- Email: [email protected]
Prevalence and Causes of Amblyopia in a Rural Adult Population of Chinese
Prevalence and Causes of Amblyopia in a Rural Adult Population of Chinese The Handan Eye Study Yue Wang, MD,1 Yuan Bo Liang, MD, PhD,1,2 Lan Ping Sun, MD,2 Xin Rong Duan, MD, PhD,1 Rui Zhi Yuan, MD,2 Tien Yin Wong, PhD,3,4 Peng Yi, MD,1 David S. Friedman, MD, PhD,5,6 Ning Li Wang, MD, PhD,1 Jie Jin Wang, MD, PhD3,7 Objective: To determine the prevalence of and factors associated with amblyopia in a rural Chinese population. Design: Population-based, cross-sectional study. Participants: Six thousand eight hundred thirty Han Chinese aged 30 years or more, recruited from Yongnian County, Handan, Hebei Province, China. Methods: Thirteen villages in the Yongnian County of Handan were selected randomly, and residents of these selected villages 30 years of age or older were invited to participate in the Handan Eye Study. Participants underwent a comprehensive eye examination, including standardized visual acuity (VA) tests using logarithm of the minimum angle of resolution charts. Prevalence rates were age- and gender-standardized to the 2000 China census. Main Outcome Measures: The proportion of rural Chinese population aged 30 years or older with amblyopia. Unilateral amblyopia was diagnosed if best-corrected VA (BCVA) was 20/32 or worse in the amblyopic eye and was not attributable directly to any underlying structural abnormality of the eye or visual pathway. Bilateral amblyopia was diagnosed if BCVA was 20/32 or less in both eyes and if there was a history of form deprivation during the sensitive period of visual development, such as media opacities or high, uncorrected ametropia. Results: Amblyopia was diagnosed in 205 participants, with an age- and gender-adjusted prevalence of 2.8%. Of these, 1.7% were unilateral cases and 1.1% were bilateral cases. Underlying causes included anisometropia (67.3%), strabismus (5.4%), mixed strabismus and anisometropia (4.4%), visual deprivation (9.8%), astigmatism association (9.8%), and other (3.4%). Of the amblyopia cases, 47.6% were hypermetropic. Conclusions: In this rural Chinese population, 2.8% of adults 30 to 80 years of age had amblyopia, a prevalence rate broadly consistent with that of most other studies. One third of the cases were bilateral, and anisometropia was the most common cause of this condition. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011;118:279 –283 © 2011 by the American Academy of Ophthalmology.
Amblyopia traditionally has been defined by what it is not, rather than what it is.1 Amblyopia manifests as a unilateral or bilateral reduction of best-corrected visual acuity (BCVA), for which no organic cause can be detected on physical examination of the eye and, in appropriate cases, is reversible by therapeutic measures.2 A commonly used definition of unilateral amblyopia is that BCVA differs by 2 or more Snellen or logarithm of the minimum angle resolution lines between the 2 eyes.1 Amblyopia has been recognized as a common cause of unilateral visual impairment.3,4 The authors recently reported that amblyopia was the second most common cause of unilateral low vision and the fourth leading cause of unilateral blindness in a rural adult Chinese population, the Handan Eye Study population.3 Persons with amblyopia are at greater risk of injury to the nonamblyopic eye and subsequently to bilateral vision loss.5 The Multi-Ethnic Pediatric Eye Disease Study reported an amblyopia prevalence of 2.6% in Hispanic/Latino children younger than 72 months and of 1.5% in African American children younger than 72 months.6 The Baltimore Pediatric © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
Eye Disease Survey reported an amblyopia prevalence of 1.8% in white children and of 0.8% in African American children of the same age.7 The prevalence of amblyopia has been estimated to be 0.2%8 to 5.3%9 among Chinese children. Zhao et al10 reported a prevalence of 0.92% among children 5 to 15 years of age in the Shunyi District in Beijing, and He et al11 reported a prevalence of 0.87% among such children in Guangzhou, China. In a remote area of the Qinghai-Tibetan Plateau of China, the prevalence was 1.02% among Tibetan children 6 to 14 years of age.12 However, there have been few data regarding amblyopia among Chinese adults. This article describes the prevalence, causes, and associated factors of amblyopia in a population-based sample of rural Chinese adults, residents of Handan, China.
Patients and Methods Study Design The Handan Eye Study is a population-based survey of vision and common eye diseases in an urban population 30 years of age and ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2010.05.026
279
Ophthalmology Volume 118, Number 2, February 2011 older from Yongnian County. The study adhered to the Declaration of Helsinki, ethics approval was obtained from the Beijing Tongren Hospital Ethical Committee, and written informed consent was obtained from all participants. Residents of Yongnian County, Handan, Hebei Province, who were 30 years of age or older were selected randomly using a stratified, clustered, and multistaged sampling technique with probabilities proportionate to the size of the population in each cluster. In Yongnian County, 90% of the adult population is engaged in farming and 98% is of Han ethnicity.3,13 Participants underwent an extensive and standardized eye examination, including a detailed questionnaire, visual acuity (VA) assessment, and slit-lamp and fundus examination before and after pupil dilation. Digital ocular images were obtained using the following procedures: optic nerve head imaging using Heidelberg Retinal Tomography II (Heidelberg Engineering, Heidelberg, Germany) and retinal photography using a Canon CR-DGi Nonmydriatic Retinal Camera (Canon, Tokyo, Japan). The study protocol was modified from the protocol used in the Singapore Malay Eye Study.14 The VA was measured using a logarithm of the minimum angle of resolution chart with 5 letters on each line while the participants were wearing current distance glasses. Subjective refraction was performed if the initial VA was worse than 0 (logarithm of the minimum angle of resolution; Snellen equivalent, 20/20), following a standardized protocol. The BCVA was defined according to the VA obtained after subjective refraction. A cover test and cover– uncover test were performed by a senior ophthalmologist (RZY) at near fixation. If any abnormalities were found, a cover test at a distance of 20 feet and an assessment of eye movements also were performed. Strabismus was coded as tropia, cranial nerve palsy, and phoria.
