- Email: [email protected]
Frequency Doubling Technology Perimetry in Normal Children
Frequency Doubling Technology Perimetry in Normal Children LAUREL M. QUINN, MD, STUART K. GARDINER, PHD, DAVID T. WHEELER, MD, MICHELLE NEWKIRK, BA, AND CHRIS A. JOHNSON, PHD
● PURPOSE:
To test visual field thresholds of normal children with frequency doubling technology (FDT) perimetry to quantify testing times and reliability characteristics in a pediatric population and to determine whether current methods of stratifying adult threshold values need revision for children. ● DESIGN: Prospective cross-sectional study. ● METHODS: Ninety-four children, ages 5 to 17 years, were recruited from local pediatric clinics and the general community and were tested at one center. Children likely to have abnormal visual fields or abnormal test taking ability because of ophthalmic, neurologic, or behavioral problems were excluded. Children were asked to perform a threshold FDT visual field with each of their eyes. Threshold results were gathered, analyzed, and compared with the standards that have been established for tests in adults. Results were validated by testing a further 72 children, with the same protocol, at a different center. ● RESULTS: For children older than 14 years, threshold mean deviation values were within normal limits according to the adult normative database that is used currently in FDT perimetry. Below 15 years of age, mean deviations for normal children decreased with decreasing age. The best linear fit was given by a mean deviation of ⴚ11.43 ⴞ 0.82 dB ⴛ age (R2 ⴝ 0.18; P < 10ⴚ5). ● CONCLUSION: This research establishes a normative model for pediatric visual field testing with FDT and, by a comparison of threshold results for normal children to established adult norms, provides evidence that parameters for normal sensitivity must be revised for children younger than 15 years. (Am J Ophthalmol 2006;142: 983–989. © 2006 by Elsevier Inc. All rights reserved.)
Accepted for publication Jun 29, 2006. From the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon (L.M.Q., D.T.W.) and Discoveries in Sight, Devers Eye Institute, Legacy Health System, Portland, Oregon (S.K.G., M.N., C.A.J.). Supported in part by an unrestricted grant from Research to Prevent Blindness, New York, New York. Dr Johnson is a paid consultant for Welch Allyn, Skaneateles Falls, New York. Inquiries to David T. Wheeler, MD, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239-4197; e-mail: [email protected] 0002-9394/06/$32.00 doi:10.1016/j.ajo.2006.06.067
©
2006 BY
V
ISUAL FIELD MEASUREMENTS PROVIDE IMPORTANT
clinical information for pediatric eye diseases such as glaucoma, retinopathy of prematurity, hereditary retinal abnormalities, visual pathway disease, and conditions that predispose to the development of glaucoma, such as aphakia, trauma, and uveitis. Visual field examinations historically have been difficult for children to perform, because the examinations require prolonged attention and visual fixation.1,2 Pediatric visual field results are difficult to evaluate because there is a scarcity of normative visual field threshold data for children. Frequency doubling technology (FDT) has made visual field testing faster and may be better suited for pediatric examinations than previous methods.3,4 FDT is a method of threshold sensitivity testing that has been shown to be reliable in normal adult eyes and to be sensitive and specific for the determination of the severity of field changes in glaucomatous adult eyes.5– 8 The stimulus that is used in FDT is a low spatial frequency sinusoidal grating with high temporal frequency counterphase flicker.9 It has been suggested that this stimulus is perceived preferentially by magnocellular mechanisms,10 which represent approximately 10% of retinal ganglion cells.11–13 There is some debate about whether the stimulus is further selective for the My subtype of magnocellular pathways and whether magnocellular pathways and specifically the My subtype are preferentially lost in glaucoma.14 The usefulness of FDT above other methods of visual field testing may be four-fold. First, the possibility that it preferentially stimulates magnocellular mechanisms would mean that the FDT stimulus would be detected by a pathway that has low redundancy in the retina; therefore, the loss of fewer retinal ganglion cells would be required for early detection of functional loss. Second, this low redundancy subset may be lost preferentially in glaucoma. Third, it is an easy procedure to administer and perform. Fourth, FDT uses test strategy technology that has brought threshold testing time for adults down from 20 minutes per eye, which is required by methods such as full threshold standard automated perimetry, to less than six minutes per eye. It is this marked shortening of testing time that has
ELSEVIER INC. ALL
RIGHTS RESERVED.
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prompted the investigation of FDT usefulness in pediatric patients.
