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The Effect of Age on the Retardation of Axial Elongation Following a Lensectomy in Infant Monkeys
Scott R. Lambert, MD
Arch Ophthalmol. 1998;116:781-784.
ABSTRACT
Objective To determine the effect of age on the retardation of axial elongation in neonatal monkey eyes following the extraction of the crystalline lens.
Methods A monocular lensectomy was performed on 4 rhesus monkeys when they were 4 days, 2 weeks, 7.5 months, and 1 year of age. Longitudinal measurements of axial lengths and keratometry readings were made.
Results The aphakic eye was 1.7 mm shorter than the unmanipulated fellow eye in the monkey undergoing surgery at 4 days of age and 1.1 mm shorter in the monkey undergoing surgery at 2 weeks of age. However, the aphakic eyes were only 0.2 mm and 0.1 mm shorter than their unmanipulated fellow eyes, respectively, in the monkeys undergoing surgery at 7.5 months and 1 year of age.
Conclusions The retardation of axial elongation following a lensectomy in infantile monkey eyes is age dependent. Little effect is observed in monkeys aged 7.5 months or older.
INTRODUCTION
BOTH RABBIT and monkey models have been used to show that removing the crystalline lens during infancy retards axial elongation.1-4 Indirect evidence also suggests that this effect occurs in children, although this has not been studied in a controlled fashion.5-6 Any change in the rate of axial elongation would have important clinical implications for eyes corrected optically with intraocular lenses, because this would result in a reduction in the myopic shift that occurs in growing eyes.7-8 Although the mechanism whereby axial elongation is retarded following a lensectomy has not been established, it occurs regardless of whether an eye is left aphakic or corrected optically.3 Preliminary results suggest that the effect may be mediated by changes in the intraocular levels of certain growth factors.9
The age at which a lensectomy will no longer retard axial elongation has not been established in either a rabbit or monkey model. Because 95% of axial elongation occurs during the first 6 years of life,10-11 it seems likely that this effect would be more pronounced if the lens is removed during early childhood. Using a monkey model, we evaluated the effect on axial growth of removing the crystalline lens at different time points during the first year of life.
MATERIALS AND METHODS
Four rhesus monkeys, ranging in age from 4 days to 51 weeks, underwent a unilateral lensectomy at the Yerkes Regional Primate Research Center, Atlanta, Ga. The operations were all performed under sterile conditions while the monkeys were deeply anesthetized. Preoperatively, biomicroscopy, biometry, keratometry, applanation tonometry, retinoscopy, and ophthalmoscopy were performed on each monkey. Two monkeys (RGN5 and ROW5) wore a plano hydroxyethylmethacrylate contact lens (LM77VP, 77% water content, Lamda Polytech Ltd, Northants, England) on their right eye for 26 and 30 weeks, respectively, prior to being enrolled in this trial. All procedures were performed in compliance with the Association for Research in Vision and Ophthalmology statement on the Use of Animals in Ophthalmic and Vision Research and approved by the Nonhuman Primate subcommittee of the Institutional Animal Care and Use Committee of Emory University, Atlanta.
LENSECTOMY
The crystalline lens was removed from the right eye of all 4 monkeys using a limbal approach when the monkeys were 4 days to 1 year of age (Table 1). After creating small conjunctival peritomies superiorly, 2 stab incisions were made into the anterior chamber at the 2- and 10-o'clock positions. The anterior chamber was then infused through 1 stab incision with isotonic saline solution (BSS Plus, Alcon Laboratories, Fort Worth, Tex) combined with 1-mg/mL adrenaline chloride and 5-U/mL low-molecular-weight heparin (Fragmin, Kabi Pharmacia, Stockholm, Sweden). After filling the anterior chamber with sodium hyaluronate (Kabi Pharmacia Ophthalmics, Monrovia, Calif), a vitreous cutting instrument (Ocutome II, model 8000, Cooper Medical Sources Co, San Leandro, Calif) was inserted through the second stab incision. It was then used to create a 5- to 6-mm anterior capsulotomy, aspirate the lens cortex, create a 5- to 6-mm posterior capsulotomy, and remove the anterior vitreous. The stab incisions were then closed with 9-0 polyglactin 910 (Vicryl, Ethicon Inc, Sommerville, NJ) sutures. Finally, 1 mg of dexamethasone sodium phosphate was injected subconjunctivally. Postoperatively, the aphakic eyes were treated for 2 weeks with topical polymyxin B sulfate and dexamethasone drops.
