Journal of Pediatric Ophthalmology and Strabismus

Original Article 

Effect of Age at Primary Intraocular Lens Implantation on Refractive Growth in Young Children

Adrianna E. Eder, MD; Kyle F. Cox, MD; T. Amerson Pegram, MD; Scott M. Barb, MD; Mary Ellen Hoehn, MD; Natalie C. Kerr, MD

Abstract

Purpose:

To evaluate the effect of age at primary intraocular lens (IOL) implantation on rate of refractive growth (RRG3) during childhood.

Methods:

A retrospective chart review was performed for children undergoing primary IOL implantation during cataract surgery. RRG3 was calculated for one eye from each patient using the first postoperative refraction, last refraction that remained stable (< 1.00 diopters [D] change/2 years), and the corresponding ages. RRG3 values for pseudophakic patients operated on from ages 0 to 5 months were compared with values for patients operated on at ages 6 to 23 months and 24 to 72 months. Patients with refractive errors that stabilized were grouped by age at surgery to compare age at refractive plateau.

Results:

Of 296 eyes identified from 219 patients, 46 eyes met the inclusion criteria. There was a statistically significant difference in RRG3 among age groups. The mean RRG3 value was −19.82 ± 5.23 D for the 0 to 5 months group, −22.32 ± 7.45 D for the 6 to 23 months group (0 to 5 months vs 6 to 23 months, P = .43), and −9.64 ± 11.95 D for the 24 to 72 months group (0 to 5 months vs 24 to 72 months, P = .01).

Conclusions:

Age at primary IOL implantation affects the RRG3, especially for children 0 to 23 months old at surgery. Surgeons performing primary IOL implantation in infants may want to use age-adjusted assumptions, because faster refractive growth rates can be expected in young children.

[J Pediatr Ophthalmol Strabismus. 2020;57(4):264–270.]

Abstract

Purpose:

To evaluate the effect of age at primary intraocular lens (IOL) implantation on rate of refractive growth (RRG3) during childhood.

Methods:

A retrospective chart review was performed for children undergoing primary IOL implantation during cataract surgery. RRG3 was calculated for one eye from each patient using the first postoperative refraction, last refraction that remained stable (< 1.00 diopters [D] change/2 years), and the corresponding ages. RRG3 values for pseudophakic patients operated on from ages 0 to 5 months were compared with values for patients operated on at ages 6 to 23 months and 24 to 72 months. Patients with refractive errors that stabilized were grouped by age at surgery to compare age at refractive plateau.

Results:

Of 296 eyes identified from 219 patients, 46 eyes met the inclusion criteria. There was a statistically significant difference in RRG3 among age groups. The mean RRG3 value was −19.82 ± 5.23 D for the 0 to 5 months group, −22.32 ± 7.45 D for the 6 to 23 months group (0 to 5 months vs 6 to 23 months, P = .43), and −9.64 ± 11.95 D for the 24 to 72 months group (0 to 5 months vs 24 to 72 months, P = .01).

Conclusions:

Age at primary IOL implantation affects the RRG3, especially for children 0 to 23 months old at surgery. Surgeons performing primary IOL implantation in infants may want to use age-adjusted assumptions, because faster refractive growth rates can be expected in young children.

[J Pediatr Ophthalmol Strabismus. 2020;57(4):264–270.]

Introduction

Understanding refractive growth of the pseudo-phakic eye during childhood is important for selecting the best intraocular lens (IOL) power at the time of implantation in children and also affects the decision of whether to perform primary IOL implantation versus secondary IOL implantation. Refractive development of the normal human eye has been well documented.1,2 The emmetropization process of the unoperated eye ensures that there is minimal myopic shift during growth of the eye. However, refractive development of the aphakic or pseudophakic eye demonstrates much greater myopic shift associated with loss of the natural lens.3–10

Numerous studies suggest growth and refractive development follow a logarithmic curve in humans with the natural lens removed.4,5,11,12 This logarithmic curve is due mostly to decreases in corneal power and axial length elongation of the eye, which change at a much greater rate in earlier stages of development. Therefore, measurement of the absolute quantity of myopic shift in developing children with IOL implantation is confounded by variable age at implantation and follow-up time.4

