Longitudinal Study of Acuity and Stereopsis in Infants with or At-risk for Esotropia

Transcription

1 Ivestigative Ophthalmology & Visual Sciece, Vol. 3, No. 6, Jue 18 Copyright Associatio for Research i Visio ad Ophthalmology Logitudial Study of Acuity ad Stereopsis i Ifats with or At-risk for Esotropia Velma Dobso ad 5. Lawso Sebris Gratig acuity ad stereopsis were measured logitudially i five groups of ifats: ifatile esotropes, moderate hyperopes, high hyperopes, ifats with a family history of strabismus or amblyopia ad cotrols. Gratig acuity was measured with a forced-choice preferetial lookig procedure. Stereopsis was assessed with a radom-elemet stereogram. Testig was coducted whe subjects were 3, 6,, 12, 18, 24, 3 ad 36 moths of age. No differeces amog groups i absolute acuity scores or iterocular acuity differeces were foud util the ifats reached 3 ad 36 moths of age. At these ages, treated ifatile esotropes showed acuity scores that were, o average,.5 octave poorer tha those of cotrols for both the eye showig the better acuity ad the eye showig the worse acuity. Stereopsis testig idicated that few, if ay, of the ifatile esotropes showed stereopsis at ay of the test ages. Over 3 of the high hyperopes developed strabismus by age 3 years, but oe of the ifats i the moderate hyperopia or family history groups developed strabismus. Ivest Ophthalmol Vis Sci 3: ,18 Oe of the most commo eye disorders of early childhood is strabismus, which has bee estimated to occur i 1 to 5 of the populatio. 1 " 3 I childre less tha 12 moths of age, strabismus usually takes the form of a esodeviatio ad is termed ifatile esotropia. After ifatile esotropia, the most frequetly diagosed form of strabismus occurrig i early childhood is accommodative esotropia, which is associated with a high hyperopic refractive error ad/or a high AC/A ratio ad typically appears whe childre are 2 to 3 years of age. Youg childre with esotropia are at risk for two types of visual deficits. The first is amblyopia, a "decrease i visual acuity i oe or both eyes which o physical examiatio appear ormal...." 4 I esotropia, the amblyopia is typically reported to be a visual acuity deficit i oe eye, which is presumed to develop as a adaptive mechaism agaist the dissimilarity of foveal images i the two eyes. 5 Cliically, amblyopia is usually diagosed i ifats as a fixatio preferece of oe eye i compariso with the From the Departmet of Psychology, Uiversity of Washigto, Seattle, Washigto. Supported by NIH grats EY-2581 ad EY-584. Developmet of the push-pael apparatus was supported by a grat from the Seattle Node of the Joh D. ad Catherie T. MacArthur Foudatio Grat o the Trasitio from Ifacy to Toddlerhood. Submitted for publicatio: February 4, 188; accepted December 22, 188. Reprit requests: Velma Dobso, PhD, Departmet of Psychology, Uiversity of Pittsburgh, Pittsburgh, PA other eye. Recetly, measures of gratig acuity,* icludig forced-choice preferetial lookig (FPL) procedures ad the visually evoked potetial (VEP), have bee show to be useful i detectig amblyopia i ifats ad i moitorig the chages i acuity that occur durig amblyopia therapy. " 13 The secod visual deficit for which ifats with esotropia are at risk is lack of biocularity, which presumably results from the disruptio of simultaeous visio i the two eyes of these ifats. Studies have idicated that if surgical aligmet of the eyes occurs before age 2, a high percetage of esotropes will exhibit some degree of biocularity. 14 " 2 However, the degree of biocularity reported varies from study to study, ad appears to deped o the method of assessmet, the adequacy of surgical aligmet, ad the legth of time betwee surgery ad assessmet of biocularity. Give the visual deficits that result from earlyoset esotropia ad the importace of early treatmet, it is obvious that there is a eed for idetificatio of risk factors associated with esotropia. Studies of iheritace patters have cofirmed the commo belief that strabismus teds to ru i families. However, the iheritace appears to be multifactorial rather tha simple Medelia, 21 which meas that it * Gratig acuity is kow to uderestimate the degree of acuity deficit preset i strabismic amblyopes. 6 " 8 However, measures of recogitio acuity such as those used to measure amblyopia i older childre ad adults, e.g., Selle letters or the E Test, have ot yet bee developed for ifats Dowloaded From: o 8/17/218

2 No. 6 GRATING ACUITY AND STEREOPSIS IN INFANTS / Dobso ad Sebris 1147 is difficult to predict o the basis of family history which ifats will develop strabismus. A secod risk factor is the presece of high hyperopia durig the first postatal year. Igram et al 22 recetly reported results of a follow-up examiatio at age 3 [ h years of a large group of childre who had bee refracted at oe year of age. The results idicated that 48 of childre who had +4. D or more of meridioal hyperopia (hyperopia alog the most hyperopic meridia) at age oe developed strabismus by age 3 V2. Twety-four percet of childre with a moderate amout of meridioal hyperopia (> +3. D ad < +4. D) had developed strabismus by age 3 V2. However, oly 4 of childre who had less tha +3. D of meridioal hyperopia at age 1 developed strabismus. The purpose of the preset study was to follow visual developmet over a 3-year period i five groups of ifats: (1) ifatile esotropes; (2) ifats at risk due to high hyperopia; (3) ifats at risk due to moderate hyperopia; (4) ifats at risk due to a family history of strabismus or amblyopia; ad (5) a cotrol group of ifats. Moocular gratig acuity ad stereopsis were assessed behaviorally at 3- to 6-moth itervals util childre reached 3 years of age. Materials ad Methods Subjects Five groups of ifats were erolled i the study. Assigmet to group was made o the basis of a eye examiatio ad cycloplegic refractio performed by a pediatric ophthalmologist before each ifat reached 8 moths of age. Ifats had o kow developmetal or eurological abormalities, by parets' report. The five groups ad the criteria for iclusio i each group were: 1. Esotropia. Esotropia > 15 prism diopters. 