Definitions Adjudication was provided by senior investigators who examined all amblyopia cases that initially were diagnosed during the study examinations, confirmed the diagnosis, and assigned the underlying cause for the confirmed cases. The diagnosis of underlying causes took into account past histories of poor vision from childhood. The definitions used in the Blue Mountains Eye Study were followed.4 Unilateral amblyopia was diagnosed if BCVA was 20/32 or worse in the amblyopic eye and was not attributable directly to any underlying structural abnormality of the eye or visual pathway. Bilateral amblyopia was diagnosed if BCVA was 20/32 or less in both eyes and if there was a history of form deprivation during the sensitive period of visual development, such as media opacities or high, uncorrected ametropia.4 Myopia, emmetropia, and hypermetropia were defined as a spherical equivalent of less than ⫺0.5 diopter (D), between ⫺0.5 and ⫹0.5 D inclusive, and more than ⫹0.5 D, respectively. High hypermetropia was defined as spherical equivalent of more than ⫹5.0 D, and high myopia was defined as spherical equivalent of less than ⫺5.0 D. Subjects were classified according to the eye with a more severe degree of hypermetropia or myopia. High astigmatism was
considered present if the cylindrical refractive error was 2 D or more. Amblyopia cases were categorized into 6 types according to the underlying causes as described previously4,15: (1) anisometropic amblyopia: if there was a difference in the sphere or cylinder power between the 2 eyes of 1 D or more and no strabismus present; (2) strabismic amblyopia: if manifest strabismus was present without anisometropia or high refractive error, manifest strabismus was defined as constant or intermittent tropia of any magnitude at near fixation; (3) mixed amblyopia: if anisometropic amblyopia and strabismic amblyopia coexisted; (4) stimulus deprivation amblyopia: if congenital cataract, ptosis, corneal opacities, or other media opacities obstructed vision during the visual development period (from after birth to 7 years of age)— high refractive errors such as high hypermetropia and high myopia that were uncorrected during childhood were classified as this category as well4; (5) astigmatism-associated amblyopia: because uncorrected astigmatism can result in amblyopia,16 –18 astigmatismassociated amblyopia was identified if a high degree of astigmatism (cylindrical refractive error ⱖ2 D) was the only cause present in both eyes and if the difference in the cylindrical power between the 2 eyes was less than 1 D: (6) others: cases that did not fall into the above categories.15 If the participants were bilaterally amblyopic, the BCVA in the better-seeing eye was used.
Statistical Analysis Statistical analyses were performed using the Statistical Analysis System for Windows version 9.1.3 (SAS Inc., Cary, NC). Prevalence of amblyopia and 95% confidence intervals (CI) were estimated. The chi-square test was used to compare proportions for categorical variables. Two-sided P values ⬍0.05 were considered statistically significant. The age- and gender-standardized prevalence of amblyopia was estimated after direct standardization of the study sample to the 2000 China census.3,13,19,20
Results Of 7577 eligible residents 30 years of age or older, 6830 (90.4% response rate) participated in the study. The BCVA could be assessed accurately in 6799 (99.5%) participants. Amblyopia was diagnosed in 205 persons (3.02%), 94 of whom were men (46%). After age- and gender-standardization to the 2000 China census, the amblyopia prevalence was 2.8% (95% CI, 2.4%–3.2%; Table 1). Unilateral amblyopia was diagnosed in 114 persons (prevalence rate, 1.7%; 95% CI, 1.4%–2.0%) and bilateral amblyopia was diagnosed in 91 (1.1%; 95% CI, 0.8%–1.3%). If visual acuity of 20/40 or worse was used as the diagnostic criterion to define amblyopia, 136 persons met such a criterion and were amblyopic, with an age- and gender-adjusted prevalence rate of 1.8% (95% CI, 1.4%–2.1%). Of this group, 93 were unilateral, and 59 were amblyopic in the left eye (51.8%; P⬎0.05). There was no statistically significant difference in the prevalence of amblyopia
Table 1. Prevalence of Amblyopia* in the Handan Eye Study Visual Acuity Criterion Used
Total
Men
Women
Unilateral
Bilateral
ⱕ20/32 ⱕ20/40
205 (2.80) 136 (1.80)
94 (2.98) 60 (1.90)
111 (3.05) 76 (2.09)
114 (1.70) 93 (1.00)
91 (1.10) 43 (0.80)
Data are presented as number (%). *Age- and gender-standardized to the 2000 China census.
