Normal Emmetropization in Infants with Spectacle Correction for Hyperopia Janette Atkinson.Sbirley Anker,Willtam Bobier,Oliver Braddick,'Kim Durden, Marko Nardini'and Peter Watson I..The devekpmen cf cmmetropke'refractiom is kncrun t be unikr visual contral Dxoes partsd sprct:kd:omtn odf infornts'rfractie:rk mhach hot hoen shon iu han himn:fictal effects in reducin strabismus and amblyopi,inpede emmetropization?The purpose of the prexent study was to perform the firs longitudinal controlled trill to investigate this question in human suhjets. Mrmons.Children ientined as having signinicant hrperopia in a populatoe screening program at age 8 to9 ohs were assigned to treated (panil spectacle cocrection)or untreated groups.A control group of infants with no signiticant retractive crors at screening wus also recruited. Measurements of retinoscopic refraction under cycloplegia were taken at i to 6 month intervals up to the age of 36 months,and changes in refraction of 118 subjects were analyzed lodginadinaty. Besurs,Refractive cror decreased toward low hyperopic values beracen 9 and 56 months in both hyperopic gups.By 36 months.this redaction of byperopl soued no overall dirference hetween cdr who wen:treaend with parrttal xprtacie curn'itkm and ther who win:n. lspite the tmprenemon,boch hype'nogk gmp moom rfrkti ermir a %6 momnths remained higher thn that of the comtrol group.hen infants in all three groups were considered together, the rate of rediticn of refractive error was,an average,a linear futice of the initall level of hypemipix Coxcusioks.The benefits of spectacle correction for infints with hyperopin can be achieved without impairing the nordal developmental regulation of refraction.(uresr Oplyhalo V Sci. 20041:5726-5731) signcant proportion of infints show hyperopia of The mechinisms that regulave hunan ocular developebent more thn +5.5 D.n a largescale photocefrcthre are poorly understood.Poneering studies of other animals screening program,we detected such infants and fol inch小u走n primates-+have suggested t山ut ocular development lwrdd them up ingalmay.akingede a cunmm with ad refraction are parly regulated by visanl feedback relaced to out sigmficant refncthe emur.We have alneady rpoed that opcial defocus.Mtikinz chicks cially ayopic using plis purtial spectade comrection of hyperopia in infancy is of signif. lenses produces compenstory oculr growth that can elim- eant ben金，m that compared with uneareeted hyperpes. inate the refrctive ermr.However there has been some con- thisc wh mixrt'a sxerrcttoxn shiwnd hitier aritty feoe xngle tnwery about the extent of thest:effet mormls,fce huth and crowded letters,and a lower incidence of strabismus,at hyTn套3nprc★cs,nlrh1rpp3 ton to human years of age.Hawever,we wanted to examine whesher this develpmen.Refracsion in human infants is usually hy- currection alsn sffrcts the narmal reductinn of hyperupia due peropic,and generally develops gradially toward eumetmpia ing early life.In the current study we investigated em hiring the fine yiaflrwever,the extent to whih wetropization in the same group of infants,comparing hyper ielueais or icxmmmoctitiun incluod by ensix may aflixt this opes who were preseribed spectacles with these wha were poucess ha not yet been resalved.In particulir.there have ooc given correction. beno女dies to date comparing human emmetrop2aia鱼 micched goups of infints with comrected and uxcnrrected refncton who have hyperapic refractive emors.The purpose Fam the Val Devekpaen Unit,lendin and Carahrdge of the present study was first to examine refractive changes Department of Pwycholgy.Universicy Collte London.Uailed Kag between the ages of 9 months and 5 years in buman infants e:the 'sclod uf Upotciry,riverily心(Waterbu,《eh园 who had naturalhy occurring hyperopic refractions and com pare them with intnts with comal refractions,and second to hridse.Tnbned kirgfon. S划pported年Gnnt G79i857 frome the Medical Research compare chnges i鱼refraction鱼infants with Iperopia who Council. were given comecting spectades with changes in those who Suhmied fre pulieatlon Nrweraher 16,1999:rerird Mrch 7 did nont reecive overection.Wc present results fur thnee:groeps and Mry 22.2000r acoepeed hane 25.3000 tnf:mts wha win'sgnthicamnty hypercgk:at y minthsandl wen Cutrental rdatiaupo puliLy:N. tneated with partsll spectacle curnectim《界-H.nfanes who were sigrificantly hypempic at 9 months and were noc treated .kot等过.k (n 57).andl a comtral gnoup with nmmall refractinn at 9 wvesinoave cpddlu★了&Yw和la文程e.0 wreser ML Ve.dt.N银12 375 C%r年0 araion far Bwcai白n Yhdon and0 phehualrodogy
