T]He Course of Myopia in Children with Mild Retinopathy of Prematurity CHUNG-LIN LUE,*#RONALD M

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T]he Course of Myopia in Children with Mild Retinopathy of Prematurity CHUNG-LIN LUE,*#RONALD M. HANSEN,* DARRELL S. REISNER,* OLIVER FINDL,* ROBERT A. PETERSEN,* ANNE B. FULTON* Received 24 January 1994; in revised form 2 August 1994

The courses of spherical equivalent in patients (n = 62) who had mild, non-cicatricial retinopathy of prematurity (ROP), and in those without a history of ROP (n = 25) were modeled as a linear function of age; an exponential model was also considered. A few (n = 5) without ROP have abnormal courses characterized by hyperopia in early infancy; none have poor acuity. Although the majority of patients with ROP have courses indistinguishable from those of term born controls, 27 (43.5%) have abnormal courses, most of which are toward myopia. Optotype acuities were significantly poorer among the ROP patients with abnormal than normal refractive courses. Thus abnormal refractive development and acuity deficits are associated in eyes that have had mild ROP.

Myopia Development Human Retina Retinopathy of prematurity

Refractive errors are understood to be a mismatch of (Ehrlich, Sattayasi, Zappia & Barrington, 1990); and the axial length of the eye and its optical components. endogenous retinal neurochemicals are altered in eyes Over the ages when the human eye normally grows with induced myopia (Laties & Stone, 1991). (Larsen, 1971), the absence of normal emmetropization To consider the possible effects of mild ROP on the and the presence of high refractive errors suggests that regulation of eye growth and foveal maturation we coordinated growth of ocular components, which is examine herein the course of spherical equivalent and necessary to match optics and eye size, has not occurred. optotype acuities in children with mild, non-cicatricial High refractive errors, particularly myopic errors, are ROP. Children with more severe, cicatricial ROP are not frequent in retinopathy of prematurity (ROP) (Gallo, considered because scarring could cause mechanical Holmstrom, Kugelberg, Hedquist & Lennerstrand, 1991; distortion of the developing retina, including the fovea. Nissenkorn, Yassur, Mashkowski, Sherf & Ben-Sira, 1983; Quinn, Dobson, Repka, Reynolds, Kivlin, Davis, METHODS Buckley, Flynn & Palmer, 1992; Shapiro, Yanko, Nawratzki & Merin, 1980). ROP is typically active Patients at preterm and early post term ages (Palmer, Flynn, Only patients with a history of preterm birth (36 weeks Hardy, Phelps, Phillips, Schaffer & Tung, 1991) when the gestation or less) who had been examined and monitored eye is only about a quarter of the adult volume, the serially from the postnatal period by staff ophthalmolo- fovea is immature (Hendrickson, 1992; Isenberg, 1986), gists, and had at least two cycloplegic refractions after and normal acuity is much poorer than that of adults term (40 weeks gestation) were included. Also required (Banks & Bennett, 1988; Hamer & Mayer, 1994; Wilson, were explicit statements in the record that the retina at 1988). the posterior pole was normal. Any sign of cicatricial Retinal factors are strongly implicated in the regu- ROP at any examination was exclusionary. No patient lation of eye growth (Wallman, 1990; Raviola & Wiesel, with macular pigmentary distrubance or heterotopia, or 1990) because in experimental animals growth of the retinal folds was included. Inclusion required normal globe can be manipulated even if the optic nerve is cut globes except for mild ROP and refractive errors. (Troilo & Wallman, 1991; Raviola & Wiesel, 1990); Patients who were small for gestational age were substances toxic to retinal neurons disturb eye growth excluded as were those who developed neuromotor handicaps. The demographic characteristics of the patients are summarized in Table 1. *Department of Ophthalmology, Children's Hospital and Harvard Sixty-two children with a history of mild ROP Medical School, 300 Longwood Avenue, Boston, MA 02115, U.S.A. (Table 1) met the criteria. Although 54 of these children tOn leave from National Cheng Kung University Medical School, were born before 1984 and the International Classifi- Tainan. Taiwan, R.O.C. cation of Retinopathy of Prematurity (Committee for 1329 1330 CHUNG-LIN LUE et al.

