BMJ 2002;324:1549-1551 ( 29 June )

Papers

Amblyopia treatment outcomes after screening before or at age 3 years: follow up from randomised trial

C Williams, consultant ophthalmologist a, K Northstone, research fellow in statistics a, R A Harrad, consultant ophthalmologist b, J M Sparrow, consultant ophthalmologist b, I Harvey, professor of epidemiology and public health c, ALSPAC Study Team. 

a Division of Child Health, University of Bristol, Bristol BS8 1TQ, b Bristol Eye Hospital, Lower Maudlin St, Bristol BS1 2LX, c School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ

Correspondence to: C Williams Cathy.Williams{at}bristol.ac.uk


    Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References

Objective: To assess the effectiveness of early treatment for amblyopia in children.
Design: Follow up of outcomes of treatment for amblyopia in a randomised controlled trial comparing intensive orthoptic screening at 8, 12, 18, 25, 31, and 37 months (intensive group) with orthoptic screening at 37 months only (control group).
Setting: Avon, southwest England.
Participants: 3490 children who were part of a birth cohort study.
Main outcome measures: Prevalence of amblyopia and visual acuity of the worse seeing eye at 7.5 years of age.
Results: Amblyopia at 7.5 years was less prevalent in the intensive group than in the control group (0.6% v 1.8%; P=0.02). Mean visual acuities in the worse seeing eye were better for children who had been treated for amblyopia in the intensive group than for similar children in the control group (0.15 v 0.26 LogMAR units; P<0.001). A higher proportion of the children who were treated for amblyopia had been seen in a hospital eye clinic before 3 years of age in the intensive group than in the control group (48% v 13%; P=0.0002).
Conclusions: The intensive screening protocol was associated with better acuity in the amblyopic eye and a lower prevalence of amblyopia at 7.5 years of age, in comparison with screening at 37 months only. These data support the hypothesis that early treatment for amblyopia leads to a better outcome than later treatment and may act as a stimulus for research into feasible screening programmes.

What is already known on this topic
Observational studies have produced conflicting results about whether early treatment for amblyopia gives better results than later treatment

A recent systematic review highlighted the lack of high quality data available and recommended the cessation of preschool vision screening programmes

This has led to fierce debate and to confusion about the provision of vision screening services

What this study adds
Children treated for amblyopia are four times more likely to remain amblyopic if they were screened at 37 months only than if they were screened repeatedly between 8 and 37 months

Children screened early can see an average of one line more with their amblyopic eye after treatment than children screened at 37 months

Early treatment is more effective than later treatment for amblyopia, supporting the principle of preschool vision screening




    Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References

Preschool screening of vision is carried out to detect amblyopia (reduced visual acuity that is not instantly alleviated by wearing spectacles, in an otherwise apparently healthy eye). It is treated by long term wearing of spectacles when appropriate and by temporarily patching the better seeing eye. A recent systematic review discussed the poor clinical evidence base underpinning these programmes and emphasised the lack of evidence that treatment for amblyopia is better than placebo or that early treatment is more effective than later treatment.1-4 We present the follow up results from a population based randomised controlled trial, which was nested within a birth cohort study.


    Methods
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Abstract
Introduction
Methods
Results
Discussion
References
Participants ---The participants were part of the ongoing Avon longitudinal study of parents and children (ALSPAC). 5 6 Further details are given on bmj.com. The nested randomised controlled trial reported here was open to all children in the cohort born during the last six months of the study period. We excluded children whose parents had declined to continue with the study or had more than one participating child.

Routine services provided in the study area ---One institution provides hospital eye services for all children in the study area. All children received the usual recommended surveillance by their general practitioners and health visitors and were offered screening for reduced visual acuity by a school nurse at school entry (4-5 years).

Randomisation, assignment, and masking ---We allocated children into different arms of the study by a "pseudo-random" process according to the last digit in the day of the mother's date of birth: 1, 3, and 5 for the intensive group, and 2 and 4 for the control group. The orthoptists carrying out the vision tests had no knowledge of the mothers' dates of birth, the rules determining allocation into the different groups, or the screening history of the children.

Protocols ---In the intensive group, children were invited to attend a research clinic at 8, 12, 18, 25, 31, and 37 months, where an orthoptist examined them and carried out a battery of tests appropriate to the age of the child (see bmj.com). The children in the control group were offered similar testing by an orthoptist at 37 months only. Any child failing the acuity test or cover test in either of the groups was referred to the hospital eye service.

Final assessment ---We invited all children to a vision assessment at 7.5 years, including measurement of visual acuity both with and without a pinhole (with pinhole as a proxy for correction by spectacles). We sent out a questionnaire on family history and previous treatment with patching beforehand.

