Infant Aphakia Treatment Study Research Articles

Is Patching After Age 4 Beneficial for Children Born with a Unilateral Congenital Cataract?

The goal of these analyses is to provide evidence that can help parents and health care providers determine whether or not to continue occlusion therapy once a reliable measure of optotype acuity can be obtained in children who are born with a unilateral congenital cataract. Data from the Infant Aphakia Treatment Study (IATS) are used in a cohort design. 105 children who participated in the IATS and did not have a vision-threatening adverse event. We assessed the relationship between visual acuity at age 10.5 years and average daily hours of patching reported by caregivers on quarterly 48-hour recall interviews and annual 7-day patching diaries obtained between 48 and 60 months of age. Monocular visual acuity was assessed at the clinic visit closest to 48 months of age using the Amblyopia Treatment Study-HOTV protocol. Final visual acuity was measured at age 10.5 years using the E-ETDRS testing protocol. Visual acuity measurements obtained at age 4 were reliable, with a single measure intraclass correlation coefficient of 0.83 (95% CI 0.78,0.88) and were predictive of those obtained at age 10.5 (rSpearman = 0.83 (p<0.01)). Forty percent (n=48) of the children, the visual acuity measured at age 10.5 years was within +0.15 logMAR of the measurement obtained at age 4. The amount of patching that was received between the 4th and 5th birthdays was unrelated to changes in visual acuity. These analyses suggest that optotype acuity measures obtained early in the 5th year of life are reliable and are predictive of final visual outcomes. Additionally, our results suggest that less aggressive patching protocols, or discontinuing patching altogether, may be justified in some children, particularly those with poor vision, once optotype acuity can be measured. However, the potential impact of latent nystagmus on uniocular visual acuity measurement and the effect of patching on the child's quality of life, family relationships, and binocular visual field need to be considered before discontinuing occlusion therapy.

Patching in Children With Unilateral Congenital Cataract and Child Functioning and Parenting Stress

Parents may be concerned about the adverse outcomes of occlusion therapy in children treated for unilateral congenital cataract (UCC). To determine whether occlusion therapy in children treated for UCC with poor visual outcomes is negatively associated with poorer child and/or family functioning. This cohort study was conducted in 2023 using data collected between 2006 and 2016 in the Infant Aphakia Treatment Study (IATS). IATS participants with a visual acuity (VA) of 20/200 or worse were included. Statistical analysis was performed from July 2022 to October 2023. Caregivers reported the mean daily minutes of patching during the 12 months prior to the VA assessment at 4.5 years of age. Patching was categorized as minimal (<15 minutes per day), moderate (15 to <120 minutes per day), or extensive (≥120 minutes per day). At 4.25 and 10.5 years of age, caregivers reported stress associated with the parenting role using the Parenting Stress Index and the Ocular Treatment Index and child behavior problems using the Achenbach Child Behavior Checklist. Motor skills were assessed at age 54 months using the Movement Assessment Battery for Children-Second Edition. Children completed the Harter Self-Perception Profile for Children at age 10.5 years. One-way analysis of variance and χ2 tests were used to compare outcomes by amount of patching. Patching data were available for 47 of 53 children (88.7%) with a VA of 20/200 or worse. Among these 47 children with patching data included in the study, 20 (42.5%) were female, 27 (57.5%) were male, 12 (25.5%) were reported to have been patched fewer than 15 minutes per day, 11 (23.4%) were patched 16 to 119 minutes per day, and 24 (51.1%) were patched at least 120 minutes per day. Parenting stress, child behavior problems, motor functioning, and child self-perception were similar in all groups. For example, after adjusting for gender and insurance status, there was a nonsignificant difference between mean stress scores of 11.0 (95% CI, -4.5 to 26.5) points for parents who reported minimal patching vs parents who reported patching at least 120 minutes per day, and there was no significant difference in children's report of their global self-worth (0.0 [95% CI, -0.4 to 0.3] points). Occlusion therapy was not negatively associated with family or child functioning. Although the sample size was limited, these results do not support changes to the current practice guidelines.

