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Pseudoexfoliation syndrome at a Singapore eye clinic

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Background: The purpose of this study was to investigate the demographics of pseudoexfoliation syndrome (PXF) and pseudoexfoliative glaucoma (PXG) in a Singapore hospital eye outpatient clinic. Methods: A retrospective study of 93 consecutive patients (146 eyes) with PXF was undertaken by a single ophthalmologist over a period of 37 months (July 1, 2006, to July 31, 2009). Results: Ninety-three (2.8%) of 3,297 patients seen during the study period were diagnosed with PXF. Forty-three (46.2%) of the 93 PXF patients were male. Indians were 5.04 times more likely to develop PXF than Chinese (P<0.001, 95% confidence interval 3.05-8.33), while Malays were 2.22 times more likely to develop PXF as compared with Chinese (P=0.029, 95% CI 1.08-4.55). Twenty-two (23.7%) of the 93 PXF patients had PXG at the time of diagnosis. There was no statistically significant difference in mean age between PXF and PXG patients. There was a larger proportion of males with PXG than females (P<0.001). Conclusion: PXF is not infrequent in elderly Singapore eye clinic patients, and is more likely to occur in Indians than in Chinese. In the Singapore eye clinic setting, males may be more likely to develop PXG, although larger studies will be required to confirm this.
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Clinical Ophthalmology 2015:9 1619–1624
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ORIGINAL RESEARCH
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/OPTH.S87155
Pseudoexfoliation syndrome at a Singapore eye
clinic
Jason Kian Seng Lee
Elizabeth Poh Ying Wong
Su Ling Ho
National Healthcare Group Eye
Institute, Tan Tock Seng Hospital,
Singapore
Background: The purpose of this study was to investigate the demographics of pseudoexfoliation
syndrome (PXF) and pseudoexfoliative glaucoma (PXG) in a Singapore hospital eye outpatient
clinic.
Methods: A retrospective study of 93 consecutive patients (146 eyes) with PXF was undertaken
by a single ophthalmologist over a period of 37 months (July 1, 2006, to July 31, 2009).
Results: Ninety-three (2.8%) of 3,297 patients seen during the study period were diagnosed
with PXF. Forty-three (46.2%) of the 93 PXF patients were male. Indians were 5.04 times more
likely to develop PXF than Chinese (P,0.001, 95% confidence interval 3.05–8.33), while
Malays were 2.22 times more likely to develop PXF as compared with Chinese (P=0.029, 95%
CI 1.08–4.55). Twenty-two (23.7%) of the 93 PXF patients had PXG at the time of diagnosis.
There was no statistically significant difference in mean age between PXF and PXG patients.
There was a larger proportion of males with PXG than females (P,0.001).
Conclusion: PXF is not infrequent in elderly Singapore eye clinic patients, and is more likely
to occur in Indians than in Chinese. In the Singapore eye clinic setting, males may be more
likely to develop PXG, although larger studies will be required to confirm this.
Keywords: exfoliation syndrome, pseudoexfoliation syndrome, exfoliation glaucoma, glau-
coma capsulare
Introduction
Pseudoexfoliation syndrome (PXF) is thought to be an ocular manifestation of a
systemic extracellular matrix disorder characterized by accumulation of fibrillar
material in tissues, including ocular tissues.
1–5
It is characterized by the presence of
small, white pseudoexfoliative material in the anterior segment, predominantly on the
pupillary margin and anterior lens capsule.
6
The association between PXF and glaucoma is well recognized.
3,7
In fact, PXF
has been described as the most common identifiable cause of open-angle glaucoma
worldwide.
8
Studies have also shown that glaucomatous damage progresses more rapidly
in patients with PXF and glaucoma when compared with those having chronic open-angle
glaucoma.
9–14
Visual field defects have also been shown to be more severe at the time of
diagnosis in patients with pseudoexfoliative glaucoma (PXG)
11,15
and to deteriorate more
rapidly when compared with chronic open-angle glaucoma.
16
Cataracts have been reported
to be more common in PXF patients,
17,18
and PXF has also been shown to be associated
with zonulysis during cataract surgery as well as postoperative lens dislocation.
8,19
PXF is an age-related disease with significant geographic and racial variations in
prevalence.
20–23
Population-based studies have reported prevalence rates of PXF world-
wide varying from 0%
24
to over 40%.
20,21,24
The prevalence of PXF has been reported
in various parts of the world, including Europe, the Middle East, and Australia.
25–41
Correspondence: Jason Kian Seng Lee
National Healthcare Group Eye Institute,
Tan Tock Seng Hospital, 11, Jalan Tan
Tock Seng, Singapore 308433
Tel +65 6357 7726
Fax +65 6357 8675
Email jason_ks_lee@ttsh.com.sg
Journal name: Clinical Ophthalmology
Article Designation: Original Research
Year: 2015
Volume: 9
Running head verso: Lee et al
Running head recto: Pseudoexfoliation syndrome at a Singapore eye clinic
DOI: http://dx.doi.org/10.2147/OPTH.S87155
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Lee et al
Singapore is a multiracial country, comprising predomi-
nantly Chinese, Malay, and Indian populations. To date, there
have only been two studies looking at the prevalence of PXF
in the Singapore population, and both targeted specific ethnic
groups.
42,43
Therefore, this study was conducted to provide
further insight into the demographics of PXF and PXG across
all ethnic groups in Singapore.
Materials and methods
All patients aged 40 years or older seen by a single ophthal-
mologist over a period of 37 months (July 1, 2006, to July 31,
2009) at the general ophthalmology clinic of a tertiary
hospital in Singapore were recruited into the study. Patients
diagnosed with PXF were identified, and a retrospective case
review of their case sheets was performed. Appropriate ethics
approval was obtained from the National Healthcare Group
Domain Specific Review Board.
All patients underwent a comprehensive ophthalmologi-
cal assessment including visual acuity assessment, Goldmann
applanation tonometry, slit-lamp examination before and
after dilation of pupils, and dilated fundus examination. The
anterior lens surface and pupillary ruff were inspected under
high magnification. All eyes were also retroilluminated to
detect the presence of a hoarfrost ring.
