Neurotoxic effects of GABA-transaminase inhibitors in the treatment of epilepsy: ocular perfusion and visual performance.
Vigabatrin is a GABA (gamma-aminobutyric acid) transaminase inhibitor that elicits an antiepileptic effect by enhancing inhibitory neurotransmission in the brain. Vigabatrin has been previously associated with concentric peripheral visual field loss and visual electrophysiological abnormalities. Recently, visual function deficits of the central retina have been identified in a proportion of patients receiving vigabatrin; these include disturbances in colour perception, contrast sensitivity and short-wavelength automated perimetry. Consequently, it is suggested that vigabatrin-associated retinal toxicity is diffuse inducing subtle central visual dysfunction and more severe peripheral visual defects. Reductions in cerebral blood flow and cerebral metabolic rate for glucose occur in epilepsy patients receiving antiepileptic drug therapy. Despite the known cerebral haemodynamic alterations in epilepsy and the visual consequences of vigabatrin therapy, ocular blood flow has only recently been investigated in this group. We present findings from a series of novel investigations that identify compromised retinal microvascular perfusion and pulsatile ocular blood flow (POBF) in epilepsy patients. The reduction in POBF was exacerbated in epilepsy patients treated with vigabatrin compared to conventionally treated epilepsy patients. A number of theories are presented to explain compromised ocular blood flow in vigabatrin treated epilepsy patients, and the possibility of a GABAergic mechanism of toxicity is discussed.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D004596:Electroretinography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D005123:Eye / Q000098:blood supply; D006801:Humans; D012039:Regional Blood Flow / Q000187:drug effects; D020888:Vigabatrin / Q000009:adverse effects*; D014786:Vision Disorders / Q000139:chemically induced*
D004791:Enzyme Inhibitors; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin