Abstract
purpose. The development of emmetropic refraction is known to be under visual
control. Does partial spectacle correction of infants’ refractive
errors, which has been shown to have beneficial effects in reducing
strabismus and amblyopia, impede emmetropization? The purpose of the
present study was to perform the first longitudinal controlled trial to
investigate this question in human subjects.
methods. Children identified as having significant hyperopia in a population
screening program at age 8 to 9 months were assigned to treated
(partial spectacle correction) or untreated groups. A control group of
infants with no significant refractive errors at screening was also
recruited. Measurements of retinoscopic refraction under cycloplegia
were taken at 4- to 6-month intervals up to the age of 36 months, and
changes in refraction of 148 subjects were analyzed longitudinally.
results. Refractive error decreased toward low hyperopic values between 9 and 36
months in both hyperopic groups. By 36 months, this reduction of
hyperopia showed no overall difference between children who were
treated with partial spectacle correction and those who were not.
Despite the improvement, both hyperopic groups’ mean refractive error
at 36 months remained higher than that of the control group. When
infants in all three groups were considered together, the rate of
reduction of refractive error was, on average, a linear function of the
initial level of hyperopia.
conclusions. The benefits of spectacle correction for infants with hyperopia can be
achieved without impairing the normal developmental regulation of
refraction.
Asignificant proportion of infants show hyperopia of more than+
3.5 D.
1 2 In a large-scale photorefractive screening
program,
1 we detected such infants and followed them up
longitudinally, alongside a control group without significant
refractive error. We have already reported that partial spectacle
correction of hyperopia in infancy is of significant benefit, in that
compared with uncorrected hyperopes, those who wore a correction showed
better acuity for single and crowded letters, and a lower incidence of
strabismus, at 4 years of age.
3 4 However, we wanted to
examine whether this correction also affects the normal reduction of
hyperopia during early life. In the current study we investigated
emmetropization in the same group of infants, comparing hyperopes who
were prescribed spectacles with those who were not given correction.
The mechanisms that regulate human ocular development are poorly
understood. Pioneering studies of other animals including
primates
5 6 7 8 9 have suggested that ocular development and
refraction are partly regulated by visual feedback related to optical
defocus. Making chicks artificially myopic using plus lenses produces
compensatory ocular growth
6 10 that can eliminate the
refractive error. However there has been some controversy about the
extent of these effects in mammals, for both hyperopic and myopic
defocus, and their application to human development.
11 12 13 14 15 16 17 Refraction in human infants is usually hyperopic, and generally
develops gradually toward emmetropia during the first years of
life.
18 19 20 21 However, the extent to which defocus or
accommodation induced by lenses may affect this process has not yet
been resolved. In particular, there have been no studies to date
comparing human emmetropization in matched groups of infants with
corrected and uncorrected refraction who have hyperopic refractive
errors. The purpose of the present study was first to examine
refractive changes between the ages of 9 months and 3 years in human
infants who had naturally occurring hyperopic refractions and compare
them with infants with normal refractions, and second to compare
changes in refraction in infants with hyperopia who were given
correcting spectacles with changes in those who did not receive
correction. We present results for three groups: infants who were
significantly hyperopic at 9 months and were treated with partial
spectacle correction (
n = 44), infants who were
significantly hyperopic at 9 months and were not treated (
n= 37), and a control group with normal refraction at 9 months
(
n = 36). A further analysis examines the change in
refraction of the subgroup of treated infants who consistently wore the
prescribed correction.
Infants identified as having significant hyperopia but with no
meridian greater than +6 D, were alternately assigned to the treated or
untreated groups. For infants treated in the trial, spectacles
were prescribed according to the following protocol:
-
Sphere: 1 D less than the least hyperopic meridian (corrections
under 1.5 D were not prescribed)
-
Cylinder: up to 2 years of age, half of any astigmatic error if over
2.5 D; 2 to 3.5 years, half of any astigmatic refractive error; more
than 3.5 years, full correction.