Normal Emmetropization in Infants with Spectacle Correction for Hyperopia Janette Atkinson,1 Shirley Anker,1 William Bobier,2 Oliver Braddick,1 Kim Durden,1 Marko Nardini,1 and Peter Watson3 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. (Invest Ophthalmol Vis Sci. 2000;41:3726–3731) Asignificant proportion of infants show hyperopia of more than 13.5 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 primates5–9 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 growth6,10 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.11–17 Refraction in human infants is usually hyperopic, and generally develops gradually toward emmetropia during the first years of life.18–21 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 5 44), infants who were significantly hyperopic at 9 months and were not treated (n 5 37), and a control group with normal refraction at 9 From the 1 Visual Development Unit, London and Cambridge, Department of Psychology, University College London, United Kingdom; the 2 School of Optometry, University of Waterloo, Canada; and the 3 Department of Ophthalmology, Addenbrooke’s Hospital, Cambridge, United Kingdom. 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 Investigative Ophthalmology & Visual Science, November 2000, Vol. 41, No. 12 3726 Copyright © Association for Research in Vision and Ophthalmology
0 Nevember 0 Val 41,No.1 372 If at any follo METH
months (n 5 36). A further analysis examines the change in refraction of the subgroup of treated infants who consistently wore the prescribed correction. METHODS Population of Infants in this Study Children born in the central area of the Cambridge Health District (Cambridgeshire, UK) during a 2.5-year period in 1981 through 1983 were invited to attend vision screening appointments in well-infant clinics. A total of 3166 infants (74% of those invited) attended this population-based community screening program.1,3 Screening took place at 7 to 9 months of age and included an orthoptic examination and cycloplegic photorefraction (isotropic photorefractor on 35-mm camera,1 with 1 to 2 drops of 1% cyclopentolate administered 30 to 40 minutes before photorefraction). The procedure for photorefraction, its theoretical rationale, and validation against retinoscopy have been described in previous publications.1,22,23 The hyperopic groups consisted of infants identified at screening with at least one meridian of 13.5 D or greater, confirmed by a retinoscopic examination in eyes under cycloplegia at a follow-up examination within 45 days of screening. This procedure confirmed significant hyperopia, according to the criterion of at least one meridian of 13.5 D or greater, in 89% of infants deemed to have hyperopia at screening. The first infant to be screened without hyperopic, anisometropic, or myopic refraction (see Reference 1 for criteria) after an infant with refraction categorized as hyperopic at screening was recruited as part of the control group and comprised a random sample of the infants who did not meet the criteria for the refractive error categories. Refractions of control infants were also confirmed by cycloplegic retinoscopy. The goal was to obtain a control group of approximately 50% of the study population. Infants with diagnosed developmental delay were not included in this study. Children in the trial were offered appointments at 4- to 6-month intervals, at which a range of measures of visual development were made. In the present study, we describe only changes in retinoscopic refraction under cycloplegia across these follow-up visits. The research protocol adhered to the Declaration of Helsinki for research involving human subjects. All parents or guardians of the infants studied provided written consent to the screening and follow-up assessments. Spectacle Correction and Compliance Infants identified as having significant hyperopia but with no meridian greater than 16 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 11.0 D to 11.5 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-totreat, 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. Longitudinal Analysis 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 13.5 D), but in the present analysis, we considered only the 148 infants who had a meridian of more than 13.5 D. Infants with any meridian more than 16D(n 5 18), anisometropia more than 1.5 D between parallel meridians (n 5 5), or manifest strabismus (n 5 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 13.5 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. IOVS, November 2000, Vol. 41, No. 12 Emmetropization in Corrected Infant Hyperopes 3727
