Purpose To determine the prevalence and risk factors for pterygium in the adult Malay population of Singapore.
Methods A population-based survey of Malays aged 40 to 79 years living in Singapore was conducted. Pterygium was diagnosed and graded clinically by slit-lamp examination as Grade 1 (atrophic), Grade 2 (intermediate) and Grade 3 (fleshy). We asked about potential risk factors such as socioeconomic status, cigarette smoking and outdoor activity.
Results From a total of 4168 eligible subjects, 3280 (78.7%) were examined. There were 508 people with either unilateral (n=289) or bilateral (n=219) pterygium. The overall age-standardised prevalence rate of pterygia was 12.3% (95% CI 11.9% to 12.7%). In multiple logistic regression models, pterygium was independently associated with increasing age (OR, 1.3; 95% CI 1.1 to 1.4), male sex (OR, 1.9; 95% CI 1.5 to 2.6) and high systolic blood pressure (OR, 1.6; 95% CI 1.2 to 2.1). Grade 3 pterygium (n=92) was also associated with cholesterol in the fourth versus the first quartile (p=0.02) and with male sex. Outdoor occupation is only significant for severe pterygium (p=0.03).
Conclusions The prevalence of pterygium is 12.3% among urban Malays aged 40 years and older and higher than Chinese of similar ages in Singapore. Independent associations of pterygia with increasing age, male sex, outdoor occupations and systemic factors like blood pressure suggest a complex and multi-factorial aetiology for this condition.
- Malay population
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Pterygium is a wing-shaped, fibrovascular growth of the bulbar conjunctiva that if left untreated may result in significant visual morbidity. Numerous theories regarding its aetiology and pathogenesis, ranging from elastotic degeneration to altered epithelial basal cells, have been postulated, but none as yet have gained universal acceptance.1–3
Prevalence rates worldwide vary greatly from 2.8% to 23.7%.4–6 McCarty et al conducted a study on 5147 residents of Victoria, Australia, and the overall weighted population rate was 2.83% for pterygium. A study by Luthra on 2781 subjects in Barbados, West Indies, on the other hand, revealed a prevalence rate of 23.7%. In 1997, Wong et al conducted a population-based study among the adult Chinese population aged 40 and older in Singapore. One thousand two hundred and thirty-two subjects were examined, and the overall prevalence rate of pterygium was 6.9%. Prevalence was noted to increase with age and was higher among men.7 Subsequent studies by Gazzard et al8 and Tan et al9 also focused on regions near the equator, but their study populations consisted of adult Malays living in rural communities. Gazzard's group conducted a population-based prevalence survey on 1210 adults aged 21 years and above in five rural villages and one provincial town in the Riau province of Sumatra, Indonesia. Their age-adjusted rate for any pterygium was 10.0%. Tan's study was also conducted in the Riau Archipelago in an island called Pulau Jaloh. Four hundred and seventy-seven subjects from all age groups were screened, and the overall pterygium prevalence was 17.0%. To our best knowledge, no such study has ever been conducted among adult Malays in an urban setting.
The purpose of our study is to determine the prevalence and risk factors for pterygium in an urban adult Malay population in Singapore.
The study population included Malay adults aged 40–79 years residing in 15 residential areas located at the south-western part of Singapore using a sampling frame from the Ministry of Home Affairs. Disproportionate age-stratified random sampling was conducted. From this list, an initial sample size of 5600 was calculated. Four thousand one hundred and sixty-eight subjects were deemed eligible, and 3280 subjects eventually came to our centralised clinic where a standardised interview was administered and comprehensive ocular examinations were conducted. In a comparison between participants and non-participants, there was no difference in rates with regard to sex, but those who belonged to the older age groups (70 to 79 years) and those who lived further away from the examination clinic had higher rates of non-participation. The detailed methodology of The Singapore Malay Eye Study (SiMES) has been described elsewhere.10
Written informed consent was obtained after an explanation of the study in either Malay or English. This study was approved by the Institutional Review Board of the Singapore Eye Research Institute and conducted in accordance with the Declaration of Helsinki.
As part of the standard clinic-based examination, a slit lamp (Haag-Streit model BQ-900, Haag-Streit, Switzerland) was used to examine the anterior segment for evidence of pterygium. The diagnosis of pterygium was made clinically by trained ophthalmologists. It was defined as an extension of the conjunctiva onto the clear cornea for which there was no alternative explanation. Pterygium was diagnosed and graded clinically by slit lamp examination as Grade 1 (atrophic), Grade 2 (intermediate) and Grade 3 (fleshy).11 In a Grade 1 pterygium, the episcleral vessels under the body were clearly visible, whereas a Grade 3 pterygium completely obscured the episcleral vessels. Any pterygium which does not fit into the criteria of a Grade 1 or Grade 3 pterygium is labelled a Grade 2 pterygium. They were also classified as either unilateral or bilateral. Anterior segment photographs were taken for both eyes of all participants but were not used in pterygium grading.