This protocol was adopted to ensure that astigmatic errors, which
are known to reduce rapidly in infancy,
24 did not become
overcorrected during the period between follow-ups and that some
accommodative demand remained, similar to that for an infant with
average refraction of +1.0 D to +1.5 D. If at any follow-up visit
refractive error had reduced below these criteria, the spectacle
correction was discontinued, but the child was retained as part of the
treated group for analysis.
A questionnaire at each follow-up asked parents what proportion of
waking time the child had worn glasses in the current period. Every
effort was made to encourage parents to provide honest answers and not
to exaggerate the periods of spectacle wear. Infants with reported
spectacle wear of 50% or more waking time were classified as
compliant. Changes in refraction were initially analyzed according to
intention-to-treat, but the data were also reanalyzed with those
subjects who did not meet the criterion for compliance excluded from
the treated group. The former analysis respected the original alternate
assignment, whereas the latter served to evaluate more specifically the
optical effect of correction.
At screening, 208 of the 3166 infants (6.6%) met the criterion
for hyperopia. Of these, 199 (96%) who attended the follow-up
appointment and had cycloplegic retinoscopy, 177 (89%) were confirmed
hyperopic (at least one meridian of more than +3.5 D), but in the
present analysis, we considered only the 148 infants who had a meridian
of more than +3.5 D.
Infants with any meridian more than +6 D (n = 18),
anisometropia more than 1.5 D between parallel meridians (n= 5), or manifest strabismus (n = 1) were referred for
immediate appropriate ophthalmic treatment and were not included in the
trial of refractive correction. (One child’s condition fit two of
these diagnostic categories.) Of the remaining 125, the
intention-to-treat group comprised 62 infants, whereas the
no-intention-to-treat group comprised 63. An outcome measure taken
between ages 24 and 36 months was available for 46 infants in the
intention-to-treat group (74% of those entering the group) and 43 in
the no-intention-to-treat group (68%). Of those lost to the study
between 9 and 36 months, 18 had development of a visual problem that
met the criteria for referral for ophthalmic treatment, and they did
not subsequently attend the follow-up visits reported in this study.
The remaining 18 moved from the area, failed to attend, or attended but
were uncooperative during attempted retinoscopy.
In the control group, 106 of the 162 infants (65%)
recruited at screening had cycloplegic retinoscopy at 9 months;
105 of these (99%) were confirmed to have all meridians below+
3.5 D. An outcome measure is available for 59 infants (56%). The
higher rate of withdrawal in this group was mainly due to failure
to attend. Presumably, their parents perceived less benefit of
attendance than did those who had children with hyperopia.
To provide a more detailed picture of refractive development, our
primary analysis considered the infants for whom, in addition to
an initial and final retinoscopy measure, we had obtained an
intermediate measure between 16 and 24 months. This reduced our
groups to 44 intention-to-treat hyperopes (71%), 37 no
intention-to-treat (59%), and 36 control subjects (34%), totalling 53
boys and 64 girls. A subsidiary longitudinal analysis considering only
the initial and final measures was also performed.
If more than one refractive measure was available for an infant at the
intermediate ages, the earliest available measure was used for the
analysis; whereas for the outcome, the last available measure was used.
Figure 1 plots the mean level of hyperopia for each group over the course of the
study period, taking for each infant the single meridian of the four
(two for each eye) most hyperopic at each measurement. The initial
means (±SD) were +1.9 ± 0.8 D in the control group, +4.6 ±
0.5 D in the treated hyperopic group, and +4.3 ± 0.6 D in the
untreated group. All three groups showed an overall reduction in
hyperopia. On average, the treated hyperopes initially emmetropized
more slowly than the untreated group, with a mean 1.0 D more hyperopia
at 18 months, but the difference had narrowed by 36 months, with a
final mean of +3.4 D in the treated group and +3.1 D in the untreated,
an overall reduction of 1.2 D in both groups. The control group
emmetropized by a small amount, with a mean reduction of 0.3 D. The
hyperopic groups showed an increase in variability between 9 and 36
months (0.9-D increase in SD in each group).
