Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases

Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3211-21. doi: 10.1167/iovs.16-19586.


Purpose: To present stimuli with varied sizes, colors, and patterns over a large range of luminance.

Methods: The filter bar used in scotopic MP1 was replaced with a custom slide-in tray that introduces light from an external projector driven by an additional computer. MP1 software was modified to provide retinal tracking information to the computer driving the projector. Retinal tracking performance was evaluated by imaging the system input and the output simultaneously with a high-speed video system. Spatial resolution was measured with achromatic and chromatic grating/background combinations over scotopic and photopic ranges.

Results: The range of retinal illuminance achievable by the modification was up to 6.8 log photopic Trolands (phot-Td); however, in the current work, only a lower range over -4 to +3 log phot-Td was tested in human subjects. Optical magnification was optimized for low-vision testing with gratings from 4.5 to 0.2 cyc/deg. In normal subjects, spatial resolution driven by rods, short wavelength-sensitive (S-) cones, and long/middle wavelength-sensitive (L/M-) cones was obtained by the choice of adapting conditions and wavelengths of grating and background. Data from a patient with blue cone monochromacy was used to confirm mediation.

Conclusions: The modified MP1 can be developed into an outcome measure for treatments in patients with severe retinal degeneration, very low vision, and abnormal eye movements such as those for whom treatment with optogenetics is planned, as well as for patients with cone disorders such as blue cone monochromacy for whom treatment with gene therapy is planned to improve L/M-cone function above a normal complement of rod and S-cone function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Color Vision / physiology*
  • Color Vision Defects / diagnosis
  • Color Vision Defects / etiology
  • Color Vision Defects / therapy*
  • Contrast Sensitivity / physiology
  • Eye Movements / physiology
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Genetic Therapy / methods*
  • Humans
  • Light*
  • Male
  • Middle Aged
  • Optogenetics / methods*
  • Retinal Cone Photoreceptor Cells / pathology*
  • Retinal Degeneration / complications
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / therapy*
  • Severity of Illness Index
  • Visual Perception / physiology
  • Young Adult

Supplementary concepts

  • Blue cone monochromatism