METHODS THE INSTITUTIONAL REVIEW BOARDS FOR ETHICAL RE-
search on humans of Oregon Health & Science University and the Legacy Health System approved the study protocol, procedures, and Health Insurance Portability and Accountability Act (HIPAA) compliance of this prospective cross-sectional study. Ninety-four children, ages 5 to 17 years, were recruited from local primary care clinics and the general community with posted bulletins and were tested at the Casey Eye Institute. To provide an independent dataset for validation of our results, a further 75 children, ages 5 to 17 years, were recruited in the same manner and tested at Discoveries In Sight (Legacy Health System), following the same testing protocol. Parental informed consent and child assent (in children 8 years or older) were obtained before testing. Children who may have abnormal visual fields or abnormal test-taking ability because of a history of ophthalmic, neurologic, or behavioral problems were excluded from this study. This was done in a standard fashion for both testing sites by way of a parental acknowledgment that children with any history of lazy eye, eye disease, behavioral problems, neurologic problems, seizures, autism, attention deficit hyperactivity disorder, cerebral palsy, spina bifida, or developmental delay could not be included in this study. Participants were offered a free nondilated screening eye examination as an incentive for participation. Data from these eye examinations were not kept and were not used to confirm normalcy of study participants. Refractive and visual acuity data were not collected. At the beginning of the testing session, each participating child was stationed at the viewing screen of a Carl Zeiss Meditec Humphrey Matrix perimeter15 with frequency doubling technology (Welch Allyn, Skaneateles Falls, New York, USA) resting on a height-adjustable table. Significant effort was directed toward positioning each child optimally for viewing of the screen. Children either sat on a height adjustable stool or stood, whichever of these two methods allowed for the most comfortable and consistent posture and positioning. The child was then given the standard test instructions, as recommended by the manufacturer, for adults. In addition, the child was shown the examiner’s screen before testing. The child was then given time to ask questions before proceeding with further test familiarization in the form of completion of a “practice” N-30 to 5 screening examination,16 of approximately one minute duration, with their right eye. Threshold testing consisted of the performance of an FDT examination with the Zippy Estimate of Sequential Testing (ZEST) strategy, once for each eye.15 For threshold testing, sensitivity was measured in 69 visual field loca984
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FIGURE 1. A histogram of the ages of the 83 subjects who underwent full threshold testing at the first study site.
tions, which tested the central 30 degrees of the visual field. Throughout testing the examiner maintained realtime observation of the child’s fixation by way of the perimeter’s examiner screen and offered encouragement and reminders to maintain central fixation and alignment when necessary. Breaks or short rests were also provided when necessary. After first eye testing, participating children were given a break of approximately three minutes, during which time most children elected to undergo the first part of a screening eye examination. This examination included visual acuity measurement in the child’s habitual correction and examination of eye motility and alignment. Children then resumed their position at the perimeter and completed 30 to 2 ZEST threshold testing with their left eye. Second eye tests were entered into the FDT unit as new single eye tests of the left eye, because more than three minutes passed between first and second eye testing; therefore, the unit appropriately did not account for adaptation of the second eye.16 Pupil testing and direct ophthalmoscopy components of the free screening eye examination were not performed until after testing of the second eye to avoid light saturation effects on the retina from these activities. Qualitative data regarding the most useful methods of preparing and positioning children for FDT testing were gathered. Changes with age in testing time, fixation losses, and in the mean deviation (MD) were assessed by a regression of each measure against age, with the use of commercially available curve fitting software (TableCurve 2 diopters; AISN Software Inc, SPSS, Science, Chicago, Illinois, USA). Regressions were adjusted for the correlation between eyes with the generalized estimating equation method of Liang and Zeger.17 Ages were grouped by whole year intervals. Test results for the first and second eyes were compared with the use of paired t tests, where appropriate, or, when normality of the data could not be assumed, the use of a nonparametric Mann-Whitney U test. OF
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FIGURE 2. A linear regression fit of full threshold testing time (seconds) against subject age (years) for the subjects tested at the first study site. The regression is based on only subjects who were 6 to 14 years old; data points above and below this age range are shown in gray. The solid black line represents the best linear fit of the data; the two parallel gray lines represent the resulting 95% confidence interval for individual data points.
FIGURE 3. A linear regression fit of fixation losses (a proportion of the 10 catch trials that are presented) against subject age (years) for the subjects tested at the first study site. The regression is again based on only subjects who were 6 to 14 years old; data points outside this age range are shown in gray. The solid black line represents the best linear fit of the data; the two parallel gray lines represent the resulting 95% confidence interval for individual data points.
RESULTS NINETY-FOUR CHILDREN, AGES 5 TO 17 YEARS, CAME TO
the testing site for FDT perimetry. One half of the children were female. Nine children (9%) were deemed too unreliable on the screening examination to proceed with VOL. 142, NO. 6
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threshold testing (three 5-year-old children, two 6-yearold children, one 7-year-old child, two 8-year-old children, and one 10-year-old child). This amounted to 60% of the 5-year-old children, 28% of the 6-year-old children, and 21% of the 5- to 9-year-old children. There was a very low rate of children who elected to quit the testing process
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FIGURE 4. A linear regression fit of mean deviation (decibels) against subject age (years) for the subjects tested at the first study site. Again, the regression is based on only subjects who were 6 to 14 years old; data points outside of this age range are shown in gray. The solid black line represents the best linear fit of the data; the two parallel gray lines represent the resulting 95% confidence interval for individual data points.