2. High Hyperopia. No strabismus. Refractive error > +4. D alog oe or more meridia. 3. Moderate Hyperopia. No strabismus. Refractive error betwee +3. D ad D alog oe or more meridia. 4. Family History. No strabismus. Refractive error betwee -.75 D ad D alog all meridia. Two or more close relatives (parets, sibligs, gradparets, auts or ucles) with strabismus or amblyopia. 5. Cotrols. No strabismus. Refractive error betwee.75 D ad D alog all meridia. No family history of strabismus or amblyopia. Each cotrol subject was matched to oe of the subjects i the Esotropia or High Hyperopia group o the basis of gestatioal age at birth (withi ±12 days) ad age at first test (±21 days). At the time of their iitial refractio, two of the 2 Esotropes showed aisometropia, defied as a differece of 1. D or more i spherical equivalet or cylider betwee eyes. Noe of the ifats i the remaiig four groups were aisometropic at the time of the first refractio. Subjects i the Esotropia group were recruited with the assistace of local pediatric ophthalmologists. Subjects i the other four groups were recruited by letters set to parets listed i the birth aoucemets sectio of the ewspaper ad assiged to the appropriate group followig their iitial eye examiatio. Twety ifats were recruited ito the Esotropia group, te ito the High Hyperopia group, 14 ito the Moderate Hyperopia group, 14 ito the Family History group, ad 3 ito the Cotrol group. Of the 2 Esotropes i the study, two (1) had two or more close relatives (parets, sibligs, gradparets, auts, or ucles) with strabismus or amblyopia. Three (21) of the Moderate Hyperopes ad two (2) of the High Hyperopes also had a family history of strabismus or amblyopia. Thus, if these childre had ot had strabismus or hyperopia, they would have qualified for iclusio i the Family History group. Of the iitial 88 ifats, 16 i the Esotropia group, eight i the High Hyperopia group, ie i the Moderate Hyperopia group, ie i the Family History group, ad 23 i the Cotrol group remaied i the study util they reached three years of age. The remaiig subjects either moved out of the area ( = 14) or withdrew from the study ( = ) before age three. All Esotropes who remaied i the study util 36 moths of age had udergoe occlusio therapy ad at least oe surgical procedure for eye aligmet by this age. Target test ages, calculated from the ifat's due date, were the followig: 3, 6,, 12, 18, 24, 3 ad 36 moths. Ifats 12 moths of age ad youger were tested withi ±1 moth of these ages, ad childre older tha 12 moths were tested withi ±2 moths of the target test ages. Prior to begiig testig, the procedures were explaied to the paret(s) ad iformed coset was obtaied. Apparatus Visual acuity assessmet: A automated forcedchoice preferetial lookig (FPL) apparatus was used for assessmet of gratig acuity. This apparatus has bee described i detail elsewhere. 23 Briefly, the apparatus cosisted of a gray cardboard (Crescet #651) scree cotaiig two 8 cm circular stimulus apertures, the ceters of which were located 17 cm to the Dowloaded From: o 8/17/218

3 1148 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Jue 18 Vol. 3 Fig. 1. Push-pael FPL apparatus used to test gratig acuity i childre 3 ad 36 moths of age. Pressure o the glass pael i frot of the test gratig resulted i release of a piece of cereal ito a food cup or activatio of a aimated toy o the same side of the FPL scree as the test gratig. left ad right, respectively, of a 4 mm cetral peephole. Gratig stimuli (Itergraphics Icorporated, Kirklad, WA) were mouted i pairs located 18 apart o a 62 cm disk located behid the scree. Each pair of stimuli cosisted of a high spatial frequecy black-ad-white square-wave gratig (either 58 or 86 cycles/deg, depedig o the test distace) ad a secod gratig, the test gratig, which differed i spatial frequecy from pair to pair. Rotatio of the disk was computer cotrolled, so that the pair of gratigs ad the left-right positio of the gratigs withi a pair could be varied quickly from trial to trial. Behid the cetral peephole a video camera was mouted; this camera trasferred a image of the subject's face to a televisio moitor positioed above the FPL scree. Whe youg ifats were tested, this video system allowed the adult experimeter to hold the ifat durig testig ad to serve as observer i the FPL procedure. Whe childre reached the age where they preferred to be held by the paret, the camera could be swug away ad the experimeter could observe the child's face directly through the peephole. A set of door chimes, a trai whistle ad a darkeed plexiglas box that cotaied oe of a variety of aimated toys, were located to the left ad right, respectively, of the stimulus scree. Activatio of oe or more of these items was used with subjects 6 moths of age ad older to reward them for lookig at or poitig to the test gratig ad to maitai their iterest i the test procedure. For childre tested at the oldest test ages (3 ad 36 moths), push paels ad a cereal reiforcemet system were added to the apparatus (see Fig. 1). The push paels were two 25 X 25 cm glass paels mouted 31 cm from the scree, directly i frot of the stimulus apertures, with oe pael located to the left ad oe pael located to the right of ceter. Pressure o a pael triggered a microswitch that activated oe or more of the reiforcers ad/or a food dispeser (Gerbrads) that released a piece of cereal through a plastic tube ito a cup located at the lower outside corer of the push pael. Although a attempt was made to use the FPL apparatus for all tests, some childre would ot cooperate log eough for testig to be completed. For test ages up to ad icludig 24 moths, we had o other optio but to score these tests as icomplete. By the time most of the childre i the study reached 3 moths, the acuity card procedure 24 " 26 had bee developed. I 23 childre at 3 moths ad three childre at 36 moths, we used acuity cards to assess acuity i childre who refused to complete FPL testig. The acuity cards used were 28 X 62 cm cardboard cards, each cotaiig two apertures, the ceters of which were located 12 to the left ad right, respectively, of a 4 mm cetral peephole. As i the FPL apparatus, a high