Role of Intraocular Lens Implantation in Children

ABSTRACT Purpose To summarize recent literature and provide an update on the role of intraocular lens implantation in children. Design AOC/AACO/AAO 2022 Symposium Summary Intervention None Results Literature review surrounding the use of intraocular lenses in children. Attention was given to multicenter study efforts including the Infant Aphakia Treatment Study, the Toddler Aphakia and Pseudophakia Study, and the Pediatric Eye Disease Investigator Group Cataract Registry. Conclusions Intraocular lenses are a valuable tool in the care of children with lens abnormalities. Recent studies and advancements in fixation techniques have complimented our care and highlighted age and ocular dependent risks. Thorough initial clinical assessment and long-term postoperative management are critical in maximizing outcomes.

Refractive Growth of the Crystalline Lens in the Infant Aphakia Treatment Study

To compare the rate of refractive growth (RRG3) of the crystalline lens ("lens") versus the eye excluding the lens ("globe") for the fellow, noncataractous eyes of participants in the Infant Aphakia Treatment Study. Retrospective cohort study. A total of 114 children who had unilateral cataract surgery as infants were recruited. Biometric and refraction data were obtained from the normal eyes at surgery and at 1, 5, and 10 years. Subjects were included if complete data (axial length [AL], corneal power, and refraction) were available at surgery and at 10 years of age. At surgery and at 1, 5, and 10 years, AL, corneal power, and cycloplegic refraction were measured in the normal eyes. For each eye, the RRG3 was defined by linear regression of refraction at the intraocular lens (IOL) plane against log10 (age+ 0.6 years). The RRG3 for the globe was based on IOL power for emmetropia; the RRG3 for the lens was based on IOL power calculated to give the observed refractions. Intraocular lens powers were calculated with the Holladay 1 formula. The means were compared with a paired 2-tailed t test, and linear regression was used to look for a correlation between RRG3 of the lens globe. The RRG3 of the lens and globe. Complete data were available for 107 normal eyes. The mean RRG3 of the lenses was-12.0 ± 2.5 diopters (D) and the mean RRG3 of the globes was-14.1 ± 2.7 D (P < 0.001). The RRG3 of the lens correlated with the RRG3 of the globe (R 2 = 0.25, P < 0.001). The RRG3 was 2 D more negative in globes compared with lenses in normal eyes. Globes witha greater rate of growth tended to have lenses with a greater rate of growth.

The contribution of intraocular lens calculation accuracy to the refractive error predicted at 10 years in the Infant Aphakia Treatment Study

To determine the relative contribution of intraocular lens (IOL) calculation accuracy and ocular growth variability to the long-term refractive error predicted following pediatric cataract surgery. Pseudophakic eyes of children enrolled in the Infant Aphakia Treatment Study (IATS) were included in this study. Initial absolute prediction error (APE) and 10-year APE were calculated using the initial biometry, IOL parameters, postoperative refractions, and mean rate of refractive growth. The cohort was divided into children with a low-initial APE (≤1.0 D) and a high-initial APE ( >1.0 D). The 10-year APE was compared between the two groups using the Mann-Whitney U test. Linear regression was used to estimate the variability in prediction error explained by the initial IOL calculation accuracy. Forty-two children with IOL placement in infancy were included. Seventeen eyes had a low initial APE, and 25 eyes had a high initial APE. There was no significant difference in APE 10 years following surgery between individuals with a low initial APE (median, 2.67 D; IQR, 1.61-4.12 D) and a high initial APE (median, 3.45 D; IQR, 1.64-5.10 D) (P = 0.7). Initial prediction error could explain 12% of the variability in the prediction error 10 years following surgery. IOL calculation accuracy contributed minimally to the refractive error predicted 10 years after cataract surgery in the setting of high variability in the rate of refractive growth.

