Congenital Cataract
Conditions
Keywords
cataract surgery, intraocular lens, contact lens, infants, aphakia
Brief summary
The primary purpose is to determine whether infants with a unilateral congenital cataract are more likely to develop better vision following cataract extraction surgery if they undergo primary implantation of an intraocular lens or if they are treated primarily with a contact lens. In addition, the study will compare the occurrence of postoperative complications and the degree of parental stress between the two treatments.
Detailed description
Intraocular lenses are now a commonly accepted treatment for cataracts in older children and are used increasingly in younger children and infants. Intraocular lenses are superior to contact lenses in that they more closely replicate the optics of the crystalline lens, do not require daily ongoing care, and ensure at least a partial optical correction at all times. The simplicity and improved visual outcome of an intraocular lens correction may make caring for a child with a unilateral congenital cataract less stressful for parents. However, contact lenses remain the accepted treatment for children under 1 year of age due to concerns about the long-term safety of intraocular lenses and the potential for a large myopic shift developing in these eyes as they grow. Contact lenses provide excellent visual results in infants treated for bilateral congenital cataracts; however, two-thirds of infants treated with contact lenses for unilateral congenital cataracts remain legally blind in their aphakic eye. These poor visual outcomes are usually ascribed to competition from the sound eye and poor compliance with patching and contact lens wear regimens. Data from our pilot study and the literature suggest that superior visual results can be obtained if an intraocular lens is used to correct unilateral aphakia during infancy, but these eyes will experience more complications. Intraocular lenses will be increasingly implanted in infants regardless of whether or not we perform this trial. By performing this clinical trial, we can determine if the higher rate of complications with intraocular lenses is offset by improved visual outcome and decreased parenting stress. The Infant Aphakia Treatment Study (IATS) is a multi-center randomized clinical trial comparing intraocular lens and contact lens correction for monocular aphakia. Infants will be enrolled over a 4 year period. Infants 28 to 210 days of age with a visually significant cataract in one eye are eligible. Cataract surgery will be performed in a standardized fashion by a surgeon who has been certified for the study. Surgery consists of a lensectomy, posterior capsulotomy, and anterior vitrectomy. Infants will be randomized at the time of surgery to one of two treatment groups. Infants randomized to the intraocular lens group will have an intraocular lens implanted into the capsular bag. Spectacles will subsequently be used to correct the residual refractive errors. Infants randomized to the contact lens group will be fitted with a contact lens immediately after surgery. Both groups will receive the same patching therapy and follow-up. All children will be examined by Investigators at fixed intervals using standard protocols with the major endpoint assessed at age 12 months by a Traveling Vision Examiner. We are currently in a continuation of this project (beyond 5 years) in order to assess which of these patients have glaucoma or glaucoma suspect at age 10.5 years. Our goal is to understand which type of initial optical correction, an IOL or a CL, results in the best long-term visual outcome following unilateral congenital cataract surgery during infancy. Our central hypothesis is that primary IOL implantation will result in a better visual outcome. The rationale for this proposal is that final visual acuity cannot be determined by 5 years of age and the recommendation for early treatment can only be substantiated by adequate long-term assessment in this unique cohort. We chose a follow-up to age 10.5 years because it will provide a more accurate assessment of visual acuity and will allow us to diagnosis most cases of glaucoma.
Interventions
DEVICEContact lens correction of aphakia
optical correction of infant surgical aphakia with Contact lens
optical correction of surgical aphakia with intraocular lens
Sponsors
National Eye Institute (NEI)
Alcon Research
Bausch & Lomb Incorporated
BSN-JOBST Inc.
Eye Care and Cure
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 3 is 10.5-year follow-up study since Phase 1. There is no intervention.
Eligibility
Sex/Gender
ALL
Age
28 Days to 210 Days
Healthy volunteers
No
Inclusion criteria
* Visually significant unilateral congenital cataract (central opacity equal to or greater than 3 mm in size). * Cataract surgery performed when the patient is 28 to 210 days of age and at least 41 post-conceptional weeks.