Each participant's height was measured in centimeters using a wall-mounted measuring tape, while weight was measured in kilograms using a digital scale (SECA, model 782-2321009:Vogel and Halke, Hamburg, Germany). Body mass index (BMI) was calculated as kilograms per square metre. Blood pressure was taken with the participant seated and after 5 min of rest. Systolic and diastolic pressures were measured with a digital blood pressure monitor (Dinamap model Pro Series DP 110X-RW, 100V2; GE Medical Systems Information Technologies, Inc., Milwaukee, Wisconsin, USA) on two occasions 5 min apart. If the blood pressures differed by more than 10 mm systolic and 5 mm diastolic, a third measurement was made. The blood pressure of the individual was then taken as the mean between the two closest readings.
A 40-ml non-fasting sample of venous blood was collected to determine levels of serum glucose and glycosylated haemoglobin (Hb A1C), serum lipids (total cholesterol, high-density lipoprotein (HDL)-cholesterol, direct low-density lipoprotein (LDL)-cholesterol) and serum creatinine. All serum biochemistry tests were sent to National University Hospital Reference Laboratory for measurement on the same day. Diabetes mellitus was defined as having non-fasting glucose levels ≥11.1 mmol/l, the use of diabetic medication or self-reported history of diabetes.
A standardised interview using a standardised questionnaire translated into the Malay language was used to collect information about medical history (eg, diabetes, hypertension), cigarette smoking (defined as ever or never) and alcohol intake (defined as ever or never). Socioeconomic assessment included questions on completed educational level, current occupation and whether the occupation was primarily indoor or outdoor, housing type and marital status.
For analysis based on clinical grades of pterygium, if a person had bilateral pterygium, he or she was classified according to the higher grade in either eye (worse eye). Multiple logistic regression models were developed to compute multivariate-adjusted odds ratios and corresponding 95% CI adjusting for relevant confounders. The commercially available software SAS V.9.0 was used, and significance level was assessed at 0.05.
From a total of 4168 eligible subjects, 3280 (78.7%) were examined. 14 respondents had missing data and were excluded from the statistical analysis. There were 508 people with pterygium in either eye (adjusted rate=12.3%). Of these, 219 had bilateral disease (adjusted prevalence of 4.9%). The highest prevalence occurred in the 70–79-year-old group, and there was a significant increase in prevalence rates with age in both men and women. Men had prevalence rates almost twice that of women for both any and bilateral pterygium (16.1% vs 8.8% and 7.0% vs 2.9%, respectively) (table 1).
Older subjects, male sex, higher systolic and diastolic blood pressure and higher total cholesterol were associated with any pterygium (table 2). Other risk factors which were examined but were not associated with any pterygium, bilateral pterygia or severe pterygia include socio-economic status (assessed by individual monthly income and housing type), marital status, level of alcohol intake, presence of diabetes including serum glucose and HBA1c levels, diastolic blood pressure, BMI, HDL and LDL levels and serum creatinine.
In final multiple-logistic regression models, older age (OR=1.3 for each 10-year increase), male sex (OR=1.9) and systolic blood pressure (OR=1.6 for fourth vs first quartile) were associated with any pterygium, after adjusting for cigarette smoking, total cholesterol, education and occupation. In similar models, older persons and men were associated with bilateral pterygia, while those who ever smoked had increased odds of pterygia (OR=1.5), but this relationship was of borderline significance (p=0.04). Adults with serum cholesterol in the fourth versus first quartile had increased risks of severe pterygia (OR=2.2; 95% CI 1.1 to 4.5) in a multiple logistic regression model (table 3).
In summary, 12.3% of ethnic urban Malays older than 40 years old had pterygium in either eye, with 4.9% having pterygium in both eyes. Our prevalence is higher compared to those of the Tanjong Pagar Study, a population-based survey conducted by Wong et al7 in 1999 on the ethnic Chinese population of Singapore using the same sampling methods and methodology. Wong's group examined 1232 out of 1717 eligible subjects (71.8% participation rate), with 120 people having either unilateral or bilateral pterygium, equivalent to an overall prevalence of 6.9% in the Chinese population aged 40 to 79 years. The higher prevalence of pterygia in Singapore Malays compared with Chinese may be attributed to differences in lifestyle including outdoor activity patterns, outdoor occupations and exposure to UV light, as well as differences in genetic susceptibility. Our rates were more similar to those from two studies conducted on rural Malays in the Sumatra province of Indonesia. Gazzard et al had an overall prevalence rate of 10% with a rate of 4.1% for bilateral pterygium, while Tan et al had an overall prevalence of 17.0%. However, one should bear in mind that these comparisons are limited by differences in the study methodology such as participation rate, age ranges, etc. It is tempting to attribute the fairly high prevalence for pterygium among the urban Malay population of Singapore to geographic proximity to the equator. Indeed, Cameron12 and other investigators have written numerous articles about the presence of a “pterygium belt” located 37° north and south of the equator within which pterygium prevalence increased correspondingly with greater proximity to the equator.13 However, Wong et al pointed out that this hypothesis may be oversimplistic and tends to mask the effect of other factors such as racial or genetic predisposition. He disproved the geographic theory by noting similar rates between Singapore and Sydney (which are 34° apart in latitude) and between Singapore and Greenland (which are 60° apart in latitude).7
Other population-based surveys with high prevalence rates include the Meiktila Eye Study14 and the Barbados Eye Study.6 In Meiktila, Central Myanmar, ophthalmologists examined 2076 rural villagers aged 40 years and above. The prevalence rate for any and bilateral pterygium was 19.6% and 8.0%, respectively. The Barbados Eye Study in the West Indies reported a prevalence rate of 23.4% for pterygium among its black population, which is more than twice the prevalence rate of 10.2% for its white population. The high rates of pterygia in Barbados may be attributed to differences in outdoor lifestyle as well as genetic susceptibility. The rates are in stark contrast to those from the Beijing Eye Study,15 where a mixed population of urban and rural communities yielded a prevalence rate of approximately 3.0% for any and 0.9% for bilateral pterygium. There were also significant associations with rural versus urban populations (with higher rates in the rural communities), increasing age and male sex.
