The Pediatric Eye
Disease Investigator Group was formed in 1997. A collaborative network that is funded by the National Eye Institute, PEDIG is dedicated to facilitating multicenter research in eye disorders that affect children. There are more than 100 participating sites with more than 200 pediatric ophthalmologists and pediatric optometrists in the network. One of the major focuses has been the evaluation of different treatment modalities for amblyopia. The results of their Amblyopia Treatment Studies have revolutionized the treatment of amblyopia.
Amblyopia was selected because it is the most common cause of monocular vision loss in children. Amblyopia is unilateral, or less commonly bilateral, reduced visual acuity that is not due to any structural aspect of the eye or visual pathway. Major causes of amblyopia include anisometropia, strabismus and visual deprivation.
Standard treatment practices for amblyopia include spectacle correction, occlusion therapy and atropine penalization. In the past, patients were typically treated with full-time occlusion therapy. Lack of compliance with this standard treatment practice was a common problem. The PEDIG amblyopia treatment studies sought to determine if other alternatives were effective.
Atropine vs. Patching
The first of the amblyopia studies was a randomized trial of atropine versus patching for the treatment of moderate amblyopia, which was defined as vision of 20/40 to 20/100 in children age 3 to 7. The results of this study found that atropine and patching produced similar improvements in vision.
Amblyopia Treatment Studies involving members of the Pediatric Eye Disease Investigator Group have revolutionized the treatment of the condition. |
Although both treatments were well-tolerated, the atropine treatment did have a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group had a reduction in visual acuity of the sound eye at six months; however, this finding did not persist with further follow-up.1
In addition, some of these children were enrolled in a subsequent study to determine the visual acuity at age 10. After six months of treatment in either the atropine or patching group, further treatment was determined at the discretion of the ophthalmologist. This study found that at age 10, the improvement in the vision in the amblyopic eye was maintained and that the outcome was similar regardless of initial treatment with atropine or patching.2
Since the first PEDIG study found that atropine was comparable to patching therapy for the treatment of amblyopia, the next study addressed the question of atropine frequency. The PEDIG investigators conducted a randomized clinical trial comparing daily atropine to weekend atropine in patients with moderate amblyopia, defined as vision 20/40 to 20/80, in children less than 7 years of age. The study found that in approximately half of patients, in both groups, the vision improved to either 20/25 or better than or equal to the vision in the sound eye.3
The PEDIG group then investigated whether weekend atropine could be beneficial in cases of severe amblyopia, defined as vision of 20/125 to 20/400. For this trial, in contrast to other amblyopia treatment studies, the subjects included children age 3 to 12 years of age. In the younger group of children ages 3 to 6, subjects were randomized to weekend atropine with a plano lens or weekend atropine and full-spectacle correction. The results showed similar levels of improvement in both groups. The older children in this study, ages 7 to 12, were randomized to either weekend atropine or two hours of daily patching. While there were similar levels of improvement in the vision of the amblyopic eye, the improvement was significantly less than the results for the younger subjects.4
Full-time vs. Part-time Patching
The PEDIG network also sought to determine the necessity of the typically prescribed full-time patching regimens.
At one time, it was commonly accepted that near activities produced better results than distance activities when performing patching for the treatment of amblyopia. PEDIG investigators conducted a randomized trial to determine if this was true. ... Results showed similar improvements in vision in both groups.
In a randomized trial they compared full-time, or all but one hour per day, to six hours of patching per day in children younger than 7 years of age with vision in the range of 20/100 to 20/400. Fortunately for patients, they found that both treatment protocols produced similar improvements in vision.5
Next, they looked at the treatment of moderate amblyopia, defined as vision in the range of 20/40 to 20/80, to determine if two hours of patching was as effective as six hours per day in children younger than 7. The results of this study showed that two hours per day produced similar improvements in visual acuity when compared with six hours per day in children with moderate amblyopia.6
This change in treatment has had a major impact on families struggling to patch their children.
Near vs. Distance Activities
At one time, it was commonly accepted that near activities produced better results than distance activities when performing patching for the treatment of amblyopia. PEDIG investigators conducted a randomized trial to determine if this was true. Children age 3 to 7 with amblyopia ranging from 20/40 to 20/400 were randomized to two hours of patching per day with near versus distance activities. Results showed similar improvements in vision in both groups.7
Investigators were also curious if spectacle correction alone, without patching, could be enough to treat anisometropic amblyopia. Results of this trial showed that in one-third of 3- to 7-year-old children with untreated anisometropic amblyopia, resolution of amblyopia occurred with refractive correction alone. Children with moderate amblyopia, vision in the range of 20/40 to 20/100, were more likely to have resolution of amblyopia, while children with denser levels, on average, had a three-line improvement in visual acuity.8
This result has had a major impact on treatment and significantly reduced families’ patching burden.
