June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Microscopic Imaging of Photoreceptor-RPE-Choriocapillaris Complex in Late-Onset Retinal Degeneration with 3.4 MHz AO-OCT
Author Affiliations & Notes
  • Zhuolin Liu
    US Food and Drug Administration White Oak Campus, Silver Spring, Maryland, United States
  • Samira Aghayee
    US Food and Drug Administration White Oak Campus, Silver Spring, Maryland, United States
  • Somayyeh Soltanian-Zadeh
    Department of Biomedical Engineering, Duke University, North Carolina, United States
  • Katherine Kovalick
    US Food and Drug Administration White Oak Campus, Silver Spring, Maryland, United States
  • Achyut Raghavendra
    US Food and Drug Administration White Oak Campus, Silver Spring, Maryland, United States
  • Osamah Saeedi
    University of Maryland Baltimore, Baltimore, Maryland, United States
  • Sina Farsiu
    Department of Biomedical Engineering, Duke University, North Carolina, United States
  • Catherine Cukras
    National Institutes of Health, Bethesda, Maryland, United States
  • Daniel X Hammer
    US Food and Drug Administration White Oak Campus, Silver Spring, Maryland, United States
  • Footnotes
    Commercial Relationships   Zhuolin Liu Indiana University, Code P (Patent); Samira Aghayee None; Somayyeh Soltanian-Zadeh None; Katherine Kovalick None; Achyut Raghavendra None; Osamah Saeedi None; Sina Farsiu None; Catherine Cukras None; Daniel Hammer None
  • Footnotes
    Support  FDA Critical Path Initiative; he Foundation Fighting Blindness (BR-CL-0621-0812-DUKE), National Institutes of Health (P30EY005722); Duke University (Research to Prevent Blindness Unrestricted Grant); Hartwell Foundation (Postdoctoral Fellowship); National Eye Institute Intramural Research Program.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1972. doi:
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      Zhuolin Liu, Samira Aghayee, Somayyeh Soltanian-Zadeh, Katherine Kovalick, Achyut Raghavendra, Osamah Saeedi, Sina Farsiu, Catherine Cukras, Daniel X Hammer; Microscopic Imaging of Photoreceptor-RPE-Choriocapillaris Complex in Late-Onset Retinal Degeneration with 3.4 MHz AO-OCT. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1972.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To characterize photoreceptor (PR)-retinal pigment epithelium (RPE)-choriocapillaris (CC) cellular changes in patients with late-onset retinal degeneration (L-ORD).

Methods : Four participants with L-ORD (CTRP5 mutation; P1, P2: pre-clinical; P3, P4: advanced) and two healthy control (HC) volunteers were imaged with the FDA 3.4 MHz Fourier-domain mode-locked-adaptive optics (AO) system. AO-OCT and AO-OCT angiography modes were applied to resolve the cellular details in the PR-RPE-CC complex from the fovea to 12° temporal retina. Morphological parameters were quantified in terms of cone PR density and outer segment length (OSL), RPE density and area, and normalized CC density. The PR analysis was performed with an automated volumetric cone segmentation method based on a deep-learning approach, while RPE and CC quantification was done manually.

Results : The two pre-clinical stage participants demonstrate differences in OSL, but no other measured parameter, when compared to HCs. The cone density monotonically decreases from ~44,300 cells/mm2 at 1° to 7,100 cells/mm2 at 12°. The RPE density decreases at a slower rate from ~7,100 cells/mm2 at the fovea to 5,500 cells/mm2 at 12°, resulting in an RPE area increase from 143 um2 to 182 um2 at the corresponding locations. The normalized CC density exhibits very little difference across the macula with an average density of 58%. Conversely, the OSL is shorter than HCs at all locations with an overall reduction of 48.8% and 25% in P1 and P2, respectively. In an advanced stage, further structural disruptions are evident: the OSL is further shortened and the PR density is reduced; RPE cell density decreases by an average of 60% resulting in a 268% increase in cell area; many reticular pseudo-drusen appear across the macula; and there is a loss of CC vasculature that accompanies the cellular changes. Overall, a widespread collapse in the PR-RPE-CC complex was observed in P3 and P4.

Conclusions : The 3.4 MHz AO-OCT allows characterization of cellular-level structural changes in L-ORD. The results in preclinical LORD suggests that although CTRP5 is expressed in the RPE, the early insults include subtle structural changes to the photoreceptors. Further investigation will yield insights into the pre-clinical disease stage, which may stimulate development of targeted therapies and provide imaging outcomes to monitor in interventional trials.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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