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Wang et al 䡠 Amblyopia in a Rural Chinese Population Table 2. Prevalence of Amblyopia by Age and Gender in the Handan Eye Study Men
Women
Total
Age Group (yrs)
No. (%)
95% Confidence Interval
No. (%)
95% Confidence Interval
No. (%)
95% Confidence Interval
30–39 40–49 50–59 60–69 70– Total 50⫹ 30⫹
14 (2.50) 12 (1.98) 34 (2.96) 26 (4.70) 8 (2.79)
1.21–3.79 0.87–3.09 1.98–3.94 2.94–6.46 0.88–4.70
13 (1.93) 14 (1.95) 51 (3.88) 23 (4.13) 10 (2.63)
0.89–2.97 0.94–2.96 2.84–4.92 2.48–5.78 1.02–4.24
27 (2.19) 26 (1.96) 85 (3.45) 49 (4.41) 18 (2.70)
1.37–3.01 1.21–2.71 2.73–4.17 3.20–5.62 1.47–3.93
68 (3.42) 94 (2.98)
2.62–4.2 2.39–3.57
84 (3.73) 111 (3.05)
2.95–4.51 2.49–3.60
152 (3.58) 205 (3.02)
3.02–4.14 2.61–3.42
between men and women or an age-related trend of increasing or decreasing prevalence (Table 2). Anisometropia was responsible for most amblyopia cases (67.3%; 95% CI, 60.9%–73.7%; Table 3). Strabismus was present in 11 persons (5.4%; 95% CI, 2.3%– 8.5%), mixed types were present in 9 persons (4.4%; 95% CI, 1.6%–7.2%), visual deprivation was present in 20 persons (9.8%; 95% CI, 5.7%–13.8%), astigmatism-associated amblyopia was present in 20 persons (9.8%; 95% CI, 5.7%–13.8%), and other causes were present in 7 persons (3.4%; 95% CI, 0.9%–5.9%). Of the 16 persons with strabismic or mixed amblyopia, esotropia was detected in 8 (50%), exotropia was detected in 7 (43.8%), and exophoria was detected in 1 (6.3%). Table 4 shows proportions of amblyopic cases by the absolute difference in the degrees of spherical equivalent between the 2 eyes among the 138 cases with anisometropic amblyopia. Of those with a 3.00-D or more difference in the spherical equivalent between the 2 eyes, 57.6% had amblyopia. Of the all unilateral amblyopic eyes, 55% were hypermetropic. Among all amblyopic eyes, 47.6% were hypermetropic.
Discussion The prevalence of amblyopia in a rural adult Chinese sample was approximately 3%, if defined using the VA criterion of 20/30 or worse. The prevalence rate was reduced to 1.8% if a more stringent definition of VA 20/40 or worse was used. The prevalence of amblyopia seems to be higher in this sample compared with previously reported prevalence rates from Chinese children or teenage populations, all of which were conducted in populations younger than 20 years.10,11,15 The prevalence of amblyopia in Chinese children 5 to 15 years of age was reported to be less than 1% in 2 previous studies.10,11 Another study— of Singapore teenagers— using a VA criterion worse than 20/40 found an overall
prevalence of 0.35%.15 Possible explanations for the higher prevalence rate of amblyopia in the present study sample include the following: a possible decrease in prevalence of amblyopia over time (because the cohort was born 3 or more decades ago), different methodologies and diagnostic criteria used in different studies, and probable misclassification of some cases in the present study sample if the cases with reduced VA were in fact a measurement error resulting from poor attention or poor testing. Nevertheless, the prevalence of amblyopia found in the present study population is consistent with the prevalence rates found from most previous studies conducted in white adults.4,21 A study of older persons who had no previous screening or treatment of amblyopia found that the prevalence of amblyopia was 2.9%.21 The prevalence of amblyopia in the Blue Mountains Eye Study sample (age, ⱖ49 years) was 3.2%.4 In another Australian study of adults 40 years of age or older, the corresponding prevalence was 3.06%.22 The most recent population-based study of children in the United States, the Multi-Ethnic Pediatric Eye Disease Study, reported an amblyopia prevalence of 2.6% in Hispanic or Latino children younger than 72 months and of 1.5% in African American children younger than 72 months.6 Unilateral anisometropic amblyopia accounts for 58% of the amblyopia cases in Hispanic or Latino children and for 53% in African American children.6 The Baltimore Pediatric Eye Disease Survey used the same examination protocols and reported amblyopia prevalence of 1.8% in white children and 0.8% in African American children within the same age range as the Multi-Ethnic Pediatric Eye Disease Study.7 The prevalence of amblyopia in the current finding was similar to the results for Hispanic or Latino children in the Multi-Ethnic Pediatric Eye Disease Study.6
Table 3. Visual Acuity Category by Underlying Amblyopia Causes in the Handan Eye Study Visual Impairment
Visual Acuity
None Mild Moderate Severe Total
20/32 20/40–20/63 20/80–20/160 ⱕ20/200
Anisometropia
Strabismus
Mixed
Visual Deprivation
Astigmatism Associated
Others
Total
49 (23.90) 62 (30.24) 19 (9.27) 8 (3.90) 138 (67.32)
5 (2.44) 0 (0.00) 0 (0.00) 6 (2.93) 11 (5.37)
1 (0.49) 3 (1.46) 1 (0.49) 4 (1.95) 9 (4.39)
3 (1.46) 13 (6.34) 2 (0.98) 2 (0.98) 20 (9.76)
10 (4.88) 7 (3.41) 1 (0.49) 2 (0.98) 20 (9.76)
1 (0.49) 4 (1.95) 0 (0.00) 2 (0.98) 7 (3.41)
69 (33.66) 89 (43.41) 23 (11.22) 24 (11.71) 205 (100)
Data are presented as number (%).
