Ocular Immunology and Inflammation

ISSN: 0927-3948 (Print) 1744-5078 (Online) Journal homepage: http://www.tandfonline.com/loi/ioii20

Serum Vitamin D Levels in Patients with Acute

Anterior Uveitis

Zeynep Dadaci MD, Servet Cetinkaya MD, Nursen Oncel Acir MD, Mufide
Oncel MD & Mehmet Borazan MD

To cite this article: Zeynep Dadaci MD, Servet Cetinkaya MD, Nursen Oncel Acir MD, Mufide
Oncel MD & Mehmet Borazan MD (2016): Serum Vitamin D Levels in Patients with Acute
Anterior Uveitis, Ocular Immunology and Inflammation, DOI: 10.3109/09273948.2016.1139735

To link to this article: http://dx.doi.org/10.3109/09273948.2016.1139735

Published online: 22 Mar 2016.

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 Ocular Immunology & Inflammation, 2016; 00(00): 1–5
© Taylor & Francis Group, LLC
ISSN: 0927-3948 print / 1744-5078 online
DOI: 10.3109/09273948.2016.1139735

ORIGINAL ARTICLE

Serum Vitamin D Levels in Patients with Acute

Anterior Uveitis
1
Zeynep Dadaci, MD , Servet Cetinkaya, MD2, Nursen Oncel Acir, MD
1
, Mufide Oncel, MD
3
, and
Mehmet Borazan, MD1

1
Mevlana University School of Medicine, Department of Ophthalmology, Konya, Turkey, 2Ophthalmology
Clinics, Turkish Red Crescent Hospital, Konya, Turkey, and 3Mevlana University School of Medicine,
Downloaded by [University of California, San Diego] at 10:03 25 March 2016

Department of Clinical Biochemistry, Konya, Turkey

ABSTRACT
Purpose: To evaluate serum 25-hydroxyvitamin D levels in patients with acute anterior uveitis (AAU).
Methods: This observational case–control study involved 20 patients with AAU, and 20 consecutive, age and sex-
matched healthy subjects without any ocular or systemic diseases. Serum 25-hydroxyvitamin D was quantified
with electrochemiluminescence technique.
Results: No significant differences were found between the groups with respect to age (p = 0.185) and sex (p =
0.465). Serum vitamin D levels of the subjects with AAU (mean 5.75 ± 4.50 ng/mL, median 4.00 ng/mL, range:
3.00–19.00 ng/mL) were significantly lower than the control group (mean 12.96 ± 5.89 ng/mL, median 11.00 ng/
mL, range: 5.20–25.92 ng/mL) (p<0.001).
Conclusions: We found significantly low serum levels of vitamin D in patients with AAU, which suggest that
vitamin D deficiency may play a role in the pathogenesis of anterior uveitis. Further studies are necessary to
demonstrate the efficacy of vitamin D supplementation in the management of patients with anterior uveitis.
Keywords: Acute anterior uveitis, immune system, pathogenesis, rheumatologic diseases, vitamin D

Acute anterior uveitis (AAU), a common cause of
intraocular inflammation, is a potentially blinding
disease. Although AAU is frequently considered as
an idiopathic condition,1 a substantial portion of the
patients have associated systemic rheumatologic
diseases.2 It is reported that more than half of the
patients with AAU carries the allele human leuco-
cyte antigen (HLA) B27. However, the majority of
population positive for HLA-B27 allele will never
develop AAU.3
Vitamin D is mainly synthesized in the skin from
cholesterol upon exposure to sunlight and is well
known for its effects on skeletal health and calcium
homeostasis.4 Recently, upon the discovery of the reg-
ulatory effects of vitamin D on the immune system,5
vitamin D deficiency has been associated with several
chronic health problems, including cardiovascular dis-
ease and hypertension,6 cancers,7 allergies,8,9 and auto-
immune rheumatologic diseases.10 Also, vitamin D
deficiency is reported to be involved in the pathogen-
esis of some diseases commonly associated with uvei-
tis such as Vogt–Koyanagi–Harada (VKH) and Behçet
disease.11,12
Although most cases of anterior uveitis can readily
be treated with topical corticosteroid therapy, a group
of patients with recurrent AAU or chronic uveitis may
have a worse course and regress to blindness.13 The
side-effects of the treatment may give as much harm as
the disease itself, and may threaten vision by leading
to cataract and glaucoma.14 Moreover, the treatment of
both the disease and its complications is associated
with high costs. In a study from Spain, AAU was
presented to be among the first three uveitis types
associated with highest costs and a burden for the
National Health System.15
Decreasing the frequency of uveitis attacks in
patients with recurrent AAU might be sight-saving.
Demonstration of a link between vitamin D status and