3728 V,November 2000.Vol 41.No 12 ,d 2 Age (montha) 47
Statistics Treated and untreated infants were compared on measures of hyperopia and astigmatism, using repeated-measures analyses of variance with age as a within-subjects factor, and treatment and gender as between-subjects factors. The initial (9 month) values were used as covariates to remove any effects due to small differences in the distributions of initial refractions between the two groups. For assessments of outcome, independent samples t-tests were used to compare the final (36 month) means. In addition, linear regression analyses were performed to determine the relation between initial hyperopia or astigmatism and change over the course of the study. RESULTS Emmetropization 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 (6SD) were 11.9 6 0.8 D in the control group, 14.6 6 0.5 D in the treated hyperopic group, and 14.3 6 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 13.4 D in the treated group and 13.1 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 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 12.7 D for the untreated hyperopes and 13.0 D for the treated, a reduction of 1.6 D in both groups. The control group had a final mean of 11.4 D, a reduction of 0.5 D. Analysis of variance for the two hyperopic groups again found a significant age– treatment interaction (F 5 9.35, P , 0.005), and an independent samples t-test found no difference at 36 months (power 5 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 14.5 D at 9 months, compared with 14.3 D in the untreated group. The compliant treated group mean at 18 months was 13.7 D, 0.8 D higher than the untreated mean, but decreased to 13.3 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 5 6.31, P , 0.02). An independent samples t-test found no significant difference at 36 months FIGURE 1. Hyperopia in the treated (i.e, assigned to treatment), untreated (assigned to no treatment), and control groups for children with measurements available at 9, 18, and 36 months of age. The most hyperopic meridian for each individual was determined at the age given. The data plotted are the means of these values. Error bars, positive SD for the group. FIGURE 2. Hyperopia in the treated compliant, treated noncompliant, untreated, and control groups for children with measurements available at 9, 18, and 36 months of age. The most hyperopic meridian for each individual was determined at the age given. The data plotted are the means of these values. Error bars, positive SD for the group. 3728 Atkinson et al. IOVS, November 2000, Vol. 41, No. 12
2000.Vol 41.No 576 2 Age(months) of 1.0 D:0.32 for 0.5 D a 11 5 plts th 00 Age (monthsl
(power 5 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 13.4 D, 1.1 D higher than the treated compliant group, but by 36 months the mean had declined to 12.9 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 5 11.81, P , 0.02), but the final difference in means was not (power 5 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 5 148), 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 5 56.35, P , 0.0001). Astigmatism Figure 5 plots the course of astigmatism, calculated as the difference between orthogonal meridians of the eye more astigmatic at 9 months, for the 117 infants for whom we had a 9-, 18- and 36-month measure. The treated group plotted comprised all intention-to-treat subjects, both compliant and noncompliant. The mean astigmatism of all three groups reduced over time: In controls it declined from 0.8 D at 9 months to 0.3 D at 36 months; in treated hyperopes, from 1.9 to 1.0 D; and in FIGURE 3. Hyperopia in the treated (assigned to treatment), untreated (assigned to no treatment), and control groups for all children with measurements available at 9 and 36 months of age. The most hyperopic