Association of Reading Performance in Geographic Atrophy Secondary to Age-Related Macular Degeneration With Visual Function and Structural Biomarkers

Künzel, Sandrine H.; Lindner, Moritz; Sassen, Josua; Möller, Philipp T.; Goerdt, Lukas; Schmid, Matthias; Schmitz-Valckenberg, Steffen; Holz, Frank G.; Fleckenstein, Monika; Pfau, Maximilian

doi:10.1001/jamaophthalmol.2021.3826

Cited by 25 publications

(24 citation statements)

References 46 publications

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“…The area of RPE-atrophy has been established as the primary structural endpoint to quantify disease progression in eyes with GA 2 . For this purpose, RPE-atrophy is well suited since it represents the boundary of deep scotomata in eyes with GA as shown by fundus-controlled perimetry studies 17 , 34 , is prognostic for reading ability 35 – 37 , as for quality of life 20 , 35 . While early studies typically used fundus photography for the quantification of the area of RPE-atrophy 38 , FAF-based quantification using semiautomated software such as the RegionFinder software (Heidelberg Engineering, Germany) is currently the gold standard used in large-scale clinical trials 39 – 41 More recently, GA quantification with other semi and fully automated approaches for FAF or OCT data has been proposed 42 – 45 .…”

Section: Discussionmentioning

confidence: 99%

Association of complement C3 inhibitor pegcetacoplan with reduced photoreceptor degeneration beyond areas of geographic atrophy

Pfau

Schmitz-Valckenberg

Ribeiro

et al. 2022

Sci Rep

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Preservation of photoreceptors beyond areas of retinal pigment epithelium atrophy is a critical treatment goal in eyes with geographic atrophy (GA) to prevent vision loss. Thus, we assessed the association of treatment with the complement C3 inhibitor pegcetacoplan with optical coherence tomography (OCT)-based photoreceptor laminae thicknesses in this post hoc analysis of the FILLY trial (NCT02503332). Retinal layers in OCT were segmented using a deep-learning-based pipeline and extracted along evenly spaced contour-lines surrounding areas of GA. The primary outcome measure was change from baseline in (standardized) outer nuclear layer (ONL) thickness at the 5.16°-contour-line at month 12. Participants treated with pegcetacoplan monthly had a thicker ONL along the 5.16° contour-line compared to the pooled sham arm (mean difference [95% CI] + 0.29 z-score units [0.16, 0.42], P < 0.001). The same was evident for eyes treated with pegcetacoplan every other month (+ 0.26 z-score units [0.13, 0.4], P < 0.001). Additionally, eyes treated with pegcetacoplan exhibited a thicker photoreceptor inner segment layer along the 5.16°-contour-line at month 12. These findings suggest that pegcetacoplan could slow GA progression and lead to reduced thinning of photoreceptor layers beyond the GA boundary. Future trials in earlier disease stages, i.e., intermediate AMD, aiming to slow photoreceptor degeneration warrant consideration.

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Section: Discussionmentioning

confidence: 99%

Association of complement C3 inhibitor pegcetacoplan with reduced photoreceptor degeneration beyond areas of geographic atrophy

Pfau

Schmitz-Valckenberg

Ribeiro

et al. 2022

Sci Rep

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show abstract

“…The area of RPE-atrophy has been established as the primary structural endpoint to quantify disease progression in eyes with GA. 2 For this purpose, RPE-atrophy is well suited since it represents the boundary of deep scotomata in eyes with GA as shown by fundus-controlled perimetry studies, 8,26 is prognostic for reading ability, [27][28][29] as for quality of life. 11,27 While early studies typically used fundus photography for the quantification of the area of RPE-atrophy, 30 FAF-based quantification using semiautomated software such as the RegionFinder software (Heidelberg Engineering, Germany) is currently the gold standard used in large-scale clinical trials [31][32][33] More recently, GA quantification with other semi and fully automated approaches for FAF or OCT data has been proposed. [34][35][36][37] However, the area of RPE-atrophy depicts only partially the severity of AMD in a patient with GA.…”