Received 5 December 2015; revised 30 December 2015; accepted 5 January 2016; published online 18 March 2016
Correspondence: Zeynep Dadaci, Department of Ophthalmology, Mevlana University School of Medicine, Aksinne M., Esmetas S., No: 16,
Meram, Konya, Turkey. E-mail: zdadaci@hotmail.com

1
 2 Z. Dadaci et al.
AAU may provide the basis for future studies evaluat-
ing the effect of vitamin D supplementation for the
prevention of the attacks. Therefore, we aimed to inves-
tigate serum vitamin D levels of patients with AAU and
compare them with healthy age- and sex-matched con-
trols in our preliminary study. We are unaware of any
previous reports demonstrating serum vitamin D levels
in patients presenting with AAU.
METHODS
Study Population
This prospective, observational, case–control study
comprised of 40 subjects (20 patients with idiopathic
Downloaded by [University of California, San Diego] at 10:03 25 March 2016
or HLA-B27-associated AAU and 20 control subjects).
All patients were recruited in the study between May
and October 2015, and evaluated at the Mevlana
University and Turkish Red Crescent eye clinics.
Patients with signs and symptoms of acute anterior
uveitis (conjunctival hyperemia, pain, photophobia,
flare, and anterior chamber cells) without any evidence
of posterior segment inflammation were included in the
AAU group. Patients with granulomatous, infective or
traumatic uveitis, and known uveitic syndromes were
excluded. The control group was composed of 20 con-
secutive subjects of similar age (18–67 years) and gen-
der as the study group, with normal ocular
examination, except refractive disorders, without any
history of systemic diseases, drug or dietary supple-
ment consumption. To minimize cultural influences or
geographic effects on the findings, the study was con-
ducted in the central region of Turkey, and all partici-
pants lived in the same region. The research protocol
was approved by the Mevlana University Ethics
Committee (2015/154). The study was performed in
compliance with good clinical practice guidelines and
in accordance with the tenets of the Declaration of
Helsinki. Written informed consent was obtained from
each patient prior to enrollment into the study.
Pregnant or breast-feeding women were excluded
from the study. Subjects with any ocular pathology
other than AAU, such as allergic conjunctivitis and
dry eye syndrome, were also excluded. Subjects who
were smokers and who had a history of consumption
of vitamin supplements or alcohol during the 4 weeks
prior to the study, and obese patients, were also
excluded. The associated systemic diseases and the
drugs of the patients with AAU were noted and
patients were consulted with internists for systemic
evaluation and vitamin D supplementation.
All subjects underwent a full ophthalmologic exam-
ination, including: best-corrected visual acuity (BCVA)
obtained with a Snellen projection chart; refraction; slit-
lamp biomicroscopy; intraocular pressure (IOP) mea-
surement with Goldmann applanation tonometry; and
dilated fundoscopy with a 90 Diopter lens. The intensity
of cellular reaction in the anterior chamber is evaluated
by slit-lamp microscopy and graded according to the
number of inflammatory cells seen in a 1 × 3 mm high-
powered beam with maximum light intensity at a
45–60º angle. The reaction is graded as 1+ (5–10 cells),
2+ (10–20 cells), 3+ (20–30 cells), and 4+ (>30 cells).
Biochemical Analysis
Fasting venous blood sample was obtained from each
subject from the antecubital vein into the serum
separator tubes. After centrifugation at 2000 g for 15
min serum samples were aliquoted, labeled and stored
at –20ºC for a maximum of 30 days until analysis.
When we reached the targeted sample size, serum
samples were thawed and serum 25-hydroxyvitamin
D levels were quantified with electrochemilumines-
cence technique on Modular Analytics E 170 analyzer
(Roche Diagnostics, GmbH, Germany). Measuring
range for 25-hydroxyvitamin D was 3–70 ng/mL
(7.5–175 nmol/L). Between run precision values deter-
mined with analysis of serum pools were as follows:
13.1% for low and 3.4% for high concentrations of 25-
hydroxyvitamin D, respectively.
Statistical Analysis
Statistical analyses were performed using a statistical
program (SPSS version 15.0, SPSS Science, Chicago,
IL). The distribution of the numeric data was tested
with the Shapiro–Wilk test. The Mann–Whitney U-
test was used for testing the difference between vita-
min D levels for both patient and control groups. The
mean age of groups were compared with the Mann–
Whitney U-test and the distribution of sex between
the groups was compared using the χ2-test with con-
tinuity correction. All p values <0.5 were considered
as statistically significant.
RESULTS
In total, 20 patients with AAU (4 men, 16 women) and
20 control subjects (6 men, 14 women) were enrolled in
our study. The mean ages of patients with AAU and
control subjects were 43.50 ± 16.25 years (range: 18–66
years) and 36.30 ± 13.59 years (range: 18–68 years),
respectively (Table 1). No statistically significant dif-
ferences were found between the groups with respect
to age (p = 0.185) and sex (p = 0.465).
All subjects with AAU had an anterior chamber cel-
lular reaction of grade 3+ or 4+. Serum vitamin D levels
(mean ± SD) of the subjects with AAU (5.75 ± 4.50 ng/
mL, median 4.00 ng/mL, range: 3.00–19.00 ng/mL) were
significantly lower than the control group (12.96 ± 5.89
ng/mL, median 11.00 ng/mL, range: 5.20–25.92 ng/mL)
Ocular Immunology & Inflammation
 Vitamin D Levels in Acute Anterior Uveitis 3

