- Email: [email protected]
Refractive error in premature infants
Refractive Error in Premature Infants Yokrat Ton, MD,a Yigal S. Wysenbeek, MD,b and Abraham Spierer, MDb Purpose: To determine the incidence and the degree of refractive error between the ages of 2 weeks and 6 months in premature infants without retinopathy of prematurity and to seek a correlation between refractive error and age at examination, birth weight, or gestational age. Subjects and methods: In this observational cross-sectional study, eye refraction in 390 premature infants, with no ocular pathology, was measured by cycloplegic retinoscopy at the age of 2 weeks to 6 months. A correlation was sought between refractive error and perinatal variables. Results: Of the 390 infants reviewed, 347 (89%) had a refractive error and 43 (11%) were emmetropic in both eyes. Most of the infants were hyperopic (76.8%). Myopia was observed in only 11.9%. Astigmatism was found in 24.4% of the infants. The mean age at examination was 2.1 ⫾ 1 months; the mean birth weight was 1639 ⫾ 444 g, and the mean gestational age at birth was 32.2 ⫾ 2.4 weeks. The mean spherical equivalent of refraction was ⫹1.56 ⫾ 1.82 diopters (D) in the right eye and ⫹1.55 ⫾ 1.78 D in the left eye. Refractive error was positively correlated with age at examination (R ⫽ 0.16, P ⫽ 0.001). The mean refractive error was ⫹1.24 D in infants aged 1 month or less and reached ⫹2.50 D at the age of 4 to 6 months. Refractive error was not correlated with birth weight or gestational age. Conclusions: The incidence of refractive error in premature infants without retinopathy of prematurity in the first 6 months of life may be as high as 89%. Most of these infants are hyperopic. Eye refraction is correlated with age at examination, but not with birth weight or gestational age. (J AAPOS 2004;8:534-538) rematurity is associated with morbid ocular conditions and among them is refractive error.1-3 The incidence of this sequel is higher in premature infants with retinopathy of prematurity (ROP). However, prematurity itself has been reported as a risk factor for the development of this ophthalmic problem.1,4-6 Some authors thought ROP was related to low birth weight,3,5-6 although others have failed to verify that correlation.2,4,7 This pathology may be diagnosed during the neonatal period or may develop at the age of a few years.1,5,6,8 Longitudinal studies on full-term infants show that eye refraction changes with age.9-10 Wood et al9 found a significant change toward hyperopia during the first 3 months of life, with an increase of 2.6 diopters (D) in 75% of the children examined during that period. After the age of 6 months there was a gradual significant decrease in the spherical equivalent. Ehrlich et al10 described a trend toward emmetropia in full-term myopic infants between the ages of 8.5 and 38.5 months. According to most reports, premature infants are generally hyperopic,2,7,11 and many of them subsequently be-
P
From the Sapir Medical Center, Department of Ophthalmology,a Meir Hospital, Kefar Sava, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; The Chaim Sheba Medical Center, Goldschleger Eye Institute,b Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Submitted September 4, 2003. Revision accepted September 13, 2004. Reprint requests: Yokrat Ton, MD, 30 Sirkin St., 53255 Givataim, Israel (e-mail: [email protected]). Copyright © 2004 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2004/$35.00 ⫹ 0 doi:10.1016/j.jaapos.2004.09.002
534
December 2004
come myopic.4-5 Shapiro et al7 failed to find a significant change in refraction or a trend toward emmetropia in premature children aged between 6 months and 3.5 years. Some authors report myopia as a common finding in premature children in the first months of life.3,12 In the present study, we investigated the incidence and degree of refractive error during the first months of life in premature infants without ROP. Since studies showed that the occurrence of the refractive error among premature infants was different than in full term, we sought a possible correlation between the refractive error and baseline perinatal parameters.
SUBJECTS AND METHODS The sectional study population comprised 390 premature infants who were born at the Chaim Sheba Medical Center, Israel, between January 1997 and July 2000. Refractive power was measured at the postnatal age of 2 weeks and 6 months. Children with ROP or any other ocular morbidity were excluded from the study. Cycloplegia for retinoscopy was achieved by instilling cyclomydril eye drops (cyclopentolate hydrochloride 0.2% and phenylephrine hydrochloride 1%, preserved with 0.01% benzalkonium chloride, Alcon, Fort Worth, TX, USA) twice at an interval of 10 minutes. Retinoscopy was performed 40 minutes afterward. All refractive measurements were performed by an experienced optometrist. The values obtained for all parameters are expressed as means ⫾ SD. Correlations between eye refraction and the different variables were investigated by regression and correlation tests. Student’s t-test was used to compare the refractive error between different groups according to age, Journal of AAPOS
Journal of AAPOS Volume 8 Number 6 December 2004
Ton, Wysenbeek, and Spierer
TABLE 1. Statistical analysis of variables of 390 premature infants Postnatal Birth age (months) weight (g) Mean SD Median Minimum Maximum
2.1 1 2 0.5 6
1639 444 1638 675 3650
535
Gestational age (weeks)
Sph equ RE (D)
Sph equ LE (D)
32.2 2.4 33 26 36
⫹1.56 ⫹1.82 ⫹1.5 ⫺4.0 ⫹8.25
⫹1.55 ⫹1.78 ⫹1.5 ⫺3.5 ⫹8
Sph equ, spherical equivalent; RE, right eye; LE, left eye.
