Tafamidis in hereditary ATTR amyloidosis – our experience on monitoring the ocular manifestations

Hereditary transthyretin (TTR)V30M-associated amyloidosis is an autosomal dominant inherited disorder caused by an amino acid substitution of methionine for valine at position 30 of TTR, a transport protein [1]. This leads to an extracellular amyloid deposition in nerves, in solid organs and in the eye [1–3]. The major site of production of circulating TTR is the liver but there is also production in the choroid plexus and the retinal pigmented epithelium [2,3]. Many ocular manifestations have been reported such as abnormal conjunctival vessels, keratoconjunctivitis sicca, glaucoma, deposition of amyloid at the anterior capsule of the lens and at the pupillary border, scalloped iris, vitreous opacities and retinal amyloid angiopathy [4,5]. This is a severe and progressive disorder, and liver transplantation is an accepted procedure that has been shown to increase patient survival and delay the progression of the neuropathy [6]. However, TTR production continues in the eye and ocular manifestations become more frequent with time, an if not promptly treated can lead to blindness [2,3,6,7]. Recently, other therapeutic strategies have been approved to treat the neuropathy, such as TTR tetramers stabilizer – tafamidis, which are bringing hope to these patients by slowing the process of amyloid fibril formation and deposition, but the impact in ocular manifestations is still uncertain [8]. Our purpose was to assess the impact of tafamidis therapy in our patients with hereditary ATTRV30M amyloidosis. In our department, we evaluated patients with ATTRV30M amyloidosis under treatment with tafamidis. In this paper we describe the cases of four of these patients. The assessment included: age at which tafamidis therapy started; ocular manifestations and performed treatments previous to tafamidis; ocular manifestations and medical or surgical additional treatment after tafamidis therapy. Patient 1 is a 48-year-old female observed for the first time in our department even before starting treatment with tafamidis. In this observation there were no ophthalmologic manifestations of the disease. Thirty months later, she presented scalloped iris in the right eye and an intraocular pressure of 34 mmHg with a pale optic disc. Patient 2 is a 37-year-old female who in the last ophthalmologic examination before starting treatment with tafamidis did not show any manifestations of the disease. Five months after starting treatment, she presented amyloid deposition at the border of the iris of the right eye which in the last observation – 12 months after tafamidis treatment – had evolved to scalloped iris of the same eye. Patient 3 is a 62-year-old female with diagnose of dry eye in the first ophthalmologic observation. Before starting tafamidis, she was observed in our department and maintained a mild dry eye already medicated with preservative free ocular lubricants and no other manifestations of the disease. Two years after starting treatment with tafamidis, she presented amyloid deposition at the border of the iris of the right eye and amyloid deposition in the anterior capsule of the lens of the left eye. Patient 4 is a 49-year-old male who presented mild dry eye in the first ophthalmologic examination and was medicated with preservative free ocular lubricants. This first observation was coincident with the beginning of the tafamidis treatment. Six months later, he was observed because of aggravated dry eye symptoms and decreased visual acuity. He presented severe dry eye and vitreous amyloidosis. Despite liver transplantation, ocular manifestations progress due to the production of mutant TTR by the retinal pigmented epithelium. We found it important to report these clinical cases concluding that the ocular manifestations can also progress despite the tafamidis therapy. Patients treated with tafamidis require a careful and long-term ophthalmologic follow-up to monitor ocular manifestations of ATTRV30M amyloidosis.