Ocular Manifestations and Therapeutic Options in Patients with Familial Amyloid Polyneuropathy: A Systematic Review

Abstract

Purpose. This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations. Methods. The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. Pathophysiology and Treatment. FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease. Conclusion. The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein.

Corneal confocal microscopy and familial amyloidotic polyneuropathy

“…Finally, abnormalities due to the production of TTR by the retinal pigment epithelium are observed, including vitreous amyloidosis and amyloid retinal angiopathy [2]. Other ophthalmological manifestations have been reported: corneal hypoesthesia, pupillary light-near dissociation and more rarely bilateral optic neuropathy [3]. As the TTR is mainly produced by the liver, hepatic transplantation slows or even stops disease progression and increases the survival of patients with FAP [4].…”

<p>Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care</p>

“…Ocular disorders include dry eye syndrome (nearly 70%), amyloid deposition on the iris (38%) or on the anterior capsule of the lens (33%), pupillary disorders (as scalloped iris in about 28%), glaucoma (20%), vitreous opacity (17%), abnormal conjunctiva vessels (14%), and amyloidotic retinal angiopathy (4%). 37,38 Finally, central nervous system (CNS) involvement, resulting from leptomeningeal amyloid angiopathy, has also been described, sometimes in combination with eye impairment (oculoleptomeningeal amyloidosis). Leptomeningeal and meningovascular amyloidosis are rare forms of amyloidosis caused by a limited spectrum of TTR variants, such as Notes: The number of "+" provides an indication of the likelihood of presence of symptoms, with "±" indicating an unknown likelihood as the symptom is present in some patients and not in others.…”

“…When ocular manifestations are present, the frequency of ophthalmological evaluations varies depending on severity of eye involvement, and should include measurement of visual acuity and of intraocular pressure, Schirmer test, ocular fundus and slit-lamp examination. 38 Renal evaluation is also crucial, and usually based on measurement of serum creatinine, proteinuria and microalbuminuria, and on the estimated glomerular filtration rate (eGFR). 2,36 Determination of serum cystatin C may represent another valid marker for non-invasive estimation of GFR: since serum cystatin C concentration seems to be independent of sex, age, and muscle mass, it has been suggested to be a more sensitive marker of renal dysfunction compared with serum creatinine level.…”

Apolipoprotein AI-Derived Vitreous Amyloidosis: An Elusive Diagnosis

“…Ocular manifestations are observed in only 10% of the cases of familial amyloidosis polyneuropathy [4]. The incidence of vitreous opacities in familial amyloidosis polyneuropathy varies from 5.4 to 35%.…”

“…The incidence of vitreous opacities in familial amyloidosis polyneuropathy varies from 5.4 to 35%. [4,5]. Vitreous amyloidosis is almost always related to mutant transthyretin, which is a plasma protein carrier of thyroxine and vitamin [5].…”