The present study aimed to investigate ocular findings in hereditary transthyretin amyloidosis (ATTRv) pre-symptomatic carriers. Fourteen ATTRv pre-symptomatic carriers, who are patients with positive genetic testing but without signs or symptoms of the disease, were retrospectively evaluated. Retinal morphology was assessed using optical coherence tomography (OCT) and OCT-angiography. Retinal function was evaluated using cone b-wave and photopic negative response (PhNR). Pupillometry and in vivo corneal confocal microscopy (IVCM) were performed. ATTRv pre-symptomatic carriers presented a significantly reduced central macular thickness (CMT) (p = 0.01) and outer nuclear layer (ONL) thickness (p = 0.01) in comparison to normal controls. No differences were found when analyzing sub-foveal choroidal thickness, retinal nerve fiber layer and ganglion cell complex. In comparison to healthy controls, pre-symptomatic carriers presented an attenuated superficial retinal vascular network and a significantly augmented PhNR amplitude (p = 0.01). However, PhNR implicit times, B-wave amplitude and B-wave peak time did not show significant differences in comparison to controls. No differences were found for pupillometric values. All the examined eyes presented alterations in the IVCM. Preclinical ocular structural and functional abnormalities can be found in ATTRv pre-symptomatic carriers. Thus, an extensive ophthalmological evaluation should be included at the baseline visit and during follow-up. Considering the availability of new drugs potentially able to prevent or delay disease progression, the identification of new disease biomarkers appears to be particularly promising.
Keywords: ATTRv pre-symptomatic carriers; OCT-angiography; electroretinogram (ERG); in vivo corneal confocal microscopy (IVCM); ocular biomarkers; optical coherence tomography (OCT); personalized medicine; transthyretin amyloidosis (ATTRv).