Researchers make strides in amblyopia

Accumulating evidence suggests that multiple treatments can help people with amblyopia, according to a review of the literature.

Research over the past 20 years has provided “reliable scientific evidence to show that prescribing refractive correction and atropine or occlusion with additional interventional material should optimise visual outcomes in amblyopic patients with minimal side effects,” wrote Gail DE Maconachie and Irene Gottlob of the Ulverscroft Eye Unit at the University of Leicester, UK. They published their findings in Biomedical Journal.

In amblyopia, one eye doesn’t function as well as the other. This mostly occurs because something forces the visual system to prefer one eye. The most common reason is a difference in refractive error between the two eyes.

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A difference in spherical correction (anisometropic amblyopia) and strabismus are the two most frequent underlying causes. But other problems such as unilateral cataract or ptosis can also bring about amblyopia.

As far back as the 1st century AD, physicians have treated amblyopia by covering the dominant eye, forcing the visual system to develop capacities in the affected eye, a treatment known as occlusion therapy. It has often been used to treat children on the theory that the condition will become more difficult as the visual system matures.

But a path-breaking review by Snowdon and colleagues found that few trials had rigorously tested this treatment or any other. Also, few studies have explored the hypothesis that amblyopia can only be treated before the nervous system matures.

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Since then, many randomised controlled trials have been done, and Monachie and Gottlop set about distilling their conclusions.

They found evidence that occlusion therapy works, but children naturally resist wearing eye patches. Therefore, some studies have examined just how much occlusion is necessary. The results indicated that 2 hours per day of occlusion worked as well as 6 hours per day for moderate amblyopia. Likewise, 2 hours per day worked as well as 6 hours per day for severe amblyopia.

Treatment adherence

Another study suggested that children end up wearing their eye patches for less than half the prescribed time, calling into question the importance of prescribing a precise time period for occlusion.

Conversely, some researchers have found that prescribing tasks requiring near vision can speed the results of occlusion therapy. And others have found that providing educational cartoons, decorating the patches, and providing rewards resulted in children wearing the patches longer.

But therapists have other alternatives for treating amblyopia. Some research suggests that fully correcting the patient’s refraction can significantly improve amblyopia, and is sometimes the only therapy needed.  And surveys show that many orthoptists begin treatment of amblyopia with refractive correction before trying other methods.

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However, children often don’t want to wear glasses, and studies suggest a wide variation in adherence. Questions also remain about whether some patients are more likely to benefit from refractive correction than others, and how long this treatment should be tried before moving on to other therapies. Some concerns have also been raised that refractive therapy can delay emmetropisation.

Because of the challenges of getting children to wear patches or glasses, some therapists have used atropine to temporarily blur vision in the dominant eye by paralysing the ciliary muscles that control accommodation and constriction of the pupil.

Comparisons between atropine and occlusion therapy have shown similar outcomes, regardless of the type of amblyopia. Still, practitioners seem to use it as a fall-back method for patients who don’t adhere to occlusion therapy.

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A fourth alternative gaining attention is perceptual learning. In this therapy, patients practice perceptual tasks. The approach dates back at least to 1963 and the Cambridge Visual Stimulator (CAM), which used high-contrast rotating sine-wave gratings. The CAM fell out of favour when it could not demonstrate superior outcomes to occlusion.

But the advent of computer programs for perceptual learning has reawakened interest. Often patients work on contrast sensitivity tasks while the non-amblyopic eye is occluded. Game play formats may increase simulation of the amblyopic eye. In one example, patients play a game such as Tetris with only half the blocks visible to each eye. Transcranial direct current stimulation may hasten the benefits.

Future research

Perceptual learning still awaits validation with long-term randomised controlled trials, and research has not indicated whether one type of amblyopia might benefit more than another. Two studies have shown a decline in visual outcomes after 8–10 weeks, although this finding was less significant in a group that practiced binocular therapy than one that practiced monocular therapy.

Researchers have also experimented with pharmacological treatments of amblyopia, with levodopa being the most commonly prescribed drug. It is a precursor to dopamine, a neurotransmitter shown in animal models to be reduced in amblyopia. Treatment with levodopa has shown good results in several studies, especially when combined with occlusion therapy and with carbidopa, which increases levodopa uptake across the blood-brain barrier.

However, many patients lose visual acuity after they stop taking levodopa. And many researchers have reported side effects.

Other molecules might prove beneficial. Discoveries in mice have shown that the lynx1 gene codes for a protein that suppresses acetylcholine receptor signalling in the brain and regulates plasticity of the mature brain. Research is underway on cholinesterase inhibitors that could prevent the expression of lynx1 to extend the period of plasticity in the brain.

Finally, acupuncture has shown some promise, with two randomised controlled trials recording good results, including one in which patients improved more with acupuncture than with occlusion therapy. This approach may work by stimulating blood flow in the visual cortex. But Maconachie and Gottlob point out that a placebo effect could be particularly marked in acupuncture, which requires frequent clinic visits.

They conclude that much research remains to be done.