Abstract
PURPOSE:
Primary open-angle glaucoma (POAG) is a clinical progressive neuropathy which can lead to irreversible blindness if left untreated. A low level of serum Vitamin D3 is a major risk factor for glaucoma, and hence, represents a second target for glaucoma therapy following intraocular pressure (IOP). However, there is still controversy about whether there is a direct correlation between Vitamin D3 deficiency and the risk of increased IOP. This study aims to investigate the correlation between low serum levels of 1,24-dihydroxycholecalciferol and the development of open-angle glaucoma.
METHODS:
The study included a total of forty-one patients with POAG. Patients were classified into whether they have chronic illnesses such as type 2 diabetes and hypertension. Matching control subjects of 20 healthy controls were also included in the study. Anthropometric measures and venous blood samples were taken from all participants for serum analysis of various biochemical markers including serum 1,25-dihydroxycholecalciferol (1,25(OH)2D) levels.
RESULTS:
Overall, serum Vitamin D3 levels were 15% significantly lower in the patient's cohort with open-angle glaucoma as compared to the healthy participants (P < 0.05). Among those, 63% of type 2 diabetic participants had significantly low levels of Vitamin D3 (P < 0.01). There was also a significant 70% reduction in serum Vitamin D3 levels among the hypertensive participants, (P < 0.001).
CONCLUSION:
We concluded that lower serum 1,25(OH) 2D levels were significantly associated with an increased risk of open-angle glaucoma in patients with chronic illnesses.
Keywords: 1,25-dihydroxycholecalciferol; hypertension; open-angle glaucoma; type 2 diabetes mellitus
INTRODUCTION
Glaucoma is a clinical condition characterized by progressive degenerative condition to the optic nerve and loss of retinal ganglion cells.[1] It occurs as a result of multifactorial factors including genetic and environmental factors including. Statistically, glaucoma represents the second major cause of blindness which is usually an irreversible condition.[1] Previous studies showed that an estimated 57.5 million people worldwide are affected by primary open-angle glaucoma (POAG)-affecting mostly old age group people with chronic conditions such as diabetes and cardiovascular disease.[1,2]
Glaucoma can be of several types, POAG, angle-closure glaucoma, congenital glaucoma, childhood glaucoma, and secondary glaucoma. Sixty percent to seventy percent of the cases are of POAG. The condition is usually occurred bilateral,[2] and it is distinguished from other glaucoma types by the evidence of characteristic glaucomatous optic nerve and visual field damage; occurs in adult-onset; open type with normal-appearing anterior chamber angles; and the absence of secondary causes such as trauma.[2,3]
The main pathology for POAG is unknown, but it is thought to be related to elevated resistance to the outflow of aqueous humor through the trabecular meshwork. This progressive condition may result in glaucomatous optic nerve damage in susceptible patients. Early stages of the disease include nonelevated intraocular pressures (IOP); hence, it may be asymptomatic. However, in advanced conditions, patients will suffer from diminished vision. If left untreated, a large proportion of patients will suffer total optic nerve atrophy and blindness.[3,4]
To identify controllable risk factors other than IOP, many researchers have investigated the systemic factors that affect the development of glaucoma. However, the mechanisms underlying this association remain unclear. This study aims to illustrate the relationship between POAG and Vitamin D 1,25-dihydroxycholecalciferol (1,25(OH)2D) deficiency.
METHODS
This was a cross-sectional study that included forty-one participants who were clinically diagnosed with POAG. A matching group of 20 subjects without glaucoma were also included in this study. Participants were attended the Ophthalmology Clinic at Al-Diwaniyah General Hospital, for the period between June 2021 and March 2022. The study was reviewed and approved by the Human Research Ethics Committee, College of Pharmacy, Al-Qadisiyah University.
Venous blood samples were collected to measure various biomarkers including the serum levels of Vitamin D, using the automated MINDRAY CL-900i, Shenzhen, China.
Statistical analysis: Data were analyzed using the Statistical package for social sciences (SPSS) version 22, IMB, New York, United States. Numeric variables were presented as mean ± standard deviation. Categorical variables were expressed as numbers and percentage. Student's t-test (one side) was also performed to identify any significance between the mean values of the two study groups. The level of significance is considered at P ≤ 0.05.
RESULTS
The demographic characteristics of the study groups are shown in Table 1. Forty-one participants with POAG were included in this study. A matching of twenty control subjects was also included in the study. Of the POAG study group, 63% were diagnosed with type 2 diabetes mellitus, while only 48.7% had hypertension, Table 1.
Table 1.