PXF was diagnosed if typical pseudoexfoliative material
was present on the anterior lens capsule and/or pupillary
margin in either one or both eyes. PXG was defined as the
presence of typical pseudoexfoliative material in combina-
tion with a raised intraocular pressure of .21 mmHg and
a reproducible visual field loss with optic disc cupping and
neuroretinal rim thinning, with no evidence of other second-
ary causes of glaucoma.
The medical records of patients diagnosed with PXF
and PXG were reviewed for demographic characteristics,
including age, sex, and ethnic origin. Ethnic origin was
ascertained based on the patients’ registration information
sheet.
All statistical analyses were performed using IBM SPSS
Statistics (version 19, IBM Corp, Armonk, NY, USA) and
R (version 2.15.2, The R Foundation for Statistical Com-
puting, Vienna, Austria). The mean ± standard deviation
for age and frequencies of other demographic and clinical
characteristics were calculated. The mean age was compared
between groups using the independent-samples t-test, while
categorical data, such as sex, race, and laterality, were com-
pared using the Pearson chi-square test or Fisher’s Exact
test if expected counts within a category were less than 5 for
more than 20% of cells. Logistic regression was performed
to calculate the odds ratio of likelihood of having PXF, with
the 95% confidence interval (CI) for each demographic fac-
tor. A P-value of less than 0.05 was considered to indicate
statistical significance.
Results
Overall demographics
A total of 3,297 patients were identified, of whom 1,459
(44.3%) were male and 1,838 (55.7%) were female. The
ethnic distribution of the patients included 2,779 (84.3%)
Chinese, 199 (6.0%) Malays, 237 (7.2%) Indians, and 82
(2.5%) from other races.
Pseudoexfoliation syndrome
Ninety-three patients (2.8%, 146 eyes) were identified as
having PXF, of whom 46.2% were male. PXF was bilateral
in 53 patients (57.0%). The mean age of patients with PXF
was 72.2±8.7 (range 44–94) years, with the majority (95.7%)
being 60 years or older (Table 1). We found no significant sex
predilection in the patients with PXF whether we analyzed
the data as a cohort or in separate ethnic groups. The sex
distribution of the patients with PXF according to ethnicity
is summarized in Table 2.
The major ethnic groups among the 93 PXF patients
were Chinese, Malay, and Indian (Table 3). In the Chinese
population, 2.1% were found to have PXF. About twice the
Table 1 Population with and without pseudoexfoliation syndrome
based on age groups
Age
(years)
Non-PXF,
n (%)
PXF,
n (%)
All patients,
n (%)
40–49 340 (10.6) 1 (1.1) 341 (10.3)
50–59 806 (25.2) 3 (3.2) 809 (24.5)
60–69 984 (30.7) 32 (34.4) 1,016 (30.8)
70–79 735 (22.9) 41 (44.1) 776 (23.5)
$80
339 (10.6) 16 (17.2) 355 (10.8)
Total 3,204 93 3,297
Abbreviation: PXF, pseudoexfoliation syndrome.
Table 2 Sex distribution based on ethnicity in patients with
pseudoexfoliation syndrome
Sex Total
Male Female
Ethnicity n (%)
Chinese
Malay
Indian
Others
Total
22 (51.2)
5 (11.6)
15 (34.9)
1 (2.3)
43
36 (72.0)
4 (8.0)
8 (16.0)
2 (4.0)
50
58 (62.4)
9 (9.7)
23 (24.7)
3 (3.2)
93
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Pseudoexfoliation syndrome at a Singapore eye clinic
percentage of Malays (4.5%) was found to have PXF. The
Indian population were found to have the highest percentage
of PXF (9.7%) among the three major races.
Indians were found to be 5.04 times more likely to
develop PXF than Chinese (P,0.001, 95% CI 3.05–8.33),
while Malays were 2.22 times more likely to develop PXF
than Chinese (P=0.029, 95% CI 1.08–4.55). The relation-
ship between sex and likelihood of developing PXF was not
statistically significant (P=0.696). The results were similar
in the full model (Table 3). Our study found no statistically
significant relationship between laterality and age, sex, or
ethnicity (Table 4).
Pseudoexfoliative glaucoma
Of the 93 patients with PXF, 22 (23.7%) were identified
as having PXG, among whom almost three quarters of
cases were bilateral (16 patients, 72.7%). The mean age of
patients with PXG was 73.1±9.1 years. There was no statis-
tically significant difference in mean age between patients
with PXG and those with PXF only (P=0.390; Table 5).
Eighteen (81.8%) of the 22 patients were male. There was
a significantly larger proportion of males with PXG than
without PXG (P,0.001; Table 5).
The ethnic distribution of the patients with PXG included
12 Chinese (55.5%), three Malays (13.6%), and seven Indians
(31.8%). There was no statistically significant difference in
ethnic distribution of PXG patients when compared with
non-PXG patients (P=0.531, Table 5). Subgroup analysis
also revealed no sex predilection in the various ethnic
groups. Our study found a larger proportion of bilateral eye
involvement of PXF in the PXG group when compared with
the non-PXG group, although the difference did not reach
statistical significance (P=0.088).
