The role of Müller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission

Andrea Govetto; Jean Pierre Hubschman; David Sarraf; Marta S. Figueroa; Ferdinando Bottoni; Roberto Dell'Omo; Christine A. Curcio; Patrizio Seidenari; Giulia Delledonne; Robert Gunzenhauser; Mariantonia Ferrara; Adrian Au; Gianni Virgili; Antonio Scialdone; Rodolfo Repetto; Mario R. Romano

doi:10.1136/bjophthalmol-2019-314245

The role of Müller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission

Andrea Govetto^*, Jean Pierre Hubschman, David Sarraf, Marta S. Figueroa, Ferdinando Bottoni, Roberto Dell'Omo, Christine A. Curcio, Patrizio Seidenari, Giulia Delledonne, Robert Gunzenhauser, Mariantonia Ferrara, Adrian Au, Gianni Virgili, Antonio Scialdone, Rodolfo Repetto, Mario R. Romano

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

Background: To explore the role of foveal and parafoveal Müller cells in the morphology and pathophysiology of tractional macular disorders with a mathematical model of mechanical force transmission. Methods: In this retrospective observational study, spectral-domain optical coherence tomography images of tractional lamellar macular holes and patients with myopic foveoschisis were reviewed and analysed with a mathematical model of force transmission. Parafoveal z-shaped Müller cells were modelled as a structure composed of three rigid rods, named R1, R2 and R3. The angle formed between the rods was referred to as θ. R1, R2 and R3 lengths as well as the variation of the angle θ were measured and correlated with best corrected visual acuity (BCVA). Results: In tractional lamellar macular holes, there was a significant reduction of the angle θ towards the foveal centre (p<0.001). By contrast, there were no significant differences in θ in myopic foveoschisis (p=0.570). R2 segments were more vertical in myopic foveoschisis. There was a significant association between lower θ angles at 200 μm temporal and nasal to the fovea and lower BCVA (p<0.001 and p=0.005, respectively). The stiffness of parafoveal Müller cells was predicted to be function of the angle θ, and it grew very rapidly as the θ decreased. Conclusion: Parafoveal Müller cells in the Henle fibre layer may guarantee structural stability of the parafovea by increasing retinal compliance and resistance to mechanical stress. Small values of the angle θ were related to worse BCVA possibly due to damage to Müller cell processes and photoreceptor's axons.

Original language	English
Pages (from-to)	466-472
Number of pages	7
Journal	British Journal of Ophthalmology
Volume	104
Issue number	4
Early online date	20 Jul 2019
DOIs	https://doi.org/10.1136/bjophthalmol-2019-314245
Publication status	Published - 01 Apr 2020
Externally published	Yes

Bibliographical note

Funding Information:
1Department of Ophthalmology, Fatebenefratelli-Oftalmico Hospital, ASST-Fatebenefratelli-Sacco, Milan, Italy 2Retina Division, Stein Eye Institute, UCLA, Los Angeles, California, USA 3Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute, UCLA, Los Angeles, California, USA 4Department of Ophthalmology, Greater Los Angeles VA Healthcare Center, Los Angeles, California, USA 5Department of Ophthalmology, Ramon y Cajal University Hospital, Madrid, Spain 6Eye Clinic, Department of Biomedical and Clinical Science ’Luigi Sacco’, Sacco Hospital, University of Milan, Milan, Italy 7Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy 8Department of Ophthalmology, University of Alabama at Birmingham College of Arts and Sciences, Birmingham, Alabama, USA 9Eye Unit, Humanitas University, Humanitas-Gavazzeni Hospital, Bergamo, Italy 10Department of Ophthalmology, Careggi University Hospital, University of Florence, Florence, Italy 11Department of Civil, Chemical and Environmental Engineering, University of Genoa, Genoa, Italy Funding J-PH: consultant for Alcon (Fort Wort, TX, USA), Allergan (Dublin, Ireland); DS: consultant for Amgen (Thousand Oaks, CA, USA), consultant and speaker for Bayer (Leverkusen, Germany), consultant and researcher for Genentech (San Francisco, CA, USA), researcher for Heidelberg (Heidelberg, Germany), speaker for Novartis (Basel, Switzerland), consultant, researcher and speaker for Optovue (Freemont, CA, USA), researcher for Regeneron (Tarrytown, NY, USA); MSF: consultant for Novartis (Basel, Switzerland), Alcon (Fort Wort, TX, USA), Bayer (Leverkusen, Germany), Allergan (Dublin, Ireland), Hoffman LaRoche (Basel, Switzerland), Zeiss (Oberkochen, Germany); FB: consultant for Novartis (Basel, Switzerland), Bayer (Leverkusen, Germany); CC: Consultant for Genentech (San Francisco, California, USA), Merck (Whitehouse Station, New Jersey, USA) Janssen Cell Therapy (Raritan, New Jersey, USA); research support from Hoffman LaRoche (Basel, Switzerland). MRR: research grants from Alcon (Fort Wort, TX, USA); DORC (Zuidland, Holland); Baush & Lomb (Rochester, NY, USA); Bayer (Leverkusen, Germany), consultant for Leica (Wetzlar, Germany).

