OBJECTIVE: Evaluation of ophthalmologic safety with focus on retinal safety in 
patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI®), a 
survival of motor neuron 2 splicing modifier associated with retinal toxicity in 
monkeys. Risdiplam was approved recently for the treatment of patients with SMA, 
aged ≥ 2 months in the United States, and is currently under Health Authority 
review in the EU.
METHODS: Subjects included patients with SMA aged 2 months-60 years enrolled in 
the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. 
Ophthalmologic assessments, including functional assessments (age-appropriate 
visual acuity and visual field) and imaging (spectral domain optical coherence 
tomography [SD-OCT], fundus photography, and fundus autofluorescence [FAF]), 
were conducted at baseline and every 2-6 months depending on study and 
assessment. SD-OCT, FAF, fundus photography, and threshold perimetry were 
evaluated by an independent, masked reading center. Adverse events (AEs) were 
reported throughout the study.
RESULTS: A total of 245 patients receiving risdiplam were assessed. 
Comprehensive, high-quality, ophthalmologic monitoring assessing retinal 
structure and visual function showed no retinal structural or functional 
changes. In the youngest patients, SD-OCT findings of normal retinal maturation 
were observed. AEs involving eye disorders were not suggestive of 
risdiplam-induced toxicity and resolved with ongoing treatment.
INTERPRETATION: Extensive ophthalmologic monitoring conducted in studies in 
patients with SMA confirmed that risdiplam does not induce ophthalmologic 
toxicity in pediatric or adult patients with SMA at the therapeutic dose. These 
results suggest that safety ophthalmologic monitoring is not needed in patients 
receiving risdiplam, as also reflected in the United States Prescribing 
Information for risdiplam.