Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 2  |  Page : 856-863

Effect of vitamin D on the efficacy of topical artificial tears in patients with dry-eye disease


1 Department of Ophthalmology, Faculty of medicine, Menoufia University, Shibin El Kom, Menoufia, Egypt
2 Ophthalmology Hospitals, Shibin El Kom, Menoufia, Egypt

Date of Submission13-Nov-2021
Date of Decision05-Dec-2021
Date of Acceptance06-Dec-2021
Date of Web Publication27-Jul-2022

Correspondence Address:
Dina G. H. Abd Elmonem
Ophthalmology Hospitals, Shibin El Kom, Menoufia
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_245_21

Rights and Permissions
  Abstract 


Background
The tear film is a complex mix of electrolytes, proteins (lipocalins, lactoferrin, transferrin, defensin, and lysozyme), phospholipids, oligopeptides, glycopeptides, and immunoglobulins.
Objective
The aim was to investigate the efficacy of topical carbomer-based lipid-containing artificial tears and hyaluronate in patients with dry-eye disease (DED) based on serum 25-hydroxy vitamin D (25HD) levels and cholecalciferol (vitamin D) supplementation.
Patients and methods
A nonrandomized clinical trial study was conducted on 42 patients with DED by Schirmer tear-secretion test (mm) who were examined by Ophthalmology Department, Menoufia University Hospital, Egypt, during the study period from March 2020 to March 2021.
Results
Serum 25HD levels were significantly decreased among vitamin D deficiency (VDD) group than non-VDD group at baseline and after 2 weeks of treatment. International Ocular Surface Disease Index grade was significantly increased among the VDD group after 2 weeks and 4 months of treatment as compare with non-VDD group (P < 0.05). Tear break-up time was significantly decreased among VDD group than non-VDD group after 4 months of treatment (P = 0.015). Lid hyperemia was significantly increased among the VDD group (2.00 ± 0.853) than non-VDD group (1.29 ± 0.659) after 4 months of treatment (P = 0.029). While Schirmer tear-secretion test was significantly decreased among the VDD group (5.75 ± 1.603) than non-VDD group (7.18 ± 1.188) after 2 weeks of treatment (P = 0.009). While Schirmer tear-secretion test did not show any significant difference between the VDD group (6.50 ± 1.567) and non-VDD group (7.75 ± 2.066) after 4 months of treatment.
Conclusion
The effect of topical topical carbomer-based lipid-containing artificial tears and hyaluronate was dependent on serum 25HD levels. Cholecalciferol supplementation enhanced the efficacy of topical treatment and may be a useful adjuvant therapy for patients with DED refractory to topical lubricants.

Keywords: carbomer, disease, dry eye, hyaluronate, topical artificial tears, vitamin D


How to cite this article:
Zaky MA, Marey HM, Elmonem DG, Fayed A M. Effect of vitamin D on the efficacy of topical artificial tears in patients with dry-eye disease. Menoufia Med J 2022;35:856-63

How to cite this URL:
Zaky MA, Marey HM, Elmonem DG, Fayed A M. Effect of vitamin D on the efficacy of topical artificial tears in patients with dry-eye disease. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:856-63. Available from: http://www.mmj.eg.net/text.asp?2022/35/2/856/352171




  Introduction Top


The tear film is a thin fluid layer providing a smooth surface over the cornea. It is composed of 3 layers: the innermost mucin layer, an aqueous layer, and the outermost lipid layer[1]. Furthermore, the tear film is a complex mix of electrolytes, proteins (lipocalins, lactoferrin, transferrin, defensin, and lysozyme), phospholipids, oligopeptides, glycopeptides, and immunoglobulins. The tear film also includes a variety of surfactants, including surfactant proteins A and D. It is essential for the health of the eye that tear-film components work in harmony[2]. Tear-film stability is, therefore, the result of the harmonious balance between tear components. A disturbance in one or more of the tear layers leads to the occurrence of dry-eye disease (DED)[3]. DED is a disease of the tear film and ocular surface, leading to ocular discomforts and pain (3). The pathophysiology of DED includes tear-film instability and ocular surface inflammation[2].

