma patients. Considering that the serum iron and ferritin level may not be correlated with the brain iron and ferritin levels, we believe that detailed neuropathology studies investigating brain iron and ferritin levels in glaucoma patients are required.
We therefore concluded that it was not necessary to change the frequency of follow-ups and number of antiglaucomatous agents in glaucoma patients who are found to have IDA.
The strengths of this study are that it is a prospective, controlled study. Also, to the best of our knowledge, this is the first study that demonstrates the IDA frequency in glaucoma. Limitation of our study is that the study includes mild and moderate anemia patients. Large sample sized studies with severe anemia patients are needed to better understand the effect of anemia on glaucoma.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.