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Ophthalmology Volume 118, Number 2, February 2011 Table 4. The Absolute Value of the Difference in the Degree of Spherical Equivalent between 2 Eyes among Participants with Anisometropic Amblyopia and the Entire Population in the Handan Eye Study Difference in the Degree of Spherical Equivalent between 2 Eyes (Diopters)
Anisometropic Amblyopia, No. (%)
Entire Population, No. (%)
Proportion of Anisometropic Amblyopia in Entire Population (%)
ⱕ0.99 1.00–1.99 2.00–2.99 3.00–3.99 ⱖ4.00
34 (24.63) 45 (32.61) 22 (15.94) 12 (8.70) 25 (18.12)
5683 (91.62) 331 (5.34) 90 (1.45) 22 (0.35) 77 (1.24)
0.59 12.00 11.73 33.33 24.27
Although there was no overall statistically significant difference in amblyopia prevalence across different age groups in the present sample, the prevalence was lowest among the youngest age group (30 to 39 years). It is possible that a cohort difference exists because of better screening and treatment of amblyopia provided to the younger generations. Supporting evidence for this includes the fact that most anisometropia cases were not detected and corrected during early childhood in this rural Chinese sample. Amblyopia results from degradation of the retinal image during a sensitive period of visual development, traditionally considered to be within the first 7 years of life.23 The main cause of amblyopia in Handan was anisometropia, responsible for nearly two thirds of the cases. Others studies have not found such a high proportion of cases with anisometropia. A study of persons 60 to 80 years of age found that anisometropic amblyopia accounted for 21% of all untreated amblyopia cases, whereas strabismic amblyopia accounted for 79%.21 In the Blue Mountains Eye Study, which used the same definitions of amblyopia as the present study, anisometropia accounted for 50% of the amblyopia cases, strabismus accounted for 19%, and mixed strabismus and anisometropia accounted for 27%,4 all of which were close to the proportions found in our study. We also found a higher degree of anisometropia in our amblyopic cases compared with that found in other studies.4,21 Some studies have reported that strabismus is the most common cause of amblyopia.24 –26 The apparent discrepancy could be the result of an underestimation of strabismus in the present study, if small angle strabismus were missed, or if spectacles led to correction of strabismus. Limitations of this study include the following. First, it is possible that early treatment may have reduced the true prevalence of amblyopia. However, information regarding previous treatment was collected, and few persons were ever treated in this sample. Second, decreased vision from amblyopia may have been masked by other age-related eye diseases such as cataract or age-related macular degeneration, leading to an underestimation of amblyopia prevalence. Third, amblyogenic causes might have changed over time.27–29 Finally, past histories of ocular treatments were self-reported and subject to recall bias and measurement errors.
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In conclusion, in this rural Chinese adult population (30 years of age or older) of Northern China, amblyopia prevalence (2.8%, after age and gender standardization) was similar to findings from adult white populations, particularly findings from the Blue Mountains Eye Study, given the same diagnostic definitions were used by the 2 studies. Anisometropia, which can be treated easily in young age, accounted for more than half of the amblyopia cases.
References 1. Holmes JM. Clarke MP. Amblyopia. Lancet 2006;367: 1343–51. 2. von Noorden GK. Binocular Vision and Ocular Motility: Theory and Management of Strabismus. 4th ed. St Louis, MO: Mosby; 1990:208. 3. Liang YB, Friedman DS, Wong TY, et al, Handan Eye Study Group. Prevalence and causes of low vision and blindness in a rural Chinese adult population: the Handan Eye Study. Ophthalmology 2008;115:1965–72. 4. Attebo K, Mitchell P, Cumming R, et al. Prevalence and causes of amblyopia in an adult population. Ophthalmology 1998;105:154 –9. 5. Rahi JS, Logan S, Borja MC, et al. Prediction of improved vision in the amblyopic eye after visual loss in the nonamblyopic eye. Lancet 2002;360:621–2. 6. Multi-ethnic Pediatric Eye Disease Study Group. Prevalence of amblyopia and strabismus in African American and Hispanic children ages 6 to 72 months: the Multi-ethnic Pediatric Eye Disease Study. Ophthalmology 2008;115:1229 –36. 7. Friedman DS, Repka MX, Katz J, et al. Prevalence of amblyopia and strabismus in white and African American children aged 6 through 71 months: the Baltimore Pediatric Eye Disease Study. Ophthalmology 2009;116:2128 –34. 8. Bremner MH. Visual acuity in the primary school child aged four to twelve years: a review of amblyopia treatment in this age group at Princess Margaret Hospital. Aust J Ophthalmol 1984;12:395–9. 9. Cole RB. The problem of unilateral amblyopia: a preliminary study of 10,000 National Health patients. Br Med J 1959;1: 202– 6. 10. Zhao J, Pan X, Sui R, et al. Refractive Error Study in Children: results from Shunyi District, China. Am J Ophthalmol 2000; 129:427–35. 11. He M, Zeng J, Liu Y, et al. Refractive error and visual impairment in urban children in southern China. Invest Ophthalmol Vis Sci 2004;45:793–9. 12. Lu P, Chen X, Zhang W, et al. Prevalence of ocular disease in Tibetan primary school children. Can J Ophthalmol 2008;43: 95–9. 13. Liang YB, Friedman DS, Wong TY, et al, Handan Eye Study Group. Rationale, design, methodology, and baseline data of a population-based study in rural China: the Handan Eye Study. Ophthalmic Epidemiol 2009;16:115–27. 14. Foong AW, Saw SM, Loo JL, et al. Rationale and methodology for a population-based study of eye diseases in Malay people: the Singapore Malay Eye Study (SiMES). Ophthalmic Epidemiol 2007;14:25–35. 15. Rosman M, Wong TY, Koh CL, Tan DT. Prevalence and causes of amblyopia in a population-based study of young adult men in Singapore. Am J Ophthalmol 2005;140:551–2. 16. Harvey EM, Dobson V, Clifford-Donaldson CE, Miller JM. Optical treatment of amblyopia in astigmatic children: the
Wang et al 䡠 Amblyopia in a Rural Chinese Population
17. 18. 19.
