NA-AION Risk Factors: New Perspectives (NARROW)

Non-Arteritic Anterior Ischemic Optic Neuropathy Risk Factors: New Perspectives

The purpose of the study is to use new diagnostic methods (OCT and OCT-A) to shed light on risk factors for the development of NA-AION. The risk factors we are focusing on are comorbidities along with anatomical and vascular characteristics of the optic nerve.

Study Overview

• Status: Recruiting
• Conditions: Non-arteritic Ischemic Optic Neuropathy; Optic Disk Drusen

Detailed Description

Non-arteritic anterior ischemic optic neuropathy (NA-AION) is the most common acute optic neuropathy in the middle-aged and elderly population and can also occur in children and young adults. NA-AION leads to irreversible vision loss, and there is currently no effective treatment. In recent years, acellular calcified deposits in the optic nerve head called optic disc drusen (ODD) have been investigated as an important risk factor for NA-AION in patients under the age of 50.

The purpose of the study is to use new diagnostic methods optical coherence tomography (OCT) and OCT-angiography (OCTA) to shed light on risk factors for the development of NA-AION. We will perform two sub-studies:

1. Characteristics of the optic nerve head anatomy including the presence of ODD as risk factors for the development of NA-AION.
2. Vascular comorbidities and in vivo vasculature as a risk factor for developing NA-AION.

The study is an international prospective multicenter study including 20 sites in 9 different countries. The study population is patients diagnosed with NA-AION in a 1.5-year inclusion period. Each included patient gets 1-2 follow up visits during a 3-month follow up time.

Included patients will be examined as per standard clinical care for that site including OCT and OCT-A. Standard clinical care includes at least: obtaining medical history, measurement of visual acuity, slit lamp examination, and automated perimetry.

Characteristics and risk factors in NA-AION patients with ODD (ODD-AION) will be compared with NA-AOIN patients without ODD (nODD-AION).

• Study Type: Observational
• Enrollment (Anticipated): 650

Contacts and Locations

• Study Contact: Name: Lykkebirk; Phone Number: +4540889817; Email: lea.lykkebirk.01@regionh.dk
• Study Contact Backup: Name: Hamann; Email: steffen.ellitsgaard.hamann@regionh.dk

Study Locations

• Australia
  • Sydney, Australia
    • Not yet recruiting
    • Sydney Eye Hospital
    • Principal Investigator: Clare Fraser
    • Sub-Investigator: Mitchell Lawlor
• Canada
  • Calgary, Canada
    • Not yet recruiting
    • University of Calgary
    • Principal Investigator: Fiona Costello
  • Hamilton, Canada
    • Recruiting
    • Research St. Joseph's
    • Principal Investigator: Amadeo Rodriguez
  • London, Canada
    • Recruiting
    • Lawson Health Research Institute
    • Principal Investigator: Lulu Bursztyn
    • Sub-Investigator: Alex Fraser
• Denmark
  • Aalborg, Denmark
    • Recruiting
    • Aalborg University Hospital
    • Principal Investigator: Suganiah Ragunathan
    • Sub-Investigator: Nirrooja Roshanth
  • Aarhus, Denmark
    • Recruiting
    • Aarhus University Hospital
    • Contact: Line Petersen
    • Sub-Investigator: Toke Bek
    • Principal Investigator: Line Petersen
  • Odense, Denmark
    • Recruiting
    • Odense University Hospital
    • Principal Investigator: Sasikala Thineshkumar
    • Sub-Investigator: Laleh Molander
  • Roskilde, Denmark
    • Recruiting
    • Zealand University Hospital
    • Principal Investigator: Mads Falk
• France
  • Bordeaux, France
    • Not yet recruiting
    • Bordeaux University Hospital
    • Principal Investigator: Marie-Bénédicte Rougier
    • Sub-Investigator: Emilie Tournaire-Marques
• Iran, Islamic Republic of
  • Teheran, Iran, Islamic Republic of
    • Recruiting
    • Farabi Eye Hospital
    • Principal Investigator: Masoud A Fard
• Israel
  • Tel Aviv, Israel
    • Not yet recruiting
    • Sheba Medical Center
    • Principal Investigator: Ruth H Baron
• New Zealand
  • Wellington, New Zealand
    • Recruiting
    • Capital and Coast DHB
    • Principal Investigator: Jesse Gale
• United Kingdom
  • Cambridge, United Kingdom
    • Not yet recruiting
    • University of Cambridge
    • Principal Investigator: Patrick Yu Wai Man
  • London, United Kingdom
    • Not yet recruiting
    • King's College Hospital
    • Principal Investigator: Eion O'Sullivan
  • London, United Kingdom
    • Not yet recruiting
    • Moorfield's Eye Hospital
    • Principal Investigator: Axel Petzold
    • Sub-Investigator: Sui Wong
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Not yet recruiting
      • Stanford Medicine
      • Principal Investigator: Yaping J Liao
      • Sub-Investigator: Heather Moss
      • Sub-Investigator: Shannon Beres
      • Sub-Investigator: Sangeethabalasri Pugazhendhi
    • San Francisco, California, United States, 94143
      • Not yet recruiting
      • UCSF Medical Center
      • Principal Investigator: Nailyn Rasool
      • Sub-Investigator: Leslie Small
  • Colorado
    • Boulder, Colorado, United States, 80309
      • Recruiting
      • University og Colorado
      • Principal Investigator: Prem Subramanian
      • Sub-Investigator: Mary Preston
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Not yet recruiting
      • Massachusetts Eye and Ear
      • Principal Investigator: Bardia Abbasi
      • Sub-Investigator: Eric Gaier
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • John A. Moran Eye Center
      • Principal Investigator: Bradley Katz
      • Sub-Investigator: Kathleen Digre
      • Sub-Investigator: Judith Warner

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population is patients diagnosed with NA-AION in a 1.5-year inclusion period.

