Myopic Shift at 10 Years Follow-up in the Infant Aphakia Treatment Study

Abstract

We studied the myopic shift and anisometropia at 10.6 (+/−0.3) years of age in the Infant Aphakia Treatment Study. We found myopic shift continues in the operated eye from 5-10.5 years at a lower rate than that prior to age five years while anisometropia increases proportionally.

The Infant Aphakia Treatment Study (IATS) is a randomized clinical trial initially designed to compare outcomes in infants under seven months of age who underwent primary implantation of an intraocular lens (IOL) versus being left aphakic and receiving a contact lens correction following cataract surgery in infancy.¹ Patients were enrolled from 2004 through 2009 with the last 10-year follow-up exam completed in 2019. The study design was approved by the institutional review boards of the 12 participating sites and followed the tenets of the Declaration of Helsinki. The off-label use of the AcrySof SN60AT and MA60AC IOLs (Alcon Laboratories, Fort Worth Tx.) was covered under the United States Food and Drug Administration investigational device exemption. The trial is registered at www.ClinicalTrials.gov (identifier, NCT00212134).

In patients randomized to IOL implantation, IOL power was calculated using the Holladay 1 formula with the initial goal of 8 diopters (D) of residual hypermetropia in infants aged 28 to<48 days, and 6 D in infants 48-210 days to offset anticipated eye growth and myopic shift.² We previously reported myopic shift and anisometropia in the children randomized to IOL correction up to age five years.^3,4 The rate of myopic shift prior to age five years was found to be bimodal in nature with a mean rate of 4.12 D/year until age 18 months decreasing to a mean rate of 0.97 D/year from age 18 months to five years. We calculated an overall mean myopic shift of 8.97 D by age five if the IOL was implanted at age one month and 7.22 D if implanted at age six months.³ The median level of anisometropia at the 5-year follow-up visit was −2.75 D in non-glaucomatous eyes and −8.25 D in eyes with glaucoma.⁴

The purpose of this report is to describe the additional myopic shift between the 5- and 10-year follow-up examinations in these eyes as well as the degree of anisometropia present at the 10-year follow-up examination.

Patients who developed glaucoma were analyzed separately at both the 5- and 10-year follow-up examinations. Glaucoma was defined as IOP >21 mmHg with one or more of the following anatomical changes: 1) corneal enlargement; 2) asymmetrical progressive myopic shift coupled with enlargement of the corneal diameter and/or axial length; 3) increased optic nerve cupping defined as an increase of ≥ 0.2 in the cup-to-disc ratio, or 4) the use of a surgical procedure for IOP control.

The overall mean change in refractive error between the 5- and 10-year follow-up exams and mean annual change were compared for patients with and without glaucoma using a two-sample t-test. Wilcoxon’s Rank Sum test was used to compare the median amount of anisometropia at 10.5 years for patients with and without glaucoma. A multivariable linear regression with Gaussian errors was used to model the relationship between the change in refractive errors and baseline characteristics, including age at surgery (years), axial length (mm), average keratometry (D), and IOL power implanted (D). However, given that the sample size was not based upon assessing these associations in a multivariable model the results should not be considered definitive. SAS software (version 9.4, SAS Institute, Cary, NC) was used to perform all analyses.

The original IATS randomized 114 infants (57 each to CL and IOL): 110 completed clinical examination at approximately ten years after surgery (mean age 10.6 years (n=55, for each group). Of the 57 IOL patients, 44 patients were analyzed in this report, eight with glaucoma, and 36 without. Six patients underwent IOL exchange due to high refractive error and were excluded from the primary analysis. These six patients had a mean refraction of −12.5 D ±4.9 D (range −7.0 D to −19.5 D) in the operated eyes at the time of the IOL exchange. After IOL exchange these patients had a mean additional myopic shift of −1.3 D (range +0.8D to −2.4 D) (Table 2 available at aaojournal.org). Seven patients were excluded due to incomplete data or lost to follow-up prior to the 10-year visit. Four of these patients did not have a ten-year exam but had a mean age at surgery and mean refractive error and median anisometropia at five years that was not significantly different from included patients. Two patients were excluded for protocol violations (one with IOL not implanted, one with Stickler’s syndrome) and one patient did not have 5 or 10-year refractive data.