Anterior segment optical coherence tomography findings in the Infant Aphakia Treatment Study (IATS): a secondary analysis of a randomized clinical trial

To correlate the diagnosis of glaucoma among children in the Infant Aphakia Treatment Study (IATS) by age 10 years with anterior segment optical coherence tomography (AS-OCT) findings. A multicenter randomized controlled trial of 114 infants with unilateral congenital cataract who were 1-6 months of age at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old. Participants were randomized at cataract surgery to either primary intraocular lens (IOL) or no IOL implantation (contact lens [CL]). AS-OCT findings in eyes with glaucoma were compared to eyes which did not have glaucoma and to the fellow eyes, between fellow and treated eyes, and between the IOL and CL groups. There were no significant differences in the mean nasal and temporal anterior chamber angle (ACA) or mean nasal and temporal angle opening distance (AOD) for nonglaucomatous, glaucomatous, and fellow eyes (P = 0.31, 0.16, 0.43, 0.08 resp.). There were also no significant differences in mean nasal and temporal ACA and AOD between fellow and treated eyes (P = 0.44, 0.67, 0.57, 0.38 resp.), or between IOL and CL groups (P=0.36, 0.35, 0.49, 0.44, resp.). AS-OCT confirmed that eyes with glaucoma in IATS had predominantly open angles with similar ACA and AOD to eyes without glaucoma and to fellow eyes. Furthermore, congenital cataract surgery with or without an IOL did not result in a significant difference in ACA or AOD compared to fellow eyes in IATS.

Long-term strabismus outcomes after unilateral infantile cataract surgery in the Infant Aphakia Treatment Study

To characterize long-term strabismus outcomes in children in the Infant Aphakia Treatment Study (IATS).

Reading ability in children with a unilateral congenital cataract

Amblyopia has been associated with reading skills, but this association has not been observed with deprivation amblyopia. We analyzed data from the Infant Aphakia treatment Study (IATS) to see if unilateral congenital cataract, or visual acuity (VA) in the treated eye, was associated with reading.

Stereopsis in the Infant Aphakia Treatment Study: comparison between ages 4½ and 10½

Infants born with a unilateral congenital cataract (UCC) are frequently unable to perceive depth based on binocular cues because of the patching regimen employed to ensure optimal vision in the treated eye, as well as the disparity in acuity between their eyes. At the 4½ year visual assessment approximately 25% of the IATS patients demonstrated some level of binocular functioning. We determined that retesting stereopsis at age 10½ years would provide valuable information.

Association between motor ability at 4½ years and physical activity at 10½ years in the Infant Aphakia Treatment Study

Children with amblyopia have impaired fine and gross motor skills which may lead to reduced physical activity, and increased risk of obesity and cardiovascular disease. The goal of this analysis was to see if motor delay was associated with reduced participation in physical activity in IATS participants.

Effective lens position and pseudophakic refraction prediction error at 10½ years of age in the Infant Aphakia Treatment Study

The refraction prediction error (PE) for infants with intraocular lens (IOL) implantation is large, possibly related to an effective lens position (ELP) that is different than in adult eyes. If these eyes still have nonadult ELPs as they age, this could result in persistently large PE. We aimed to determine whether ELP or biometry at age 10½ years correlated with PE in children enrolled in the Infant Aphakia Treatment Study (IATS). We compared the measured refraction of eyes randomized to primary IOL implantation to the "predicted refraction" calculated by the Holladay 1 formula, based on biometry at age 10½ years. Eyes with incomplete data or IOL exchange were excluded. The PE (predicted - measured refraction) and absolute PE were calculated. Measured anterior chamber depth (ACD) was used to assess the effect of ELP on PE. Multiple regression analysis was performed on absolute PE versus axial length, corneal power, rate of refractive growth, refractive error, and best-corrected visual acuity. Forty-three eyes were included. The PE was 0.63 ± 1.68 D; median absolute PE, 0.85 D (IQR, 1.83 D). The median absolute PE was greater when the measured ACD was used to calculate predicted refraction instead of the standard A-constant (1.88 D [IQR, 1.72] D vs 0.85 D [IQR, 1.83], resp. [P = 0.03]). Absolute PE was not significantly correlated with any other parameter. Variations in ELP did not contribute significantly to PE 10 years after infant cataract surgery.