before completing threshold examinations with each eye (two children; 2.1%). Therefore, threshold data were obtained for 83 children, the ages of whom are shown in histogram form in Figure 1. The parents of 80% of the children elected to have their child undergo a free, nondilated screening eye examination as compensation for participating. Eighty-eight children (94%) performed a 30-degree FDT screening examination for the purpose of familiarization with the test-taking tasks. Mean test times for this screening examination were 50 seconds for 5- to 9-year-old children, 42 seconds for 10- to 13-year-old children, and 36 seconds for 14- to 17-year-old children. With each of the three full threshold outcome measures fully analyzed (testing time, fixation losses, and MD), it was found that subjects over the age of 14 years exhibited the same results as would be predicted from the adult normative database.15 Therefore, the linear regressions quoted later were, in each case, restricted to those subjects aged 14 years or younger. Data points above that age are still presented on the corresponding graphs. Because there were insufficient subjects aged 5 years to provide reliable results, this age group was also excluded from the regression analyses. Polynomial, exponential, and logarithmic regressions did not improve the fits to the data statistically significantly, so linear fits were chosen. Although some potential outliers were apparent when the data were plotted, these were not excluded, because none of these subjects was consistently an outlier for all three analyses. Threshold testing took approximately 7.5 minutes for the youngest children and progressively less time with increasing age such that, for the older teens, threshold 986
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FIGURE 5. A histogram of the ages of the 72 subjects in the validation group who underwent full threshold testing at the second study site.
testing required 6.5 minutes per eye. A graph of test time against age is presented in Figure 2. The best linear fit was given by test time ⫽ 493.8 ⫺ 7.73 ⫻ age, where age is given in years and test time is given in seconds (R2 ⫽ 0.35; P ⬍ 10–9). Fixation losses also decreased as age increased (Figure 3). However, the relationship was not as strong, with an R2 value of just 0.05 (P ⫽ .009). The best linear fit was given by fixation losses ⫽ 0.45 ⫺ 0.02 ⫻ age, with fixation losses expressed as a proportion of the 10 catch trials that were undertaken. OF
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FIGURE 6. Histograms of the mean deviations (MD; decibels) of both eyes of children in the validation dataset, with the raw mean deviation output by the perimeter (gray bars) and the mean deviation adjusted according to the formula that was derived for this article (black bars).
MD increased significantly with age, again up to the age of 14 years (Figure 4). The best linear fit was given by MD ⫽ ⫺11.43 ⫹ 0.82 ⫻ age with MD given in dB (R2 ⫽ 0.18; P ⬍ 10–5). That is, MD improves by 0.82 dB/yr toward the adult normal value, which is reached at age 14 years. Note that a negative MD indicates visual performance worse than that expected from the adult normative database. MD results for the children older than 14 years did not differ significantly from those results that were predicted by the current adult normative database.15 Threshold testing time, false positive, false negative, fixation loss, MD, and pattern standard deviation (PSD) results were compared between the first and second eyes of the subjects; none of these measures exhibited statistically significant differences at the 5% level. To validate these results, an additional 72 children were tested at a second center (Discoveries In Sight). Seventyfive eligible children came for testing. Two children were too unreliable on screening examination to proceed with full threshold testing. One other child quit the testing process before completing full threshold testing. Figure 5 is a histogram of the ages of these participants. Figure 6 presents histograms of the MDs of both eyes of these children, along with the adjusted MDs that were given by MDa ⫽ MD ⫹ 11.43 ⫻ 0.82 ⫻ age for children aged 14 and younger, and MDa ⫽ MD for older children (where age is rounded down to the whole year as before). It can be seen that the raw MDs produce a negatively skewed histogram with a mean and median below 0 dB, whereas VOL. 142, NO. 6
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adjusting the results according to the aforementioned formula results in a histogram approximately symmetric about 0 dB. Testing time and reliability indices gave similar results and have not been shown here for conciseness.