spatial frequecy "blak" gratig was located behid oe aperture ad a secod gratig, the test gratig, which varied i spatial frequecy from card to card, was located behid the other aperture. Durig testig, the child was seated o the paret's lap i frot of a gray cardboard scree, ad the experimeter preseted the cards to the child by holdig them up sequetially to a 2 X 46 cm opeig i the scree. A more detailed descriptio of the cards ad scree ca be foud i McDoald et al. 24 Stereopsis: Stereopsis was tested with a dyamic radom-elemet stereogram similar to that described by Shea et al. 27 The stereogram was a aaglyph composed of two radom-elemet matrices (red-black ad gree-black) preseted o a 1 ich color televisio moitor. Elemet size averaged 3 mi arc ad all elemets i each matrix were replaced radomly every 16 msec. O stereoscopic trials, the spatial positio of a 12 X 13 cm (18 X 2 ) portio of oe matrix was shifted slightly, relative to the correspodig set of radom elemets i the other matrix, to produce a retial disparity of 76 mi visual agle at our test distace of 36 cm. To a adult viewig the display through chromatic iters, with a gree (Wratte 58) filter i frot of the right eye ad a red (Wratte 2) filter i frot of the left eye, the display had the appearace of a backgroud of radomly movig spatial oise, with a rectagle of radomly movig spatial oise floatig several cetimeters i frot of the backgroud. Closure of oe eye, so that display was viewed through oly oe chromatic filter, resulted i the disappearace of the rectagle. The cotrol, or ostereoscopic, stimulus cosisted of a 12 Dowloaded From: o 8/17/218

4 No. 6 GRATING ACUITY AND STEREOPSIS IN INFANTS / Dobso ad Sebris 114 X 13 cm rectagle of black-ad-gree radom elemets o a dark backgroud. The positio of the rectagle o the stereogram display was uder computer cotrol. At the begiig of each trial, the rectagle was located at the ceter of the display. Whe the observer pressed a butto to begi the trial, the computer moved the rectagle out to the left or the right edge, respectively, of the scree ad the back to the ceter, accordig to a pseudoradom order. Total excursio time for movemet of the rectagle out ad back was approximately 5 sec. The computer also recorded the observer's forced-choice judgmet cocerig the directio of target movemet o each trial ad provided feedback cocerig the correctess of the judgmet. Procedure Visual acuity testig: The Diagostic Gratig procedure 28 was used to estimate moocular visual acuity. I this procedure, the subject is first tested with a low spatial frequecy gratig that has bee show to be well above threshold for a ormal child of the subject's age. If the observer's FPL results meet certai prespecified criteria (six of the first six trials, eight of the first ie trials, or seve i a row correct), the subject is show a series of trials of the "diagostic" gratig frequecy appropriate for his/her age. At each age, the diagostic gratig frequecy is the spatial frequecy that to 5 of ormal childre give evidece of detectig i a FPL acuity test procedure, as determied empirically. 23 If the observer's resuits idicate that the child ca see the diagostic gratig (ie, if the observer gets six of the first six, ie of the first te, 13 of the first 15, or 15 of the first 2 trials correct), the child is tested ext with a gratig oe octave higher i spatial frequecy tha the diagostic gratig. If the observer's results fail to idicate the child ca see the diagostic gratig, the child is tested ext with a gratig oe octave lower i spatial frequecy tha the diagostic gratig. I the curret study, testig cotiued i this fashio util acuity threshold was bracketed by oe spatial frequecy o which the observer met criterio ad a adjacet spacial frequecy oe octave higher o which the observer failed to meet criterio. If the child remaied cooperative, he/she was the tested with the middle spatial frequecy, oe-half octave away from the two bracketig spatial frequecies. Acuity was estimated to be the highest spatial frequecy o which the observer met criterio. Twety-three (33) of the 3-moth-olds ad three (5) of the 36-moth-olds could ot be tested with the Diagostic Gratig procedure. Subsequetly, 21 (81) of these childre were tested successfully with the acuity card procedure. The acuity card procedure used was idetical to that described by McDoald et al, 25 ' 26 i which the observer tested the child with a subset of ie acuity cards, arraged i ascedig order of spatial frequecy ad differig from oe aother i half-octave steps. The observer kew the relative order of spatial frequecies, but ot the absolute spatial frequecies of the cards o each test. The back of each card was marked to idicate the positio of the test gratig ad "blak" stimulus. Observers typically preseted each card without kowig the positio of the stimuli ad the used the markigs to cofirm their judgmet cocerig stimulus locatio after the gratig had bee show several times to the child. Test distace from the peephole to the child's eyes was 31 ± 3 cm at the 3-, 6-, ad -moth test ages ad 54 ± 3 cm for test ages older tha moths. Childre who had bee prescribed optical correctio by their referrig pediatric ophthalmologist wore their prescribed correctio durig testig. Stereopsis testig: At the 6-moth test age ad all subsequet test ages, presece vs absece of stereopsis was assessed with the dyamic radom-elemet stereogram. The child was seated o the paret's lap at a distace of approximately 36 cm from the stereogram scree. Glasses cotaiig a red filter (Wratte #2) over the left eye ad a gree filter (Wratte #58) over the right eye were placed o the child. For childre who already wore glasses, the filters were taped over their ow leses. The paret wore a pair of glasses with red filters over both eyes, which preveted detectio of the stereoscopic target. The experimeter, who was masked to the directio of stimulus movemet, observed the child's eye movemets, head movemets ad reachig behavior ad made a forced-choice judgmet o each trial as to whether the stimulus had moved to the left or to the right. Observers also recorded whether or ot the child reached for the stereoscopic stimulus. Iitially, the child was show four trials with the cotrol (gree square o a dark backgroud) target. If the experimeter correctly judged stimulus directio o at least three trials, testig with the stereoscopic stimulus was begu. Testig with the stereoscopic square cotiued util the experimeter met oe of three criteria five of the first five trials correct (Pass), eight of the first ie trials correct (Pass), or two trials icorrect (Fail) or util the child refused to cooperate. Experimeters: To miimize bias i acuity testig, the two experimeters who tested subjects were masked to the diagosis of each subject ad were allowed to see subjects oly after they had bee patched for moocular acuity testig. It was ot pos- Dowloaded From: o 8/17/218

