Circularity Index as a Risk Factor for Progression of Geographic Atrophy

Published:October 25, 2013DOI:https://doi.org/10.1016/j.ophtha.2013.07.047

      Objective

      To develop a parameter that can assess the relative rate of progression of geographic atrophy (GA) based on the hypothesis that noncircular configuration of the atrophic lesion may be a risk factor for enlargement.

      Design

      Cohort study.

      Participants

      Digitized color photographs of 593 eyes with GA from the Age-Related Eye Disease Study (AREDS).

      Methods

      A novel parameter called the "Geographic Atrophy Circularity Index" (GACI) was developed on the basis of area and perimeter measurements to categorize the irregularity of the shape of GA. The GACI ranges from 0.0 to 1.0 and is categorized into 3 groups: 0.25 (very irregular), 0.25 to <0.75 (partly irregular), and ≥0.75 (circular).

      Main Outcome Measures

      Growth rate of GA.

      Results

      The mean growth rate in the 3 categories was 0.40 (±0.18), 0.36 (±0.30), and 0.21 (±0.22) mm/year, respectively ( P < 0.001). By adjusting for known confounders, baseline area, duration of GA, and configuration, GACI categories were significantly associated with increased growth rate of GA ( P < 0.001).

      Conclusions

      The GACI was associated with the progression rate of GA and may be a useful measure for clinical trial eligibility. The association also suggests that enlargement of GA may be related to the extent of the junctional zone of damaged retinal pigment epithelium, which increases with noncircularity for a given GA area.

      Financial Disclosure(s)

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

        • Sunness J.S.
        The natural history of geographic atrophy, the advanced atrophic form of age-related macular degeneration.
        Mol Vis [serial online]. 1999; 5 (Available at:) (Accessed June 14, 2013): 25
        • Sunness J.S.
        • Margalit E.
        • Srikumaran D.
        • et al.
        The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials.
        Ophthalmology. 2007; 114: 271-277
        • Sarks J.P.
        • Sarks S.H.
        • Killingsworth M.C.
        Evolution of geographic atrophy of the retinal pigment epithelium.
        Eye (Lond). 1988; 2: 552-577
        • Maguire P.
        • Vine A.K.
        Geographic atrophy of the retinal pigment epithelium.
        Am J Ophthalmol. 1986; 102: 621-625
        • Eye Diseases Prevalence Research Group
        Prevalence of age-related macular degeneration in the United States.
        Arch Ophthalmol. 2004; 122: 564-572
        • Sunness J.S.
        • Applegate C.A.
        • Bressler N.M.
        • Hawkins B.S.
        Designing clinical trials for age-related geographic atrophy of the macula: enrollment data from the Geographic Atrophy Natural History Study.
        Retina. 2007; 27: 204-210
        • Csaky K.G.
        • Richman E.A.
        • Ferris III, F.L.
        Report from the NEI/FDA Ophthalmic Clinical Trial Design and Endpoints Symposium.
        Invest Ophthalmol Vis Sci. 2008; 49: 479-489
        • AREDS Research Group
        Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS report number 26.
        Arch Ophthalmol. 2009; 127: 1168-1174
        • Holz F.G.
        • Bindewald-Wittich A.
        • Fleckenstein M.
        • et al.
        Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration.
        Am J Ophthalmol. 2007; 143: 463-472
        • Yehoshua Z.
        • Rosenfeld P.J.
        • Gregori G.
        • et al.
        Progression of geographic atrophy in age-related macular degeneration imaged with spectral domain optical coherence tomography.
        Ophthalmology. 2011; 118: 679-686
        • Feuer W.J.
        • Yehoshua Z.
        • Gregori G.
        • et al.
        Square root transformation of geographic atrophy area measurements to eliminate dependence of growth rates on baseline lesion measurements: a reanalysis of Age-Related Eye Disease study report no. 26.
        JAMA Ophthalmol. 2013; 131 ([letter]): 110-111
        • Klein R.
        • Meuer S.M.
        • Knudtson M.D.
        • Klein B.E.
        The epidemiology of progression of pure geographic atrophy: the Beaver Dam Eye Study.
        Am J Ophthalmol. 2008; 146: 692-699
        • Fleckenstein M.
        • Schmitz-Valckenberg S.
        • Adrion C.
        • et al.
        Tracking progression with spectral-domain optical coherence tomography in geographic atrophy caused by age-related macular degeneration.
        Invest Ophthalmol Vis Sci. 2010; 51: 3846-3852
        • Khanifar A.A.
        • Lederer D.E.
        • Ghodasra J.H.
        • et al.
        Comparison of color fundus photographs and fundus autofluorescence images in measuring geographic atrophy area.
        Retina. 2012; 32: 1884-1891
        • Schmitz-Valckenberg S.
        • Brinkmann C.K.
        • Alten F.
        • et al.
        Semiautomated image processing method for identification and quantification of geographic atrophy in age-related macular degeneration.
        Invest Ophthalmol Vis Sci. 2011; 52: 7640-7646
        • Yehoshua Z.
        • Rosenfeld P.J.
        • Gregori G.
        • Penha F.
        Spectral domain optical coherence tomography imaging of dry age-related macular degeneration.
        Ophthalmic Surg Lasers Imaging. 2010; 41: S6-14