Demographic characteristics of study groups (Iraqi patients with primary open-angle glaucoma)
| Characteristic | Group 1: Patients with OAG | Group 2: Healthy Control | Total | P |
|---|---|---|---|---|
| Number of cases | 41 | 20 | 61 | - |
| Age | ||||
| Mean±SD | 54.5±6.29 | 52.0±5.5 | 53.6±3.7 | 0.494”? |
| Range | 41–62 | 39–59 | 39–62 | NS |
| Gender | ||||
| Male | 15 | 8 | 23 | 0.888* |
| Female | 26 | 12 | 48 | NS |
| Diagnosis | ||||
| POAG | 41 | 0 | 41 | |
| Type 2 diabetes | 26 | 13 | 49 | NS |
| Hypertension | 20 | 11 | 31 | NS |
| No underlying medical condition | 0 | 7 | 7 | 0.001”? |
| Vitamin D Levels | 10.2±4.9 | 31.5±1. 5 | 19.4±7.8 | 0.001”? |
*Chi-square test, ”?Independent samples t-test. Group 1: Patients with POAG with and without T2DM and hypertension, Group 2: Healthy control participants with or without T2DM and hypertension. SD: Standard deviation, NS: Not significant, OAG: Open-angle glaucoma, POAG: Primary OAG, DM: Diabetes mellitus
Overall, there was a significant reduction in serum levels of Vitamin D among the OPAG study groups as compared to the control group, P = 0.001, Table 1. Among the participants with type 2 diabetes, 80.7% had a significant reduction of Vitamin D levels below 20 ng/ml, Table 2.
Table 2.
Primary open-angle glaucoma participants with type 2 diabetes mellitus
| Number of participants | Vitamin D levels (ng/mL) | IOP (mmHg) |
|---|---|---|
| Females: 6 Males: 8 |
8–10 | 17–27 6–27.5 |
| Females: 5 Males: 2 |
10.1–20 | 18–27 15–25 |
| Females: 4 Males: 1 |
>20 | 15–27.3 21–24 |
IOP: Intraocular pressure
While 75% of participants with hypertension had a significant low serum level of Vitamin D below 20 ng/ml, Table 3.
Table 3.
Primary open-angle glaucoma participants with hypertension
| Number of participants | Vitamin D levels (ng/mL) | IOP (mmHg) |
|---|---|---|
| Females: 8 Males: 4 |
8–10 | 17–27.3 21–27.5 |
| Females: 2 Males: 1 |
10.1–20 | 18–22.3 16–18 |
| Females: 3 Males: 2 |
>20 | 14–27.3 14–19 |
IOP: Intraocular pressure
In addition, there were significant differences in the levels of Vitamin D and the IOP between the two genders. Our data showed a significant negative association in females as compared to males. Females with lower Vitamin D levels were at a significantly greater risk of glaucoma compared with those with higher Vitamin D levels, Tables 2 and 3.
DISCUSSION
Previous studies report a variation in the levels of serum Vitamin D, and increased IOP.[5,6,7,8,9] Two previous studies showed an inverse association between serum levels of Vitamin D and increased IOP. Kutuzova et al. in 2012 did a study on monkeys with topical application of 1,25(OH)2D; and reduction of IOP in one-fifth of the cases.[10]
In addition, there are several studies which indicated a significant correlation between serum levels of Vitamin D and glaucoma development.[5,6,7,8] However, there was no detailed information provided on the severity of the Vitamin D deficiency. Ayyagari et al., in 2019, looked into this issue and they suggested that 1,25(OH)2D has an independent effect on the development of POAG, with no relation to the IOP.[5]
It is worth mentioning that 1,25(OH)2D levels could affect the IOP through genetic manifestation, which may affect the rate of production of aqueous humor or it could modulate its outflow.[11] Besides, 1,25(OH)2D has been found to act as an immune modulatory factor.[12] This may ultimately result in reducing the severity of inflammation in neurodegenerative disorders with Vitamin D supplementation.[12] Accordingly, Vitamin D supplementation may provide beneficial effects in patients with neurodegenerative disorders.[13] Treatments with the biologically active form of Vitamin D resulted in reduced production of reactive oxygen species and improve the levels of inflammation.[14]
POAG may also occur due to altered Vitamin D metabolism, or due to low levels. This is because previous studies have showed a significant correlation between these two conditions. Hence, it is essential to assess Vitamin D levels in patients with glaucoma and aim to manage low levels in those patients.[15]
CONCLUSION
Lower serum levels of Vitamin D were significantly associated with an elevated risk of glaucoma in our patients. The females were more significantly affected as compared to males. Our data suggest that Vitamin D status independently affects the pathophysiology of glaucoma in women. Although the exact mechanism is not very clear, considering both the results of previous reports and the present study, Vitamin D influences the pathophysiology of glaucoma as a secondary aggravating factor rather than a primary cause. With the presence of a primary factor, a low Vitamin D level might render the optic nerve or its environment more vulnerable to glaucomatous insult.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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