TABLE 1. Demographic characteristics of the study subjects.

AAU group (n = 20) Control group (n = 20) p value

Age (years; mean ± SD) 43.50 ± 16.25 36.30 ± 13.59 0.185

Sex (male/female) 4/16 6/14 0.465

AAU, acute anterior uveitis; SD, standard deviation.

(minimum detection limit), none of the control subjects

had serum vitamin D levels of ≤3 ng/mL.
In the AAU group, most of the patients had coex-
isting rheumatologic and/or systemic diseases: eight
subjects had fibromyalgia; two had ankylosing spon-
dylitis; and one had gout. There were also seven
patients with systemic hypertension, three with dia-
betes mellitus, and two with asthma. The data of all
Downloaded by [University of California, San Diego] at 10:03 25 March 2016

patients in the AAU group are shown in Table 2.

DISCUSSION

This is a novel study evaluating the relationship

FIGURE 1. Comparison of serum 25-hydroxyvitamin D (ng/
mL) levels of patients with acute anterior uveitis (AAU group;
n = 20) and control subjects (n = 20). The central box covers the
interquartile range, and the horizontal line indicates the median.
The end of whiskers corresponds to the most extreme observa-
tions, and shapes indicate outliers.
(p<0.001) (Figure 1). While 8 out of 20 patients in the
AAU group had serum vitamin D levels of ≤3 ng/mL
between acute anterior uveitis (idiopathic or HLA-
B27 associated) and vitamin D status. Serum levels of
vitamin D in patients with AAU were significantly
lower than the control group. This finding may lead
to the development of new strategies in the manage-
ment of patients with recurrent AAU.
Uveitis, in general, is reported to be the cause of
about 10% of all legal blindness and may have worse
socioeconomic impact because it commonly affects
younger people.16 The etiology of AAU, which is
the most frequent form, is largely unclear. To date,

TABLE 2. Data of all patients in the acute anterior uveitis group.

Patient number Gender Age (years) Grade of AC cellular reaction Associated diseases Vitamin D levels (ng/mL)

1. F 58 +3 HT, gout 3.0

2. F 45 +4 Fibromyalgia 3.0
3. F 66 +4 HT, DM, asthma 5.0
4. F 57 +4 HT 3.0
5. F 62 +3 HT 8.0
6. F 57 +4 HT 4.0
7. M 19 +3 – 19.0
8. F 65 +4 HT, DM 3.0
9. F 43 +4 Fibromyalgia 4.0
10. M 39 +4 AS 16.6
11. F 30 +3 Fibromyalgia 5.6
12. F 25 +4 Fibromyalgia 3.0
13. F 20 +4 Fibromyalgia 3.0
14. F 18 +4 Fibromyalgia 4.8
15. M 53 +3 HT 3.4
16. F 62 +3 DM, asthma 3.0
17. F 32 +4 AS 4.6
18. F 37 +4 Fibromyalgia 7.0
19. M 50 +3 – 9.0
20. F 32 +4 Fibromyalgia 3.0

M, male; F, female; AC, anterior chamber; HT, hypertension; DM, diabetes mellitus; AS, ankylosing spondylitis.