TABLE I. Demographic characteristics of the patients Gestational age at birth Birth weights Duration of follow-up Number of Birth (weeks) (g) (months) Group patients dates Median (range) Median(range) Median (range)

ROP 62 1976-1985 27 (24-32)* 971 (610-2200)* 39 (3.0-156.8)* No ROP 25 1975-1988 30 (24-35)* 1400 (820-3000)* 34.25 (4.75-118.255)* *Comparison of preterms with vs without ROP, Mann-Whitney U: Gestational age, U = 1316, P < 0.0001; Birth weight, U = 1310, P < 0.0001; Duration of follow-up, U = 747, P = 0.793.

Classification of Retinopathy of Prematurity, 1984), child's course was represented by the slope and intercept records appeared to indicate that zone 2 involvement, of the best fit !ine (method of least squares). stage 1-3 in severity, had occurred in each eye included. The longitudinal measures of refraction of the 22 No patient with apparent plus disease was included. normal subjects were used to define the 99% prediction Twenty-five preterms without ROP (Table 1) met limits (Whitmore~ 1986) of normal slope and intercept. the inclusion/exclusion criteria. Examinations of each These are the limits within which 99% of normal included ophthalmoscopy between gestational ages individuals' slope and intercept would be expected to 36-40 weeks, the period during which ROP incidence fall. An individual patient whose slope and intercept fall peaks (Palmer et al., 1991). Thus, the possibility that within the limits is presumed to have a normal course. these children had ROP which regressed without detec- The 99% prediction limit (Whitmore, 1986) is tion appeared unlikely. PL = mean + t0.00s, d.f.=(n-I)[S(I + 1/n) I/2] Normal term born control subjects where t is the t statistic, n is the sample size and s is the We wished to know if an individual patient's course standard deviation. of spherical equivalent was within the limits of normal Exponential model. For all patients with ~>4 refrac- development. To define the normal limits, longitudi- tions (n = 25) (whether they had normal or abnormal nal measures of the spherical equivalents of normal, courses according to the linear model) a simple exponen- term born children were obtained from the records of tial model children who had previously participated in studies of normal visual development in this laboratory. These y=A +Be-'/k children had no family history of eye disease including high refractive errors. Twenty-two were identified was also fit. All parameters were free to vary. In this who had at least one refraction by age 12 months equation, (A + B) is the ordinate (spherical equivalent) and a second after 12 months. Additionally, cross- at term, k the time constant in months, and A the sectional spherical equivalent data from large samples predicted, final refraction. If the exponential accounted (Larsen, 1971; Fulton, Dobson, Salem, Petersen & for a higher proportion of tla'e variance in a patient's Hansen, 1980) were available for comparison to the course than the linear model, the exponential was chosen longitudinal data. to represent the patient's course. An exponential course may suggest that a feedback system is operative (Medina Refractions & Fariza, 1993). All refractions were done by experienced staff ophthalmologists with a Copeland streak retinoscope in a dimly lit room 30-45 min after instillation of 1% TABLE 2. Courses of spherical equivalents. Parameters of linear model cyclopentolate. The working distance was 2/3 m. Data from right eyes were analyzed except in patients Mean (SD) with anisometropia or left-eye fixation preference. Thus Slope Intercept at term the possibility that an amblyopic eye was included in the (D/month) (D) analyses was low. Normal, Term born children Analyses of course of spherical equivalent Longitudinal measures 22 -0.011 (0.029) 1.26 (0.98) Fulton et al. (1980)* 997 -0.013 1.59 Linear model. Spherical equivalent was examined as Larsen (1971)# 1692 - 0.008 1.33 a function of age. Thirty-seven of the patients with a Patients, Preterm birth history of ROP had only two or three refractions Mild ROP 62 -0.019 (0.168) 0.08 (3.03) (median 3; range 2-10), and all but four of those without No ROP 25 -0.032 (0.082) 1.86 (1.53) ROP had only two or three refractions. We also noted *Data from sample studied by Fulton et al. (1980), The line was fit that previously reported cross sectional spherical equiv- (method of least squares) to mean spherical equivalent (1 yr age alent data were well represented as a linear function blocks) as a function of age, 1-10 yr; r 2 = 0.84; P < 0.001. of age (Table 2). Therefore, spherical equivalent was tLarsen's (1971) data for boys and girls. The line was fit (method of least squares) to mean spherical equivalent (1 yr age blocks) as a modeled primarily as a linear function of age. Each function of age, 1 13yr; r2=0.91; P<0.001. DEVELOPMENT OF MYOPIA IN ROP 1331

