Evaluation of residual retinal function by pupillary constrictions and phosphenes using transcorneal electrical stimulation in patients with retinal degeneration

  • Takeshi Morimoto
  • Takehiro Fukui
  • Kenji Matsushita
  • Yoshitaka Okawa
  • Hiroshi Shimojyo
  • Shunji Kusaka
  • Yasuo Tano
  • Takashi Fujikado
Clinical Investigation
First Online:
Received:
Revised:
Accepted:

Abstract

Background

To evaluate inner-retinal function by pupillary constrictions and phosphenes evoked by transcorneal electrical stimulation (TES) in patients with hereditary retinal degeneration.

Methods

Consecutive 20 eyes of 20 patients (16 with retinitis pigmentosa (RP); and four with cone-rod dystrophy (CRD)) whose visual acuity was equal to or worse than 20/2000 at Osaka University Hospital and eight eyes of eight healthy subjects were enrolled. TES was performed on with a contact lens stimulating electrode. The electrically evoked pupillary response (EEPR) was recorded by a pupillometer, and the phosphenes by the subjective responses. Three electrical current thresholds were determined: T1, threshold current for initial phosphene; T2, threshold for eliciting a phosphene extending into the central field; and P, threshold for a relative pupillary constriction ≥3%.The EEPR and phosphene thresholds were compared with the visual acuity or the visual field.

Results

All T1, T2 and P were significantly higher in patients than in normals (Mann-Whitney, P<0.001). Both T1 and T2 were not correlated with visual acuity but depended on the area and location of the residual visual field. T1 and T2 in RP eyes with a EEPR was significantly lower than that in RP eyes without an EEPR. During TES, all subjects and patients had no pain, and no complications except for a slight corneal superficial punctuate keratopathy.

Conclusions

The safety and the efficacy of TES to estimate the residual inner-retinal function in patients with retinal degeneration indicate that TES can be used as one of the most important test to select candidates for retinal prostheses.

Keywords

Retinitis pigmentosa Cone-rod dystrophy Pupillary reflex Phosphene Transcorneal electrical stimulation 
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Notes

Acknowledgements

The authors thank Yozo Miyake, Satoshi Suzuki, Mineo Kondo and Yutaka Fukuda for advice and discussions.

