Documenta Ophthalmologica

, Volume 139, Issue 1, pp 11–20 | Cite as

Two-color pupillometry in KCNV2 retinopathy

  • Frederick T. Collison
  • Jason C. Park
  • Gerald A. FishmanEmail author
  • Edwin M. Stone
  • J. Jason McAnany
Original Research Article



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.


KCNV2 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

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Wu H, Cowing JA, Michaelides M et al (2006) Mutations in the gene KCNV2 encoding a voltage-gated potassium channel subunit cause “cone dystrophy with supernormal rod electroretinogram” in humans. Am J Hum Genet 79:574–579. CrossRefGoogle Scholar
  2. 2.
    Michaelides M, Holder GE, Webster AR et al (2005) A detailed phenotypic study of “cone dystrophy with supernormal rod ERG”. Br J Ophthalmol 89:332–339. CrossRefGoogle Scholar
  3. 3.
    Hood DC, Cideciyan AV, Halevy DA, Jacobson SG (1996) Sites of disease action in a retinal dystrophy with supernormal and delayed rod electroretinogram b-waves. Vis Res 36:889–901CrossRefGoogle Scholar
  4. 4.
    Sergouniotis PI, Holder GE, Robson AG et al (2012) High-resolution optical coherence tomography imaging in KCNV2 retinopathy. Br J Ophthalmol 96:213–217. CrossRefGoogle Scholar
  5. 5.
    Zobor D, Kohl S, Wissinger B et al (2012) Rod and cone function in patients with KCNV2 retinopathy. PLoS ONE 7:e46762. CrossRefGoogle Scholar
  6. 6.
    Zelinger L, Wissinger B, Eli D et al (2013) Cone dystrophy with supernormal rod response: novel KCNV2 mutations in an underdiagnosed phenotype. Ophthalmology 120:2338–2343. CrossRefGoogle Scholar
  7. 7.
    Robson AG, Webster AR, Michaelides M et al (2010) “Cone dystrophy with supernormal rod electroretinogram”: a comprehensive genotype/phenotype study including fundus autofluorescence and extensive electrophysiology. Retina 30:51–62. CrossRefGoogle Scholar
  8. 8.
    Gouras P, Eggers HM, MacKay CJ (1983) Cone dystrophy, nyctalopia, and supernormal rod responses. A new retinal degeneration. Arch Ophthalmol 101:718–724CrossRefGoogle Scholar
  9. 9.
    Khan AO, Alrashed M, Alkuraya FS (2012) “Cone dystrophy with supranormal rod response” in children. Br J Ophthalmol 96:422–426. CrossRefGoogle Scholar
  10. 10.
    Vincent A, Wright T, Garcia-Sanchez Y et al (2013) Phenotypic characteristics including in vivo cone photoreceptor mosaic in KCNV2-related “cone dystrophy with supernormal rod electroretinogram”. Invest Ophthalmol Vis Sci 54:898–908. CrossRefGoogle Scholar
  11. 11.
    Thiagalingam S, McGee TL, Weleber RG et al (2007) Novel mutations in the KCNV2 gene in patients with cone dystrophy and a supernormal rod electroretinogram. Ophthalmic Genet 28:135–142. CrossRefGoogle Scholar
  12. 12.
    Ben Salah S, Kamei S, Sénéćhal A et al (2008) Novel KCNV2 mutations in cone dystrophy with supernormal rod electroretinogram. Am J Ophthalmol 145:1099–1106. CrossRefGoogle Scholar
  13. 13.
    Friedburg C, Wissinger B, Schambeck M et al (2011) Long-term follow-up of the human phenotype in three siblings with cone dystrophy associated with a homozygous p. G461R mutation of KCNV2. Invest Ophthalmol Vis Sci 52:8621–8629. CrossRefGoogle Scholar
  14. 14.
    Gayet-Primo J, Yaeger DB, Khanjian RA, Puthussery T (2018) Heteromeric KV2/KV8.2 channels mediate delayed rectifier potassium currents in primate photoreceptors. J Neurosci 38:3414–3427. CrossRefGoogle Scholar
  15. 15.
    Czirják G, Tóth ZE, Enyedi P (2007) Characterization of the heteromeric potassium channel formed by kv2.1 and the retinal subunit kv8.2 in Xenopus oocytes. J Neurophysiol 98:1213–1222. CrossRefGoogle Scholar
  16. 16.
    Hart NS, Mountford JK, Voigt V et al (2019) The role of the voltage-gated potassium channel proteins Kv8.2 and Kv2.1 in vision and retinal disease: insights from the study of mouse gene knock-out mutations. eNeuro 6:1. CrossRefGoogle Scholar
  17. 17.
    McCulloch DL, Marmor MF, Brigell MG et al (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12. CrossRefGoogle Scholar
  18. 18.
    Park JC, Moura AL, Raza AS et al (2011) Toward a clinical protocol for assessing rod, cone, and melanopsin contributions to the human pupil response. Invest Ophthalmol Vis Sci 52:6624–6635. CrossRefGoogle Scholar
  19. 19.
    Park JC, McAnany JJ (2015) Effect of stimulus size and luminance on the rod-, cone-, and melanopsin-mediated pupillary light reflex. J Vis 15:1. Google Scholar
  20. 20.
    Collison FT, Park JC, Fishman GA et al (2015) Full-field pupillary light responses, luminance thresholds, and light discomfort thresholds in CEP290 leber congenital amaurosis patients. Invest Ophthalmol Vis Sci 56:7130–7136. CrossRefGoogle Scholar
  21. 21.
    Wissinger B, Dangel S, Jägle H et al (2008) Cone dystrophy with supernormal rod response is strictly associated with mutations in KCNV2. Invest Ophthalmol Vis Sci 49:751–757. CrossRefGoogle Scholar
  22. 22.
    Khan AO (2013) Recognizing the KCNV2-related retinal phenotype. Ophthalmology 120:e79–e80. CrossRefGoogle Scholar
  23. 23.
    Fujinami K, Tsunoda K, Nakamura N et al (2013) Molecular characteristics of four Japanese cases with KCNV2 retinopathy: report of novel disease-causing variants. Mol Vis 19:1580–1590Google Scholar
  24. 24.
    Stockman A, Henning GB, Michaelides M et al (2014) Cone dystrophy with “supernormal” rod ERG: psychophysical testing shows comparable rod and cone temporal sensitivity losses with no gain in rod function. Invest Ophthalmol Vis Sci 55:832–840. CrossRefGoogle Scholar
  25. 25.
    Tanimoto N, Usui T, Ichibe M et al (2005) PIII and derived PII analysis in a patient with retinal dysfunction with supernormal scotopic ERG. Doc Ophthalmol 110:219–226. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Frederick T. Collison
    • 1
  • Jason C. Park
    • 2
  • Gerald A. Fishman
    • 1
    • 2
    Email author
  • Edwin M. Stone
    • 3
  • J. Jason McAnany
    • 2
  1. 1.The Pangere Center for Inherited Retinal DiseasesThe Chicago LighthouseChicagoUSA
  2. 2.Department of Ophthalmology and Visual SciencesUniversity of Illinois at Chicago College of MedicineChicagoUSA
  3. 3.Department of Ophthalmology and Visual Sciences, Stephen A. Wynn Institute for Vision Research, Howard Hughes Medical InstituteThe University of Iowa Carver College of MedicineIowa CityUSA

Personalised recommendations