Investigators also found that optical correction alone resulted in improvement in vision for patients with combined strabismic-anisometropic amblyopia. In fact, one-quarter of children did not require any further amblyopia treatment.9
Typically, amblyopia has been thought of as a disease that can be treated until approximately the age of 9, and if not diagnosed and treated by this age, permanent vision loss results. The PEDIG investigators performed a randomized trial to determine if treatment in older children could be beneficial. In the 7- to 12-year age group, children were randomized to optical correction in combination with patching two to six hours per day or optical correction alone.
... these studies have also shown that improvements can still be made in older children who have never been treated previously.
In this group, 53 percent of children in the treatment group responded compared with 25 percent of those provided with only optical correction.10
In addition, 82 percent of patients age 7 to 12 years maintained an increase in visual acuity one year after cessation of treatment other than glasses correction.11
In the 13- to 17-year age group, participants were randomized to optical correction combined with two to six hours of patching per day and atropine or optical correction alone. In this age group, the response rate was the same in both groups, indicating little benefit to treatment in older children. The study did find that children who had never been treated in the past showed some improvement with amblyopia treatment.10
The results of this study bring hope to families whose children were either non-compliant with treatment when younger or not detected until an older age.
Given that there was benefit to treating children age 7 to 12 years, investigators questioned whether success was equal with patching and atropine. A randomized trial comparing two hours of patching per day to weekend atropine in children age 7 to 12 with moderate amblyopia, vision 20/40 to 20/100, was performed. The results showed similar levels of improvement with both treatment options.12
PEDIG currently has a number of trials under way as well. Fifteen-year follow-up will be available in the near future for the Atropine vs. Patching study.
One current study will compare the efficacy and safety of oral levodopa and patching versus oral placebo and patching for amblyopia in children 7 to <13 years old. Another will evaluate the effectiveness of increasing prescribed patching treatment from two to six daily hours after visual acuity has stabilized with initial treatment and amblyopia is still present. Other related studies named on the PEDIG website include:
• A Randomized Trial of Bilateral Lateral Rectus Recession versus Unilateral Lateral Rectus Recession with Medial Rectus Resection for Intermittent Exotropia;
• Glasses versus Observation for Moderate Hyperopia in Young Children;
• Pediatric Cataract Surgery Outcomes Registry;
• Effectiveness of Home-Based Therapy for Symptomatic Convergence Insufficiency;
• Data Collection for Esotropia Treated with Botulinum Toxin-A Injection; and
• A Randomized Clinical Trial of Observation versus Occlusion Therapy for Intermittent Exotropia.
These studies revolutionized the treatment of amblyopia. Previously, families faced full-time occlusion therapy for their child. Today, they may only need spectacle correction alone as curative treatment. For patients who do require treatment, results can be obtained with either two hours of daily patching or weekend atropine treatment. In addition, these studies have also shown that improvements can still be made in older children up to the age of 12, and even in older children who have never been treated previously. Pediatric ophthalmologists and patients’ families are anxiously awaiting the results of the current trials, which may have an equally profound impact on our understanding of amblyopia.
Dr. Hendricks is an attending pediatric ophthalmologist at Nemours/AI duPont Children’s Hospital in Wilmington, Del.
1. Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002;120:268-278.
2. Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs. patching for treatment of moderate amblyopia: Follow-up at age 10 years. Arch Ophthalmol 2008;126:1039-44.
3. Repka MX, Cotter SA et al. A randomized trial of atropine regimens for treatment of moderate amblyopia in children. Ophthalmology 2004;111:2076-85.
4. Repka MX, Kraker RT, et al. Treatment of severe amblyopia with weekend atropine: results from 2 randomized clinical trials. J AAPOS 2009;13(3):258-63.
5. Pediatric Eye Disease Investigator Group. A randomized trial of prescribed regimens for treatment of severe amblyopia in children. Ophthalmology 2003;110:2075-87.
6. Repka MX, Beck RW et al. A randomized trial of patching regimens for treatment of moderate amblyopia in children. Arch Ophthalmol 2003;121:603-11.
7. Holmes JM, Pediatric Eye Disease Investigator Group, et al. A randomized trial of near versus distance activities while patching for amblyopia in children 3 to <7 years old. Arch Ophthalmol 2008 Nov; 115(11):2071-2078.
8. Cotter SA, Pediatric Eye Disease Investigator Group et al. Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology 2006;113:895-903.
9. Writing Committee for the Pediatric Eye Disease Investigator Group, Cotter SA, et al. Optical Treatment of Strabismic and combined Strabismic-Anisometropic Amblyopia. Ophthalmology 2012;119:150-8.
10. Scheiman MM, Hertle RW, Pediatric Eye Disease Investigator Group, et al. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Arch Ophthalmol 2005;123:437-47.
11. Hertle RW, Pediatric Eye Disease Investigator Group, et al. Stability of visual acuity improvement following discontinuation of amblyopia treatment in children aged 7 to 12 years. Arch Ophthalmol 2007;125:655-9.
12. Scheiman MM, Pediatric Eye Disease Investigator Group et al. Patching vs atropine to treat amblyopia in children aged 7 to 12 years: A randomized trial. Arch Ophthalmol 2008;126:1634-42.