Our results are consistent with the long-held belief that UV radiation plays a role in pterygium pathogenesis. Subjects with increased outdoor exposure were more likely to develop severe pterygium compared to those who spent most of their time indoors.16–19 Older subjects were also noted to be more likely to develop pterygium, which is consistent with the expected effects of greater cumulative UV exposure and also suggesting that there may be other factors at play such as chronic ocular surface inflammation, Meibomian gland dysfunction or dry eye.20 21 Interestingly, our study did not show any association between Meibomian gland dysfunction and pterygium (p=0.584). The study by Tongg et al22 on the same population also failed to find any correlation between dry eye symptoms and pterygium. A prospective survey focusing on Meibomian gland dysfunction and dry eye is currently underway, and the results may shed further light on the relationship of these conditions to pterygium. Abnormalities in the tear film may cause predisposition to proliferation of fibrovascular tissue; Taylor23 noted that aborigines with pterygium were found to have a disruption in the marginal tear strip compared to those without pterygium. Increased tear osmolarity could possibly stimulate production of matrix metalloproteinases, alter function of limbal epithelial cells and induce pterygium.2 If pterygium is due to a stem cell disorder, advancing age may be related to a depletion of stem cell reserves as older individuals would presumably have been exposed to longer periods of chronic ocular irritation and/or low-grade inflammation. It may be interesting to note that weak associations were found between pterygium prevalence and two previously unexplored risk factors: systolic blood pressure and total cholesterol levels. Subjects with systolic blood pressure measurements in the highest quartile were at higher risk of developing Grade 1 or Grade 2 pterygium. There are experimental models where hypertension has been shown to aggravate pre- existing oxidative stress.24 This mechanism may play a putative role in pterygium pathogenesis by increasing the damage caused by UV radiation on the limbal basal stem cells and accelerating the multistep mutation pathway that leads to pterygium formation.2 Subjects with cholesterol levels in the highest quartile were noted to be twice as likely to develop Grade 3 pterygium compared to those whose cholesterol values belonged to the lowest quartile. However, cholesterol levels were not significantly associated with bilateral pterygium and were only of borderline significance for any pterygium. Peiretti and his colleagues25 26 have elucidated that pterygium and pinguecula have altered cholesterol metabolism and that intracellular modifications of cholesterol homeostasis may be relevant to pterygium development. Overall, the strength of our study lies in our large sample size of a population-based study, a high response rate, utilisation of an objective means of grading pterygia and the comprehensive assessment of risk factors. The limitations of our study include the lack of detailed ultraviolet light models, limited cumulative occupational history and, possibly, a misclassification of pterygium grading as well as a failure to distinguish primary from recurrent pterygium. Furthermore, despite having a response rate of 78.7% for our study, the demographics and ophthalmic profile of our participants may be different from non-participants.
The prevalence of pterygium in Singapore is 12.3% among Malays aged 40 years and older. This is twice the rate compared to the adult Chinese population in Singapore and comparable to the rural Malay communities in Indonesia. Further studies of pterygia in Asian populations with emphasis on racial or genetic predisposition and with precise measures of lifestyle risk factors are warranted.
Our study was funded by the National Medical Research Council (NMRC), 0796/2003 and the Biomedical Research Council (BMRC), 501/1/25-5, with support from the Singapore Prospective Study Program and the Singapore Tissue Network, A *STAR.
Funding National Medical Research Council (NMRC) Singapore, Biomedical Research Council (BMRC) Singapore.
Competing interests None.
Ethics approval This study was conducted with the approval of the Institutional Review Board of the Singapore Eye Research Institute.
Provenance and peer review Not commissioned; externally peer reviewed.
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