A prospective study of ocular manifestations in transthyretin-related familial amyloid polyneuropathy

Abstract

Purpose: To study the prevalence and the clinical characteristics of ocular manifestations of transthyretin-related familial amyloid polyneuropathy (TTR-FAP).

Methods: This prospective monocentric observational study was conducted at the french national reference center for TTR-FAP. Genetically confirmed TTR-FAP patients had a complete neurologic and ophthalmologic evaluation. Sensorimotor polyneuropathy (SPN) was staged with the Polyneuropathy Disability (PND) score, vegetative neuropathy was staged with the Compound Autonomic Dysfuncton Test (CADT). Ophthalmic examination included best corrected visual acuity (BCVA), Schirmer test, intraocular pressure (IOP), slit lamp photographs, gonioscopy, fundus examination with retinography, ultrasound pachymetry, and RNFL-OCT. Automated perimetry was performed when glaucoma was suspected. Medical and surgical treatments were analysed for all patients.

Results: Fifty seven patients (31 males and 26 females, aged 26-83 years, mean 53.6±13.6 years, were included between august 2011 and november 2013. Mean delay between inclusion and TTR-FAP diagnosis was 52.4±61.5 months. Patients were mainly of Portuguese origin (N=28; 49%). Val30Met mutation was present in 42 patients (73.7%). Ocular Hypertension (IOP>21mmHg) and glaucoma (defined by visual field abnormalities, neuroretinal rim thinning, excavation or RNFL defects) occurred in 11 patients (19.3%) and were associated with amyloid deposits in the anterior chamber with a "clamshell" pupil in 91.3% of cases. Amyloid vitreous deposits were present in 12 patients (21%) and had already required vitrectomy in 9 eyes of 5 patients. A BCVA of 20/200 or worse in one eye was found in 9 patients (15.8%) and was caused by secondary glaucoma in 66% of cases. Lacrimal hyposecretion (Schirmer < 5 mm/5 minutes) was found in at least one eye in 43.2% of cases. OHT and glaucoma were found only in carriers of the val30met mutation and were more frequent in patients affected by autonomic neuropathy (CADT score <16) (p≤0.05). A BCVA of 20/200 or worse in one eye was more frequent in patients with severe SPN (PND score >2)(p≤0.05).

Conclusions: In our series of TTR-FAP patients, amyloid glaucoma was exclusively found in carriers of the Val30Met mutation. OHT and glaucoma occurred more frequently in patients with autonomicneuropathy. Severe visual impairment was mainly caused by secondary glaucoma and associated with severe SPN.

Keywords: 539 genetics • 571 iris • 763 vitreous