Impact of Liver Transplantation on Transthyretin-Related Ocular Amyloidosis in Japanese Patients

Abstract

Objective: To evaluate the long-term impact of liver transplantation on ocular manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients.Methods: Medical records were retrospectively reviewed in a long-term follow-up study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients underwent liver transplantation. We assessed ocular manifestations, including amyloid deposition at the pupillary border, pupillary border with irregularity, vitreous opacities, and glaucoma, in patients who underwent liver transplantation. In addition, we compared the clinical characteristics of vitreous opacities-the most common ocular manifestation of FAP-in patients who underwent liver transplantation and those who did not to determine the effect of transplantation on the progression of ocular amyloidosis.Results: Mean time after FAP onset was 10 years and after liver transplantation was 7 years in patients who underwent liver transplantation. All ocular manifestations increased with time after transplantation. Eight patients (36%) developed vitreous opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time from FAP onset to vitreous opacities onset was significantly shorter in patients with early-onset disease who underwent liver transplantation than in those who did not. Conclusions:Patients with FAP who undergo liver transplantation continue to have a long-term risk of severe ocular manifestations, especially vitreous opacities and glaucoma, which can restrict their daily lives, even after liver transplantation.

Ophthalmic manifestations in a Chinese family with familial amyloid polyneuropathy due to a TTR Gly83Arg mutation

“…[5][6][7][8][9][10] TTR Val30Met mutation is the most common pathogenic variant overall and in Portugal, Brazil, Sweden, and Japan, and TTR Val122Ile is the most common pathogenic variant in the United States. 4,11 In China, only six pathogenic TTR variants (Gly54Arg, Gly83Arg, Lys35Thr, Leu55Arg, Val30Ala, Y114C) have been reported, and hot spots of TTR mutations have not yet been identified. [12][13][14][15][16][17] Here, we describe the clinical manifestations, management, and long-term follow-up of a large Chinese family with a heterozygous missense mutation in TTR Gly83Arg (c.307 C4G).…”

“…In addition, ophthalmic manifestations such as vitreous opacity and glaucoma continue to worsen after liver transplantation because the retinal pigment epithelium continues to produce mutant TTR. 11 Panretinal laser photocoagulation (PRP) was recently reported to prevent the progression of amyloid depositions in the vitreous in two patients with FAP. 30,31 PRP may also be helpful in managing secondary glaucoma associated with FAP as the RPE is the source of mutant TTR in the eye, but further investigations are needed to evaluate the efficacy and safety of PRP in FAP patients with ocular involvement.…”

Manifestations of transthyretin-related familial amyloidotic polyneuropathy: Long-term follow-up of Japanese patients after liver transplantation

“…The retinal pigment epithelium continues to synthesize variant TTR even after LT; therefore, it is well established that LT cannot prevent the progression of ocular amyloidosis. 19,21 In this study, we found that aging was one of the most important factors affecting the progression of ocular symptoms. Eight patients underwent eye surgery for glaucoma and/or vitreous opacity occurring after LT.…”

“…10,11 Although LT is widely accepted as the only life-saving treatment for patients with FAP, the continued progression of cardiac and ocular amyloidosis after LT has been reported. [12][13][14][15][16][17][18][19][20][21] Despite this, no detailed serial clinical evaluations of the long-term effects of LT on FAP symptoms have been conducted. 22 Thus, we investigated post-LT changes in the clinical manifestations of FAP, focusing on cardiac, kidney, and ocular tissues.…”

The Use of Intravitreal Ranibizumab to Treat Neovascular Glaucoma Because of Retinal Amyloid Angiopathy in Familial Amyloidosis Transthyretin V30m Related

“…1 The increase in survival of these patients with liver transplantation 2 seems to be associated with an increase in ocular complications. 3,4 Vascular abnormalities including rubeotic glaucoma and retinal neovascularization [4][5][6][7] have been observed, usually with catastrophic consequences for the patients' visual acuity.…”