DISCUSSION TO DATE THERE ARE ONLY THREE STUDIES IN THE LITERA-
ture that describe FDT perimetry performance in children. Becker and Semes18 published a study in March 2003 that concluded that children 10 years of age and older could complete the FDT screening examination reliably. Blumenthal and associates19 concluded that children above the age of 8 years could complete a threshold FDT examination reliably. Nesher and associates20 concluded that threshold FDT examination is feasible for testing children, although they reported higher rates of fixation losses than with adults. The objective of this study therefore was to contribute to what is known about a perimetry method that, by its property of relatively short testing time, may be better suited for use in pediatric patients than other methods. In addition, we have examined whether it is appropriate to compare pediatric FDT results with adult results and have contributed to a normative database for FDT in children. Based on our experience of testing 169 children with FDT perimetry, we can offer qualitative observations on
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testing procedures that may be useful. Most children were able to understand the testing tasks that were requested of them when given the manufacturers recommended explanation for adults. Children seemed to be more cooperative and more comfortable with the examiner’s frequent reminders on alignment and fixation when they were shown how the examiner was able to watch their eye in real-time on the examiner’s screen. The protocol of this study used an FDT screening examination for familiarization before full threshold testing. This seemed helpful to children of all ages. Most children tolerated the office visit simulation protocol of our study well, which suggests that children can successfully endure an eye examination interspersed with visual field testing in a clinical setting. Alignment is of the utmost importance for testing children by FDT, so we would recommend the use of height-adjustable tables and stools. Of concern, some of the youngest children, with the smallest faces, had difficulty using the machine because of their nose being too close to their viewing lens and either obstructed their view or fogged the instrument with their breath. An area of possible improvement that would be of interest to us is the possibility of building voice technology into the instrument to provide encouraging messages to the children while they are testing. This study contributes to what is known about testing time and reliability characteristics for children with the use of FDT perimetry. Our study is in line with the previously mentioned work by Becker and Semes18 and Blumenthal and associates19 in that a percentage of our youngest children were not able to reliably perform testing. This is reminiscent of the historic difficulty of obtaining clinical visual field information for children. However, because FDT testing times are relatively short, we think this technology may be able to provide reliable visual field information for children who may not complete field-testing successfully by other methods. Furthermore, because no parameters were significantly different between first and second eye tests, it would appear that there is not a significant fatigue or learning component within this office visit simulation of bilateral threshold testing. The literature to date contains a variety of disparate findings about the extent and shape of the pediatric peripheral visual field and about whether it changes with age after early childhood or resembles the adult peripheral visual field from early in life.21–23 It is generally accepted that field extent increases between 2 and 12 months of age and then more slowly, to reach adult field extent around the age of 12 years.24 A parallel body of discordant research findings exists regarding pediatric visual field sensitivity thresholds. Some studies have found no significant difference in threshold sensitivities between children and adults, although other studies have concluded that sensitivity improves with age to adult values sometime during childhood.25,26 When significant differences between threshold results for normal children and adults have been found, investi988
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gators have postulated several possible explanations, which include the possibility that functional, nonophthalmic, attention, and endurance differences may account for the sensitivity differences that are seen.26 Other possible explanations include that there are differences in retinal development or retino-striate pathway maturation between pediatric and adult peripheral retina or that cognitive or cortical mechanisms may either suppress peripheral information in children to allow perceptual foveal development or, for some other reason, allocate attention across the visual field differently in children than in adults.27,28 Perhaps most interesting of all, this work on threshold testing indicates that sensitivity parameters for FDT must be revised for children younger than 15 years. More data could be collected to confirm these results, because a limitation of this study is the small number of participants in each age group. We have added to the limited quantity of previous work with FDT in children to develop and validate a database of normative pediatric thresholds that will enhance the interpretation of pediatric visual field results and provide a foundation for further study and clinical usefulness of FDT in pediatric vision disease. This now exists as an advantage for the use of FDT in children because there is no Swedish Interactive Threshold Algorithm (SITA) algorithm normative database for children.
REFERENCES 1. Safran AB, Laffi GL, Bullinger A, et al. Feasibility of automated visual field examination in children between 5 and 8 years of age. Br J Ophthalmol 1996;80:515–518. 2. Tschopp C, Safran AB, Viviani P, Bullinger A, Reicherts M, Mermoud C. Automated visual field examination in children aged 5 to 8 years; part I, experimental validation of a testing procedure. Vision Res 1998;38:2203–2210. 3. Johnson C, Samuels S. Screening for glaucomatous visual field loss with frequency-doubling perimetry. Invest Ophthalmol Vis Sci 1997;38:413– 425. 4. Johnson C, Cioffi GA, van Buskirk EM. Frequency doubling technology perimetry using a 24 –2 stimulus presentation pattern. Optom Vis Sci 1999;76:571–581. 5. Cello KE, Nelson-Quigg JM, Johnson CA. Frequency doubling technology perimetry for detection of glaucomatous visual field loss. Am J Ophthalmol 2000;129:314 –322. 6. Chauhan BC, Johnson CA. Test-retest variability of frequencydoubling perimetry and conventional perimetry in glaucoma patients and normal subjects. Invest Ophthalmol Vis Sci 1999;40:648 – 656. 7. Cioffi GA, Mansberger S, Spry P, Johnson C, van Buskirk EM. Frequency doubling perimetry and the detection of eye disease in the community. Trans Am Ophthalmol Soc 2000;98:195–202. 8. Artes PH, Hutchison DM, Nicolela MT, LeBlanc RP, Chauhan BC. Threshold and variability properties of matrix frequency-doubling technology and standard automated perimetry in glaucoma. Invest Ophthalmol Vis Sci 2005;46: 2451–2457. OF
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9. Anderson AJ, Johnson CA. Mechanisms isolated by frequencydoubling technology perimetry. Invest Ophthalmol Vis Sci 2002;43:398 – 401. 10. Sample PA, Bosworth CF, Blumenthal ZE, et al. Visual function-specific perimetry for indirect comparison of different ganglion cell populations in glaucoma. Invest Ophthalmol Vis Sci 2000;41:1783–1790. 11. Meissirel C, Wikler KC, Chalupa LM, Rakic P. Early divergence of magnocellular and parvocellular functional subsystems in the embryonic primate visual system. Proc Natl Acad Sci USA 1997;94:5900 –5905. 12. Perry VH, Oehler R, Cowey A. Retinal ganglion cells that project to the dorsal lateral geniculate nucleus in the macaque monkey. Neuroscience 1984;12:1101–1123. 13. Lennie P, Trevarthen C, van Essen D, Wassle H. Parallel processing of visual information. In: Spillman L, Werner J, editors. Visual perception: the neurophysiological foundations. San Diego, California: Academic Press; 1990. p. 103–128. 14. Johnson CA. Selective vs nonselective losses in glaucoma. J Glaucoma 1994;3:S32–S44. 15. Anderson AJ, Johnson CA, Fingeret M, et al. Characteristics of the normative database for the Humphrey matrix perimeter. Invest Ophthalmol Vis Sci 2005;46:1540 –1548. 16. Johnson C, Cioffi G, van Buskirk E. Evaluation of two screening tests for frequency doubling technology perimetry. In: Wall M, Wild J, editors. Perimetry update. The Hague, The Netherlands: Kugler; 1999. p. 103–109. 17. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13–22. 18. Becker K, Semes L. The reliability of frequency-doubling technology (FDT) perimetry in a pediatric population. Optometry 2003;74:173–179.
