Amblyopia therapy options expand beyond patching for children and adults


Continual progress is being made in the area of amblyopia therapy, and patients of all ages are seeing benefits. Shortened patching times, computer-based vision training, video game therapy, electronic eyeglasses and spectacle lenses that correct for predicted aniseikonia are all emerging as effective treatments.


“There’s been more movement in terms of research in amblyopia over the last 10 to 12 years than in any other area of binocular vision and childhood eye disease,” Susan Cotter, OD, MS, vice chair of the Pediatric Eye Disease Investigator Group (PEDIG), said in an interview with Primary Care Optometry News. “Many people used to think that amblyopia treatment required patching for all waking hours. However, based on the results from PEDIG’s randomized clinical trials, we found less treatment to be just as effective as more treatment. For instance, 2 hours of prescribed patching is just as effective as 6 hours for children with moderate amblyopia, and 6 hours of prescribed patching is just as effective as patching all waking hours for children with severe amblyopia.


“This means that the child wears a patch fewer hours per day, and that the parent has to supervise the child fewer hours per day, which is less of a burden for all those involved,” she said.


Another boon to compliance, according to Cotter, lies in the correction of the refractive error. “Recent PEDIG studies have shown that optical correction of refractive error alone has a true treatment effect on amblyopia beyond the immediate visual acuity gains from simply eliminating optical blur,” she said.


“We put the kids in glasses, have them come back in a month, and if acuity is improved we have them come back every 4 to 6 weeks until it stops improving,” Cotter said. “We found that about one-third of the children won’t require patching at all because they actually get better on glasses alone.”


Once visual acuity has improved, those who still require patching will have a much easier time walking around being patched because their visual acuity will be better, which often translates into better compliance with the treatment, she said.


Susan Cotter, OD, MS, pictured here with a patient, said less patching time has been found to be as effective as more.

Susan Cotter, OD, MS, pictured here with a patient, said less patching time has been found to be as effective as more.

Image: Cotter S

Another factor that could improve compliance is the finding that there is no significant clinical difference between the treatment effects of patching vs. those of using atropine drops, Cotter said.


“Before, if there were compliance problems with patching, there was nothing you could do. Now I can give the parents a choice up front: patching or atropine drops. If one doesn’t work, we can always switch to the other,” she said.


Amblyopia in adults


New evidence suggests that cortical plasticity can be recovered in adults with amblyopia, and that treatment options can actually be effective after an amblyope reaches age 8 or 9, according to Dennis Levi, OD, PhD, FAAO, dean of the School of Optometry at the University of California, Berkeley.


“Brain plasticity is more restricted in adulthood than during development. Some of these ‘brakes’ on plasticity are structural, such as perineural nets or myelin, which inhibit neurite outgrowth; others are functional, acting directly on the balance of excitation and inhibition within local neural circuits,” Levi wrote in a recently published article.


One way in which those brakes can be lifted is through perceptual learning, which is a therapy where a patient repetitively practices a difficult visual task, one that is close to the patient’s threshold ability to accomplish, Levi told PCON.


During the RevitalVision training sessions, the user is presented with a series of precise visual tasks consisting of patterned images with subtle differences in orientation, size and contrast. 


During the RevitalVision training sessions, the user is presented with a series of precise visual tasks consisting of patterned images with subtle differences in orientation, size and contrast. 


“When we first did this with adults with amblyopia, we found that they got better on those tasks, but we also found that they got better in terms of visual acuity,” he said. “However, there are two problems with perceptual learning.”


First, a major constraint, is that it bears a “curse of specificity,” meaning that it tends to be “quite specific for the thing that you’re practicing, so if you learn to detect a target that has horizontal stripes, it doesn’t necessarily transfer to the same target with vertical stripes. Then the question is, do you have to learn every different possible stimulus?” Levi said.


RevitalVision’s technique employs Gabor targets that function as effective stimuli for the primary vision cortex, reducing the noise-to-signal ratio.

RevitalVision’s technique employs Gabor targets that function as effective stimuli for the primary vision cortex, reducing the noise-to-signal ratio.

“The other problem is that it’s super boring,” he added.


Video games


Another approach Levi and his associates have been considering comes from work on the effect of video games on visual performance by one of Levi’s colleagues in Rochester, N.Y., Daphne Bavelier.


“She had a graduate student participating in some vision experiments, and the student’s results were always better than everybody else’s; he showed better performance, was more accurate,” Levi said. “And he was a video game player. So, for his thesis, he studied the effect of video game play on visual performance and found that gamers were better than non-gamers on almost everything measured.” 