+4.0 A° Normal Courses Normal (n=22) +3.0

C= +2.0 +10 Normal (n=22) ll- +1.0 u~ '~' +6 0 Piano E +2 L.. -1.0 i I , I , I ~ I ' i * I , I ® Piano Io 2 4 6 8 10 12 14 I- +4.0 N -2 LU B,

® +3.0 Norma~ n=22; .... ~ -6 o Larsan 1971,-- L,. 03 • Chil~an~Hospita~ ...... C +2.0 m -10 , I,],l,I, I, I,I, I +1.0 -0.50 0.00 +030 +1 Slope {diopters/month) Piano

-1.0 i I i I I I I I I I I I I I 0 2 4 6 8 10 12 14 Age [years) FIGURE 1. Normal courses of spherical equivalent. (A) The courses for the 22 normal subjects are represented by the individual straight lines. The heavy dashed line shows the average course of these subjects. (B) The average course of the 22 children (heavy dashed line) compared to cross sectional data. The means (_ SE) of Larsen's (1971: open circles) and Children's Hospital (Fulton et al., 1980: solid circles) data are plotted. The fit lines (Table 2) to the cross sectional data are also shown. (C) The relationship of slope and intercept for the 22 normal subjects. The 99% prediction limits of normal slope and intercept are indicated by the box.

Optotype acuities, which can be measured routinely born children (Table 2), and the standard deviations of once a child has reached age 3 yr (Hamer & Mayer, the intercept at term and slope are about twice those 1994), were available for those who were followed until of the patients without a history of ROP (Table 2). at least this age. Acuities were measured with the Allen The relationship between the intercept and slope for picture cards (Allen, 1957), the HOTV test (Sheridan, the individual patients is shown in Fig. 4. As in Fig. 1(C), 1969), lines of Es, or Snellen letters. For patients requir- the boxes in Fig. 4 indicate the 99% prediction limits ing glasses, only corrected acuities were considered. (Whitmore, 1986) for the normal intercept and slope. The patients in this sample wore glasses by age 12 A patient's course is defined as abnormal if slope or months for myopia /> - 2.0 D spherical equivalent and intercept exceed the normal limits. for cylindrical errors ~> 2 D. 60 in ROP (n=62} 13 RESULTS r-7 no ROP (n=25} The courses of the normal subjects are summarized in Fig. 1. The average course of the 22 normal subjects 4O [Fig. I(A)] is similar to the age-dependent changes in spherical equivalent of the large cross sectional samples [Fig. I(B); Table 2]. The relationship of intercept and i 8 li 21 slope for each of the 22 normal subjects is shown by the 20 points plotted in Fig. I(C). The 99% prediction limits for normal slope are + 0.06 to -0.09 D/month, and for 5 4 42 normal intercept at term are + 3.75 to -1.24 D. These limits are represented by the box in Fig. I(C). The results of the linear analysis of the patients' -9.5 -7.5 -5.5 -3.5 -1.5 +.5 +2.5 +4,5 +6.5 courses are shown in Figs 2, 3 and 4. In contrast to the Intercept at Term patients without a history of ROP, those with a history (diopters) of ROP have a distribution of intercepts (Fig. 2) skewed FIGURE 2. Distribution of intercepts at term (40 weeks post con- toward myopia and a broader distribution of slopes ception) of lines fitted to the patients' spherical equivalents as a (Fig. 3). For the patients with ROP, the average inter- function of age. The midpoints of 2 D intervals are indicated on the cept at term is less hyperopic than that of normal, term horizontal axis. 1332 CHUNG-LIN LUE et al.