Discussion
PXF has been shown in previous studies to be associated
with increasing age, typically being more common after the
age of 60 years. Forsius et al
20
found that the incidence of
PXF doubled every decade after the age of 50 years. Our
study observed a similar trend. However, we also observed
a decrease in the number of patients with PXF from the
age of 80 years onwards. There are two possible explana-
tions for this observation. The average life expectancy of
Table 3 Age, ethnicity, and sex of patients with pseudoexfoliation syndrome
Non-PXF
population
PXF
population
Unadjusted
OR
95% CI P-value Adjusted OR
(full model)
95% CI P-value
Age (years)
Mean ± SD 64.3±11.6 72.2±8.7
1.06 1.04–1.08
,0.001
1.07 1.05–1.09
,0.001
Ethnicity n (%)
Chinese 2,721 (84.9) 58 (62.4) Ref Ref
Malay 190 (5.9) 9 (9.7) 2.22 1.08–4.55 0.029 2.49 1.20–5.15 0.014
Indian 214 (6.7) 23 (24.7) 5.04 3.05–8.33
,0.001
6.00 3.57–10.09
,0.001
Others 79 (2.5) 3 (3.2) 1.78 0.55–5.81 0.338 1.71 0.51–5.67 0.381
Sex n (%)
Female 1,788 (55.8) 50 (53.8) Ref Ref
Male 1,416 (44.2) 43 (46.2) 1.09 0.72–1.64 0.696 1.08 0.70–1.64 0.734
Abbreviations: CI, condence interval; OR, odds ratio; SD, standard deviation; PXF, pseudoexfoliation syndrome; Ref, reference.
Table 4 Association of laterality with age, sex, and ethnicity of
patients in PXF population
Unilateral Bilateral P-value
Patients, n (%) 40 (43.0) 53 (57.0)
Age (years)
Mean ± SD 70.9±7.9 73.1±9.1
0.237*
Ethnicity n (%) 0.937***
Chinese 26 (65.0) 32 (60.4)
Malay 3 (7.5) 6 (11.3)
Indian 10 (25.0) 13 (24.5)
Others 1 (2.5) 2 (3.8)
Sex, n (%) 0.530**
Male 17 (42.5) 26 (49.1)
Female 23 (57.5) 27 (50.9)
Notes: *Independent samples t-test; **Pearson chi-square test; ***Fisher’s Exact test.
Abbreviations: SD, standard deviation; PXF, pseudoexfoliation syndrome.
Table 5 Age, ethnicity, and sex of PXG patients
Non-PXG
population
PXG
population
Age (years)
Mean ± SD 70.9±7.9 73.1±9.1
Ethnicity n (%)
Chinese
Malay
Indian
Others
46 (64.8)
6 (8.5)
16 (22.5)
3 (4.2)
12 (54.5)
3 (13.6)
7 (31.8)
0 (0.0)
Sex, n (%)
Female 46 (64.8) 4 (18.2)
Male 25 (35.2) 18 (81.8)
Abbreviations: PXG, pseudoexfoliative glaucoma; SD, standard deviation.
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Lee et al
Singapore’s population around the time of data collection
was 81.4 years,
44
so the decrease in numbers of patients
aged over 80 years could be attributed to a higher death
rate in that age group. Another possible explanation could
be that more people over 80 years of age are pseudophakic,
and mild underlying PXF may have been undetected after
surgery. Various studies have shown conflicting results for
sex predisposition.
25,28,40,45
However, our present study found
no significant sex predilection.
The prevalence of PXF has been shown to vary signifi-
cantly between populations
7,25,26,28–30,32–37,39–43,45–55
(Table 6).
The underlying reason for the large demographic variation
in PXF is still undetermined. However, factors including
genetics
56–58
and environmental influences such as living in
lower latitudes,
21
sun exposure,
20,46
dietary factors,
50
altitude,
53
and even iris color
59
have been postulated.
Data from previous studies have shown that the preva-
lence of PXF in East Asians is low when compared with
Europeans.
25,28,29,40–43
It has been postulated that this may be
the result of both genetic composition and environmental
influences.
PXF has been described as being rare in the Chinese
population. Lee et al
60
showed that the G allele of rs3825942
within LOXL1 confers a tenfold increase in risk for
PXF/PXG in the Chinese population. However, they found
a similar allelic architecture between Chinese and other
Caucasian populations, and went on to postulate that there
might be other genetic and/or strong environmental factors
that could be modulating the phenotypic expression of PXF
in the Chinese population, resulting in a lower prevalence
of the disease.
In this study, we observed that approximately 2.1% of the
Chinese population had PXF. This value was similar to that
reported by the Beijing Eye Study,
41
which found an overall
prevalence of definite PXF in a Northern Chinese population
of 2.38%, but this is much higher than that reported by the
Tanjong Pagar survey
42
or a hospital-based cohort study in
Hong Kong. The Tanjong Pagar survey looked specifically
at Chinese Singaporean adults aged 40 years and older and
observed a prevalence of 0.2% that rose to 0.7% in those over
60 years of age. Young et al
45
investigated a hospital-based
cohort of Chinese in Hong Kong and observed a prevalence
of 0.4%.
In our study, 9.7% of Indians were found to have PXF.
Krishnadas et al,
32
Arvind et al,
29
and Thomas et al
40
looked
at the South Indian populations and reported prevalences of
6.0%, 3.8%, and 3.01%, respectively, in individuals over
the age of 40 years. Jonas et al
55
looked at Central Indian
populations aged 30 and above and reported the prevalence
of PXF to be 0.95%.
Data on the prevalence of pseudoexfoliation in the Malay
ethnic group is very limited. The Singapore Malay Eye
Study
43
is the only research that has looked at the preva-
lence of PXF in the Malay population aged 40–80 years,
and reported the prevalence of PXF in Malays to be 0.46%.
Our study observed a much higher percentage, with 4.5% of
Malays having PXF.
The higher proportion of PXF found in all ethnic
groups in our study could be attributed to the fact that our
research was hospital-based. PXF has been described to be
more prevalent in patients with ocular conditions such as
cataracts and glaucoma,
3
and determining prevalence in a
hospital-based cohort would have resulted in some degree
of selection bias.
