Consecutive unilateral recording of the two eyes affects dark-adapted ERG responses, when compared to simultaneous bilateral recording

Abstract

Purpose

Our aim was to compare the electroretinographic (ERG) responses of two eyes obtained by consecutive unilateral recordings to those obtained by a simultaneous bilateral recording in sheep.

Methods

Eight sheep underwent two full-field ERG recordings, using two recording strategies of the standard ISCEV protocol: consecutive unilateral recordings of one eye after the other, and simultaneous bilateral recording of both eyes. The order of recording strategy within an animal (unilateral/bilateral), eye recording sequence in the unilateral session (OD/OS), and amplifier channel assignment for each eye were all randomized. To test whether duration of dark adaptation and/or anesthesia affect the results, the ISCEV protocol was recorded bilaterally in six additional eyes following 38 min of patched dark adaptation, as was done for the second eye recorded in the consecutive unilateral recordings.

Results

The second recorded eye in the unilateral session had significantly higher scotopic b-wave amplitudes compared to the first recorded eye and to the bilaterally recorded eyes. A-wave amplitudes of the dark-adapted mixed rod–cone responses to a high-intensity flash were also significantly higher in the second eye compared to the first eye recorded unilaterally and to the bilaterally recorded eyes. Light-adapted responses were unaffected by the recording strategy. When the ISCEV protocol was recorded after 38 min of dark adaptation, the scotopic responses were higher than in the first eyes, and similar to those of the second eyes recorded unilaterally, suggesting that indeed the longer duration of anesthesia and dark adaptation are responsible for the increased scotopic responses of the second eye.

Conclusions

Consecutive unilateral ERG recordings of two eyes result in higher amplitudes of the dark-adapted responses of the eye recorded second, compared to the eye recorded first and to bilaterally recorded eyes. The differences in scotopic responses can be attributed to different duration of dark adaptation and/or anesthesia of the two consecutively recorded eyes. Photopic responses are not affected. Therefore, simultaneous bilateral ERG responses should be recorded when possible, especially for evaluation of scotopic responses.

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References

  1. 1.

    Young B, Eggenberger E, Kaufman D (2012) Current electrophysiology in ophthalmology: a review. Curr Opin Ophthalmol 23(6):497–505

    Article  Google Scholar 

  2. 2.

    Ekesten B, Komáromy AM, Ofri R, Petersen-Jones SM, Narfström K (2013) Guidelines for clinical electroretinography in the dog: 2012 update. Doc Ophthalmol 127(2):79–87

    Article  Google Scholar 

  3. 3.

    Robson JG, Frishman LJ (2014) The rod-driven a-wave of the dark-adapted mammalian electroretinogram. Prog Retin Eye Res 39:1–22

    Article  Google Scholar 

  4. 4.

    Liu Y, McDowell CM, Zhang Z, Tebow HE, Wordinger RJ, Clark AF (2014) Monitoring retinal morphologic and functional changes in mice following optic nerve crush. Invest Ophthalmol Vis Sci 55(6):3766–3774

    Article  Google Scholar 

  5. 5.

    Shaikh S, Shaikh N, Chun SH, Spin JM, Blumenkranz MS, Marmor MF (2003) Retinal evaluation of patients on chronic amiodarone therapy. Retina 23(3):354–359

    Article  Google Scholar 

  6. 6.

    Tzekov RT, Serrato A, Marmor MF (2004) ERG findings in patients using hydroxychloroquine. Doc Ophthalmol 108(1):87–97

    Article  Google Scholar 

  7. 7.

    Messias A, Gekeler F, Wegener A, Dietz K, Kohler K, Zrenner E (2008) Retinal safety of a new fluoroquinolone, pradofloxacin, in cats: assessment with electroretinography. Doc Ophthalmol 116(3):177–191

    Article  Google Scholar 

  8. 8.

    Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 358(21):2231–2239

    CAS  Article  Google Scholar 

  9. 9.

    Narfström K, Katz ML, Bragadottir R, Seeliger M, Boulanger A, Redmond TM, Caro L, Lai CM, Rakoczy PE (2003) Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Invest Ophthalmol Vis Sci 44(4):1663–1672

    Article  Google Scholar 

  10. 10.

    Banin E, Gootwine E, Obolensky A, Ezra-Elia R, Ejzenberg A, Zelinger L, Honig H, Rosov A, Yamin E, Sharon D, Averbukh E, Hauswirth WW, Ofri R (2015) Gene augmentation therapy restores retinal function and visual behavior in a sheep model of CNGA3 achromatopsia. Mol Ther 23(9):1423–1433

    CAS  Article  Google Scholar 

  11. 11.

    Dalkara D, Sahel JA (2014) Gene therapy for inherited retinal degenerations. C R Biol 337(3):185–192

    Article  Google Scholar 

  12. 12.

    Ye GJ, Komáromy AM, Zeiss C, Calcedo R, Harman CD, Koehl KL, Stewart GA, Iwabe S, Chiodo VA, Hauswirth WW, Aguirre GD, Chulay JD (2017) Safety and efficacy of AAV5 vectors expressing human or canine CNGB3 in CNGB3-mutant dogs. Hum Gene Ther Clin Dev 28(4):197–207

    CAS  Article  Google Scholar 

  13. 13.