5 115 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Jue 18 Vol. 3 Table 1. Cliical outcome at 36 moths Esotropia = 16 High hyperopia 8 Moderate hyperopia Family history Cotrol 23 Strabismus (# of childre) Ortho Deviatio <1A Deviatio >1A Sigle Surgery Multiple Surgeries Hyperopia (# of eyes) (most hyperopic meridia) Noe or Miimal (-.75 to D) Moderate (+3. to D) High (> +4. D) Astigmatism (# of eyes) <1.D fcl.ood Aisometropia (# of childre) <1.D differece i spherical equivalet or cylider il.oo D differece i spherical equivalet or cylider sible, however, to completely mask the experimeter to latet ystagmus, extreme deviatio or the presece of the optical correctio. The experimeter for stereopsis testig was ot the same experimeter who coducted acuity testig. This experimeter kew the diagosis of the child ad, of ecessity, viewed the child whe the child was ot wearig a patch. Eye Examiatios I additio to the iitial eye examiatio, performed whe the child etered the study, each child i the High Hyperopia, Moderate Hyperopia, Family History ad Cotrol groups received a eye examiatio ad cycloplegic refractio by a pediatric ophthalmologist whe they reached 1, 2, ad 3 years of age. Childre i the Esotropia group ad childre i the High Hyperopia group who developed strabismus received examiatios as required by cliical protocol. Results Cliical Outcome at Age Three Years The cliical outcome at age 3 of the childre i each of the five groups is summarized i Table 1. Several geeral coclusios ca be draw from Table 1. First, the oly childre who became strabismic after 8 moths of age were three childre i the High Hyperopia group, who developed strabismus 2: 15 prism diopters betwee 21 f ad 2 moths of age. Of the three, oe uderwet surgery at 33 moths, spectacle correctio elimiated the esotropia i oe ad the third had ot yet udergoe surgery by age 3. Secod, all childre i the Esotropia group had udergoe at least oe surgical procedure for eye aligmet by 3 years of age. Despite surgical itervetio, 12 cotiued to show some deviatio. Third, a sigificat reductio i the amout of hyperopia preset occurred betwee ifacy ad age 3, as evideced by the fidig that 16/18 eyes i the Moderate Hyperopia group ad 8/16 eyes i the High Hyperopia group showed miimal or o hyperopia at age 3. The two childre i the High Hyperopia group who cotiued to show high hyperopia i both eyes ad oe of the two childre who showed high hyperopia i oe eye ad moderate hyperopia i the other eye developed esotropia ^ 15 prism diopters betwee 21 ad 2 moths. All three had received spectacle correctio betwee 14 ad 24 moths, oe at 14 moths, prior to ay strabismus, oe at 14 moths, whe 4 prism diopters of esotropia was oted, ad oe at 24 moths, whe esotropia of 15 prism diopters was oted. t A small agle deviatio (4 prism diopters) was oted for oe of these childre at 14 moths. A deviatio of 3 to 4 prism diopters developed by 24 moths. Dowloaded From: o 8/17/218

6 No. 6 GRATING ACUITY AND STEREOPSIS IN INFANTS / Dobso ad Sebris A The iitial refractio of subjects i the Esotropia group, coducted whe subjects were betwee oe ad eight moths of age, revealed that 12 ifats had o sigificat refractive errors i either eye, five had moderate hyperopia i oe or both eyes ad three had high hyperopia i both eyes. At age 3, the icidece of moderate ad high hyperopia i this group had icreased, i cotrast to the Moderate Hyperopia ad High Hyperopia groups, both of which showed a decrease i the icidece of hyperopia at age 3. 3 ' Fourth, all groups except the Esotropia group showed a reductio i the icidece of astigmatism 3: 1. D by age 3. The prevalece of astigmatism > 1. D i oe or both eyes at the time of the iitial refractio was 55 (11/2) i the Esotropes, 2 (2/1) i the High Hyperopes, 21 (3/14) i the Moderate Hyperopes, 14 (2/14) i the Family History group ad 13 (4/3) i the Cotrol group. At age 3, ie of the Esotropes (56 of those refracted at age 3) had at least 1. D of astigmatism i oe or both eyes; six of the ie were i the group of 11 Esotropes who had > 1. D of astigmatism at the time of the iitial refractio. Fially, four of the 16 Esotropes showed aisometropia S: 1. D spherical equivalet or cylider at age 3. Two of the four were the oly two childre i the study with aisometropia at the time of the iitial refractio. Oly oe other child (oe of the High Hyperopes who became strabismic) developed aisometropia by age 3. Visual Acuity Results Success rates: The percetage of childre from whom oe or both moocular acuity estimates could be obtaied varied widely across the various test ages. Table 2 shows for each test age the percetage of eyes tested o eough spatial frequecies to allow a acuity estimate to be obtaied. The most strikig feature of Table 2 is the low success rate for the 18- ad 24-moth-olds, similar to that reported previously for biocular testig of childre at these ages. 32 The success rates at 18 ad 24 moths i the preset study were so low that it is ulikely that the data obtaied provide a represetative sample of visual acuity i the five groups of subjects. Therefore, we did ot aalyze the moocular acuity data at these two ages. Overall success rates for the five groups were 88, 1, 83, ad 3 for the Esotropia, High Hyperopia, Moderate Hyperopia, Family History ad Cotrol groups, respectively. For the 3- ad 36- moth test ages, where acuity