Another explanation could be that the prevalence of PXF
is in fact higher in the general population and that we may
be underdiagnosing the condition. Making a diagnosis of
Table 6 Prevalence of PXF in populations around the world
Country Age (years) Prevalence (%)
Australia (Central Australia)
46
$61
16.3
Australia (Blue Mountains)
7
49–97 2.3
Australia (Victoria)
33
$40
0.98
People’s Republic of China
41
$50
2.38
Finland
17
$70
22.1
France
49
.50
5.5
Greece (Epirus)
51
$50
24.3
Greece (Crete)
53
$40
16.1
Greenland
50
$70
4.5
Hong Kong
45
$60
0.4
Iceland
28
$50
10.7
India (South India)
29
$40
3.8
India (Tamil Nadu)
32
$40
6.0
India (Andhra Pradesh)
40
$40
3.01
India (Central India)
55
$30
0.95
Iran
35
$50
13.1
Japan
34
$50
3.4
Jordan
26
40–90 9.1
Myanmar
25
$40
3.4
Nepal (Gurungs)
37
$30
8.2
Nepal (Tamangs)
37
$30
0.3
Nigeria
54
30–90 2.7
Norway
48
.65
16.9
Pakistan
36
$45
6.45
Singapore (Chinese)
42
$40
0.2
Singapore (Malay)
43
40–80 0.46
Turkey
52
$50
7.2
USA (Framingham)
47
52–85 1.8
USA (Southeastern USA)
30
$60
3.2
Notes: Current study: Chinese 2.1%; Malays 4.5%; Indians 9.7%.
Abbreviation: PXF, pseudoexfoliation syndrome.
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Pseudoexfoliation syndrome at a Singapore eye clinic
PXF requires a careful slit-lamp examination
3
after pupil-
lary dilatation, and the condition may be underdiagnosed in
the community.
When comparing the three ethnic groups in our present
study, we observed that Indians were five times more likely
to have PXF than Chinese, whereas Malays were about twice
as likely to have PXF when compared with Chinese. This is
consistent with the available data on the prevalence of PXF
in these three races.
29,32,40,42,43,45
Almost one in four (23.6%) PXF patients in our study had
glaucoma. Studies that have looked at PXG in PXF patients
have reported variable percentages. The Andhra Pradesh
Eye Disease study
40
reported that 5.5% of PXF patients had
glaucoma. In the Aravind Comprehensive Eye Survey,
32
23 (7.5%) of 308 patients had definite glaucoma, while the
Blue Mountain Eye Study
7
reported a 14.2% incidence of
glaucoma. A possible explanation for this variation in the
percentage of glaucoma could be due to genetic as well as
environmental differences. Previously mentioned studies
had focused on Indian or Caucasian populations; our present
study, however, focused on a predominantly Chinese popu-
lation in a hospital clinic setting where ocular diseases are
expected to be encountered more frequently. Our study also
found a significantly larger proportion of males than female
with PXG. Nevertheless, the reliability of this finding may
be limited given the small sample size.
Our current study is one of the largest of its kind to
address PXF among the Chinese and Malay populations liv-
ing in Southeast Asia. It is also the first study to make direct
comparisons between PXF sufferers in the Chinese, Malay,
and Indian populations within the unique multiracial setting
of Singapore. There was also consistency in clinical examina-
tions, as all were performed by the same ophthalmologist.
The limitations of the present study include its retrospec-
tive design, and its hospital-based nature, which may have
possibly resulted in selection bias. A larger prospective study
looking at the prevalence of PXF in the local community
would be helpful to decipher the unique epidemiology of PXF
in our local population. In conclusion, PXF is not infrequently
encountered in elderly Singapore eye clinic patients, and is
more likely to occur in Indians and less likely in Chinese.
In the Singapore clinic setting, males may be more likely
to develop PXG, although larger studies will be required to
confirm this.
Acknowledgment
The authors would like to thank Dr Rupesh Agrawal for his
advice regarding the writing of this article.
Disclosure
The authors report no conflicts of interest in this work.
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... As the largest continent globally, the most populous, and with many different cultures and communities in every region, the prevalence of PXF varies across Asia [133,134]. In Northern China, in one hospitalbased study of 8,205 cataract patients aged 60+ years old, PXF was found to be quite low and found in only 0.55% of study participants [135]. ...
... This was confirmed by a prospective study of 1,890 participants aged 45 to 87 years old that found that 40% of those with PXF had high IOP [136]. In Singapore, the prevalence of PXF was reported to be 2.8% [134] and confirmed by a retrospective study of 1,459 male and 1,858 female participants, aged 40+ years old. The Singapore study also observed that those with PXF were more likely to be of Indian ethnicity than Chinese [134]. ...
... In Singapore, the prevalence of PXF was reported to be 2.8% [134] and confirmed by a retrospective study of 1,459 male and 1,858 female participants, aged 40+ years old. The Singapore study also observed that those with PXF were more likely to be of Indian ethnicity than Chinese [134]. This variation by region reinforces the need to conduct further research across populations to understand the prevalence of the PXF and associated risks. ...
Article
Full-text available
Pseudoexfoliation (PXF) syndrome is an important public health concern requiring individual population level analysis. Disease prevalence differs by geographic location and ethnicity, and has environmental, demographic, genetic, and molecular risk factors have been demonstrated. Epidemiological factors that have been associated with PXF include age, sex, environmental factors, and diet. Genetic and molecular components have also been identified that are associated with PXF. Underserved populations are often understudied within scientific research, including research about eye disease such as PXF, contributing to the persistence of health disparities within these populations. In each population, PXF needs may be different, and by having research that identifies individual population needs about PXF, the resources in that population can be more efficiently utilized. Otherwise, PXF intervention and care management based only on the broadest level of understanding may continue to exacerbate health disparities in populations disproportionally burdened by PXF.
... years. 7,8 The greater number of male cases might be due to our male dominated society and negligence towards female health care. 6,7,8 In present study 84 (75%) patients had unilateral and 28 (25%) bilateral involvement. ...
... 7,8 The greater number of male cases might be due to our male dominated society and negligence towards female health care. 6,7,8 In present study 84 (75%) patients had unilateral and 28 (25%) bilateral involvement. In 124 eyes (88.6%) angle was open and 16 (11.4%) ...