Exclusion criteria
* The cataract is known to be acquired from trauma or as a side-effect of a treatment administered postnatally such as radiation or medical therapy. * A corneal diameter less than 9 mm measured in the horizontal meridian using calipers. * An intraocular pressure of 25 mm Hg or greater in the affected eye measured with a Perkins tonometer, tonopen, or pneumatonometer. * Persistent fetal vasculature (PFV) causing stretching of the ciliary processes or a tractional retinal detachment. * Active uveitis or signs suggestive of a previous episode of uveitis such as posterior synechiae or keratic precipitates. * The child is the product of a pre-term pregnancy (\<36 gestational weeks). Screening for prematurity will be based on the clinician's best assessment of gestational age. If a physician is uncertain regarding the gestational age, review of medical records or contact with the pediatrician and/or obstetrician should be used to confirm gestational age at delivery. Unless a clinician is uncertain as to whether a child was born at less than 36 weeks or not, confirmation of gestational age via medical record review may be delayed until after enrollment. * Retinal disease that may limit the visual potential of the eye such as retinopathy of prematurity. * Previous intraocular surgery. * Optic nerve disease that may limit the visual potential of the eye such as optic nerve hypoplasia. * The fellow eye has ocular disease that might reduce its visual potential. * The child has a medical condition known to limit the ability to obtain visual acuity at 12 months or 4 years of age. * Refusal by the Parent/Legal Guardian to sign an informed consent or to be randomized to one of the two treatment groups. * Follow-up of the child is not feasible because the child would not be able to return for regular follow-up examinations and the outcome assessments (e.g. transportation difficulties, relocation, etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity | Phase 1 - Age 12 months | Visual acuity was measured by standard objective testing procedures at 12 months of age. Monocular grating acuity was assessed by the traveling examiner with the Teller Acuity Cards. This test uses cards with black-on-white lines of varying widths and a set distance apart in a square with fixed dimensions, so the thinner the lines, the more there will be on any given card (cycles/cm). The ability to see thinner lines indicates better vision. The cards with lines are presented simultaneously with a gray card and the child's visual attention is noted. It is presumed that the child will preferentially look at the card with the stripes as it is more interesting. When the lines are too thin and close together so as to be indistinguishable from the gray card, no preferential looking will be noted. The card with the thinnest lines that the child will look at is recorded as the best visual acuity in logMAR units. |
| Visual Acuity - Subjective Assessment at Age 4.5 Years. | Phase 2 - Age 4.5 Years | Visual acuity estimates were standardized by using the Electronic Visual Acuity Tester (EVAT) at each clinical site. The IATS patients were tested at 4.5 years of age allowing the use of the HOTV recognition acuity test. The Amblyopia Treatment Study protocol for presentation and determination of best corrected visual acuity was followed. Monocular visual acuity was evaluated using single letter optotypes with surround bars presented on the EVAT. The staircase procedure of the ATS projects was followed as this has documented success and reliability with this age group. In order to familiarize the subjects with the HOTV matching test, this test was introduced at the 4.0 year visit and the 4.25 year visit by experienced site personnel. |
| Visual Acuity - Subjective Assessment at Age 10 Years. | Phase 3 - Age 10.5 Years | Visual acuity estimates were standardized by using the Electronic Visual Acuity Tester (EVAT) at each clinical site. The IATS patients were tested at 10.5 years of age allowing the use of the electronic early treatment diabetic retinopathy study (E-ETDRS) testing protocol. LogMAR typically ranges from -0.3 (20/10 vision on the Snellen chart) to 1 (20/200 vision). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients With 1 or More Intraoperative Complications at Cataract Surgery | Cataract surgery immediately after enrollment | Percent of Patients with 1 or More Intraoperative Complications at Cataract Surgery |
| Adherence to Occlusion Therapy | Phase 1 - 12 months follow-up | Parental report of the number of hours children wore an patch to occlude the fellow eye. |
| Percent of Patients With 1 or More Adverse Events | Study enrollment to age 5 years | — |
| Parenting Stress | Phase 1 - 3 months post surgery | The PSI is a 120-item validated self-report measure of parenting stress. PSI is a continuous scale measuring stress with a range of 131 (low stress) to 320 (high stress); the average person's stress scores are between 188 and 252. |
Countries
United States
Participant flow
Recruitment details
Recruitment 12/23/04 to 01/16/09 at 12 medical clinics.
Pre-assignment details
Final eligibility determined at pre-operative ocular examination under anesthesia.