20. 21.
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sensitive period for successful treatment. Ophthalmology 2007;114:2293–301. Dobson V, Miller JM, Harvey EM, Mohan KM. Amblyopia in astigmatic preschool children. Vision Res 2003;43:1081–90. Harvey EM, Dobson V, Miller JM, Sherrill DL. Treatment of astigmatism-related amblyopia in 3- to 5-year-old children. Vision Res 2004;44:1623–34. Duan XR, Liang YB, Friedman DS, et al. Prevalence and associations of epiretinal membranes in a rural Chinese adult population: the Handan Eye Study. Invest Ophthalmol Vis Sci 2009;50:2018 –23. Wang FH, Liang YB, Zhang F, et al. Prevalence of diabetic retinopathy in rural China: the Handan Eye Study. Ophthalmology 2009;116:461–7. Vinding T, Gregersen E, Jensen A, Rindziunski E. Prevalence of amblyopia in old people without previous screening and treatment: an evaluation of the present prophylactic procedures among children in Denmark. Acta Ophthalmol (Copenh) 1991;69:796 – 8. Brown SA, Weih LM, Fu CL, et al. Prevalence of amblyopia and associated refractive errors in an adult population in Victoria, Australia. Ophthalmic Epidemiol 2000;7:249 –58.
23. von Noorden GK, Crawford ML. The sensitive period. Trans Ophthalmol Soc U K 1979;99:442– 6. 24. Woodruff G, Hiscox F, Thompson JR, Smith LK. Factors affecting the outcome of children treated for amblyopia. Eye (Lond) 1994;8:627–31. 25. Thompson JR, Woodruff G, Hiscox FA, et al. The incidence and prevalence of amblyopia detected in childhood. Public Health 1991;105:455– 62. 26. Oliver M, Nawratzki I. Screening of pre-school children for ocular anomalies. II. Amblyopia. Prevalence and therapeutic results at different ages. Br J Ophthalmol 1971;55:467–71. 27. Hopkisson B, Clarke JR, Oelman BJ. Residual amblyopia in recruits to the British Army. Br Med J (Clin Res Ed) 1982; 285:940. 28. Abrahamsson M, Fabian G, Sjostrand J. Changes in astigmatism between the ages of 1 and 4 years: a longitudinal study. Br J Ophthalmol 1988;72:145–9. 29. Abrahamsson M, Fabian G, Sjostrand J. A longitudinal study of a population based sample of astigmatic children. II. The changeability of anisometropia. Acta Ophthalmol (Copenh) 1990;68:435– 40.
Footnotes and Financial Disclosures Originally received: December 13, 2009. Final revision: April 26, 2010. Accepted: May 28, 2010. Available online: September 24, 2010.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2009-1706.
1
Beijing Tongren Eye Center, Capital Medical University, Beijing Ophthalmology & Visual Science Key Laboratory, Beijing, China.
2
Handan Eye Hospital, Hebei Province, China.
3
Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
4
Singapore Eye Research Institute, National University of Singapore, Singapore, Republic of Singapore.
5
Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland.
6
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
7
Centre for Vision Research, University of Sydney, Sydney, Australia.
Supported by the National Basic Research Program of China (973 Program); Grant 2007CB512201 from the Ministry of Science and Technology, Beijing, People’s Republic of China; Program of Health Policy for Blindness Prevention from the Ministry of Health, The People’s Republic of China; partially funded by the Bureau of Science and Technology of Handan City, Hebei Province, China (Key Technologies R&D Program no.: 2006-10903); with additional support from Beijing Tongren Hospital, Beijing, People’s Republic China; and the Key Discipline Fund of Bureau of Health, Handan City, Hebei Province, China. Correspondence: Ningli Wang, MD, PhD, Beijing Tongren Eye Center, Capital University of Medical Sciences, No. 1 Dongjiaominxiang, Dongcheng District, Beijing 100730, China. E-mail: [email protected].
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Amblyopia traditionally has been defined by what it is not, rather than what it is.1 Amblyopia manifests as a unilateral or bilateral reduction of best-corrected visual acuity (BCVA), for which no organic cause can be detected on physical examination of the eye and, in appropriate cases, is reversible by therapeutic measures.2 A commonly used definition of unilateral amblyopia is that BCVA differs by 2 or more Snellen or logarithm of the minimum angle resolution lines between the 2 eyes.1 Amblyopia has been recognized as a common cause of unilateral visual impairment.3,4 The authors recently reported that amblyopia was the second most common cause of unilateral low vision and the fourth leading cause of unilateral blindness in a rural adult Chinese population, the Handan Eye Study population.3 Persons with amblyopia are at greater risk of injury to the nonamblyopic eye and subsequently to bilateral vision loss.5 The Multi-Ethnic Pediatric Eye Disease Study reported an amblyopia prevalence of 2.6% in Hispanic/Latino children younger than 72 months and of 1.5% in African American children younger than 72 months.6 The Baltimore Pediatric © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
Eye Disease Survey reported an amblyopia prevalence of 1.8% in white children and of 0.8% in African American children of the same age.7 The prevalence of amblyopia has been estimated to be 0.2%8 to 5.3%9 among Chinese children. Zhao et al10 reported a prevalence of 0.92% among children 5 to 15 years of age in the Shunyi District in Beijing, and He et al11 reported a prevalence of 0.87% among such children in Guangzhou, China. In a remote area of the Qinghai-Tibetan Plateau of China, the prevalence was 1.02% among Tibetan children 6 to 14 years of age.12 However, there have been few data regarding amblyopia among Chinese adults. This article describes the prevalence, causes, and associated factors of amblyopia in a population-based sample of rural Chinese adults, residents of Handan, China.