In an attempt to accurately model refractive development, McClatchey and Parks,4 McClatchey and Hofmeister,9 and Whitmer et al13 developed a semi-logarithmic model defining rate of refractive growth (RRG3) as the slope of the aphakic refraction at the natural lens plane divided by the logarithm of the age plus 0.6 years, to account for ocular growth in utero. RRG3 removes bias in the youngest patients, making this formula independent of age of surgery and thus applicable to patients of all ages. In simpler terms, RRG3 tells us the expected change in diopters of IOL power (ie, the myopic shift at the IOL plane) needed to maintain emmetropia over the course of increasing patient age using the following formula:

RRG3=Final Adjusted Aphakic Equivalent Refraction-Initial Adjusted Aphakic Equivalent Refractionlog(Age at Final Refraction +0.6 year)-log (Age at Initial Refraction+0.6 year)

Because this formula takes into account the first and last postoperative refractions, there is no need for a uniform follow-up period or uniform cutoff age. Although Whitmer et al,13 found that aphakic and pseudophakic eyes from the Infant Aphakia Treatment Study (IATS) had similar RRG3, few other studies have been conducted analyzing the effect of cataract surgery with primary IOL implantation on refractive growth in children younger than 6 months.3,4,9,14,15

Patients and Methods

A retrospective chart review was performed for children undergoing primary IOL implantation at the time of cataract removal surgery by two ophthalmologists (MEH and NCK) at two tertiary care pediatric ophthalmology practices, Hamilton Eye Institute and St. Jude Children's Research Hospital, between 1999 and 2016. All children undergoing surgery during this time period were reviewed for inclusion in the study. This study was approved by the Institutional Review Boards of both the University of Tennessee Health Science Center (of which Hamilton Eye Institute is a part) and St. Jude Children's Research Hospital and conformed to the requirements of the United States Health Insurance Portability and Privacy Act.

Patients were excluded if they had secondary IOL implantation, poor postoperative compliance with follow-up visits, less than 35 months of refractive error follow-up, a delay of more than 3 months between surgery and first postoperative follow-up visit, had congenital or infantile glaucoma prior to surgery, or were older than 6 years at time of implantation. Patients were not matched for gender or age. In cases of bilateral surgery, only data from the right eye were included in the study.

Preoperative and operative data included patient identification number, date of birth, gender, preoperative diagnosis or etiology of cataract, laterality of cataract(s), family history, preoperative refraction, and date of IOL implantation. Postoperative data included length of follow-up, refraction at each postoperative visit, any postoperative complications of surgery, and ocular conditions that developed after surgery (nystagmus, posterior capsular opacity, or glaucoma). Presence of postoperative glaucoma was determined by assessment of whether a diagnosis code for glaucoma with corresponding elevated intraocular pressure appeared in the chart. IOL power and A-constant determinations were made by the primary surgeon at the time of implantation.

Patients were divided into subgroups based on age at primary IOL implantation: 0 to 5 months, 6 to 23 months, and 24 to 72 months. These groupings were based on those previously used in studies of refractive growth after cataract surgery. Postoperative pseudophakic refractions were made by retinoscopy and/or manifest refraction and were measured in the spectacle plane by the primary surgeon at each follow-up visit.

Each patient's IOL power required for emmetropia and the expected refractive error at the time of implantation was calculated using axial length, horizontal and vertical keratometry readings, and A-constant for the IOL. The power required for emmetropia was compared to the power of the implanted lens within each age group, whereas the expected refractive error for the implanted IOL was compared to the initial postoperative refraction within each age group. Average change in pseudophakic refraction in diopters per year (D/year) was calculated for each group for the age range shared with the adjacent group, to allow comparison between groups. The age at which the patient's refractive error plateaued was defined as less than 1.00 diopter of change over at least a 2-year period. The age at refractive plateau was recorded and compared between groups. Statistical significance was determined using a two-tailed t test assuming equal variance.