Publisher Copyright:
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

anatomy
imaging
macula
retina

ASJC Scopus subject areas

Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience

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Cite this

Govetto, A., Hubschman, J. P., Sarraf, D., Figueroa, M. S., Bottoni, F., Dell'Omo, R., Curcio, C. A., Seidenari, P., Delledonne, G., Gunzenhauser, R., Ferrara, M., Au, A., Virgili, G., Scialdone, A., Repetto, R., & Romano, M. R. (2020). The role of Müller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission. British Journal of Ophthalmology, 104(4), 466-472. https://doi.org/10.1136/bjophthalmol-2019-314245

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title = "The role of M{\"u}ller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission",

abstract = "Background: To explore the role of foveal and parafoveal M{\"u}ller cells in the morphology and pathophysiology of tractional macular disorders with a mathematical model of mechanical force transmission. Methods: In this retrospective observational study, spectral-domain optical coherence tomography images of tractional lamellar macular holes and patients with myopic foveoschisis were reviewed and analysed with a mathematical model of force transmission. Parafoveal z-shaped M{\"u}ller cells were modelled as a structure composed of three rigid rods, named R1, R2 and R3. The angle formed between the rods was referred to as θ. R1, R2 and R3 lengths as well as the variation of the angle θ were measured and correlated with best corrected visual acuity (BCVA). Results: In tractional lamellar macular holes, there was a significant reduction of the angle θ towards the foveal centre (p<0.001). By contrast, there were no significant differences in θ in myopic foveoschisis (p=0.570). R2 segments were more vertical in myopic foveoschisis. There was a significant association between lower θ angles at 200 μm temporal and nasal to the fovea and lower BCVA (p<0.001 and p=0.005, respectively). The stiffness of parafoveal M{\"u}ller cells was predicted to be function of the angle θ, and it grew very rapidly as the θ decreased. Conclusion: Parafoveal M{\"u}ller cells in the Henle fibre layer may guarantee structural stability of the parafovea by increasing retinal compliance and resistance to mechanical stress. Small values of the angle θ were related to worse BCVA possibly due to damage to M{\"u}ller cell processes and photoreceptor's axons.",

keywords = "anatomy, imaging, macula, retina",

author = "Andrea Govetto and Hubschman, {Jean Pierre} and David Sarraf and Figueroa, {Marta S.} and Ferdinando Bottoni and Roberto Dell'Omo and Curcio, {Christine A.} and Patrizio Seidenari and Giulia Delledonne and Robert Gunzenhauser and Mariantonia Ferrara and Adrian Au and Gianni Virgili and Antonio Scialdone and Rodolfo Repetto and Romano, {Mario R.}",

