Elsevier

Ophthalmology

Volume 125, Issue 4, April 2018, Pages 537-548
Ophthalmology

Original article
Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3

https://doi.org/10.1016/j.ophtha.2017.09.028Get rights and content

Purpose

To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD).

Design

Consensus meeting.

Participants

Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers.

Methods

As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy.

Main Outcome Measures

A consensus classification system for atrophy and OCT-based criteria to identify atrophy.

Results

OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear.

Conclusions

A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

Section snippets

Formation of the Classification of Atrophy Meeting Group

An international team of experts in AMD and AMD imaging research was assembled to address the problem of developing multimodal definitions of atrophy in the setting of AMD. The initial selection of Classification of Atrophy Meetings (CAM) group members was performed by the 3 CAM chairs (S.R.S., G.S., and F.G.H.). Criteria for selection included a history of relevant publications (in AMD pathogenesis and histopathology, imaging technologies, image interpretation and analysis in AMD, and AMD

What Is Atrophy in the Context of Age-Related Macular Degeneration?

In general use, atrophy means a shrinking or withering, particularly because of poor nutrition or disuse. In the context of AMD, the term atrophy means either loss of tissue (typically) or the irreversible attenuation of tissue.

Selection of a Base Imaging Method to Define Atrophy

Given the wide availability of multiple imaging methods to evaluate the fundus, it seems reasonable to incorporate information from multiple imaging sources to confirm the presence of atrophy. However, in such a multimodal system, we believed that it would be prudent to

Discussion

Through the CAM program, a consensus nomenclature and definition for atrophy based on OCT imaging was proposed. The intention of the program was to develop a system that could be used by practitioners for assessing and counseling their patients with AMD. Using OCT findings to define the earliest anatomic changes that portend the future development of atrophy are highly relevant for interventions applied early in the disease process and certainly will accelerate interventional clinical trials

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  • Cited by (0)

    Financial Disclosure(s): The author(s) have made the following disclosure(s): S.R.S.: Consultant – Allergan, Iconic Therapeutics, Novartis, Thrombogenics, Genentech, Centervue, Heidelberg Engineering; Research support – Optos, Carl Zeiss Meditec, Allergan; Research Instruments – Optos, Carl Zeiss Meditec, Nidek, Centervue, Heidelberg Engineering

    R.G.: Financial support – Novartis, Bayer, Genentech

    F.G.H.: Financial support – Heidelberg Engineering, Optos, Zeiss, Novartis, Bayer Healthcare, Genentech, Acucela, Boehringer Ingelheim, Alcon, Allergan

    S.S.-V.: Financial support – Novartis, Bayer Healthcare, Genentech, Acucela, Alcon, Allergan, Heidelberg Engineering, Formycon/Bioeq; Nonfinancial support – Optos, Heidelberg Engineering, Carl Zeiss Meditec

    C.A.C.: Financial support – Hoffman-LaRoche, Heidelberg Engineering, Regeneron, Novartis, Unity, Janssen Cell Therapy

    F.B.: Financial support – Novartis, Bayer; Nonfinancial support – Allergan, Heidelberg Engineering

    U.C.: Financial support – Novartis, Bayer, Allergan, Heidelberg Engineering, Zeiss

    K.C.: Financial support – Genentech, Regeneron, Heidelberg Engineering, Santen, Ophthotech, Acucela, GSK, Roche, Allergan; Other – Ophthotech

    R.D.: Financial support – Allergan, GSK, Thrombogenics, KangHong, Ionis; Equity owner – EyeKor, Inc; Employee – EyeKor, Inc

    M.F.: Financial support – Heidelberg Engineering, Optos, Novartis, Bayer, Genentech, Roche; Nonfinancial support: Zeiss Meditech, Heidelberg Engineering, Optos; Patent pending – US20140303013 A1

    K.B.F.: Consultant – Heidelberg Engineering, Optovue, Optos, Spark Therapeutics; Financial support – Genentech/Roche

    G.J.J.: Consultant – Heidelberg Engineering

    S.L.: Financial support – Heidelberg Engineering, Carl Zeiss Meditec, Novartis, Allergan, Bayer; Nonfinancial support – Heidelberg Engineering, Carl Zeiss Meditec