differeces betwee the Esotropes ad Cotrols were foud, the success rate was 1 (64/64 tests) for the Esotropia group ad (5/6 tests) for the Cotrol group. Table 2. Success rates of acuity ad stereopsis testig Age (moths) Acuity tests # Eyes tested successfully 113/ / / /16 65/14 45/ /138f 124/126f Stereopsis tests # Successful tests* 54/6 44/57 37/6 31/64 34/71 53/64 52/ Child completed eough trials to yield a observer's score of 5/5 or 8/ correct, or two or more icorrect. t Success rates at 3 ad 36 moths iclude tests performed with the acuity card procedure. Forty-six tests of 3-moth-olds ad six tests of 36- moth-olds required use of the acuity cards. At 3 moths, 38 (83) of the acuity card tests yielded a acuity estimate, ad at 36 moths, acuity estimates were obtaied i 4 (67) of the acuity card tests. Moocular acuity results: For the data obtaied at 3, 6,, 12, 3 ad 36 moths, the acuity results from the five groups at each age were compared usig a Kruskall-Wallis test. At each age, oe test was coducted o data from the eye showig the better acuity score, ad a secod test was coducted o data from the eye showig the worse acuity score. For data obtaied at 3, 6, ad 12 moths, the results of the Kruskall-Wallis test showed o differece amog groups i the distributio of acuity scores from either the eye showig the better acuity score or the eye showig the worse acuity score. At 3 ad 36 moths, there was a sigificat differece i the distributio of acuity scores across groups, both for the eye showig the better acuity score (H = 11.2, P <.2 at 3 moths, ad H = 12.55, P <.2 at 36 moths) ad for the eye showig the worse acuity score (H = 11.2, P <.5 at 3 moths, ad H = 17.16, P <.1 at 36 moths). Subsequet aalysis with Ma-Whitey U-tests (adjusted for multiple comparisos 33 ) comparig the distributio of acuity scores from the Cotrol group with the distributio of acuity scores from each of the experimetal groups idicated a sigificat differece betwee the distributio of acuity scores of the Cotrols vs. the Esotropes for the eye showig the better acuity score at 3 moths ad the eye showig the better acuity score at 36 moths (z = 3.1, P <.5 at 3 moths, ad z = 2.63, P <.5 at 36 moths) ad for the eye showig the worse acuity score at 3 moths ad the eye showig the worse acuity score at 36 moths (z = 2.3, P <.5 at 3 moths, ad z = 3., P <.5 at 36 moths). There were o sigificat differeces betwee the results of the Cotrol group ad the results of ay other group. Dowloaded From: o 8/17/218

7 1152 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Jue 18 Vol i i i better eye CH cotrol 3 moths H esotrope i i I i i i worse eye 3 moths D "c Q) O _ better eye 6 moths worse eye 6 moths Ml i r <D Q acuity (cycles/degree) Fig. 2. Distributio of acuity scores for the eye showig the better acuity score ad the eye showig the worse acuity score for Esotropes vs. Cotrols tested at 3, 6,, 12, 3 ad 36 moths of age. Note that acuity values o the x-axis vary with age. I the four graphs that show data from 3- ad 36-moth-olds, the Esotropic group showed sigificatly poorer acuity tha did the Cotrol group. The distributios of acuity scores obtaied at each test age for Cotrols vs Esotropes for both the eye showig the better acuity score ad the eye showig the worse acuity score are plotted i Figure 2. For data obtaied at 3, 6, ad 12 moths, there are o differeces betwee the distributios of acuity scores for the Cotrols vs. Esotropes for either the eye showig the better acuity score or the eye showig the worse acuity score at each age. At 3 ad 36 moths, however, the Esotropes show, o average, sigificatly poorer acuity scores tha do the Cotrols. The differece betwee groups i the mea acuity value for the eye showig the better acuity score is.54 octave at 3 moths ad.4 octave at 36 moths. For the data of the eye showig the worse acuity score, the differece i the mea acuity show by the Esotropes vs. Cotrols was.5 octave at 3 moths ad.7 octave at 36 moths. Because childre were tested with optical correctio oly whe it was prescribed by their referrig ophthalmologist, some childre with sigificat ucorrected hyperopia or astigmatism may have performed poorly o the acuity test. To determie whether data from ucorrected subjects may have accouted for the acuity differeces betwee the Cotrol ad Esotropic groups, we reaalyzed the data, excludig from aalysis data from eyes with ucorrected hyperopia > +4. D or astigmatism > 1. D. This reaalysis was doe oly at the 36 moth test age, because refractios were ot performed at 3 moths. Ma-Whitey U-tests cofirmed the previous fidigs that the acuity scores of the Cotrols ad Esotropes were sigificatly differet (z = 2.54, P <.5 for the eye showig the better acuity score, ad z = 3.7, P <.1 for the eye showig the worse acuity score). Thus, ucorrected hyperopia or astigmatism did ot accout for the differeces i moocular acuity betwee Esotropes ad Cotrols. Itewcular acuity differeces: Amog the esotropic subjects, iterocular acuity differeces greater tha 1. octave were ot foud i ay childre at the 3-, 6-, ad -moth test ages, ad were foud i oly oe of 11 childre tested at 12 moths, oe of 16 childre tested at 3 moths ad oe of 16 childre tested at 36 moths. These results are ot sigificatly differ- Dowloaded From: o 8/17/218

8 C - J I -J./- i v -i.t V ' - percetage of acuity scores percetage of acuity scores e e o e o to e e o I ^ <D NJ eo k> e e. ID 3 _k e eo k> e Dowloaded From: o 8/17/218