Vitamin D refers to a group of fat-soluble secosteroids responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc. It is not strictly a vitamin, and may be considered a hormone as its synthesis and activity occur in different locations. Although commonly known for its role in calcium homeostasis, vitamin D also plays important roles in immune regulation, proliferation, differentiation, apoptosis, and angiogenesis. Vitamin D deficiency (VDD) and genetic variations may cause a wide range of ocular pathologies, such as myopia, age-related macular degeneration, diabetic retinopathy, uveitis, and dry eye[4].

VDD may also cause dry eye, as studies have reported dry-eye syndrome to be a localized autoimmune disease, and researchers recently hypothesized that vitamin D plays a role in the disorder because of its anti-inflammatory properties[5]. Dry eye, described by increased osmolarity of the tear film and inflammation of the ocular surface, causes ocular discomfort, visual disturbance, and tear-film instability with potential damage to the ocular surface (hyperosmolarity provides proinflammatory stress to the ocular surface)[6]. Therefore, the aim of this study was to investigate the efficacy of topical carbomer-based lipid-containing artificial tears (CLAT) and hyaluronate (HU) in patients with DED based on serum 25-hydroxyvitamin D (25HD) levels and cholecalciferol (vitamin D) supplementation.


  Patient and methods Top


Participants

This was a nonrandomized clinical trial study that was conducted on 42 patients with DED by Schirmer tear-secretion test (mm), who were examined by Ophthalmology Department, Menoufia University Hospital, Egypt, during the study period from March 2020 to March 2021. Ethical consideration: all participants were volunteers. All of them signed written informed consent after explaining the aim of the study. Approval of the study protocol was obtained by the Ethical Scientific Committee of Menoufia Faculty of Medicine (NO: 8/2020 OPHT). All participants included in the study were divided into two groups as follows: case group VDD included 12 patients with DED (<12 ng/ml) and control group (non-VDD) included 28 patients who did not have any eye pathology and who were age-matched and sex-matched with the patient group (≥12 ng/ml). Inclusion criteria: both sex patients with DED who were treated with a CLAT formulation and 0.15% sodium HU and their tear break-up time (TBUT) less than 10 s and Shirmer test is less than 10 mm for 5 min. Exclusion criteria included patients who were excluded if they are presented with primary Sjogren syndrome or other systemic rheumatic disease history, vitamin B12 deficiency, a history of smoking, current or recent drug use that could affect the lacrimal functional unit, active ocular infection or allergy, ocular surface scarring, corneal dystrophies, sclerites, previous eye surgery, current contact-lens use, history of autoimmune diseases, corneal surgery and corneal diseases, and the presence of corneal opacity. All of the patients were subjected to the following: general and medical history of all the cases was taken, initially, patients completed the International Ocular Surface Disease Index (OSDI) survey using OSDI Questionnaire, all participants were undergoing a full ophthalmological examination in the same order, including visual acuity assessment, standardized slit-lamp examination, and fundus examination. Best-corrected visual acuity testing using standard Landolt visual acuity chart and converted into logarithm of the minimal angle of resolution (log MAR) units for statistical analysis. Ocular examination included (external eye examination included) [eyelid skin, for rosacea, seborrhea, tear glands, swelling in the lateral upper-lid area (eyelids, ectropion, entropion, eversiopuncti lacrimalis, lid defect, scars, and redness/swelling of lid margin), (eyelid closure, voluntary, involuntary, and Bell's phenomenon), proptosis (blinking, frequency, and increased (normal value approx. 12 blinks per minute)] and Meibomian glands, sufficient in number, and gland openings blocked G-corneal sensation assessed when trigeminal nerve dysfunction was suspected (history of HZO) and slit-lamp examination: It includes: [examination for tear-film abnormalities including (tear-meniscus height: in dry eye, it is concave, decreased in volume, and may be absent in severe cases (normal tear-meniscus height = 268 ± 68 μm), tear-meniscus floater: they could be seen as tiny bits of debris in the upper and lower tear menisci and mucous strands), conjunctival surface examination including (dilated vessels, strings of mucus, loss of luster, and elasticity of the conjunctiva), papillary conjunctivitis that was a nonspecific sign results from irritation (nodular, sectorial, diffuse episcleritis, and scleromalacia provided evidence for associated connective-tissue disease], subepithelia fibrosis, and keratinization of the conjunctiva. We inspect carefully the inferior and superior fornices, looking for symblepharon in cases of cicatrizing diseases, the lid parallel conjunctival folds (conjunctivochaisis) and Bitot's spot, corneal examination to detect, including (punctate epitheliopathy, corneal filaments: they are short tails (usually <2-mm filaments), mucous plaques: they were semitransparent, white-to-gray slightly elevated lesions of different shapes and sizes) and (corneal thinning and perforation: it can complicate keratoconjunctivitis sicca, especially in the presence of rheumatoid arthritis), Anterior-chamber examination: in patients with connective-tissue disease for anterior uveitis detection and fundus examination including (as a routine examination in hypertensive and diabetic patients, in patients with connective-tissue disease for posterior uveitis detection, and by slit-lamp biomicroscopy)].