25 100 are summarized in Table 3. The calculated spherical equivalents at term are widely distributed from + 5.37 II ROP (n=62) 48 [ZZ no ROP (n=25) to -7.16 D. 80 Ten of the 21 have fewer than four refractions (which precludes meaningful fit of the exponential model), but 60 according to the linear model, have increases toward (.) myopia that exceed the normal limit. The remaining 3 of

13. 40 the 21 have abnormal courses characterized by more myopia than normal in early infancy (myopic intercept), but thereafter have little increase in myopia (small slope 20 I within the normal range). Even though /> 4 refractions 1 1 II 1 are available, the courses of these myopic children are 0 =" i 'li m better described by the linear model. -.6 -.4 -.2 0 +.2 +.4 +.6 +.8 The distributions of the patients' optotype acuities are Slope shown in Fig. 6. Nearly all in both the no ROP and ROP {diopters/month) groups had acuities of 20/40 (0.5) or better. However, FIGURE 3. Distribution of slopes of lines fitted to the patients' among the ROP group, the mean acuity of those with spherical equivalents as a function of age. Midpoints of 0.2 D/month abnormal courses of refractive development is signifi- intervals are indicated on the horizontal axis. A negative slope cantly poorer than that of children with normal refrac- represents a change toward more myopia, and a positive slope a change tive development (t =4.12; d.f. = 38; P <0.01). Also toward more hyperopia. among the ROP group, the distributions of acuities

+10 Five of the 25 patients without ROP have points A. No ROP (n=25) outside the normal limits [Fig. 4(A)]. They have hyperopic intercepts or negative slopes exceeding the +6 normal limits. These patients were followed until

ages 2-6 yr. Interestingly four of the five developed +2 esotropia. Among the six with a history of ROP, Piano a hyperopic intercept or negative slope, only one developed esotropia. -2 The majority of patients (35/62; 56.5%) with a history of ROP have normal refractive courses. Their points fall -6 within the box [Fig. 4(B)]. Six of the ROP patients with e-, D. abnormal courses have positive slopes that exceed the O ~5 -10 I I I I I I normal limits, but have normal intercepts. Each of these -0.50 0.00 +0.50 +1 patients has refractive data only from early infancy. E Possibly some of these courses reflect emmetropization I-- because a high percentage (,,~ 50%) of preterm infants +10 are myopic at preterm ages even if refracted under B. ROP (n=62)

cycloplegia and free of ROP (Dobson, Fulton, Manning, tJ +6 Salem & Petersen, 1981). An incidence of 50% exceeds i- the percentage of myopes found in any population of I +2 former preterms when refracted at postterm ages. For instance, in one large study (Quinn et al., 1992), about Piano 20% of the population was myopic. Thus, some must -2 lose their preterm myopia. Such infants would have a ./ positive slope. -6 Courses of myopia Twenty-one of the patients with a history of ROP -10 I I I I I I I I - -0.50 0.00 +0.50 + 1 [Fig. 4(B)] have abnormal courses characterized by changes toward myopia (negative slope), myopic inter- Slope (diopters/month) cepts that significantly exceed the normal limits, or both. FIGURE 4. Relationshipof slope and intercept at term of patients (A) The intercepts, calculated with the linear model, are without and (B) with ROP. As in Fig. I(C) the box in each panel broadly distributed from -t- 5.16 to - 9.35 D. Of the 21, indicates the 99% prediction limits for slope and intercept of normal eight have courses better fitted by the exponential than children (n = 22). (A) Patients with no history of ROP. Five have courses outside the normal limits. (B) Patients with a history of ROP. linear model (Fig. 5). An exponential accounts for a The majority (n = 35; open circles inside box) have both slope and higher proportion of the variance in these courses than intercept within the normal limits. The 27 with abnormal courses are does a straight line. The parameters of the exponentials represented by the solid circles. DEVELOPMENT OF MYOPIA IN ROP 1333

Normal (n=22} m m .-, ,,, -5 111 ,~ 0¢

o -10 L-

-15 w

-20 : : : : ', : I : I : I = I , I , I , I , I ' I 0 1 2 3 4 5 6 7 8 9 10 11 Postterrn Age (years)

FIGURE 5. The exponential courses of eight patients with ROP and rapidly increasing myopia. The smooth curves, exponentials fitted to the patients' data, provide a reasonable description of these courses. For each of these subjects, the exponential model accounted for a larger proportion of the variance (r 2) than the linear model. The values of the parameters of the exponentials are listed in Table 3. The average course of the 22 normal children, replotted from Fig. 1(A), is represented by the dashed line.

