the retina, as documented by fundus photography 3 months and 12 months after ... 9. ACUITY CARD TESTING IN THE CRYO-ROP TRIAL / Dobson er ol. 1703.
Investigative Ophthalmology & Visual Science, Vol. 31, No. 9, September 1990 Copyright © Association for Research in Vision and Ophthalmology
Acuity Card Assessment of Visual Function in the Cryotherapy for Retinopathy of Prematurity Trial Velma Dobson,* Graham E. Quinn,f Albert W. Biglan,^: Berry Tung,§ John T. FlynnJ and Earl A. PalmerU The primary outcome measure of the effectiveness of cryotherapy in the original design of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was the anatomic status of the retina, as documented by fundus photography 3 months and 12 months after infants had received treatment. The authors describe the addition of a measurement of visual function, the Acuity Card procedure, to the CRYO-ROP study. After training, four visual-acuity testers attempted to measure monocular grating acuity in all randomized infants and approximately one fourth of the natural-history infants in the study, tested at 1 year postcryotherapy or 1 year postterm. In 95% of infants on whom testing was attempted, monocular acuity values from each eye were obtained. Interobserver test-retest results on 25 eyes of 13 randomized infants agreed to within one octave or better in all but one of the eyes. The high testability rate and good interobserver agreement suggest that the Acuity Card procedure has been a successful method of assessing visual function in the CRYO-ROP study. Invest Ophthalmol Vis Sci 31:1702-1708, 1990
In the original design of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP), the primary measure of the effectiveness of cryotherapy was the anatomic status of the retina, as documented by fundus photography, 3 months and 1 year after treatment.1 A quantitative measure of visual function was not included because the quantitative measures available were laboratorybased techniques that were still in the developmental stage, were time consuming, and required technical expertise that precluded their incorporation into this multicenter trial. Subsequent to the initiation of the CRYO-ROP study, the Acuity Card procedure2 emerged as a rapid, easy-to-administer, behavioral method for assessment of grating (spatial resolution)
visual acuity in infants and nonverbal children. Because of the need to evaluate the effect of cryotherapy on vision, the Executive Committee of the CRYOROP study incorporated the measurement of monocular grating acuity at the 1-year follow-up examination as a measure of functional visual outcome after cryotherapy. We describe the incorporation of Acuity Card testing into the CRYO-ROP trial and evaluate the effectiveness and reliability of the Acuity Card Procedure as a measure of visual acuity in that trial. Materials and Methods Patients were enrolled into the CRYO-ROP trial from January 1986 to November 30, 1987. All infants were < 1250 g at birth, and they participated in either the "natural history" or "randomized" segments of the clinical trial. Details of enrollment, randomization, and follow-up are available elsewhere.1 As part of the 1-year examination, questions designed to assess developmental status were asked concerning the infant's ability to sit, to grasp an object and resist having it removed from his or her hand, and to show a clear response to sound. Developmental status was judged to be satisfactory if the infant could perform two of these three tasks. Incorporation of Acuity Card testing into the CRYO-ROP trial involved three phases: (1) the development of a protocol, (2) training of testers, and (3) the testing of infants in the study.
From the Departments of *Psychiatry and Psychology, and ^Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; fDivision of Pediatric Ophthalmology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania; §School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas; ||Department of Ophthalmology, University of Miami, Miami, Florida; and UDepartment of Ophthalmology, Oregon Health Sciences University. On behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group. A full listing of the Cryotherapy for Retinopathy of Prematurity Cooperative Group can be found in the first report of the results of the Cryotherapy for Retinopathy of Prematurity study. Supported by a cooperative agreement (5 U01 EY05874) from the National Eye Institute. Reprint requests: Velma Dobson, PhD, Department of Psychology, Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260.