Patients and Methods Study Design The Handan Eye Study is a population-based survey of vision and common eye diseases in an urban population 30 years of age and ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2010.05.026
279
Ophthalmology Volume 118, Number 2, February 2011 older from Yongnian County. The study adhered to the Declaration of Helsinki, ethics approval was obtained from the Beijing Tongren Hospital Ethical Committee, and written informed consent was obtained from all participants. Residents of Yongnian County, Handan, Hebei Province, who were 30 years of age or older were selected randomly using a stratified, clustered, and multistaged sampling technique with probabilities proportionate to the size of the population in each cluster. In Yongnian County, 90% of the adult population is engaged in farming and 98% is of Han ethnicity.3,13 Participants underwent an extensive and standardized eye examination, including a detailed questionnaire, visual acuity (VA) assessment, and slit-lamp and fundus examination before and after pupil dilation. Digital ocular images were obtained using the following procedures: optic nerve head imaging using Heidelberg Retinal Tomography II (Heidelberg Engineering, Heidelberg, Germany) and retinal photography using a Canon CR-DGi Nonmydriatic Retinal Camera (Canon, Tokyo, Japan). The study protocol was modified from the protocol used in the Singapore Malay Eye Study.14 The VA was measured using a logarithm of the minimum angle of resolution chart with 5 letters on each line while the participants were wearing current distance glasses. Subjective refraction was performed if the initial VA was worse than 0 (logarithm of the minimum angle of resolution; Snellen equivalent, 20/20), following a standardized protocol. The BCVA was defined according to the VA obtained after subjective refraction. A cover test and cover– uncover test were performed by a senior ophthalmologist (RZY) at near fixation. If any abnormalities were found, a cover test at a distance of 20 feet and an assessment of eye movements also were performed. Strabismus was coded as tropia, cranial nerve palsy, and phoria.
Definitions Adjudication was provided by senior investigators who examined all amblyopia cases that initially were diagnosed during the study examinations, confirmed the diagnosis, and assigned the underlying cause for the confirmed cases. The diagnosis of underlying causes took into account past histories of poor vision from childhood. The definitions used in the Blue Mountains Eye Study were followed.4 Unilateral amblyopia was diagnosed if BCVA was 20/32 or worse in the amblyopic eye and was not attributable directly to any underlying structural abnormality of the eye or visual pathway. Bilateral amblyopia was diagnosed if BCVA was 20/32 or less in both eyes and if there was a history of form deprivation during the sensitive period of visual development, such as media opacities or high, uncorrected ametropia.4 Myopia, emmetropia, and hypermetropia were defined as a spherical equivalent of less than ⫺0.5 diopter (D), between ⫺0.5 and ⫹0.5 D inclusive, and more than ⫹0.5 D, respectively. High hypermetropia was defined as spherical equivalent of more than ⫹5.0 D, and high myopia was defined as spherical equivalent of less than ⫺5.0 D. Subjects were classified according to the eye with a more severe degree of hypermetropia or myopia. High astigmatism was
considered present if the cylindrical refractive error was 2 D or more. Amblyopia cases were categorized into 6 types according to the underlying causes as described previously4,15: (1) anisometropic amblyopia: if there was a difference in the sphere or cylinder power between the 2 eyes of 1 D or more and no strabismus present; (2) strabismic amblyopia: if manifest strabismus was present without anisometropia or high refractive error, manifest strabismus was defined as constant or intermittent tropia of any magnitude at near fixation; (3) mixed amblyopia: if anisometropic amblyopia and strabismic amblyopia coexisted; (4) stimulus deprivation amblyopia: if congenital cataract, ptosis, corneal opacities, or other media opacities obstructed vision during the visual development period (from after birth to 7 years of age)— high refractive errors such as high hypermetropia and high myopia that were uncorrected during childhood were classified as this category as well4; (5) astigmatism-associated amblyopia: because uncorrected astigmatism can result in amblyopia,16 –18 astigmatismassociated amblyopia was identified if a high degree of astigmatism (cylindrical refractive error ⱖ2 D) was the only cause present in both eyes and if the difference in the cylindrical power between the 2 eyes was less than 1 D: (6) others: cases that did not fall into the above categories.15 If the participants were bilaterally amblyopic, the BCVA in the better-seeing eye was used.
Statistical Analysis Statistical analyses were performed using the Statistical Analysis System for Windows version 9.1.3 (SAS Inc., Cary, NC). Prevalence of amblyopia and 95% confidence intervals (CI) were estimated. The chi-square test was used to compare proportions for categorical variables. Two-sided P values ⬍0.05 were considered statistically significant. The age- and gender-standardized prevalence of amblyopia was estimated after direct standardization of the study sample to the 2000 China census.3,13,19,20
Results Of 7577 eligible residents 30 years of age or older, 6830 (90.4% response rate) participated in the study. The BCVA could be assessed accurately in 6799 (99.5%) participants. Amblyopia was diagnosed in 205 persons (3.02%), 94 of whom were men (46%). After age- and gender-standardization to the 2000 China census, the amblyopia prevalence was 2.8% (95% CI, 2.4%–3.2%; Table 1). Unilateral amblyopia was diagnosed in 114 persons (prevalence rate, 1.7%; 95% CI, 1.4%–2.0%) and bilateral amblyopia was diagnosed in 91 (1.1%; 95% CI, 0.8%–1.3%). If visual acuity of 20/40 or worse was used as the diagnostic criterion to define amblyopia, 136 persons met such a criterion and were amblyopic, with an age- and gender-adjusted prevalence rate of 1.8% (95% CI, 1.4%–2.1%). Of this group, 93 were unilateral, and 59 were amblyopic in the left eye (51.8%; P⬎0.05). There was no statistically significant difference in the prevalence of amblyopia
Table 1. Prevalence of Amblyopia* in the Handan Eye Study Visual Acuity Criterion Used
Total
Men
Women
Unilateral
Bilateral
ⱕ20/32 ⱕ20/40
205 (2.80) 136 (1.80)
94 (2.98) 60 (1.90)
111 (3.05) 76 (2.09)
114 (1.70) 93 (1.00)
91 (1.10) 43 (0.80)
Data are presented as number (%). *Age- and gender-standardized to the 2000 China census.