The RRG3 was calculated using a spreadsheet, courtesy of Dr. Scott McClatchey, MD, and included age at surgery, initial refraction, age at initial refraction, refraction plateau (< 1.00 diopter change/2 years), age at refraction plateau, IOL power, and A-constant. RRG3 values for each patient group were compared via two-tailed t test assuming equal variance and also with the Mann-Whitney U test, which can be useful with small sample sizes.

Results

Of 296 eyes identified from 219 patients, 46 eyes met the inclusion criteria (28 with unilateral and 18 bilateral cataracts (Table 1). The ages of children in our data series ranged from 1 to 72 months at time of surgery. The mean age of all patients was 35 months at surgery. Average follow-up time was 108.10 ± 51.23 months (range = 43 to 170 months) for the 0 to 5 months group, 108.15 ± 69.12 months (range = 45 to 226 months) for the 6 to 23 months group, and 103.85 ± 54.15 months (range = 35 to 218 months) for the 24 to 72 months group. There was no significant difference between the average length of follow-up between the three age groups (P = .83 to .99). The average age at final refraction was 8.44 years for the 0 to 5 months group, 9.00 years for the 6 to 23 months group, and 11.06 years for the 24 to 72 months group. The 0 to 5 months group had the largest proportion of postoperative glaucoma (0.30), whereas the 24 to 72 months group had the smallest proportion (0.14). The 0 to 5 months group had the highest average number of surgeries in the first postoperative year (1.70), whereas the 24 to 72 months group had the lowest (0.61). Comparing the average number of surgeries in the first postoperative year of the 0 to 5 months and 6 to 23 months groups with the 24 to 72 months group was statistically significant (0 to 5 vs 6 to 23 months, P = .76; 0 to 5 vs 24 to 72 months, P = .005; 6 to 23 vs 24 to 72 months, P = .003).

Patient Characteristics

Table 1:

Patient Characteristics

No difference was seen in change in pseudophakic refraction per year between similarly aged groups (Table 2). The change in refraction per year in the 0 to 6 months group was similar to that in the 6 to 23 months group when only refractions from overlapping ranges of age were compared (P = .09). The same applied for comparison of the 6 to 23 months group to the 24 to 72 months group (P = .53). A total of 7 patients were excluded from this test due to refractions that fell outside of the specified time frame.

Comparison of Change in Pseudophakic Refraction (D) per Year Between Age Groups

Table 2:

Comparison of Change in Pseudophakic Refraction (D) per Year Between Age Groups

Table 3 shows the IOL power required for emmetropia versus the power of IOL implanted in each age group. Table 3 also shows the expected refractive error, predicted by the appropriate biometric IOL formula using A-scan measurements, versus the initial refractive error. The Theoretic-T formula was used in the majority of patients, but a small minority of IOL calculations were done with the SRK II and Regression II formulas. The difference between expected refractive error versus actual initial refractive error was, on average, 1.20 D for all age groups. The average age refractive error plateau was 8.34 ± 1.31 in the 0 to 5 months group, 14.14 ± 1.08 in the 6 to 23 months group, and 10.75 ± 4.02 in the 24 to 72 months group. The 0 to 5 months and 6 to 23 months groups only had 2 patients meeting plateau criteria.

Comparison of IOL Power Required for Emmetropia Versus Power of IOL Implanted and Expected Versus Initial Refractive Error Between Age Groups

Table 3:

Comparison of IOL Power Required for Emmetropia Versus Power of IOL Implanted and Expected Versus Initial Refractive Error Between Age Groups