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ACUITY CARD TESTING IN THE CRYO-ROP TRIAL / Dobson er ol
Protocol Development
The initial phase created a protocol that would provide monocular acuity estimates in both the treated and untreated eyes of all infants who had been randomized to cryotherapy. Four aspects of measurement of visual acuity were considered: (1) the best method to use, (2) when to measure visual acuity, (3) how to measure visual acuity in the widely scattered study population, and (4) incorporation of measures to ensure quality control. The Acuity Card procedure was chosen as the method for measuring visual acuity because of the speed and ease with which it can be administered and because previous research had shown that it could be used effectively in infants.3 The decision concerning when to test was straightforward: follow-up eye evaluations of all infants in the CRYO-ROP study were being scheduled 3 and 12 months after treatment, so that acuity testing could be added at either age with minimal inconvenience to the parents or study-center coordinators. Because visual acuity in normal, full-term infants is better at 12 than at 3 months of age and because most study infants had already completed the 3-month examination, it was decided to add acuity testing to the 12month follow-up examination. The issue of how to test all treated (randomized) infants was complicated because the infants were located at 23 centers distributed across the United States. The most efficient method would have been to certify a person as an acuity tester at each center. However, because the Acuity Card procedure was a newly developed technique, it was not clear that adequate quality control of the data could be maintained with a part-time tester at each center. In addition, the Acuity Card procedure requires frequent practice for a tester to maintain skills at the level required to assess visually or neurologically compromised infants reliably. Therefore, four full-time testers were selected, each of whom was based at one of the CRYOROP centers and assigned to assess all study infants (both randomized and nonrandomized) at their base (home) center and the randomized infants at five to six remote centers. In addition to limiting the number of acuity testers to four, the following quality-control measures were incorporated into the protocol: 1. Testers were masked to the medical/ocular history of the infants, particularly to which eye of each infant had been randomized to cryotherapy. 2. Every 6 months, the testers were reassigned to different centers for testing randomized infants. This minimized the possibility of the testers' learning which eye of an infant had been treated. It also dis-
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tributed across all study centers any individual differences among testers. 3. Testers participated in a 1-day quality-control session every 6 months. During this session, the testers watched each other conduct Acuity Card assessment of several infants and discussed testing-related issues with the experimental psychologist (V.D.) and pediatric ophthalmologist (G.Q.) directing the acuity-assessment protocol. 4. Between June 1988 and June 1989, each available, cooperative randomized infant at the testers' home centers was tested twice: first by a tester from another center and then by the home tester. This part of the protocol provided data on interobserver testretest reliability. 5. In addition to assessing randomized infants at five to six remote centers, each tester also measured the acuity of all natural-history (not randomized) infants at her own center. This assured that testers evaluated infants without significant visual disorders, maintained skill in the technique, and provided visual acuity data on a subset of the natural-history population. Training of Testers
Four visual-acuity testers were trained. Each tester studied the Teller Acuity Card Handbook,4 the manual of procedures for visual-acuity testing in the CRYO-ROP study, and a review of the Acuity Card procedure by Teller et al.3 The testers then attended a 1-day training session: they first watched two experienced testers conduct the Acuity Card procedure, then the experienced testers watched the four CRYO-ROP testers conduct the procedure with five to seven infants. To gain more experience, each tester then tested 10-18 nonstudy infants with and without ocular abnormalities at their home center. Testers were certified when they completed monocular acuity assessment of both eyes of at least eight infants who had no ocular abnormalities and whose scores fell within the normal range. All testers were certified within 6 weeks of the initial training session. As a final check on the testers' proficiency, one of the trainers observed the testers' technique during a 1-day session held 2 months after the initial training session. Testing of Infants
Each tester carried a set of 17 Acuity Cards, including the "Low Vision" card, with her to the centers. Each of the 23 study centers was provided with an Acuity Card screen (Vistech). Figure 1 illustrates the use of the cards and screen during testing.
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INVESTIGATIVE OPHTHALMOLOGY & VI5UAL SCIENCE / September 1990
*
fr
Fig. 1. Measurement of grating acuity with the Teller Acuity Card Procedure. Infant is seated on parent's lap with eyes 38 cm from the center of the Acuity Card. The tester (behind the screen) presents a series of Acuity Cards {the 0.32 cycle/cm card is shown here) and watches the infant's eye and head movements through a peephole in the center of the card. Based on the infant's preferential fixation of the gratings on the Acuity Cards presented, the tester estimates acuity as the finest grating that the infant gave evidence of being able to resolve.