The dry-eye examinations were performed in a specific order: the TBUT, corneal fluorescein staining scoring, and the anesthetized Schirmer test: the testing for all participants was performed in the same room at the same stable conditions (humidity, temperature, etc.). The interval between each of the measurements/tests on the ocular surface is at least 5 min 1. The dry-eye examinations were performed in a specific order, the TBUT test, fluorescein is applied into the lower fornix and the patient is first asked to blink several times and then to avoid blinking. A broad slit-lamp beam with cobalt-blue filter is used to scan the tear film. The presence of black spots or lines indicates the appearance of dry spots in the tear film. TBUT is the interval between the blink and the appearance of the first randomly distributed dry spot. A TBUT of less than 10 s is considered abnormal. Corneal fluorescein staining scoring using the Oxford grading schema as shown[7].

Special tests

Measurement of serum vitamin D level was done to calculate the needed dose for supplementation.

Methods

We used oral method 2000 IU of cholecalciferol every day and were checked at the outpatient clinic. Patients who did not want to take any supplements were observed only with eye drops and without supplementation. The effects of cholecalciferol supplementation on the tear film and ocular surface were evaluated 2 weeks later. OSDI score, visual analog pain scale (VAPS) score, lid hyperemia, TBUT, corneal fluorescein staining score, and Schirmer test was compared between baseline and 2 weeks post-treatment after topical applications and between before and after four months of cholecalciferol supplementation. DED symptoms were quantified using the OSDI questionnaire and VAPS score. Individuals were asked to complete questionnaires about the DED symptoms during a 1-week recall period. TBUT and CFSS evaluation was performed as previously described. A fluorescein strip was used to measure the TBUT and CFSS.

Vitamin D assessment using human vitamin D-binding protein ELISA (sensitivity: 2.168 ng/ml, dynamic range: 6.25–200 ng/ml). The principle of the double-antibody sandwich ELISA: in this assay, the VDBP present in samples reacts with the anti-VDBP antibodies that have been adsorbed to the surface of polystyrene microtiter wells. After the removal of unbound proteins by washing, anti-VDBP antibodies conjugated with horseradish peroxidase, are added. These enzyme-labeled antibodies form complexes with the previously bound VDBP. Following another washing step, the enzyme bound to the immunosorbent is assayed by the addition of a chromogenic substrate, 3,3′, 5, 5′-tetramethylbenzidine. The quantity of bound enzyme varies directly with the concentration of VDBP in the sample tested; thus, the absorbance, at 450 nm, is a measure of the concentration of VDBP in the test sample. The quantity of VDBP in the test sample can be interpolated from the standard curve constructed from the standards, and corrected for sample dilution. The VAPS is a scale used to determine the pain intensity experienced by individuals. It consists of a line, ~10–15 cm in length, with the left side signifying no pain with a smiling-face image and the right side signifying the worst pain ever with a frowning-face image[8]. Based on the distribution of pain VAPS scores in postsurgical patients (knee replacement, hysterectomy, or laparoscopic myomectomy) who described their postoperative pain intensity as none, mild, moderate, or severe, the following cut points on the pain VAPS have been recommended: no pain (0–4 mm), mild pain (5–44 mm), moderate pain (45–74 mm), and severe pain (75–100 mm)[8].

Statistical analysis

Data were collected, tabulated, and statistically analyzed using Statistical Package of Social Science (SPSS) version 235 (SPSS Inc. Released 2015. IBM SPSS Statistics for Windows, version 20; IBM Corp., Armonk, NY). Descriptive data were presented in the form of mean, SD, range, and qualitative data were presented in the form of numbers and percentages. Analytical statistics: χ2, Spearman correlation, and receiver-operating characteristic curves. The results were considered significant if P less than or equal to 0.05 and highly significant if P less than or equal to 0.01.