Section: Discussionmentioning

confidence: 99%

Association of Complement C3 Inhibitor Pegcetacoplan with Photoreceptor Degeneration Beyond Areas of Geographic Atrophy

Pfau

Schmitz-Valckenberg

Ribeiro

et al. 2022

Preprint

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Preservation of photoreceptors beyond areas of retinal pigment epithelium atrophy is a critical treatment goal in eyes with geographic atrophy (GA) to prevent vision loss. Thus, we assessed the association of treatment with the complement C3 inhibitor pegcetacoplan with optical coherence tomography (OCT)-based photoreceptor laminae thicknesses in this post hoc analysis of the FILLY trial (NCT02503332). Retinal layers in OCT were segmented using a deep-learning-based pipeline and extracted along evenly spaced contour-lines surrounding areas of GA. The primary outcome measure was change from baseline in (standardized) outer nuclear layer (ONL) thickness at the 5.16 degree contour-line at month 12. Participants treated with pegcetacoplan monthly had a thicker ONL along the 5.16 degree contour-line compared to the pooled sham arm (mean difference [95% CI] +0.29 z-score units [0.16, 0.42],P<.001). The same was evident for eyes treated with pegcetacoplan every other month (+0.26 z-score units [0.13, 0.4],P<.001). Additionally, eyes treated with pegcetacoplan exhibited a thicker photoreceptor inner segment layer along the 5.16 degree contour-line at month 12. These findings suggest that pegcetacoplan could slow GA progression and lead to a lesser thinning of photoreceptor layers beyond the GA boundary. Future trials in earlier disease stages, i.e., intermediate AMD, aiming to slow photoreceptor degeneration warrant consideration.

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“…The most commonly used measure of visual function is best corrected visual acuity (BCVA) [8]. However, there is overwhelming evidence that other visual function markers, such as contrast sensitivity, perimetry, low luminance visual acuity, dark adaptation or metamorphopsia could provide a more accurate and comprehensive assessment of degenerative eye diseases [9][10][11][12]. These markers are especially important at early stages when BCVA is not sensitive enough to detect any changes [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

VisualR: a novel and scalable solution for assessing visual function using virtual reality

Sozzi,

Groß,

Ljubisic

et al. 2023

Preprint

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Background: Diagnosis and treatment of progressive eye diseases require effective monitoring of visual structure and function. However, current methods for measuring visual function are limited in accuracy, reliability, and usability. We propose a novel approach that leverages virtual reality (VR) technology to overcome these challenges, enabling more comprehensive measurements of visual function endpoints. Results: We developed VisualR, a low-cost VR-based application that consists of a smartphone app and a simple VR headset. The virtual environment allows precise control of visual stimuli, full control over the field of view, separating visual input to the left and right eyes, controlling visual angles and blocking background visual noise. We developed novel tests for metamorphopsia, contrast sensitivity and reading speed that can be performed by following simple instructions and providing verbal responses to visual cues, without the need for expert supervision. The smartphone app does not require an internet connection, handles all data processing and image display, and all data is stored locally and owned by the user. Conclusion: VisualR demonstrates the feasibility of building a visual function test device using consumer-grade hardware. Eventually, this technology could be used to measure visual function endpoints during clinical development of new treatments and to support disease diagnosis and monitoring. We open-sourced the application code and provide guidelines for creating reliable and user-friendly VR-based tests. We believe VR can open a new paradigm in visual function testing, and invite the wider community to build upon our work.

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Association of Reading Performance in Geographic Atrophy Secondary to Age-Related Macular Degeneration With Visual Function and Structural Biomarkers

Cited by 25 publications

References 46 publications

Association of complement C3 inhibitor pegcetacoplan with reduced photoreceptor degeneration beyond areas of geographic atrophy

Association of complement C3 inhibitor pegcetacoplan with reduced photoreceptor degeneration beyond areas of geographic atrophy

Association of Complement C3 Inhibitor Pegcetacoplan with Photoreceptor Degeneration Beyond Areas of Geographic Atrophy

VisualR: a novel and scalable solution for assessing visual function using virtual reality

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