GEOGRAPHIC ATROPHY: Semantic Considerations and Literature Review

Abstract

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.

Figure 1. Prior to the introduction of the term “geographic atrophy”

A. This illustrative fundus drawing was published in Nettleship’s case report of 1884 on “central senile areolar atrophy of choroid” in a 60 year old female whose father had gone blind six years before his death [Plate VIII, fig. 1]. B. In the first atlas of ophthalmic photography (1927), Pillat and Dimmer included a case of focal atrophy of the choriocapillaris [“Herdförmige Atrophie der Choriokapillaris”] in a 69 year old female [Plate 75]. C. Fundus drawing of “senile macular degeneration” in 1943 [Plate 23, 3]. D. Two fundus drawings in the Atlas of the Ocular Fundus by Marchesani and Sautter (1957) which were called an example of heredodegeneration of the central retina [Plate 104, c and d, p. 209. Copyright with friendly permission by Elsevier]. E. Color photograph of “senile macular degeneration” with multiple areas of depigmentation in a 70 year old male, by Hollwich in “Der Augenarzt” (1963) [Fig. 95, p. 685].

Figure 2. Coining of the term “geographic atrophy” in the context of “senile macular degeneration”

A. Initial description by Gass of “sharply circumscribed geographic areas of atrophy of the pigment epithelium at the posterior pole”, exposing the large underlying choroidal vessels, in a 67-year old woman with “central areolar pigment epithelial atrophy secondary to senile macular choroidal degeneration “, published in 1970 in the first edition of the “Stereoscopic Atlas of Macular Diseases” (left: fundus photograph, right: arteriovenous stage of fluorescein angiography) [Fig. 2-17, A and B, p. 37. Copyright with friendly permission by Elsevier]. B. Development and progression of geographic atrophy by Gass, reported in 1972/73 (middle row: imaged 1964 and 1968, lower row: 1969 and 1971) [Fig. 4, p. 209. Copyright with friendly permission by American Ophthalmological Society]^, .

Figure 3. Quantification of atrophy and definition of minimal lesion size

A. Measuring geographic atrophy in advanced age-related macular degeneration, as developed by Sunness et al. in 1999, based on stereoscopic color fundus photograph, projected on a microfilm reader, followed by manual outlining of atrophic borders and retinal landmarks [Fig. 1, p. 1762. Copyright with friendly permission by ARVO]. B. The Early Treatment Diabetes Retinopathy Study (ETDRS) grid and the size of the circles I₁ (1/8 disc diameters) and I₂ (1/4 disc diameters) are drawn in a normal fundus photograph. The former represents the minimal requirement in terms of lesion size for an atrophic lesion according to the Age-Related Eye Disease Study (AREDS) System for Classifying Age-related macular degeneration [modified according to fig. 1, p.670. Copyright with friendly permission by Elsevier]. In 2013, AREDS2 suggested to use circle I₂ instead of I₁ as the minimal area of a definite GA area. C. Detection and quantification of atrophy based on fundus autofluorescence imaging as reported by Schmitz-Valckenberg et al. in 2002 [Fig. 1 and 2, p. 74]. Rather than manually outlining atrophic areas, they were defined using a semi-automated segmentation algorithm.

Figure 4

“Serpiginous or geographic choroiditis – a mild disease of the choriocapillaris and pigment epithelium”, published in the textbook “Essentials in Uveitis” by Schlaegel in 1969 [Fig. 5-9, p.101. Copyright with friendly permission by Elsevier].

Figure 5

Timeline of the development of the term “geographic atrophy” in the ophthalmological literature