Description

Inclusion Criteria:

1. Diagnosis of first episode of NA-AION in study eye with symptom onset within 14 days prior
2. Subject age: Age >10

3. NA-AION diagnosis requires:

   • disc edema seen and documented by site PI
   • visual field defect in the study eye consistent with NA-AION and mean deviation worse than 3.0 dB using the study visual field examination protocol
   • relative afferent pupillary defect (unless the fellow eye had previous NA-AION or other optic nerve or retinal disease that is not exclusionary)

Exclusion Criteria:

1. Previous episode of NA-AION in the study eye only
2. Intraocular pressure of >21 mm Hg in the study eye
3. Clinical or pathological evidence of giant cell arteritis
4. Diseases that may affect the optic nerve: glaucoma, multiple sclerosis, Alzheimer disease, and Parkinson disease. Evidence of optic disc drusen and optic nerve hypoplasia are not exclusion criteria given they are important parts of the study. We will not exclude significant retinal diseases, since they may be related to underlying etiologies giving rise to ODD, such as macular degeneration, retinal dystrophies, but eyes with significant retinal diseases will be analyzed separately.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ODD-AION; NA-AION patients with ODD aka. Optic disc drusen associated non-arteritic anterior ischemic optic neuropathy.
nODD-AION; NA-AION patients without ODD aka Non-optic disc drusen associated non-arteritic anterior ischemic optic neuropathy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anatomical characteristics on OCT	Presence of ODD. Diameter of the scleral canal, disc area and rim on each quadrant of the optic disc, thickness of the peripapillary choroid, presence of peripapillary hyperreflective ovoid mass-like structures, and prelaminar hyperreflective lines.	At enrollment
Anatomical characteristics on OCT	Presence of ODD. Diameter of the scleral canal, disc area and rim on each quadrant of the optic disc, thickness of the peripapillary choroid, presence of peripapillary hyperreflective ovoid mass-like structures, and prelaminar hyperreflective lines.	3-months follow-up visit
Vascular characteristics on OCT-A	Transient versus persistent findings of ischemia, segmental location and extent of reduced vessel density. If ODD is present the vessel density will be compared to ODD location and volume.	3-months follow-up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ODD characteristics	If ODD is present the volume and location of the ODD (superficial vs. deep) is measured using 3D-segmentation	At 3-months follow-up visit
Best corrected visual acuity	Assessed on Snellen or ETDRS chart	At enrollment
Best corrected visual acuity	Assessed on Snellen or ETDRS chart	3-months follow-up visit
Visual field test	Autoperimetry: SITA fast or standard 24-2	At enrollment
Visual field test	Autoperimetry: SITA fast or standard 24-2	3-months follow-up visit
Questionnaire score: NEI-VFQ-25 including 10-item NO supplement score	Score on questionnaire: National Eye Institute Visual Function Questionnaire 25 and 10-item Neuro-Ophthalmic Supplement A vision-targeted composite score of the NEI-VFQ-25 together with the 10-item NO supplement score is calculated. The scale is 0-100 where a high score represents better functioning.	At enrollment
Questionnaire score: NEI-VFQ-25 including 10-item NO supplement score	Score on questionnaire: National Eye Institute Visual Function Questionnaire 25 and 10-item Neuro-Ophthalmic Supplement. A vision-targeted composite score of the NEI-VFQ-25 together with the 10-item NO supplement score is calculated. The scale is 0-100 where a high score represents better functioning.	3-months follow-up visit
Prevalence of comorbidities	ischemic heart disease, stroke (ischemic or hemorrhagic), arterial hypertension, diabetes mellitus, end stage renal disease, smoking (now or previous), dyslipidemia, obstructive sleep apnea/continuous positive airway pressure (CPAP) use, phosphodiesterase-5 inhibitor use or ocular surgery.	At enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eye refraction in diopters	Spherical and cylindrical refraction. Measurements in diopters.	At enrollment
Color vision test score as fraction	Assessed on Ishihara or Hardy-Rand-Rittler plates. Measured as the fraction of how many correct plates out how many plates are used in the assessment in total. A score of 0 means no plates were read correctly and 1 means all plates were read correctly.	At enrollment
Color vision test score as fraction	Assessed on Ishihara or Hardy-Rand-Rittler plates. Measured as the fraction of how many correct plates out how many plates are used in the assessment in total. A score of 0 means no plates were read correctly and 1 means all plates were read correctly.	3-months follow-up visit
Eye biometry: Axial length	axial length of the eye in mm	At enrollment
Eye biometry: Keratometry	The curvature of the cornea in diopters	At enrollment

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: University of Colorado, Denver; King's College Hospital NHS Trust; Odense University Hospital; Zealand University Hospital; Aarhus University Hospital; University of Copenhagen; Stony Brook University; University of California, San Francisco; Stanford University; University Hospital, Bordeaux; University of Calgary; Hamilton Health Sciences Corporation; University of Utah; Lawson Health Research Institute; Sheba Medical Center; Moorfields Eye Hospital NHS Foundation Trust; University of Sydney; Aalborg University Hospital; Massachusetts Eye and Ear Infirmary; Velux Fonden; Fight for Sight; Synoptik-Fonden; Farabi Eye Hospital; Wellington Hospital
• Investigators: Principal Investigator: Steffen Hamann, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): August 31, 2023

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Optical Coherence Tomography; Optical Coherence Tomography Angiography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Eye Diseases; Cranial Nerve Diseases; Optic Nerve Diseases; Optic Neuropathy, Ischemic; Optic Disk Drusen
• Other Study ID Numbers: H-20073063

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No