TABLE 2. Distribution of refraction in 780 eyes of premature infants at the age of 2 weeks to 6 months Refractive error
RE (%)
LE (%)
Total No. of eyes (%)
Emmetropia Hypermetropia Myopia Astigmatism ⬍ ⫺1 Astigmatism ⬍ ⫺2 ⬎ ⫹4D ⬍ ⫺2D ⬍ ⫺3D
45 (11.5) 299 (76.7) 46 (11.8) 68 (17.4) 21 (5.4) 24 (6.2) 14 (3.6) 3 (0.8)
43 (11) 300 (77) 47 (12) 64 (16.4) 14 (3.6) 20 (5.1) 13 (3.3) 2 (0.5)
88 (11.3) 599 (76.8) 93 (11.9) 132 (16.9) 35 (4.5) 44 (5.6) 27 (3.5) 5 (0.6)
RE, right eye; LE, left eye.
birth weight, or gestational age. A P value below 0.05 was considered significant.
RESULTS The mean, SD, median, and range of the infants’ age at examination, birth weight, gestational age, and spherical equivalent in each eye are presented in Table 1. Of the 390 subjects, 76.8% had hyperopia, 11.9% had myopia, and 11.3% were emmetropic, as shown in Table 2. The mean refractive error was ⫹1.56 ⫾ 1.82 D in the right eye and ⫹1.55 ⫾ 1.78 D in the left eye. Hyperopia reached as much as ⫹8.25 D (Table 1). However, the refractive error of most of the hyperopic infants (94%) did not exceed ⫹4 D. Myopia exceeded ⫺3 D in only three cases (0.6%) (Table 2, Figure 1). Astigmatism was found in 95 (24.4%) of the subjects in the right eye, and in 85 (21.8%) subjects in the left eye. The mean astigmatism was ⫺1.23 ⫾ 0.76 D in the right eye and ⫺1.2 ⫾ 0.8 D in the left eye. Astigmatism exceeded ⫺1 D in 7.2% of the infants (Table 2). A high correlation coefficient (R ⫽ 0.95) was found between the spherical equivalents in the two eyes of the same infant. The mean refractive error showed a positive linear correlation with age (R ⫽ 0.16, P ⫽ 0.001) (Table 3). Furthermore, when the infants were grouped according to age at examination, significant difference in the mean refractive error was found between infants aged less than 3 months and 3 to 6 months (P ⬍ 0.0001). The incidence and degree of myopia decreased with age. No correlation was found between mean refractive error and birth weight. When the infants were grouped according to birth weight, the differences in mean refrac-
tive error between the groups were not significant (Table 4). No significant linear correlation was detected between mean refractive error and gestational age (Table 5). However, infants born at 29 to 30 weeks of gestation were significantly less hyperopic than those born at 26 to 28 weeks (P ⫽ 0.014) or at 33 to 34 weeks (P ⫽ 0.02).
DISCUSSION Prematurity is often related to ocular morbidity. Possible risk factors that have been repeatedly investigated are birth weight and gestational age. The age at which the premature infants in those studies underwent ophthalmic examination varies from close to birth to school years. Studies of refractive error in premature infants were initiated in the 1950’s.3,13 Fletcher and Brandon3 reported that, during the first 6 months of life, premature infants have a high and fluctuating myopia that is more pronounced in those with low birth weight or in those suffering from ROP. The relationship between ROP and the development of myopia is well established. Cats and Tan1 compared 42 premature infants suffering from ROP with 42 matched non-ROP premature controls at the age of 6 to 10 years. The incidence of refractive error was significantly higher in the former group, but it was unexpectedly high in the non-ROP infants as well. Low-weight neonates were found to be at greater risk for subsequent development of ocular problems. Myopia and astigmatism were detected in 29% of the ROP children and in 10% of the non-ROP children at the age of 6 to 10 years. Moreover, these authors found that the myopia in premature infants without ROP tends to regress during the first year of life, resulting in emmetropic or hyperopic refraction. Other authors have failed to demonstrate a correlation between refraction and birth weight. In a study of the refraction of 177 non-ROP premature infants aged between 2 and 6 weeks, Scharf et al14 found that the majority of eyes could be divided into two main groups: one in which the range of refraction was 0 to ⫹2 D, and the other with a refraction range of ⫺3 to ⫺5 D. They were unable to explain this bimodal phenomenon. No correlation was found between myopia and birth weight. At the age of 6 months, these premature infants showed a change toward emmetropia. In a follow-up study,15 the authors examined the refraction in 67 premature children at the age of 7 years. The tendency of changes in refraction toward em-
Journal of AAPOS Volume 8 Number 6 December 2004
536 Ton, Wysenbeek, and Spierer 200 180 160
No. of eyes
140 120 100 80 60 40 20 0 -4.0
-3.0
-2.0
-1.0
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
Spherical equivalent (D)
