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1From the Department of Ophthalmology, Rabin Medical Center, and the 4Pediatric Ophthalmology and 3Neonatology Intensive Care Units, Schneider Childrens Medical Center of Israel, Petah Tiqva, Israel; and the 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| Abstract |
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METHODS. Biometric and keratometric values, intraocular pressure, and retinal vascular status were assessed in a cohort of 133 premature infants. These values were compared between premature infants conceived by IVF or naturally, and the relationship between these parameters and postconceptional age and weight at examination were evaluated.
RESULTS. The sample consisted of 133 premature infants, 62 (46.6%) born by IVF and 71 (53.4%) by natural conception. Postconceptional age at examination was 28 to 46 weeks. In both groups, axial length, anterior chamber depth, and corneal radius correlated with the postconceptional age and weight at examination and followed a linear growth pattern. Lens thickness changed very slightly. The rate of retinal vascularization correlated with the postconceptional age as well. No correlation was found between intraocular pressure and corrected age or weight at examination. There was no difference between the study and control groups in any of the biometric or keratometric parameters or in intraocular pressure, according to two-way analysis of variance.
CONCLUSIONS. IVF apparently does not affect early ocular growth, intraocular pressure, changes in corneal curvature, or retinal vascularization in premature infants. These findings may aid ophthalmologists in assessing ocular dimensions in this patient population.
There is little information in particular on the ocular outcome of IVF-conceived infants. Anteby et al.,10 in a study of 47 children conceived by IVF, noted reduced visual acuity in 9% and anisometropia of >1.0 D in 17%. Major ocular malformations were documented in 26%, including Coats disease, congenital cataract, coloboma of the uvea, hypoplastic optic nerve heads, idiopathic optic atrophy, congenital glaucoma, and retinoblastoma.
The purpose of the present comparative study was to evaluate the effects of IVF on the early development of the eye in premature infants.
| Methods |
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All ophthalmic examinations were performed by the same examiner (DB) and included measurement of intraocular pressure (IOP), keratometry and ultrasound biometry, and funduscopy.
IOP was measured with the Tonopen (Solan, Jacksonville, FL) after instillation of two drops of topical anesthetic (oxybuprocaine HCl 0.4%; Fischer Pharmaceuticals, Tel Aviv, Israel). The eyelids were retracted gently, without using a speculum and without applying pressure on the globe. The measurement was performed only when the infants were quiet, to prevent IOP fluctuations.11 Three measurements with no more than a 2-mm Hg difference were obtained for each eye, and the average IOP was recorded.
Corneal curvature was measured with a hand-held autokeratometer (model KM 500; Nidek, Gamagori, Japan) after manual retraction of the eyelids, as just described. The keratometer was placed perpendicular to the eye and focused until three readings were obtained. The cornea was kept moist by instillation of saline solution. The average horizontal and vertical radii were recorded for each eye.
Biometry was performed with an ultrasound biometer (model 820; Carl Zeiss Meditec, Dublin, CA), using the technique described by Butcher and OBrian.12 This involved applanation of the cornea with the A-scan probe after instillation of topical anesthetic (oxybuprocaine HCl 0.4%). The eyelids were retracted manually without exerting direct pressure on the globe, and the probe was placed lightly on the center of the cornea, perpendicular to its axis. Special care was taken to avoid corneal indentation. The probe was maintained in this position until three clear traces were obtained on the screen. The average value of the three best images was recorded for each eye. Data included axial length, anterior chamber depth, and lens thickness.
For the funduscopic examination, an additional drop of oxybuprocaine HCl 0.4% was instilled, and a lid speculum was placed gently between the eyelids. Scleral indentation was performed for examination of the peripheral retina. Vascular development was measured according to the zone reached by the normal vasculature.13 The presence and stage of retinopathy of prematurity (ROP) were noted as well.
Statistical Methods
Statistical analysis was performed on computer (BMDP Statistical Software, Los Angeles, CA).14 We performed one- and two-way analysis of variance (ANOVA), analysis of covariance (ANCOVA), Fisher exact test, and Pearson correlation, when appropriate.
| Results |
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32 weeks, 3336 weeks, 3741 weeks, and >41 weeks), and the average biometric, keratometric, and IOPs were calculated for each age group separately and compared by ANOVA. The findings are shown in Table 4 . A significant difference was noted between the groups for axial length and horizontal corneal radius. Further division of the four age groups by type of conception yielded no difference between the IVF and natural-conception subgroups in any of the parameters by two-way ANOVA.
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Conception Groups.
Pearson correlations performed separately for the IVF and natural-conception groups for the same parameters in relation to PCA and weight at examination yielded similar results to those for the whole group, as shown in Table 6 .
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| Discussion |
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Although earlier studies have reported on ocular biometry, keratometry, refraction and IOP in preterm infants, to the best of our knowledge, there are no published data on biometric values and IOP specifically in premature infants conceived by IVF. Our findings both in the whole sample of infants and in the IVF and natural-conception groups separately, correspond with the previous data.
In our series, axial length and anterior chamber depth showed a linear growth pattern in both the IVF and natural-conception groups, and correlated with the PCA and weight at examination. Fledelius22 noted similar findings, in addition to a direct relationship between the two parameters. The rate of increase in axial length in our series was 0.13 mm per week. Studies of the general population of preterm infants revealed that axial length increased from 12.6 to 16.2 mm from 25 to 27 weeks of age,11 and from 15.38 to 16.88 mm from 33 to 41 weeks postmenstrual age,23 for a linear rate of 0.18 mm per week. Cook et al.24 reported a fitted value of 16.02 mm at 36 weeks, similar to our values of 16.02 for the right eye and 15.96 for the left in infants up to 32 weeks. Isenberg et al.25 had similar findings.