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19. Blumenthal EZ, Haddad A, Horani A, Anteby I. The reliability of frequency-doubling perimetry in young children. Ophthalmology 2004;111:435– 439. 20. Nesher R, Norman G, Stern Y, et al. Frequency doubling technology threshold testing in the pediatric age group. J Glaucoma 2004;13:278 –282. 21. Quinn GE, Fea AM, Minguini N. Visual fields in 4- to 10year-old children using Goldmann and double-arc perimeters. J Pediatr Ophthalmol Stabismus 1991;28:314 –319. 22. Wilson M, Quinn G, Dobson V, Breton M. Normative values for visual fields in 4- to 12-year-old children using kinetic perimetry. J Pediatr Ophthalmol Strabismus 1991;28: 151–153. 23. Schwartz TL, Dobson V, Sandstrom DJ, van Hof-van Duin J. Kinetic perimetry assessment of binocular visual field shape and size in young infants. Vision Res 1987;27:2163–2175. 24. Lakowski R, Aspinall PA. Static perimetry in young children. Vision Res 1969;9:305–311. 25. Tschopp C, Viviani P, Reicherts M, et al. Does visual sensitivity improve between 5 and 8 years? A study of automated visual field examination. Vision Res 1999;39: 1107–1119. 26. Tschopp C, Safran AB, Viviani P, Reicherts M, Bullinger A, Mermoud C. Automated visual field examination in children aged 5– 8 years; part II, normative values. Vision Res 1998; 38:2211–2218. 27. Taylor HG. Age differences in peripheral letter perception. J Exp Psychol Hum Percept Perform 1982;8106 – 8112. 28. Hendrickson A, Drucker D. The development of parafoveal and mid-peripheral human retina. Behav Brain Res 1992;49: 21–31.
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● PURPOSE:
To test visual field thresholds of normal children with frequency doubling technology (FDT) perimetry to quantify testing times and reliability characteristics in a pediatric population and to determine whether current methods of stratifying adult threshold values need revision for children. ● DESIGN: Prospective cross-sectional study. ● METHODS: Ninety-four children, ages 5 to 17 years, were recruited from local pediatric clinics and the general community and were tested at one center. Children likely to have abnormal visual fields or abnormal test taking ability because of ophthalmic, neurologic, or behavioral problems were excluded. Children were asked to perform a threshold FDT visual field with each of their eyes. Threshold results were gathered, analyzed, and compared with the standards that have been established for tests in adults. Results were validated by testing a further 72 children, with the same protocol, at a different center. ● RESULTS: For children older than 14 years, threshold mean deviation values were within normal limits according to the adult normative database that is used currently in FDT perimetry. Below 15 years of age, mean deviations for normal children decreased with decreasing age. The best linear fit was given by a mean deviation of ⴚ11.43 ⴞ 0.82 dB ⴛ age (R2 ⴝ 0.18; P < 10ⴚ5). ● CONCLUSION: This research establishes a normative model for pediatric visual field testing with FDT and, by a comparison of threshold results for normal children to established adult norms, provides evidence that parameters for normal sensitivity must be revised for children younger than 15 years. (Am J Ophthalmol 2006;142: 983–989. © 2006 by Elsevier Inc. All rights reserved.)