Analysis of variance comparing treated and untreated groups found that
the age–treatment interaction that marks the temporary advantage of
the untreated group at 18 months was significant (F = 5.42, P < 0.03), but an independent samples t-test comparing the treated and untreated means at 36
months found no significant difference between the two groups. Power
calculations indicate that these samples would have a power of 0.88 in
detecting a true difference of 1.0 D in the final level of hyperopia
and 0.34 in detecting a 0.5-D difference at the 0.05 significance
level.
The analysis considered overall refractive outcome by taking whichever
meridian was most hyperopic at each point. However, this is not
necessarily a measure of developmental changes in any specific meridian
or eye, because it may compare different meridians at different times.
An alternative approach is to track whichever meridian is most
hyperopic at 9 months for each child. This yielded an overall pattern
of change very similar to that in the previous analysis, with a mean
difference of 1.1 D between the treated and untreated groups at 18
months. The overall reduction of hyperopia was greater using this
measure, however, with a final mean of +2.7 D for the untreated
hyperopes and +3.0 D for the treated, a reduction of 1.6 D in both
groups. The control group had a final mean of +1.4 D, a reduction of
0.5 D. Analysis of variance for the two hyperopic groups again found a
significant age–treatment interaction (F = 9.35, P < 0.005), and an independent samples t-test found no difference at 36 months (power = 0.89
for a true difference of 1.0 D; 0.35 for 0.5 D at P <
0.05).
Of the 44 treated-group subjects in our main longitudinal analysis, 13
did not meet the criterion for compliance. We reanalyzed the data for
the treated group, omitting these children.
Figure 2 plots the mean level of hyperopia, calculated as the most hyperopic
meridian at the time of measurement, distinguishing the treated
hyperopes who were compliant from those who were not.
The mean greatest axis in the compliant treated group was +4.5 D at 9
months, compared with +4.3 D in the untreated group. The compliant
treated group mean at 18 months was +3.7 D, 0.8 D higher than the
untreated mean, but decreased to +3.3 D by 36 months, leaving a final
difference of only 0.2 D between the two, an overall reduction of 1.2 D
in both groups. Analysis of variance again found a significant
age–treatment interaction (F = 6.31, P < 0.02).
An independent samples t-test found no significant
difference at 36 months (power = 0.85 for a true difference of 1.0
D; 0.32 for 0.5 D at P < 0.05).
Again, the data were reanalyzed in terms of the single greatest
axis at 9 months. At 18 months the untreated group mean was +3.4
D, 1.1 D higher than the treated compliant group, but by 36 months the
mean had declined to +2.9 D, leaving a difference of 0.2 D between the
two, an overall mean reduction of 1.6 D in both groups. Analysis of
variance again found that the age–treatment interaction was
significant (F = 11.81, P < 0.02), but the final
difference in means was not (power = 0.90 for a true difference of
1.0 D; 0.37 for 0.5 D at P < 0.05).
When we included in these four analyses the infants without a midpoint
refraction (total
n = 148), the results were essentially
unchanged, although the control group showed slightly less reduction in
hyperopia than in the analyses shown in
Figures 1 and 2 . An example of
these analyses is shown in
Figure 3 (the larger samples increase power to 0.96 for a true difference of 1.0
D, 0.45 for 0.5 D at
P < 0.05).
All these analyses found a greater overall change in refraction in the
hyperopic groups than in the control subjects. To study the
relationship between level of hyperopia at 9 months and amount of
emmetropization by 36 months, we put aside our groupings and examined
the continuum across the full range of refractions. Because treatment
had been shown to make no significant difference to outcome at 36
months, we considered both hyperopic groups together in the same
analysis. In addition to the 148 infants for whom we have a 9-month and
a 36-month measure, we also included 11 of the 18 high hyperopes who
had been excluded from the trial of treatment but still participated in
the study for a 36-month measure, extending the range over which we
could examine the relationship.
Figure 4 plots change in hyperopia against refraction at 9 months, for the
meridian initially most hyperopic in each case. The plot indicates that
subjects across the whole range of initial measurements tended to
converge toward emmetropia, and that a subject’s overall change was
proportional to the initial degree of hyperopia. A regression
analysis found this linear relationship to be highly significant
(F = 56.35,
P < 0.0001).