meridian for each individual was determined at the age given. The data plotted are the means of these values. Error bars, positive SD for the group. FIGURE 4. Emmetropization as a function of initial refraction. Abscissa: initial refraction of the most hyperopic meridian for each individual at age 9 months. Ordinate: change in refraction between 9 to 36 months for the same meridian. Data points have been jittered by 6 0.1 D in both axes to avoid overlap. The regression line (r2 5 0.26) has the equation (y 5 0.37 2 0.43x). () Untreated group (n 5 43); (E) compliant treated group (n 5 31); (!) noncompliant treated group (n 5 15); (F) 5 control group (n 5 59); (u) high hyperopes excluded from trial (n 5 11). FIGURE 5. Astigmatism in the treated, untreated, and control groups for children with measurements available at 9, 18, and 36 months of age. The absolute difference between orthogonal meridians for the eye that was most astigmatic at 9 months was determined at each age. Data plotted are the means of these values. Error bars: positive SD for the group. IOVS, November 2000, Vol. 41, No. 12 Emmetropization in Corrected Infant Hyperopes 3729
3730 Atkinson et al. NOVS Newemher 200N1,Vnl.41.No.12 As Hyure fi ihcates.thene a very string tundluncy fur astigmatism af ether rype to dimensh in propartion to its orginal extent.The bottom kft and top right quadrants,which cntain suhjects in wfxmm aigmttsm tnercancd,wen'very sparsey populated.Our longitudinal analysis of the group means (Fig.5)indicates that thes proess of reduction was not impaired by the prescribed partial correction:The prococol appheil meamt that in cnly 22 cooex dd this inchuale a cylindri- cal carreetion. Possible Biases Tn evsltite differertial witldrawal from the study as a possihle source of bis,we compared the initial mouth)retinoscopy mcamincx of greallest axtx andl istigmartm cif suhjectx whc remalned in白esud少y with those who were withdrawn-lnd pundent simpks ftests found no Ngnificant chfferences.n either hyperopic group or in the control subjects.There was also no staitistcally significunt didlerence in numbers of boys and gids in aoy of the three groups Astigmatism at 9 months (D) DISCUSSION n6。《ee4en标attm asa fuection国红t包l标日tin Abrcicta:inirial aecrarisnt of the more agignaric eve for cach ind Although the effccts of visil fexedback cm cmmetroptzatton vidual at aze 9 mnths expeessed as (hyperopia in borzontal seri eary fe are well documented,the implicatioos of these effects b)-(hyperupta in vercal merdt)-.c,polthr values nprewent hnriannr.l uith-the-nile aurignatien,nrgthr valnes reprarnt wrkeal for the practie of refractive comrection in Infancy and eary ghs建orule astigmarisn.Ofina:chatge i this value berwce鱼9 chiildhood have not yet been well uoxderstood.Tis study d 46 itoullt for the cmne eye.Dua potub Lave boen puter Iry nrexentx the fint evilnoe,to pur knuwlexdlge.hooked in 0.1 D in both axrs to anid overlap.The mgmwinn line (r=n6 has controlled trial in bumin suh线，of whether early spectacle the eqmrion (=-0.11 -0.77x Symbols and group sizes as in cmction atfeots nefractiwe develupencnt. e4. Emmetropization untreated hyperopes.from 1.7 to 0.7 D.Anahsis of varlance Our daa show that,for the group as a wlsode.a suhstantial neilution of hopcrupea.hoth spherical amdl cylineal,ocrus age-treatment interaction.and an independent samples ftest durin the second and thirdl years of bfe The avenge reductice found no signiticant dfference between the final means at 56 of refractne error is a linear function of the initlal kvel.The months (power 20.99 for a true dfference of 1.0 D.0.79 for n'grexsiun hnox imply that x rhikl with am imttal nfractsom of 0.5 D at P<005)The somme analysex eampxrring dila froen +0.86 D would on average sho'zero change in this meridian. only the complint sbjects in鱼ee道d2oup(e=3I)%i and so the peocess of emmetropization can he coedidered as a the imtrateil gromup agin foxundl no Ngnificant interetiin ur coovergence of refractions toward a low hyperopic vlue.The final differenee (power 2099 far a true differenee of 10 D: Enear relatinship dhireeted to a low hypempee end paint is 081 for 05 D at P 005). coeistent with our data in ccher groups of boch hyperopic nd mopk infants.,”The chmge n》rn months.19 were vertical fagainst the rule.the most hyperopic tinnal to initial refractive emr,implying convergence tomand a meridian between 45"and 135")and 36 horizontal (with the near cmmctropk walue tn the case of the cylindrical as well as nule,the most hyperopic meridian o'to 45"or 135"to 180"). the spberical component of refraction.consistent wich eartier dta on the reduction of infant astgmism agin fond no sigrifcant effects or ieractions,and to sig It must be apprecited,however,taat there is suhstantial nfnt山fn'noc hetwein满xl ondl antreated g.nsu mcoms variability in the extent of emmetropization within the hyper. at 56 months.This result remains the same wbether we analyze opie gre山p.