Testing was conducted either before the ophthalmologist's examination at the i-year follow-up visit or at another visit, separated from the rest of the eye examination. Informed consent was obtained from each infant's parent or guardian after the procedure was explained and before testing. During testing, the parent held the infant 38 cm in front of the opening in the screen where the Acuity Cards were presented. The cards were stacked face down behind the screen, from the lowest to the highest spatial frequency (from larger to smaller stripe widths). Placing the cards face down allowed the tester to present each card without knowledge of whether the grating was located to the left or to the right of the peephole on each individual card. Initially, the tester presented the card containing the 1.3 cycles/cm* grating and decided, on the basis of the infant's eye and head movements, whether the child could resolve the grating.f If the tester judged that the child could resolve the grating, cards containing finer and finer gratings were pre* A cycle consists of one black and one white stripe. The width of each stripe in the 1.3-cycles/cm grating is 0.4 cm, the width of each stripe in the 0.32-cycle/cm grating is 1.6 cm, and the width of each stripe in the "Low Vision" card is 2.2 cm. At a test distance of 38 cm, the 1.3-cycles/cm grating produces a visual target of 0.9 cycle/ degree. | More detail about the manner in which the tester uses the infant's behavior to judge whether or not the infant can resolve the grating is reported in Teller et al.3
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sented, until the infant showed no evidence of resolving the gratings. If the child's eye and/or head movements provided no evidence that he or she could resolve the 1.3 cycles/cm grating, the tester presented the card containing the 0.32 cycle/cm* grating (very large stripes). If the child's eye and head movement response to that card indicated to the tester that he or she child could resolve that grating, then cards containing finer and finer gratings were presented until the tester judged that the child showed no evidence that he or she could resolve the grating. If the child provided no evidence that they could resolve the 0.32 cycle/cm grating, the tester used the "Low Vision" (0.23 cycle/cm*) card as a final attempt to document pattern vision. The acuity threshold was estimated by the finest grating that the tester judged that the child could resolve. During the examination, the testers were required to present each card at least twice, once with the grating on either side of the peephole, and they were permitted to present each card as many times as necessary to reach a decision concerning whether or not the infant could resolve the grating on the card. Testers were required to remain masked to the location of the grating on each card until they had reached a decision as to whether the infant resolved the grating. After they reached a decision about the visibility of the grating to the infant, testers were allowed to examine the front of the card to confirm their judgment about the location of the grating on the card. The test distance was changed under two circumstances. First, if the infant began to play with the shield that blocked the parent's view of the screen, the infant was moved back to a measured distance of 55 cm. Second, if the infant was unresponsive to the lowest spatial frequency grating at 38 cm, the tester came out from behind the screen and presented the cards directly in front of the infant at 38 cm or, if necessary, at 19 cm or 10 cm. Other modifications in protocol included vertical presentation of the cards for children with nystagmus, and presentation of the cards at various field locations in low-vision patients, in an attempt to find an area of form vision. Scoring of results: The tester recorded the test distance, the spatial frequency (cycles/cm) of the finest grating that the tester judged that the infant could resolve, and a confidence rating. Nonstandard procedures (eg, testing without the screen and testing with the cards held vertically) and general comments were also recorded. If a tester was unable to obtain an acuity estimate from one or both eyes, the reason for the incomplete test (eg, fussiness or sleepiness) was recorded.
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ACUITY CARD TESTING IN THE CRYO-ROP TRIAL / Dobson er ol
The testers did not discuss acuity results with the parents. A graph showing the child's results relative to age norms was given to the examining ophthalmologist after he or she completed the ophthalmologic examination. Acuity results were provided to the parent by the ophthalmologist, in the context of the complete eye examination. One copy of each infant's data sheet was sent to the CRYO-ROP Coordinating Center, one copy was given to the Study Center Coordinator for placement in the child's medical record, and one copy was retained by the tester. Acuity scores were converted to cycles/degree by the Coordinating Center, based on the raw score in cycles/cm and the distance at which the test was conducted. Retests: Retests were required if one or more of the following occurred: 1. The tester was unable to obtain an acuity estimate from each eye of the infant. 2. The eye examination conducted at the 12month follow-up revealed a substantial refractive error, denned as uncorrected myopia greater than -4.75 diopters (D), uncorrected hyperopia greater than +6.00 D, uncorrected astigmatism greater than 3.00 D in one or both eyes, or anisometropia greater than 2.00 D spherical equivalent or cylinder if amblyopia was suspected by the examining ophthalmologist. In this case, retest with correction was required, after the infant had worn the prescribed correction for at least 1 month. 3. The eye examination conducted at the 12month follow-up revealed the presence of amblyopia,
