Outcome measure for the treatment of cone photoreceptor diseases: orientation to a scene with cone-only contrast.

Abstract

BACKGROUND:

Inherited retinal degenerations (IRDs) preferentially affecting cone photoreceptor function are being considered for treatment trials aiming to improve day vision. The purpose of the current work was to develop cone-specific visual orientation outcomes that can differentiate day vision improvement in the presence of retained night vision.

METHODS:

A lighted wall (1.4 m wide, 2 m high) resembling a beaded curtain was formed with 900 individually addressable red, blue and green LED triplets placed in 15 vertical strips hanging 0.1 m apart. Under computer control, different combination of colors and intensities were used to produce the appearance of a door on the wall. Scotopically-matched trials were designed to be perceptible to the cone-, but not rod-, photoreceptor based visual systems. Unmatched control trials were interleaved at each luminance level to determine the existence of any vision available for orientation. Testing started with dark-adapted eyes and a scene luminance attenuated 8 log units from the maximum attainable, and continued with progressively increasing levels of luminance. Testing was performed with a three-alternative forced choice method in healthy subjects and patients with Leber congenital amaurosis (LCA) caused by mutations in GUCY2D, the gene that encodes retinal guanylate cyclase-1.

RESULTS:

Normal subjects could perform the orientation task using cone vision at 5 log attenuation and brighter luminance levels. Most GUCY2D-LCA patients failed to perform the orientation task with scotopically-matched test trials at any luminance level even though they were able to perform correctly with unmatched control trials. These results were consistent with a lack of cone system vision and use of the rod system under ambient conditions normally associated with cone system activity. Two GUCY2D-LCA patients demonstrated remnant cone vision but at a luminance level 2 log brighter than normal.

CONCLUSIONS:

The newly developed device can probe the existence or emergence of cone-based vision in patients for an orientation task involving the identification of a door on the wall under free-viewing conditions. This key advance represents progress toward developing an appropriate outcome measure for a clinical trial to treat currently incurable eye diseases severely affecting cone vision despite retained rod vision.

• Authors: Alejandro J Roman, Artur V Cideciyan, Rodrigo Matsui, Rebecca Sheplock, Sharon B Schwartz, Samuel G Jacobson
• Journal: BMC ophthalmology (BMC Ophthalmol) Vol. 15 Pg. 98 (Aug 08 2015) ISSN: 1471-2415 [Electronic] England
• PMID: 26253563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Cell Surface
• guanylate cyclase 1
• Guanylate Cyclase

Topics

• Adolescent
• Child
• Color Vision Defects (physiopathology, therapy)
• Contrast Sensitivity (physiology)
• Dark Adaptation
• Female
• Guanylate Cyclase (genetics)
• Humans
• Leber Congenital Amaurosis (genetics, physiopathology, therapy)
• Male
• Middle Aged
• Psychomotor Performance (physiology)
• Receptors, Cell Surface (genetics)
• Retinal Cone Photoreceptor Cells (physiology)
• Retinal Degeneration (physiopathology, therapy)
• Retinal Rod Photoreceptor Cells (physiology)
• Visual Acuity (physiology)
• Visual Prosthesis