Regarding anterior chamber depth, the weekly rate of increase in the series of Cook et al.24 was 0.04 mmhigher than our depth of 0.016 and 0.010 mm in the right and left eyes, respectivelyalthough the average depth at term (2.25 mm) was similar (Table 4) . OBrian and Clark23 reported an increase from 1.92 mm at 33 weeks to 2.43 mm at 41 weeks for a rate of 0.064 mm per week, and Isenberg et al.25 reported a depth of 2 mm at term, with a correlation with PCA. All these studies, like ours, show a constant, linear growth pattern related to PCA. The small variations may be attributable to differences in the study populations or the measuring instruments used.
Correlations with PCA and weight at examination were also documented for the corneal radius of curvature. Cook et al.,24 noted that the curvature increased at 0.0947 mm per week, compared to 0.08 and 0.07 mm for the horizontal radius of the right and left eyes respectively, and 0.06 for the vertical radius, in the present study. They found a radius of 6.94 mm at 40 weeks postmenstrual age, which is slightly higher than the radii discovered in the present study in the right and left eyes at 37 to 41 weeks (horizontal: 6.61 and 6.55, respectively; vertical: 6.29 and 6.43, respectively, Figs. 4 5 ). However, extension of their observations to 60 weeks postmenstrual age showed that growth slowed after 40 weeks, yielding a quadratic pattern overall. As our measurements were performed from 27 to 46 weeks, with most infants examined up to 41 weeks, the data are not directly comparable. Findings Similar to ours were noted in other studies. Friling et al.,26 in a study including full-term infants, reported a mean horizontal radius of curvature of 5.76 mm and vertical radius of 6.25 mm; both meridians declined with an increase in birth weight and PCA. In the series of Snir et al.,27 the mean keratometric reading at 40 weeks was 6.82 mm in the premature infants versus 7.03 mm in the term infants (compared with horizontal radii of 7.03 and 6.82 mm in the right and left eyes, respectively, and vertical corneal radius of 6.54 in both eyes in infants over 41 weeks PCA in the present study). Others noted an average radius in premature infants of 5.63 mm at 28 weeks and 6.62 mm at term,28 6.35 at term,29 6.65 mm at term,30 and 7.0 mm at 2 to 4 weeks after birth.31 Yuji32 found a rapid change in corneal curvature (6.897.34 mm) in the first 2 to 4 weeks of life, followed by a deceleration after 8 weeks (7.57 mm). In the present study, we observed a correlation of the corneal radii not only to age at examination, but to weight at examination as well.
Lens thickness, however, showed little change in correlation with PCA (weeks 3042) or weight at examination. Mean thickness at term was 3.98 mm in the right eye and 3.87 mm in the left. Similar data were reported by Cook et al.24 (3.843.98 mm from 32 weeks to term), OBrian and Clark23 (3.833.90 mm from 33 to 41 weeks), and Isenberg et al.25 (3.8 mm at term).
In preterm infants, with maturation, the axial length enlarges, the anterior chamber depth deepens, and the corneal curvature flattens, whereas the lens thickness remains stable. This is true for both infants born after IVF and natural conception.
IOP did not correlate with PCA or weight at examination, being slightly, but not significantly, higher in the IVF group (14 mm Hg in the right eye, 14.2 mm Hg in the left) than in the control group (13.4 and 13.6 mm Hg, respectively). These data agree with those in an earlier study by our team in a different group of premature infants,33 although a lower value of 10.3 mm Hg was reported by Tucker et al.11 This difference may be explained by the techniques used: Tucker et al.11 inserted an eye speculum, and then performed keratometry and biometry, followed by IOP measurement. Performing tonometry several minutes after introducing an eye speculum may have lowered the reading. Conversely, we measured the IOP at the beginning of the ocular examination, before performing any ocular manipulations.
The positive correlation noted between the zone of retinal vascularization and the axial length and PCA in both the IVF and natural-conception groups is in line with the well-established knowledge that retinal vascularization matures with elongation of the eye. Although complete vascularization was observed in a similar proportion of infants in the two groups, the IVF infants had a slightly higher rate of ROP stage 2; this difference was not significant.
Watts and Adams5 reported an increased percentage (41.6%) of IVF-conceived premature infants reaching threshold ROP, which was unaccounted for by multiple pregnancies alone. The difference in outcomes for assisted conception has been suggested to result from exposing the gametes to physical and pharmacological manipulations, as well as to potential hazardous nurturing conditions and inappropriate uterine environment.5 In our series we excluded infants with birth weight <700 g, with intraventricular hemorrhage and necrotizing enterocolitis, as well as infants with previous laser treatment, thus lowering the likelihood of including infants with threshold ROP. Moreover, because the average PCA and weight at examination were similar in both groups, it is not surprising that there were no differences in the rates of ROP between the IVF and naturally conceived infants.
In summary, all biometric and IOP calculations performed in the present series of premature infants born after IVF concur with previous studies performed in preterm infants with slight variations that are probably attributable to the different study populations and study designs. The biometric and IOP values in our IVF-conceived neonates did not differ from those in the infants conceived naturally. These findings may reflect either a true similarity in ocular growth between the groups, or they may mask differences due to prematurity per se. Our findings may help ophthalmologists in assessing ocular dimensions in premature infants conceived by IVF.
| Acknowledgements |
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Disclosure: R. Axer-Siegel, None; D. Bourla, None; L. Sirota, None; D. Weinberger, None; M. Snir, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C.
1734 solely to indicate this fact.
Corresponding author: Ruth Axer-Siegel, Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49 100, Israel; seegs{at}netvision.net.il.
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