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Table 1. Longitudinal Changes in Axial Length Measurements
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EXAMINATIONS UNDER ANESTHESIA
Ophthalmic examinations were performed weekly or biweekly on each monkey while they were sedated with intramuscularly administered ketamine hydrochloride and acepromazine maleate. Each examination included biomicroscopy, biometry, keratometry, applanation tonometry, retinoscopy, and ophthalmoscopy. Biometry was performed using a Sonomed (Lake Success, NY) A-1000 unit fitted with a short-focal-length crystal and modified software developed for the small, steep eyes of these monkeys. Tissue velocity settings were 1550 m/s for the phakic eyes and 1532 m/s for the aphakic eyes. Ten axial length measurements were obtained from each eye and averaged. Keratometry was performed using a handheld keratometer (Alcon Renaissance, Alcon Laboratories). Three measurements were obtained from each eye and then averaged. Retinoscopy was performed 30 minutes after instilling a drop of 1% cyclopentolate hydrochloride and 2.5% phenylephrine hydrochloride using handheld lenses at a vertex distance of approximately 1 cm.
RESULTS
One week after lensectomy, the aphakic eye of the monkey undergoing surgery at 4 days of age (RZA6) was 0.4 mm shorter than its unmanipulated fellow eye (Figure 1, A). Whereas the fellow eye continued to grow normally during the next month, the aphakic eye of RZA6 essentially stopped elongating after the first postoperative week, resulting in an axial length difference between the 2 eyes of 1.7 mm at the end of the 5-week follow-up. The interocular axial length difference was even greater 1 week after surgery for the monkey undergoing surgery at 13 days of age (RGZ5). However, unlike RZA6, the aphakic eye of RGZ5 continued to elongate, albeit at a slower rate than the fellow eye, during the course of the next 6 weeks (Figure 1, B). Whereas the aphakic eye of RZA6 only elongated 0.7 mm during a 5-week interval, vs 2.4 mm for its unmanipulated fellow eye, the aphakic eye of RGZ5 elongated 1.5 mm, vs 2.6 mm for its unmanipulated fellow eye, during a 6-week follow-up interval. As a result, while there was a large difference in the axial lengths of the aphakic and unmanipulated eye of RGZ5 at the end of the follow-up interval (1.1 mm), it was less than the difference for RZA6 (1.7 mm), suggesting that removing the crystalline lens at 4 days of age retards axial elongation more than removing the lens at 13 days of age.
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Axial length plotted against age for the right and left eyes of monkeys RZA6 (A), RGZ5 (B), ROW5 (C), and RGN5 (D). The arrow indicates the age at which a lensectomy was performed on the right eye.
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Both ROW5 and RGN5 were beyond the age when monkey eyes undergo rapid axial elongation when they had the crystalline lens removed from their right eyes. Therefore, it was not surprising that neither monkey experienced much axial elongation in either their unmanipulated (0.4 and 0.3 mm) or aphakic (0.3 and 0.2 mm) eyes during the 14 and 18 weeks they were followed up postoperatively (Figure 1, C and D). While the aphakic eyes were slightly shorter at the end of the trial for both animals (0.1 and 0.2 mm), the difference was sufficiently small that it is uncertain whether this represented a real effect or a measurement artifact.
There was no consistent effect of a lensectomy on the keratometry readings for the 4 monkeys. The interocular keratometry differences were small for all 4 monkeys prior to surgery and the keratometry readings were similar for both eyes at the end of the trial. While 2 of the monkeys had slightly steeper corneas in their aphakic eyes, the other 2 monkeys had slightly flatter corneas in their aphakic eyes at the end of the trial (Table 2).
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Table 2. Longitudinal Changes in Keratometry Readings*
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The interocular intraocular pressure difference was 2 mm Hg or less for all 4 monkeys prior to surgery and throughout the trial. The interocular difference in refractive errors was 0.5 diopters (D) or less for all 4 monkeys preoperatively. At the end of the trial, the refractive errors for the unmanipulated eyes were 0.5 D or less for all 4 monkeys, whereas the refractive errors for the aphakic eyes ranged from 21 to 27 D.