[Fig. 6(B)] differ significantly between those with normal 3, 12 and 24 months. Of course, an epidemiology and abnormal courses of development of spherical of myopia in preterm infants cannot be based on our equivalent (Z2= 11.45; d.f. = 1; P < 0.01). sample of ophthalmology patients. The four ROP patients who had acuities poorer than The broad distribution of intercepts and slopes, or 0.5, specifically 20/50, 20/50, 20/60 and 20/70, all had of the ordinates at term calculated with the exponen- myopic intercepts but small slopes within the normal tial model, suggests that regulation of eye growth and reange. In other words, they were myopic in early optical power is compromised in some eyes with a infancy, and their myopia changed little over the early history of ROP, but, of course, does not identify which childhood years. of the ocular components of refraction account for the courses. In the patients who have a normal course (35/62; 56.5%) and attain good acuity, the mild DISCUSSION retinopathy appears to have caused no sustained mis- Previous studies of refractive errors in children with a match of eye size and optical power. Normal, or nearly history of preterm birth have dealt little with the course normal, maturation of the fovea must have occurred to of myopia in individuals. The data of Figs 4(B) and 5 mediate the development of good acuities (Hendrickson, show that myopia progresses rapidly in some but not all 1992; Banks & Bennett, 1988). patients with a history of mild ROP which caused no An abnormal course of refractive development ophthalmoscopic abnormalities of the posterior retina occurred in only 5/25 (20%) of patients without a history or fovea. Perhaps individuals with courses similar to of ROP and none developed the high myopia that was those shown in Fig. 5 account for the increased incidence found among those with a history of ROP. It has been of high myopia reported by Quinn et al. (1992). In that suggested previously that unrecognized ROP largely large sample, the incidence of myopia > 5 D increased accounts for high myopia in children born preterm from 2% at 3 months to 4.6% at 12 months while the (Shapiro, Yanko, Nawratzki & Merin, 1980). overall incidence of myopia remained about 20% at A retinal basis for compromised regulation of eye growth is suspected in patients with a history of retinopathy of prematurity. Possibly the immature TABLE 3. Parameters of exponential model, y = A + Be-t'k retina, which continues to develop its function even after Ordinate at term Predicted final term (Fulton & Hansen, 1992) is rendered dysfunctional A + B refraction, A k by ROP (Francois & DeRouck, 1983; Nagata, 1977) Patient (D) (D) (months) and so alters eye growth signals. It has previously 1 1.54 - 13.86 11.85 been reported, based on ophthalmoscopic criteria that 2 4.04 - 6.47 0.56 the course of foveal development is delayed in eyes 3 - 2.92 - 7.95 9.00 4 1.73 - 7.86 12.77 with ROP and normal posterior pole (Isenberg, 1986). 5 0.02 - 7.73 2.16 In a few patients with ROP, poor VEP acuity is 6 - 7.16 - 15.14 25.54 reported and is unexplained by uncorrected refrac- 7 0.39 - 16.38 4.77 tive error, ophthalmoscopically visible lesions or 8 5.37 - 5.12 7.76 brain abnormalities (Norcia, Tyler, Piecuch, Clyman Median + 0.97 - 7.91 8.38 & Grobstein, 1987). Thus, ROP may alter foveal devel- Range -7.16 to + 5.37 - 16.38 to -5.12 0.56 to 25.54 opment. The data contained herein on the courses of 1334 CHUNG-LIN LUE et al.

A. No ROP (n=20) to resolve mid spatial frequencies (Ciuffreda & Kenyon, 1983; Hamer & Mayer, 1994) may conspire to cause the 80 12 i Normal course rapid courses shown in Fig. 5. More marked delays in Abnormal course foveal development are suspected in patients with early myopia that does not progress. These are the patients 60 who had poorer acuity. Longitudinal measures of the ocular components and visual functions can test this 40 hypothesis.