    J.M.M.: Financial support – Eyerisk Consortium 2020, Novartis, Bayer, Alcon, Roche, Ophthotech; Consultant – Novartis, Bayer, Alcon, Roche, Genentech; Equity owner – Ophthotech, Notalvision

    D.P.: Consultant – Novartis, Bayer; Clinical study participation – Roche, Novartis, Bayer

    P.J.R.: Research support – Astellas Institute for Regenerative Medicine (AIRM), Carl Zeiss Meditec, Genentech, Tyrogenex; Consultant – Acucela, Apellis, Boehringer-Ingelheim, Carl Zeiss Meditec, Cell Cure Neurosciences, Chengdu Kanghong Biotech, Isarna Therapeutics, Genentech, Healios K.K., Hemera Biosciences, F. Hoffmann-La Roche Ltd., Ocudyne, Ocunexus, Tyrogenex, Unity Biotechnology; Equity Interest – Apellis, Digisight, Ocudyne

    D.S.: Consultant – Genentech, Optovue, Bayer, Novartis; Financial support – Allergan, Genentech, Heidelberg Engineering, Regeneron, Optovue, Optovue; Lecturer – Optovue

    R.F.S.: Consultant – Topcon Medical Systems, Heidelberg Engineering; Royalties – Topcon Medical Systems, DORC

    R.T.: Financial support – Alcon, Allergan, Alimera, Novartis, Bayer, B+L, FCI, Zeiss, Thromgenics, Genentech, Roche; Nonfinancial support – Alcon, Allergan, Novartis, Bayer, B+L, Zeiss

    A.T.: Financial support – Novartis, Roche, Bayer Healthcare, Genentech, Allergan, Alcon, Heidelberg Engineering

    S.W.: Financial support – Allergan, Bayer, Novartis; Other – Zeiss, Heidelberg Engineering, Optos

    G.S.: Financial support – Heidelberg Engineering, Zeiss Meditec, Optovue, Optos, Centervue, Nidek, Novartis, Bayer; Other – Heidelberg Engineering, Zeiss Meditec, Optos, Centervue, Novartis, Bayer, Boeheringer, Allergan, Alcon

    Acquisition of human donor eyes and the Project MACULA web site were supported by the National Institutes of Health, Bethesda, Maryland (grant nos.: R01EY06019 and P30 EY003039 [C.A.C.]); EyeSight Foundation of Alabama (C.A.C.); International Retinal Research Foundation (C.A.C.); the Edward N. and Della L. Thome Foundation (C.A.C.); the Arnold and Mabel Beckman Initiative for Macular Research (C.A.C.); and Research to Prevent Blindness, Inc, New York, New York (C.A.C.). Supported by the Lowy Research Medical Institute (travel grant, A.C.B.).

    HUMAN SUBJECTS: No human subjects were included in this study.

    Author Contributions:

    Conception and design: Sadda, Guymer, Holz, Rosenfeld, Spaide, Staurenghi

    Analysis and interpretation: Sadda, Guymer, Holz, Schmitz-Valckenberg, Curcio, Bird, Blodi, Bottoni, Chakravarthy, Chew, Csaky, Danis, Fleckenstein, Freund, Grunwald, Hoyng, Jaffe, Liakopoulos, Monés, Pauleikhoff, Rosenfeld, Sarraf, Spaide, Tadayoni, Tufail, Wolf, Staurenghi

    Data collection: Sadda, Guymer, Holz, Schmitz-Valckenberg, Curcio, Rosenfeld, Spaide, Staurenghi

    Overall responsibility: Sadda, Guymer, Holz, Schmitz-Valckenberg, Curcio, Bird, Blodi, Bottoni, Chakravarthy, Chew, Csaky, Danis, Fleckenstein, Freund, Grunwald, Hoyng, Jaffe, Liakopoulos, Monés, Pauleikhoff, Rosenfeld, Sarraf, Spaide, Tadayoni, Tufail, Wolf, Staurenghi

    Supplemental material available at www.aaojournal.org.

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