COMMENT
These data suggest that axial elongation is retarded if the crystalline lens is removed during the first 2 weeks of a monkey's life. Little if any effect on axial growth was noted if the lens was removed at 7.5 months of age or later. Because monkeys mature approximately 4 times more rapidly than humans, a 2-week-old monkey would be equivalent to an 8-week-old infant and a 7.5-month-old monkey to a 2 -year-old child.12 If this same effect occurs in human infants, it would be expected that less axial growth would occur in a human eye if the lens is removed during the first 2 months of life but not after 2 years of age. We have not established at what intermediate time point this effect may stop occurring.
It would be nearly impossible to perform a similar study in human infants because of the difficulty of obtaining serial axial length measurements and the many confounding variables usually present in eyes with congenital cataracts, including microphthalmos, glaucoma, and preexisting amblyopia. Nonetheless, the few reports that have been published on this subject suggest that a similar effect may occur after neonatal cataract extraction in humans. Manzitti and coworkers11 reported that the axial lengths of eyes with bilateral complete cataracts that underwent early cataract extraction were shorter than the eyes of age-matched controls. Lorenz and coworkers13 also noted that the difference between axial lengths of the eyes of children with bilateral congenital cataracts who underwent cataract surgery during the first 6 months of life and age-matched controls increased throughout early childhood. On the other hand, Rasooly and BenEzra14 noted no difference in the mean axial length (23.3 ± 0.37 mm) of 14 children who underwent bilateral cataract surgery at a mean age of 8 months compared with 8 children with bilateral partial cataracts who did not undergo cataract surgery (23.1 ± 0.3 mm) after a mean follow-up of 9.6 and 11.4 years, respectively. A difference may not have been noted in the axial elongation of these children's eyes compared with the children reported in the 2 previous studies11, 13 owing to the older age of the children in the Rasooly and BenEzra study at the time of cataract surgery. While other studies have compared the axial lengths of aphakic and fellow eyes following unilateral cataract surgery, these studies are confounded by the dense amblyopia often present in the aphakic eyes.13 In addition, many of these aphakic eyes were longer than their fellow eyes preoperatively.
Our study has certain limitations. First, only one eye was studied at each time point. While ideally several monkeys would have been studied at each time point, we have noted a fairly consistent effect of a lensectomy on axial growth in a larger series of monkeys in the past3; the size of the current study was limited because of the scarcity of monkeys. Second, only 4 time points were studied. It would be helpful to establish at what time point between 2 weeks and 7.5 months a lens extraction no longer affects axial elongation. Third, none of the aphakic eyes were corrected optically. We chose not to correct these eyes optically because we were unable to demonstrate in earlier trials that an optical correction with either a contact lens or an intraocular lens altered axial growth.3 Nonetheless, some authors have hypothesized that amblyopia results in excessive axial elongation in children.14-15 While emmetropization can be altered by defocusing an eye, the effect is most pronounced with a small degree of defocus.16 Large amounts of defocus do not seem to have a consistent effect on axial growth. It is likely that the large degree of defocus of the monkeys in this study (20-30 D) exceeded the threshold for visually directed changes in ocular growth. Finally, our study examined the effect of a lensectomy on a normal infantile eye. The effect may be different on an eye with a congenital cataract, either because of intrinsic differences in the growth patterns of these eyes or the effect of a lens opacity on ocular growth.
Our findings would suggest that if cataract extraction is performed early in infancy, axial elongation may be retarded. Because intraocular lenses are being increasingly implanted in infant eyes following cataract surgery,6, 15, 17-20 these findings have important clinical implications. Assuming this effect also occurs in human infants, it would suggest that the myopic shift occurring in infantile eyes following cataract surgery13, 21-22 is less than would occur if axial growth was normal in these eyes. As a corollary, it would seem to be inappropriate to implant the same power of intraocular lens in an infantile eye after cataract surgery as would be appropriate for an adult under the assumption that these eyes will achieve a normal axial length when these patients are older.
AUTHOR INFORMATION
Accepted for publication February 11, 1998.
This work was supported in part by grants EY08544 and P30 EY06360 from the National Institutes of Health and a departmental grant and a Lew Wasserman Merit Award from Research to Prevent Blindness Inc, New York, NY.
I thank Alcides Fernandes, MD, Tracy Louden, and Alicia Izquierdo for their assistance with this project.
Reprints: Scott R. Lambert, MD, Emory Eye Center, Emory University School of Medicine, 1365-B Clifton Rd NE, Suite B4610, Atlanta, GA 30322 (e-mail: slamber{at}emory.edu)
From the Yerkes Regional Primate Research Center and Emory Eye Center, Emory University School of Medicine, Atlanta, Ga.
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