note = "Funding Information: 1Department of Ophthalmology, Fatebenefratelli-Oftalmico Hospital, ASST-Fatebenefratelli-Sacco, Milan, Italy 2Retina Division, Stein Eye Institute, UCLA, Los Angeles, California, USA 3Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute, UCLA, Los Angeles, California, USA 4Department of Ophthalmology, Greater Los Angeles VA Healthcare Center, Los Angeles, California, USA 5Department of Ophthalmology, Ramon y Cajal University Hospital, Madrid, Spain 6Eye Clinic, Department of Biomedical and Clinical Science {\textquoteright}Luigi Sacco{\textquoteright}, Sacco Hospital, University of Milan, Milan, Italy 7Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy 8Department of Ophthalmology, University of Alabama at Birmingham College of Arts and Sciences, Birmingham, Alabama, USA 9Eye Unit, Humanitas University, Humanitas-Gavazzeni Hospital, Bergamo, Italy 10Department of Ophthalmology, Careggi University Hospital, University of Florence, Florence, Italy 11Department of Civil, Chemical and Environmental Engineering, University of Genoa, Genoa, Italy Funding J-PH: consultant for Alcon (Fort Wort, TX, USA), Allergan (Dublin, Ireland); DS: consultant for Amgen (Thousand Oaks, CA, USA), consultant and speaker for Bayer (Leverkusen, Germany), consultant and researcher for Genentech (San Francisco, CA, USA), researcher for Heidelberg (Heidelberg, Germany), speaker for Novartis (Basel, Switzerland), consultant, researcher and speaker for Optovue (Freemont, CA, USA), researcher for Regeneron (Tarrytown, NY, USA); MSF: consultant for Novartis (Basel, Switzerland), Alcon (Fort Wort, TX, USA), Bayer (Leverkusen, Germany), Allergan (Dublin, Ireland), Hoffman LaRoche (Basel, Switzerland), Zeiss (Oberkochen, Germany); FB: consultant for Novartis (Basel, Switzerland), Bayer (Leverkusen, Germany); CC: Consultant for Genentech (San Francisco, California, USA), Merck (Whitehouse Station, New Jersey, USA) Janssen Cell Therapy (Raritan, New Jersey, USA); research support from Hoffman LaRoche (Basel, Switzerland). MRR: research grants from Alcon (Fort Wort, TX, USA); DORC (Zuidland, Holland); Baush & Lomb (Rochester, NY, USA); Bayer (Leverkusen, Germany), consultant for Leica (Wetzlar, Germany). Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = apr,

day = "1",

doi = "10.1136/bjophthalmol-2019-314245",

language = "English",

volume = "104",

pages = "466--472",

journal = "British Journal of Ophthalmology",

issn = "0007-1161",

publisher = "BMJ Publishing Group",

number = "4",

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Govetto, A, Hubschman, JP, Sarraf, D, Figueroa, MS, Bottoni, F, Dell'Omo, R, Curcio, CA, Seidenari, P, Delledonne, G, Gunzenhauser, R, Ferrara, M, Au, A, Virgili, G, Scialdone, A, Repetto, R & Romano, MR 2020, 'The role of Müller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission', British Journal of Ophthalmology, vol. 104, no. 4, pp. 466-472. https://doi.org/10.1136/bjophthalmol-2019-314245

TY - JOUR

T1 - The role of Müller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission

AU - Govetto, Andrea

AU - Hubschman, Jean Pierre

AU - Sarraf, David

AU - Figueroa, Marta S.

AU - Bottoni, Ferdinando

AU - Dell'Omo, Roberto

AU - Curcio, Christine A.

AU - Seidenari, Patrizio

AU - Delledonne, Giulia

AU - Gunzenhauser, Robert

AU - Ferrara, Mariantonia

AU - Au, Adrian

AU - Virgili, Gianni

AU - Scialdone, Antonio

AU - Repetto, Rodolfo

AU - Romano, Mario R.

