Dataset Information

The Rate of Progression of Geographic Atrophy Decreases With Increasing Baseline Lesion Size Even After the Square Root Transformation.

ABSTRACT:

Purpose

To determine the relationship between the progression of geographic atrophy (GA) and its baseline area (BA) using the square root transformation (sqrt) for different atrophy sizes.

Methods

Single eyes of patients with GA visiting the Institut de la Màcula (Barcelona, Spain) between December 2009 and January 2018 with a follow-up of ?6 months were included. The main outcome was the correlation between BA and growth after the sqrt using Pearson's r and Spearman's rho. The graphical relationship was explored using linear and LOWESS regression. In a secondary, prespecified analysis, progression was compared by BA categories (Age-Related Eye Disease Study [AREDS] classification and BA tertiles). In post hoc analyses, the results were evaluated in subgroups defined by location of atrophy, number of lesions, fundus autofluorescence pattern, and fellow-eye status.

Results

We included 128 eyes (mean follow-up, 3.1 years). The correlation between BA and progression was negative (r = -0.30, P = 0.0005; rho = -0.25, P = 0.0042). There was a decrease in the rate of progression in mm/year with increasing BA, but this was significant for tertiles (P = 0.0078) and not AREDS (P = 0.20). The descending trend was driven by high-risk features.

Conclusions

The correlation between GA progression and BA using the sqrt is negative. This has implications for the expected prediction of progression of a given lesion and to avoid overestimating the beneficial effects of interventional therapies.

Translational relevance

The GA progression/BA relationship using the sqrt currently is regarded as independent. Our results suggest the sqrt slope actually is negative, which should be kept in mind to avoid misinterpretation of results in advanced therapies.

SUBMITTER: Mones J

PROVIDER: S-EPMC6314221 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

The Rate of Progression of Geographic Atrophy Decreases With Increasing Baseline Lesion Size Even After the Square Root Transformation.

Monés Jordi J Biarnés Marc M

Translational vision science & technology 20181101 6

<h4>Purpose</h4>To determine the relationship between the progression of geographic atrophy (GA) and its baseline area (BA) using the square root transformation (sqrt) for different atrophy sizes.<h4>Methods</h4>Single eyes of patients with GA visiting the Institut de la Màcula (Barcelona, Spain) between December 2009 and January 2018 with a follow-up of ≥6 months were included. The main outcome was the correlation between BA and growth after the sqrt using Pearson's <i>r</i> and Spearman's <i>r ...[more]

PMID: 30619660

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Project description:ImportanceAge-related macular degeneration (AMD) is a common threat to vision loss in individuals older than 50 years. While neovascular complications in AMD are treatable, there is currently no therapy for geographic atrophy secondary to AMD. Geographic atrophy lesion progression over time shows considerable interindividual variability, but little is known about prognostic factors.ObjectiveTo elucidate the contribution of common genetic variants to geographic atrophy lesion growth.Design, setting, and participantsThis pooled analysis combined 4 independent studies: the Fundus Autofluorescence Imaging in Age-Related Macular Degeneration (FAM) study, the Directional Spread in Geographic Atrophy (DSGA) study, the Age-Related Eye Disease Study (AREDS), and the Geographic Atrophy Treatment Evaluation (GATE) study. Each provided data for geographic atrophy lesion growth in specific designs. Patients with geographic atrophy secondary to AMD were recruited to these studies. Genotypes were retrieved through the database of Genotypes and Phenotypes (for AREDS) or generated at the Cologne Center for Genomics (for FAM, DSGA, and GATE).Main outcomesThe correlation between square root-transformed geographic atrophy growth rate and 7 596 219 genetic variants passing quality control was estimated using linear regression. The calculations were adjusted for known factors influencing geographic atrophy growth, such as the presence of bilateral geographic atrophy as well as the number of lesion spots and follow-up times.Main outcomes and measuresSlopes per allele, 95% CIs, and P values of genetic variants correlated with geographic atrophy lesion growth.ResultsA total of 935 patients (mean [SD] age, 74.7 [7.8] years; 547 female participants [59.0%]) were included. Two gene loci with conservative genome-wide significance were identified. Each minor allele of the genome-wide associated variants increased the geographic atrophy growth rate by a mean of about 15% or 0.05 mm per year. Gene prioritization within each locus suggests the protein arginine methyltransferase 6 gene (PRMT6; chromosome 1; slope, 0.046 [95% CI, 0.026-0.066]; P = 4.09 × 10-8) and the lanosterol synthase gene (LSS; chromosome 21; slope, 0.105 [95% CI, 0.068-0.143]; P = 4.07 × 10-7) as the most likely progression-associated genes.Conclusions and relevanceThese data provide further insight into the genetic architecture of geographic atrophy lesion growth. Geographic atrophy is a clinical outcome with a high medical need for effective therapy. The genes PRMT6 and LSS are promising candidates for future studies aimed at understanding functional aspects of geographic atrophy progression and also for designing novel and targeted treatment options.

Project description:PURPOSE:There is a lack of agreement regarding the types of lesions and clinical conditions that should be included in the term "geographic atrophy." Varied and conflicting views prevail throughout the literature and are currently used by retinal experts and other health care professionals. METHODS:We reviewed the nominal definition of the term "geographic atrophy" and conducted a search of the ophthalmologic literature focusing on preceding terminologies and the first citations of the term "geographic atrophy" secondary to age-related macular degeneration. RESULTS:According to the nominal definition, the term "geography" stands for a detailed description of the surface features of a specific region, indicating its relative position. However, it does not necessarily imply that the borders of the region must be sharply demarcated or related to any anatomical structures. The term "geographical areas of atrophy" was initially cited in the 1960s in the ophthalmologic literature in the context of uveitic eye disease and shortly thereafter also for the description of variants of "senile macular degeneration." However, no direct explanation could be found in the literature as to why the terms "geographical" and "geographic" were chosen. Presumably the terms were used as the atrophic regions resembled the map of a continent or well-defined country borders on thematic geographical maps. With the evolution of the terminology, the commonly used adjunct "of the retinal pigment epithelium" was frequently omitted and solely the term "geographic atrophy" prevailed for the nonexudative late-stage of age-related macular degeneration itself. Along with the quantification of atrophic areas, based on different imaging modalities and the use of both manual and semiautomated approaches, various and inconsistent definitions for the minimal lesion diameter or size of atrophic lesions have also emerged. CONCLUSION:Reconsideration of the application of the term "geographic atrophy" in the context of age-related macular degeneration seems to be prudent given ongoing advances in multimodal retinal imaging technology with identification of various phenotypic characteristics, and the observation of atrophy development in eyes under antiangiogenic therapy.

Dataset Information

The Rate of Progression of Geographic Atrophy Decreases With Increasing Baseline Lesion Size Even After the Square Root Transformation.

Purpose

Methods

Results

Conclusions

Translational relevance

Publications

The Rate of Progression of Geographic Atrophy Decreases With Increasing Baseline Lesion Size Even After the Square Root Transformation.

Similar Datasets

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