  Results Top


A total of 42 patients were included in this study, age ranged from 24 to 78 years with mean value 55.10 ± 12.576 years. Most of the studied patients (52.3) were females. More than half of them were from rural places (66.7%). Also, the mean level of 25-hydroxyvitamin D (25HD) among the studied patients ranged from 8 to 24 ng/ml with mean of 15.75 ± 5.764 ng/ml [Table 1].
Table 1: Demographic data and 25-hydroxy vitamin D level among the studied patients

Click here to view


There was a significant difference between the studied groups regarding sex (P < 0.05). On the other hand, there was no significant difference between the studied groups regarding residence (P > 0.05) [Table 2].
Table 2: Comparison between the studied groups regarding demographic data (n=42)

Click here to view


Serum 25HD levels were significantly decreased among VDD group than non-VDD group at baseline and after 2 weeks of treatment (P < 0.001). There was no significant difference between the studied groups regarding serum 25HD levels after 4 months (P = 0.115). Also, serum 25HD levels were significantly improved after 2 weeks and 4 months compared with baseline among the studied groups (P < 0.001) [Table 3].
Table 3: Comparison between the studied groups regarding 25-hydroxy vitamin D levels before and after 2 weeks and 4 months of treatment (n=42)

Click here to view


OSDI grade was significantly increased among the VDD group after 2 weeks and 4 months of treatment as compared with non-VDD group (P < 0.05). Also, OSDI grades were significantly decreased after 2 weeks and 4 months of treatment compared with baseline among the studied groups (P < 0.001). VAPS did not show any significant differences between VDD group and non-VDD group after 2 weeks and 4 months of treatment (P > 0.05). Also, VAPS grades were not significantly different after 2 weeks and 4 months of treatment compared with baseline among the studied groups [Table 4].
Table 4: Comparison between the studied groups regarding OSDI grades and VAPS after 2 weeks and 4 months of treatment (n=42 patients)

Click here to view


TBUT was significantly decreased among the VDD group than non-VDD group after 2 weeks and 4 months of treatment. While TBUT did not show any significant difference between the VDD group and non-VDD group after 2 weeks and 4 months of treatment (P > 0.05). CFSS did not show any significant difference between VDD group and non-VDD group after 2 weeks and 4 months of treatment. Also, CFSS was not significantly different after 2 weeks and 4 months of treatment compared with baseline among the studied groups [Table 5].
Table 5: Comparison between the studied groups regarding TBUT and CFSS after 2 weeks and 4 months of treatment (n=42 patients)

Click here to view


Lid hyperemia was significantly increased among the VDD group than non-VDD group after 2 weeks and 4 months of treatment. While lid hyperemia did not show any significant difference between the VDD group and non-VDD group after 2 weeks and 4 months of treatment (P > 0.05). Also, Schirmer tear-secretion test was significantly decreased among the VDD group than non-VDD group after 2 weeks of treatment. On the other hand, Schirmer tear-secretion test did not show any significant difference between the VDD group and non-VDD group after 4 months of treatment. Also, Schirmer tear-secretion test was significantly decreased after 4 months of treatment compared with baseline among the studied groups [Table 6].
Table 6: Comparison between the studied groups regarding lid hyperemia and Schirmer tear-secretion test after 2 weeks and 4 months of treatment (n=42 patients)

Click here to view



  Discussion Top


In the current study, mean age of patients was 55.10 ± 12.576 years. Most of them (52.3) were females and 66.7% live in rural places. In the same line, Hwang et al.[2] found that there were 34 men and 82 women. Mean age was 55.1 ± 12.4 years (range: 23–84 years). Also, Bae et al.[9] found that mean age of the patients was 58.21 ± 12.94 years. There were 21 men and 84 women. Another study by Watts et al.[10] revealed that, out of a total of 90 patients, 52 were females and 38 were males with the mean age of 44.87 ± 14.77. Moreover, Banik et al.[11] reported age group peak of 31–40 years (11%) after above 70-year (11.4%) age group in the prevalence of dry eye. Furthermore, the study by Al-Nashar et al.[12] reported that the mean age of the patients was 37.3 years. The patients were evaluated for ocular symptoms (burning, pain, and foreign-body sensation). In addition, Yildirim et al.[13] reported that the mean age was 40.28 ± 7.03 in the group with D deficiency and 37.77 ± 7.02 in the control group. Age did not significantly differ among the groups.