自apparent froe曲Figure4 hat some ind白shaw the grops acconding to intention-to-treat ur inclde onh cum- marked rductions in hyperopl aver the first s years of hfe. pliant subjects in the treated group To determire whether a relationship exists between initial i not yet known. astigmaism and its reduction by 36 months,a regression anal. The occmence of withdrawal bctwcen 9 and 56 manths ywis wans penirmad (Pig.6)fur the oime gnu of mnfants ustxd maises the question of whether those who remained in the in aur regrrxsion analysis of emmetmpizatim (n 159).In udy were a beased sampk.However,we found no evidenee ckh infant.we tracked the cye that was mon astigmatic at 9 for any differences in initil refractioa between children who obtained by subtracting the vertical meridian from the horizon tal),with change (expressed as the dirference between astig Effect of Spectacle Correctlon matismn values at 56 months and 9 mooths),we agnin found a highly signifieant linear relatkinship (F=315.85.P D.0MM)) ttrewient eflixt af nfrctive correction Itween 9 d 18
untreated hyperopes, from 1.7 to 0.7 D. Analysis of variance comparing the two hyperopic groups found no significant age–treatment interaction, and an independent samples t-test found no significant difference between the final means at 36 months (power .0.99 for a true difference of 1.0 D; 0.79 for 0.5 D at P , 0.05). The same analyses comparing data from only the compliant subjects in the treated group (n 5 31) with the untreated group again found no significant interaction or final difference (power .0.99 for a true difference of 1.0 D; 0.81 for 0.5 D at P , 0.05). Of the 85 subjects with 1 D or more of astigmatism at 9 months, 49 were vertical (against the rule, the most hyperopic meridian between 45° and 135°) and 36 horizontal (with the rule, the most hyperopic meridian 0° to 45° or 135° to 180°). Analyzing these two types of astigmatism individually, we once again found no significant effects or interactions, and no significant difference between treated and untreated group means at 36 months. This result remains the same whether we analyze the groups according to intention-to-treat or include only compliant subjects in the treated group. To determine whether a relationship exists between initial astigmatism and its reduction by 36 months, a regression analysis was performed (Fig. 6) for the same group of infants used in our regression analysis of emmetropization (n 5 159). In each infant, we tracked the eye that was more astigmatic at 9 months. Comparing astigmatism (expressed as a signed value obtained by subtracting the vertical meridian from the horizontal), with change (expressed as the difference between astigmatism values at 36 months and 9 months), we again found a highly significant linear relationship (F 5 315.86, P , 0.0001). As Figure 6 indicates, there is a very strong tendency for astigmatism of either type to diminish in proportion to its original extent. The bottom left and top right quadrants, which contain subjects in whom astigmatism increased, were very sparsely populated. Our longitudinal analysis of the group means (Fig. 5) indicates that this process of reduction was not impaired by the prescribed partial correction: The protocol applied meant that in only 22 cases did this include a cylindrical correction. Possible Biases To evaluate differential withdrawal from the study as a possible source of bias, we compared the initial (9 month) retinoscopy measures of greatest axis and astigmatism of subjects who remained in the study with those who were withdrawn. Independent samples t-tests found no significant differences, in either hyperopic group or in the control subjects. There was also no statistically significant difference in numbers of