A total of 5 patients were excluded from our RRG3 analysis. Two of these patients had less than 1.00 diopter change in refractive error from their initial refraction, and thus the age of refractive plateau was equal to the age of initial refraction. When this occurs, the denominator of the RRG3 formula is zero. An outlier analysis showed that the RRG3 values from 3 patients (two from the 24 to 72 months group and one from the 6 to 23 months group) were outliers, and these values were excluded from statistical analysis. The average time between surgery and the first postoperative refraction was 33 days in the 0 to 5 months group and 104 days in both the 6 to 23 and 24 to 72 months groups. There was a statistically significant difference in RRG3 among pseudophakic groups. For the 0 to 5 months group, the mean RRG3 value was −19.82 ± 5.23. The mean RRG3 value was −22.32 ± 7.45 for the 6 to 23 months group (0 to 5 vs 6 to 23 months, P = .43) and −9.64 ± 11.95 for the 24 to 72 months group (0 to 5 vs 6 to 23 months, P = .01). There was not a statistically significant difference when comparing RRG3 between those who developed postoperative glaucoma and those who did not within each age group (data not shown). A Mann-Whitney U test comparison between the three groups yielded similar results (Table 4).

Comparison of RRG3 Between Age Groups

Table 4:

Comparison of RRG3 Between Age Groups

Discussion

The purpose of our study was to validate the presupposition that age at IOL implantation does not change refractive growth rate for the youngest of patients. To best assess expected growth of a child's pseudophakic eye, use of a logarithmic model such as RRG3 is helpful due to its ability to eliminate confounding variables associated with non-linear refractive changes and IOL variation among patients. The use of these logarithmic models in pseudophakic patients relies largely on one assumption: that natural growth of the eye is not affected by the IOL implantation itself when compared to aphakia. In 2016, Lambert et al15 attempted to prove this assumption using the IATS patient population. They found that aphakic and pseudophakic eyes had similar RRG3 after unilateral surgery during the first 5 years of life.

The IATS also found that leaving infants younger than 6 months old aphakic results in lower reoperation rates with similar outcomes. Our study also confirms this finding, because the average number of operations within the first year of primary IOL implantation decreased as the age at surgery increased. However, a statistically significant decrease in reoperation rates did not occur until after 2 years of age.

Some, but not all, of our RRG3 results were similar to those seen by Whitmer et al13 and Lambert et al15 in their RRG3 studies. Whitmer et al's 2013 study divided patients (both pseudophakic and aphakic) into two age groups, not three as was done in our study. These groups were children younger than 6 months at the time of surgery and those 6 months or older at the time of surgery. Analyzed in the same manner, our older patients (average of the 6 to 23 and 24 to 72 months groups, n = 31) had a slightly less negative mean RRG3 value: −13.00 ± 12.00 vs −14.00 ± 7.00 D for the older pseudophakic patients in their study. However, our results for the younger age group (younger than 6 months old at surgery) were different: −20.00 ± 5.00 vs −11.00 ± 4.00 D in their study. Interestingly, the analysis of Lambert et al15 done in 2016 of RRG3 with the IATS cohort revealed RRG3 values more comparable to our 0 to 5 months group RRG3 values: −20.00 ± 5.00 vs −19.00 ± 9.00 D in their study. This study also commented on the effect of glaucoma on RRG3. Previous studies have documented that uncontrolled glaucoma is a known cause of axial elongation in young children,16,17 but Lambert et al15 only found an upward trend, not a correlation, of RRG3 in patients with glaucoma or glaucoma suspect status. Importantly, in our study, the largest proportions of patients with postoperative glaucoma were in the 0 to 5 and 6 to 23 months groups, with 30% and 25% developing postoperative glaucoma, respectively. These two groups also had significantly more negative RRG3 values than the 24 to 72 months group, but whether this is a correlation will require further study with a larger patient population.

Of particular note, the RRG3 values of Whitmer et al13 became more negative (faster growth rate) with increasing age (albeit without statistical significance), whereas ours became less negative (slower growth rate) with increasing age (with statistical significance). Although standard deviations were large, none of our youngest patients (those in the 0 to 5 months group) had RRG3 values approaching the mean (−11.00 D) seen in their study, because our least negative value was −14.00 D. Moreover, in our study, the 24 to 72 months group had the least negative RRG3 value (−10.00 ± 12.00 D) and this was statistically significant when compared to both the 0 to 5 and 6 to 23 months groups (P = .01 and .01, respectively). This finding is noteworthy because we had comparable follow-up with the 2013 study by Whitmer et al13 (8.8 vs 9.5 years) but a slower rate of refractive growth in older age groups when the refractive plateau and corresponding date were used in the RRG3 formula. Using the age of the refractive plateau instead of the final refraction removes years of static refractive growth in the pediatric eye from the RRG3 formula and should give a more accurate growth rate.

