Questions remain about use of refractive surgery in pediatric patients

The idea of offering surgical refractive correction to some pediatric patients has received increased attention in the ophthalmic community, but serious questions remain regarding its implementation.

The use of refractive surgery – LASIK, PRK and even lens exchange – in pediatric patients is relatively new. While some investigators suggest theoretical benefits, others contend that either there is insufficient data to date to support its widespread adoption or the studies to date have been improperly constructed to decipher feasibility.

According to Evelyn A. Paysse, MD, the use of surgical refractive correction should be considered an option in certain patients with severe anisometropia or bilateral ametropia who are unresponsive to traditional amblyopia therapy such as glasses or contacts.

She thinks that the amblyopia in these children is not garden-variety amblyopia but more a form of deprivation amblyopia, such as one gets with congenital cataract. And just as there is an effective surgical treatment for cataracts and preventing deprivation amblyopia, there is an effective surgical treatment to normalize high refractive error and thereby treat, or in the future even prevent, this severe form of amblyopia.

“This is severe, potentially blinding amblyopia,” Dr. Paysse said, adding that many studies have now shown improvements in vision and amblyopia with this treatment.

Evelyn A. Paysse, MD, is conducting studies of surgical refractive correction in pediatric patients who are noncompliant and non-responsive to traditional amblyopia therapy. Image: Sanchez A

According to Sandra M. Brown, MD, studies to date have shown an ability to address the refractive error but not the amblyopia that results from these conditions.

“The surgery is not going to treat their amblyopia. The surgery is just going to treat their refractive error,” Dr. Brown said. “You can’t get them to comply with amblyopia therapy any better after surgery than before surgery.”

A feasible option?

Anisometropic amblyopia is thought to affect around 1% to 2% of the population. Studies have shown a positive correlation with prevalence and degree of amblyopia and age: Approximately 40% of children age 2 years with diagnosed anisometropia have resulting amblyopia, whereas around 76% of 5-year-old children have amblyopia secondary to their anisometropia. Accordingly, children with higher levels of anisometropia have both higher prevalence and more profound amblyopia as a result.

Studies have also shown that a vast proportion of children with anisometropia can be managed adequately with glasses or contact lenses. However, a subset of children will reject glasses or contact lens wear for a variety of reasons, and studies have reported a greater proportion of spectacle or contact lens rejection among patients with higher magnitudes of anisometropia. It is for this subset of children who fail traditional therapy that refractive surgery appears to be a viable option, according to Dr. Paysse.

“At one point we were only enrolling children who were noncompliant with traditional therapy, but we have changed eligibility criteria to now accept children who are also non-responsive to traditional therapy because there are studies that show that normalizing the refractive error with refractive surgery in this subset of children can result in improved visual acuity here, too,” she said.

Dr. Paysse has published numerous studies on the use of refractive surgery in pediatric patients, mainly from a cohort of 11 children between the ages of 2 years and 11 years who had severe anisometropia with unilateral high myopia or high hyperopia and amblyopia of the affected eye.

After 3 years of follow-up, mean refractive error was reduced from –13.7 D to –3.55 D in myopic patients and from +4.75 D to +1.41 D in hyperopic patients. In seven children capable of preoperative and postoperative visual acuity testing, five had uncorrected visual acuity improvements of at least two lines, and four had improvements in best corrected visual acuity of at least two lines. Younger children tended to have greater visual acuity improvement, with one child gaining seven lines of improvement.

Most of the PRK procedures were performed under general anesthesia. Dr. Paysse said the young age of the patient at the time of surgical intervention and the anesthetic requirement may present special considerations. Logistically, the means and methods, not to mention the staff, to deliver general anesthesia are not usually found in an ophthalmic surgical theater, nor is the excimer laser portable enough to bring it to the anesthesiologist.

Of practical concern is that volatile gases used in general anesthesia, if leaked, can affect the laser’s effect on the cornea and may even shut down the excimer laser, so a special protocol is utilized. Lastly, the general anesthesia requirement creates a need for manual centration of the eye perpendicular to the axis of the laser beam, which introduces the potential for a decentered ablation, although this has not been found to be a common problem.

Children resistant to standard therapy

Despite the difficulties in performing the actual surgery, some pediatric ophthalmologists see a need for amblyopia intervention that does not rely on compliance with glasses or contact lenses.

“There will always be a need for this because there will always be children who will be noncompliant with glasses and will not be suitable for contact lenses,” Lawrence Tychsen, MD, said.

