De novo intraocular amyloid deposition after hepatic transplantation in familial amyloidotic polyneuropathy

Abstract

The familiar amyloid polyneuropathy (FAP) is a rare autosomal-dominant systemic amyloidosis. Amyloid deposition occurs more frequently and extensively in the vitq. The increase in intraocular pressure (IOP) is a result of deposition of transthyretin (TTR) in trabecular meshwork. Rarely, the amyloid deposition in anterior segment can be more exuberant than in posterior segment. A 42 years old man, with FAP (Val30Met mutation), liver transplantation in 1997. He was asymptomatic, without any significant ocular abnormality until 2011. In 2011 he had an episode of pain in right eye (RE). Scalloped pupils, pupillary amyloid deposits and subtle vitreous opacities were detected. The IOP was 40 mmHg in RE and 28 mmHg in left eye (LE) with open angle. Optical coherence tomography detected a temporal superior retinal nerve fiber layer defect in LE and perimetry was normal. Topical timolol was initiated, and brimonidine was subsequently added to improve IOP control, which was achieved with topical medication until last evaluation. No progression occurred since 2011. Actually, with longer life expectancies, there is an increased risk of ocular involvement in FAP, even after liver transplantation. Although rare, a more exuberant amyloid deposition in anterior segment vs posterior segment can occur, and supports an important role of amyloid production in ciliary pigment epithelium in these patients. Medical control of IOP and a stable course are unusual in this secondary glaucoma. Ophthalmologists have an important task in the follow-up of patients and early diagnosis of risk factors for secondary glaucoma, such as scalloped pupils with amyloid deposits.

Small gauge vitrectomy for vitreous amyloidosis and subsequent management of secondary glaucoma in patients with hereditary transthyretin amyloidosis

“…Liver transplantation slows disease progression and increases the survival rate among patients with hereditary ATTR amyloidosis 9,10 . However, as TTR is produced not just in the liver, but also in ocular tissues 11,12 , eyesight deterioration due to vitreous amyloidosis and secondary glaucoma, has become relatively common among patients with hereditary ATTR amyloidosis 6,9,13 .…”

Interplay between Oxidative Stress, Inflammation, and Amyloidosis in the Anterior Segment of the Eye; Its Pathological Implications

“…Furthermore, an increased lipid peroxidation, being the result of ROS-induced cell damage, was noticed as well as an impairment of metalloproteinases-2 (MMP-2) expression, resulting in an accumulation of extracellular matrix. This accumulation (i.e., plaques) in TM could be seen several years before by electron microscopy studies [77,78].…”

“…It acts as a thyroxine and vitamin A transporter, and it carries retinol and in a lesser amount, thyroxine (T4) when mutated, its tetramer conformation turns into monomers that aggregate and form amyloid deposits [75,76]. The most serious ocular manifestation of FAP is glaucoma [76][77][78], and it has been suggested that the loss of peripheral nerve fibers in FAP, and the consequent ischemia, is caused by endoneurial amyloid deposits and the toxicity of amyloid deposits to TM cells [75].…”

“…Vitrectomy increases oxidative conditions in the TM and, in the absence of the vitreous, the amyloid aggregates reach the TM and Schlemm's canal more easily. This suggests that the vitreous acts like a filter that retains the amyloid fibrils and prevents their progression to the TM [75][76][77][78][79]. In spite of all these studies identifying amyloid deposition as a risk factor for FAP, there is no more information about the molecular and biochemical mechanisms participating in the development and progression of this disease.…”