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Macular and optic disc edema and retinal vascular leakage in familial amyloid polyneuropathy with a transthyretin Val30Met mutation: a case report
© Dias-Santos et al.; licensee BioMed Central Ltd. 2014
Received: 14 December 2013
Accepted: 15 August 2014
Published: 4 October 2014
Familial amyloid polyneuropathy is a group of autosomal dominant disorders characterized by extracellular amyloid deposition in several target organs. This paper aims to report an unusual manifestation of retinal vascular leakage including optic disc and macular edema in a patient with familial amyloid polyneuropathy.
A 37-year-old Portuguese Caucasian man with Val30Met transthyretin-related familial amyloid polyneuropathy presented with rapidly progressing visual loss in his left eye. He had undergone liver transplantation at the age of 30 with neurologic stabilization. Fundoscopy and fluorescein angiogram revealed optic disc and macular edema as well as vessel wall staining with leakage in the posterior pole and mid-periphery, without vitreous opacities. A diagnostic work-up for infectious, autoimmune and neoplasic conditions was negative. Systemic immunosuppression was increased but without improvement. Sustained resolution of macular edema was observed after intravitreal injection of dexamethasone implant and laser panretinal photocoagulation.
To the best of our knowledge, this is the first report of a rare ocular manifestation of familial amyloid polyneuropathy which represents a new therapeutic challenge. Intravitreal injection of sustained release dexamethasone implant and panretinal photocoagulation may be an effective eye-saving therapeutic approach.
Familial amyloid polyneuropathy (FAP) or paramyloidosis is a heterogenous group of autosomal dominant disorders characterized by extracellular amyloid deposition in peripheral nerves, cardiac muscle, kidneys and eyes. There are three precursor proteins that can give rise to amyloid production: transthyretin (TTR), apolipoprotein A-1 and gelsolin, each resulting in a distinct type of FAP. TTR-related FAP is the most frequent type and more than 80 mutations involving this protein have been described[3, 4]. A single amino acid substitution of valine for methionine at position 30 of TTR (Val30Met) is the most frequent TTR-related FAP causing mutation. The liver is the major site of synthesis of circulating TTR, but there is also evidence of TTR production in other tissues like the retinal pigment epithelium, the choroid plexus of the brain and the visceral yolk sac endoderm. Since 1990, liver transplantation has been considered the main therapeutic approach, halting the progression of neurologic complications. However, ocular complications have been reported to continue or even increase after liver transplantation[9, 10]. The most frequently reported ocular manifestations of FAP are keratoconjunctivitis sicca, abnormal conjunctival vessels, pupillary abnormalities, glaucoma and vitreous opacities.
The purpose of this paper is to report a case of retinal vascular leakage including optic disc and cystoid macular edema in a patient with Val30Met TTR-related FAP.
Here we describe unusual ocular findings in a patient with paramyloidosis. FAP-related retinal vascular leakage is rare and it is usually associated with amyloid vitreous deposits, which were not observed in this patient. Causes of ocular inflammation were excluded with an extensive diagnostic work-up. We cannot exclude the hypothesis of toxic microangiopathy related to drugs such as sirolimus or tacrolimus. However, the limitation of this reaction to the eye and the positive response to local intravitreal therapy favors, in our opinion, the hypothesis of FAP-related ocular complications. Thus, this is probably the first report of optic disc edema, retinal vascular leakage and cystoid macular edema in a patient with FAP.
Amyloid deposition within the walls of retinal vessels had been previously described. It has been hypothesized that this impregnation may lead to retinal ischemia and vessel wall weakening which would ultimately lead to perivascular exudation as well as retinal and vitreous hemorrhages. O’Hearn et al. reported that vitreous vascular endothelial growth factor (VEGF) levels in FAP patients were raised to similar levels as those found in patients with inactive proliferative diabetic retinopathy. Retinal neovascularization is a rare complication of this disease, supporting the important role of VEGF upregulation in its pathogenesis. Zou and colleagues also reported elevated levels of VEGF in vitreous samples and in the serum of patients with ocular complications of TTR-related FAP. Such elevated vitreous VEGF levels could also account for the macular edema observed in our patient. In this patient we observed a positive response to both anti-VEGF and triamcinolone intravitreal injection; however, the effect was more pronounced following triamcinolone. A more sustained response was obtained following intravitreal injection of dexamethasone implant. To date there are no other reports or studies regarding the efficacy of intravitreal anti-VEGF or corticosteroids for the treatment of ocular complications of FAP.
LPP therapy has been recently proposed to treat ocular complications of FAP. During 3 years of follow up, LPP prevented the progression of vitreous and retinal amyloid deposits in two patients. After liver transplantation, the retinal pigment epithelium plays the major role in ocular amyloid production. Therefore, the destruction of this tissue by retinal photocoagulation would theoretically decrease the production of abnormal TTR in the eye. In our patient we performed LPP in his LE in an attempt to halt the natural history of the disease and, at the same time, to try to reduce the burden of intravitreal injections.
As a result of a longer life expectancy in patients with FAP obtained with liver transplantation, more frequent and more complex ocular complications are expected to appear in our clinical practice. Intravitreal corticosteroid therapy in isolation or combined with laser photocoagulation is a promising therapeutic approach to these patients. However, additional and larger multicenter studies are needed to evaluate the efficacy and safety of these therapies in the management of ocular manifestations of FAP.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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