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Wang et al 䡠 Amblyopia in a Rural Chinese Population Table 2. Prevalence of Amblyopia by Age and Gender in the Handan Eye Study Men
Women
Total
Age Group (yrs)
No. (%)
95% Confidence Interval
No. (%)
95% Confidence Interval
No. (%)
95% Confidence Interval
30–39 40–49 50–59 60–69 70– Total 50⫹ 30⫹
14 (2.50) 12 (1.98) 34 (2.96) 26 (4.70) 8 (2.79)
1.21–3.79 0.87–3.09 1.98–3.94 2.94–6.46 0.88–4.70
13 (1.93) 14 (1.95) 51 (3.88) 23 (4.13) 10 (2.63)
0.89–2.97 0.94–2.96 2.84–4.92 2.48–5.78 1.02–4.24
27 (2.19) 26 (1.96) 85 (3.45) 49 (4.41) 18 (2.70)
1.37–3.01 1.21–2.71 2.73–4.17 3.20–5.62 1.47–3.93
68 (3.42) 94 (2.98)
2.62–4.2 2.39–3.57
84 (3.73) 111 (3.05)
2.95–4.51 2.49–3.60
152 (3.58) 205 (3.02)
3.02–4.14 2.61–3.42
between men and women or an age-related trend of increasing or decreasing prevalence (Table 2). Anisometropia was responsible for most amblyopia cases (67.3%; 95% CI, 60.9%–73.7%; Table 3). Strabismus was present in 11 persons (5.4%; 95% CI, 2.3%– 8.5%), mixed types were present in 9 persons (4.4%; 95% CI, 1.6%–7.2%), visual deprivation was present in 20 persons (9.8%; 95% CI, 5.7%–13.8%), astigmatism-associated amblyopia was present in 20 persons (9.8%; 95% CI, 5.7%–13.8%), and other causes were present in 7 persons (3.4%; 95% CI, 0.9%–5.9%). Of the 16 persons with strabismic or mixed amblyopia, esotropia was detected in 8 (50%), exotropia was detected in 7 (43.8%), and exophoria was detected in 1 (6.3%). Table 4 shows proportions of amblyopic cases by the absolute difference in the degrees of spherical equivalent between the 2 eyes among the 138 cases with anisometropic amblyopia. Of those with a 3.00-D or more difference in the spherical equivalent between the 2 eyes, 57.6% had amblyopia. Of the all unilateral amblyopic eyes, 55% were hypermetropic. Among all amblyopic eyes, 47.6% were hypermetropic.
Discussion The prevalence of amblyopia in a rural adult Chinese sample was approximately 3%, if defined using the VA criterion of 20/30 or worse. The prevalence rate was reduced to 1.8% if a more stringent definition of VA 20/40 or worse was used. The prevalence of amblyopia seems to be higher in this sample compared with previously reported prevalence rates from Chinese children or teenage populations, all of which were conducted in populations younger than 20 years.10,11,15 The prevalence of amblyopia in Chinese children 5 to 15 years of age was reported to be less than 1% in 2 previous studies.10,11 Another study— of Singapore teenagers— using a VA criterion worse than 20/40 found an overall
prevalence of 0.35%.15 Possible explanations for the higher prevalence rate of amblyopia in the present study sample include the following: a possible decrease in prevalence of amblyopia over time (because the cohort was born 3 or more decades ago), different methodologies and diagnostic criteria used in different studies, and probable misclassification of some cases in the present study sample if the cases with reduced VA were in fact a measurement error resulting from poor attention or poor testing. Nevertheless, the prevalence of amblyopia found in the present study population is consistent with the prevalence rates found from most previous studies conducted in white adults.4,21 A study of older persons who had no previous screening or treatment of amblyopia found that the prevalence of amblyopia was 2.9%.21 The prevalence of amblyopia in the Blue Mountains Eye Study sample (age, ⱖ49 years) was 3.2%.4 In another Australian study of adults 40 years of age or older, the corresponding prevalence was 3.06%.22 The most recent population-based study of children in the United States, the Multi-Ethnic Pediatric Eye Disease Study, reported an amblyopia prevalence of 2.6% in Hispanic or Latino children younger than 72 months and of 1.5% in African American children younger than 72 months.6 Unilateral anisometropic amblyopia accounts for 58% of the amblyopia cases in Hispanic or Latino children and for 53% in African American children.6 The Baltimore Pediatric Eye Disease Survey used the same examination protocols and reported amblyopia prevalence of 1.8% in white children and 0.8% in African American children within the same age range as the Multi-Ethnic Pediatric Eye Disease Study.7 The prevalence of amblyopia in the current finding was similar to the results for Hispanic or Latino children in the Multi-Ethnic Pediatric Eye Disease Study.6
Table 3. Visual Acuity Category by Underlying Amblyopia Causes in the Handan Eye Study Visual Impairment
Visual Acuity
None Mild Moderate Severe Total
20/32 20/40–20/63 20/80–20/160 ⱕ20/200
Anisometropia
Strabismus
Mixed
Visual Deprivation
Astigmatism Associated
Others
Total
49 (23.90) 62 (30.24) 19 (9.27) 8 (3.90) 138 (67.32)
5 (2.44) 0 (0.00) 0 (0.00) 6 (2.93) 11 (5.37)
1 (0.49) 3 (1.46) 1 (0.49) 4 (1.95) 9 (4.39)
3 (1.46) 13 (6.34) 2 (0.98) 2 (0.98) 20 (9.76)
10 (4.88) 7 (3.41) 1 (0.49) 2 (0.98) 20 (9.76)
1 (0.49) 4 (1.95) 0 (0.00) 2 (0.98) 7 (3.41)
69 (33.66) 89 (43.41) 23 (11.22) 24 (11.71) 205 (100)
Data are presented as number (%).
