April 2010




Pharmaceutical Corner

Investigating pediatric patient treatment options

by Vanessa Caceres EyeWorld Contributing Editor 


At a glance

• IATS is a multicenter trial that compares randomized IOL implantation versus contact lens insertion and patching/eyeglass use in 114 patients with unilateral congenital cataract. The final test in these patients as part of the study takes place when they are 4.5 years old • Results from the first group of IATS patients will be available in the coming months • Genetic testing for eye disease is another area of growing interest in pediatric ophthalmology • Ophthalmologists can use genetic testing to better diagnose eye disease and determine proper treatment


Aphakia in children and genetic testing are two areas of interest

Unilateral congenital cataract in a 4-month-old infant enrolled in IATS. The child was randomized to IOL implantation and had a AcrySof SN60AT IOL (Alcon) implanted into the capsular bag using the IATS protocol Source: Scott R. Lambert, M.D.

First, pediatric subspecialists are eagerly awaiting the anticipated results from the Infant Aphakia Treatment Study (IATS), which compares treatment for unilateral cataract in infancy with a contact lens and patching versus IOL implantation. The first round of results should be published in Archives of Ophthalmology in the coming months, said Scott R. Lambert, M.D., R. Howard Dobbs Professor of Ophthalmology, Emory University, Atlanta.

Second, research on genetic testing for congenital eye diseases such as Leber congenital amaurosis and retinoblastoma may broaden treatment possibilities, Dr. Lambert said.

Infant aphakia study

The IATS is a randomized 12-site clinical trial that involves 114 children with unilateral congenital cataracts. Study enrollment began at the end of 2004 and ended in January 2009. Fifty of the children involved had cataract surgery at 4-6 weeks of age; the median age at the time of surgery was 1.8 months. Children were randomly selected for IOL implantation or treatment with a contact lens followed by patching and eyeglass use. The main outcome measures are grating acuity at 12 months of age and optotype acuity assessment at 4.5 years, according to “The Infant Aphakia Treatment Study: Design and Clinical Measures at Enrollment,” published in Archives of Ophthalmology in January. Investigators found shorter axial lengths and steeper corneas in the eyes with cataracts.

Visual outcome is the main outcome under investigation, but adverse events, strabismus incidence, and how the eyes grow are secondary areas they will also track. The study also monitors parenting stress, adherence to patching and optical correction, stereopsis, pachymetry, biometry, tonometry, and eye movements.

Although contact lens insertion followed by patching is a standard treatment after unilateral cataract removal, drawbacks, such as the development of amblyopia, can become problematic, said Richard W. Hertle, M.D., Pittsburgh. Other problems with contact lens use in this young population include patient cooperation, contact lens cost, and the difficulty of fitting a lens in infants. These reasons seem to contribute to the poor visual outcomes in unilateral aphakia in children, according to the Archives of Ophthalmology report from January.

Some studies have shown better visual outcomes with IOL implantation in this population, but the long-term effect is not known—at least not until the IATS study is available. Clinicians are still unsure about the proper IOL power to use, and some studies report more post-op complications. Plus, IOL implantation in children and infants is technically demanding and requires the patient to undergo multiple procedures throughout early childhood, said Dr. Hertle, who is a member of the study’s Data and Safety Monitoring Committee.

“The study will really give a definitive answer on the efficacy and safety of IOLs in infants,” Dr. Hertle said.

“The results will provide guidelines on how to treat infants with monocular cataract,” said Rupal H. Trivedi, M.D., assistant research professor, Storm Eye Institute, Medical University of South Carolina, Charleston. “Like most other clinical trials, the results of the IATS will represent the efficacy of the treatment (IOL versus contact lens), not the effectiveness of the treatment.”

Although investigators now have results for 20 of the 114 children who have reached age 5, Dr. Lambert said he cannot discuss those statistics until they are formally published. The IATS has some implications for general ophthalmology as well. “I think general ophthalmologists would be interested in knowing the results. The trend is putting IOLs in younger children, and some question whether that’s a good thing,” Dr. Lambert said.

Once outcomes are available, general ophthalmologists will likely want to know if they need special training to perform IOL implantation in children to offer the best possible treatment, Dr. Hertle said. The study should also shed light on which procedure has a higher rate of glaucoma incidence—the existing research presents evidence both ways, Dr. Hertle added.

