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Rod- versus cone-driven ERGs at different stimulus sizes in normal subjects and retinitis pigmentosa patients

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Abstract

Purpose

To study how rod- and cone-driven responses depend on stimulus size in normal subjects and patients with retinitis pigmentosa (RP), and to show that comparisons between responses to full-field (FF) and smaller stimuli can be useful in diagnosing and monitoring disorders of the peripheral retina without the need for lengthy dark adaptation periods.

Method

The triple silent substitution technique was used to isolate L-cone-, M-cone- and rod-driven ERGs with 19, 18 and 33% photoreceptor contrasts, respectively, under identical mean luminance conditions. Experiments were conducted on five normal subjects and three RP patients. ERGs on control subjects were recorded at nine different temporal frequencies (between 2 and 60 Hz) for five different stimulus sizes: FF, 70°, 60°, 50° and 40° diameter circular stimuli. Experiments on RP patients involved rod- and L-cone-driven ERG measurements with FF and 40° stimuli at 8 and 48 Hz. Response amplitudes were defined as those of the first harmonic component after Fourier analysis.

Results

In normal subjects, rod-driven responses displayed a fundamentally different behavior than cone-driven responses, particularly at low temporal frequencies. At low and intermediate temporal frequencies (≤ 12 Hz), rod-driven signals increased by a factor of about four when measured with smaller stimuli. In contrast, L- and M-cone-driven responses in this frequency region did not change substantially with stimulus size. At high temporal frequencies (≥ 24 Hz), both rod- and cone-driven response amplitudes decreased with decreasing stimulus size. Signals obtained from rod-isolating stimuli under these conditions are likely artefactual. Interestingly, in RP patients, both rod-driven and L-cone-driven ERGs were similar using 40° and FF stimuli.

Conclusion

The increased responses with smaller stimuli in normal subjects to rod-isolating stimuli indicate that a fundamentally different mechanism drives the ERGs in comparison with the cone-driven responses. We propose that the increased responses are caused by stray light stimulating the peripheral retina, thereby allowing peripheral rod-driven function to be studied using the triple silent substitution technique at photopic luminances. The method is effective in studying impaired peripheral rod- and cone- function in RP patients.

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Acknowledgements

The present work was performed in (partial) fulfillment of the requirements for obtaining the degree “Dr. rer. biol. hum” for AJA. NRAP’s participation was facilitated by the Manchester Biomedical Research Center and the Greater Manchester Comprehensive Local Research Network.

Funding

Bundesministerium fur Bildung und Forschung (BMBF) provided financial support in the form of project funding to JK (Grant#: 01DN14009). Deutsche Forschungsgemeinschaft (DFG) provided financial support in the form of project funding to JK (Grant#: KR1317/13-1). The sponsor had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany

    Avinash J. Aher, Tina I. Tsai, Cord Huchzermeyer & Jan Kremers

  2. School of Optometry and Vision Science, University of Bradford, Bradford, UK

    Declan J. McKeefry, Neil R. A. Parry, John Maguire & Jan Kremers

  3. Center for Hearing and Vision Research, Institute of Human Development, University of Manchester, Manchester, UK

    Neil R. A. Parry

  4. Vision Science Center, Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, UK

    Neil R. A. Parry

  5. Faculty of Life Sciences, University of Manchester, Manchester, UK

    I. J. Murray

Authors
  1. Avinash J. Aher
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  2. Declan J. McKeefry
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  3. Neil R. A. Parry
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  4. John Maguire
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  6. Tina I. Tsai
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Correspondence to Jan Kremers.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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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.

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Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.

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Aher, A.J., McKeefry, D.J., Parry, N.R.A. et al. Rod- versus cone-driven ERGs at different stimulus sizes in normal subjects and retinitis pigmentosa patients. Doc Ophthalmol 136, 27–43 (2018). https://doi.org/10.1007/s10633-017-9619-5

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  • DOI: https://doi.org/10.1007/s10633-017-9619-5

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