Bavelier’s graduate student then took those non-gamers — because it was posited that a potential confounder could be that people with good vision are drawn to playing video games — and split them into two groups, one to play an action game and one to play a non-action game. They found that the action game groups did better, according to Levi.


“In contrast to perceptual learning, action game play is extremely varied in its demands and rich in the set of visual experiences it offers,” Levi wrote in his article. “Thus, they suggest that the very act of action game playing seems to train the brain to learn, on the fly, how to make the best use of the available information in the display, independent of the specifics of this display, allowing for the broad transfer of learning.”


After learning of Bavelier’s findings, Levi and Li conducted their own study at Berkeley where 20 subjects with amblyopia played video games with their good eye patched. 


All 20 subjects improved. On average, they had about a 30% improvement, 1.5 to 2 lines in visual acuity. Also, of the five subjects included in the study who were anisometropic, all of them also showed improvement in stereo acuity, Levi said.


“The thing about using a commercial video game over a vision training program is that the game makers are really good at making games that are engaging,” he said, more engaging than perceptual learning.


Computerized Gabor targets


Conceptually parallel to Levi’s perceptual learning is RevitalVision’s vision training systems (RevitalVision LLC, Lawrence, Kan.), a series of computer-based visual cortex training programs that utilize the Gabor patch science created by Nobel Prize winner Dennis Gabor. This technique employs Gabor targets that function as effective stimuli for the primary vision cortex, reducing the noise-to-signal ratio. 


The therapy programs can be used at home by amblyopia patients and anyone else wishing to improve their visual performance, Glenn Moro, vice president and general manager of amblyopia at
 RevitalVision, told PCON.


“This approach focuses on the idea that the connectivity between the eye and visual cortex of the brain could be improved by retraining, or ‘rewiring’ the neural connections,” Moro said.


“Patients in the clearance study achieved an improvement of 2.5 lines of visual acuity and a 100% improvement in contrast sensitivity, which allows patients to enjoy sharper, clearer vision in daily activities, as well as an increase in depth perception,” he said.


The program consists of 40 individualized sessions lasting about 40 minutes each, during which the user is presented with a series of precise visual tasks consisting of patterned images with subtle differences in orientation, size and contrast, according to company literature. 


Clinical findings have shown that the noise of individual cortical neurons can be modulated by the appropriate choice of stimulus conditions. Contrast sensitivity at low levels can be increased through a lateral masking technique, which displays the target Gabor image with collinearly oriented flanking Gabors. This technique is tailored to an individual, computerized training regimen using various parameters of the stimulus including spatial frequencies, spatial arrangement of the Gabor patches, contrast level, orientation (local and global), task order, context and exposure duration, the literature said.


The system puts these principles together in a patient-specific learning regimen that facilitates neural connections at the cortical level to improve the optical input received from the eye and the neural processing of that input in the visual cortex, both of which are necessary for vision enhancement.


The sessions are customized to the patient’s pace and visual ability and are monitored by a personal RevitalVision specialist. The length of the individual sessions and duration of the program vary by patient and specific need, Moro said.


The therapy has device approval from the U.S. Food and Drug Administration for patients with amblyopia who are 9 years and older, he added. 


Electronic eye glasses 


XPand 3D has developed Amblyz, electronic glasses designed to treat amblyopia in children.


Outwardly appearing similar to a regular prescription pair of spectacles, Amblyz, designed for children 3 to 7 years old, features an electronic shutter that is controlled by a preprogrammed microchip embedded in the glasses frame. The microchip, a microprocessor, controls the shutter, creating short intermittent occlusions of the strong eye.


“The Amblyz allows for hundreds of daily ‘exercises’ without any effort or need for cooperation from the child. In the glasses, a microchip controls a liquid crystal lens, making the lens opaque for short, preprogrammed intervals,” Abraham Spierer, MD, director for the Unit of Pediatric Ophthalmology and Strabismus at the Sheba Medical Center in Tel Aviv, Israel, said in an interview. “Each time the lens performs a transition from clear to opaque, the visual system of the amblyopic eye is forced to exercise.”


“This is a great aid for us because treating amblyopia with eye patches or penalization is cumbersome for the children and their parents,” Spierer said.


“The strong eye ends up being shuttered about 50% of the time, but the child doesn’t notice it,” Ami Dror, chief strategy officer for XPand 3D, told PCON. The lens opens and closes every 10 seconds.


“To the child, they’re just normal glasses — almost all children with amblyopia have to wear glasses — but to the parent and the doctor, it’s like a secret recipe,” Dror said, commenting on the potential for improved compliance.