Article
BACKGROUND Pseudoexfoliative material, the presence of which in the eye is termed as pseudoexfoliative syndrome (PXS), is a common cause of secondary open angle glaucoma world-wide.1 Pseudoexfoliation (PXF) should be differentiated from true capsular exfoliation, which occurs due to chronic Infrared exposure in glassblowers. We wanted to study the presentation, clinical features, management, and visual prognosis of pseudoexfoliation glaucoma cases in our department. METHODS This hospital based prospective study included 1253 patients with pseudoexfoliative material in one or more of the anterior segment structures with intraocular pressure (IOP)>21 mmHg and /or glaucomatous optic disc changes selected from the ophthalmology OPD of SCB Medical college from April 2016 to March 2018. RESULTS Incidence of pseudoexfoliation was found to be 1.3% among OPD patients who were >40 years of age and 8.9% of patients of pseudoexfoliation had glaucoma. CONCLUSIONS After medical and surgical management, most of the patients showed visual improvement with >6/60 in 70% of cases except those who had poor visual acuity at presentation because of advanced glaucomatous damage.
... PXF may also contribute to 25% of primary open-angle glaucoma worldwide for all people aged 60 years and older [18]. These prevalence rates include 1.73% in a Congolese population [25], 2.8% in a Singaporean population [26], 2.3% in the Blue Mountain Eye Study [14], 38% in the Navajo American Indian population [27], 4.4% in a population in Peru [28], and no documented cases in the Greenland indigenous population [13,29]. Further studies of the individual population-level prevalence of PXF and its associations are needed to further understand PXF globally. ...
Article
Full-text available
The Mayan population of Guatemala is understudied within eye and vision research. Studying an observational homogenous, geographically isolated population of individuals seeking eye care may identify unique clinical, demographic, environmental and genetic risk factors for blinding eye disease that can inform targeted and effective screening strategies to achieve better and improved health care distribution. This study served to: (a) identify the ocular health needs within this population; and (b) identify any possible modifiable risk factors contributing to disease pathophysiology within this population. We conducted a cross-sectional study with 126 participants. Each participant completed a comprehensive eye examination, provided a blood sample for genetic analysis, and received a structured core baseline interview for a standardized epidemiological questionnaire at the Salama Lions Club Eye Hospital in Salama, Guatemala. Interpreters were available for translation to the patients’ native dialect, to assist participants during their visit. We performed a genome-wide association study for ocular disease association on the blood samples using Illumina’s HumanOmni2.5-8 chip to examine single nucleotide polymorphism SNPs in this population. After implementing quality control measures, we performed adjusted logistic regression analysis to determine which genetic and epidemiological factors were associated with eye disease. We found that the most prevalent eye conditions were cataracts (54.8%) followed by pseudoexfoliation syndrome (PXF) (24.6%). The population with both conditions was 22.2%. In our epidemiological analysis, we found that eye disease was significantly associated with advanced age. Cataracts were significantly more common among those living in the 10 districts with the least resources. Furthermore, having cataracts was associated with a greater likelihood of PXF after adjusting for both age and sex. In our genetic analysis, the SNP most nominally significantly associated with PXF lay within the gene KSR2 (p < 1 × 10−5). Several SNPs were associated with cataracts at genome-wide significance after adjusting for covariates (p < 5 × 10−8). About seventy five percent of the 33 cataract-associated SNPs lie within 13 genes, with the majority of genes having only one significant SNP (5 × 10−8). Using bioinformatic tools including PhenGenI, the Ensembl genome browser and literature review, these SNPs and genes have not previously been associated with PXF or cataracts, separately or in combination. This study can aid in understanding the prevalence of eye conditions in this population to better help inform public health planning and the delivery of quality, accessible, and relevant health and preventative care within Salama, Guatemala.
... and the prevalence of advanced glaucoma cases from them was 84(28.4%), and although showed statistically insignificant relationship with age and with sex, there was an increase in prevalence of PEG and advanced glaucoma with increasing age and slightly more in males, this result was comparable to results of Jasna Pavičić-Astaloš, et al. (Pavičić-Astaloš et al., 2016) who showed the prevalence of PEG to be 23.6% with no sex difference, also the result of Seng Lee (2015) in Singapore ( Lee, Wong, & Ho, 2015) showed that the mean age for PEX patients with or without PEG had no statistically significant difference, and there were statistically significant more males having PEG than females, on the other hand, Jonas, et al., (Jonas et al., 2013) reported that after age adjustment for a multivariate analysis; PEX was not related to open-angle glaucoma. Another study was done by Tanushree and Gowda, (2014) in India, they examined 100 patients diagnosed with PEX and screened them for glaucoma, 17.0% of them had PEG, 10 (58.8%) was male and 7(41.2%) were females, who also reported that, although the prevalence of PEX was higher in females, PEG was more in male. ...