FIG 1. Distribution of the mean spherical equivalent of 780 eyes of 390 premature infants. TABLE 3. Mean refractive error in 390 premature infants according to age at examination Postnatal age (months)
<1
1–2
2–3
3–4
No. of children % of children Mean refractive error (⫾SD) Range No. of myopic children (% of overall population)
82 21 ⫹1.24 (⫾1.84) ⫺3.25 to ⫹5.5 15 (18.3)
191 49 ⫹1.44 (⫾1.75) ⫺3.5 to ⫹8.0 23 (12)
69 17.7 ⫹1.65 (⫾1.81) ⫺2.5 to ⫹6.0 9 (13)
35 9 ⫹2.4 (⫾1.34) ⫺1.0 to ⫹5.0 1 (2.9)
TABLE 4. Mean refractive error in 390 premature infants according to birth weight Birth weight (g) <1000 1000–1500 No. of children % of children Mean refractive error (⫾SD) Range
33 8.5 ⫹1.47 (⫾1.9) ⫺2.25 to ⫹5.0
109 27.9 ⫹1.6 (⫾2) ⫺3.5 to ⫹8.0
TABLE 5. Mean refractive error in 390 premature infants according to gestational age Gestational age (weeks) <28 29–30 No. of children % of children Mean refractive error (⫾SD) Range
35 9 ⫹2.15 (⫾2.2) ⫺2.0 to ⫹6.0
58 14.9 ⫹1.05 (⫾1.7) ⫺3.5 to ⫹4.0
metropia had evidently continued, as 46% of the children who were myopic at birth were emmetropic by the age of 7 years. A similar shift toward hyperopia at the age of 2 to 3 months in preterm infants was described by Fledelius.16 In a 7- to 10-year follow-up, Fledelius had found myopia of prematurity in 25% of all preterm children. In 60 children without ROP, myopia was found merely in 5%.17 Kalina11 concluded that premature infants without ROP tend to have hyperopia or no refractive error at all, rather than myopia. Of the 36 children without ROP in
4–6 13 3.3 ⫹2.5 (⫾1.65) 0 to ⫹5.0 0 (0)
Total 390 100 ⫹1.55 (⫾1.77) ⫺3.0 to ⫹8.0 48 (58.3)
1500–2000
2000–2500
>2500
169 43.3 ⫹1.53 (⫾1.6) ⫺3.25 to ⫹6
70 18 ⫹1.54 (⫾1.8) ⫺3.0 to ⫹7.0
9 2.3 ⫹1.97 (⫾1.3) ⫺0.50 to ⫹3.5
31–32
33–34
35–36
87 22.3 ⫹1.39 (⫾1.6) ⫺3.5 to ⫹4.75
154 39.5 ⫹1.69 (⫾1.8) ⫺3.25 to ⫹8.0
56 14.3 ⫹1.6 (⫾1.5) ⫺2.5 to ⫹6.0
their study, 90.5% were either hyperopic or emmetropic at the age of 2 months to 6 years. Nissenkorn et al4 examined the refraction at the age of 2 weeks in 113 premature babies without ROP and found that 16% were myopic. The extent of myopia was not significantly related to birth weight. Koole et al2 found a mean spherical equivalent of ⫹0.9 D in 185 infants with very low birth weight (⬍1500 g) at the age of 9 months, corrected for the duration of pregnancy. There was no significant correlation between refraction and birth weight, gestational age, or other peri-
Journal of AAPOS Volume 8 Number 6 December 2004
natal parameters including Apgar score, hyaline membrane disease, oxygen therapy, mechanical ventilation, hyperbilirubinemia, or hypoglycemia. In the above-mentioned studies, hyperopia was found to be the dominant feature in premature infants. The incidence of myopia in those studies was 9.5 to 17%, a finding that is compatible with our results. In the present study we investigated the refraction of 390 premature infants without ROP in the first 6 months of life. This is a large cohort of infants within a narrow age group close to birth. The significance of the study data are in providing the normal values for premature infants. This will avoid prescribing unnecessary refractive correction for the young infants. Most of the infants were hypermetropic (76.8%), and a minority were either myopic (11.9%) or emmetropic (11.3%). As in most of the previous studies, no correlation between refraction and birth weight or gestational age could be detected. We found a positive linear correlation between mean refractive error and age at examination, as well as significant differences between different age groups. This tendency toward hyperopia in the first months of life has also been described in full-term infants.9 Myopia was higher and more prevalent in younger infants. This could be related to insufficient relaxation of accommodation. Hainline et al18 found that infants under 2 months tend to accommodate appropriately for near targets, but fail to relax their accommodation sufficiently for distant targets. Thus, the focusing error increases with increasing target distance, resulting in a spuriously myopic behavior. Therefore, the cycloplegic effect obtained after using cycloplegic drugs might be insufficient on very young babies. Infants born at 29 to 30 weeks of gestation were significantly less hyperopic than those born at 26 to 28 weeks or at 33 to 34 weeks. It seems that the premature infants simply “catch up” to the normal refractive development process. The premature birth of a child results in underdeveloped organs and tissues in the child’s body. One might expect that the smaller eye of the premature infant as well as the immature cornea and lens might cause a certain