A new study investigating ocular findings in presymptomatic carriers of hereditary transthyretin amyloidosis (hATTR) found consistent abnormalities. The study, published in Diagnostics, found that the carriers had significantly reduced central macular thickness (CMT) and outer nuclear layer (ONL) thickness, as well as reduced vascularization of the superficial retinal network.

“The early identification of disease onset in [hATTR] pre-symptomatic carriers could allow prompt treatment as soon as minor, but clinically meaningful, disease signs are detected,” the authors wrote.

“The aim of the present study was to investigate ocular findings in [hATTR] presymptomatic carriers using optical coherence tomography, OCT-angiography, electrophysiology, pupillometry, and in vivo corneal confocal microscopy in order to find novel potential ocular biomarkers of the disease.”

The research team enrolled 14 individuals who were presymptomatic carriers of hATTR between January 2021 and September 2022 at a single center in Italy. Genetic characterization of the patients’ variants, neurological assessments, and nerve conduction studies were performed on all participants, in addition to a full ophthalmological examination.

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The results revealed structural and functional ocular abnormalities in all patients, particularly reductions in vascularization of the superficial retinal network, CMT, and ONL thickness as well as increased photopic negative response amplitude compared with those of healthy controls.

The authors noted that the alterations were not entirely surprising, given that there is evidence that ocular and systemic manifestations can be dissociated due to the eye’s ability to produce its own transthyretin. Symptomatic patients with hATTR have also been shown to have subclinical ocular abnormalities.

The researchers caution that the small sample size limits the ability to draw firm conclusions, but given the rarity of the disease and lack of literature on carriers, the data are useful. Based on these results, they recommend thorough ophthalmological assessments at baseline and during follow-up for all presymptomatic carriers of hATTR.


Maceroni M, Falsini B, Luigetti M, et al. Ocular morpho-functional evaluation in ATTRv pre-symptomatic carriers: a case series. Diagnostics (Basel). 2023;13(3):359. doi.10.3390/diagnostics13030359