20 REFERENCES

Allen, H. H. (1957). A new picture series for preschool vision testing. '~ 0 II mJ i h American Journal of Ophthalmology, 44, 38-41. (3 1.33 1.00 .80 .67 .50 .40 .33 .29 Banks, M. S. (1980). The development of visual accommodation L- during early infancy. Child Development, 51, 6464566. B. ROP {n=40) Banks, M. S. & Bennet, P. J. (1988). Optical and photoreceptor immaturities limit the spatial and chromatic vision of human 80 Normal course neonates. Journal of the Optical Society of America, 5, 2059 2079. Blakemore, C. (1990). Maturation of mechanisms for efficient spatial 16 Abnormal course vision. In Blakemore, C. (Ed.), Vision: Coding and efficiency (pp. 254-266). Cambridge University Press. 60 Ciuffreda, K. J. & Kenyon, R. V. (1983). Accommodative vergence and accommodation in normals, amblyopes and strabismics. In Schor, C. M. & Ciuffreda, K. J. (Eds), Vergence eye movements: Basic and 40 clinical aspects (pp. 101 112). Boston, Mass.: Butterworths. Committee for the Classification of Retinopathy of Prematurity (1984). 5 5 An international classification of retinopathy of prematurity. Archives of Ophthalmology, 102, 1130~1134. 0 Diaz-Araya, C. & Provis, J. M. (1992). Evidence of photoreceptor migration during early foveal development: A quantitative analysis of human fetal retinal. Visual Neuroscienee, 8, 505-514. o [1 ll Dobson, V., Fulton, A. B., Manning, K., Salem, D. & Petersen, R. A. 1.33 1.00 .80 .67 .50 .40 .33 .29 (1981). Cycloplegic refractions in premature infants. American Journal of Ophthalmology, 91, 49~495. Optotype Acuity Ehrlich, D., Sattayasai, J., Zappia, J. & Barrington, M. (1990). Effects FIGURE 6. Distributions of optotype acuities for patients with no of selective neurotoxins on eye growth in the young chick. In Block, history of ROP (A) and for patients with a history of ROP (B). Patients G. & Widddows, K. (Eds), Myopia and the control of eye growth with normal courses of spherical equivalents are depicted by solid bars, (pp. 63-88). Chichester: Wiley. those with abnormal courses by open bars. The mid-points of the Francois, J. & DeRouck, A. (1983). Retrolental fibroplasia and ERG. intervals for decimal acuities are indicated on the horizontal axes; 1.0 Documenta Ophthalmologica Proceeding Series, 37, 287-291. corresponds to 20/20, 0.5 to 20/40, and so forth. Fulton, A. B. & Hansen, R. M. (1992). The rod sensitivity of dark adapted human infants. Current Eye Research, 11, 1193 1198. Fulton, A. B., Dobson, V., Salem, D., Petersen, R. A. & Hansen, R. M. (1980). Cycloplegic refractions in infants and young children. refractive development and optotype acuities of the American Journal of Ophthalmology, 90, 239-247. patients with a history of mild ROP that produced no Gallo, J. E., Holmstrom, G., Kugelberg, U., Hedquist, B. & ophthalmoscopically visible changes at the posterior Lennerstrand, G. (1991). Regressed retinopathy of prematurity and its sequelae in children aged 5 10 years. British Journal o[ pole suggest an association of refractive and foveal Ophthalmology', 75, 527-.531. development. Hamer, R. D. & Mayer, D. L. (1994). Development of spatial vision. Neural retinal cells rendered dysfunctional by ROP In Albert, D. M. & Jakobiec, F. A. (Eds), Principles and practice may not only alter eye growth signals, but may delay of ophthalmology: basic sciences (pp. 5784508). Philadelphia, Pa: Saunders. or halt the normal centrad migration of the develop- Hendrickson, A, E. (1992). A morphological comparison of foveal ing photoreceptors from the fovea (Hendrickson, 1992; development in man and monkey. Eye, 6, 136-144. Diaz-Araya & Provis, 1992). This predicts alterations in Isenberg, S. J. (1986). Macular development in the premature infant. the microscopic topography of the central retina, includ- American Journal of Ophthalmology, 101, 74-80. ing the fovea, which, after early infancy, is a determinant Larsen, J. (1971). The saggital growth of the eye. I. Ultrasonic of acuity (Banks & Bennett, 1988; Hamer & Mayer, measurement of the depth of the anterior chamber from birth to puberty. Acta Ophthalmologica, 49, 239 262. 1994; Blakemore, 1990). Laties, A. M. & Stone, R. A. (199l). Some visual and neurochem- The progression of experimental myopia requires ical correlates of refractive development. Visual Neuroscience, 7, visual resolution, perhaps adequate to stimulate accom- 125-128. modation, and vision mediated feedback (Schaeffel & Medina, A. & Fariza, E. (1993). Emmetropization as a first-order Howland, 1991; Rohrer, Schaeffel & Zrenner, 1992). feedback system. Vision Research, 33, 21-26. Nagata, M. (1977) Treatment of acute proliferative retrolental fibro- Young infants' burgeoning capacities for accommo- plasia with xenon-arc photocoagulation. Japanese Journal of dation (Banks, 1980) and foveal development sufficient Ophthalmology, 21, 436-459. DEVELOPMENT OF MYOPIA IN ROP 1335