in the absence of retrolental membrane, retinal detachment involving the macula, or a macular fold. Amblyopia was diagnosed by an ocular preference in the fixation behavior. If amblyopia was judged to be present, a retest was required after 1 month of amblyopia therapy, as prescribed and monitored by the treating physician. Results Testability Rates
Table 1 presents the testability rates for Acuity Card testing of the 190 infants in the randomized group and the 624 infants in the natural-history group who were tested between October 1987, when the first tester was certified, and June 1989. Within each group, the developmental status of infants was broken down into three categories: satisfactory, abnormal, and unknown. A successful Acuity Card test was defined as any of the following: measurable grating acuity, resolution of only the 0.2 cycle/cm grating on the "Low Vision" card, light perception only, or no light perception. Success rates for completing two monocular tests were similar in the randomized and natural-history groups, irrespective of developmental status. For the group of infants on whom a monocular acuity test was completed for each eye, Table 2 shows the number of tests each infant completed. In most infants, in both the randomized and the natural-history groups, it was necessary for the tester to conduct only two acuity tests (one per eye). For 33 infants
Table 1. Success rates for acuity card testing (12 months) Tests completed Group and developmental status Randomized Satisfactory Abnormal Unknown Total randomized Natural History Satisfactory Abnormal Unknown Total natural history
Number tested
Two monocular
174
164 (94.2%) 15 (100.0%) 1 (100.0%)
5 (2.9%) 0 (0.0%) 0 (0.0%)
180 (94.8%)
5 (2.6%)
574 (95.7%) 18 (94.7%) 4 (80.0%)
14 (2.3%)
(20.0%)
596 (95.5%)
(2.4%)
15 1 190
600 19 5 624
Only one monocular
0 (0.0%)
1 15
Only binocular
5 (2.9%)
No tests completed
0 (0.0%)
0
0
(0.0%)
(0.0%)
0
0
(0.0%)
(0.0%)
5 (2.6%) 12 (2.0%) 1 (5.3%) 0 (0.0%) 13 (2.1%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
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Table 2. Number of tests required to obtain two monocular acuity estimates (12 months) Group
Number tested
2 Tests
3-4 Tests
>4 Tests
25 (13.9%) 24 (4.0%)
(4.4%) 4 (0.7%)
Randomized
180
147 (81.7%)
Natural history
596
568 (95.3%)
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mary tester said the acuity was 3.3 cycles/degree, and the home tester said that the child had no spatial vision. For the 14 test pairs on which measurable grating acuity values were obtained by both testers, the mean interobserver difference was 0.44 octave (standard deviation = 0.3 octave). The minimum interobserver difference was 0 octave, and the maximum was 1.0 octave.
(18%) in the randomized group and 28 infants (5%) in the natural-history group, however, more than one test per eye was needed because the eye was tested initially without adequate optical correction, because the eye was tested before amblyopia therapy, or because the infant did not cooperate during the initial test.
Discussion Our results indicate that the Acuity Card procedure was incorporated successfully into the Multicenter CRYO-ROP Trial. Thus far, acuity assessment has been undertaken at 12 months postcryotherapy in 190 infants who were randomized to cryotherapy, and at 12 months corrected age in 624 infants in the natural-history segment of the study. In 95% of infants in the randomized and in the natural-history groups, an estimate of monocular acuity was obtained from both eyes of the infant. In all remaining infants, either a monocular acuity estimate was obtained from one eye or a binocular acuity estimate was obtained. The success rate for obtaining monocular acuity results in infants who failed two of three motor/neurologic screening tests was as good as the success rate in the rest of the study population. Interobserver agreement was examined in 25 eyes of 13 randomized infants, and in only one case (4%) did the observers differ by more than one octave in their estimates of acuity. The finding that the Acuity Card procedure pro-
Interobserver Agreement
Figure 2 shows interobserver test-retest agreement for the 13 randomized infants on whom one or both eyes were tested by two testers. (Interobserver testretest comparisons were not conducted on infants in the natural-history group.) With one exception, all data points in which a measurable grating acuity was obtained fall within the solid lines indicating interobserver agreement of one octave$ (two cards) or better. The one exception is a case in which the pri-
$ An octave is a halving or doubling of spatial frequency; eg, from 38 to 19 cycles/cm or from 15 to 30 cycles/degree.
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