Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 1;139(7):743-750.
doi: 10.1001/jamaophthalmol.2021.1407.

Enlargement of Geographic Atrophy From First Diagnosis to End of Life

Johanna M Colijn  1   2 , Bart Liefers  3 , Nichole Joachim  4 , Timo Verzijden  1   2 , Magda A Meester-Smoor  1   2 , Marc Biarnés  5   6 , Jordi Monés  5   6 , Paulus T V M de Jong  7 , Johannes R Vingerling  1 , Paul Mitchell  8 , Clara I Sánchez  9   10 , Jie J Wang  8   11 , Caroline C W Klaver  1   2   12   13 ; EyeNED Reading Center and EYE-RISK Consortium
Affiliations

Enlargement of Geographic Atrophy From First Diagnosis to End of Life

Johanna M Colijn et al. JAMA Ophthalmol. .

Abstract

Importance: Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the long term, life expectancy, and visual course is lacking.

Objective: To determine long-term enlargement of GA.

Design, setting, and participants: In this study, participant data were collected from 4 population-based cohort studies, with up to 25 years of follow-up and eye examinations at 5-year intervals: the Rotterdam Study cohorts 1, 2, and 3 and the Blue Mountains Eye Study. Data were collected from 1990 to 2015, and data were analyzed from January 2019 to November 2020.

Main outcomes and measures: Area of GA was measured pixel by pixel using all available imaging. Area enlargement and enlargement of the square root-transformed area, time until GA reached the central fovea, and time until death were assessed, and best-corrected VA, smoking status, macular lesions according to the Three Continent AMD Consortium classification, a modified version of the Wisconsin age-related maculopathy grading system, and AMD genetic variants were covariates in Spearman, Pearson, or Mann-Whitney analyses.

Results: Of 171 included patients, 106 (62.0%) were female, and the mean (SD) age at inclusion was 82.6 (7.1) years. A total of 147 of 242 eyes with GA (60.7%) were newly diagnosed in our study. The mean area of GA at first presentation was 3.74 mm2 (95% CI, 3.11-4.67). Enlargement rate varied widely between persons (0.02 to 4.05 mm2 per year), with a mean of 1.09 mm2 per year (95% CI, 0.89-1.30). Stage of AMD in the other eye was correlated with GA enlargement (Spearman ρ = 0.34; P = .01). Foveal involvement was already present in incident GA in 55 of 147 eyes (37.4%); 23 of 42 eyes (55%) developed this after a mean (range) period of 5.6 (3-12) years, and foveal involvement did not develop before death in 11 of 42 eyes (26%). After first diagnosis, 121 of 171 patients with GA (70.8%) died after a mean (SD) period of 6.4 (5.4) years. Visual function was visually impaired (less than 20/63) in 47 of 107 patients (43.9%) at last visit before death.

Conclusions and relevance: In this study, enlargement of GA appeared to be highly variable in the general population. More than one-third of incident GA was foveal at first presentation; those with extrafoveal GA developed foveal GA after a mean of 5.6 years. Future intervention trials should focus on recruiting those patients who have a high chance of severe visual decline within their life expectancy.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Drs Colijn, Verzijden, Meester-Smoor, and Klaver have received grants from the European Union Horizon 2020 research and innovation programme during the conduct of the study. Dr Biarnés has received personal fees from Roche and nonfinancial support from Bayer outside the submitted work. Dr Monés has received grants from Novartis, Roche, and Kodiak; personal fees from Cellcure and Lineage Cell Therapeutics; and owns stock options in Notal Vision and Iveric outside the submitted work. Dr Wang has received grants from the Australian National Health and Medical Research Council during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Inclusion and Follow-up
Patients with incident geographic atrophy (GA) are included in the total mentioned in each box. Number of people died is included in the number of people lost to follow-up.
Figure 2.
Figure 2.. Correlation of Geographic Atrophy (GA) Between Both Eyes
Data points indicate patients with bilateral GA. There was high correlation between eyes (r = 0.86; P < .001).
See this image and copyright information in PMC

Comment in

References

    1. McLeod DS, Grebe R, Bhutto I, Merges C, Baba T, Lutty GA. Relationship between RPE and choriocapillaris in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50(10):4982-4991. doi:10.1167/iovs.09-3639 - DOI - PMC - PubMed
    1. Sadda SR, Guymer R, Holz FG, et al. . Consensus definition for atrophy associated with age-related macular degeneration on OCT: Classification of Atrophy report 3. Ophthalmology. 2018;125(4):537-548. doi:10.1016/j.ophtha.2017.09.028 - DOI - PMC - PubMed
    1. Cheng QE, Gao J, Kim BJ, Ying GS. Design characteristics of geographic atrophy treatment trials: systematic review of registered trials in ClinicalTrials.gov. Ophthalmol Retina. 2018;2(6):518-525. doi:10.1016/j.oret.2017.08.018 - DOI - PubMed
    1. Liao DS, Grossi FV, El Mehdi D, et al. . Complement C3 inhibitor pegcetacoplan for geographic atrophy secondary to age-related macular degeneration: a randomized phase 2 trial. Ophthalmology. 2020;127(2):186-195. doi:10.1016/j.ophtha.2019.07.011 - DOI - PubMed
    1. Jaffe GJ, Westby K, Csaky KG, et al. . C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: a randomized pivotal phase 2/3 trial. Ophthalmology. 2021;128(4):576-586. - PubMed

Publication types