Secondary outcomes from this study aimed to evaluate and compare change in pseudophakic refraction per year and the age of plateau in refractive error between age groups. The change in pseudo-phakic refraction per year was not statistically different between age groups, but did show a trend of decreasing rate with increasing age.

Weakley et al18 and the IATS group recently published data showing the rate of myopic shift in the first 5 years after IOL implantation in infants 0 to 5 months old. Their study did not involve children undergoing IOL implantation at different age ranges, only infants comparable to our 0 to 5 months group. Although RRG3 values do not appear to have been calculated, their estimated rates of refractive change per year compare favorably with those in our study. As shown in Table 2, our average change in refraction per year for infants younger than 5 months at IOL placement (the 0 to 5 months group) was −5.79 ± 2.09 D/year when refractive data from 6 to 23 months of age were used. Weakley et al found a refractive change of 4.19 D/year (95% CI = −3.53 to −4.85 D/year), measuring refractive error in infants through 18 months of age.

Of note, we used contact A-scan technique, rather than immersion, and the difference in the expected refractive error given the IOL implanted compared to the initial postoperative refractive error was less than 0.50 D in children younger than 2 years and less than 1.20 D in children older than 2 years.19 Previous studies have suggested that error is induced by contact methods, but we did not find that to be a significant issue.

The current study was most limited by the number of patients in the younger aged cohorts (0 to 5 months and 6 to 23 months). Because primary IOL implantation is more common in older rather than younger children, our 24 to 72 months age group was disproportionately larger. As a retrospective chart review, some of the data were not uniformly gathered and the eyes were not randomized. Another limitation of our study was the large variances seen in refractive change in developing eyes and in individual measurements of refraction. The effect of these variances is reduced by the long follow-up period, but large standard deviations still resulted. Similar large variances were seen in previous studies using RRG21,3–9 and RRG3.13,15 The current study was also limited by the lack of our own aphakic patient group for comparison, because leaving patients aphakic following cataract extraction is not a current practice for the study surgeons. However, leaving infants aphakic has been practiced and recommended by other surgeons and the IATS group.20

Our study found a significant difference in rate of refractive growth attributable to IOL implantation in children younger than 2 years old. Knowing this allows ophthalmologists to more accurately choose appropriate IOL powers for their infant patients with cataract, promising the best long-term visual outcomes. Based on the large standard deviations in RRG3 seen in this study, and the statistical significance reached, surgeons performing primary IOL implantation on infants may want to use age-adjusted assumptions. Importantly, a more negative RRG3 (faster growth rate) might be expected initially. It follows that leaving the eye hyperopic after surgery will often reduce the need for large amounts of myopic spectacle correction as the child ages.

References

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  14. Weakley DR, Lynn MJ, VanderVeen DK, et al. Refractive change after intraocular lens implantation: three year follow-up from the Infant Aphakia Treatment Study. Poster presented at the annual meeting of the American Academy of Ophthalmology. , New Orleans, LA. ; November 2013. .
  15. Lambert SR, Cotsonis G, DuBois L, et al. Infant Aphakia Treatment Study Group. Comparison of the rate of refractive growth in aphakic eyes versus pseudophakic eyes in the Infant Aphakia Treatment Study. J Cataract Refract Surg. 2016;42(12):1768–1773. doi:10.1016/j.jcrs.2016.09.021 [CrossRef]
  16. Kugelberg U, Zetterstrom C, Lundgren B, Syrén-Nordqvist S. Ocular growth in newborn rabbit eyes implanted with a poly or silicone IOL. J Cataract Refract Surg. 1997;23:629–634. doi:10.1016/S0886-3350(97)80045-4 [CrossRef]
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  20. Lambert SR, Lynn MJ, Hartmann EE, et al. Infant Aphakia Treatment Study Group. Comparison of contact lens and intraocular lens correction of monocular aphakia during infancy: a randomized clinical trial of HOTV optotype acuity at age 4.5 years and clinical findings at age 5 years. JAMA Ophthalmol. 2014;132(6):676–682. doi:10.1001/jamaophthalmol.2014.531 [CrossRef]