deviation in the refractive error of the eye. However, our results do not support this assumption. Probably, all the ocular tissues are equally affected by the immaturity of the eye, thus avoiding the development of either high myopia or hypermetropia. The high range of accommodation found in very young infants may have resulted in a more myopic refraction despite the cycloplegic drugs used for the refraction. This power of accommodation drops during the infant’s growth, resulting in more hyperopic measurements. In contrast to the above, Gordon and Donzis12 found normal premature children at the age of 30 to 35 weeks, including gestation, to be slightly myopic, with a mean refractive error of ⫺1.0 D (refraction range ⫺3.0 to ⫹1.0 D). When analyzing the refractive components of myopia
Ton, Wysenbeek, and Spierer
537
in infants with ROP, Gordon and Donzis19 revealed a significant lenticular component. They suggested that vitreoretinal influences, responsible for the normal postnatal reduction of the crystalline lens power, are disturbed by ROP. The refractive error obtained in the premature infants is comparable to the refractive error of full-term infants. At age 2 to 3 months a ⫹1.65 ⫾ 1.81 D was found in the premature infants (Table 3). At that age similar refraction of ⫹1.0 D20 to ⫹2.5 D21 was found in full-term infants. In conclusion, hyperopia was found in 76.8% of the premature babies in our study during the first 6 months of life, and myopia was found in 11.9%. Both the incidence and the degree of the refractive error were correlated with age at examination, but not with birth weight or gestational age. The incidence of refractive error in premature babies is high not only in those with ROP. References 1. Cats BP, Tan KEWP. Prematures with or without regressed retinopathy of prematurity: comparison of long term (6-10 years) ophthalmological morbidity. J Pediatr Ophthalmol Strabismus 1989;26: 271-5. 2. Koole FD, Bax PP, Samson JF, Van Der Lei J. Ocular examination in nine-month-old infants with very low birth weights. Ophthalmic Pediatr Genet 1990;11:89-94. 3. Fletcher MC, Brandon S. Myopia of prematurity. Am J Ophthalmol 1955;40:474-81. 4. Nissenkorn Y, Yassur D, Mashkoeski IS, Sherf I, Ben-Sira I. Myopia in premature babies with or without retinopathy of prematurity. Br J Ophthalmol 1983;67:170-3. 5. Page JM, Schneeweiss S, Whyte HEA, Harvey P. Ocular sequelae in premature infants. Pediatrics 1993;92:787-90. 6. Quinn GE, Dobson V, Repka MX, Reynolds J, Kivlin J, Davis B, Buckley E, Flynn JT, Palmer EA. Development of myopia in infants with birth weight less than 1251 grams. Ophthalmology 1992;99: 329-40. 7. Shapiro A, Yanko L, Nawratzki I, Merin S. Refractive power of premature children at infancy and early childhood. Am J Ophthalmol 1980;90:234-8. 8. Keith CG, Kitchen WH. Ocular morbidity in infants of very low birth weight. Br J Ophthalmol 1983;67:302-5. 9. Wood ICJ, Hodi S, Morgan L. Longitudinal change of refractive error in infants during the first year of life. Eye 1995;9:551-7. 10. Ehrlich DL, Atkinson J, Braddick O, Bobier W, Durden K. Reduction of infant myopia: a longitudinal cycloplegic study. Vision Res 1995;9:1313-24. 11. Kalina RE. Ophthalmic examination of children of low birth weight. Am J Ophthalmol 1969;67:134-6. 12. Gordon RA, Donzis PB. Refractive development of the human eye. Arch Ophthalmol 1985;103:785-9. 13. Alfano JE. Myopia of prematurity. Am J Ophthalmol 1958;46:45-9. 14. Scharf J, Zonis S, Zeltzer M. Refraction in Israeli premature babies. J Pediatr Ophthalmol Strabismus 1975;12:193-6. 15. Scharf J, Zonis S, Zeltzer M. Refraction in premature babies: a prospective study. J Pediatr Ophthalmol Strabismus 1978;15:48-50. 16. Fledelius HC. Ocular features other than retinopathy of prematurity in the pre-term infant. Acta Ophthalmol (Copenh) 1990;68:214-7. 17. Fledelius HC. Pre-term delivery and subsequent ocular development. A 7-10 year follow-up of children screened 1982-84 for ROP. 3) Refraction. Myopia of prematurity. Acta Ophthalmol Scand 1996;74:297-300.
538 Ton, Wysenbeek, and Spierer 18. Hainline L, Riddell P, Grose Fifer J, Abramov I. Development of accommodation and convergence in infancy. Behav Brain Res 1992;49:33-50. 19. Gordon RA, Donzis PB. Myopia associated with retinopathy of prematurity. Ophthalmology 1986;93:1593-8. 20. Wood ICG, Hodi S. Refractive findings of a longitudinal study of infants
Journal of AAPOS Volume 8 Number 6 December 2004 from birth to one year of age (abstract). Invest Ophthalmol Vis Sci 1992;32(Suppl.):971. 21. Saunders KJ, Westall CA. Comparison between near and cycloplegic retinoscopy in the refraction of infants and children. Optom Vis Sci 1992;69:615-22.