The mean ± SD refractive error in the 36 operated eyes without glaucoma at the 10-year follow-up was −5.6 ± 5.9 D compared to −2.1± 4.6 D at the 5-year follow-up examination. The mean change in refractive error between years five and ten was −3.4 ± 2.4 D (95% CI −4.3 D to −2.6 D) or −0.6 ± 0.4 D/year (95% CI −0.7 to −0.5 D/year). For the eight eyes with glaucoma the mean ± SD refractive error at 10-year follow-up was −10.8 ± 9.2 D compared to −6.0 ± 7.1D at the 5-year follow-up examination. The mean change in refractive error between years five and ten was −4.0 ± 3.0 D (95% CI −6.7 to −1.7D). or −0.8 ± 0.6 D/year (95% CI −1.2 to −0.3 D/year). The cumulative and annual rates of the myopic shift were not significantly different in eyes with or without glaucoma (p=0.45) and (p=0.51), respectively. Between years five and ten all but one operated eye became more myopic.

The median amount of anisometropia at the 10-year follow-up for patients without glaucoma in the operated eye was −5.4 D (IQR, −8.8, −2.6) and for the patients with glaucoma in the operated eye was −10.9 D (IQR −17.1, −7.8); these medians were significantly different (p=0.03). (Table 1)

Table 1.

Summary of mean refractive error of operated eye and median anisometropia at 5- and 10-years follow-up an in patients with and without glaucoma (IQR = Interquartile range).

Mean refraction	5 years	10 years	Change 5-10 years	Annual Change
No glaucoma	−2.1+/− 4.6D	−5.6 +/− 5.9D	−3.4 +/− 2.4D	−0.6 +/− 0.4D
Glaucoma	−6.0 +/− 7.1 D	−10.8 +/− 9.2D	−4.0 +/− 3.0D (p=0.45)	−0.8 +/− 0.6D (p=0.51)
Median Anisometropia
No Glaucoma	−2.8D (IQR −6.4, −0.8)	−5.4D (IQR −8.8, −2.6)
Glaucoma	−8.3D (IQR −11.4, −5.3)	−10.9 (IQR −17.1, −7.8)

In summary, follow-up during years six through 10 in patients undergoing unilateral cataract extraction with IOL implantation in infancy, myopic shift continues in the operated eye, although at a substantially lower rate than that prior to age five years while anisometropia increases proportionally. While we reported significantly more myopic shift and anisometropia in glaucomatous than non-glaucomatous eyes at the 5-year follow-up, no significant difference was found between the 5- and 10-year follow-up visits between these two groups. We postulate this is due to the decreased scleral elasticity of older eyes. No significant relationship between the change in refractive error and baseline characteristics, including age at surgery (years), axial length (mm), average keratometry (D), and IOL power implanted (D) was noted.

The magnitude and high variability of myopic shift with ten years of follow-up, particularly in eyes that develop glaucoma, continues to make IOL power selection in very young eyes a significant challenge. In spite of targeting high initial hypermetropia many patients develop significant anisometropia. Additionally, because some of the patients with the greatest myopic shift had an IOL exchange and were excluded, these summary statistics may underestimate the mean refractive change in this population as well as the range and variability of that change. These findings support the authors’ recommendation that infants with unilateral cataracts operated prior to seven months of age should generally be left aphakic.