9 1154 INVESTIGATIVE OPHTHALMOLOGY & VISUAL 5CIENCE / Jue 18 Vol. 3 Table 3. Percetage of subjects with stereopsis based o the criteria of 5/5 or 8/ correct Test age 6 mo. mo. 12 mo. 18 mo. 24 mo. 3 mo. 36 mo. Group Esotropia High hyperopia Moderate hyperopia Family history Cotrol (ID (5) (1) () (1) 13 () (15) 2 13 (11) (5) (5) (4) (3) ' () (2) (3) (14) ot (14) (2) ot (14) (7) (7) (18) */><.5. fp<.l. */><O.OI. et from the percetages of Cotrols who showed iterocular differeces greater tha 1. octave at these ages (1/17 at 3 moths, 2/23 at 6 moths, 1/23 at moths, 1/21 at 12 moths, /24 at 3 moths ad /23 at 36 moths). Kruskall-Wallis tests showed o differeces i iterocular acuity differeces amog the five groups at ay of the test ages. Stereopsis Results Success rates: Assessmet of stereopsis with the dyamic radom dot stereogram was attempted at the 6-moth ad all subsequet test ages. As idicated i Table 2, the percetage of subjects o whom presece vs absece of stereopsis could be determied, based o the forced-choice preferetial lookig criteria of 5/5 or 8/ correct or two icorrect by the observer, raged from 48 at 18 ad 24 moths to at 6 moths. Success rates for idividual groups were 82 for the Esotropes, 66 for the High Hyperopes, 6 for the Moderate Hyperopes, 75 for the Family History group, ad 67 for the Cotrol group. Icomplete tests were largely due to the uwilligess of childre to wear the red-gree glasses. Stereopsis data: The percetage of testable subjects i each group who showed evidece of stereopsis accordig to the forced-choice preferetial lookig criteria of 5/5 or 8/ correct is show i Table 3 for the seve test ages. The stereopsis results from each of the four experimetal groups were compared with the data from the Cotrol group at each of the test ages usig the Chi-Square Test whe sample sizes i all or all but oe cell werefive or greater or the Fisher's Test whe sample sizes were small. Aalyses revealed sigificat differeces betwee the prevalece of stereopsis i the group of Esotropes as compared to the Cotrols at test ages of 24, 3 ad 36 moths. No sigificat differeces were foud betwee the remaiig experimetal groups ad the Cotrol group. I additio to makig a judgmet about whether the stereoscopic square moved to the left or right o each trial, observers also recorded other idicatios that the child could detect the stereoscopic square, such as followig the square with the eyes or had, or reachig for the square i frot of the scree. Some childre would cooperate for oly a few trials, but would reach for the stereoscopic square i frot of the scree ad follow its movemet for oe or two trials. Others would seem to discover the stereoscopic square after several trials ad suddely reach for it or follow it. By strict forced-choice preferetial lookig criteria, the results from such childre were scored as a failure to exhibit stereopsis or a icomplete test. However, it was clear from their behavior that they could detect a target movig i frot of the scree. Therefore, we also aalyzed the data based o the observer's judgmet cocerig whether or ot a child exhibited ay evidece of stereopsis. These results are preseted i Table 4. Overall, may more childre showed evidece for stereopsis tha was evidet from Table 3. Nevertheless, Chi-Square Tests ad Fisher's Tests comparig the results of each experimetal group with the results of the Cotrol group cofirmed the results from Table 3, that oly the Esotropia group showed a sigificatly lower prevalece of stereopsis tha the Cotrol group. Examiatio of the results of idividual childre i the Esotropia group revealed that oly oe child showed evidece of stereopsis at more tha oe test age (at 18 ad 3 moths, although ot at 24 ad 36 moths), ad this child was also the oly child i the Esotropia group who met the forced-choice criteria for stereopsis (with a score of 7/7 correct). I the High Hyperopia group, oe of the three childre who developed strabismus showed stereopsis at ay of the ages at which they were tested. Discussio The purpose of the preset study was to examie prospectively moocular visual acuity ad stereopsis developmet i ifats who had or who were at risk v Dowloaded From: o 8/17/218

10 No. 6 GRATING ACUITY AND STEREOPSIS IN INFANTS / Dobso ad Sebris 1155 Table 4. Percetage of subjects with stereopsis based o all available iformatio, icludig percet correct, reachig behavior, ad lookig behavior Test age 6 mo. mo. 12 mo. 18 mo. 24 mo 3 mo. 36 mo Group Esotropia High hyperopia Moderate hyperopia Family history Cotrol o (11) (5) (1) () (1) () (15) (11) (5) (5) (1) 13* 8 (5) 1 (3) 78 () 75 22f () (3) (15) 7t (15) (7) (22) ot 1 (15) (7) (2) P <.5. tp<.1. for strabismus ad amblyopia. O the basis of a eye examiatio ad cycloplegic refractio coducted before they reached 8 moths of age, ifats were erolled ito oe of five groups: (1) Esotropes; (2) High Hyperopes; (3) Moderate Hyperopes; (4) Ifats with a Family History of strabismus or amblyopia; ad (5) Cotrols. Visual acuity results idicated that subjects i the Esotropia group showed sigificatly poorer moocular acuity scores tha did the Cotrols at the 3- ad 36-moth test ages. This differece was sigificat for data from the eye showig the better acuity score of each subject, as well as for data from the eye showig the worse acuity score of each subject, ad was ot due to ucorrected refractive errors. Previously, two groups of researchers compared the absolute acuity scores of the eye showig the better acuity score i esotropic vs. oesotropic ifats 12 moths of age ad youger. Oe group 1234 tested acuity i 3- to 14-moth-olds with a FPL procedure ad foud o differece betwee esotropic vs. oesotropic ifats' acuity i the eye showig the better acuity score. Our results for ifats i the 3- to 12-moth age rage are i agreemet with these FPL results. I cotrast, the other group of researchers, 35 who measured acuity with the visual evoked potetial (VEP), showed reduced acuity i esotropes less tha oe year of age, whe the esotropes' results were compared with data obtaied from oesotropic ifats tested with the same procedure. The magitude of the acuity reductio foud was large eough (1.4 octaves for the right eye, 1.6 octaves for the left eye, ad.75 octave for biocular testig) that oe would expect it to be detectable i FPL, as well as VEP, acuity testig. The fact that either of the two FPL studies reported a sigificat acuity deficit i the better eye of esotropes less tha 1 year of age suggests that youg esotropes may have a acuity deficit that is preset at the level of the visual system tapped by the VEP, but ot preset, or preset at a reduced magitude, at the level of the visual system tapped by FPL testig. At our oldest test ages, 3 ad 36 moths, the FPL results did show a acuity deficit i both the better eye ad the worse eye of former esotropes. A