In the present study, 25HD of the studied group ranged from 8 to 24 ng/ml with mean of 15.75 ± 5.764 ng/ml. In the same line, Hwang et al.[2] found that the mean serum 25HD level was 15.46 6 8.32 ng/ml. Also, Yang et al.[14] reported that 25(OH) D levels were lower in patients with dry-eye syndrome than in healthy controls. Serum 25(OH) D level was 10.52 ± 4.61 ng/ml. Another study by El Said et al.[3] revealed that 25HD level of the studied group ranged from 6 to 18.50 ng/ml with a mean value of 8.22 ± 4.814 ng/ml. Also, 92.3% of the studied sample had bilateral affected eyes, followed by Gelinya (30%). Moreover, Shahraki et al.[15] found that mean vitamin D level in patients with dry-eye syndrome was 20.86 ± 10.88 ng/dl. Furthermore, the study by Yildirim et al.[13] revealed that the mean vitamin D level was 13.45 ± 4.81 in the women with D deficiency and 47.64 ± 24.83 in controls. Lin et al.[16] demonstrated that oral vitamin D supplementation affects vitamin D metabolite concentrations in the anterior segment of the eye. Reins et al.[17] furthers our understanding of vitamin D's protective function, showing that vitamin D is able to diminish inflammation even after removal of the stimulus. Bang et al.[18] have shown that vitamin D metabolism may be involved in the pathogenesis of primary Sjögren's syndrome.

Our study showed that OSDI grade was significantly increased among VDD group after 2 weeks and 4 months of treatment as compared with non-VDD group. While VAPS did not show any significant differences between the VDD group and non-VDD group after 2 weeks and 4 months of treatment. In the same line, the study by Hwang et al.[2] found that the mean OSDI score was 39.2 ± 23.0 at baseline and decreased to 33.8 ± 23.2 at 2 weeks after topical application of CLAT and HU. The mean VAPS score was 3.0 ± 2.5 at baseline and decreased to 2.1 - 2.3 at 2 weeks after topical application of CLAT and HU. Another study by Demirci et al.[4] revealed that the mean OSDI was significantly higher in group 1 compared with group 2, which means a higher in OSDI scores in patients with VDD than in controls. Furthermore, Bae et al.[9] found that OSDI was 34.33 ± 24.88 at pretreatment, 29.25 ± 23.35 after 2 weeks, and 21.07 ± 16.52 after 10 weeks.

The current study showed that TBUT was significantly decreased among the VDD group than non-VDD group after 4 months of treatment. While TBUT did not show any significant difference between VDD group and non-VDD group after 2 weeks of treatment. In the same line, Hwang et al.[2] found that TBUT in the VDD group remained unaffected after topical application of CLAT and HU, whereas the TBUT of the non-VDD group was reported to have increased from baseline values. The TBUT was different between the groups at 2 different time points. The mean TBUT was 3.2 ± 1.7 s at baseline and increased to 3.7 ± 2.0 s at 2 weeks after topical application of CLAT and HU. Also, the study by Yildirim et al.[13] demonstrated that patients with VDD developed dry eye and impaired tear function. They reported lower scores in TBUT. Another study by Kurtul et al.[19] reported that VDD decreases the TBUT value and may be associated with dry-eye symptoms in non-Sjögren syndrome. They found that TBUT score results of the study group were significantly lower than the control group. Furthermore, the study by Bae et al.[9] found that TBUT was 3.16 ± 2.27 s at pretreatment, increased to 5.58 ± 2.44 s after 2 weeks, and to 5.19 ± 2.34 s after 6 weeks, before returning to the pretreatment levels after 10 weeks. Also, the study by Karaca et al.[20], which aimed to analyze the clinical outcomes of the ocular surface in patients with VDD after oral replacement, reported that TBUT improved from 5.53 ± 3.12 s to 9.13 ± 3.01. Tear osmolarity was 307.4 ± 15.4 mOsm/l at baseline and 302.7 ± 10.6 after 24 weeks.

