A range of new therapies for treatment-resistant

New approaches to amblyopia

A range of new therapies may offer hope to treatment-resistant amblyopes. Roibeard Ó hÉineacháin reports

There are many new treatments under investigation for the treatment of amblyopia that may provide useful alternatives to patients who are not amenable or unresponsive to traditional patching, reports Shira L Robbins MD, Professor of Ophthalmology at the Shiley Eye Institute, University of California, San Diego, California, US.

“The best treatment is whatever treatment the family can do. And every family unit is different and we as paediatric ophthalmologists know that almost better than anyone else,” Dr Robbins told the 2020 WSPOS Virtual Meeting.

She noted that occlusion therapy for amblyopia has a long history, dating back to 800 AD, when Thābit ibn Qurrah al-Harrānī first described occlusion of the better eye to improve vision of the strabismic eye.

In more modern times, David Hubel and Torsten Wiesel were able to explain why occlusion therapy works on a histologic level and subsequently received the Nobel Prize for their work, the first to be awarded for ophthalmic disease.

She pointed out that amblyopia affects many different aspects of visual function, including colour and contrast perception, peripheral vision. Moreover, amblyopic patients have a three times greater likelihood of losing vison in their fellow eye during the course of their life, making the search for new treatments all the more urgent.

PHARMACOTHERAPY Pharmacotherapy with various agents is among the new lines of research in the treatment of amblyopia, Dr Robbins noted. Prominent among the agents under investigation is levodopa, a precursor of the neurotransmitter dopamine, which is found in the brain and the retina. The theory behind its use is that will increase neuroplasticity.

Research where levodopa has been combined with patching has been confined to small studies, yielding mixed results. On the other hand, some functional MRI studies have shown increased activation of the occipital lobe following levodopa therapy. However, other studies have yielded contradictory results. Moreover, the agents may also have only a temporary effect. And as with any neurotransmitter there are potential concerns regarding long-term side-effects, she said.

Another medication that has been investigated is citicoline, which is an intermediate in the creation of phospholipid cell membranes and which may blunt nerve cell damage. However, like levodopa it has had mixed results when used to augment occlusion therapy. In addition, the studies have only had short term follow-up.

LIQUID CRYSTAL GLASSES A new approach to occlusion therapy is the use of electronically controlled liquid crystal glasses. Through a shuttering effect they occlude the amblyopic eye at intervals of 30 seconds throughout the day. In a small study they were noninferior to patching at three months follow-up. However, the expected increased compliance with this treatment was only at 50%.

“I can tell you from my own experience that these glasses can be very well accepted even among the children who are most adamantly resistant to patching. I have had cases where other treatments failed miserably and these have done the trick,” Dr Robbins said when measured with temperature monitors.

PERCEPTUAL LEARNING Perceptual learning is an approach that has been researched for over 40 years. It is designed to induce changes in visual perception through repetitive practice of specific controlled visual tasks. There have been studies involving a small number of patients that have shown an improvement in orientation discrimination stereoacuity and contrast sensitivity. However, the studies lacked long-term follow-up. TRANSCRANIAL MAGNETIC STIMULATION Transcranial magnetic stimulation, a technology that is now used in neurology and psychiatry, is also being investigated as a treatment for amblyopia. The magnetic field is applied to the visual cortex, which induces a weak electrical current that stimulates the cortical areas transiently.

A study conducted in Canada showed that adult amblyopic patients undergoing this treatment had improvements in their contrast sensitivity. In another study, conducted in Portugal, the treatment appeared to produce transient improvements in both visual acuity and stereoacuity when applied to the right occipital lobe.

ACUPUNCTURE Acupuncture is currently the subject of fairly intensive investigation as a treatment of amblyopia with 14 randomised controlled trials involving over more than 2,000 patients.

“This a well-studied modality and it should not be overlooked,” Dr Robbins said.

DARKNESS THERAPY Another means of potentially stimulating visual rehabilitation is to place the patient in total darkness for three-to-10 days. The theory is that darkness can biochemically prime the brain for reactivation of synaptic plasticity, thereby encouraging synaptic modifications and promoting visual recovery. Animal studies have shown it to be very effective. However, it would probably be an unattractive option for paediatric amblyopes.

EXERCISE FOR SIGHT Exercise may be another useful tool in the treatment of amblyopia. In a recent clinical trial out of Italy involving 10 adult amblyopes, interval cycling combined with patching resulted in a mean visual acuity improvement of 0.15 logMAR, and six of the patients also recovered stereopsis.

“We have come a long way since 800AD, but sometimes simple can still be good – patching is still powerful,” Dr Robbins concluded. Shira L Robbins: srobbins@ucsd.edu