boys and girls in any of the three groups. DISCUSSION Although the effects of visual feedback on emmetropization in early life are well documented, the implications of these effects for the practice of refractive correction in infancy and early childhood have not yet been well understood. This study presents the first evidence, to our knowledge, based on a controlled trial in human subjects, of whether early spectacle correction affects refractive development. Emmetropization Our data show that, for the group as a whole, a substantial reduction of hyperopia, both spherical and cylindrical, occurs during the second and third years of life. The average reduction of refractive error is a linear function of the initial level. The regression lines imply that a child with an initial refraction of 10.86 D would on average show zero change in this meridian, and so the process of emmetropization can be considered as a convergence of refractions toward a low hyperopic value. The linear relationship directed to a low hyperopic end point is consistent with our data in other groups of both hyperopic and myopic infants.21,25 The change in astigmatism is also proportional to initial refractive error, implying convergence toward a near emmetropic value in the case of the cylindrical as well as the spherical component of refraction, consistent with earlier data on the reduction of infant astigmatism.26,27,24 It must be appreciated, however, that there is substantial variability in the extent of emmetropization within the hyperopic group. It is apparent from Figure 4 that some infants show marked reductions in hyperopia over the first 3 years of life, whereas others show little change. The basis of this variability is not yet known. The occurrence of withdrawal between 9 and 36 months raises the question of whether those who remained in the study were a biased sample. However, we found no evidence for any differences in initial refraction between children who were withdrawn and those who remained in the study. Effect of Spectacle Correction The comparison of corrected and uncorrected groups suggests a small, transient effect of refractive correction between 9 and 18 FIGURE 6. Change in astigmatism as a function of initial astigmatism. Abscissa: initial astigmatism of the more astigmatic eye for each individual at age 9 months expressed as (hyperopia in horizontal meridian) 2 (hyperopia in vertical meridian)—i.e, positive values represent horizontal with-the-rule astigmatism, negative values represent vertical against-the-rule astigmatism. Ordinate: change in this value between 9 and 36 months for the same eye. Data points have been jittered by 6 0.1 D in both axes to avoid overlap. The regression line (r2 5 0.67) has the equation (y 5 20.11 2 0.77x). Symbols and group sizes as in Figure 4. 3730 Atkinson et al. IOVS, November 2000, Vol. 41, No. 12
OUS Nowember 2000.Vol.dl.No.12 Emmetropization in Corrected Intant Hyperopes 3731 months of ae.However,by 36 months this effect had disap 2.Houland IC.Early refractive development.In:Simons K.ed. peared,and the infants with iniil byperopia had reached a common refracticn irespeetive of trealment.This condusion Onfond Deiversry Press 199%5-11. nematnod the some whuther we analycd in terms of the cnginil strabistus and ambly op from refractive scrcening in the Cam agmint to mnannd or tinsitrxl gmops sir whrthr we cun- brulge phukeefnactin pruren he Sirsu K.eu.Forfy Vhu sidered as treated only those who consstently wore their specta Dvrelpueut Nornl amf rol.New York:Oxfoed Uriven dos Thus.we find no evkknce that parttal spectade corncction 师Pe深199朗：335-3M for infintile hyperopia interered in any persistem way with the 4.Mlimon J.Beaddick QL Bobeer B.et al.Two infan vision sorce. developmental trend toward emmetropl. The aalysis that included the larges number of byper blyopta from photo an vilourefractive strecntig.Ere 19926. 1019-1w epe-il thase with a 9 munth and 56 month messurement .guc,(hc心D,iata￥，Fgl-Wenleck L Lucal (talal a 89)-bad a power of 096 in detecting a true rtinal regias control lncal epe gmwth and myop白. chffererce af 1 D at(.Thu although there is wide 172775-7. vanshihty in initicl mfrartion and refrktive 4ingr,with udaseratise in chicks (oauu tis so1 可up5ahb2 e we can shoo'a家h5ume0 ontdence that spectack comrection does not subozantially interfere with em. tmiling eye powth and fefractive stale in the chicken.Visio Pes. metropization. 