An Eye on the Arts – The Arts on the Eye
One whose two eyes are above or whose two eyes are below. What [does the Mishnah mean by the expression] both eyes above and both eyes below? Shall I say both eyes above mean that they [continuously] see above, the expression both eyes below, that they see below; and one eye above and one eye below [means] that one eye sees below and the other above? Then the latter case would be identical with the case one who takes in the room and the ceiling in one glance [mentioned later in the Mishnah]?—Rather this is the explanation: The expression both eyes above means that they stand above, [the expression] both eyes below means that they stand below, [the expression] one eye above and one eye below means that one eye stands above and one eye below. And even where the eyes are in their normal places, there is a case of unfitness where one takes in the room and the ceiling in one glance. Whence do we prove this?—Our Rabbis taught, Scripture says: ‘In his eye’, every [defect] in connection with the eye. Hence [the Sages] say: One who has both eyes below or both eyes above or one eye above and one eye below or one who takes in the room and the ceiling in one glance or one who speaks with his friend, and another says, ‘He is looking at me—[all these defects render a priest unfit for the priesthood]. —Babylonian Talmud, Bekoroth, p. 44A
P
From the Sapir Medical Center, Department of Ophthalmology,a Meir Hospital, Kefar Sava, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; The Chaim Sheba Medical Center, Goldschleger Eye Institute,b Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Submitted September 4, 2003. Revision accepted September 13, 2004. Reprint requests: Yokrat Ton, MD, 30 Sirkin St., 53255 Givataim, Israel (e-mail: [email protected]). Copyright © 2004 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2004/$35.00 ⫹ 0 doi:10.1016/j.jaapos.2004.09.002
534
December 2004
come myopic.4-5 Shapiro et al7 failed to find a significant change in refraction or a trend toward emmetropia in premature children aged between 6 months and 3.5 years. Some authors report myopia as a common finding in premature children in the first months of life.3,12 In the present study, we investigated the incidence and degree of refractive error during the first months of life in premature infants without ROP. Since studies showed that the occurrence of the refractive error among premature infants was different than in full term, we sought a possible correlation between the refractive error and baseline perinatal parameters.
SUBJECTS AND METHODS The sectional study population comprised 390 premature infants who were born at the Chaim Sheba Medical Center, Israel, between January 1997 and July 2000. Refractive power was measured at the postnatal age of 2 weeks and 6 months. Children with ROP or any other ocular morbidity were excluded from the study. Cycloplegia for retinoscopy was achieved by instilling cyclomydril eye drops (cyclopentolate hydrochloride 0.2% and phenylephrine hydrochloride 1%, preserved with 0.01% benzalkonium chloride, Alcon, Fort Worth, TX, USA) twice at an interval of 10 minutes. Retinoscopy was performed 40 minutes afterward. All refractive measurements were performed by an experienced optometrist. The values obtained for all parameters are expressed as means ⫾ SD. Correlations between eye refraction and the different variables were investigated by regression and correlation tests. Student’s t-test was used to compare the refractive error between different groups according to age, Journal of AAPOS
Journal of AAPOS Volume 8 Number 6 December 2004
Ton, Wysenbeek, and Spierer
TABLE 1. Statistical analysis of variables of 390 premature infants Postnatal Birth age (months) weight (g) Mean SD Median Minimum Maximum
2.1 1 2 0.5 6
1639 444 1638 675 3650
535
Gestational age (weeks)
Sph equ RE (D)
Sph equ LE (D)
32.2 2.4 33 26 36
⫹1.56 ⫹1.82 ⫹1.5 ⫺4.0 ⫹8.25
⫹1.55 ⫹1.78 ⫹1.5 ⫺3.5 ⫹8
Sph equ, spherical equivalent; RE, right eye; LE, left eye.
TABLE 2. Distribution of refraction in 780 eyes of premature infants at the age of 2 weeks to 6 months Refractive error
RE (%)
LE (%)
Total No. of eyes (%)
Emmetropia Hypermetropia Myopia Astigmatism ⬍ ⫺1 Astigmatism ⬍ ⫺2 ⬎ ⫹4D ⬍ ⫺2D ⬍ ⫺3D
45 (11.5) 299 (76.7) 46 (11.8) 68 (17.4) 21 (5.4) 24 (6.2) 14 (3.6) 3 (0.8)
43 (11) 300 (77) 47 (12) 64 (16.4) 14 (3.6) 20 (5.1) 13 (3.3) 2 (0.5)
88 (11.3) 599 (76.8) 93 (11.9) 132 (16.9) 35 (4.5) 44 (5.6) 27 (3.5) 5 (0.6)
RE, right eye; LE, left eye.
birth weight, or gestational age. A P value below 0.05 was considered significant.