N1 - Funding Information: 1Department of Ophthalmology, Fatebenefratelli-Oftalmico Hospital, ASST-Fatebenefratelli-Sacco, Milan, Italy 2Retina Division, Stein Eye Institute, UCLA, Los Angeles, California, USA 3Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute, UCLA, Los Angeles, California, USA 4Department of Ophthalmology, Greater Los Angeles VA Healthcare Center, Los Angeles, California, USA 5Department of Ophthalmology, Ramon y Cajal University Hospital, Madrid, Spain 6Eye Clinic, Department of Biomedical and Clinical Science ’Luigi Sacco’, Sacco Hospital, University of Milan, Milan, Italy 7Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy 8Department of Ophthalmology, University of Alabama at Birmingham College of Arts and Sciences, Birmingham, Alabama, USA 9Eye Unit, Humanitas University, Humanitas-Gavazzeni Hospital, Bergamo, Italy 10Department of Ophthalmology, Careggi University Hospital, University of Florence, Florence, Italy 11Department of Civil, Chemical and Environmental Engineering, University of Genoa, Genoa, Italy Funding J-PH: consultant for Alcon (Fort Wort, TX, USA), Allergan (Dublin, Ireland); DS: consultant for Amgen (Thousand Oaks, CA, USA), consultant and speaker for Bayer (Leverkusen, Germany), consultant and researcher for Genentech (San Francisco, CA, USA), researcher for Heidelberg (Heidelberg, Germany), speaker for Novartis (Basel, Switzerland), consultant, researcher and speaker for Optovue (Freemont, CA, USA), researcher for Regeneron (Tarrytown, NY, USA); MSF: consultant for Novartis (Basel, Switzerland), Alcon (Fort Wort, TX, USA), Bayer (Leverkusen, Germany), Allergan (Dublin, Ireland), Hoffman LaRoche (Basel, Switzerland), Zeiss (Oberkochen, Germany); FB: consultant for Novartis (Basel, Switzerland), Bayer (Leverkusen, Germany); CC: Consultant for Genentech (San Francisco, California, USA), Merck (Whitehouse Station, New Jersey, USA) Janssen Cell Therapy (Raritan, New Jersey, USA); research support from Hoffman LaRoche (Basel, Switzerland). MRR: research grants from Alcon (Fort Wort, TX, USA); DORC (Zuidland, Holland); Baush & Lomb (Rochester, NY, USA); Bayer (Leverkusen, Germany), consultant for Leica (Wetzlar, Germany). Publisher Copyright: © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Background: To explore the role of foveal and parafoveal Müller cells in the morphology and pathophysiology of tractional macular disorders with a mathematical model of mechanical force transmission. Methods: In this retrospective observational study, spectral-domain optical coherence tomography images of tractional lamellar macular holes and patients with myopic foveoschisis were reviewed and analysed with a mathematical model of force transmission. Parafoveal z-shaped Müller cells were modelled as a structure composed of three rigid rods, named R1, R2 and R3. The angle formed between the rods was referred to as θ. R1, R2 and R3 lengths as well as the variation of the angle θ were measured and correlated with best corrected visual acuity (BCVA). Results: In tractional lamellar macular holes, there was a significant reduction of the angle θ towards the foveal centre (p<0.001). By contrast, there were no significant differences in θ in myopic foveoschisis (p=0.570). R2 segments were more vertical in myopic foveoschisis. There was a significant association between lower θ angles at 200 μm temporal and nasal to the fovea and lower BCVA (p<0.001 and p=0.005, respectively). The stiffness of parafoveal Müller cells was predicted to be function of the angle θ, and it grew very rapidly as the θ decreased. Conclusion: Parafoveal Müller cells in the Henle fibre layer may guarantee structural stability of the parafovea by increasing retinal compliance and resistance to mechanical stress. Small values of the angle θ were related to worse BCVA possibly due to damage to Müller cell processes and photoreceptor's axons.

AB - Background: To explore the role of foveal and parafoveal Müller cells in the morphology and pathophysiology of tractional macular disorders with a mathematical model of mechanical force transmission. Methods: In this retrospective observational study, spectral-domain optical coherence tomography images of tractional lamellar macular holes and patients with myopic foveoschisis were reviewed and analysed with a mathematical model of force transmission. Parafoveal z-shaped Müller cells were modelled as a structure composed of three rigid rods, named R1, R2 and R3. The angle formed between the rods was referred to as θ. R1, R2 and R3 lengths as well as the variation of the angle θ were measured and correlated with best corrected visual acuity (BCVA). Results: In tractional lamellar macular holes, there was a significant reduction of the angle θ towards the foveal centre (p<0.001). By contrast, there were no significant differences in θ in myopic foveoschisis (p=0.570). R2 segments were more vertical in myopic foveoschisis. There was a significant association between lower θ angles at 200 μm temporal and nasal to the fovea and lower BCVA (p<0.001 and p=0.005, respectively). The stiffness of parafoveal Müller cells was predicted to be function of the angle θ, and it grew very rapidly as the θ decreased. Conclusion: Parafoveal Müller cells in the Henle fibre layer may guarantee structural stability of the parafovea by increasing retinal compliance and resistance to mechanical stress. Small values of the angle θ were related to worse BCVA possibly due to damage to Müller cell processes and photoreceptor's axons.

KW - anatomy

KW - imaging

KW - macula

KW - retina

U2 - 10.1136/bjophthalmol-2019-314245

DO - 10.1136/bjophthalmol-2019-314245

M3 - Article

C2 - 31326893

AN - SCOPUS:85078661372

SN - 0007-1161

VL - 104

SP - 466

EP - 472

JO - British Journal of Ophthalmology

JF - British Journal of Ophthalmology

IS - 4

ER -

The role of Müller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission

Abstract

Bibliographical note

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