Geographic Atrophy in Age-Related Macular Degeneration

Keenan, Tiarnán D L

doi:10.1016/j.xops.2023.100306

Cited by 15 publications

(7 citation statements)

References 78 publications

(131 reference statements)

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“…The latter corresponded to stacking of RPE cells. 13–15 The macular atrophy, having a larger en-face vertical dimension, may even extend up to the far periphery. The authors suggested a replacement of the associated pseudo-drusen by paving stones as the disease progressed.…”

Section: Discussionmentioning

confidence: 99%

Fundus autofluorescence of retinal atrophy progression between fundus flavimaculatus and extensive macular atrophy with pseudo-drusen

Rabinovich,

Mehanna,

Lopez

et al. 2023

European Journal of Ophthalmology

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Objective To analyze the progression of macular atrophy in Fundus Flavimaculatus (FFM) versus Extensive Macular Atrophy with Pseudo-drusen (EMAP), using Spectralis® RegionFinder™ tool. Methods Retrospective review of patients diagnosed with FFM and EMAP. Ophthalmic imaging features were reviewed by retina specialists for each patient in both eyes. The atrophic zones were measured on fundus autofluorescence acquisitions using the RegionFinder™ tool. Results FFM group included 16 eyes of 8 patients, whose mean age was 61.42 ± 10.76 years, with a mean 4.54 ± 2.73 years of follow-up. EMAP group contained 16 eyes of 8 patients, whose mean age was 67.81 ± 3.03 years ( p = 0.12), with a mean 3.62 ± 2.49 years of follow-up ( P = 0.63). The atrophy progression rates were 3.73 ± 6.75 and 0.70 ± 0.98 mm2/year, for EMAP and FFM respectively. The yearly rate of progression of the atrophic areas in EMAP was 5.3 times higher than in FFM (mm2/year) ( p = 0.03). Conclusion The progression of the atrophy in eyes with Extensive Macular Atrophy with Pseudo-drusen (EMAP) is significantly more rapid than in eyes with Fundus Flavimaculatus (FFM).

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Section: Discussionmentioning

confidence: 99%

Fundus autofluorescence of retinal atrophy progression between fundus flavimaculatus and extensive macular atrophy with pseudo-drusen

Rabinovich,

Mehanna,

Lopez

et al. 2023

European Journal of Ophthalmology

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“…Contradictory findings are seen for GA lesion growth: genetic associations at the CFH and CFI loci point towards increased complement activity with increased risk of GA lesion growth, while an inverse effect is seen at the level of C3, where increased complement activity is associated with decreased risk of GA lesion growth. It has been suggested that the C3 genotype may invoke mechanisms with opposing effects at different disease stages (Heesterbeek, Lores‐Motta, et al., 2020; Keenan, 2023). Further studies are needed to better understand this paradoxical finding, in addition to better understanding the molecular disease mechanisms at the ARMS2/HTRA1 locus.…”

Section: Genetic Biomarkers Associated With Gamentioning

confidence: 99%

“…Several studies have identified phenotypic, demographic and environmental risk factors that are associated with GA (Heesterbeek, Lores‐Motta, et al., 2020). Higher age is an established risk factor for GA incidence but is not a significant risk factor for faster GA expansion (Keenan, 2023). Lifestyle factors such as cigarette smoking and dietary pattern have been associated with both development of GA and GA expansion rate (Fleckenstein et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Disease progression of neovascular AMD can effectively be slowed by intravitreal injections of anti‐vascular endothelial growth factor, while the treatment options to prevent initiation or progression of GA are limited. Inhibitors of C3 (pegcetacoplan, Syfovre) and C5 (avacincaptad pegol, Izervay) were recently FDA approved for treatment of GA but showed a modest decrease in GA lesion growth in phase 3 clinical trials (Jaffe et al., 2021; Keenan, 2023; Liao et al., 2020), while trials targeting other parts of the complement system have failed (Holz et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

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Genetic and molecular biomarkers for geographic atrophy

Riley‐Gillis,

Huh,

Shen

et al. 2023

Acta Ophthalmologica

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Geographic atrophy (GA) is characterized by atrophy of the retina, retinal pigment epithelium and choriocapillaris, causing a gradual loss of vision over time. Treatment options to prevent initiation or progression of GA are limited; two recently FDA‐approved inhibitors of the complement system (pegcetacoplan, avacincaptad pegol) showed a modest decrease in GA lesion growth in phase 3 clinical trials. Exploration of genetic and molecular biomarkers in GA plays a critical role in our battle against this blinding disease to improve early disease detection, to find more effective therapies, and to provide personalized care to patients. In this review, we provide a comprehensive overview of the current literature investigating genetic and molecular biomarkers for GA. Genetic studies identified multiple genes and variants that play a role in progression to GA and GA lesion growth, involving pathways such as complement activation, extracellular matrix interaction and lipid metabolism. The number of published studies assessing molecular biomarkers for GA initiation and progression in ocular matrices is limited. Several studies evaluated molecular biomarkers in the systemic circulation, showing higher levels of complement activation and a causal role of lipid subfractions in GA. Larger, well‐powered studies are needed to identify novel and validate existing biomarkers, and to investigate the potential of combining genetic and molecular markers with imaging techniques for more accurate diagnosis and monitoring of GA. The development of personalized medicine approaches based on individual genetic and molecular profiles could hold promise for more effective and targeted treatments for this devastating disease.

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“…When affecting individuals over the age of 50, the most common disease is age-related macular degeneration (AMD). AMD is a leading cause of legal blindness in industrialized nations, including two late-staged forms-non-neovascular (''dry'') AMD, also known as geographic atrophy (GA), and neovascular (''wet'') AMD [1]. While therapeutic options exist for wet AMD, there are currently no available treatments for its dry form, GA, in Europe.…”

Section: Introductionmentioning

confidence: 99%

Expert Consensus on Geographic Atrophy in the EU: A Call for Urgent Policy Action

Querques,

Amblard,

Andrao

et al. 2024

Ophthalmol Ther

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Geographic atrophy is an eye disease that greatly interferes with the daily lives of patients and their families, posing a serious threat to the aging European demographic. Over the past 30 months, this initiative has assembled leading experts in the field of ophthalmology to share insights on the necessary policy steps that need to be taken to overcome this challenge on an EU-wide scale. Through analyzing best practices in Germany, Italy, France, and Spain, this consensus paper sets out a series of policy recommendations, which, if implemented, could greatly benefit all individuals affected by geographic atrophy. Amongst other features, these countries have provided valuable examples of awareness campaigns and an overall commitment to inclusive and comprehensive policies. The policy recommendations emerging from this paper include the adoption of comprehensive screening programs, retinal disease screening in the EU Driving License Directive, the development of a white paper at the European Commission, and the creation of Council recommendations on eye health screening. Given the significant improvements made at the national level throughout the EU, countries will require unitary support at the European level to further develop their policies and successfully address the burden of geographic atrophy.

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Geographic Atrophy in Age-Related Macular Degeneration

Cited by 15 publications

References 78 publications

Fundus autofluorescence of retinal atrophy progression between fundus flavimaculatus and extensive macular atrophy with pseudo-drusen

Fundus autofluorescence of retinal atrophy progression between fundus flavimaculatus and extensive macular atrophy with pseudo-drusen

Genetic and molecular biomarkers for geographic atrophy

Expert Consensus on Geographic Atrophy in the EU: A Call for Urgent Policy Action

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