Dror speculated that the technology may work for adults as well, but conceded that clinical trials are necessary.


Amblyz will launch this month, and will be available to the mass market by the end of the year, according to Dror.


The Shaw lens


The Shaw lens is a spectacle lens designed by Peter J. Shaw, OD, to combat amblyopia through a refractive approach.


“The key to this system lies in sensory fusion,” Shaw said in an interview. “With a typical case of amblyopia due to anisometropia, the image in one eye (the weak, defocused eye) fails to synch with the image in the other eye (the strong, focused eye), and the brain will tend to ignore the weak, defocused eye.” 


Even though the refractive requirements are met with conventional eyeglass lenses, the image difference that is created impairs sensory fusion due to the image size difference. Dr. Shaw stated that “addressing the inter-ocular magnification is the foundation of successful treatment of refractive amblyopia and at the core of the Shaw lens design.”


In a recent case report, Bobier and Shaw prescribed spectacle lenses to a 7-year-old patient with anisometropia. The lenses used specially designed software to alter the spectacle frame and lens parameters to reduce the static and dynamic aniseikonia. The spectacles were worn consistently over a 2-year period. The authors reported that “single-letter acuity normalized by 5 months while crowded acuity took longer. Improvements of binocular vision resulted concomitantly. However, improvement in suppression and stereo acuity continued for 2 years.”


Therapies in development


There are still many therapies in development. According to PCON Editorial Board member Joseph P. Shovlin, OD, new initiatives have been studying the effects of anti-suppression therapy, methods of improving perceptual learning 
and even acupuncture.


“Coupling therapies with commonly used multimedia devices such as smart phones and iPads are commonplace today,” and will continue to be used, he said.


“There has also been a lot discussion about direct visual cortex stimulation, and transcranial approaches have recently been proposed from manufacturers outside of the country,” he added. – by Daniel R. Morgan


References:
  • Bavelier D, Levi DM, Li RW, Dan Y, Hensch TK. Removing brakes on adult brain plasticity: From molecular to behavioral interventions. J Neurosci. 2010;30:14964-14971.
  • Bobier WR, Shaw PJ. A consideration of binocular parameters in the spectacle correction of anisometropic amblyopia: A case report. Optom Vis Dev. 2012;43(2):67-71.
  • Levi DM. Prentice Award lecture 2011: Removing the brakes on plasticity in the amblyopic brain. Optom Vis Sci. 2012;89(6):827-838.
  • Li RW, Ngo C, Nguyen J, Levi DM. Video-game play induces plasticity in the visual system of adults with amblyopia. PLoS Biology. 2011;9(8):1-11.
  • Pediatric Eye Disease Investigator Group. A comparison of atropine and patching treatments for moderate amblyopia by patient age, cause of amblyopia, depth of amblyopia, and other factors. Ophthalmology. 2003;110:1632–1638.
  • Repka MX, Beck RW, Holmes JM, et al. A randomized trial of patching regimens for treatment of moderate amblyopia in children. Arch Ophthalmol. 2003;121:603–611.
For more information:
  •  Susan Cotter, OD, MS, can be reached at 2575 Yorba Linda Blvd., Fullerton, CA 92831; (714) 449-7488; fax: (714) 992-7846; scotter@scco.edu.
  • Ami Dror is chief strategy officer of XPand 3D. He can be reached at (818) 319-0381; ami.dror@xpandcinema.com; www.xpandcinema.com.
  • Dennis Levi, OD, PhD, FAAO, can be reached at 486-488 Minor Hall, University of California, Berkeley, CA 94720; (510) 642-3414; dlevi@berkeley.edu.
  • Glenn Moro is vice president and general manager of amblyopia at RevitalVision. He can be reached at 1617 St. Andrews Drive, Suite 210, Lawrence, Kansas 66047; (817) 999-6591; glenn.moro@revitalvision.com.
  • Peter J. Shaw, OD, is president of Shaw Lens Inc. He can be reached at (877) 796-9944; peter.shaw@shawlens.com.
  • Joseph P. Shovlin, OD, can be reached at Northeastern Eye Institute, 200 Mifflin Ave., Scranton, PA 18503; (570) 342-3145; jpshovlin@gmail.com
  • Abraham Spierer, MD, can be reached at Jabotinsky St. 99, Ramat Gan 5255313, Israel; 972-3-5302537; Abraham.Spierer@sheba.health.gov.il.
  • Disclosures: Cotter, Levi and Shovlin have no relevant financial disclosures. Spierer has a financial interest in OphthoCare Ltd., who is affiliated with XPand.