© Taylor & Francis Group, LLC

 4 Z. Dadaci et al.
most of the studies in uveitis have focused on genes
of the HLA system, especially HLA-B27.17,18
However, only a minority of HLA-B27-positive indi-
viduals will ever develop AAU.3 Today, there is
growing attention to the interaction between the
immune and endocrine system, and vitamin D defi-
ciency has been reported to have a role in the patho-
genesis of several autoimmune disorders. Serum
levels of 1,25-dihydroxyvitamin D3, the active meta-
bolite of vitamin D, were found to be decreased in
uveitis patients with Behçet disease, VKH syndrome,
and ankylosing spondylitis.11,12,19 1,25-dihydroxyvi-
tamin D3, was shown to inhibit Th1 and Th17 cells,
which are believed to have an important role in the
pathogenesis of autoimmune disorders.20,21 There
are also studies demonstrating that 1,25-dihydroxy-
Downloaded by [University of California, San Diego] at 10:03 25 March 2016
vitamin D3 could skew the T-cell response to an anti-
inflammatory state through inhibition of Th1 and
promotion of regulatory T cells.22
Vitamin D can be obtained from the diet but it does
not naturally occur in most food and its main source is
formation in cutaneous tissue following exposure to
ultraviolet light.4 Although our study was conducted
in the sunny period of the year in our region (May–
October), we detected very low levels of vitamin D,
especially in the AAU group. This is in accordance
with studies reporting vitamin D deficiency even in
sun-replete areas of the world.23 Also, a high fre-
quency of vitamin D deficiency and/or insufficiency
is reported in healthy Turkish subjects.24 The reason
for vitamin D deficiency may be the lack of outdoor
activity, clothing or excess use of sunblock. Also, some
medications, especially colchicine, is reported to
associate with lower vitamin D levels.25 In our study,
only one patient was using colchicine, which was pre-
scribed recently.
There is considerable evidence about the immu-
nosuppressive effect of vitamin D. Vitamin D sup-
plementation has been shown to provide beneficial
effects in several autoimmune disease models in
animals.21 There are also clinical studies demon-
strating aggravation of symptomatology in pro-
found vitamin D deficiency (<10 ng/mL) and
beneficial effect of vitamin D supplementation in
various autoimmune diseases, including multiple
sclerosis and type 1 diabetes.26 Do et al.27 reported
that toll-like receptor (TLR)2 and TLR4 are highly
expressed in the monocytes of active Behçet disease
patients and demonstrated that vitamin D3 sup-
presses the protein and mRNA expressions of
TLR2 and TLR4 in vitro. They concluded that vita-
min D may be used as a therapeutic option in
Behçet disease. This immunosuppressive effect of
vitamin D might explain the development of auto-
immune diseases in its deficiency. Supportively, we
demonstrated very low levels of vitamin D in
patients with AAU in our study.
In the present study, 40% of the subjects with AAU
had fibromyalgia. We have not encountered any pre-
vious studies reporting the frequency of fibromyalgia
in subjects with anterior uveitis. Fibromyalgia was
however, reported to associate with rheumatologic
diseases in the literature and the prevalence of fibro-
myalgia in patients with Behçet disease was reported
as 37.1% in a previous study.28
Ours is a pioneer study demonstrating decreased
vitamin D levels in patients with AAU, but there are
some limitations that should be addressed. First, is the
low study number. We have however, still demon-
strated an obvious difference between the serum vita-
min D levels of the patients with AAU and the healthy
controls. Second, we enrolled only subjects with idio-
pathic or HLA-B27 associated AAU, which is the most
frequent form, in our study. We did not check for
HLA-B27 antigen and grouped the patients. Further
studies are necessary to demonstrate the possible asso-
ciation of vitamin D deficiency in other types of uveitis
and the efficacy of vitamin D supplementation. Third,
is that we used an electrochemiluminescence technique
to quantify serum vitamin D levels. This technique
slightly underestimates vitamin D levels when com-
pared with the liquid chromatography–tandem mass
spectrometry method.29 We believe that this underes-
timation should not be important however, as we
analyzed the samples of both groups at the same
time and compared the results between the groups.
Despite these shortcomings, our preliminary study
generates valuable hypotheses and provides a basis
for future studies.
Although the outcomes of the patients after normal-
ization of their vitamin D levels were outside the scope
of the present study, none of the patients in the AAU
group experienced recurrence of uveitis attack after
vitamin D supplementation during their follow-up.
We think that the positive influence of vitamin D on
the immune system might decrease the frequency of
AAU attacks. We were able to find only one study in
the literature mentioning the effect of large dose vita-
min D in chronic uveitis, which was published in
1956.30 Further studies are necessary to define the
role of vitamin D supplementation in the follow-up
of patients with AAU.
In conclusion, we demonstrated a dramatic differ-
ence between the serum vitamin D levels of patients
with AAU and the control group. Although most
patients with acute anterior uveitis responded well to
the classic treatment, frequent recurrences are an
important problem with an increased risk of morbidity
related with both the disease itself and the treatment.
Further studies are necessary to determine whether
vitamin D supplementation can decrease the frequency
of the attacks, which might prove to be a very valuable
and easy method for saving the vision of patients with
recurrent acute anterior uveitis.
Ocular Immunology & Inflammation

DECLARATION OF INTEREST
The authors report no conflicts of interest. The authors
alone are responsible for the content and writing of the
paper.
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