Accepted for publication Jun 29, 2006. From the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon (L.M.Q., D.T.W.) and Discoveries in Sight, Devers Eye Institute, Legacy Health System, Portland, Oregon (S.K.G., M.N., C.A.J.). Supported in part by an unrestricted grant from Research to Prevent Blindness, New York, New York. Dr Johnson is a paid consultant for Welch Allyn, Skaneateles Falls, New York. Inquiries to David T. Wheeler, MD, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239-4197; e-mail: [email protected] 0002-9394/06/$32.00 doi:10.1016/j.ajo.2006.06.067
©
2006 BY
V
ISUAL FIELD MEASUREMENTS PROVIDE IMPORTANT
clinical information for pediatric eye diseases such as glaucoma, retinopathy of prematurity, hereditary retinal abnormalities, visual pathway disease, and conditions that predispose to the development of glaucoma, such as aphakia, trauma, and uveitis. Visual field examinations historically have been difficult for children to perform, because the examinations require prolonged attention and visual fixation.1,2 Pediatric visual field results are difficult to evaluate because there is a scarcity of normative visual field threshold data for children. Frequency doubling technology (FDT) has made visual field testing faster and may be better suited for pediatric examinations than previous methods.3,4 FDT is a method of threshold sensitivity testing that has been shown to be reliable in normal adult eyes and to be sensitive and specific for the determination of the severity of field changes in glaucomatous adult eyes.5– 8 The stimulus that is used in FDT is a low spatial frequency sinusoidal grating with high temporal frequency counterphase flicker.9 It has been suggested that this stimulus is perceived preferentially by magnocellular mechanisms,10 which represent approximately 10% of retinal ganglion cells.11–13 There is some debate about whether the stimulus is further selective for the My subtype of magnocellular pathways and whether magnocellular pathways and specifically the My subtype are preferentially lost in glaucoma.14 The usefulness of FDT above other methods of visual field testing may be four-fold. First, the possibility that it preferentially stimulates magnocellular mechanisms would mean that the FDT stimulus would be detected by a pathway that has low redundancy in the retina; therefore, the loss of fewer retinal ganglion cells would be required for early detection of functional loss. Second, this low redundancy subset may be lost preferentially in glaucoma. Third, it is an easy procedure to administer and perform. Fourth, FDT uses test strategy technology that has brought threshold testing time for adults down from 20 minutes per eye, which is required by methods such as full threshold standard automated perimetry, to less than six minutes per eye. It is this marked shortening of testing time that has
ELSEVIER INC. ALL
RIGHTS RESERVED.
983
prompted the investigation of FDT usefulness in pediatric patients.
METHODS THE INSTITUTIONAL REVIEW BOARDS FOR ETHICAL RE-
search on humans of Oregon Health & Science University and the Legacy Health System approved the study protocol, procedures, and Health Insurance Portability and Accountability Act (HIPAA) compliance of this prospective cross-sectional study. Ninety-four children, ages 5 to 17 years, were recruited from local primary care clinics and the general community with posted bulletins and were tested at the Casey Eye Institute. To provide an independent dataset for validation of our results, a further 75 children, ages 5 to 17 years, were recruited in the same manner and tested at Discoveries In Sight (Legacy Health System), following the same testing protocol. Parental informed consent and child assent (in children 8 years or older) were obtained before testing. Children who may have abnormal visual fields or abnormal test-taking ability because of a history of ophthalmic, neurologic, or behavioral problems were excluded from this study. This was done in a standard fashion for both testing sites by way of a parental acknowledgment that children with any history of lazy eye, eye disease, behavioral problems, neurologic problems, seizures, autism, attention deficit hyperactivity disorder, cerebral palsy, spina bifida, or developmental delay could not be included in this study. Participants were offered a free nondilated screening eye examination as an incentive for participation. Data from these eye examinations were not kept and were not used to confirm normalcy of study participants. Refractive and visual acuity data were not collected. At the beginning of the testing session, each participating child was stationed at the viewing screen of a Carl Zeiss Meditec Humphrey Matrix perimeter15 with frequency doubling technology (Welch Allyn, Skaneateles Falls, New York, USA) resting on a height-adjustable table. Significant effort was directed toward positioning each child optimally for viewing of the screen. Children either sat on a height adjustable stool or stood, whichever of these two methods allowed for the most comfortable and consistent posture and positioning. The child was then given the standard test instructions, as recommended by the manufacturer, for adults. In addition, the child was shown the examiner’s screen before testing. The child was then given time to ask questions before proceeding with further test familiarization in the form of completion of a “practice” N-30 to 5 screening examination,16 of approximately one minute duration, with their right eye. Threshold testing consisted of the performance of an FDT examination with the Zippy Estimate of Sequential Testing (ZEST) strategy, once for each eye.15 For threshold testing, sensitivity was measured in 69 visual field loca984
AMERICAN JOURNAL
FIGURE 1. A histogram of the ages of the 83 subjects who underwent full threshold testing at the first study site.