recet reaalysis 35 of behavioral acuity data obtaied by Ig 14 from treated esotropes tested at 5 ad 11 years of age suggested that Ig, too, foud reduced acuity i the better eye of a sigificat umber of former esotropes. The cause of this bilateral acuity deficit is uclear. O the oe had, it could be the behavioral maifestatio of the deficit detectable with VEP testig durig the first year of life. O the other had, the acuity deficit could be the result of the occlusio therapy that our esotropes ad the esotropes i the Ig 14 study received durig ifacy ad early childhood. Research o reverse occlusio i kittes has show that early occlusio of a odeprived eye ca result i bilateral amblyopia I either case, it is ufortuate that we were usuccessful i testig subjects at 18 ad 24 moths, sice it would be of iterest to kow how early the acuity deficit was detectable with behavioral testig. Although both esotropic ifats ad ifats with high hyperopia are kow to be at risk for amblyopia, there were o differeces amog groups at ay age i the distributio of iterocular acuity differeces obtaied. Aalysis of the data idicated that at each of the 3-, 6-, -, 12-, 3- ad 36-moth test ages, o more tha oe Esotrope showed a iterocular acuity differece of greater tha oe octave. The failure to fid sigificat iterocular differeces at 3 ad 6 moths is ot uexpected, sice eve ifats who show a fixatio preferece typically do ot show FPL iterocular acuity differeces before 7 to 8 moths of age. 12 ' 34 The failure to fid sigificat iterocular acuity differeces i older ifats ad youg childre i our study is udoubtedly related to the fact that all childre i the Esotropia group were uder treatmet Dowloaded From: o 8/17/218

11 1156 INVESTIGATIVE OPHTHALMOLOGY G VISUAL SCIENCE / Jue 18 Vol. 3 by the time they reached the -moth test age. I additio, research with older amblyopes has idicated that gratig acuity tasks may be less sesitive tha recogitio or localizatio acuity tasks to the presece of strabismic amblyopia. 6 ' 8 Therefore, it is possible that some of our former esotropes have a residual iterocular acuity differece that will appear cliically whe they reach a age at which recogitio acuity, for example, the E Test or Selle letters, ca be assessed. Absolute acuity scores for subjects i our High Hyperopia group were ot sigificatly differet from those of the Cotrol group at ay of the test ages. This result is i cotrast to data reported recetly by Atkiso ad colleagues, 383 who showed a sigificat reductio i the acuity of high hyperopes tested at 6 to moths of age ad at 3'/2 to 4 years of age. It is likely that the data of Atkiso ad colleagues are more represetative of the acuity status of high hyperopes, sice approximately 1 childre were tested i their study while our study erolled oly te high hyperopes. A strikig fidig of the preset study was that oe of the 36-moth-olds i the Esotropia group showed evidece of stereopsis. This failure to show stereopsis is i cotrast to the results of several studies i which the percetage of esotropes who had achieved early aligmet ad who demostrated stereopsis raged from approximately to well over 4. l41 ' 2 Examiatio of the test coditios used i the studies of stereopsis i treated ifatile esotropes suggests that these differeces amog the reported percetages of childre with stereopsis i the various studies may be largely due to differeces amog the test stimuli used to assess stereopsis. For example, i most of the studies that reported the presece of stereopsis i a substatial proportio of former esotropes, a static stereogram ad polarizig separatio were used for stereopsis testig ' 17>2 I cotrast, two of the three previous studies i which dyamic stereograms ad aaglyphic separatio, similar to that of the preset study, were used to assess stereopsis i former ifatile esotropes have show a prevalece of stereopsis betwee ad Cooper ad Feldma 4 have suggested that the differece may be due to the presece of moocular cues i the static stereograms. The oly study i which dyamic stereograms were used ad a high proportio of former esotropes showed stereopsis is a study by Rogers ad colleagues, 1 i which ifats were tested two weeks after strabismus surgery. Recet results of Archer ad colleagues' 8 idicate that stereopsis i these ifats is cofied to the immediate postoperative period ad is ot detectable after loger follow-up itervals. Thus, our results that few, if ay, former esotropes show stereopsis whe tested with a dyamic radom dot stereogram are cosistet with the results of other studies that have used similar stimuli to evaluate ifatile esotropes who uderwet surgery moths or years prior to stereopsis testig. The failure of most ifats i the preset study to show evidece of stereopsis by the FPL criteria of 5/5 or 8/ correct before 18 to 24 moths of age may seem surprisig, sice studies usig similar stimuli ad procedures 274 ' have idicated that ormal ifats show stereopsis by 6 moths of age. However, examiatio of results from the Shea et al study, 27 which preseted data of idividual ifats, revealed that oe of the ifats i that study would have met the FPL criteria for stereopsis used i the preset study, sice observers scored two or more icorrect trials for each ifat. Because ifats completed 1 to 2 trials, Shea et al were able to use criteria for stereopsis that allowed more icorrect trials tha did the criteria of the preset study. I cotrast to the ifats i the Shea et al study, most ifats i our study would ot cooperate for 1 to 2 trials. This is probably because they were tested after completio of two moocular acuity tests, ad therefore were tired of testig i geeral, especially with a stimulus (the stereoscopic square) that may have bee less compellig tha the black-ad-white gratigs used for acuity testig. Three groups of subjects i the preset study the Moderate Hyperopia, High Hyperopia ad Family History groups were selected because previous research has suggested that ifats i these groups are at risk for the developmet of strabismus ad/or amblyopia. Results from Igram et al, 22 based o refractios coducted whe ifats were 12 moths of age, predict that