Patient Characteristics

GroupNo. of PatientsRange of Age at Implantation (Months)Average Age at Implantation (Months)Average Length of Refractive Follow-up (Months)Average Age at Final Refraction (Years)Unilateral/Bilateral (No. of Patients)Etiology of Cataract (No. of Patients)Proportion With Postoperative GlaucomaAverage No. of Procedure Events (<1 Year From IOL implant)
0 to 5 months101 to 52.911088.447/3Trauma (0); congenital (10)0.30 (3/10)1.70
6 to 23 months87 to 2312.251089.006/2Trauma (2); congenital (6)0.25 (2/8)1.50
24 to 72 months2833 to 7252.4310411.0615/13Trauma (6); congenital (22)0.14 (4/28)0.61
Total461 to 7234.681069.5028/18Trauma (8); congenital (38)0.20 (9/46)1.27

Comparison of Change in Pseudophakic Refraction (D) per Year Between Age Groups

GroupAverage Change in Refraction per Year (D/year ± SD)P
0 to 5 months – refracted between 6 & 24 months (n = 9)−5.79 ± 2.09.09
6 to 23 months – refracted between 6 & 24 months (n = 6)−2.76 ± 4.30
6 to 23 months – refracted between 2 & 6 years (n = 7)−1.16 ± 0.40.53
12 to 24 months – refracted between 2 & 6 years (n = 23)−0.04 ± 4.59

Comparison of IOL Power Required for Emmetropia Versus Power of IOL Implanted and Expected Versus Initial Refractive Error Between Age Groups

GroupPower for Emmetropia (D ± SD)Power IOL Implanted (D ± SD)Expected Refractive Error (D ± SD)Initial Refractive Error (D ± SD)|Expected D| – |Initial D| (D)
0 to 5 months (n = 10)35.61 ± 3.9529.30 ± 1.23+4.39 ± 2.41+4.20 ± 3.110.19
6 to 23 months (n = 6)27.69 ± 7.8924.75 ± 4.99+2.21 ± 2.39+1.71 ± 2.940.50
24 to 72 months (n = 26)a24.42 ± 5.3122.84 ± 4.68+1.19 ± 1.67−0.01 ± 2.411.18

Comparison of RRG3 Between Age Groups

GroupRRG3 (D ± SD)t test P ValueMann-Whitney U Test; P Value
0 to 5 months (n = 10)−19.82 ± 5.230 to 5 vs 6 to 23 months: .430 to 5 vs 6 to 23 months: U = 26; P = .38
6 to 23 months (n = 7)−22.32 ± 7.456 to 23 vs 24 to 72 months: .01a6 to 23 vs 24 to 72 months: U = 27; P = .01a
24 to 72 months (n = 24)−9.64 ± 11.950 to 5 vs 24 to 72 months: .01a0 to 5 vs 24 to 72 months: U = 54; P = .01a
Authors

From University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee (AEE); Tomoka Eye, Ormond Beach, Florida (KFC); Southeast Eye Specialists, Nashville, Tennessee (TAP); Southeastern Retina Associates, Knoxville, Tennessee (SMB); Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee, Memphis, Tennessee (MEH, NCK); St. Jude Children's Research Hospital, Memphis, Tennessee (MEH, NCK); Le Bonheur Children's Hospital, Memphis, Tennessee (MEH, NCK).

Supported in part by an unrestricted grant from Research to Prevent Blindness.

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Adrianna E. Eder, MD, 930 Madison Avenue, Suite 470, Memphis, TN 38163. Email: aeder2@uthsc.edu

Received: February 04, 2020
Accepted: April 14, 2020

10.3928/01913913-20200504-01

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