tions, which tested the central 30 degrees of the visual field. Throughout testing the examiner maintained realtime observation of the child’s fixation by way of the perimeter’s examiner screen and offered encouragement and reminders to maintain central fixation and alignment when necessary. Breaks or short rests were also provided when necessary. After first eye testing, participating children were given a break of approximately three minutes, during which time most children elected to undergo the first part of a screening eye examination. This examination included visual acuity measurement in the child’s habitual correction and examination of eye motility and alignment. Children then resumed their position at the perimeter and completed 30 to 2 ZEST threshold testing with their left eye. Second eye tests were entered into the FDT unit as new single eye tests of the left eye, because more than three minutes passed between first and second eye testing; therefore, the unit appropriately did not account for adaptation of the second eye.16 Pupil testing and direct ophthalmoscopy components of the free screening eye examination were not performed until after testing of the second eye to avoid light saturation effects on the retina from these activities. Qualitative data regarding the most useful methods of preparing and positioning children for FDT testing were gathered. Changes with age in testing time, fixation losses, and in the mean deviation (MD) were assessed by a regression of each measure against age, with the use of commercially available curve fitting software (TableCurve 2 diopters; AISN Software Inc, SPSS, Science, Chicago, Illinois, USA). Regressions were adjusted for the correlation between eyes with the generalized estimating equation method of Liang and Zeger.17 Ages were grouped by whole year intervals. Test results for the first and second eyes were compared with the use of paired t tests, where appropriate, or, when normality of the data could not be assumed, the use of a nonparametric Mann-Whitney U test. OF
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FIGURE 2. A linear regression fit of full threshold testing time (seconds) against subject age (years) for the subjects tested at the first study site. The regression is based on only subjects who were 6 to 14 years old; data points above and below this age range are shown in gray. The solid black line represents the best linear fit of the data; the two parallel gray lines represent the resulting 95% confidence interval for individual data points.
FIGURE 3. A linear regression fit of fixation losses (a proportion of the 10 catch trials that are presented) against subject age (years) for the subjects tested at the first study site. The regression is again based on only subjects who were 6 to 14 years old; data points outside this age range are shown in gray. The solid black line represents the best linear fit of the data; the two parallel gray lines represent the resulting 95% confidence interval for individual data points.
RESULTS NINETY-FOUR CHILDREN, AGES 5 TO 17 YEARS, CAME TO
the testing site for FDT perimetry. One half of the children were female. Nine children (9%) were deemed too unreliable on the screening examination to proceed with VOL. 142, NO. 6
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threshold testing (three 5-year-old children, two 6-yearold children, one 7-year-old child, two 8-year-old children, and one 10-year-old child). This amounted to 60% of the 5-year-old children, 28% of the 6-year-old children, and 21% of the 5- to 9-year-old children. There was a very low rate of children who elected to quit the testing process
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FIGURE 4. A linear regression fit of mean deviation (decibels) against subject age (years) for the subjects tested at the first study site. Again, the regression is based on only subjects who were 6 to 14 years old; data points outside of this age range are shown in gray. The solid black line represents the best linear fit of the data; the two parallel gray lines represent the resulting 95% confidence interval for individual data points.
before completing threshold examinations with each eye (two children; 2.1%). Therefore, threshold data were obtained for 83 children, the ages of whom are shown in histogram form in Figure 1. The parents of 80% of the children elected to have their child undergo a free, nondilated screening eye examination as compensation for participating. Eighty-eight children (94%) performed a 30-degree FDT screening examination for the purpose of familiarization with the test-taking tasks. Mean test times for this screening examination were 50 seconds for 5- to 9-year-old children, 42 seconds for 10- to 13-year-old children, and 36 seconds for 14- to 17-year-old children. With each of the three full threshold outcome measures fully analyzed (testing time, fixation losses, and MD), it was found that subjects over the age of 14 years exhibited the same results as would be predicted from the adult normative database.15 Therefore, the linear regressions quoted later were, in each case, restricted to those subjects aged 14 years or younger. Data points above that age are still presented on the corresponding graphs. Because there were insufficient subjects aged 5 years to provide reliable results, this age group was also excluded from the regression analyses. Polynomial, exponential, and logarithmic regressions did not improve the fits to the data statistically significantly, so linear fits were chosen. Although some potential outliers were apparent when the data were plotted, these were not excluded, because none of these subjects was consistently an outlier for all three analyses. Threshold testing took approximately 7.5 minutes for the youngest children and progressively less time with increasing age such that, for the older teens, threshold 986
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FIGURE 5. A histogram of the ages of the 72 subjects in the validation group who underwent full threshold testing at the second study site.
testing required 6.5 minutes per eye. A graph of test time against age is presented in Figure 2. The best linear fit was given by test time ⫽ 493.8 ⫺ 7.73 ⫻ age, where age is given in years and test time is given in seconds (R2 ⫽ 0.35; P ⬍ 10–9). Fixation losses also decreased as age increased (Figure 3). However, the relationship was not as strong, with an R2 value of just 0.05 (P ⫽ .009). The best linear fit was given by fixation losses ⫽ 0.45 ⫺ 0.02 ⫻ age, with fixation losses expressed as a proportion of the 10 catch trials that were undertaken. OF
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FIGURE 6. Histograms of the mean deviations (MD; decibels) of both eyes of children in the validation dataset, with the raw mean deviation output by the perimeter (gray bars) and the mean deviation adjusted according to the formula that was derived for this article (black bars).