Those interested in the IATS should keep in mind the study’s exclusion criteria, Dr. Trivedi said. “The results of the study will not be applicable to eyes with a corneal diameter of less than 9 mm or persistent fetal vasculature causing stretching of the ciliary processes,” Dr. Trivedi said. Additionally, as the study uses a hydrophobic acrylic IOL, the visual axis opacification results will not necessarily apply to use of a PMMA IOL, Dr. Trivedi added.

Considering that parental stress is a factor in the treatment of children, if both treatments show the same results in vision improvement, investigators might recommend the treatment method that proved less stressful for parents, according to the January Archives of Ophthalmology report.

Read more about the IATS at www.sph.emory.edu/IATS.

Genetic testing in children

Pediatric subspecialists predict a growing interest in molecular genetic testing to diagnose and determine treatment for some eye diseases, said Arlene V. Drack, M.D., Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City. Dr. Drack is co-author of a report from the January issue of American Journal of Ophthalmology on the topic of molecular genetic testing.

“Many children who do not currently have a diagnosis can be diagnosed with molecular genetic testing. This will allow us to test treatments in clinical trials, which can’t be done accurately if the patients do not have a molecular genetic diagnosis,” Dr. Drack said. The report from Dr. Drack and co-authors describes how over the past 20 years, many parents have asked for a rapid and accurate molecular diagnosis of their child’s disease. “There’s a cooperative effort now between families and doctors that wasn’t there 20 years ago. Their input into their children’s care is amazing and more intense—not only their questioning but also active care,” Dr. Hertle said.

Nowadays, genetic testing itself has become a more standardized procedure, and clinicians can easily find out about testing for various diseases via Web sites such as www.genetests.org, writes Dr. Drack and co-authors.

Some pediatric eye diseases that now have fee-for-service genetic testing include Leber congenital amaurosis, achromatopsia, retinoblastoma, albinism, and aniridia/Wilm tumor, according to the American Journal of Ophthalmology report.

Molecular genetic testing can help accurately diagnose certain diseases, the authors report. “For example, in children without a family history of optic atrophy, it is possible to diagnose Kjer dominant optic atrophy definitely only using molecular genetics,” Dr. Drack and co-authors write. Alternately, molecular testing can confirm suspected diagnoses. “Many patients who have a similar clinical appearance—for example, they were born with poor vision and nystagmus and have an abnormal electroretinogram—do not have the same genetic disorder,” Dr. Drack said. “Based on their clinical findings, we say all of them have Leber congenital amaurosis, but when we do genetic testing we find that there are more than 12 genes that can cause this same kind of vision loss, and even though the end result is the same, the mechanisms are very different.” This would obviously lead to different treatments as appropriate, she added.

With identification of the patient’s disease, clinicians can sometimes implement gene therapy, another expanding area, said Dr. Lambert, a co-author of the study. Dr. Hertle calls the gene therapy available nowadays “science fact” that at one time seemed like science fiction.

The option for treatment due to the results of genetic testing will likely spark an ever-growing interest in the field, Dr. Hertle said. “If you look at the vision and mission of [ophthalmology] academic departments, each one branches into molecular biology and genetics, at least in North America,” Dr. Hertle said. Pediatric genetic testing may have implications for adult patients as well, Dr. Drack said. “Many adults who have had poor vision or blindness their entire lives also do not have a diagnosis. They may stop visiting an ophthalmologist because they think nothing can be done. These adults can now be offered genetic testing to understand what causes their vision problems and what the risk to their children or other relatives is.” These patients may eventually take part in treatment trials for adults with genetic eye disease, Dr. Drack added.

Not every patient with suspected genetic eye diseases will want to undergo testing, according to the recently published report. Patients who do not want a definitive diagnosis and patients (and their doctors) who believe the test will not yield useful results may want to pass on the testing option. Additionally, patients who undergo testing should receive careful counseling about the advantages and drawbacks of such tests, the report recommended.

Editors’ note: The physicians interviewed have no financial interests related to their comments or studies.

Contact information

Drack: arlene-drack@uiowa.edu
Hertle: rslpshot@aol.com
Lambert: 404-778-3709, slamber@emory.edu
Trivedi: trivedi@musc.edu

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