Amyloidosis is a rare disease that occurs in several forms and in the familial transthyretin form can lead to eye problems.
All types of amyloidosis are due to proteins that take on an abnormal configuration and form amyloid fibrils, which accumulate in various tissues and organs and cannot be easily broken down by the body. These deposits interfere with the normal function of the organ in which they are found and depending on the site of accumulation can lead to pathological conditions, both systemic and localised, when they affect only one organ or tissue. The severity of the pathology depends precisely on the organs affected by the amyloid deposits.
Amyloidosis generally appears in individuals in middle age and beyond, but can also occur between the ages of 30 and 40, or even earlier. Depending on which part of the body is affected, amyloid deposits may cause weight loss, fatigue, shortness of breath, dizziness while standing, swelling of the ankles and legs, numbness and tingling in the hands and feet, alternating bouts of constipation and diarrhoea, and a rapid feeling of fullness after eating. In addition, if a patient tends to bruise easily, especially around the eyes (periorbital purpura)it is very likely that the cause is amyloidosis.
Among patients with familial amyloidosis, the mutation in the transthyretin (TTR) protein is the most common type and it has been noted that patients with TTR amyloidosis often have ocular involvement, especially in the vitreous.
Researchers from the Departments of Ophthalmology, in partnership with researchers from the Department of Haematology, at the Mayo Clinic in Rochester(Minnesota, USA) have carried out an interesting study, Ocular Manifestations of Familial Transthyretin Amyloidosis in which an analysis of the types and frequency of ocular manifestations in TTR amyloidosis was presented.
263 patients with a diagnosis of transthyretin amyloidosis were enrolled, with follow-up between 1970 and 2014. The 54 patients who developed ocular problems underwent a comprehensive eye examination on average every 4.25 months after the onset of systemic symptoms. Most of the patients with ocular symptoms were women and, clinically, the most frequent problem was a significant deterioration of visual acuity compared to the phase before the onset of amyloidosis. Among the ocular problems reported were amyloid vitreous, neurotrophic keratitis, retinal neovase formation and glaucoma. The types of glaucoma ranged from POAG (primary open-angle glaucoma) to exfoliating and neovascular forms (following occlusion of the central retinal vein by amyloid fibre deposits).
10 patients required vitrectomy for visually significant vitreous amyloidosis, with significant improvement in visual acuity from a baseline value of logMAR 0.70 (Snellen equivalent 20/100 ) to logMAR 0.05 ( Snellen equivalent approx. 20/20 ), P=0.003.
From an aetiological point of view, the following have been associated with vitreous amyloidosis three TTR mutations, Glu89Lys, Gly47Arg and Gly6Ser homozygouspreviously undescribed.
On the subject of amyloidosis, Italian research has recently come to the fore in Europe with two studies carried out by the Centre for the Study and Treatment of Systemic Amyloidosis of the Fondazione Irccs Policlinico San Matteo. The first study, published in Circulation, identified a new hereditary form of amyloidosis, caused by a mutation in the Apoa1 gene. This mutation causes the deposition of amyloid fibrils formed by the protein apolipoprotein A-I in several organs. A discovery of particular note is that this rare form of amyloidosis can mimic other more common variants, challenging current diagnostic algorithms.
The second study, "Predictors of Early Death in Patients With Wild-Type Transthyretin Cardiac Amyloidosis. published in the Journal of the American Heart Association', focused on wild-type transthyretin amyloidosis. The research identified key clinical characteristics at diagnosis, such as age, levels of cardiac biomarkers, and defined a frailty scale. Together, these data make it possible, among other things, to identify patients at increased risk of early death.
These are important experimental results, as they may make it possible to optimise the clinical and therapeutic resources available and ensure that pharmacological treatments are targeted at the patients most likely to benefit from them, and they highlight the central role of translational research, in which our country has peaks of excellence for improving diagnostic accuracy and therapeutic efficacy in complex and often under-diagnosed diseases
- Reynolds MM, Veverka KK, Gertz MA, et al. Ocular Manifestations of Familial Transthyretin Amyloidosis. Am J Ophthalmol. 2017 Nov;183:156-162. doi: 10.1016/j.ajo.2017.09.001. Epub 2017 Sep 11. PMID: 28911993.
- Milani P, Sanna GD, Mussinelli R, et al. Predictors of Early Death in Patients With Wild-Type Transthyretin Cardiac Amyloidosis. J Am Heart Assoc. 2025 Jan 7;14(1):e036755. doi: 10.1161/JAHA.124.036755. Epub 2024 Dec 24. PMID: 39719432.