The comparison of corrected and uncorrected groups suggests
a small, transient effect of refractive correction between 9 and 18
months of age. However, by 36 months this effect had disappeared, and
the infants with initial hyperopia had reached a common refraction
irrespective of treatment. This conclusion remained the same whether we
analyzed in terms of the original assignment to treated or untreated
groups, or whether we considered as treated only those who consistently
wore their spectacles. Thus, we find no evidence that partial spectacle
correction for infantile hyperopia interfered in any persistent way
with the developmental trend toward emmetropia.
The analysis that included the largest number of hyperopes—all those
with a 9 month and 36 month measurement (total n = 89)—had
a power of 0.96 in detecting a true difference of 1 D at P < 0.05. Thus, although there is wide variability in
initial refraction and refractive change, with groups of this size we
can show with some confidence that spectacle correction does not
substantially interfere with emmetropization.
The general reduction of hyperopia meant that many infants (n= 21) in the treated group did not fulfill the criteria for
prescription before the age of 36 months.
The finding that spectacle correction did not impede emmetropization
applied to the refractive population we have described. We cannot be
sure how refractive correction might affect the development of very
large hyperopic errors, which show very variable degrees of
emmetropization (see the squares in
Fig. 4 ), or how it would affect
children who have strabismus before receiving a correction. We did not
gather systematic data on ethnic origin or socioeconomic status.
However, the study group and the population from which it is drawn had
a very strong predominance (>90%) of white origin, and, because the
screening was based on high attendance within a socially mixed
geographic area, covers the range of socioeconomic groups. There was no
indication of differential withdrawal between different districts
within the overall area.
Our results are also specific to the practice of partial spectacle
correction as described in the Methods section. A full correction of
refractive error would ensure that the accommodative demand for an
infant with hyperopia was reduced to a lower level than for control
infants (who in general had a small, uncorrected hyperopia). It is
possible that such a reduction in accommodation would influence the
emmetropization process. However, our partial corrections did not
produce such an effect.
We have found that the partial refractive correction of infants with
hyperopia according to the protocol described in the present study has
beneficial effects of reducing the incidences of strabismus and poor
acuity by two thirds in children who comply in wearing the prescribed
correction.
3 4 The present results indicate that these
benefits can be achieved without the optical treatment’s impairing the
normal developmental regulation of eye growth and refraction.
Supported by Grant G7908507 from the Medical Research Council.
Submitted for publication November 16, 1999; revised March 7 and May 22, 2000; accepted June 23, 2000.
Commercial relationships policy: N.
Corresponding author: Janette Atkinson, Department of Psychology, University College London, Gower Street, London WC1E 6BT, UK.
j.atkinson@ucl.ac.uk
The authors thank other members of the Visual Development Unit, the
Cambridge District Health Authority, and the Ophthalmology Department,
Addenbrooke’s Hospital Cambridge, for support in running this program.
Atkinson J, Braddick OJ, Durden K, Watson PG, Atkinson S. Screening for refractive errors in 6–9 months old infants by photorefraction. Br J Ophthalmol
. 1984;68:105–112.
[CrossRef] [PubMed]Howland HC. Early refractive development. Simons K eds. Early Visual Development: Normal and Abnormal. 1993;5–11. Oxford University Press New York.
Atkinson J. Infant vision screening: prediction and prevention of strabismus and amblyopia from refractive screening in the Cambridge photorefraction programme. Simons K eds. Early Visual Development: Normal and Abnormal. 1993;335–346. Oxford University Press New York.
Atkinson J, Braddick OJ, Bobier B, et al. Two infant vision screening programmes: prediction and prevention of strabismus and amblyopia from photo- and videorefractive screening. Eye
. 1996;10:189–198.
[CrossRef] [PubMed]Wallman J, Gottlieb MD, Rajaram V, Fugate–Wentzek L. Local retinal regions control local eye growth and myopia. Science
. 1987;237:73–77.
