Müller cells and choriocapillaris in the pathogenesis of geographic atrophy secondary to age-related macular degeneration

Pilotto, Elisabetta; Midena, Edoardo; Longhin, Evelyn; Parrozzani, Raffaele; Frisina, Rino; Frizziero, Luisa

doi:10.1007/s00417-019-04289-z

Cited by 13 publications

(9 citation statements)

References 41 publications

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“…16 The decrease in visual acuity in low-luminance conditions is not fully understood but has been attributed to the involvement of Muller cells in the pathogenesis of GA-a disease in which the light sensitivity of cones may be altered because of the disruption of their optimal coupling with Muller cells. 19 Thus, increased LLD may represent an upstream event prior to degeneration of photoreceptors in fast-progressing GA lesions. If LLD is associated with faster GA growth, psychophysical tests may have implications beyond distinguishing the normal population from those with the dry form of AMD.…”

Section: Discussionmentioning

confidence: 99%

Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan

Steinle

Pearce

Monés

et al. 2021

American Journal of Ophthalmology

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To evaluate the effect of select baseline characteristics on geographic atrophy (GA) progression in eyes receiving intravitreal pegcetacoplan or sham. • DESIGN: Phase 2 multicenter, randomized, singlemasked, sham-controlled trial. • METHODS: Patients with GA received 15 mg pegcetacoplan monthly or every other month (EOM), or sham injection monthly or EOM for 12 months. Primary efficacy endpoint was change in GA lesion size (square root) from baseline. Post hoc analysis evaluated the effects of age; gender; lesion size, focality, and location (extrafoveal vs foveal); pseudodrusen status; best-corrected visual acuity (BCVA); and low-luminance deficit (LLD) on GA progression at Month 12. • RESULTS: Of 246 randomized patients, 192 with 12month data were included in this analysis. Overall mean (standard deviation) change in lesion size (mm) was 0.26 (0.17) ( P < .01), 0.27 (0.27) ( P < .05), and 0.36 (0.21) in the monthly pegcetacoplan (n = 67), EOM pegcetacoplan (n = 58), and sham (n = 67) groups, respectively.In univariate analysis, patients with extrafoveal lesions ( P < .001), BCVA ≥20/60 ( P = .001), and larger LLD ( P = .002) had greater mean changes in lesion size. Multivariate analysis confirmed significant association of extrafoveal lesions ( P = .001) and larger LLD ( P = .023)

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Section: Discussionmentioning

confidence: 99%

Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan

Steinle

Pearce

Monés

et al. 2021

American Journal of Ophthalmology

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“…66,67 Müller cell contribution to HRF features have been described as well. 68,69 The damage to the RPE in the junctional zone in GA is already remarkable with reduced intracellular autofluorescence alone. 34,35 A delineation by an adjacent hyperautofluorescent rim might indicate an increase in cellular RPE damage 70 ; however, the general quantitative autofluorescence in the junctional zone is already decreased in patients with solitary GA, 33 supporting the pathomechanism of continuous loss of RPE and its fluorophores during disease progression.…”

Section: Discussionmentioning

confidence: 99%

Role of Deep Learning–Quantified Hyperreflective Foci for the Prediction of Geographic Atrophy Progression

Schmidt‐Erfurth

Bogunović

Grechenig

et al. 2020

American Journal of Ophthalmology

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To quantitatively measure hyperreflective foci (HRF) during the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using deep learning (DL) and investigate the association with local and global growth of GA.METHODS: Eyes with GA were prospectively included. Spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence images were acquired every 6 months. A 500-mm-wide junctional zone adjacent to the GA border was delineated and HRF were quantified using a validated DL algorithm. HRF concentrations in progressing and nonprogressing areas, as well as correlations between HRF quantifications and global and local GA progression, were assessed.RESULTS: A total of 491 SDOCT volumes from 87 eyes of 54 patients were assessed with a median followup of 28 months. Two-thirds of HRF were localized within a millimeter adjacent to the GA border. HRF concentration was positively correlated with GA progression in unifocal and multifocal GA (all P < .001) and de novo GA development (P [ .037). Local progression speed correlated positively with local increase of HRF (P value range <.001-.004). Global progression speed, however, did not correlate with HRF concentrations (P > .05). Changes in HRF over time did not have an impact on the growth in GA (P > .05).CONCLUSION: Advanced artificial intelligence (AI) methods in high-resolution retinal imaging allows to identify, localize, and quantify biomarkers such as HRF. Increased HRF concentrations in the junctional zone and future macular atrophy may represent progressive migration and loss of retinal pigment epithelium. AIbased biomarker monitoring may pave the way into the era of individualized risk assessment and objective decision-making processes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

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“… 33 When the ILM is peeled off, these end feet are also removed, causing the damage of Müller cells and triggering a cascade of reactions that result in postoperative macular alterations. 34 Physiological and morphological changes, such as the swelling of retinal nerve fiber, the appearance of unstable retinal fiber tissue, are noted. The purpose of the fovea-sparing ILM peeling technique is to interrupt the continuity of the ILM around the macular fovea with the peripheral ILM.…”

Section: Discussionmentioning

confidence: 99%

Fovea-Sparing Versus Complete Internal Limiting Membrane Peeling in Vitrectomy for Vitreomacular Interface Diseases

Wang

Zhao

Zhang

et al. 2021

Retina

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Müller cells and choriocapillaris in the pathogenesis of geographic atrophy secondary to age-related macular degeneration

Cited by 13 publications

References 41 publications

Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan

Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan

Role of Deep Learning–Quantified Hyperreflective Foci for the Prediction of Geographic Atrophy Progression

Fovea-Sparing Versus Complete Internal Limiting Membrane Peeling in Vitrectomy for Vitreomacular Interface Diseases

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