Prognostic value of intermediate age-related macular degeneration phenotypes for geographic atrophy progression

Thiele, Sarah; Nadal, Jennifer; Pfau, Maximilian; Saßmannshausen, Marlene; Fleckenstein, Monika; Holz, Frank G.; Schmid, Matthias; Schmitz-Valckenberg, Steffen

doi:10.1136/bjophthalmol-2020-316004

Cited by 25 publications

(15 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The term macular degeneration indicates a degenerative process of the retina at the level of the fovea, which impairs visual acuity, and it is characterized at the pathological level by the presence of drusen between the retinal pigment epithelium (RPE) and the Bruch’s membrane, as defined in the authoritative review papers by de Jong and Jager et al [ 3 , 4 ]. Similar to drusen, “pseudo-drusen” or “subretinal drusenoid deposits” occurring between the RPE and the boundary between the inner and outer segments of the photoreceptors are associated with an increased risk of developing advanced AMD [ 10 , 11 , 12 , 13 ]. In AMD, extra-macular areas may be involved early on, while in later stages, a widespread degeneration often appears involving both macular and extra-macular regions, which is defined as “geographic atrophy” (GA) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals

Pinelli

Biagioni

Limanaqi

et al. 2020

IJMS

View full text Add to dashboard Cite

Which pathogenic mechanisms underlie age-related macular degeneration (AMD)? Are they different for dry and wet variants, or do they stem from common metabolic alterations? Where shall we look for altered metabolism? Is it the inner choroid, or is it rather the choroid–retinal border? Again, since cell-clearing pathways are crucial to degrade altered proteins, which metabolic system is likely to be the most implicated, and in which cell type? Here we describe the unique clearing activity of the retinal pigment epithelium (RPE) and the relevant role of its autophagy machinery in removing altered debris, thus centering the RPE in the pathogenesis of AMD. The cell-clearing systems within the RPE may act as a kernel to regulate the redox homeostasis and the traffic of multiple proteins and organelles toward either the choroid border or the outer segments of photoreceptors. This is expected to cope with the polarity of various domains within RPE cells, with each one owning a specific metabolic activity. A defective clearance machinery may trigger unconventional solutions to avoid intracellular substrates’ accumulation through unconventional secretions. These components may be deposited between the RPE and Bruch’s membrane, thus generating the drusen, which remains the classic hallmark of AMD. These deposits may rather represent a witness of an abnormal RPE metabolism than a real pathogenic component. The empowerment of cell clearance, antioxidant, anti-inflammatory, and anti-angiogenic activity of the RPE by specific phytochemicals is here discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals

Pinelli

Biagioni

Limanaqi

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Future investigations could include GA subgroup analysis (such as SDD presence/absence) and the effect on GA growth. 32 , 33 Extensions could include further study of the square root transformation applied to GA subgroups using the best three regression models in the comparison (linear, logarithmic, and Q2 models).…”

Section: Discussionmentioning

confidence: 99%

Model Structure Uncertainty in the Characterization and Growth of Geographic Atrophy

Arslan

Benke

Samarasinghe

et al. 2021

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

To identify the most suitable model for assessing the rate of growth of total geographic atrophy (GA) by analysis of model structure uncertainty.Methods: Model structure uncertainty refers to unexplained variability arising from the choice of mathematical model and represents an example of epistemic uncertainty. In this study, we quantified this uncertainty to help identify a model most representative of GA progression. Fundus autofluorescence (FAF) images and GA progression data (i.e., total GA area estimation at each presentation) were acquired using Spectralis HRA+OCT instrumentation and RegionFinder software. Six regression models were evaluated. Models were compared using various statistical tests, [i.e., coefficient of determination (r 2 ), uncertainty metric (U), and test of significance for the correlation coefficient, r], as well as adherence to expected physical and clinical assumptions of GA growth.Results: Analysis was carried out for 81 GA-affected eyes, 531 FAF images (range: 3-17 images per eye), over median of 57 months (IQR: 42, 74), with a mean baseline lesion size of 2.62 ± 4.49 mm 2 (range: 0.11-20.69 mm 2 ). The linear model proved to be the most representative of total GA growth, with lowest average uncertainty (original scale: U = 0.025, square root scale: U = 0.014), high average r 2 (original scale: 0.92, square root scale: 0.93), and applicability of the model was supported by a high correlation coefficient, r, with statistical significance (P = 0.01).Conclusions: Statistical analysis of uncertainty suggests that the linear model provides an effective and practical representation of the rate and progression of total GA growth based on data from patient presentations in clinical settings.Translational Relevance: Identification of correct model structure to characterize rate of growth of total GA in the retina using FAF images provides an objective metric for comparing interventions and charting GA progression in clinical presentations.

show abstract

“…The results from the Age-Related Eye Disease Study (AREDS) showed a strong association between drusen and the development of MA. Drusen were found in 100% of eyes at sites where MA later developed [52, 53], and the presence of multiple large drusen increases the probability of developing MA (15-year odds ratio [OR] 14.5, 95% confidence interval 5.9–35.7; 10-year rate of 26% in patients aged 75–80 years) [9, 54]. Likewise, drusen-associated materials are linked to a higher risk of developing MA.…”

Section: Potential Risk Factors For the Development Of Mamentioning

confidence: 99%

“…Development of atrophy often follows collapse of PEDs [54, 80, 81]. There are 3 major types of PEDs that occur in AMD: serous, drusenoid, and PEDs secondary to subretinal neovascularization [82].…”

Section: Potential Risk Factors For the Development Of Mamentioning

confidence: 99%

Development of Macular Atrophy in Patients with Wet Age-Related Macular Degeneration Receiving Anti-VEGF Treatment

et al. 2021

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a leading cause of blindness. Late AMD can be classified into exudative (commonly known as wet AMD [wAMD]) or dry AMD, both of which may progress to macular atrophy (MA). MA causes irreversible vision loss and currently has no approved pharmacological treatment. The standard of care for wAMD is treatment with anti-vascular endothelial growth factors (VEGF). However, recent evidence suggests that anti-VEGF treatment may play a role in the development of MA. Therefore, it is important to identify risk factors for the development of MA in patients with wAMD. For example, excessive blockade of VEGF through intense use of anti-VEGF agents may accelerate the development of MA. Patients with type III macular neovascularisation (retinal angiomatous proliferation) have a particularly high risk of MA. These patients are characterised as having a pre-existing thin choroid (age-related choroidopathy), suggesting that the choroidal circulation is unable to respond to increased VEGF expression. Evidence suggests that subretinal fluid (possibly indicative of residual VEGF activity) may play a protective role. Patients receiving anti-VEGF agents must be assessed for overall risk of MA and there is an unmet medical need to prevent the development of MA without undertreating wAMD.

show abstract

Prognostic value of intermediate age-related macular degeneration phenotypes for geographic atrophy progression

Cited by 25 publications

References 37 publications

A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals

A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals

Model Structure Uncertainty in the Characterization and Growth of Geographic Atrophy

Development of Macular Atrophy in Patients with Wet Age-Related Macular Degeneration Receiving Anti-VEGF Treatment

Contact Info

Product

Resources

About