Clinical and Mechanistic Review of Amiodarone-Associated Optic Neuropathy

Abstract

Amiodarone-associated optic neuropathy (AAON) is a complex clinical diagnosis, requiring distinction from non-arteritic ischemic optic neuropathy (NAION) due to a shared at-risk patient population. Diagnosis of AAON is complicated by a varied clinical presentation and incomplete pathophysiologic mechanisms. This article reviews pertinent literature for describing and clinically delineating AAON from NAION, as well as newly reported protective mechanisms of insulin-like growth factor 1 (IGF-1) and PI3K/Akt against amiodarone-induced oxidative and apoptotic injury in retinal ganglion and pigment epithelial cells. These studies offer a basis for exploring mechanisms of amiodarone toxicity in the optic nerve.

Non-Arteritic Anterior Ischemic Optic Neuropathy (NA-AION): A Comprehensive Overview

“…amiodarone: several authors have described an association between NA-AION and the assumption of amiodarone [84]. NA-AION related to the treatment with amiodarone are mostly described as bilateral, with an insidious onset, generalized rather than altitudinal VF defect, and OD swelling persisting for months rather weeks after the onset of the visual loss [84].…”

“…amiodarone: several authors have described an association between NA-AION and the assumption of amiodarone [84]. NA-AION related to the treatment with amiodarone are mostly described as bilateral, with an insidious onset, generalized rather than altitudinal VF defect, and OD swelling persisting for months rather weeks after the onset of the visual loss [84]. It is important to note that patients treated with amiodarone generally have severe vascular risk factors that may predispose them to the development of NA-AION; a clear association with the therapy with amiodarone remains uncertain; d.…”

“…In this regard, avoidance of the assumption of anti-hypertensive drugs in the evening or at bedtime could be important [11]; -ask NA-AION patients to avoid sleeping in the lateral decubitus position, in particular from the site of the affected eye [51]; -suggest ocular hypotensive treatments in the presence of borderline or high IOP values to improve ONH blood flow; -use caution in prescribing treatment with intravitreal injections in NA-AION patients, because the sudden IOP increase after the intravitreal injection could impair OD circulation and predispose to progressive VA loss in the affected eye, or the development of NA-AION in the fellow eye [79]; -ask all male patients developing an NA-AION about the use of phosphodiesterase-5 inhibitors (PDI5i); moreover, before the prescription of PDI5i, patients should undergo an ophthalmological examination and, especially in the presence of a crowded OD, be informed about the risk of developing an NA-AION by using the drugs and eventually discouraged to take PDE5i. Although the association between NA-AION and the assumption of PDE5i is still debated, several authors suggest that a history of NA-AION should be an absolute contraindication to PDI5i therapy [81,82]; -ask all NA-AION patients about the possible use of amiodarone and, in positive cases, the cardiologist should be alerted about the possible association between the optic neuropathy and assumption of the drug [84]; -inform all female NA-AION patients taking oral contraceptives about a possible causal association with the development of NA-AION [85]; -supplementation with vitamin B6, B12, and folic acid is recommended in the presence of hyperhomocysteinemia, although the value of lowering the homocysteine levels for a reduction in vascular events remain unproven [3].…”

New Discoveries in Retinal Cell Degeneration and Retinal Diseases

“…Harmening et al [15] investigated the use of the SB100X transposase delivered as mRNA and showed that ARPE-19 cells as well as primary human RPE cells were successfully transfected with the Venus or the PEDF gene, followed by stable transgene expression. In human RPE cells, secretion of recombinant PEDF can be detected in cell cultures up to one year later [10]. Non-viral ex vivo transfection using SB100X-mRNA in combination with electroporation increases the biosafety of the gene therapeutic approach to treating nvAMD while ensuring high transfection efficiency and long-term transgene expression in RPE cells.…”