RESULTS The mean, SD, median, and range of the infants’ age at examination, birth weight, gestational age, and spherical equivalent in each eye are presented in Table 1. Of the 390 subjects, 76.8% had hyperopia, 11.9% had myopia, and 11.3% were emmetropic, as shown in Table 2. The mean refractive error was ⫹1.56 ⫾ 1.82 D in the right eye and ⫹1.55 ⫾ 1.78 D in the left eye. Hyperopia reached as much as ⫹8.25 D (Table 1). However, the refractive error of most of the hyperopic infants (94%) did not exceed ⫹4 D. Myopia exceeded ⫺3 D in only three cases (0.6%) (Table 2, Figure 1). Astigmatism was found in 95 (24.4%) of the subjects in the right eye, and in 85 (21.8%) subjects in the left eye. The mean astigmatism was ⫺1.23 ⫾ 0.76 D in the right eye and ⫺1.2 ⫾ 0.8 D in the left eye. Astigmatism exceeded ⫺1 D in 7.2% of the infants (Table 2). A high correlation coefficient (R ⫽ 0.95) was found between the spherical equivalents in the two eyes of the same infant. The mean refractive error showed a positive linear correlation with age (R ⫽ 0.16, P ⫽ 0.001) (Table 3). Furthermore, when the infants were grouped according to age at examination, significant difference in the mean refractive error was found between infants aged less than 3 months and 3 to 6 months (P ⬍ 0.0001). The incidence and degree of myopia decreased with age. No correlation was found between mean refractive error and birth weight. When the infants were grouped according to birth weight, the differences in mean refrac-
tive error between the groups were not significant (Table 4). No significant linear correlation was detected between mean refractive error and gestational age (Table 5). However, infants born at 29 to 30 weeks of gestation were significantly less hyperopic than those born at 26 to 28 weeks (P ⫽ 0.014) or at 33 to 34 weeks (P ⫽ 0.02).
DISCUSSION Prematurity is often related to ocular morbidity. Possible risk factors that have been repeatedly investigated are birth weight and gestational age. The age at which the premature infants in those studies underwent ophthalmic examination varies from close to birth to school years. Studies of refractive error in premature infants were initiated in the 1950’s.3,13 Fletcher and Brandon3 reported that, during the first 6 months of life, premature infants have a high and fluctuating myopia that is more pronounced in those with low birth weight or in those suffering from ROP. The relationship between ROP and the development of myopia is well established. Cats and Tan1 compared 42 premature infants suffering from ROP with 42 matched non-ROP premature controls at the age of 6 to 10 years. The incidence of refractive error was significantly higher in the former group, but it was unexpectedly high in the non-ROP infants as well. Low-weight neonates were found to be at greater risk for subsequent development of ocular problems. Myopia and astigmatism were detected in 29% of the ROP children and in 10% of the non-ROP children at the age of 6 to 10 years. Moreover, these authors found that the myopia in premature infants without ROP tends to regress during the first year of life, resulting in emmetropic or hyperopic refraction. Other authors have failed to demonstrate a correlation between refraction and birth weight. In a study of the refraction of 177 non-ROP premature infants aged between 2 and 6 weeks, Scharf et al14 found that the majority of eyes could be divided into two main groups: one in which the range of refraction was 0 to ⫹2 D, and the other with a refraction range of ⫺3 to ⫺5 D. They were unable to explain this bimodal phenomenon. No correlation was found between myopia and birth weight. At the age of 6 months, these premature infants showed a change toward emmetropia. In a follow-up study,15 the authors examined the refraction in 67 premature children at the age of 7 years. The tendency of changes in refraction toward em-
Journal of AAPOS Volume 8 Number 6 December 2004
536 Ton, Wysenbeek, and Spierer 200 180 160
No. of eyes
140 120 100 80 60 40 20 0 -4.0
-3.0
-2.0
-1.0
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
Spherical equivalent (D)
FIG 1. Distribution of the mean spherical equivalent of 780 eyes of 390 premature infants. TABLE 3. Mean refractive error in 390 premature infants according to age at examination Postnatal age (months)
<1
1–2
2–3
3–4
No. of children % of children Mean refractive error (⫾SD) Range No. of myopic children (% of overall population)
82 21 ⫹1.24 (⫾1.84) ⫺3.25 to ⫹5.5 15 (18.3)
191 49 ⫹1.44 (⫾1.75) ⫺3.5 to ⫹8.0 23 (12)
69 17.7 ⫹1.65 (⫾1.81) ⫺2.5 to ⫹6.0 9 (13)
35 9 ⫹2.4 (⫾1.34) ⫺1.0 to ⫹5.0 1 (2.9)
TABLE 4. Mean refractive error in 390 premature infants according to birth weight Birth weight (g) <1000 1000–1500 No. of children % of children Mean refractive error (⫾SD) Range
33 8.5 ⫹1.47 (⫾1.9) ⫺2.25 to ⫹5.0
109 27.9 ⫹1.6 (⫾2) ⫺3.5 to ⫹8.0
TABLE 5. Mean refractive error in 390 premature infants according to gestational age Gestational age (weeks) <28 29–30 No. of children % of children Mean refractive error (⫾SD) Range