Article
Full-text available
OBJECTIVE: Assess the prevalence ‎of PEX and identify the associated glaucoma and ‎cataract.‎ STUDY DESIGN & METHODOLOGY: A sample of 6,650 patients (age ≥40 years) that attended the single ‎ophthalmic private clinic for ‎different complaints, for five years (January 2013 until January 2018), those diagnosed with ‎PEX ‏enrolled in this study, with a total number of 296 ‎patients.‎ RESULTS: ‎14 (4.7%) patients with age from 40-49 years, 54(18.2%) from 50-‎‎59 years, 102 (34.5%) from ‎‎60-69 years, and 126(42.6%) equal or older ‎than 70 years. Close sex frequencies were observed, ‎with 153(51.7%) ‎males, and 143(48.3%) females. In the current study, the prevalence of ‎PEX ‎was 4.45% (95% confidence interval (CI), ‎‎3.98-4.97). There was a statistically insignificant ‎relationship between PEG ‎or advanced glaucoma with age or sex, but cataract was ‎significantly ‎associated with older age and male sex.‎ CONCLUSION: The prevalence of Pseudoexfoliation syndrome was 4.45%, with a sharp increase after the ‎age ‎of 50 years. Although the ‎prevalence of PEG and advanced glaucoma increased with age, it ‎was ‎neither statistically associated with it, nor with sex‏.‏‎ Cataract prevalence ‎was associated ‎with increased age and male sex.‎
... However, the distribution of XFS varies between the different ethnic populations [12]. This wide-ranging frequency of the XFS is evidenced by many studies including India (South India), 3.8% [13]; India (Tamil Nadu), 6.0% [14]; India (Central India), 0.95% [15]; India (Western India), 30% [16]; India (Andhra Pradesh), 3.01% [17], 0.6% [18], and 10.1% [19]; Nepal (Gurungs), 8.2%; Nepal (Tamangs), 0.3% [20]; Myanmar, 3.4% [21]; Kashmir, 26.32% [22]; Japan, 3.4% [23]; Republic of China, 2.38% [24]; Hong Kong (Chinese), 0.4% [25]; Singapore (Chinese), 0.2% [26]; Singapore (Malay), 0.46% [27]; Singapore (Chinese), 2.1%; Singapore (Malay), 4.5%; and Singapore (Indian), 9.7% [28]; Australia (Blue Mountains), 2.3% [29]; Australia (Victoria), 0.98% [30]; Australia (Central Australia), 16.3% [31]; Finland, 22.1% [32]; France, 5.5% [33]; Greece (Epirus), 24.3% [34]; Greece (Crete), 16.1% [35]; Greenland (Eskimos), 4.5% [36]; Iceland, 10.7% [37]; Belgrade, 17.5% [38]; Jordan, 9.1% [39]; Northern Jordan, 10.3% [40]; Iran, 13.1% [41]; Pakistan, 6.45% [42]; Saudi Arabia, 3.5% [43]; Nigeria, 2.7% [44]; Norway, 16.9% [45]; Urban South Africa, 1.4% (white population) and 20% (black population) [46]; Turkey, 7.2% [47] and 10.1% [48]; USA (Framingham), 1.8% [49]; and USA (Southeastern), 3.2% [50]. Overall, these reports suggest that genetic and environmental factors might have a major influence on the phenotypic expression of XFS. ...
Chapter
Exfoliation syndrome (XFS) is common, age-related, and systemic microfibrillopathy. XFS is also a major recognizable cause of secondary open-angle glaucoma and blindness worldwide. It is considered to be a connective tissue disorder of extracellular matrix (ECM) that targets the tissues of the anterior eye segment through abnormal production and excessive accumulation of the fibrillary-flaky white-grayish material. The etiopathogenesis of XFS is still obscure, ten decades of research with XFS from the period of its first description. On the other hand, many explanations were made with both genetic and nongenetic factors, which are believed to be one among the causal mechanisms for XFS. This chapter provides evidence regarding the well-studied genetic, nongenetic, and other associated risk factor-based argument which enriches our understanding of this complex inherited disorder for future research.
Article
Purpose Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison to XFS patients without any CYP39A1 mutation. Design Retrospective case study Participants 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation, who were randomly selected from the Japanese XFS cohort. Methods Two-sided Fisher’s Exact Test with an α-level <0.05 was used to estimate the significance of the calculated Odds Ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. Main Outcome Measures Primary analysis compared the incidence of blindness (defined as visual acuity [VA]<0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field mean deviation (MD), intraocular pressure (IOP) and vertical cup-disc ratio (CDR), between CYP39A1 G204E carriers and those without any CYP39A1 mutation. Results The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared to XFS patients without any CYP39A1 mutations (8/150 [5.3%]; OR7.1 [95%CI:2.7-20.2]; p<0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least one eye compared to the comparison group (41/150 [27.3%]; OR5.1 [95%CI:2.4-11.4]; p<0.0001). Significantly higher peak IOP, larger vertical CDR and worse visual field MD were also found in CYP39A1 G204E variant carriers (p<0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared to those without any CYP39A1 mutation (32/150 [21.3%], p<0.001). Conclusions Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG and more severe glaucoma compared to patients with XFS without any CYP39A1 mutation.
Article
INTRODUCTION: Pseudoexfoliation (PXM) is a fibrillar material deposited in the anterior chamber of the eye and can cause disintegration of zonules and make pupillary dilatation difficult. This can make surgery difficult and result in intraoperative and postoperative complications. The aim of this study was to learn about whether the presence of pseudoexfoliation caused significant complications during cataract surgery. MATERIALS AND METHODS: We did a secondary data analysis of 12,992 eyes from 2007 to 2014 using the National Eye Database of Melaka Hospital Malaysia on intraoperative and postoperative cataract surgery complications of patients with PXM. RESULTS: Patients with PXM were 2.68 times more likely to get intraoperative complications (P < 0.001). They had a higher incidence of lens subluxation, zonular dehiscence, and vitreous loss (P < 0.001). Although posterior capsule rupture (PCR) was the most common intraoperative complication during cataract surgery (4.8%), the presence of pseudoexfoliation was not associated with PCR (P > 0.05). We did not observe any association between patients with pseudoexfoliation and any of the postoperative complications such as corneal decompensation, raised intraocular pressure, and intraocular lens decentration (P > 0.05). Pseudoexfoliation did not cause corneal decompensation (P > 0.05) although corneal decompensation was the highest postoperative complication of cataract surgeries (0.18%). CONCLUSIONS: Patients with PXM had a higher rate of intraoperative complications which were mainly vitreous loss and zonular dehiscence and also lens subluxation/dislocation. We observed poorer visual outcomes in those with PXM following cataract surgery. Patients with pseudoexfoliation should be identified and precautions taken to minimize these complications to get better visual outcomes.
Article
Introduction: Pseudoexfoliation syndrome is commonly associated with pseudoexfoliation glaucoma. The two nonsynonymous single-nucleotide polymorphisms rs1048661 (R141L) and rs3825942 (G153D) within exon 1 of LOXL1 gene have been found to confer risk of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in different geographical populations. This study aims to find association between two nonsynonymous single-nucleotide polymorphisms with pseudoexfoliation syndrome and pseudoexfoliation glaucoma in North Indian population. Methods: North Indian subjects clinically diagnosed with pseudoexfoliation syndrome/pseudoexfoliation glaucoma and normal age-matched control were enrolled in the study. Genomic DNA was extracted and the two single-nucleotide polymorphisms of LOXL1 gene were genotyped by polymerase chain reaction and sequencing. The association between single-nucleotide polymorphisms with pseudoexfoliation syndrome/pseudoexfoliation glaucoma was evaluated by chi-square test. Results: A total of 30 pseudoexfoliation glaucoma, 27 pseudoexfoliation syndrome and 61 control subjects were enrolled in the study. Patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma did not show any genetic association with either single-nucleotide polymorphism rs1048661 or rs3825942. Conclusion: The study shows lack of association between LOXL1 single-nucleotide polymorphisms and pseudoexfoliation in North Indian population.