199131717-734 The general reduction of bperopia ren tlat mary in- 8.Jadge 51.Does the eye prow ino foous?Mtune.99035:177.478. fanrs (w 21)in the treated group did not the criteria for prexeripticm befier the:age of 36 momnths d the refrctive sts of yuuig moukeys.Noy Mcol.1995.1.761- The tinding that spectade correction did not impede em 761 mctropizatiun applkd to the refractne populatiun we have o,dnw由nhk.2n1s659-67 described.We cannot be sure how retractive correction might 11.Zadnic K.Mim DO.Tlow appEcahle ane asiml models mo himan aftect the develpment of very large hyperopic errors,whih show very variabl degrees af emmetropiziioe (see the 12.Edsoet CF.Ac metropirarion:evidence for ins squares in Fig 1),or bow it would affect chdren who have d ranrlicstut Iur citusl praclxe.LAbtnmie Myadof Lif. strabismus before rexceiving a cnrrection.We dd not gather 1997:17279.290 sstematic crta on cthmk nrigm or snckocunoeme status.Huw- 14.Fhcrull D.Muvilnl A.U Kee MO.Do ybpscs prevenl e. ever,the xtly gruup and the popultim fromm which itt drawn had a very strong predominance (o whke ori gn.and,bocauke the scrocning mas hased on high attendhnce miractive devekpmert t afanl miurkrys.vuion 1 within a sociaty mixed geographi area.covers the range od 1415-1155. socicecanomic groups.There was no indicatice of differential 15.Macruft DI.The lens kh包eaperinental mvuptt iukn> a严10s-l1 spectack correetion as descrihed in the Methods seclioe A full eye growth and sefeactive crror at the mimoset.Von Nez omoction af refractive cror wokl ansun that the accxrmm 1999391-m6 dative demaod for an infant with hyperopia wis redoced to a t7.Dbun￥，Scbrts 5L.C2nMR.Do Gasses prevenl e. kwer kvel than for contrul infants (wbo in general had a small. uncorrected hyperopia).It is poosible that such a reduction in Wu×名16(15∠.=Lt红2 accocnmodation would indence the emmetropztion pro bluot A.Monean.M0 ous.Mrmnus od Mroie u Mmdiutr cess.Hawever,our pxartial corrections did not peoduce sach an ..1990104-152 effect. 19.Grcovenur'I,Fit NK:Mfrativ Aamee Menurcb atudl Cfmn. oeth-lkinemann:1991 infants with hyperopia according to the protocol descnbed in 20.Iregram RM.Arrok FE.Dall S.Lucas I.Emmeemopization squint. hrpn'g碱ady h:ts hencfict中lf拆cts of rolucing the in士 5414m440 derces of strabismus and poor acuity by two thirds in children who comply in wearng the prescrbed correction The a loegoudial study of refraction componens from 9 months of present reslts indcate that these benetits can be achieved 0E.Qm17.1997:74821-815 hout the aptic士rlrf%mparirin电he normal ckvek 22.owland EC.Braddick C可以，uksm,Huww&Opeis国 mertal regulation of eye growth and refractioe 18741U1-108. Aclnoeledgments 25.ah:k口引，AkI人torefracthe techrique applicttions oaw山dpoatg clelu.ramw之bag The authoes thank oter members of the Voudl Developeteat Uuit,dhe 226-d 24.Atkinoon I.Braddick of.Feench I.Inenr asrimarisne:its dicp mtent.Arkfrshmnsr's Ifnspiral Cambripe.for sipport in ninning rhis pearaner with apr.Vaou M 19 20191-993 peoeram. 25.Ehrlich D.AtkinsonJ Braddick O.Bohier W.Durden K.Redacrion er intant mnpla:a longimdiral eyrlopirgke smdy Vclon Rec 尼feruces 19953发1313-1324 26.Huwland .Aktasee:J,Brauck UJ,Frenth J.Infanl soltgnraibtn 1.AMkironJ.Beaddick Ol.Durden K.Watson PG,Aukiron 5.Sercen uc5tb年ph00efr0.5g198232.33-333. ur refrasthe trrun m6-9months ukd inbantx昨u女s 27.k女包L,Hek K.(iwa由小，rnl山5.AMeysnalimn in irdsnts aL.BrW198468.U5-l12. 5g.18202129-30
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 5 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 5 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. Acknowledgments 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. References 1. 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. 2. Howland HC. Early refractive development. In: Simons K, ed. Early Visual Development: Normal and Abnormal. New York: Oxford University Press; 1993:5–11. 3. Atkinson J. Infant vision screening: prediction and prevention of strabismus and amblyopia from refractive screening in the Cambridge photorefraction programme In: Simons K, ed. Early Visual Development: Normal and Abnormal. New York: Oxford University Press; 1993:335–346. 4. Atkinson J, Braddick OJ, Bobier B, et al. 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