Lawrence Tychsen

The need is especially important in children who have neurobehavioral disorders and high bilateral refractive errors, he said. Children with autism, Down syndrome, cerebral palsy, Angelman syndrome or a variety of other developmental disorders live in what Dr. Tychsen has called a “cocoon of blur” in which they may be fearful of objects beyond a few inches from their face. And in the case of high myopia, this sort of “visual autism” can limit interaction with the world and, ultimately, functionality.

“Those special needs children tend to be the ones that benefit most from this treatment,” he said.

“Typically, children are more adaptive,” Dr. Tychsen said. “Your goals are different; your goal is to restore a level of functional vision or to correct amblyopia or to aid binocular function, whereas the goal of adult refractive surgery is to be spectacle and contact lens free with perfectly normal vision.”

Additionally, whereas adult refractive surgery is often an elective or cosmetic option, the same does not hold true for pediatric patients. Instead, patients should have a threshold magnitude of refractive error and failure with traditional therapy for their amblyopia or bilateral blur.

Even children beyond the suspected age of visual maturity – children for whom there is a theoretically limited benefit for reversing amblyopia – standard therapy with patching, atropine, and glasses or contacts should still be considered as front-line therapy because of the idiosyncratic response.

“But out of that, you will find children that fail standard therapy for a variety of reasons. Those who are noncompliant are the subgroup to treat with refractive surgery,” Dr. Tychsen said.

Effect on amblyopia

While some have made a case for the use of refractive surgery to help manage pockets of the population that otherwise would be left with high refractive errors, others are not sure that the procedures and the data to date are encouraging.

According to Dr. Brown, refractive surgery does not address amblyopia that is secondary to severe anisometropia. Early surgical correction could be indicated if improvements in binocularity are anticipated, but that would be only if the refractive correction induced greater compliance with amblyopia therapy. Surgical candidates might include children with milder anisometropia and a higher likelihood of compliance with amblyopia treatment because of a better underlying organic prognosis.

“Of course, the issue with those children is that they typically wear their refractive correction more willingly anyway,” Dr. Brown said.

Studies that claim to treat amblyopia due to high refractive error with refractive surgery are, therefore, “spurious,” according to Dr. Brown, especially in children past visual maturation with severe anisometropia who might not benefit from amblyopia therapy anyway.

Sandra M. Brown

Dr. Brown pointed to the studies performed by Dr. Paysse – which, she said, are well-designed and the only ones to date to properly address these issues – in reference to the effect of refractive correction on compliance with amblyopia therapy. Dr. Paysse, writing in a 2006 article in Ophthalmology, noted that “it is interesting and unfortunate to note that compliance with occlusion therapy did not improve after PRK” among patients followed to 3 years after surgical intervention.

According to Dr. Brown, several studies have offered outcomes on binocularity that are a result of less-than-perfect measurements from devices such as a synoptophore. As well, refractive correction with the intention of inducing compliance with amblyopia therapy in these children, she said, ignores that children may reject anisometropic-correcting glasses because they may have good functional binocular vision without glasses and not because of double vision or fusional asthenopia when wearing glasses.

But many think the children do not tolerate the glasses due to aniseikonia, diplopia or the cosmetic appearance, Dr. Paysse said.

“Parents neglect contact lens care when they see the child’s lack of interest and lack of observable practical benefit,” Dr. Brown wrote in an editorial in Archives of Ophthalmology.

Compliance issues

Dr. Brown acknowledged that there is a need for “involuntary” amblyopia treatment that is not child or parent dependent. However, she does not believe that surgical refractive correction promises to be the ideal therapeutic approach.

“Despite enthusiasm in the refractive community, surgical reduction of anisometropia, although effective, has not yet been shown to facilitate amblyopia treatment,” Dr. Brown wrote in Archives.

Dr. Paysse, however, disagrees. She said she has anecdotal evidence of amblyopia treatment or possibly even prevention in one child from her first 11 treated. He was 2.5 years old at the time of his PRK. He had anisometropia and approximately 14 D of myopia in one eye and would not wear glasses or a patch. This eye underwent PRK.

The child persisted in being noncompliant with further amblyopia therapy, but now, 9 years later, his UCVA in this eye is 20/40, and his BCVA with –0.75 D of correction is 20/30. Dr. Paysse said she is sure this eye would have had a visual acuity of much worse than 20/400 had no PRK been done.