Article
Full-text available
Purpose: To investigate the association of the two single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene with pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG) in a Greek population-based setting, from the Thessaloniki Eye study. Methods: A total of 233 subjects with successful DNA extraction, PCR amplification, and genotyping were included in the genetic analysis of G153D and R141L SNPs of LOXL1 gene and classified into four groups: controls (n = 93); subjects with PEX (n = 40); POAG (n = 66); and PEXG (n = 34). Multinomial logistic regression was used to test their association with LOXL1 SNPs with adjustment for covariates. The association of LOXL1 with IOP (in untreated subjects) and with systemic diseases was explored. Results: Both LOXL1 SNPs were present in high frequencies in controls and cases. The G153D was strongly associated with both PEX (odds ratio [OR] = 23.2, P = 0.003 for allele G) and PEXG (OR = 24.75, P = 0.003 for allele G) and was not associated with POAG (P = 0.451). In contrast, the R141L was not associated with PEX (P = 0.81), PEXG (P = 0.063), or POAG (P = 0.113). No association of the G153D with either intraocular pressure (IOP) or systemic diseases was found. Conclusions: In the Thessaloniki Eye Study, the G153D SNP of LOXL1 gene was strongly associated with both PEX and PEXG, whereas the R141L was not associated. No association of the LOXL1 with IOP or with systemic diseases was found. These findings further support the hypothesis that the LOXL1 gene contributes to onset of PEXG through PEX. Gene variants of LOXL1 do not help to identify those with PEX at increased risk for glaucoma development.
Article
Full-text available
To assess the prevalence of pseudoexfoliation (PEX) and its associations in a population-based setting. Population-based, cross-sectional study. The Central India Eye and Medical Study included 4711 individuals. All study participants underwent a detailed ophthalmological examination. After medical pupil dilation, PEX was assessed by an experienced ophthalmologist using slit-lamp based biomicroscopy. Slit lamp examination results were available for 4646 (98.6%) study participants with a mean age of 49.3±13.3 years (range: 30-100 years). PEX was detected in 87 eyes (prevalence: 0.95±0.10% (95%CI: 0.75, 1.15) of 69 subjects (prevalence: 1.49±0.18% (95%CI: 1.14, 1.83). PEX prevalence increased significantly (P<0.001) from 0% in the age group of 30-39 years, to 2.85±0.56% in the age group of 60-69 years, to 6.60±1.21% in the age group of 70-79 years, and to 12.3±4.11% in the age group of 80+ years. In multivariate analysis, PEX prevalence was associated with higher age (P<0.001; regression coefficient B:0.11; odds ratio (OR): 1.11 (95%CI: 1.09, 1.13)), lower body mass index (P = 0.001; B: -0.12; OR: 0.88 (95CI: 0.82, 0.95)) and higher diastolic blood pressure (P = 0.002; B: 0.02; OR: 1.03 (95%CI: 1.01, 1.04)). In the multivariate analysis, PEX was not associated with retinal nerve fiber layer cross section area (P = 0.76) and presence of open-angle glaucoma (P = 0.15). In a rural Central Indian population aged 30+ years, PEX prevalence (mean: 1.49±0.18%) was significantly associated with older age, lower body mass index and higher diastolic blood pressure. It was not significantly associated with optic nerve head measurements, refractive error, any ocular biometric parameter, nuclear cataract, early age-related macular degeneration and retinal vein occlusion, diabetes mellitus, smoking, and dyslipidemia.
Article
Full-text available
The purpose of this study was to estimate the prevalence of exfoliation syndrome (XFS) and its association with ocular disease in patients attending the eye clinic of the University College Hospital (UCH) in Ibadan, Nigeria. A total of 448 consecutive new patients, aged 30-90 years who presented to the eye clinic of UCH between December 2009 and November 2010 were evaluated. Each patient had a complete ophthalmic examination. Patients with exfoliative material on the anterior lens surface and/or pupillary margin in either or both eyes were considered to have XFS. Means, standard deviation, and 95% confidence intervals were calculated. All the patients examined were from the southern part of Nigeria. Majority (94.2%) were of the Yoruba tribe from southwestern Nigeria, while 5.8% were from southeastern Nigeria. The mean age of the study cohort was 58.5 ± 13.8, 54.8% were males, 12 (2.7%) had XFS. All patients with XFS were of the Yoruba tribe, with a mean age 65.6 ± 5.6 years. There was a male predilection (66.7%). All eyes with XFS had lenticular opacities. XFS was bilateral in eight patients (66.7%) of whom seven patients (87.5%) had glaucoma and lenticular opacities bilaterally. This is the first report of the existence of XFS in Nigeria. Larger studies are necessary in this population to further investigate the disease.
Article
Background: Pseudoexfoliation syndrome (PXS) is regarded as rare in people of Chinese ethnicity but the prevalence of this condition is not known. This epidemiology study was conducted to assess the prevalence of PXS in cataract patients and to report the clinical features present. Methods: Prospective descriptive study conducted in the period from March 1999 to May 2001 in ophthalmology departments in cluster hospitals serving a population of about 1.2 million. 500 consecutive patients aged 60 or above attending the general ophthalmic clinics with a presumed diagnosis of cataract were recruited. A detailed examination including biomicroscopy, intraocular measurement, and gonioscopy were performed on all patients. All positive PXS cases were documented photographically. Results: 500 patients were examined. They ranged from the ages of 60 to 91 years old, with a male to female ratio of 1:2. 40% suffered from hypertension while 24% were known diabetics. Only two positive cases (0.4%) of PXS were identified in the study population. 18% of all eyes were found to have narrow angles (defined as grade 0 to 2 by Shaffer grading). Nuclear sclerosis was the single most common type of lens opacity. Conclusion: PXS is a rare condition in Chinese people. A prevalence rate of 0.4% in patients aged 60 or above was identified in this hospital based epidemiology study. To the best of our knowledge, this was the first study conducted in a Chinese population to examine the prevalence of PXS.
