Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We aimed to assess the efficacy and safety of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ATTRv amyloidosis with polyneuropathy. MethodsThis multi-country, multi-centre, open-label extension (OLE) trial enrolled patients at 43 sites in 19 countries as of 24 September 2018. Patients were eligible if they had completed the phase 3 APOLLO (randomised, double-blind, placebo-controlled [2:1], 18-month study) or phase 2 OLE (single-arm, 24-month study) parent studies and tolerated the study drug. Eligible patients from APOLLO (APOLLO-patisiran [received patisiran during APOLLO] and APOLLO-placebo [received placebo during APOLLO] groups) and the phase 2 OLE (phase 2 OLE patisiran group) studies enrolled in this Global OLE trial and receive patisiran 0•3 mg/kg by intravenous infusion every 3 weeks for up to 5 years. Efficacy assessments include measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress. Patients included in the current efficacy analyses are those who had completed 12-month efficacy assessments as of the data cut-off. Safety analyses included all patients who received ≥1 dose of patisiran up to the data cut-off. The Global OLE is ongoing with no new enrolment, and current findings are based on the 12-month interim analysis. The study is registered with ClinicalTrials.gov, NCT02510261.

Purpose: To compare the functional and anatomical outcomes after a 0.2 µg/day fluocinolone acetonide (FAc) implant between vitrectomized and nonvitrectomized eyes with chronic diabetic macular edema (DME). Methods: This is a retrospective, comparative analysis of 43 eyes with chronic DME. All eyes were treated with a single 0.2 µg/day FAc implant and followed up for a mean period of 8.5 months (median, 6.0 months; range, 1-21 months). The patients with a 0.2 µg/day FAc implant were divided into 2 groups: 24 eyes which had undergone pars plana vitrectomy prior to 0.2 µg/day FAc (group 1) and 19 eyes which had not been vitrectomized (group 2). Outcome measures included mean changes in best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, central subfield foveal thickness (CSFT), and intraocular pressure (IOP), and were measured prior to administration of the 0.2 µg FAc implant, in the first week, at month 1, and quarterly thereafter. Results: Following the 0.2 μg/day FAc implant, the mean change in BCVA at the last observation point, from baseline, was +16.9 ± 3.39 (mean ± SE) letters (p ≤ 0.001) in group 1 and +8.2 ± 4.62 letters (p = 0.092) in group 2. From baseline, a gain of ≥15 letters was achieved in 37.5 and 36.8% of the eyes in group 1 and group 2, respectively. Additionally, an improvement in vision ≥20/40 in 29.2% of group 1 and 15.8% of group 2 was observed. The mean change in CSFT was -217.7 ± 40.8 µm and -155.6 ± 43.4 µm in group 1 and group 2, respectively. The mean change in IOP was +1.6 ± 0.7 mm Hg in group 1 and +0.8 ± 1.3 mm Hg in group 2, relative to baseline. At the last observation point, there were no significant differences between groups 1 and 2 (p > 0.05) in terms of their changes in BCVA, CSFT, and IOP. Conclusion: The results from the real-life practice study demonstrate that the 0.2 μg/day FAc implant is effective and well tolerated in vitrectomized and nonvitrectomized eyes of patients with chronic DME. Our results support the use of a 0.2 μg/day FAc implant to obtain long-term functional and anatomical improvements (mean, 8.5 months; median, 6.0 months) in vitrectomized and nonvitrectomized eyes.

Purpose: To evaluate the anatomical and functional results of patients who underwent pars plana vitrectomy for perforating eye injuries as well as to analyze the benefit of the chorioretinectomy procedure. Methods: Retrospective and descriptive study of 24 eyes of 22 patients with perforating eye injuries operated on at the Centro Hospitalar do Porto between January 2006 and December 2012. Results: An early vitrectomy was accomplished in 67% of the eyes and a delayed vitrectomy in 33% of the eyes. A concomitant chorioretinectomy was carried out in 78%. Final proliferative vitreoretinopathy (PVR) was found in 11%. The anatomical success was 83%. At the final follow-up, 78% had best-corrected visual acuity equal to or superior to 5/200. Of the eyes that underwent early vitrectomy, 58% regained a visual acuity of 40/200 or better, versus 17% of the cases that underwent delayed vitrectomy. Conclusion: Early vitrectomy with prophylactic chorioretinectomy seems to be an effective approach to prevent PVR and improve the visual outcome and globe survival in perforating injuries.

Hereditary transthyretin (TTR) amyloidosis associated with the TTRV30M (p.TTRV50M) mutation presents predominantly as an axonal polyneuropathy, with variable involvement of other organs. Serious central nervous system (CNS) and eye manifestations, including stroke, dementia, vitreous opacities and glaucoma, have been reported in untreated V30M TTR amyloidosis patients, and in these patients after treatment with liver transplantation (LT). Distinct therapies for V30M TTR amyloidosis developed during the last decade exhibit promising results in slowing the peripheral and autonomic nervous system pathology. However, the effect of these therapies on the CNS and eye manifestations of V30M TTR amyloidosis is not known. Herein, we show that in a small cohort of patients taking tafamidis orally (20 mg tafamidis meglumine daily) we could detect this small molecule in the cerebrospinal fluid (CSF) and the vitreous body. In the CSF, the ratio of TTR tetramer to tafamidis was ≈2:1, leading to a moderate kinetic stabilization of TTR in the CSF of these patients. Our data suggest that tafamidis can cross the CSF-blood and eye-blood barriers. Future studies comparing CNS and eye manifestations in patients treated with LT, kinetic stabilizers or TTR lowering drugs are essential to understand the clinical effect of our observations.