Amblyopia, although aided mildly in improvement with oral levodopa/carbidopa, sill remained best-treated with the eye patch occlusion.
Amblyopia, although aided mildly in improvement with oral levodopa/carbidopa, still remained best-treated with the eye patch occlusion. Photo: National Eye Institute/NIH. Click image to enlarge.

Due to the shortened window or critical period in which amblyopia treatment yields greater likelihood of success, the need for effective therapy is palpable. The standard of care includes optical correction of refractive error and occlusive path therapy, which may be effective up until 10 years of age. After this time, the brain’s plasticity is not as well maintained in neural pathways, and kids have even been shown to plateau in visual improvement at an even younger age, around seven to eight years.

Since older children outside this period may exist who have not received or have failed the traditional occlusive patch route, research has been conducted over the years in consideration of alternative therapies. As outlined in one new study in Ophthalmology, one possible way to augment amblyopia treatment is with levodopa and/or carbidopa. The report, conducted on behalf of the American Academy of Ophthalmology, reviewed published literature on the use of these agents in aiding amblyopia treatment.

Of the 55 articles found, only 12 were considered appropriate and included in final assessment and were assigned a level of evidence by panel rating. Nine studies were rated level 1, three were rated level 2 and none were rated level 3 (lowest). Reviewing said articles, the study researchers found treatment with these agents ranged from duration of three to 16 weeks, due to concerns of long-term adverse effects like tardive dyskinesia; no studies reported this complication to occur in any participants.

Levodopa dosing ranged from 1.5mg to 8.3mg/kg/day, usually divided into three doses daily. Any carbidopa used in these studies was about 25% of the levodopa dosage in all treatments. Although the authors did find evidence supporting oral administration of both agents as an effective augment to traditional patch treatment, the improved vision effect was small and only significant when compared with patching alone in two of the 12 studies. Unfortunately, vision regression was also reported in a majority of nine out of 12 studies.

Based on these statistics, the authors came to the conclusion that “given the potential for significant side effects such as tardive dyskinesia with long-term therapy, levodopa/carbidopa does not appear to be a viable option for amblyopia therapy.” While short-term side effects of the medication(s) were not consistently reported, most frequently reported were mild, including headache and nausea.

Although the improvement of amblyopia with levodopa/carbidopa was minimal and transient throughout the studies, the authors do note that both studies demonstrating statistical significance with treatment possessed two characteristics: small patient numbers and inclusion of younger patients that would benefit from patch therapy alone. Moving forward, the authors suggest that “future research may focus on changing the dosage of these medications, studying newer agents to increase dopaminergic or other neurotransmitter functions and minimizing side effects.”

Morrison DG, Heidary G, Chang MY, et al. Levodopa/carbidopa to augment the treatment of amblyopia: a report by the American Academy of Ophthalmology. Ophthalmology. August 29, 2023. [Epub ahead of print].