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Ophthalmology Volume 118, Number 2, February 2011 Table 4. The Absolute Value of the Difference in the Degree of Spherical Equivalent between 2 Eyes among Participants with Anisometropic Amblyopia and the Entire Population in the Handan Eye Study Difference in the Degree of Spherical Equivalent between 2 Eyes (Diopters)
Anisometropic Amblyopia, No. (%)
Entire Population, No. (%)
Proportion of Anisometropic Amblyopia in Entire Population (%)
ⱕ0.99 1.00–1.99 2.00–2.99 3.00–3.99 ⱖ4.00
34 (24.63) 45 (32.61) 22 (15.94) 12 (8.70) 25 (18.12)
5683 (91.62) 331 (5.34) 90 (1.45) 22 (0.35) 77 (1.24)
0.59 12.00 11.73 33.33 24.27
Although there was no overall statistically significant difference in amblyopia prevalence across different age groups in the present sample, the prevalence was lowest among the youngest age group (30 to 39 years). It is possible that a cohort difference exists because of better screening and treatment of amblyopia provided to the younger generations. Supporting evidence for this includes the fact that most anisometropia cases were not detected and corrected during early childhood in this rural Chinese sample. Amblyopia results from degradation of the retinal image during a sensitive period of visual development, traditionally considered to be within the first 7 years of life.23 The main cause of amblyopia in Handan was anisometropia, responsible for nearly two thirds of the cases. Others studies have not found such a high proportion of cases with anisometropia. A study of persons 60 to 80 years of age found that anisometropic amblyopia accounted for 21% of all untreated amblyopia cases, whereas strabismic amblyopia accounted for 79%.21 In the Blue Mountains Eye Study, which used the same definitions of amblyopia as the present study, anisometropia accounted for 50% of the amblyopia cases, strabismus accounted for 19%, and mixed strabismus and anisometropia accounted for 27%,4 all of which were close to the proportions found in our study. We also found a higher degree of anisometropia in our amblyopic cases compared with that found in other studies.4,21 Some studies have reported that strabismus is the most common cause of amblyopia.24 –26 The apparent discrepancy could be the result of an underestimation of strabismus in the present study, if small angle strabismus were missed, or if spectacles led to correction of strabismus. Limitations of this study include the following. First, it is possible that early treatment may have reduced the true prevalence of amblyopia. However, information regarding previous treatment was collected, and few persons were ever treated in this sample. Second, decreased vision from amblyopia may have been masked by other age-related eye diseases such as cataract or age-related macular degeneration, leading to an underestimation of amblyopia prevalence. Third, amblyogenic causes might have changed over time.27–29 Finally, past histories of ocular treatments were self-reported and subject to recall bias and measurement errors.
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In conclusion, in this rural Chinese adult population (30 years of age or older) of Northern China, amblyopia prevalence (2.8%, after age and gender standardization) was similar to findings from adult white populations, particularly findings from the Blue Mountains Eye Study, given the same diagnostic definitions were used by the 2 studies. Anisometropia, which can be treated easily in young age, accounted for more than half of the amblyopia cases.
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Footnotes and Financial Disclosures Originally received: December 13, 2009. Final revision: April 26, 2010. Accepted: May 28, 2010. Available online: September 24, 2010.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2009-1706.
1
Beijing Tongren Eye Center, Capital Medical University, Beijing Ophthalmology & Visual Science Key Laboratory, Beijing, China.
2
Handan Eye Hospital, Hebei Province, China.
3
Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
4
Singapore Eye Research Institute, National University of Singapore, Singapore, Republic of Singapore.
5
Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland.
6
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
7
Centre for Vision Research, University of Sydney, Sydney, Australia.
Supported by the National Basic Research Program of China (973 Program); Grant 2007CB512201 from the Ministry of Science and Technology, Beijing, People’s Republic of China; Program of Health Policy for Blindness Prevention from the Ministry of Health, The People’s Republic of China; partially funded by the Bureau of Science and Technology of Handan City, Hebei Province, China (Key Technologies R&D Program no.: 2006-10903); with additional support from Beijing Tongren Hospital, Beijing, People’s Republic China; and the Key Discipline Fund of Bureau of Health, Handan City, Hebei Province, China. Correspondence: Ningli Wang, MD, PhD, Beijing Tongren Eye Center, Capital University of Medical Sciences, No. 1 Dongjiaominxiang, Dongcheng District, Beijing 100730, China. E-mail: [email protected].
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