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Litts, Katie M. PhD*,†; Zhang, Yuhua PhD*; Freund, K. Bailey MD; Curcio, Christine A. PhD*

doi: 10.1097/IAE.0000000000001946

Purpose: Widespread adoption of optical coherence tomography has revolutionized the diagnosis and management of retinal disease. If the cellular and subcellular sources of reflectivity in optical coherence tomography can be identified, the value of this technology will be advanced even further toward precision medicine, mechanistic thinking, and molecular discovery. Four hyperreflective outer retinal bands are created by the exquisite arrangement of photoreceptors, Müller cells, retinal pigment epithelium, and Bruch membrane. Because of massed effects of these axially compartmentalized and transversely aligned cells, reflectivity can be localized to the subcellular level. This review focuses on the second of the four bands, called ellipsoid zone in a consensus clinical lexicon, with the central thesis that mitochondria in photoreceptor inner segments are a major independent reflectivity source in this band, because of Mie scattering and waveguiding.

Methods: We review the evolution of Band 2 nomenclature in published literature and discuss the origins of imaging signals from photoreceptor mitochondria that could make these organelles visible in vivo.

Results: Our recent data pertain to outer retinal tubulation, a unique neurodegenerative and gliotic structure with a highly reflective border, prominent in late age-related macular degeneration. High-resolution histology and multimodal imaging of outer retinal tubulation together provide evidence that inner segment mitochondria undergoing fission and translocation toward the nucleus provide the reflectivity signal.

Conclusion: Our data support adoption of the ellipsoid zone nomenclature. Identifying subcellular signal sources will newly inform clinical.

Supplemental Digital Content is Available in the Text.The authors review evolution of terminology for the second of four hyperreflective outer retinal bands on optical coherence tomography and describe how the ellipsoid zone nomenclature is supported by recent data showing mitochondria to be a major independent reflectivity source in photoreceptor inner segments.

*Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama;

Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin; and

Vitreous Retina Macula Consultants of New York, New York, New York.

Reprint requests: Christine A. Curcio, PhD, EyeSight Foundation of Alabama Vision Research Laboratories, Department of Ophthalmology, University of Alabama School of Medicine, 1670 University Boulevard Room 360, Birmingham, AL 35294-0099; e-mail

This article substantively reviews PhD dissertation research that was supported by the Vision Science Graduate Program at UAB (K.M.L.). Y. Zhang is supported by EY021903, EY024378, International Retina Research Foundation, and the EyeSight Foundation of Alabama. The Eye Donor Project and K. B. Freund's participation are supported by the Macula Foundation. C. A. Curcio is supported by International Retinal Research Foundation, unrestricted funds to the Department of Ophthalmology from Research to Prevent Blindness, Inc, and EyeSight Foundation of Alabama. Acquisition of donor eyes for AMD research was supported by National Eye Institute (EY06109, P30 EY003039), International Retinal Research Foundation, and the Arnold and Mabel Beckman Initiative for Macular Research. The Project MACULA website was supported by these and additionally by the Edward N. and Della L. Thome Memorial Foundation.

K. B. Freund is a Consultant to Genentech, Optos, Optovue, Heidelberg Engineering, and Spark Therapeutics; Research support from Genentech/Roche. C. A. Curcio is a Consultant to Novartis; Research support from Genentech/Roche, Heidelberg Engineering.

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© 2018 by Ophthalmic Communications Society, Inc.