“So, in essence, this child shows that amblyopia can be treated or prevented with refractive error normalization even if the occlusion regimen is still resisted,” she said.

Neurodevelopment disorders

Refractive surgery has been suggested in children with neurodevelopment disorders. However, no studies to date have independently investigated the effect of vision deficit on developmental delay, nor the effect of refractive correction on reversing or abating developmental disorders.

Dr. Tychsen noted that three of his published studies, on excimer laser correction and phakic IOL implantation in children with neurobehavioral problems, document improved social interaction, attention and reduced fearfulness.

Independent of these objective measures, he said, “How could you argue that 100-fold gains in acuity, measured after surgery for high bilateral ametropia in children noncompliant with glasses, does not improve their quality of life?”

Dr. Paysse said she is working with support from the Thrasher Foundation to investigate the plausibility of refractive correction in 20 children with neurodevelopmental delays who have bilateral severe ametropia. Patients are assessed for visual acuity, refractive error stability and corneal status, and assessed for functional changes through a rigorous battery of standardized tests after surgery. Typically, neurodevelopmentally delayed children regress on these tests over time. But significant improvements on these tests have been seen in the treated children thus far.

“These bilaterally affected neurodevelopmentally challenged children have improvements on so many more levels than just visual acuity,” Dr. Paysse said. “There are global improvements. It is not just improvement of the vision.”

The idea that refractive correction alone can improve previously untreated amblyogenic anisometropia has been shown in some studies. According to a recent invited perspective in the American Journal of Ophthalmology, studies have shown promising results in the intermediate term, but “more information is needed before pediatric refractive surgery can be widely adopted by the ophthalmic community.”

“One of the major conclusions we had from our paper was that there is a need for prospective, ideally randomized, multicenter trials to address the issue of the safety and efficacy and stability of refractive surgery in this population because there are so many issue to consider,” Terry Kim, MD, a co-author on the perspective, said.

Potential complications

One of the biggest issues to surface in the meta-analysis is the effect of corneal regression and haze in some pediatric patients after refractive surgery. Dr. Kim and colleagues speculated that haze may occur after PRK because of the ablation of Bowman’s layer, leading to a more aggressive healing response in the younger cornea as well as an induced inflammatory response. High myopia of more than –10 D, they said, may be more susceptible to postoperative haze and myopic regression because of potential corneal remodeling, less corneal and scleral rigidity, and perhaps the incompatibility of adult nomograms used in pediatric surgery.

“That’s the same thing we see in our adult patients, but it’s probably more so in our pediatric patients,” Dr. Kim said. “How much more regression is there in kids? What can we do to address the corneal haze? Is it safe to use mitomycin C on the corneas of these kids?”

So far, MMC has not been tested in the pediatric setting. There is 5 to 10 years of follow-up available in adult patients, Dr. Kim said, but in children, there is at least an additional 30 years of life to consider.

In the perspective, Dr. Kim and colleagues identified several issues that still need to be resolved, as well as two overarching controversies that should shape the debate on the use of refractive surgery in pediatric patients: the age of the patient at the time of surgical intervention and the particular technique used.

It has been suggested that surgery, if it is attempted, should occur during the neuroplastic years when there is the greatest chance of refractive reversal. However, this age group also has the greatest refractive instability and a more aggressive immune response. In addition, patients are less compliant with the procedure, and there is a lack of nomograms.

Children beyond the age of theoretical visual maturity may still benefit from refractive surgery, according to Dr. Tychsen. Surgical intervention in older children reduces a component of amblyopia, and a level of neuroplasticity persists in the patient’s brain, meaning that amblyopia can be reduced. As well, refractive surgery benefits the patient’s binocular fusion.

“Even if the absolute level of spatial vision doesn’t improve after refractive surgery, we know that their degree of binocular fusion improves, which means that their overall field of vision improves in terms of binocularity,” Dr. Tychsen said.

Some have suggested that PRK, although associated with corneal haze and a longer postoperative recovery period than LASIK, at least avoids potential issues with flap dislocation, striae or keratectasia found with LASIK.

According to Dr. Tychsen, there are several knowledge gaps that should be resolved with randomized, investigator-masked, long-term studies. For instance, the question of whether laser surgical intervention will induce iatrogenic keratoconus is of particular importance and may actually be an argument for the use of IOLs instead. However, the use of IOLs, and phakic IOL implantation in particular, raises questions about the effect of endothelial cell loss.

According to Dr. Kim, caution is still warranted in offering the intervention as an option.

