Elsevier

Ophthalmology Retina

Volume 2, Issue 9, September 2018, Pages 914-921
Ophthalmology Retina

Original article
Natural History of Geographic Atrophy in Untreated Eyes with Nonexudative Age-Related Macular Degeneration: A Systematic Review and Meta-analysis

Presented at: Retina Society Annual Meeting, October 2017; Boston, MA.
https://doi.org/10.1016/j.oret.2018.01.019Get rights and content

Topic

Systematic review and meta-analysis of the natural history of geographic atrophy (GA).

Clinical Relevance

Several different models have been used to describe the natural history of GA in untreated eyes, and the reported progression rates vary widely across clinical trials.

Methods

We searched in MEDLINE, EMBASE, Cochrane Library, Clinicaltrials.gov, and PubMed for studies that measured GA size in untreated eyes over a follow-up period ranging from the start dates of the databases through June 6, 2017. Data were analyzed using 3 models: (1) the area linear model, in which the lesion area enlarges linearly with time; (2) the radius linear model (RLM), in which the lesion radius expands linearly with time; and (3) the area exponential model, in which the lesion area changes exponentially with time. A horizontal translation factor was added to shift each data set to correct for the differences in participant entry time into the studies. The model that best fit data was determined by performing residual analyses, determining the dependence of growth rate on time, and the predicted age of GA onset. The risk of bias was assessed using the Newcastle-Ottawa scale.

Results

We included 25 studies with data from 2942 eyes. The RLM yielded the best goodness of fit and predictive performance of GA progression. Cumulative data for untreated eyes fit a straight line in the RLM (r2 = 0.986) with a randomly dispersed residual plot. The GA radius enlarged at a constant rate of 0.163 mm/year (95% confidence interval, 0.158–0.167 mm/year), which was independent of time (r = −0.108). The RLM predicted the mean age of onset of GA as 67.4±5.2 years. Our analysis also suggested that the GA progression rate may be associated with the age of onset.

Conclusions

In this meta-analysis, the progression pattern of GA was uniform across a wide range of studies, and best fit the RLM. Our analysis may shed light on the natural history of GA and may influence the design of future clinical trials.

Section snippets

Methods

This meta-analysis is reported in accordance with the Meta-analysis of Observational Studies in Epidemiology checklist (Table S2, available at www.ophthalmologyretina.org).17

Database

The final search retrieved a total of 1649 records after de-duplication. After review of the titles and abstracts, 1595 records were excluded for irrelevance. We reviewed the full text of the remaining 54 articles and identified 25 independent studies (including 2942 unique eyes) meeting our inclusion criteria (Fig S1). The descriptive information of each study is detailed in Table S3, and excluded articles are listed in Table S4 (available at www.ophthalmologyretina.org).

Study Quality and Publication Bias

Newcastle-Ottawa scale

Discussion

To our knowledge, this is the first meta-analysis to evaluate the natural progression pattern of GA secondary to nonexudative AMD. Previous studies of the natural history of GA exhibited a wide range of GA growth rates, ranging from 0.21 to 1.10 disc areas per year, which corresponds to 0.053 to 0.264 mm/year assuming circular lesions with baseline sizes of 3 disc areas.7, 8 In addition, prior authors have come to divergent conclusions on the growth pattern of GA (Table S1).7, 9, 10, 11, 13, 28

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    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported by Research to Prevent Blindness, Inc, New York, New York (principal investigator, L.V.D.P.). The sponsor or funding organization had no role in the design or conduct of this research.

    HUMAN SUBJECTS: This is a systematic review article and does not include human subjects.

    Author Contributions:

    Conception and design: Shen, Del Priore

    Analysis and interpretation: Shen, Liu, Del Priore

    Data collection: Shen, Liu, Grossetta Nardini, Del Priore

    Obtained funding: Del Priore

    Overall responsibility: Shen, Liu, Del Priore

    Supplemental material available at www.ophthalmologyretina.org.

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