Statistical analysis ---We analysed the data according to the principle of intention to treat. The outcomes were the prevalence of amblyopia and the visual acuity in the worse seeing eye for children after treatment with patching at 7.5 years. The visual acuity result used for each eye was the better of the results obtained with and without pinhole. We defined amblyopia in advance in two ways to allow comparisons with other studies: amblyopia A, where the interocular difference in acuity was 0.2 LogMAR (two lines on the chart) or more7; and amblyopia B, where the visual acuity in the amblyopic eye was worse than 0.3 LogMAR.8 We compared proportions with the chi 2 test or Fisher's exact test. We analysed continuous data by using analysis of variance or multivariate analysis.


    Results
Top
Abstract
Introduction
Methods
Results
Discussion
References

Of the 3490 children in the trial, 1929 attended the final examination. Fifteen children had organic ocular pathology or were developmentally delayed and were excluded from further analysis, leaving 1914 children---1088/2029 (54%) of the intensive group and 826/1490 (55%) of the control group as originally randomised.

Prevalence of amblyopia at 7.5 years of age ---Amblyopia was found less often at 7.5 years in the intensive group than in the control group. The prevalence of amblyopia A was 1.5% (95% confidence interval 0.9% to 2.4%) in the intensive group and 2.7% (1.8% to 4.0%) in the control group (chi 2 =3.4, df=1, P=0.06). The prevalence of amblyopia B was 0.6% (0.3% to 1.3%) in the intensive group and 1.8% (1.1% to 3.0%) in the control group (chi 2=5.6, df=1, P=0.02).

Prevalence of residual amblyopia at 7.5 years after patching treatment ---Residual amblyopia was more likely to be present despite previous treatment in the control group (10/40) than in the intensive group (3/40). The difference for amblyopia A was not significant (odds ratio 1.56, 95% confidence interval 0.62 to 3.92), but for amblyopia B the difference was more marked (4.11, 1.04 to 16.29).

Visual acuity in the worse seeing eye after patching treatment ---Visual acuity in the worse seeing (amblyopic) eye was significantly better for treated children in the intensive group than for similar children in the control group: mean acuity 0.15 (95% confidence interval 0.085 to 0.215) compared with 0.26 (0.173 to 0.347). The corresponding acuities for children who had not had patching treatment were -0.02 (-0.024 to -0.016) and -0.01 (-0.016 to -0.004) in the two groups.

Age at first referral to hospital eye service ---A higher proportion of children who received patching treatment were first seen in the hospital eye service before the age of 3 years in the intensive group (19/40) than in the control group (5/40) (chi 2=10.06, df=1, P=0.002).

Adjustment for confounding variables ---Birth weight, duration of breast feeding, maternal education, having a first degree relative with strabismus or amblyopia, sex, and use of a car were also associated with the outcome data (see bmj.com). Only maternal education remained significantly associated with the outcome in a multivariate analysis. Maternal education may be a proxy for socioeconomic status, which is associated with the likelihood of adherence to treatment for amblyopia in young children.9 Adjustment for maternal education within the multivariate model made little difference to the results: the adjusted mean acuities in the worse seeing eyes of children treated with patching were again 0.15 (0.083 to 0.217) in the intensive group and 0.26 (0.170 to 0.350) in the control group (P<0.001).


    Discussion
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Abstract
Introduction
Methods
Results
Discussion
References

The mechanisms underlying the improved results in the intensive group cannot be ascertained from this study. Potential explanations include greater effectiveness of treatment due to age dependent plasticity, referral at an earlier stage in the course of the visual defect, greater adherence to treatment, and perceptual learning due to repeated testing. More of the children who were given patches in the intensive group than in the control group had been seen in the hospital eye service when aged less than 37 months, but these referrals were made at a variety of ages (see bmj.com). The earlier report from the present study suggested that screening using only photorefraction at the ages of 8, 12, 18, 25, or 31 months alone could have increased the yield of children with amblyopia compared with the actual yield from the intensive programme, which used acuity and cover testing.10 The specificity of such an approach would have been poor initially but would have increased to over 95% when the children were aged 31 months and older; these data may help in the design of potentially feasible programmes.

A prospective UK cohort study found no difference in the prevalence of amblyopia between children who had been offered primary orthoptic screening at 3 years and children offered only surveillance by a health visitor.11 The difference between the results of that study and those presented here may be due to differences in methods. Our study included screening offered before the age of 3 years, the groups were randomised, the outcome data were detailed and prospectively collected, and additional data were available to control for confounding variables.

The limitations of this study stem from the fact that it was opportunistic and designed to fit in with the ALSPAC study. The groups were unevenly sized for pragmatic reasons. Only approximately half the children were followed up, which may have biased the results, so caution must be exercised when interpreting these data. However, the effect of the intervention was undiminished when the results were adjusted for the only potential confounder detected after investigating several known and suspected factors. The bias towards more frequent breast feeding and fewer low birth- weight babies in those who attended the final assessment would be expected to improve the visual status in these children, 12 13 whereas the greater likelihood of a family history of strabismus or eye problems would be expected to have a deleterious effect on their visual status, 14 15 compared with the children who did not attend for follow up. The overall effect of these biases is uncertain, but there is no reason to assume that they would invalidate the study findings.