approximately oe-fourth of ifats i our Moderate Hyperopia group would have developed strabismus by age three. However, oe of our Moderate Hyperopes developed strabismus, perhaps because ifats were assiged to the Moderate Hyperopia group o the basis of a refractio coducted prior to eight moths of age rather tha at 12 moths of age, as i the Igram et al study. It is also possible that oe or more of thefive Moderate Hyperopes who dropped out of the study developed strabismus. Evidece that ifats i our High Hyperopia group were at risk for strabismus comes from two previous studies. Igram et al 22 reported that 48 of ifats with +4. D or more of meridioal hyperopia developed strabismus by age 3 x h ad Atkiso et al 3 foud that approximately 16 of ifats with meridioal hyperopia of +4. D or more at 6 to moths of age had developed strabismus by age 4 years. Our results are i agreemet with these two studies, i that M- Dowloaded From: o 8/17/218

12 No. 6 GRATING ACUITY AND STEREOPSIS IN INFANTS / Dobso ad Sebris 1157 three (38) of the eight High Hyperopes whom we followed for more tha 2 years developed strabismus. It would be of iterest to kow why some ifats with high hyperopia become strabismic ad others do ot. I our sample, four ifats showed a reductio i hyperopia to below +4. D i both eyes by age 17 moths. Noe of the four became strabismic. However, three of the four ifats who retaied hyperopia S; +4. D i oe or both eyes became strabismic. Atkiso et al 383 reported that ifats with obliqueaxis astigmatism were more likely to remai hyperopic ad more likely to become strabismic tha were oastigmatic ifats. However, i our sample, oly two of the High Hyperopes showed more tha 1. D of astigmatism at the time of the iitial refractio ad oly oe of these ifats became strabismic. Thus, i our sample, it is uclear why some ifats retaied their hyperopia ad became strabismic, ad others showed a sigificat reductio i hyperopia by 1 to 2 years of age. Our data provide a small amout of evidece that high hyperopes who show evidece of stereopsis do ot develop strabismus, sice oe of the three High Hyperopes who developed strabismus showed stereopsis at ay test age. However, failure of a ifat to show stereopsis is ot ecessarily predictive of future strabismus, sice there were several High Hyperopes who failed to exhibit stereopsis i ifacy but did ot go o to develop strabismus by age 3 years. The presece of a geetic compoet i the occurrece of strabismus has bee reported. 21 The fidig that oe of the childre i our Family History group developed strabismus by age 3 does ot ecessarily cotradict the presece of a geetic compoet, sice two of the childre i our Esotropia group had two or more close relatives with strabismus or amblyopia. It could be argued that the geetic factor associated with strabismus is associated with early oset of strabismus, so that ifats who developed strabismus i cojuctio with a family history did so early eough that they were icluded i the Esotropia rather tha the Family History group i the study. I additio, it is possible that oe or more of the five ifats i the Family History group who dropped out of the study could have developed strabismus after leavig the study. Of the three ifats i the High Hyperopia group who developed strabismus, oly oe had a family history of strabismus ad/or amblyopia. Thus, it is likely that factors other tha simple geetic trasmissio iflueced the developmet of strabismus i this group. I summary, we followed five groups of ifats prospectively, to examie the developmet of visual acuity ad stereopsis i ifats with esotropia ad i ifats at various degrees of risk for strabismus or amblyopia. Our results showed o differeces i absolute acuity scores or i iterocular acuity differeces amog groups of ifats util the 3- ad 36- moth test ages, whe the group of childre who had bee treated for ifatile esotropia showed below ormal acuity i both the eye with the better acuity score ad the eye with the worse acuity score. Stereopsis testig with a dyamic radom-elemet stereogram showed evidece of stereopsis i o more tha oe or two childre i the ifatile esotropia group at ay test age, ad o evidece of stereopsis i ay of the former esotropes at 36 moths. Noe of the ostrabismic ifats at risk due to a family history of strabismus or amblyopia ad oe of the ifats with moderate hyperopia (SL +3. D ad < D alog the most hyperopic meridia) diagosed by age 8 moths developed strabismus over the 2- to 3-year follow-up. However, over 3 of the ifats with hyperopia greater tha +4. D alog the most hyperopic meridia before age eight moths developed strabismus by age 3 years. This fidig cofirms previous reports that ifats with high hyperopia are at sigificat risk for strabismus ad highlights the importace of cotiued follow-up of ifats who show high hyperopia at a early age. Key words: visual acuity, stereopsis, esotropia, hyperopia, ifats Ackowledgmets We thak Melvi Carlso, MD ad Howard Freedma, MD for referrig the esotropic ifats, Melvi Carlso, MD for performig eye examiatios o o-strabismic subjects, MaryAlice McDoald, PhD for assistace i testig subjects, Carol Jerome for illustratios, ad Luisa Mayer, PhD for commets o the mauscript. Refereces 1. Fradse AD: A cliical-statistical study o the prevalece of squit ad associated sigs i differet groups ad ages of the Daish populatio. Acta Ophthalmol 62(Suppl), Graham PA: Epidemiology of strabismus. Br J Ophthalmol 58:224, Friedma Z, Neuma E, Hyams SW, ad Peleg B: Ophthalmic screeig of 38, childre, age 1 to 2 'A years, i child welfare cliics. J Pediatr Ophthalmol Strabismus 17:261, vo Noorde GK: Amblyopia: A multidiscipliary approach. Ivest Ophthalmol Vis Sci 26:174, vo Noorde GK: Factors ivolved i the productio of amblyopia. Br J Ophthalmol 58:158, Levi DM ad Klei S: Differeces i verier discrimiatio for gratigs betwee strabismic ad aisometropic amblyopes. Ivest Ophthalmol Vis Sci 23:38, Howell ER, Mitchell DE, ad Keith CG: Cotrast thresholds for sie gratigs of childre with amblyopia. Ivest Ophthalmol Vis Sci 24:782, Mayer DL: Acuity of amblyopic childre for small field grat- Dowloaded From: o 8/17/218