Spatial Summation in the Glaucomatous Macula: A Link With Retinal Ganglion Cell Damage

Giovanni Montesano; Tony Redmond; Padraig Mulholland; David F. Garway-Heath; Giovanni Ometto; Dario Romano; Federica  Antonacci; Lucia Tanga; Carmela  Carnevale; Luca Rossetti; David P Crabb; Francesco  Oddone

doi:10.1167/iovs.64.14.36

Spatial Summation in the Glaucomatous Macula: A Link With Retinal Ganglion Cell Damage

Giovanni Montesano, Tony Redmond, Padraig Mulholland, David F. Garway-Heath, Giovanni Ometto, Dario Romano, Federica Antonacci, Lucia Tanga, Carmela Carnevale, Luca Rossetti, David P Crabb, Francesco Oddone

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Abstract

PURPOSE. The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco’s area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity. METHODS. One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in patients with glaucoma and age-matched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H ₁: change in RA) or vertically (H ₂: loss of sensitivity without a change in RA). Root mean squared error (RMSE) of the model fits to perimetric sensitivity were compared. Ninety-five percent confidence intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and 99th percentiles. RESULTS. The RMSE was 2.09 (95% CI = 1.92–2.26) under H ₁ and 2.49 (95% CI = 2.24–2.72) under H ₂ (P < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. CONCLUSIONS. Macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range.

Original language	English
Article number	36
Pages (from-to)	1-14
Number of pages	14
Journal	Investigative Ophthalmology and Visual Science
Volume	64
Issue number	14
DOIs	https://doi.org/10.1167/iovs.64.14.36
Publication status	Published (in print/issue) - 27 Nov 2023

Bibliographical note

Funding Information:
Supported in part, by the National Institute for Health & Care Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology (PJM, DGH). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. DGH’s chair at UCL is supported by funding from Glaucoma UK.

Publisher Copyright:
Copyright 2023 The Authors.

Keywords

glaucoma
spatial summation
perimetry
retinal ganglion cells (RGCs)
structure-function

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1167/iovs.64.14.36

i1552-5783-64-14-36_1700652658.5152Final published version, 6.7 MBLicence: CC BY

Cite this

Montesano, G., Redmond, T., Mulholland, P., Garway-Heath, D. F., Ometto, G., Romano, D., Antonacci, F., Tanga, L., Carnevale, C., Rossetti, L., Crabb, D. P., & Oddone, F. (2023). Spatial Summation in the Glaucomatous Macula: A Link With Retinal Ganglion Cell Damage. Investigative Ophthalmology and Visual Science, 64(14), 1-14. Article 36. https://doi.org/10.1167/iovs.64.14.36

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abstract = "PURPOSE. The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco{\textquoteright}s area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity. METHODS. One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in patients with glaucoma and age-matched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H 1: change in RA) or vertically (H 2: loss of sensitivity without a change in RA). Root mean squared error (RMSE) of the model fits to perimetric sensitivity were compared. Ninety-five percent confidence intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and 99th percentiles. RESULTS. The RMSE was 2.09 (95% CI = 1.92–2.26) under H 1 and 2.49 (95% CI = 2.24–2.72) under H 2 (P < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. CONCLUSIONS. Macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range.",

keywords = "glaucoma, spatial summation, perimetry, retinal ganglion cells (RGCs), structure-function",

author = "Giovanni Montesano and Tony Redmond and Padraig Mulholland and Garway-Heath, {David F.} and Giovanni Ometto and Dario Romano and Federica Antonacci and Lucia Tanga and Carmela Carnevale and Luca Rossetti and Crabb, {David P} and Francesco Oddone",

note = "Funding Information: Supported in part, by the National Institute for Health & Care Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology (PJM, DGH). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. DGH{\textquoteright}s chair at UCL is supported by funding from Glaucoma UK. Publisher Copyright: Copyright 2023 The Authors.",

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AU - Montesano, Giovanni

AU - Redmond, Tony

AU - Mulholland, Padraig

AU - Garway-Heath, David F.

AU - Ometto, Giovanni

AU - Romano, Dario

AU - Antonacci, Federica

AU - Tanga, Lucia

AU - Carnevale, Carmela

AU - Rossetti, Luca

AU - Crabb, David P

AU - Oddone, Francesco

N1 - Funding Information: Supported in part, by the National Institute for Health & Care Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology (PJM, DGH). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. DGH’s chair at UCL is supported by funding from Glaucoma UK. Publisher Copyright: Copyright 2023 The Authors.

PY - 2023/11/27

Y1 - 2023/11/27

N2 - PURPOSE. The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco’s area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity. METHODS. One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in patients with glaucoma and age-matched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H 1: change in RA) or vertically (H 2: loss of sensitivity without a change in RA). Root mean squared error (RMSE) of the model fits to perimetric sensitivity were compared. Ninety-five percent confidence intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and 99th percentiles. RESULTS. The RMSE was 2.09 (95% CI = 1.92–2.26) under H 1 and 2.49 (95% CI = 2.24–2.72) under H 2 (P < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. CONCLUSIONS. Macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range.

AB - PURPOSE. The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco’s area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity. METHODS. One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in patients with glaucoma and age-matched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H 1: change in RA) or vertically (H 2: loss of sensitivity without a change in RA). Root mean squared error (RMSE) of the model fits to perimetric sensitivity were compared. Ninety-five percent confidence intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and 99th percentiles. RESULTS. The RMSE was 2.09 (95% CI = 1.92–2.26) under H 1 and 2.49 (95% CI = 2.24–2.72) under H 2 (P < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. CONCLUSIONS. Macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range.

KW - glaucoma

KW - spatial summation

KW - perimetry

KW - retinal ganglion cells (RGCs)

KW - structure-function

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Spatial Summation in the Glaucomatous Macula: A Link With Retinal Ganglion Cell Damage

Abstract

Bibliographical note

Keywords

UN SDGs

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