Risdiplam Not Associated With Retinol Toxicity in SMA, Study Says

Treatment with risdiplam may not elicit ophthalmologic toxicity in older patients, as well as infants with immature retinas.

Ophthalmologic safety monitoring is not necessary for patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam (Evrysdi), say researchers, who studied the impact of the treatment in patients across 3 trials. Their results were published in Annals of Clinical and Translational Neurology.

Reviewing data from the FIREFISH, SUNFISH, and JEWELFISH studies, the researchers assessed outcomes of 245 risdiplam-treated patients, who ranged from age 2 months to 60 years at enrollment, including infants with retinas that were not fully matured. From the data, they determined that the treatment does not elicit ophthalmologic toxicity in these patients.

The results follow a previous study in which retinal toxicity was observed in cynomolgus monkeys receiving risdiplam daily for 39 weeks. In that study, photoreceptor degeneration was only observed with mid and high doses of the treatment.

In the current study, monitoring determined that there were no retinal structural or functional changes for the risdiplam-treated patients, and adverse events involving eye disorders were unrelated to risdiplam treatment, not suggestive of risdiplam-induced effects, and resolved with ongoing treatment.

“The comprehensive set of ophthalmologic assessments, which included imaging and visual function testing, was tailored to evaluate all aspects of ophthalmologic safety, with a special focus on retinal structure using [spectral domain optical coherence tomography (SDOCT)],” explained the researchers. “The central reader developed an innovative SD-OCT protocol scan that was capture following nasal, temporal, superior, and inferior fixation when possible to enhance even further the exploration of the peripheral retina.”

No risdiplam-treated patients who received the recommended dose of treatment had a change that indicated risdiplam-induced toxicity at their last visit.

Throughout the studies, 206 patients accounted for 477 ophthalmologic findings at the last visit, most of which were attributable to: changes in retinal layer thickness due to angulation variability during SD-OCT assessment, measurement variability in intraocular pressure, Best Corrected Visual Acuity, Sloan Low Contrast Visual Acuity, or threshold perimetry, which were not clinically significant.

According to the researchers, the high number of these findings compared with baseline was not surprising because of variability in optical coherence tomography image angles due to patients’ head and neck weakness.


Sergott R, Amorelli G, Baranello G, et al. Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy. Ann Clin Transl Neurol. Published online November 24, 2020. doi:10.1002/acn3.51239.