Nissenkorn, I., Yassur, Y., Mashkowski, D., Sherf, I. & Ben-Sira, I. Shapiro, A., Yanko, L., Nawratzki, I. & Merin, S. (1980). Refractive (1983). Myopia in premature babies with and without retinopathy power of premature children at infancy and early childhood. of prematurity. British Journal of Ophthalmology, 67, 170-173. American Journal of Ophthalmology, 90, 234-238. Norcia, A. M., Tyler, C. W., Piecuch, R., Clyman, R., & Grobstein, Sheridan, M. D. (1969). Vision screening procedures for very young J. (1987). Visual acuity development in normal and abnormal or handicapped children. Clinical Developmental Medicine, 32, preterm human infants. Journal of Pediatric Ophthalmology & 39-47. Strabismus, 24, 70-74. Troilo, D. & Wallman, J. (1991). The regulation of eye growth and Palmer, E. A., Flynn, J. T., Hardy, R. J., Phelps, D. L., Phillips, refractive state: An experimental study of emmetropization. Vision C. L., Schaffer, D. B. & Tung, B. (1991). Incidence and early course Research, 31, 1237 1250. of retinopathy of prematurity. Ophthalmology, 98, 1628-1640. Wallman, J. (1990). Retinal influences on sclera underlie visual Quinn, G. E., Dobson, V., Repka, M. X., Reynolds, J., Kivlin, J., deprivation myopia. In Block, G. & Widdows, K. (Eds), Myopia and Davis, B., Buckley, E., Flynn, J. T. & Palmer, E. A. (1992). the control of eye growth (pp. 126-141). Chichester: Wiley. Development of myopia in infants with birth weights less than 1251 Whitmore, G. A. (1986). Prediction limits for a univariate normal grams. Ophthalmology, 99, 329--340. observation. American Statistician, 40, 141--143. Raviola, E. & Wiesel, T. (1990). Neural control of eye growth Wilson, H. R. (1988). Development of spatiotemporal mechanisms in and experimental myopia in primates. In Block, G. & Widdows, K. infant vision. Vision Research, 28, 611 628. (Eds), Myopia and the control of eye growth (pp, 22-44). Chichester: Wiley. Rohrer, B., Schaeffel, F. & Zrenner, E. (1992). Longitudinal chromatic aberration and emmetropization: results from the chicken eye. Acknowledgements--Presented in part at the Association for Research Journal of Physiology, 449, 363-376. in Vision and Ophthalmology Annual Meeting, Sarasota, Florida, Schaeffel, F. & Howland, H. C. (1991). Properties of feedback loops 3 May 1993. This study was supported by NIH grant EY05329 and the controlling eye growth and refractive state in the chicken. Vision William Randolf Hearst Fund. Dr Lue was supported by NIH Fogarty Research, 31, 717-734. International Fellowship 1 F05 TW04776.

VR 35/9 H