35 9 ⫹2.15 (⫾2.2) ⫺2.0 to ⫹6.0
58 14.9 ⫹1.05 (⫾1.7) ⫺3.5 to ⫹4.0
metropia had evidently continued, as 46% of the children who were myopic at birth were emmetropic by the age of 7 years. A similar shift toward hyperopia at the age of 2 to 3 months in preterm infants was described by Fledelius.16 In a 7- to 10-year follow-up, Fledelius had found myopia of prematurity in 25% of all preterm children. In 60 children without ROP, myopia was found merely in 5%.17 Kalina11 concluded that premature infants without ROP tend to have hyperopia or no refractive error at all, rather than myopia. Of the 36 children without ROP in
4–6 13 3.3 ⫹2.5 (⫾1.65) 0 to ⫹5.0 0 (0)
Total 390 100 ⫹1.55 (⫾1.77) ⫺3.0 to ⫹8.0 48 (58.3)
1500–2000
2000–2500
>2500
169 43.3 ⫹1.53 (⫾1.6) ⫺3.25 to ⫹6
70 18 ⫹1.54 (⫾1.8) ⫺3.0 to ⫹7.0
9 2.3 ⫹1.97 (⫾1.3) ⫺0.50 to ⫹3.5
31–32
33–34
35–36
87 22.3 ⫹1.39 (⫾1.6) ⫺3.5 to ⫹4.75
154 39.5 ⫹1.69 (⫾1.8) ⫺3.25 to ⫹8.0
56 14.3 ⫹1.6 (⫾1.5) ⫺2.5 to ⫹6.0
their study, 90.5% were either hyperopic or emmetropic at the age of 2 months to 6 years. Nissenkorn et al4 examined the refraction at the age of 2 weeks in 113 premature babies without ROP and found that 16% were myopic. The extent of myopia was not significantly related to birth weight. Koole et al2 found a mean spherical equivalent of ⫹0.9 D in 185 infants with very low birth weight (⬍1500 g) at the age of 9 months, corrected for the duration of pregnancy. There was no significant correlation between refraction and birth weight, gestational age, or other peri-
Journal of AAPOS Volume 8 Number 6 December 2004
natal parameters including Apgar score, hyaline membrane disease, oxygen therapy, mechanical ventilation, hyperbilirubinemia, or hypoglycemia. In the above-mentioned studies, hyperopia was found to be the dominant feature in premature infants. The incidence of myopia in those studies was 9.5 to 17%, a finding that is compatible with our results. In the present study we investigated the refraction of 390 premature infants without ROP in the first 6 months of life. This is a large cohort of infants within a narrow age group close to birth. The significance of the study data are in providing the normal values for premature infants. This will avoid prescribing unnecessary refractive correction for the young infants. Most of the infants were hypermetropic (76.8%), and a minority were either myopic (11.9%) or emmetropic (11.3%). As in most of the previous studies, no correlation between refraction and birth weight or gestational age could be detected. We found a positive linear correlation between mean refractive error and age at examination, as well as significant differences between different age groups. This tendency toward hyperopia in the first months of life has also been described in full-term infants.9 Myopia was higher and more prevalent in younger infants. This could be related to insufficient relaxation of accommodation. Hainline et al18 found that infants under 2 months tend to accommodate appropriately for near targets, but fail to relax their accommodation sufficiently for distant targets. Thus, the focusing error increases with increasing target distance, resulting in a spuriously myopic behavior. Therefore, the cycloplegic effect obtained after using cycloplegic drugs might be insufficient on very young babies. Infants born at 29 to 30 weeks of gestation were significantly less hyperopic than those born at 26 to 28 weeks or at 33 to 34 weeks. It seems that the premature infants simply “catch up” to the normal refractive development process. The premature birth of a child results in underdeveloped organs and tissues in the child’s body. One might expect that the smaller eye of the premature infant as well as the immature cornea and lens might cause a certain deviation in the refractive error of the eye. However, our results do not support this assumption. Probably, all the ocular tissues are equally affected by the immaturity of the eye, thus avoiding the development of either high myopia or hypermetropia. The high range of accommodation found in very young infants may have resulted in a more myopic refraction despite the cycloplegic drugs used for the refraction. This power of accommodation drops during the infant’s growth, resulting in more hyperopic measurements. In contrast to the above, Gordon and Donzis12 found normal premature children at the age of 30 to 35 weeks, including gestation, to be slightly myopic, with a mean refractive error of ⫺1.0 D (refraction range ⫺3.0 to ⫹1.0 D). When analyzing the refractive components of myopia
Ton, Wysenbeek, and Spierer
