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Geographic atrophy
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From Detection to Progression
Imaging plays a critical role in both early diagnosis of GA and in the monitoring of disease progression.
Diagnostic Hallmarks of Dry AMD
Early
Multiple small (<63 µm) and few intermediate (63-124 µm) drusen, or RPE abnormalities.1-3
Intermediate
Extensive intermediate drusen (63-124 µm) or more than 1 large druse (≥125 µm). May also be accompanied by pigmentary and degenerative changes in the choriocapillaris, RPE, and photoreceptors.1-4
Advanced (GA)
Progressive atrophy of choriocapillaris,
RPE, and photoreceptors.2,3 As well as new and growing lesions.3
Optical Coherence
Tomography (OCT)
Intermediate AMD
Image courtesy of Dr. Arshad Khanani
Advanced AMD (Geographic Atrophy)
Image courtesy of Dr. Arshad Khanani
Key Features1,4
- (1) Degeneration of overlying photoreceptors increases reflectivity below Bruch’s membrane
- (2) Hyperreflective foci corresponds to attenuation or disruption of the RPE
- (3) Atrophy of the RPE
- (4) Area of choroidal hypertransmission
Images are from separate patients.
Color Fundus Photography
(CFP)
Intermediate AMD
Image courtesy of Dr. Arshad Khanani
Advanced AMD (Geographic Atrophy)
Image courtesy of Dr. Mohammad Rafieetary
Key Features4-6
- (1) Drusen and
- (2) hyperpigmentary RPE abnormalities
- (3) GA lesion borders are sharply demarcated with increased choroidal vessel visibility (dashed circle)
Images are from separate patients.
Fundus Autofluorescence
(FAF)
Intermediate AMD
Image courtesy of Dr. Arshad Khanani
Advanced AMD (Geographic Atrophy)
Image courtesy of Dr. David Lally
Key Features1,8
- (1) Reticular pseudodrusen appearing as multiple, clustered, regularly networked, round areas of low-contrast hypo-autofluorescence may be prognostic of advancing AMD
- (2) Abnormal patterns of
hyperautofluorescence surrounding atrophic lesions - (3) Areas of hypoautofluorescence with sharply demarcated borders
indicate atrophic lesions
Images are from separate patients.
References
- Holz FG, Schmitz-Valckenberg S, Fleckenstein M. Recent developments in the treatment of age-related macular degeneration. J Clin Invest. 2014;124(4):1430-1438.
- Boyer DS, Schmidt-Erfurth U, van Lookeren Campagne M, Henry EC, Brittain C. The pathophysiology of geographic atrophy secondary to age-related macular degeneration and the complement pathway as a therapeutic target. Retina. 2017;37(5):819-835.
- Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390.
- Sadda SR, Chakravarthy U, Birch DG, et al. Clinical endpoints for the study of geographic atrophy secondary to age-related macular degeneration. Retina. 2016;36(10):1806-1822.
- Monés J, Garcia M, Biarnés M, Lakkaraju A, Ferraro L. Drusen ooze: a novel hypothesis in geographic atrophy. Ophthalmol Retina. 2017;1(6):461-473.
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- Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP. Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol. 2003;48(3):257-293.
- Flaxel CJ, Adelman RA, Bailey ST, et al. Age-related macular degeneration preferred practice pattern(R). Ophthalmology. 2020;127(1):P1-P65.
- Sunness JS, Rubin GS, Applegate CA, et al. Visual function abnormalities and prognosis in eyes with age-related geographic atrophy of the macula and good visual acuity. Ophthalmology. 1997;104(10):1677-1691.
- Lindblad AS, Lloyd, PC, Clemons TE, et al. Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS report number 26. Arch Ophthalmol. 2009;127(9):1168-1174.
- Holz FG, Strauss EC, Schmitz-Valckenberg S, van Lookeren Campagne M. Geographic atrophy: clinical features and potential therapeutic approaches. Ophthalmology. 2014;121(5):1079-1091.
- Desai D, Dugel PU. Complement cascade inhibition in geographic atrophy: a review. Eye (Lond). 2022;36(2):294-302.
- Bakri SJ, Bektas M, Sharp D, Luo R, Sarda SP, Khan S. Geographic atrophy: mechanism of disease, pathophysiology, and role of the complement system. J Manag Care Spec Pharm. 2023;29(5-a Suppl):S2-S11.
- Carlton J, Barnes S, Haywood A. Patient perspectives in geographic atrophy (GA): exploratory qualitative research to understand the impact of GA for patients and their families. Br Ir Orthopt J. 2019;15(1):133-141.
- Stahl A. The diagnosis and treatment of age-related macular degeneration. Dtsch Arztebl Int. 2020;117(29-30):513-520.
- Sayegh RG, Sacu S, Dunavölgyi R, et al. Geographic atrophy and foveal-sparing changes related to visual acuity in patients with dry age-related macular degeneration over time. Am J Ophthalmol. 2017;179:118-128.
- Chakravarthy U, Bailey CC, Johnston RL, et al. Characterizing disease burden and progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(6):842-849.
- Patel PJ, Ziemssen F, Ng E, et al. Burden of illness in geographic atrophy: a study of vision-related quality of life and health care resource use. Clin Ophthalmol. 2020;14:15-28.
- Singh RP, Patel SS, Nielsen JS, Schmier JK, Rajput Y. Patient-, caregiver-, and eye care professional-reported burden of geographic atrophy secondary to age-related macular degeneration. Am J Ophthalmic Clin Trials. 2019;2(1):1-6.
- Sivaprasad S, Tschosik EA, Guymer RH, et al. Living with geographic atrophy: an ethnographic study. Ophthalmol Ther. 2019;8(1):115-124.
- Higgins BE, Taylor DJ, Binns AM, Crabb DP. Are current methods of measuring dark adaptation effective in detecting the onset and progression of age-related macular degeneration? A systematic literature review. Ophthalmol Ther. 2021;10(1):21-38.
- Meleth AD, Mettu P, Agron E, et al. Changes in retinal sensitivity in geographic atrophy progression as measured by microperimetry. Invest Ophthalmol Vis Sci. 2011;52(2):1119-1126.
- Xu H, Chen M. Targeting the complement system for the management of retinal inflammatory and degenerative diseases. Eur J Pharmacol. 2016;787:94-104.
- Coulthard LG, Woodruff TM. Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. J Immunol. 2015;194(8):3542-3548.
- Xie CB, Jane-Wit D, Pober JS. Complement membrane attack complex: new roles, mechanisms of action, and therapeutic targets. Am J Pathol. 2020;190(6):1138-1150.
- Brandstetter C, Holz FG, Krohne TU. Complement component C5a primes retinal pigment epithelial cells for inflammasome activation by lipofuscin-mediated photooxidative damage. J Biol Chem. 2015;290(52):31189-31198.
- Kumar-Singh R. The role of complement membrane attack complex in dry and wet AMD – from hypothesis to clinical trials. Exp Eye Res. 2019;184:266-277.