Outcomes of unilateral cataract surgery in children 2-7 years of age: a comparison to surgery in toddlers and infants

To compare outcomes of unilateral cataract surgery in children aged 2-7 years with the outcomes reported in younger children. The medical records of patients who underwent unilateral cataract surgery between the ages of 2-7 years were reviewed retrospectively. Traumatic cataracts and ectopia lentis were excluded. Outcomes were compared to those of the Infant Aphakia Treatment Study (IATS) for infants up to 7 months of age and the Toddler Aphakia and Pseudophakia Study (TAPS) for toddlers between 7-24 months of age who underwent unilateral cataract surgery. A total of 68 children were included, with a mean follow-up of 4.3 years. The proportion of intraoperative complications (7%) was significantly lower than that reported in IATS but not significantly different from that of TAPS. In our older cohort, more children (41%) had visual acuity better than 20/40 compared to infants (23% [P < 0.05]) and toddlers (11% [P < 0.001]), with a final median visual acuity of 20/44. The proportion of adverse events in our older cohort was reduced (7%) compared to that of infants (81%) and toddlers (24%). Additional unplanned intraocular surgeries occurred less often (6%) than in the infant cohort (72%). No patients developed glaucoma. Cataract surgery in slightly older children carries less risk of vision-threatening complications and adverse events compared to infants and results in better visual outcomes than in toddlers. Once the decision is made to pursue surgery on a visually significant cataract, the age of the child should determine which relevant risks are emphasized in the informed consent discussion.

Long-term strabismus outcomes after unilateral infantile cataract surgery in the Infant Aphakia Treatment Study

To characterize long-term strabismus outcomes in children in the Infant Aphakia Treatment Study (IATS). This study was a secondary data analysis of long-term ocular alignment characteristics of children aged 10.5 years who had previously been enrolled in a randomized clinical trial evaluating aphakic management after unilateral cataract surgery between 1 and 6 months of age. In the IATS study, 96 of 109 children (88%) developed strabismus through age 10.5 years. Half of the 20 children who were orthophoric at distance through age 5 years maintained orthophoria at distance fixation at 10.5 years. Esotropia was the most common type of strabismus prior to age 5 years (56/109 [51%]), whereas exotropia (49/109 [45%]) was the most common type of strabismus at 10.5 years (esotropia, 21%; isolated hypertropia, 17%). Strabismus surgery had been performed on 52 children (48%), with 18 of these (35%) achieving microtropia <10Δ. Strabismus was equally prevalent in children randomized to contact lens care compared with those randomized to primary intraocular lens implantation (45/54 [83%] vs 45/55 [82%]; P = 0.8). Median visual acuity in the study eye was 0.56 logMAR (20/72) for children with orthotropia or microtropia <10Δ versus 1.30 logMAR (20/400) for strabismus ≥10Δ (P = 0.0003). Strabismus-in particular, exotropia-is common irrespective of aphakia management 10 years following infant monocular cataract surgery. The delayed emergence of exotropia with longer follow-up indicates a need for caution in managing early esotropia in these children. Children with better visual acuity at 10 years of age are more likely to have better ocular alignment.

The accuracy of intraocular lens calculation varies by age in the Infant Aphakia Treatment Study

Refraction predictions from intraocular lens (IOL) calculation formulae are inaccurate in children. We sought to quantify the relationship between age and prediction error using a model derived from the biometry measurements of children enrolled in the Infant Aphakia Treatment Study (IATS) when they were ≤7 months of age. We calculated theoretical predicted refractions in diopters (D) using axial length, average keratometry, and IOL powers at each measurement time point using the Holladay 1 formula. We compared the predicted refraction to the actual refraction and calculated the absolute prediction error (APE). We found that the median APE was 1.60 D (IQR, 0.73-3.11 D) at a mean age (corrected for estimated gestational age) of 0.20 ± 0.14 years and decreased to 1.11 D (IQR, 0.42-2.20 D) at 10.60 ± 0.27 years. We analyzed the association of age with APE using linear mixed-effects models adjusting for axial length, average keratometry, and IOL power and found that as age doubled, APE decreased by 0.25 D (95% CI, 0.09-0.40 D). The accuracy of IOL calculations increases with age, independent of biometry measurements and IOL power.

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

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).