Participants by arm
| Arm | Count |
|---|---|
| Aphakic Contact Lens optical correction of infant aphakia with aphakic Contact lens
INTERVENTION: aphakic contact lens | 57 |
| Aphakic Intraocular Lens optical correction of infant aphakia with aphakic Intraocular Lens
INTERVENTION: aphakic intraocular lens | 57 |
| Total | 114 |
Baseline characteristics
| Characteristic | Aphakic Intraocular Lens | Total | Aphakic Contact Lens |
|---|---|---|---|
| Age, Continuous mean/sd | 2.5 months STANDARD_DEVIATION 1.6 | 2.5 months STANDARD_DEVIATION 1.6 | 2.4 months STANDARD_DEVIATION 1.6 |
| Age, Customized 28 - 48 days | 25 participants | 50 participants | 25 participants |
| Age, Customized 3.1 - 5.0 months | 10 participants | 19 participants | 9 participants |
| Age, Customized 49 days - 3.0 months | 15 participants | 32 participants | 17 participants |
| Age, Customized 5.1 - 6.8 months | 7 participants | 13 participants | 6 participants |
| Axial Length - Cataractous Eye | 18.1 mm STANDARD_DEVIATION 1.3 | 18.0 mm STANDARD_DEVIATION 1.3 | 18.0 mm STANDARD_DEVIATION 1.3 |
| Axial Length - Fellow Eye | 18.7 mm STANDARD_DEVIATION 0.9 | 18.6 mm STANDARD_DEVIATION 0.9 | 18.4 mm STANDARD_DEVIATION 0.9 |
| Corneal Diameter - Cataractous Eye | 10.5 mm STANDARD_DEVIATION 0.8 | 10.5 mm STANDARD_DEVIATION 0.7 | 10.5 mm STANDARD_DEVIATION 0.7 |
| Corneal Diameter - Fellow Eye | 10.8 mm STANDARD_DEVIATION 0.7 | 10.8 mm STANDARD_DEVIATION 0.6 | 10.8 mm STANDARD_DEVIATION 0.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 19 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 95 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Intraocular Pressure - Cataractous Eye | 11.8 mmHg STANDARD_DEVIATION 4.9 | 12.2 mmHg STANDARD_DEVIATION 4.9 | 12.7 mmHg STANDARD_DEVIATION 4.9 |
| Intraocular Pressure - Fellow Eye | 12.9 mmHg STANDARD_DEVIATION 4.3 | 12.9 mmHg STANDARD_DEVIATION 4.7 | 12.8 mmHg STANDARD_DEVIATION 5.1 |
| Keratometric Power - Cataractous Eye | 46.4 diopters STANDARD_DEVIATION 2.7 | 46.4 diopters STANDARD_DEVIATION 2.7 | 46.4 diopters STANDARD_DEVIATION 2.7 |
| Keratometric Power - Fellow Eye | 45.4 diopters STANDARD_DEVIATION 1.9 | 45.5 diopters STANDARD_DEVIATION 1.8 | 45.5 diopters STANDARD_DEVIATION 1.8 |
| Private Insurance No | 24 participants | 44 participants | 20 participants |
| Private Insurance Yes | 33 participants | 70 participants | 37 participants |
| Pupil Diameter - Cataractous Eye | 3.2 mm STANDARD_DEVIATION 1 | 3.3 mm STANDARD_DEVIATION 1 | 3.3 mm STANDARD_DEVIATION 1 |
| Pupil Diameter - Fellow Eye | 3.4 mm STANDARD_DEVIATION 0.9 | 3.4 mm STANDARD_DEVIATION 0.9 | 3.5 mm STANDARD_DEVIATION 0.9 |
| Qualified for Medicaid No | 35 participants | 75 participants | 40 participants |
| Qualified for Medicaid Yes | 22 participants | 39 participants | 17 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 48 Participants | 97 Participants | 49 Participants |
| Refractive Error - Fellow Eye | 2.3 diopters STANDARD_DEVIATION 2.2 | 2.3 diopters STANDARD_DEVIATION 2 | 2.4 diopters STANDARD_DEVIATION 1.8 |
| Region of Enrollment United States | 57 participants | 114 participants | 57 participants |
| Sex: Female, Male Female | 28 Participants | 60 Participants | 32 Participants |
| Sex: Female, Male Male | 29 Participants | 54 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 32 / 57 | 46 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 |
Outcome results
Primary
Visual Acuity
Visual acuity was measured by standard objective testing procedures at 12 months of age. Monocular grating acuity was assessed by the traveling examiner with the Teller Acuity Cards. This test uses cards with black-on-white lines of varying widths and a set distance apart in a square with fixed dimensions, so the thinner the lines, the more there will be on any given card (cycles/cm). The ability to see thinner lines indicates better vision. The cards with lines are presented simultaneously with a gray card and the child's visual attention is noted. It is presumed that the child will preferentially look at the card with the stripes as it is more interesting. When the lines are too thin and close together so as to be indistinguishable from the gray card, no preferential looking will be noted. The card with the thinnest lines that the child will look at is recorded as the best visual acuity in logMAR units.
Time frame: Phase 1 - Age 12 months
Population: The number of participants was determined by the sample size estimate necessary to detect a 0.2 logMAR difference (2 lines on the Snellen chart) in the visual acuity between the two groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aphakic Contact Lens | Visual Acuity | 0.80 logMAR units |
| Aphakic Intraocular Lens | Visual Acuity | 0.97 logMAR units |
p-value: 0.19Wilcoxon (Mann-Whitney)
Primary
Visual Acuity - Subjective Assessment at Age 10 Years.
