Amblyopia - Emerging treatments

Binocular video games

The possibility of using binocularity-stimulating video games in the treatment of amblyopia may be more appealing to children and families than patching. However, compliance with binocular treatment is a significant issue. Currently, there is insufficient evidence to recommend binocular therapy to treat amblyopia; further research is required to determine whether there is a role for binocular treatments for amblyopia in clinical practice.[1][77][87][88][89][90][91]

Modulation of the plasticity in the visual system

This may increase the success rate of amblyopia treatment for older children and possibly even for adults. Preliminary studies of candidate drugs, such as levodopa and cytidinediphosphocholine (CDP-choline), have not shown dramatic benefits. However, larger studies are needed, and other pharmacological and non-pharmacological agents may prove beneficial.

Levodopa

Levodopa is converted in the body to the neurotransmitter dopamine. Initial studies in adults with amblyopia found that levodopa improved visual function by enhancing the plasticity of the visual pathways.[92][93] It is now being studied as an adjunct to patching treatment in older amblyopic children. One randomised controlled trial (RCT) of levodopa/carbidopa or placebo combined with full-time occlusion for the treatment of strabismic or anisometropic amblyopia in older children found no beneficial effect of levodopa. Visual acuity improvement was the same in both groups, and the levodopa group had an initial decline in contrast sensitivity.[94] Another RCT confirmed this finding by using levodopa for residual amblyopia in older children, aged 7-12 years.[95] No significant difference was found in prescribing placebo versus oral levodopa while continuing to patch for 2 hours each day. These results suggest that adjunctive levodopa is unlikely to have a meaningful benefit in the management of amblyopia in children.

Liquid crystal glasses

Liquid crystal glasses (LCG) combine refractive correction and occlusion via a liquid crystal shutter that is electronically controlled by a microprocessor. During treatment, an electric charge intermittently changes the spatial orientation of the crystal molecules in the lens (applied to the non-amblyopic eye) such that the lens alternates between transparent and opaque states. The frequency and duration of each state is pre-programmed. In a small prospective trial, using liquid crystal glasses for 8 hours per day (with average occlusion/transparent times of 40 seconds/20 seconds each minute, respectively) significantly improved visual acuity among 24 children ages 4-7 years during the 9 months of treatment.[96] These findings were replicated in a similar prospective study with 14 subjects.[97] Early findings from a 2016 RCT, which enrolled 34 subjects to patching for 2 hours or LCG for 4 hours, have revealed significant improvements in vision for both groups, but no difference in the overall improvement between groups, suggesting LCG is not inferior to occlusion.[98] Further research is currently underway.

CDP-choline

CDP-choline is a potential neuroprotective agent that maintains neuronal cell membranes and contributes to synthesis of neurotransmitters such as acetylcholine. A randomised non-masked study of 61 children aged 5-10 years with strabismic or anisometropic amblyopia compared the effect of CDP-choline plus 2 hours of patching with 2 hours of patching alone.[99] Visual acuity improvement was similar in the 2 groups at 30 days. However, the CDP-choline plus patching group maintained the visual improvement at 90 days, whereas visual acuity in the patching alone group regressed compared with baseline.[99] The study suggested that CDP-choline may improve the long-term stability of amblyopia treatment. However, despite randomisation, the baseline mean visual acuity in the patching-alone group was slightly better than in the CDP-choline plus patching group, which could have limited the number of lines of potential visual improvement possible in the patching-alone group. In addition, other studies have shown that patching alone continued for longer than 30 days results in long-term stability.[72][84]

Transcranial magnetic stimulation

The mechanism by which transcranial magnetic stimulation (TMS) might change the plasticity of the brain is unknown. TMS is thought to alter the excitability of neurons. One study of 9 amblyopic patients found transient improvements in contrast sensitivity after they underwent TMS of the visual cortex.[100] The study included some controls, such as TMS of the motor cortex in the amblyopic patients, and TMS of the visual cortex in non-amblyopic patients. The study did not find improvements in contrast sensitivity when the motor cortex of amblyopic patients was stimulated, but it did find a small improvement in contrast sensitivity of non-amblyopic patients undergoing TMS of the visual cortex.[100] A study that randomises and masks amblyopic patients to true or placebo TMS of the visual cortex would be valuable.

Acupuncture

Acupuncture could theoretically influence amblyopia treatment by affecting blood flow to the eye and brain, or by leading to metabolic changes that would activate the visual cortex. Two studies performed in China evaluated acupuncture as a treatment for amblyopia.[101][102] A prospective randomised crossover trial evaluated spectacle wear alone compared with spectacle wear plus acupuncture for the treatment of anisometropic amblyopia in children aged 3-6 years. Children treated with spectacles plus acupuncture had an average 0.8-line greater improvement in visual acuity at 15 weeks compared with children treated with spectacles alone. However, the visual acuity improvement of 2.2 lines in the spectacle alone group was slightly less than that seen in other studies evaluating spectacles alone for the treatment of anisometropic amblyopia. When the spectacle alone group was then crossed over to spectacle wear plus acupuncture for weeks 16-30 of the trial, children gained an additional 1.2 lines of vision, whereas visual acuity plateaued at 15 weeks for those who began with spectacles plus acupuncture and then went on to treatment with spectacles alone during weeks 16-30.[101] Another study randomised children aged 7-12 years with anisometropic amblyopia to 2 hours' daily patching or acupuncture treatment after they had already worn appropriate spectacle correction for 16 weeks. After 15 weeks of patching or atropine treatment, both groups had similar improvement in visual acuity of approximately 2 lines; however, the patches were felt patches worn over the spectacles rather than sticky patches applied to the skin, which can allow the patient to peek and may not be as effective.[102] Despite this limitation, the magnitude of treatment effect was similar to that observed in other studies using sticky patches for the treatment of anisometropic amblyopia.

Refractive surgery for refractive amblyopia and amblyogenic refractive errors

In children with significant refractive errors who cannot successfully wear spectacles or contact lenses, refractive surgery is an option.[103][104][105] Corneal refractive surgery, such as photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK), and intraocular surgery (e.g., phakic intra-ocular lens implantation, clear lens extraction, refractive lens exchange) have been used in children who did not benefit from traditional treatment, including those with non-compliance due to neurobehavioural disorders.[103][105][106][107][108] Laser refractive surgery may not only address amblyogenic refractive error but also decrease anisometropia.[105] One meta-analysis of children aged 7-17 years undergoing refractive surgery for accommodative esotropia found improvement in both uncorrected and corrected visual acuity after refractive surgery. Uncorrected visual acuity was superior in patients undergoing PRK compared with laser assisted in-situ keratomileusis (LASIK).[109] Corneal haze was the most common complication, occurring in 5.3% of LASIK cases and 8.5% of PRK cases.[109] Multi-centre studies are needed to determine the long-term paediatric outcomes and to assess the benefits and risks of newer refractive technologies.[103][105][109]