Our study showed that lid hyperemia was significantly increased among VDD group than non-VDD group after 4 months of treatment. While lid hyperemia did not show any significant difference in groups after 2 weeks of treatment. In the same line, Hwang et al.[2] found that the scores of the lid margin hyperemia parameter in the VDD group were not affected by topical application of CLAT and HU, whereas a decrease in the severity of lid margin hyperemia was reported in the non-VDD group after topical application of CLAT and HU. The severity of lid margin hyperemia was different between the groups at 2 separate time points. The mean lid hyperemia score was 2.2 ± 0.8 at baseline and 2.1 ± 0.8 at 2 weeks after topical application of CLAT and HU.

In the present study, Schirmer tear-secretion test was significantly decreased among VDD group than non-VDD group after 2 weeks of treatment. Also, CFSS did not show any significant difference between both groups after 2 weeks and 4 months of treatment. In the same line, Hwang et al.[2] found that the tear-secretion values of the Schirmer test in the VDD group were reduced after topical application of CLAT and HU, whereas those of the non-VDD group were unaffected. However, the values of the Schirmer tear-secretion test were not different between the groups at 2 separate time points. Reduction in Schirmer test values in the VDD group may be due to the high variability of the Schirmer test without anesthesia or due to the decreased-reflex tear flow in response to the decreased ocular surface symptoms. Also, Chung et al.[21] reported that Schirmer-I value also showed significant improvement from 4.4 ± 2.4 to 6.1 ± 2.8 in the switching group and from 4.3 ± 1.9 to 6.0 ± 1.8 in the add-on group. After 4 weeks of treatment, the mean Schirmer-I value increase was 1.2 ± 2.6 in the switching group and 1.1 ± 3.2 in the add-on group. Yildirim et al.[13] found that vitamin D level, Schirmer's test, and TBUT scores were lower; and OSDI, VAS-pain, and FSS scores were higher in the group with VDD than in the control group. Moreover, Yildirim et al.[13] demonstrated that patients with VDD developed dry eye and impaired tear function. They reported lower scores in Schirmer test among patients with VDD than in controls. Another study by Kurtul et al.[19] reported that VDD decreases the Schirmer test values and may be associated with dry-eye symptoms in non-Sjogren syndrome. They found that Schirmer-1 results of the study group were significantly lower than the control group.


  Conclusion Top


Dry eye and impaired tear function in patients with VDD may indicate a protective role of vitamin D in the development of dry eye, probably by enhancing tear-film parameters and reducing ocular surface inflammation. Patients with VDD should be evaluated for dry-eye syndromes. The effect of CLAT and HU was dependent on serum 25HD levels. Vitamin D supplementation leads to earlier and significant improvement in TBUT, Schirmer's, and OSDI scores in patients with vitamin D deficient DED. VDD is strongly associated with dry eye in terms of the quantity of tears, the stability of the tear-film layer, and symptoms of ocular irritation, and vitamin D plays a protective role in the development of dry eye, probably by enhancing tear-film parameters and reducing ocular surface inflammation. Patients with VDD should be evaluated for dry-eye syndromes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Yokoi N, Bron AJ, Georgiev GA. The precorneal tear film as a fluid shell: the effect of blinking and saccades on tear film distribution and dynamics. Ocul Surf 2014; 12:252-266.  Back to cited text no. 1
    
2.
Hwang JS, Lee YP, Shin YJ. Vitamin D enhances the efficacy of topical artificial tears in patients with dry eye disease. Cornea 2019; 38:304-310.  Back to cited text no. 2
    
3.
El Said SH, Basiony AI, Amin MM, El-deen SK. Impact of vitamin D supplementation on dry eye in people with low serum vitamin D. Egypt J Hosp Med 2021; 84:2008-2013.  Back to cited text no. 3
    
4.
Demirci G, Erdur SK, Ozsutcu M, Eliacik M, Olmuscelik O, Aydin R, et al. Dry eye assessment in patients with vitamin D deficiency. Eye Contact Lens 2018; 44:S62-S65.  Back to cited text no. 4
    
5.
Arab A, Golpour-Hamedani S, Rafie N. Arab A, et al. The Association Between Vitamin D and Premenstrual Syndrome: A Systematic Review and Meta-Analysis of Current Literature. J Am Coll Nutr 2019; 38:648-656. Epub 2019 May 10. J Am Coll Nutr. 2019.  Back to cited text no. 5
    
