Two-color pupillometry in KCNV2 retinopathy
To investigate receptor and post-receptor function in KCNV2 retinopathy [cone dystrophy with supernormal rod electroretinogram (ERG)], using the pupillary light reflex (PLR) and the ERG.
Two unrelated patients (1 male and 1 female) with molecularly confirmed KCNV2 retinopathy underwent full-field two-color pupillometry testing in one eye, with monitoring of the stimulated eye by an infrared digital camera. Pupillometry stimuli consisted of 1-s duration, short-wavelength (465-nm, blue) and long-wavelength (642-nm, red) stimuli. Pupillometry intensity series were performed under both a dark-adapted condition and a light-adapted condition (on a 0.76-log cd m−2 blue background). The transient PLR, defined as the maximum constriction following flash onset, was measured under all conditions. The melanopsin-mediated sustained constriction was measured 5–7 s following flash offset for the highest flash luminance presented in the dark. Both patients were also tested in one eye with the full-field ERG, including a dark-adapted intensity series and ISCEV standard stimuli.
Dark-adapted PLRs were markedly attenuated or extinguished for low-luminance stimuli, but the responses to higher-luminance blue stimuli were within normal limits. Light-adapted PLRs to blue stimuli were generally within normal limits, exceeding the responses to photopically matched red stimuli. Thus, light-adapted responses were consistent with either rod or S-cone mediation of the PLR. Melanopsin-mediated sustained PLRs were within normal limits. ERG showed the characteristic findings previously reported in this condition. Cone-mediated ERG responses were markedly decreased in amplitude. Rod-mediated ERG responses were absent for low-luminance stimuli (− 3 log cd s m−2), but had normal amplitude for stimuli of − 2 log cd s m−2 and above (although none were “supernormal”). The b-wave for the dark-adapted ISCEV standard − 2 log cd s m−2 stimulus was markedly delayed, whereas the b-wave timing was generally normal for higher flash luminances.
The abnormalities measured by pupillometry have a similar pattern to the outer-retinal abnormalities measured by ERG in KCNV2 retinopathy. These findings as well as the normal sustained PLR suggest that inner-retinal function may be preserved in KCNV2 retinopathy and highlight the potential for therapies designed to restore outer-retinal function in these individuals.
KeywordsKCNV2 KCNV2 retinopathy Cone dystrophy with supernormal rod ERG Pupillometry Pupillary light reflex
The Pangere Family Foundation, Gary, Indiana (GAF), National Institutes of Health research grant P30EY001792 (core grant), an unrestricted departmental grant, and a Dolly Green Scholar award (JM) from Research to Prevent Blindness.
Compliance with ethical standards
Conflict of interest
All of the authors (Frederick T. Collison, Jason C. Park, Gerald A. Fishman, Edwin M. Stone, and J. Jason McAnany) declare that they have no conflict of interest.
Statement of human rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Statement on the welfare of animals
This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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