Visual acuity estimates were standardized by using the Electronic Visual Acuity Tester (EVAT) at each clinical site. The IATS patients were tested at 10.5 years of age allowing the use of the electronic early treatment diabetic retinopathy study (E-ETDRS) testing protocol. LogMAR typically ranges from -0.3 (20/10 vision on the Snellen chart) to 1 (20/200 vision).
Time frame: Phase 3 - Age 10.5 Years
Population: Participants who completed the third phase of the study are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aphakic Contact Lens | Visual Acuity - Subjective Assessment at Age 10 Years. | 0.86 logMAR units |
| Aphakic Intraocular Lens | Visual Acuity - Subjective Assessment at Age 10 Years. | 0.89 logMAR units |
p-value: 0.82Chi-squared
Primary
Visual Acuity - Subjective Assessment at Age 4.5 Years.
Visual acuity estimates were standardized by using the Electronic Visual Acuity Tester (EVAT) at each clinical site. The IATS patients were tested at 4.5 years of age allowing the use of the HOTV recognition acuity test. The Amblyopia Treatment Study protocol for presentation and determination of best corrected visual acuity was followed. Monocular visual acuity was evaluated using single letter optotypes with surround bars presented on the EVAT. The staircase procedure of the ATS projects was followed as this has documented success and reliability with this age group. In order to familiarize the subjects with the HOTV matching test, this test was introduced at the 4.0 year visit and the 4.25 year visit by experienced site personnel.
Time frame: Phase 2 - Age 4.5 Years
Population: One patient in the intraocular lens group was lost to follow-up.at age 18 months. A second patient in that group had developmental delay and the visual acuity could not be assessed. Therefore, the visual acuity measurements at 4.5 years of age are reported for 55 of the 57 patients randomized to the intraocular lens group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aphakic Contact Lens | Visual Acuity - Subjective Assessment at Age 4.5 Years. | 0.90 logMAR units |
| Aphakic Intraocular Lens | Visual Acuity - Subjective Assessment at Age 4.5 Years. | 0.90 logMAR units |
p-value: 0.54Wilcoxon (Mann-Whitney)
Secondary
Adherence to Occlusion Therapy
Parental report of the number of hours children wore an patch to occlude the fellow eye.
Time frame: Phase 1 - 12 months follow-up
Population: Analysis is limited to those with at least 3 reports of adherence before 12 months of age.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aphakic Contact Lens | Adherence to Occlusion Therapy | 3.92 Hours patched per day | Standard Deviation 1.55 |
| Aphakic Intraocular Lens | Adherence to Occlusion Therapy | 3.63 Hours patched per day | Standard Deviation 1.68 |
Secondary
Parenting Stress
The PSI is a 120-item validated self-report measure of parenting stress. PSI is a continuous scale measuring stress with a range of 131 (low stress) to 320 (high stress); the average person's stress scores are between 188 and 252
Time frame: Phase 1 - Age 12 Months
Population: All those who completed the PSI 3 months after surgery and the PSI at age 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aphakic Contact Lens | Parenting Stress | 202.6 units on a scale | Standard Deviation 34.4 |
| Aphakic Intraocular Lens | Parenting Stress | 208.3 units on a scale | Standard Deviation 30.8 |
Comparison: ITT comparison of mean PSI scoresp-value: >0.05t-test, 2 sided
Secondary
Parenting Stress
The PSI is a 120-item validated self-report measure of parenting stress. PSI is a continuous scale measuring stress with a range of 131 (low stress) to 320 (high stress); the average person's stress scores are between 188 and 252.
Time frame: Phase 1 - 3 months post surgery
Population: All those who completed the PSI 3 months after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aphakic Contact Lens | Parenting Stress | 197.4 units on a scale | Standard Deviation 35.7 |
| Aphakic Intraocular Lens | Parenting Stress | 231.1 units on a scale | Standard Deviation 36.8 |
Comparison: ITT analyses comparing parents of children randomized to receive an IOL to those left aphakic.p-value: <0.05t-test, 2 sided
Secondary
Percent of Patients With 1 or More Adverse Events
Time frame: Study enrollment to age 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aphakic Contact Lens | Percent of Patients With 1 or More Adverse Events | 56 percentage of patients |
| Aphakic Intraocular Lens | Percent of Patients With 1 or More Adverse Events | 81 percentage of patients |
p-value: 0.008Fisher Exact
Secondary
Percent of Patients With 1 or More Intraoperative Complications at Cataract Surgery
Percent of Patients with 1 or More Intraoperative Complications at Cataract Surgery
Time frame: Cataract surgery immediately after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aphakic Contact Lens | Percent of Patients With 1 or More Intraoperative Complications at Cataract Surgery | 11 percentage of patients |
| Aphakic Intraocular Lens | Percent of Patients With 1 or More Intraoperative Complications at Cataract Surgery | 28 percentage of patients |
p-value: 0.03Fisher Exact