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in infants with ROP, Gordon and Donzis19 revealed a significant lenticular component. They suggested that vitreoretinal influences, responsible for the normal postnatal reduction of the crystalline lens power, are disturbed by ROP. The refractive error obtained in the premature infants is comparable to the refractive error of full-term infants. At age 2 to 3 months a ⫹1.65 ⫾ 1.81 D was found in the premature infants (Table 3). At that age similar refraction of ⫹1.0 D20 to ⫹2.5 D21 was found in full-term infants. In conclusion, hyperopia was found in 76.8% of the premature babies in our study during the first 6 months of life, and myopia was found in 11.9%. Both the incidence and the degree of the refractive error were correlated with age at examination, but not with birth weight or gestational age. The incidence of refractive error in premature babies is high not only in those with ROP. References 1. Cats BP, Tan KEWP. Prematures with or without regressed retinopathy of prematurity: comparison of long term (6-10 years) ophthalmological morbidity. J Pediatr Ophthalmol Strabismus 1989;26: 271-5. 2. Koole FD, Bax PP, Samson JF, Van Der Lei J. Ocular examination in nine-month-old infants with very low birth weights. Ophthalmic Pediatr Genet 1990;11:89-94. 3. Fletcher MC, Brandon S. Myopia of prematurity. Am J Ophthalmol 1955;40:474-81. 4. Nissenkorn Y, Yassur D, Mashkoeski IS, Sherf I, Ben-Sira I. Myopia in premature babies with or without retinopathy of prematurity. Br J Ophthalmol 1983;67:170-3. 5. Page JM, Schneeweiss S, Whyte HEA, Harvey P. Ocular sequelae in premature infants. Pediatrics 1993;92:787-90. 6. Quinn GE, Dobson V, Repka MX, Reynolds J, Kivlin J, Davis B, Buckley E, Flynn JT, Palmer EA. Development of myopia in infants with birth weight less than 1251 grams. Ophthalmology 1992;99: 329-40. 7. Shapiro A, Yanko L, Nawratzki I, Merin S. Refractive power of premature children at infancy and early childhood. Am J Ophthalmol 1980;90:234-8. 8. Keith CG, Kitchen WH. Ocular morbidity in infants of very low birth weight. Br J Ophthalmol 1983;67:302-5. 9. Wood ICJ, Hodi S, Morgan L. Longitudinal change of refractive error in infants during the first year of life. Eye 1995;9:551-7. 10. Ehrlich DL, Atkinson J, Braddick O, Bobier W, Durden K. Reduction of infant myopia: a longitudinal cycloplegic study. Vision Res 1995;9:1313-24. 11. Kalina RE. Ophthalmic examination of children of low birth weight. Am J Ophthalmol 1969;67:134-6. 12. Gordon RA, Donzis PB. Refractive development of the human eye. Arch Ophthalmol 1985;103:785-9. 13. Alfano JE. Myopia of prematurity. Am J Ophthalmol 1958;46:45-9. 14. Scharf J, Zonis S, Zeltzer M. Refraction in Israeli premature babies. J Pediatr Ophthalmol Strabismus 1975;12:193-6. 15. Scharf J, Zonis S, Zeltzer M. Refraction in premature babies: a prospective study. J Pediatr Ophthalmol Strabismus 1978;15:48-50. 16. Fledelius HC. Ocular features other than retinopathy of prematurity in the pre-term infant. Acta Ophthalmol (Copenh) 1990;68:214-7. 17. Fledelius HC. Pre-term delivery and subsequent ocular development. A 7-10 year follow-up of children screened 1982-84 for ROP. 3) Refraction. Myopia of prematurity. Acta Ophthalmol Scand 1996;74:297-300.
538 Ton, Wysenbeek, and Spierer 18. Hainline L, Riddell P, Grose Fifer J, Abramov I. Development of accommodation and convergence in infancy. Behav Brain Res 1992;49:33-50. 19. Gordon RA, Donzis PB. Myopia associated with retinopathy of prematurity. Ophthalmology 1986;93:1593-8. 20. Wood ICG, Hodi S. Refractive findings of a longitudinal study of infants
Journal of AAPOS Volume 8 Number 6 December 2004 from birth to one year of age (abstract). Invest Ophthalmol Vis Sci 1992;32(Suppl.):971. 21. Saunders KJ, Westall CA. Comparison between near and cycloplegic retinoscopy in the refraction of infants and children. Optom Vis Sci 1992;69:615-22.
An Eye on the Arts – The Arts on the Eye
One whose two eyes are above or whose two eyes are below. What [does the Mishnah mean by the expression] both eyes above and both eyes below? Shall I say both eyes above mean that they [continuously] see above, the expression both eyes below, that they see below; and one eye above and one eye below [means] that one eye sees below and the other above? Then the latter case would be identical with the case one who takes in the room and the ceiling in one glance [mentioned later in the Mishnah]?—Rather this is the explanation: The expression both eyes above means that they stand above, [the expression] both eyes below means that they stand below, [the expression] one eye above and one eye below means that one eye stands above and one eye below. And even where the eyes are in their normal places, there is a case of unfitness where one takes in the room and the ceiling in one glance. Whence do we prove this?—Our Rabbis taught, Scripture says: ‘In his eye’, every [defect] in connection with the eye. Hence [the Sages] say: One who has both eyes below or both eyes above or one eye above and one eye below or one who takes in the room and the ceiling in one glance or one who speaks with his friend, and another says, ‘He is looking at me—[all these defects render a priest unfit for the priesthood]. —Babylonian Talmud, Bekoroth, p. 44A