Choroidal and retinal angiopathy in V30M hereditary transthyretin amyloidosis

Abstract

Purpose : To identify retinal and choroidal vasculature abnormalities associated with hereditary amyloidosis secondary to V30M transthyretin mutation (V30M H-TTR-A) using fluorescein and indocyanin (ICG) green angiography.

Methods : This prospective monocentric observational study was conducted at the French National Reference Center for H-TTR-A between April 2014 and October 2015. Consecutive genetically confirmed and biopsy proven V30M H-TTR-A patients were included. All patients underwent complete neurological examination, including autonomic and sensorimotor polyneuropathy staging with validated clinical scores, and complete ophthalmological evaluation, including staging of intraocular amyloid deposits, color retinography, fluorescein (FA) and ICG angiograms (ICG-A).

Results : Eighteen H-TTR-A patients (11 males, 7 females, mean age 61.6 ± 12.1 years) with symptomatic polyneuropathy of variable severity were included. Mean disease duration at inclusion was 11 ± 5.6 years (range: 3.3 - 20.7). Retinal amyloid angiopathy (RAA) was detected in 24 eyes (92%) of 13 patients, including microaneurysms, retinal hemorrhages, vascular sheathing, and retinal ischemia of variable extent, the latter being mostly underestimated with ophthalmoscopy and color retinography. Three patients (5 eyes) presented neovascular glaucoma and two (2 eyes) showed pre-retinal neovascularization. ICG-A revealed choroidal amyloid angiopathy (CAA) in all patients, with 3 distinct patterns: diffuse (9/18 patients), focal (5/18 patients) or punctiform (4/18 patients) late hyperfluorescence along the choroidal arteries.

Conclusions : Retinal amyloid angiopathy is a frequent and severe complication of H-TTR-A that may lead to anterior and posterior segment neovascularization. It may be underestimated with color retinography. Fluorescein angiograms should thus be performed in presence of fundoscopic signs for early detection and evaluation of this complication. Choroidal amyloid angiopathy was detected in all patients, with late hyperfluorescent delineation of the choroidal arterial vasculature that was very typical and reproducibly found in this series. This sign could be considered as of great help in patient who present with potential vitreous amyloid deposits, as the triad of suspected vitritis, RAA and CAA could help to differentiate H-TTR-A patients with other causes of uveitis masquerading syndrome, reducing the need for further investigations.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.