“I think that there is enough experience in the literature and within this patient population to offer it as an option, but I don’t think it’s going to be more the latter option after going through glasses and contact lenses,” he said. – by Bryan Bechtel

What should be the preferred technique in pediatric refractive surgery, PRK or LASIK?

References:

• Ali A, Packwood E, Lueder G, Tychsen L. Unilateral lens extraction for high anisometropic myopia in children and adolescents. J AAPOS. 2007;11(2):153-158.
• Brown SM. Pediatric refractive surgery. Arch Ophthalmol. 2009;127(6):807-809.
• Cotter SA, Edwards AR, Wallace DK, et al; Pediatric Eye Disease Investigator Group. Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology. 2006;113(6):895-903.
• Daoud YJ, Hutchinson A, Wallace DK, Song J, Kim T. Refractive surgery in children: treatment options, outcomes, and controversies. Am J Ophthalmol. 2009;147(4):573-582.
• Donahue SP. The relationship between anisometropia, patient age, and the development of amblyopia. Trans Am Ophthalmol Soc. 2005;103:313-336.
• Ghasia F, Brunstrom J, Gordon M, Tychsen L. Frequency and severity of visual sensory and motor deficits in children with cerebral palsy: gross motor function classification scale. Invest Ophthalmol Vis Sci. 2008;49(2):572-580.
• O’Keefe M, Kirwan C. Pediatric refractive surgery. J Pediatr Ophthalmol Strabismus. 2006;43(6):333-336.
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• Paysse EA. Photorefractive keratectomy for anisometropic amblyopia in children. Trans Am Ophthalmol Soc. 2004;102:341-371.
• Paysse EA, Coats DK, Hussein MA, Hamill MB, Koch DD. Long-term outcomes of photorefractive keratectomy for anisometropic amblyopia in children. Ophthalmology. 2006;113(2):169-176.
• Paysse EA, Hamill MB, Hussein MA, Koch DD. Photorefractive keratectomy for pediatric anisometropia: safety and impact on refractive error, visual acuity, and stereopsis. Am J Ophthalmol. 2004;138(1):70-78.
• Paysse EA, Hamill MB, Koch DD, Hussein MA, Brady McCreery KM, Coats DK.. Epithelial healing and ocular discomfort after photorefractive keratectomy in children. J Cataract Refract Surg. 2003;29(3):478-481.
• Paysse EA, Hussein MA, Koch DD, et al. Successful implementation of a protocol for photorefractive keratectomy in children requiring anesthesia. J Cataract Refract Surg. 2003;29(9):1744-1747.
• Stahl ED. Current thoughts in pediatric refractive surgery. J Pediatr Ophthalmol Strabismus. 2008;45(6):331-337; quiz 338-339.
• Tychsen L. Refractive surgery for children: excimer laser, phakic intraocular lens, and clear lens extraction. Curr Opin Ophthalmol. 2008;19(4):342-348.
• Tychsen L. Refractive surgery for special needs children. Arch Ophthalmol. 2009;127(6):810-813.
• Tychsen L, Hoekel J. Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 2. Laser-assisted subepithelial keratectomy (LASEK). J AAPOS. 2006;10(4):364-370.
• Tychsen L, Hoekel J, Ghasia F, Yoon-Huang G. Phakic intraocular lens correction of high ametropia in children with neurobehavioral disorders. J AAPOS. 2008;12(3):282-289.
• Tychsen L, Packwood E, Berdy G. Correction of large amblyopiogenic refractive errors in children using the excimer laser. J AAPOS. 2005;9(3):224-233.
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• Sandra M. Brown, MD, can be reached at Cabarrus Eye Center, 201 LePhillip Court, Concord, NC 28025; 704-782-1127; fax: 704-782-1207; e-mail: sbrownmd@cabarruseye.com.
• Terry Kim, MD, can be reached at Duke University Eye Center, Erwin Road, P.O. Box 3802, Durham, NC 27710-3802; 919-681-3568; fax: 919-681-7661; e-mail: terry.kim@duke.edu.
• Evelyn A. Paysse, MD, can be reached at Texas Children’s Hospital; 832-822-3230; fax: 713-796-8110; e-mail: epaysse@bcm.tmc.edu.
• Lawrence Tychsen, MD, can be reached at Department of Ophthalmology and Visual Sciences, St Louis Children’s Hospital at Washington University Medical Center, One Children’s Place, St Louis, MO 63110; 314-454-6026; e-mail: tychsen@vision.wustl.edu.