Article
Pseudoexfoliation (PEX) syndrome is a common age-related disorder affecting intraocular and extraocular tissues. This review focuses on recent publications related with the pathogenesis and associations of PEX syndrome with intraocular pressure (IOP), glaucoma and systemic diseases. In PEX tissues, expression of lysyl oxidase-like 1 (LOXL1) was found to be markedly dysregulated. This may adversely affect elastin metabolism and lead to elastotic alteration in tissues such as lamina cribrosa. There is increasing evidence that cellular stress conditions and low-grade chronic inflammatory processes are involved in the pathogenesis of PEX. Although there is an increased risk for glaucoma development in patients with PEX and ocular hypertension as compared with non-PEX patients with ocular hypertension, LOXL1 single nucleotide polymorphisms were not associated with intraocular pressure (IOP) differences. Lack of association of PEX with all-cause mortality or dementia has been reported recently. The association with vascular diseases is not consistent among different studies. Despite the high prevalence of the LOXL1 variants in the general population, a much lower proportion of the population develops PEX, suggesting that in addition to LOXL1, other genetic, epigenetic and environmental factors may contribute to the development of PEX. Also, LOXL1 cannot help to identify those with PEX at increased risk for glaucoma development. Increased risk for glaucoma development in PEX patients who present with increased IOP may be related to other factors beyond IOP, contributing to increased vulnerability of the optic nerve to glaucoma development in the presence of PEX.
Article
Purpose To assess the prevalence of pseudoexfoliation (PEX) and its associations in a population-based setting. Methods The population-based Central India Eye and Medical Study included 4711 individuals. All study participants underwent a detailed ophthalmological examination. After medical pupil dilation, PEX was assessed by an experienced ophthalmologist using slit-lamp based biomicroscopy. Results PEX was detected in 87 eyes (prevalence: 0.950.10% (95%CI:0.75,1.15) of 69 subjects (prevalence: 1.490.18% (95%CI:1.14,1.83). In multivariate analysis, PEX prevalence was associated with higher age (P
Article
Exfoliation syndrome (XFS) is an age-related disease in which abnormal fibrillar extracellular material is produced and accumulates in many ocular tissues. Its ocular manifestations involve all of the structures of the anterior segment, as well as conjunctiva and orbital structures. Glaucoma occurs more commonly in eyes with XFS than in those without it; in fact, XFS has recently been recognized as the most common identifiable cause of glaucoma. Patients with XFS are also predisposed to develop angle-closure glaucoma, and glaucoma in XFS has a more serious clinical course and worse prognosis than primary open-angle glaucoma.
Article
Objective: To assess the prevalence of pseudoexfoliation syndrome (PEX) and its associations in a population-based setting. Design: Population-based, cross-sectional cohort study. Participants: Of 4403 eligible subjects with an age of ≥ 50 years, 3468 individuals (78.8%) participated in the Beijing Eye Study 2011 (mean age, 64.6 ± 9.8 years; range, 50-93 years). Methods: All study participants underwent a detailed ophthalmologic examination. After medical pupil dilation, PEX was assessed by an experienced ophthalmologist using slit-lamp-based biomicroscopy. Main outcome measures: Prevalence and associations of PEX. Results: Slit-lamp examination results were available for 3022 study participants (87.1%). Definite pseudoexfoliation was observed in 72 of the 3022 subjects, with a prevalence of 2.38% (95% confidence interval [CI], 1.84-2.93). Suspected PEX was detected in 104 of the subjects (3.44%; 95% CI, 2.8-4.1). The overall prevalence of PEX (definite and suspected) was 176 of 3022 or 5.82% (95% CI, 4.99-6.66). In 80 subjects (45.5%), PEX was detected in both eyes, whereas it was detected only in the right eye in 42 subjects (23.9%) and only in the left eye in 54 (30.7%). The prevalence of PEX increased from 1.1% in among those 50 to 54 years old, to 3.5%, 5.7%, and 11.8% among those 60 to 64 years, 70 to 74 years, and ≥ 80 years, respectively. In multivariate analysis, presence of PEX was significantly associated with older age (P<0.001; odds ratio [OR], 1.08; 95% CI, 1.04-1.10), shorter axial length (P = 0.03; OR, 0.82; 95% CI, 0.68,0.98), and shallower anterior chamber (P = 0.03; OR, 0.59; 95% CI, 0.36-0.95). We found that PEX was not associated (all P>0.05) with sex, diabetes mellitus, blood pressure, psychological depression, smoking, dyslipidemia, body mass index, central corneal thickness, corneal diameter, optic nerve head measurements, choroidal thickness, retinal vessel diameters, early age-related macular degeneration, or retinal vein occlusion. Conclusions: In a North Chinese population aged ≥ 50 years, the prevalence of definite PEX was 2.38% (95% CI, 1.84-2.93), suspect PEX was 3.4% (95% CI, 2.8-4.1) and overall PEX was 5.82% (95% CI, 4.99-6.66). We found PEX to be associated with older age, shorter axial length, and shallower anterior chamber. The relationship between PEX and glaucomatous optic neuropathy remained inconclusive among our population. Financial disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.
Article
To study the prognosis of capsular glaucoma (102 eyes) as compared to simplex glaucoma (58) eyes), a retrospective comparison of the functional status of these diseases when first diagnosed and five years afterwards was made. At the first examination the capsular glaucoma eyes were on average more seriously damaged. After five years this tendency was more marked with several amaurotic eyes, 17% as compared to 10% of the simplex glaucoma group. Severe visual field loss in the eyes with advanced glaucoma after five years was present in 48% of the capsular glaucoma group but only 19% of the simplex glaucoma group.