Refractive growth of the crystalline lens

The refractive development of the normal lens is the change in its power with age. Gordon and Donzis calculated the lens powers of children’s eyes in several age range, groups, based on cross-sectional data. We analyzed the longitudinal power and rate of refractive growth (RRG3) of the crystalline lenses of fellow eyes in the Infant Aphakia Treatment Study (IATS) cohort.

Anterior segment optical coherence tomography (AS-OCT) findings in the Infant Aphakia Treatment Study (IATS)

Anterior segment optical coherence tomography (AS-OCT) findings in the Infant Aphakia Treatment Study (IATS)

Glaucoma-Related Adverse Events at 10 Years in the Infant Aphakia Treatment Study

Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking. To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment. Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019. Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs. In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9% (95% CI, 5%-16%) at 1 year, to 17% (95% CI, 11%-25%) at 5 years, to 22% (95% CI, 16%-31%) at 10 years. The risk of glaucoma plus glaucoma suspect diagnosis after cataract removal rose from 12% (95% CI, 7%-20%) at 1 year, to 31% (95% CI, 24%-41%) at 5 years, to 40% (95% CI, 32%-50%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years. Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years. ClinicalTrials.gov Identifier: NCT00212134.

Refractive growth variability in the Infant Aphakia Treatment Study.

Prediction of refraction after cataract surgery in children is limited by the variance in rate of refractive growth (RRG3). This study compared RRG3 in aphakic and pseudophakic eyes with their fellow, normal eyes in the Infant Aphakia Treatment Study. Twelve clinical sites in the United States. Randomized clinical trial. Infants randomized to unilateral cataract extraction had RRG3 calculated based on biometric data (axial length and keratometry) at cataract surgery and at 10 years of age, for both the normal and cataract eyes. Subjects were included if complete biometric data from both eyes were available both at surgery and at 10 years. Variance in RRG3 was compared between the groups with Pitman test for equality of variance between correlated samples. Longitudinal biometric data were available for 103 of the 114 patients enrolled. RRG3 was -15.00 diopters (D) (3.00 D) for normal eyes (reported as mean [SD]), -17.70 D (6.20 D) for aphakic eyes, and -16.70 D (6.20 D) for pseudophakic eyes (P < .0001 for comparison of variances in RRG3 between normal and all operated eyes). Further analysis found differences in the variance in axial length growth (P < .0001) between operated and normal eyes; the variance in keratometry measurement change did not reach significance. The standard deviation in the RRG3 of normal eyes in our study was half of that found in eyes that underwent cataract surgery.

Outcomes of secondary intraocular lens implantation in the Infant Aphakia Treatment Study.

To report outcomes of secondary intraocular lens (IOL) implantation in the Infant Aphakia Treatment Study (IATS). Multicenter clinical practice. Secondary analysis of patients enrolled in a randomized clinical trial. Details regarding all secondary IOL surgeries conducted in children enrolled in the IATS were compiled. Visual outcomes, refractive outcomes, and adverse events at the age of 10½ years were evaluated. Comparisons were made with eyes that remained aphakic and with eyes randomized to primary IOL placement. The study included 114 infants, 57 in the aphakic group and 57 in the primary IOL group; 55 of 57 patients randomized to aphakia with contact lens correction were seen for the 10½-year study visit; 24 (44%) of 55 eyes had secondary IOL surgery. Median age at IOL surgery was 5.4 years (range 1.7 to 10.3 years). Mean absolute prediction error was 1.00 ± 0.70 diopters (D). At age 10½ years, the median logarithm of the minimum angle of resolution visual acuity (VA) was 0.9 (range 0.2 to 1.7), similar to VA in the 31 eyes still aphakic (0.8, range 0.1 to 2.9); the number of eyes with stable or improved VA scores between the 4½-year and 10½-year study visits was also similar (78% secondary IOL eyes; 84% aphakic eyes). For eyes undergoing IOL implantation after the 4½-year study visit (n = 22), the mean refraction at age 10½ years was -3.20 ± 2.70 D (range -9.90 to 1.10 D), compared with -5.50 ± 6.60 D (n = 53, range -26.50 to 3.00 D) in eyes with primary IOL (P = .03). Delayed IOL implantation allows a more predictable refractive outcome at age 10½ years, although the range of refractive error is still large.