[CrossRef] [PubMed]Irving EL, Callender MG, Sivak JG. Inducing myopia, hyperopia, and astigmatism in chicks. Optom Vis Sci
. 1991;68:364–368.
[CrossRef] [PubMed]Schaeffel F, Howland HC. Properties of the feedback loops controlling eye growth and refractive state in the chicken. Vision Res
. 1991;31:717–734.
[CrossRef] [PubMed]Hung L, Crawford MLJ, Smith EL. Spectacle lenses alter eye growth and the refractive status of young monkeys. Nat Med
. 1995;1:761–765.
[CrossRef] [PubMed]Schaeffel F, Glasser A, Howland HC. Accommodation, refractive error, and eye growth in chickens. Vision Res
. 1988;28:639–657.
[CrossRef] [PubMed]Zadnik K, Mutti DO. How applicable are animal models to human juvenile onset myopia?. Vision Res
. 1995;35:1283–1288.
[CrossRef] [PubMed]Wildsoet CF. Active emmetropization: evidence for its existence and ramifications for clinical practice. Ophthalmic Physiol Opt
. 1997;17:279–290.
[CrossRef] [PubMed]Flitcroft DI, Mulvihill A, O’Keefe MO. Do glasses prevent emmetropization in accommodative esotropia? [ARVO Abstract]. Invest Ophthalmol Vis Sci. 1988;39(4)S639.Abstract nr 2977
Smith EL, Hung LF. The role of optical defocus in regulating refractive development in infant monkeys. Vision Res
. 1999;39:1415–1435.
[CrossRef] [PubMed]Flitcroft DI. The lens paradigm in experimental myopia: oculomotor, optical and neurophysiological considerations. Ophthalmic Physiol Opt
. 1999;19:103–111.
[CrossRef] [PubMed]Graham B, Judge SJ. The effects of spectacle wear in infancy on eye growth and refractive error in the marmoset. Vision Res. 1999;39:186–206.
Dobson V, Sebris SL, Carlson MR. Do Glasses prevent emmetropization in strabismic infants? [ARVO Abstract]. Invest Ophthalmol Vis Sci. 1986;27(3)S2.Abstract nr 2
Baldwin WR. Refractive status of infants and children. Rosenbloom A Morgan MW eds. Principles and Practice of Paediatric Optometry. 1990;104–152. Lippincott Philadelphia.
Grosvenor T, Flom MC. Refractive Anomalies: Research and Clinical Applications. 1991; Butterworth–Heinemann Boston.
Ingram RM, Arnold PE, Dally S, Lucas J. Emmetropization, squint, and reduced visual acuity after treatment. Br J Ophthalmol
. 1991;75:414–416.
[CrossRef] [PubMed]Ehrlich D, Braddick OJ, Atkinson J, et al. Infant emmetropization: a longitudinal study of refraction components from 9 months of age. Optom Vis Sci
. 1997;74:822–843.
[CrossRef] [PubMed]Howland HC, Braddick OJ, Atkinson J, Howland B. Optics of photorefraction: orthogonal and isotropic methods. J Opt Soc Am
. 1983;73:1701–1708.
[CrossRef] [PubMed]Braddick OJ, Atkinson J. Photorefractive techniques: applications in testing infants and young children. Trans Br Coll Ophthalmic Opticians (Optometrists). 1984;2:26–34.
Atkinson J, Braddick OJ, French J. Infant astigmatism: its disappearance with age. Vision Res
. 1980;20:891–893.
[CrossRef] [PubMed]Ehrlich D, Atkinson J, Braddick O, Bobier W, Durden K. Reduction of infant myopia: a longitudinal cycloplegic study. Vision Res
. 1995;35:1313–1324.
[CrossRef] [PubMed]Howland HC, Atkinson J, Braddick OJ, French J. Infant astigmatism measured by photorefraction. Science
. 1978;202:331–333.
[CrossRef] [PubMed]Mohindra I, Held R, Gwiazda J, Brill S. Astigmatism in infants. Science
. 1978;202:329–330.
[CrossRef] [PubMed]