    Rosa M, Botteon PdTL, Pereira JdS, Brooks DE, Rosa MVD (2014) Evaluation of equine electroretinographic responses by using two different electrodes and four different Alpha-2 agonist sedatives. Rev Bras Med Vet 36(4):367–374

    Google Scholar 

  14. 14.

    Ross JW, Fernandez de Castro JP, Zhao J, Samuel M, Walters E, Rios C, Bray-Ward P, Jones BW, Marc RE, Wang W, Zhou L, Noel JM, McCall MA, DeMarco PJ, Prather RS, Kaplan HJ (2012) Generation of an inbred miniature pig model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 53(1):501–507

    CAS  Article  Google Scholar 

  15. 15.

    Barliya T, Ofri R, Sandalon S, Weinberger D, Livnat T (2017) Changes in retinal function and cellular remodeling following experimental retinal detachment in a rabbit model. J Ophthalmol 2017:4046597

    Article  Google Scholar 

  16. 16.

    Sandalon S, Ofri R (2009) The effect of topical anesthesia on the rat electroretinogram. Doc Ophthalmol 118(2):101–108

    Article  Google Scholar 

  17. 17.

    Giansanti F, Ramazzotti M, Vannozzi L, Rapizzi E, Fiore T, Iaccheri B, Degl’ Innocenti D, Moncini D, Menchini U (2008) A pilot study on ocular safety of intravitreal infliximab in a rabbit model. Invest Ophthalmol Vis Sci 49(3):1151–1156

    Article  Google Scholar 

  18. 18.

    Whiting RE, Narfström K, Yao G, Pearce JW, Coates JR, Castaner LJ, Jensen CA, Dougherty BN, Vuillemenot BR, Kennedy D, O’Neill CA, Katz ML (2014) Enzyme replacement therapy delays pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis. Exp Eye Res 125:164–172

    CAS  Article  Google Scholar 

  19. 19.

    Petit L, Lhériteau E, Weber M, Le Meur G, Deschamps JY, Provost N, Mendes-Madeira A, Libeau L, Guihal C, Colle MA, Moullier P, Rolling F (2012) Restoration of vision in the pde6β-deficient dog, a large animal model of rod-cone dystrophy. Mol Ther 20(11):2019–2030

    CAS  Article  Google Scholar 

  20. 20.

    Del Sole MJ, Sande PH, Fernandez DC, Sarmiento MI, Aba MA, Rosenstein RE (2012) Therapeutic benefit of melatonin in experimental feline uveitis. J Pineal Res 52(1):29–37

    Article  Google Scholar 

  21. 21.

    Ezra-Elia R, Banin E, Honig H, Rosov A, Obolensky A, Averbukh E, Hauswirth WW, Gootwine E, Ofri R (2014) Flicker cone function in normal and day blind sheep: a large animal model for human achromatopsia caused by CNGA3 mutation. Doc Ophthalmol 129(3):141–150

    Article  Google Scholar 

  22. 22.

    Shamir MH, Ofri R, Bor A, Brenner O, Reicher S, Obolensky A, Averbukh E, Banin E, Gootwine E (2010) A novel day blindness in sheep: epidemiological, behavioural, electrophysiological and histopathological studies. Vet J 185(2):130–137

    Article  Google Scholar 

  23. 23.

    Reicher S, Seroussi E, Gootwine E (2010) A mutation in gene CNGA3 is associated with day blindness in sheep. Genomics 95(2):101–104

    CAS  Article  Google Scholar 

  24. 24.

    Gootwine E, Abu-Siam M, Obolensky A, Rosov A, Honig H, Nitzan T, Shirak A, Ezra-Elia R, Yamin E, Banin E, Averbukh E, Hauswirth WW, Ofri R, Seroussi E (2017) Gene augmentation therapy for a missense substitution in the cGMP-binding domain of ovine CNGA3 gene restores vision in day-blind sheep. Invest Ophthalmol Vis Sci 58(3):1577–1584

    CAS  Article  Google Scholar 

  25. 25.

    Gootwine E, Ofri R, Banin E, Obolensky A, Averbukh E, Ezra-Elia R, Ross M, Honig H, Rosov A, Yamin E, Ye GJ, Knop DR, Robinson P, Chulay JD, Shearman MS (2017) Safety and efficacy evaluation of rAAV2tYF-PR1.7-hCNGA3 vector delivered by subretinal injection in CNGA3 mutant achromatopsia sheep. Hum Gene Ther Clin Dev 28(2):96–107

    CAS  Article  Google Scholar 

  26. 26.

    Lalonde MR, Chauhan BC, Tremblay F (2006) Retinal ganglion cell activity from the multifocal electroretinogram in pig: optic nerve section, anaesthesia and intravitreal tetrodotoxin. J Physiol 570(Pt 2):325–338

    CAS  Article  Google Scholar 

  27. 27.

    Maffei L, Fiorentini A, Bisti S, Holländer H (1985) Pattern ERG in the monkey after section of the optic nerve. Exp Brain Res 59(2):423–425

    CAS  Article  Google Scholar 

  28. 28.

