A Nonarteritic Anterior Ischemic Optic Neuropathy Clinical Trial: An Industry and NORDIC Collaboration.

N onarteritic anterior ischemic optic neuropathy (NAION) is the leading cause of sudden optic nerve–related vision loss in individuals over 50 years old and is caused by inadequate blood supply to the optic nerve head (1). In the United States, it affects 2.3 to 10.2 per 100,000 people over 50 years, resulting in 10,000 to 12,000 new cases per year (2,3). Little is understood concerning the pathophysiology of the disease, and there currently is no medical or surgical treatment that has been proven to be consistently beneficial (4). The QRK207 NAION study, sponsored by Quark Pharmaceuticals, Inc. in collaboration with the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC), is the first clinical trial designed to test therapy with potential to provide neuroprotection for acute optic nerve injury due to NAION. In addition, this is the first major collaboration with industry involving neuro-ophthalmologists, who are integrated into the study design, conduct, performance, analysis, and reporting of the trial. A recent review details the many reports of attempted therapies (5). These previous studies reported treatment successes and failures. Some of the possible pathophysiological mechanisms considered by the interventions include 1) blocking sodium channels, which have been shown to be neuroprotective in in vitro hypoxic injury to the optic nerve; 2) vasodilation, hemodilution, anticoagulation, and increasing blood pressure to increase presumed arterial or capillary perfusion of the optic nerve head; and 3) reduction of compression of optic nerve axons in the neural canal by reducing swelling or enlarging the scleral opening or decompressing the optic nerve sheath. Other procedures seem to have no scientific basis for the treatment of an acute ischemic white matter pathway injury; including intravitreal (IVT) antivascular endothelial growth factor agents and oral L-Dopa. In addition, only 1 study, the Ischemic Optic Neuropathy Decompression Trial (IONDT), was designed, powered, and conducted in a manner appropriate to collect Class I evidence (6). As if clinical research design challenges were not enough, most of the interventions in these studies have been initiated well beyond the time point where permanent axon injury and retinal ganglion cell (RGC) loss or atrophy have occurred (7).