An important question is whether feasible programmes could deliver the same benefits as the intensive programme without repeated testing, which would be extremely expensive. Future research needs to investigate whether cost effective strategies can be designed that produce similar results. The data presented here support the hypothesis that treatment given for amblyopia is more effective if it starts as early as possible and may contribute to the debate on the management of amblyopia.

    Acknowledgments

We thank all the mothers who took part, the midwives for their cooperation and help in recruitment, and the orthoptists who did all the testing. The ALSPAC study team includes interviewers, computer technicians, laboratory technicians, clerical workers, research scientists, volunteers, and managers who continue to make the study possible. This study could not have been undertaken without the financial support of the Medical Research Council; Wellcome Trust; UK Department of Health, Department of the Environment, and Department for Education and Employment; National Institutes of Health; and a variety of medical research charities and commercial companies. The ALSPAC study is part of the WHO initiated European longitudinal study of pregnancy and childhood.

Contributors: See bmj.com

    Footnotes

Funding: Medical Research Council (CW was an MRC training fellow in health services research); R&D Directorate, NHS Executive South West; and National Eye Research Centre.

Competing interests: None declared.

The full version of this paper appears on bmj.com


    References
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Abstract
Introduction
Methods
Results
Discussion
References

1. Snowdon S, Stewart-Brown S. Preschool vision screening: results of a systematic review. York: NHS Centre for Reviews and Dissemination, University of York, 1997. (CRD Report 9.)
2. Fielder A. Review article did not separate review and implementation processes [letter]. BMJ 1998; 316: 938[Free Full Text].
3. Rahi JS, Dezateux C. The future of preschool vision screening services in Britain [editorial]. BMJ 1997; 315: 1247-1248[Free Full Text].
4. Harrad RA, McKee SP. Preschool vision screening: results of a systematic review. Surv Ophthalmol 1999; 43: 374-376[Medline].
5. Golding J, Pembrey M, Jones R, ALSPAC Study Team. ALSPAC---the Avon longitudinal study of parents and children. I. Study methodology. Paediatr Perinat Epidemiol 2001; 15: 74-87[CrossRef][Web of Science][Medline].
6. ALSPAC. www.alspac.bris.ac.uk/alspacext/Default.html (accessed 13 May 2002).
7. Attebo K, Mitchell P, Cumming R, Smith W, Jolly N, Sparkes R. Prevalence and causes of amblyopia in an adult population. Ophthalmology 1998; 105: 154-159[CrossRef][Web of Science][Medline].
8. Rahi J, Logan S, Timms C, Russell-Eggitt I, Taylor D. Incidence and causes of new visual loss affecting the non-amblyopic eye of individuals with unilateral amblyopia in the United Kingdom [abstract]. Investig Ophthalmol Vision Sci 2000; 41: S296.
9. Smith LK, Thompson JR, Woodruff G, Hiscox F. Factors affecting treatment compliance in amblyopia. J Pediatr Ophthalmol Strabismus 1995; 32: 98-101[Web of Science][Medline].
10. Williams C, Harrad RA, Harvey I, Sparrow JM, ALSPAC Study Team. Screening for amblyopia in preschool children: results of a population-based, randomized controlled trial. Ophthalmic Epidemiol 2001; 8: 279-295[Medline].
11. Bray L, Clarke M, Jarvis S, Francis P, Colver A. Preschool vision screening: a prospective comparative evaluation. Eye 1996; 10: 714-718.
12. Powls A, Botting N, Cooke R, Stephenson G, Marlow N. Visual impairment in very low birthweight children. Arch Dis Child Fetal Neonatal Ed 1997; 76: F82-F87.
13. Williams C, Birch E, Emmet P, Northstone K, ALSPAC Study Team. Stereoacuity at 3.5 years of age is associated with prenatal and post-natal dietary factors: a report from a population-based cohort study. Am J Clin Nutrition 2001; 73: 316-322[Abstract/Free Full Text].
14. Abrahamsson M, Magnusson G, Sjostrand J. Inheritance of strabismus and the gain of using heredity to determine populations at risk of developing strabismus. Acta Ophthalmol Scand 1999; 77: 653-657[CrossRef][Web of Science][Medline].
15. Ingram RM. Refraction as a basis for screening children for squint and amblyopia. Br J Ophthalmol 1977; 61: 8-15[Abstract/Free Full Text].

(Accepted 28 February 2002)

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Rapid Responses:

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The ALSPAC study did not address the utility of preschool vision screening
Michael P Clarke, et al.
bmj.com, 2 Jul 2002 [Full text]
Should children be screened repeatedly between 8-37 months for amblyopia?
P.R. Sankari, et al.
bmj.com, 16 Jul 2002 [Full text]
Author's responses
C Williams, et al.
bmj.com, 1 Aug 2002 [Full text]
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