Early Diagnosis of Eye Manifestations Essential in FAP Patients, Review Says

Although uncommon, eye manifestations can affect patients with familial amyloid polyneuropathy (FAP). These are mostly caused by opacities in the jelly liquid of the eye and usually treated by surgery, a review study reports.

In rare cases, these problems can further complicate and lead to vision loss. A comprehensive, multidisciplinary evaluation and follow-up “is essential” for the early diagnosis and prevention of such complications, researchers stressed.

The study, titled “Amyloidosis and Ocular Involvement: an Overview” was published in the journal Seminars in Ophthalmology.

In this review, a team of researchers looked in detail at the eye manifestations and strategies to treat it in patients with different types of amyloidosis – a range of disorders characterized by the deposition and accumulation of misfolded proteins, known as amyloid fibrils, in several organs including the eye.

Eye signs and symptoms vary greatly across the different types of amyloidosis. While eye problems can be a significant, and sometimes the only, manifestation of some forms of amyloidosis, they are less common in other types of the disease, such as familial amyloid polyneuropathy (FAP).

For their analysis, researchers did a literature review and conducted a study in 178 patients with amyloidosis, referred to a single center in Italy.

They found ocular symptoms in 41 patients (23%), 32 of whom had AL amyloidosis, five had AA amyloidosis and four had familial transthyretin amyloidosis (ATTR) caused by Val30Met mutations in the transthyretin (TTR) gene, also known as FAP.

Familial ATTR usually does not affect the eyes. Ocular manifestations develop in about 10% of the patients with this type of amyloidosis, tend to appear later in the course of the disease and are unrelated to the involvement of other organs.

These manifestations are mostly caused by vitreous amyloid, opacities of glass-wool appearance that form in the vitreous, the gel-like substance that fills most of the eyeball. All four patients with familial ATTR and eye involvement in the present study had vitreous amyloid.

Other eye manifestations that can occur in FAP patients include neurotrophic keratitis (loss of sensitivity in the cornea), glaucoma (damage to the optical nerve that can cause permanent vision loss), or abnormalities of vessels in the retina, the tissue responsible for detecting light intensity and colors.

Treatment usually consists of pars plana vitrectomy, a type of eye surgery able to clear the haze and improve visual acuity. In cases where the problem returns, it may be necessary to repeat vitrectomy.

Glaucoma is the most worrying of all eye manifestations, has it can result in vision loss and is frequently resistant to medical treatment. In such cases, patients need to be treated by filtering surgery.

Neither liver transplant nor treatment with Pfizer’s Vyndaqel (tafamidis) seem to work to halt eye problems, possibly due to the fact that amyloid fibrils can be produced by the eye itself.

The frequency of ocular involvement may vary depending on the genetic cause of the disease. The most common TTR mutation in patients with eye manifestations is Val30Met, which is also the most common mutation associated with FAP.

However, at least 27 variants in the TTR gene have been associated with cases where eye symptoms are the main complaint or the eye is one of the several organs affected.

Although eye manifestations affect a minority of FAP patients, “a comprehensive, multidisciplinary evaluation is essential, which implies an important role for the ophthalmologist in the early diagnosis of vitreous amyloid, in the prevention and early recognition of secondary glaucoma, and in the careful follow-up of these patients,” researchers stated.

They also recommend that, at least in tertiary referral centers, “an ophthalmologic examination should be included in the follow-up of all patients with established or suspected amyloidosis,” independently of its underlying cause.