References

  1. 1.
    Brindley GS (1955) The site of electrical excitation of the human eye. J Physiol 127:189–200PubMedGoogle Scholar
  2. 2.
    Chow AY, Chow VY (1997) Subretinal electrical stimulation of the rabbit retina. Neurosci Lett 225:13–16PubMedCrossRefGoogle Scholar
  3. 3.
    Chow AY, Chow VY, Packo KH, Pollack JS, Peyman GA, Schuchard R (2004) The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch Ophthalmol 122:460–469PubMedCrossRefGoogle Scholar
  4. 4.
    Delbeke J,Pins D, Michaux G, Wanet-Defalque MC, Parrini S, Veraart C (2001)Electrical stimulation of anterior visual pathways in retinitis pigmentosa. Invest Ophthalmol Vis Sci 42:291–297PubMedGoogle Scholar
  5. 5.
    Fariss RN, Li ZY, Milam AH (2000) Abnormalities in rod photoreceptors, amacrine cells, and horizontal cells in human retinas with retinitis pigmentosa. Am J Ophthalmol 129:215–223PubMedCrossRefGoogle Scholar
  6. 6.
    Gebhard JW (1952) Thresholds of the human eye for electric stimulation by different wave forms. J Exp Psychol 44:132–140PubMedCrossRefGoogle Scholar
  7. 7.
    Haruta M, Kosaka M, Kanegae Y, Saito I, Inoue T, Kageyama R, Nishida A, Honda Y, Takahashi M (2001) Induction of photoreceptor-specific phenotypes in adult mammalian iris tissue. Nat Neurosci 4:1163–1164PubMedCrossRefGoogle Scholar
  8. 8.
    Hesse L, Schanze T, Wilms M, Eger M (2000) Implantation of retina stimulation electrodes and recording of electrical stimulation responses in the visual cortex of the cat. Graefe’s Arch Clin Exp Ophthalmol 238:840–845CrossRefGoogle Scholar
  9. 9.
    Humayun MS, Price M, de Juan Jr E, Barron Y, Moskowitz M, Klock IB, Milam AH (1999) Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa. Invest Ophthalmol Vis Sci 40:143–148PubMedGoogle Scholar
  10. 10.
    Humayun MS, Weiland JD, Fujii GY, Greenberg RJ, Williamson R, Little J, Mech B, Climmarusti V, Van Boemel G, Dagnelie G, de Juan Jr E (2003) Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vision Res 43:2573–2581PubMedCrossRefGoogle Scholar
  11. 11.
    Jensen RJ, Rizzo JF 3rd, Ziv OR, Grumet A, Wyatt J (2003) Thresholds for activation of rabbit retinal ganglion cells with an ultrafine, extracellular microelectrode. Invest Ophthalmol Vis Sci 44:3533–3543PubMedCrossRefGoogle Scholar
  12. 12.
    Johnson LN, Guy ME, Krohel GB, Madsen RW (2000) Levodopa may improve vision loss in recent-onset, nonarteritic anterior ischemic optic neuropathy. Ophthalmology 107:521–526PubMedCrossRefGoogle Scholar
  13. 13.
    Kanda H, Morimoto T, Fujikado T, Tano Y, Fukuda Y, Sawai H (2004) Electrophysiological studies on the feasibility of suprachoroidal-transretinal stimulation for artificial vision in normal and RCS rat. Invest Ophthalmol Vis Sci 45:560–566PubMedCrossRefGoogle Scholar
  14. 14.
    Kawasumi M (1985) Distribution of current intensities inside the electrically stimulated eye. Nippon Ganka Gakkai Zasshi 89:766–772PubMedGoogle Scholar
  15. 15.
    Li ZY, Kjavin IJ, Milam AH. (1995) Rod photoreceptor neurite sprouting in retinitis pigmentosa. J Neurosci 15:5429–5438PubMedGoogle Scholar
  16. 16.
    Majji AB, Humayun MS, Weiland JD, Suzuki S, D’Anna SA, de Juan Jr E (1999) Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs. Invest Ophthalmol Vis Sci 40:2073–2081PubMedGoogle Scholar
  17. 17.
    Margalit E, Maia M, Weiland JD, Greenberg RJ, Fujii GY, Torres G, Piyathaisere DV, O’Hearn TM, Liu W, Lazzi G, Dangnelie G, Scribner DA, de Juan Jr E, Humayun MS (2002) Retinal prosthesis for the blind. Surv Ophthalmol 47:335–356PubMedCrossRefGoogle Scholar
  18. 18.
    Marmor MF, Aguirre G, Arden G (1983) Retinitis pigmentosa: a symposium on terminology and methods of examination. Ophthalmology 90:126–131Google Scholar
  19. 19.
    Motokawa K, Iwama K (1950) Resonance in electrical stimulation of the eye. Tohoku J. Exp Med 53:201–206PubMedCrossRefGoogle Scholar
  20. 20.
    Motokawa K, Ebe M (1952) Selective stimulation of color receptors with alternating currents. Science 25:115:92–94Google Scholar
