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Review
. 2021 Jun 22;12(7):955.
doi: 10.3390/genes12070955.

Ocular Involvement in Hereditary Amyloidosis

Angelo Maria Minnella  1   2 , Roberta Rissotto  3 , Elena Antoniazzi  4 , Marco Di Girolamo  5 , Marco Luigetti  6   7 , Martina Maceroni  1 , Daniela Bacherini  8 , Benedetto Falsini  1   2 , Stanislao Rizzo  1   2 , Laura Obici  9
Affiliations
Review

Ocular Involvement in Hereditary Amyloidosis

Angelo Maria Minnella et al. Genes (Basel). .

Abstract

The term amyloidosis describes a group of rare diseases caused by protein conformation abnormalities resulting in extracellular deposition and accumulation of insoluble fibrillar aggregates. So far, 36 amyloid precursor proteins have been identified, and each one is responsible for a specific disease entity. Transthyretin amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, due to the deposition of transthyretin (TTR), which is a transport protein mainly synthesized in the liver but also in the retinal pigment epithelial cells. ATTRv amyloidosis may be misdiagnosed with several other conditions, resulting in a significant diagnostic delay. Gelsolin and keratoepithelin are other proteins that, when mutated, are responsible for a systemic amyloid disease with significant ocular manifestations that not infrequently appear before systemic involvement. The main signs of ocular amyloid deposition are in the cornea, irido-corneal angle and vitreous, causing complications related to vasculopathy and neuropathy at the local level. This review aims at describing the main biochemical, histopathological and clinical features of systemic amyloidosis associated with eye involvement, with particular emphasis on the inherited forms. We discuss currently available treatments, focusing on ocular involvement and specific ophthalmologic management and highlighting the importance of a prompt treatment for the potential sight-threatening complications derived from amyloid deposition in ocular tissues.

Keywords: ATTR; amyloid; amyloidosis; corneal lattice dystrophy; gelsolin; keratoepithelin; ocular amyloidosis; personalized medicine; transthyretin; vitrectomy; vitreous opacities.

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Conflict of interest statement

The authors declare no conflict of interest related to this topic.

Figures

Figure 1
Figure 1
Clinical manifestations in ATTRv patients.
Figure 2
Figure 2
Phenotypic heterogeneity according to genotype.
Figure 3
Figure 3
Biochemical mechanisms leading to amyloidosis formation.
Figure 4
Figure 4
Sural nerve biopsy from a late onset ATTRv patient. H&E showing abundant eosinophilic deposits suggestive of amyloid.
Figure 5
Figure 5
Classical appearance of retrolental vitreous amyloid opacities in ocular TTR amyloidosis examined by slit-lamp examination: multiple sheet-like, cobweb-like and glass wool-like fibrils are present (magnification 16×).
Figure 6
Figure 6
Fundus ophthalmoscopic examination before (a) and after (b) vitreoretinal surgery (50-degree angle of view).
Figure 7
Figure 7
Slit-lamp examination showing areas with altered fluorescein distribution (BUT < 10 sec) and localized fluorescein staining (arrow) in amyloidosis patients (magnification 10× and diffuse illumination).
Figure 8
Figure 8
Poorly represented corneal nervous plexa with corneal confocal microscopy in amyloidosis.
Figure 9
Figure 9
Slit-lamp examination of pupillary indentations considered as a pathognomonic sign of ocular amyloidosis caused by amyloid deposition at the inner pupillary margin (magnification 10× and diffuse illumination).
Figure 10
Figure 10
Steps of amyloid formation and corresponding therapeutic strategies. Modified from: Recent advances in transthyretin amyloidosis therapy, Mitsuharu Ueda and Yukio Ando [8].
Figure 11
Figure 11
Slit-lamp examination of corneal lattice dystrophy in amyloidotic patients (magnification 16×).
See this image and copyright information in PMC

References

    1. Reynolds M.M., Veverka K.K., Gertz M.A., Dispenzieri A., Zeldenrust S.R., Leung N., Pulido J.S. Ocular Manifestations of Familial Transthyretin Amyloidosis. Am. J. Ophthalmol. 2017;183:156–162. doi: 10.1016/j.ajo.2017.09.001. - DOI - PubMed
    1. De Larrea C.F., Verga L., Morbini P., Klersy C., Lavatelli F., Foli A., Obici L., Milani P., Capello G.L., Paulli M., et al. A practical approach to the diagnosis of systemic amyloidoses. Blood. 2015;125:2239–2244. doi: 10.1182/blood-2014-11-609883. - DOI - PubMed
    1. Venkatesh P., Selvan H., Singh S.B., Gupta D., Kashyap S., Temkar S., Gogia V., Tripathy K., Chawla R., Vohra R. Vitreous Amyloidosis: Ocular, Systemic, and Genetic Insights. Ophthalmology. 2017;124:1014–1022. doi: 10.1016/j.ophtha.2017.03.011. - DOI - PubMed
    1. Sipe J.D., Cohen A.S. Review: History of the Amyloid Fibril. J. Struct. Biol. 2000;130:88–98. doi: 10.1006/jsbi.2000.4221. - DOI - PubMed
    1. Cohen A.S., Calkins E. Electron Microscopic Observations on a Fibrous Component in Amyloid of Diverse Origins. Nature. 1959;183:1202–1203. doi: 10.1038/1831202a0. - DOI - PubMed

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Supplementary concepts