Study explores neuroprotection for acute optic nerve injury

Neil Miller
Neil R. Miller

QPI-1007 is being investigated for providing neuroprotection against nonarteritic anterior ischemic optic neuropathy, which has no standard treatment and is a leading cause of sudden optic nerve-related vision loss in individuals older than 50 years.

Study director, Neil R. Miller, MD, told Primary Care Optometry News in an interview that QPI-1007 could have quite an impact on patients who are typically told that nothing can be done for them.

PCON: Please explain how QPI-1007 works.

Miller: One of the mechanisms for cell death, including that which occurs in retinal ganglion cells (RGCs) in patients with NAION [nonarteritic anterior ischemic optic neuropathy], is apoptosis. This is a form of programmed cell death; the cell essentially commits "suicide." One of the key elements in the apoptotic pathway is an enzyme called caspase-2. QPI-1007 inhibits caspase-2, thus, theoretically blocking the pathway and protecting the RGCs (and, thus, the optic nerve) from further damage.

PCON: What would a best-case scenario look like for the phase 3?

Miller: All patients receiving the drug in the 14-day time window following onset of visual symptoms would have less severe loss of visual acuity and less severe visual field defects than would occur if they had no treatment (ie, the natural history of the disorder).

PCON : How is the trial going so far? How many people are enrolled?

Miller: The trial is going extremely well. Thus far, about two-thirds of the planned number of 500+ subjects have been enrolled.

PCON: Why is NAION so difficult to treat?

Miller: The optic nerve is an unforgiving structure. It can be thought of as one of the white-matter tracks of the brain. Once damaged, it does not regenerate or repair itself the way peripheral nerves do.

PCON: When can clinicians expect to hear results from the trial?

Miller: We hope to have results by the end of 2018.

PCON: What is the current diagnosis method, treatment and monitoring plan for NAION?

Miller: The diagnosis of NAION is made by the combination of symptoms, usually in patients over the age of 60 who also have underlying systemic vascular disease such as hypertension, diabetes mellitus and/or hyperlipidemia. The patients typically experience painless monocular visual loss associated with an arcuate or altitudinal field defect, a relative afferent pupillary defect and ipsilateral optic disc swelling. There is no standard treatment for the condition, although a variety of agents, including anti-VEGF drugs and corticosteroids, have been tried. In most cases, patients are either treated and advised to return in 1 to 2 months for a repeat assessment or are told that there is nothing that can be done for them. They are advised to undergo an evaluation by their internist or primary care physician so that any underlying modifiable vascular condition can be treated. – Interviewed by Abigail Sutton

Disclosure: Miller is the compensated study director for the trial. He is also a co-primary investigator on an NEI grant to study NAION animal models.

Neil Miller
Neil R. Miller

QPI-1007 is being investigated for providing neuroprotection against nonarteritic anterior ischemic optic neuropathy, which has no standard treatment and is a leading cause of sudden optic nerve-related vision loss in individuals older than 50 years.

Study director, Neil R. Miller, MD, told Primary Care Optometry News in an interview that QPI-1007 could have quite an impact on patients who are typically told that nothing can be done for them.

PCON: Please explain how QPI-1007 works.

Miller: One of the mechanisms for cell death, including that which occurs in retinal ganglion cells (RGCs) in patients with NAION [nonarteritic anterior ischemic optic neuropathy], is apoptosis. This is a form of programmed cell death; the cell essentially commits "suicide." One of the key elements in the apoptotic pathway is an enzyme called caspase-2. QPI-1007 inhibits caspase-2, thus, theoretically blocking the pathway and protecting the RGCs (and, thus, the optic nerve) from further damage.

PCON: What would a best-case scenario look like for the phase 3?

Miller: All patients receiving the drug in the 14-day time window following onset of visual symptoms would have less severe loss of visual acuity and less severe visual field defects than would occur if they had no treatment (ie, the natural history of the disorder).

PCON : How is the trial going so far? How many people are enrolled?

Miller: The trial is going extremely well. Thus far, about two-thirds of the planned number of 500+ subjects have been enrolled.

PCON: Why is NAION so difficult to treat?

Miller: The optic nerve is an unforgiving structure. It can be thought of as one of the white-matter tracks of the brain. Once damaged, it does not regenerate or repair itself the way peripheral nerves do.

PCON: When can clinicians expect to hear results from the trial?

Miller: We hope to have results by the end of 2018.

PCON: What is the current diagnosis method, treatment and monitoring plan for NAION?

Miller: The diagnosis of NAION is made by the combination of symptoms, usually in patients over the age of 60 who also have underlying systemic vascular disease such as hypertension, diabetes mellitus and/or hyperlipidemia. The patients typically experience painless monocular visual loss associated with an arcuate or altitudinal field defect, a relative afferent pupillary defect and ipsilateral optic disc swelling. There is no standard treatment for the condition, although a variety of agents, including anti-VEGF drugs and corticosteroids, have been tried. In most cases, patients are either treated and advised to return in 1 to 2 months for a repeat assessment or are told that there is nothing that can be done for them. They are advised to undergo an evaluation by their internist or primary care physician so that any underlying modifiable vascular condition can be treated. – Interviewed by Abigail Sutton

Disclosure: Miller is the compensated study director for the trial. He is also a co-primary investigator on an NEI grant to study NAION animal models.