    Wilsey L, Gowrisankaran S, Cull G, Hardin C, Burgoyne CF, Fortune B (2017) Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure. Doc Ophthalmol 134(2):111–128

    Article  Google Scholar 

  29. 29.

    Fortune B, Cull GA, Burgoyne CF (2008) Relative course of retinal nerve fiber layer birefringence and thickness and retinal function changes after optic nerve transection. Invest Ophthalmol Vis Sci 49(10):4444–4452

    Article  Google Scholar 

  30. 30.

    McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130(1):1–12

    Article  Google Scholar 

  31. 31.

    Abramson JH (2011) WINPEPI updated: computer programs for epidemiologists, and their teaching potential. Epidemiol Perspect Innov 8(1):1

    Article  Google Scholar 

  32. 32.

    Mentzer AE, Eifler DM, Montiani-Ferreira F, Tuntivanich N, Forcier JQ, Petersen-Jones SM (2005) Influence of recording electrode type and reference electrode position on the canine electroretinogram. Doc Ophthalmol 111(2):95–106

    Article  Google Scholar 

  33. 33.

    Yin H, Pardue MT (2004) Performance of the DTL electrode compared to the jet contact lens electrode in clinical testing. Doc Ophthalmol 108(1):77–86

    Article  Google Scholar 

  34. 34.

    Jeong MB, Son WG, Park YW, Kim SE, Park SA, Seo KM (2011) Comparison of two electroretinography systems used in dogs: the HMsERG and the RETIport. J Vet Med Sci 73(4):431–438

    Article  Google Scholar 

  35. 35.

    Varela Lopez O, Alvarez Vazquez JC, Gonzalez Cantalapiedra A, Rosolen SG (2010) Effects of hypercapnia on the electroretinogram in sevoflurane and isoflurane anaesthetized dogs. Doc Ophthalmol 121(1):9–20

    CAS  Article  Google Scholar 

  36. 36.

    Kong J, Gouras P (2003) The effect of body temperature on the murine electroretinogram. Doc Ophthalmol 106(3):239–242

    Article  Google Scholar 

  37. 37.

    Del Sole MJ, Nejamkin P, Cavilla V, Schaiquevich P, Moreno L (2017) Comparison of two sedation protocols for short electroretinography in cats. J Feline Med Surg 20(2):172–178

    Article  Google Scholar 

  38. 38.

    Nair G, Kim M, Nagaoka T, Olson DE, Thulé PM, Pardue MT, Duong TQ (2011) Effects of common anesthetics on eye movement and electroretinogram. Doc Ophthalmol 122(3):163–176

    Article  Google Scholar 

  39. 39.

    Freeman KS, Good KL, Kass PH, Park SA, Nestorowicz N, Ofri R (2013) Effects of chemical restraint on electroretinograms recorded sequentially in awake, sedated, and anesthetized dogs. Am J Vet Res 74(7):1036–1042

    CAS  Article  Google Scholar 

  40. 40.

    Reid J, Nolan AM, Welsh E (1993) Propofol as an induction agent in the goat: a pharmacokinetic study. J Vet Pharmacol Ther 16(4):488–493

    CAS  Article  Google Scholar 

  41. 41.

    Cameron AM, Mahroo OA, Lamb TD (2006) Dark adaptation of human rod bipolar cells measured from the b-wave of the scotopic electroretinogram. J Physiol 575(Pt 2):507–526

    CAS  Article  Google Scholar 

  42. 42.

    Hamilton R, Graham K (2016) Effect of shorter dark adaptation on ISCEV standard DA 0.01 and DA 3 skin ERGs in healthy adults. Doc Ophthalmol 133(1):11–19

    CAS  Article  Google Scholar 

  43. 43.

    Sandalon S, Könnecke B, Levkovitch-Verbin H, Simons M, Hein K, Sättler MB, Bähr M, Ofri R (2013) Functional and structural evaluation of lamotrigine treatment in rat models of acute and chronic ocular hypertension. Exp Eye Res 115:47–56

    CAS  Article  Google Scholar 

  44. 44.

    Lachapelle P (1987) Analysis of the photopic electroretinogram recorded before and after dark adaptation. Can J Ophthalmol 22(7):354–361

    CAS  PubMed  Google Scholar 

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Funding

This study was funded by the Israel Science Foundation (Grant 1257/15).

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Correspondence to Ron Ofri.

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Conflict of interest

RO received speaker honoraria from OcuScience.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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This article does not contain any studies with human participants performed by any of the authors.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Volcani Center Animal Care and Use Committee and conformed with the ARVO Statement for the use of animals.

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Ross, M., Honig, H., Ezra-Elia, R. et al. Consecutive unilateral recording of the two eyes affects dark-adapted ERG responses, when compared to simultaneous bilateral recording. Doc Ophthalmol 137, 183–192 (2018). https://doi.org/10.1007/s10633-018-9661-y

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Keywords

  • Electroretinography (ERG)
  • Unilateral
  • Bilateral
  • Dark-adapted responses
  • ISCEV
  • Sheep