6.
Tsubota K, Yokoi N, Shimazaki J, Watanabe H, Dogru M, Yamada M, et al. New perspectives on dry eye definition and diagnosis: a consensus report by the Asia Dry Eye Society. Ocul Surf 2017; 15:65-76.  Back to cited text no. 6
    
7.
Bron AJ, Evans VE and Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 2003; 22:640-650.  Back to cited text no. 7
    
8.
Crichton N. Visual analogue scale (VAS). J Clin Nurs. 2001; 10:706-706.  Back to cited text no. 8
    
9.
Bae SH, Shin YJ, Kim HK, Hyon JY, Wee WR, Park SG. Vitamin D supplementation for patients with dry eye syndrome refractory to conventional treatment. Sci Rep 2016; 6:33083.  Back to cited text no. 9
    
10.
Watts P, Sahai A, Kumar PR, Shamshad MA, Trivedi GK, Tyagi L. A prospective study to assess the role of vitamin D individually and in combination with cyclosporine in the treatment of dry eye in patients with deficient serum 25 (OH) D levels. Indian J Ophthalmol 2020; 68:1020.  Back to cited text no. 10
    
11.
Banik AK, Adhikari S, Datta S, Datta N, Choudhury N, Mukherjee K. Estimating the prevalence of dry eye among patients attending a tertiary ophthalmology clinic in Eastern India. Asian Pac J Health Sci 2018; 5:202-207.  Back to cited text no. 11
    
12.
Al-Nashar HY. Efficacy of topical cyclosporine 0.05% eye drops in the treatment of dry eyes. J Egypt Ophthalmol Soc 2015; 108:233.  Back to cited text no. 12
    
13.
Yildirim P, Garip Y, Karci AA, Guler T. Dry eye in vitamin D deficiency: more than an incidental association. Int J Rheum Dis 2016; 19:49-54.  Back to cited text no. 13
    
14.
Yang CH, Albietz J, Harkin DG, Kimlin MG, Schmid KL. Impact of oral vitamin D supplementation on the ocular surface in people with dry eye and/or low serum vitamin D. Contact Lens Anterior Eye 2018; 41:69-76.  Back to cited text no. 14
    
15.
Starr CE, Gupta PK, Farid M, Beckman KA, Chan CC, et al. Yeu E, An algorithm for the preoperative diagnosis and treatment of ocular surface disorders. J Cataract Refract Surg 2019; 45:669-684. J Cataract Refract Surg. 2019. Review.  Back to cited text no. 15
    
16.
Lin Y, Ubels JL, Schotanus MP, Yin Z, Pintea V, Hammock BD, et al. Enhancement of vitamin D metabolites in the eye following vitamin D3 supplementation and UV-B irradiation. Curr Eye Res 2012; 37:871-878.  Back to cited text no. 16
    
17.
Reins R, McDermott AM, Badour H. Vitamin D decreases IL-8 expression after induction of inflammation and influences Gene expression in human corneal epithelial cells. Paper presented at American Academy of Optometry Meeting, Denver, CO, 12 November 2014.  Back to cited text no. 17
    
18.
Bang K, Asmussen OH, Sorensen P, Oxholm B. Reduced 25-hydroxyvitamin D levels in primary Sjögren's syndrome: correlations to disease manifestations. Scand J Rheumatol 1999; 28:180-183.  Back to cited text no. 18
    
19.
Kurtul BE, Ozer PA, Aydinli MS. The association of vitamin D deficiency with tear break-up time and Schirmer testing in non-Sjögren dry eye. Eye 2015; 29:1081-1084.  Back to cited text no. 19
    
20.
Karaca EE, Kemer OE, Ozek D, Berker D, Imga NN. Clinical outcomes of ocular surface in patients treated with vitamin D oral replacement. Arq Bras Oftalmol 2020; 83:312-317.  Back to cited text no. 20
    
21.
Chung SH, Lim SA, Tchach H. Efficacy and safety of carbomer-based lipid-containing artificial tear formulations in patients with dry eye syndrome. Cornea 2016; 35:181-186.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patient and methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed817    
    Printed22    
    Emailed0    
    PDF Downloaded99    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]