MD increased significantly with age, again up to the age of 14 years (Figure 4). The best linear fit was given by MD ⫽ ⫺11.43 ⫹ 0.82 ⫻ age with MD given in dB (R2 ⫽ 0.18; P ⬍ 10–5). That is, MD improves by 0.82 dB/yr toward the adult normal value, which is reached at age 14 years. Note that a negative MD indicates visual performance worse than that expected from the adult normative database. MD results for the children older than 14 years did not differ significantly from those results that were predicted by the current adult normative database.15 Threshold testing time, false positive, false negative, fixation loss, MD, and pattern standard deviation (PSD) results were compared between the first and second eyes of the subjects; none of these measures exhibited statistically significant differences at the 5% level. To validate these results, an additional 72 children were tested at a second center (Discoveries In Sight). Seventyfive eligible children came for testing. Two children were too unreliable on screening examination to proceed with full threshold testing. One other child quit the testing process before completing full threshold testing. Figure 5 is a histogram of the ages of these participants. Figure 6 presents histograms of the MDs of both eyes of these children, along with the adjusted MDs that were given by MDa ⫽ MD ⫹ 11.43 ⫻ 0.82 ⫻ age for children aged 14 and younger, and MDa ⫽ MD for older children (where age is rounded down to the whole year as before). It can be seen that the raw MDs produce a negatively skewed histogram with a mean and median below 0 dB, whereas VOL. 142, NO. 6
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adjusting the results according to the aforementioned formula results in a histogram approximately symmetric about 0 dB. Testing time and reliability indices gave similar results and have not been shown here for conciseness.
DISCUSSION TO DATE THERE ARE ONLY THREE STUDIES IN THE LITERA-
ture that describe FDT perimetry performance in children. Becker and Semes18 published a study in March 2003 that concluded that children 10 years of age and older could complete the FDT screening examination reliably. Blumenthal and associates19 concluded that children above the age of 8 years could complete a threshold FDT examination reliably. Nesher and associates20 concluded that threshold FDT examination is feasible for testing children, although they reported higher rates of fixation losses than with adults. The objective of this study therefore was to contribute to what is known about a perimetry method that, by its property of relatively short testing time, may be better suited for use in pediatric patients than other methods. In addition, we have examined whether it is appropriate to compare pediatric FDT results with adult results and have contributed to a normative database for FDT in children. Based on our experience of testing 169 children with FDT perimetry, we can offer qualitative observations on
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testing procedures that may be useful. Most children were able to understand the testing tasks that were requested of them when given the manufacturers recommended explanation for adults. Children seemed to be more cooperative and more comfortable with the examiner’s frequent reminders on alignment and fixation when they were shown how the examiner was able to watch their eye in real-time on the examiner’s screen. The protocol of this study used an FDT screening examination for familiarization before full threshold testing. This seemed helpful to children of all ages. Most children tolerated the office visit simulation protocol of our study well, which suggests that children can successfully endure an eye examination interspersed with visual field testing in a clinical setting. Alignment is of the utmost importance for testing children by FDT, so we would recommend the use of height-adjustable tables and stools. Of concern, some of the youngest children, with the smallest faces, had difficulty using the machine because of their nose being too close to their viewing lens and either obstructed their view or fogged the instrument with their breath. An area of possible improvement that would be of interest to us is the possibility of building voice technology into the instrument to provide encouraging messages to the children while they are testing. This study contributes to what is known about testing time and reliability characteristics for children with the use of FDT perimetry. Our study is in line with the previously mentioned work by Becker and Semes18 and Blumenthal and associates19 in that a percentage of our youngest children were not able to reliably perform testing. This is reminiscent of the historic difficulty of obtaining clinical visual field information for children. However, because FDT testing times are relatively short, we think this technology may be able to provide reliable visual field information for children who may not complete field-testing successfully by other methods. Furthermore, because no parameters were significantly different between first and second eye tests, it would appear that there is not a significant fatigue or learning component within this office visit simulation of bilateral threshold testing. The literature to date contains a variety of disparate findings about the extent and shape of the pediatric peripheral visual field and about whether it changes with age after early childhood or resembles the adult peripheral visual field from early in life.21–23 It is generally accepted that field extent increases between 2 and 12 months of age and then more slowly, to reach adult field extent around the age of 12 years.24 A parallel body of discordant research findings exists regarding pediatric visual field sensitivity thresholds. Some studies have found no significant difference in threshold sensitivities between children and adults, although other studies have concluded that sensitivity improves with age to adult values sometime during childhood.25,26 When significant differences between threshold results for normal children and adults have been found, investi988
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gators have postulated several possible explanations, which include the possibility that functional, nonophthalmic, attention, and endurance differences may account for the sensitivity differences that are seen.26 Other possible explanations include that there are differences in retinal development or retino-striate pathway maturation between pediatric and adult peripheral retina or that cognitive or cortical mechanisms may either suppress peripheral information in children to allow perceptual foveal development or, for some other reason, allocate attention across the visual field differently in children than in adults.27,28 Perhaps most interesting of all, this work on threshold testing indicates that sensitivity parameters for FDT must be revised for children younger than 15 years. More data could be collected to confirm these results, because a limitation of this study is the small number of participants in each age group. We have added to the limited quantity of previous work with FDT in children to develop and validate a database of normative pediatric thresholds that will enhance the interpretation of pediatric visual field results and provide a foundation for further study and clinical usefulness of FDT in pediatric vision disease. This now exists as an advantage for the use of FDT in children because there is no Swedish Interactive Threshold Algorithm (SITA) algorithm normative database for children.
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