  21. 21.
    Miyake Y, Yanagida K, Yagasaki K (1980) Clinical application of EER (electrically evoked response). (1) Analysis of EER in normal subjects. Nippon Ganka Gakkai Zasshi 84:354–360Google Scholar
  22. 22.
    Miyake Y, Yanagida K, Yagasaki K (1980) Clinical application of EER (electrically evoked response) (2) Analysis of EER in patients with dysfunctional rod or cone visual pathway. Nippon Ganka Gakkai Zasshi 84:502–509PubMedGoogle Scholar
  23. 23.
    Pagon RA (1988) Retinitis pigmentosa. Surv Ophthalmol 33:137–177PubMedCrossRefGoogle Scholar
  24. 24.
    Potts AM, Inoue J (1968) The electrically evoked response of the visual system (EER). Invest Ophthalmol 7:269–278PubMedGoogle Scholar
  25. 25.
    Potts AM, Inoue J (1969) The electrically evoked response of the visual system (EER) II. Effect of adaptation and retinitis pigmentosa. Invest Ophthalmol 8:605–613PubMedGoogle Scholar
  26. 26.
    Rizzo JF 3rd, Wyatt J, Loewenstein J, Kelly S, Shire D (2003) Perceptual efficacy of electrical stimulation of human retina with a microelectrode array during short-term surgical trials. Invest Ophthalmol Vis Sci 44:5362–5369PubMedCrossRefGoogle Scholar
  27. 27.
    Santos A, Humayun MS, de Juan E Jr, Greenberg RJ, Marsh MJ, Klock IB, Milam AH (1997) Preservation of the inner retina in retinitis pigmentosa: a morphometric analysis. Arch Ophthalmol 115:511–515PubMedGoogle Scholar
  28. 28.
    Schwahn HN, Gekeler F, Kohler K,Kobuch K, Sachs HG, Schulmeyer F, Jacob W, Gabel VP, Zrenner E (2001) Studies on the feasibility of a subretinal visual prosthesis: data from Yucatan micropig and rabbit. Graefe’s Arch Clin Exp Ophthalmol 239:961–967CrossRefGoogle Scholar
  29. 29.
    Stone JL, Barlow WE, Humayun MS, de Juan E Jr, Milam AH (1992) Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch Ophthalmol 110:1634–1639PubMedGoogle Scholar
  30. 30.
    Tanino T, Kato S, Kawasumi M (1981) Studies on electrically evoked pupillary reflex-Indirect reflex and its frequency characteristics. Jpn J Ophthalmol 25:423–429Google Scholar
  31. 31.
    Tanino T, Kurihara K (1982) Electrically evoked direct and consensual reflexs of the pupil. Jpn J Ophthalmol 26:462–467PubMedGoogle Scholar
  32. 32.
    Tanino T. (1982) Studies on electrically evoked pupillary reaction 1. Indirect electrical reaction and its frequency characteristic. Nippon Ganka Gakkai Zasshi (Japanese) 61:397–402Google Scholar
  33. 33.
    Veraart C, Raftopoulos C, Mortimer JT, Delbeke J, Pins D, Michaux G, Vanlierde A, Parrini S, Wanet-Defalque MC (1998) Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode. Brain Res 813:181–186PubMedCrossRefGoogle Scholar
  34. 34.
    Walter P, Heimann K (2000) Evoked cortical potentials after electrical stimulation of the inner retina in rabbits. Graefe’s Arch Clin Exp Ophthalmol 238:315–318CrossRefGoogle Scholar
  35. 35.
    Yanai D, Lakhanpal RR, Weiland JD, Mahadevappa M, Van Boemel G, Fujii G, Greenberg R, Caffey S, de Juan Jr E (2003) The value of preoperative tests in the selection of blind patients for a permanent microelectronic implant. Trans Am Ophthalmol Soc 101:223–230PubMedGoogle Scholar
  36. 36.
    Young MJ, Ray J, Whiteley RS, Klassen H, Gage FH (2000) Neuronal differentiation and morphological integration of hippocampal progenitor cells transplanted to the retina of immature and mature dystrophic rats. Mol Cell Neurosci 16:197–205PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Takeshi Morimoto
    • 1
  • Takehiro Fukui
    • 1
  • Kenji Matsushita
    • 2
  • Yoshitaka Okawa
    • 1
  • Hiroshi Shimojyo
    • 2
  • Shunji Kusaka
    • 1
  • Yasuo Tano
    • 2
  • Takashi Fujikado
    • 1
  1. 1.Department of Applied Visual ScienceOsaka University Graduate School of MedicineOsakaJapan
  2. 2.Department of OphthalmologyOsaka University Graduate School of MedicineOsakaJapan

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