Collaborators: The Infant Aphakia Treatment Study Group

Administrative Units

Study Chair (Stanford University): Scott R. Lambert, MD

Clinical Coordinating Center (Emory University): Lindreth DuBois, MEd, MMSc (National Coordinator)

Contact Lens Committee: Buddy Russell, COMT; Michael Ward, MMSc

Data and Safety Monitoring Committee: Robert Hardy, PHD (Chair); Eileen Birch, PhD; Ken Cheng, MD; Richard Hertle, MD; Craig Kollman, PhD; Marshalyn Yeargin-Allsopp, MD (resigned); Cyd McDowell; Donald F. Everett, MA (ex officio)

Data Coordinating Center (Emory University): Azhar Nizam, MS (Director); Qi Long, PhD (Former Director); Michael Lynn MS (Former Director); Betsy Bridgman, BS; Marianne Celano PhD; Julia Cleveland, MSPH; George Cotsonis, MS; Nana Freret, MSN; Lu Lu, MS; Neeta Shenvi, MS; Seegar Swanson; Thandeka Tutu-Gxashe, MPH

Study Epidemiologist (George Mason University): Carey Drews-Botsch, PhD

Eye Movement Reading Center (University of Alabama, Birmingham and Retina Foundation of the Southwest, Dallas, TX): Claudio Busettini, PhD, Samuel Hayley, Joost Felius, PhD

Medical Safety Monitor: Allen Beck, MD

Program Office (National Eye Institute): Donald F. Everett, MA

Steering Committee: Scott R. Lambert, MD; Edward G. Buckley, MD; David A. Plager, MD; M. Edward Wilson, MD; Michael Lynn, MS; Lindreth DuBois, Med MMSc; Carolyn Drews-Botsch, PhD; E. Eugenie Hartmann, PhD; Donald F. Everett, MA

Vision and Developmental Testing Center (University of Alabama, Birmingham): E. Eugenie Hartmann, PhD (Director); Anna K Carrigan, MPH, Clara Edwards

Participating Clinical Centers (In order by the number of patients enrolled):

Medical University of South Carolina; Charleston, South Carolina (14): M. Edward Wilson, MD; Margaret Bozic, CCRC, COA

Harvard University; Boston, Massachusetts (14): Deborah K. Vanderveen, MD; Theresa A. Mansfield, RN; Kathryn Bisceglia Miller, OD

University of Minnesota; Minneapolis, Minnesota (13): Stephen P. Christiansen, MD; Erick D. Bothun, MD; Ann Holleschau, B.A.; Jason Jedlicka, OD; Patricia Winters, OD; Jacob Lang, O.D.

Cleveland Clinic; Cleveland, Ohio (10): Elias I. Traboulsi, MD; Susan Crowe, BS, COT; Heather Hasley Cimino, OD

Baylor College of Medicine; Houston, Texas (10): Kimberly G. Yen, MD; Maria Castanes, MPH; Alma Sanchez, COA; Shirley York

Emory University; Atlanta, Georgia (9): Scott R. Lambert, MD; Amy K. Hutchinson, MD; Lindreth Dubois, Med, MMSc; Rachel Robb, MMSc; Marla J. Shainberg, CO

Oregon Health and Science University; Portland, Oregon (9): David T Wheeler, MD; Ann U. Stout, MD; Paula Rauch, OT, CRC; Kimberly Beaudet, CO, COMT; Pam Berg, CO, COMT

Duke University; Durham, North Carolina (8): Edward G. Buckley, MD; Sharon F. Freedman, MD; Lois Duncan, BS; B.W. Phillips, FCLSA; John T. Petrowski, OD

Vanderbilt University: Nashville, Tennessee (8): David Morrison, MD; Sandy Owings COA, CCRP; Ron Biernacki CO, COMT; Christine Franklin, COT

Indiana University, Indianapolis, Indiana (7): David A. Plager, MD; Daniel E. Neely, MD; Michele Whitaker, COT; Donna Bates, COA; Dana Donaldson, OD

Miami Children’s Hospital, Miami, Florida (6): Stacey Kruger, MD; Charlotte Tibi, CO; Susan Vega

University of Texas Southwestern; Dallas, Texas (6): David R. Weakley, MD; David R. Stager Jr M.D.; Joost Felius, PhD; Clare Dias, CO; Debra L. Sager; Todd Brantley, OD

Case Western Reserve, Cleveland, Ohio (1): Faruk Orge, M.D.