June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Deciphering hypereflective foci in age related macular degeneration using adaptive optics in the PINNACLE Study
Author Affiliations & Notes
  • Christopher Holmes
    Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Syed Ahmer Raza
    Institute of Ophthalmology, University College London, London, London, United Kingdom
  • Ahmed M Hagag
    Institute of Ophthalmology, University College London, London, London, United Kingdom
    Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Thomas Taylor
    University of Southampton, Southampton, Hampshire, United Kingdom
  • Sophie Riedl
    Medizinische Universitat Wien, Wien, Wien, Austria
  • Julia Mai
    Medizinische Universitat Wien, Wien, Wien, Austria
  • Toby Prevost
    King's College London, London, London, United Kingdom
  • Daniel Rueckert
    Technische Universitat Munchen, Munchen, Bayern, Germany
  • Hrvoje Bogunovic
    Medizinische Universitat Wien, Wien, Wien, Austria
  • Hendrik P Scholl
    Institute of Molecular and Clinical Ophthalmology Basel, Basel, Basel-Stadt, Switzerland
  • Ursula Schmidt-Erfurth
    Medizinische Universitat Wien, Wien, Wien, Austria
  • Lars G Fritsche
    Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States
  • Andrew J Lotery
    University of Southampton, Southampton, Hampshire, United Kingdom
  • Sobha Sivaprasad
    Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Christopher Holmes None; Syed Raza None; Ahmed Hagag Boehringer Ingelheim, Code E (Employment); Thomas Taylor None; Sophie Riedl None; Julia Mai None; Toby Prevost None; Daniel Rueckert None; Hrvoje Bogunovic Heidelberg Engineering, Apellis, RetInSight, Code F (Financial Support), Bayer, Apellis, Code R (Recipient); Hendrik Scholl None; Ursula Schmidt-Erfurth Apellis, Code C (Consultant/Contractor), Genentech, Kodiak, Novartis, Roche, Apellis, RetinSight, Code F (Financial Support), RetinSight, Code P (Patent); Lars G Fritsche None; Andrew Lotery None; Sobha Sivaprasad None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2171. doi:
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      Christopher Holmes, Syed Ahmer Raza, Ahmed M Hagag, Thomas Taylor, Sophie Riedl, Julia Mai, Toby Prevost, Daniel Rueckert, Hrvoje Bogunovic, Hendrik P Scholl, Ursula Schmidt-Erfurth, Lars G Fritsche, Andrew J Lotery, Sobha Sivaprasad; Deciphering hypereflective foci in age related macular degeneration using adaptive optics in the PINNACLE Study. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2171.

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

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Abstract

Purpose : Hyper-reflective foci (HRF) on optical coherence tomography (OCT) in age-related macular degeneration (AMD) are seen as hypo-reflective dots (HRDs) in flood illumination Adaptive Optics Ophthalmoscopy (AOO). These HRDs may represent detached retinal pigment epithelial (RPE) and/or inflammatory cells. Microglial activation in AMD may result in outer retinal accumulation of melanosome laden macrophages. Both migrated RPE cells and macrophages may relocate over time, but unlike RPE cells, macrophages can migrate up to 0.02µm/s in healthy retinas and faster (2.37µm/s) when inflamed. We hypothesize that HRDs moving rapidly are more likely to be macrophages than detached RPE, and so we evaluated repeat AOO within hours to determine an HRD’s cellular origin.

Methods : Patients with intermediate AMD with HRF in at least one eye were imaged with the rtx1 AO retinal camera at baseline and 1-3 hours later. Overlapping AOO images were taken covering 12o horizontal by 4o vertical, centred on the fovea, and further images centred on areas with high density of HRDs. Images were assessed unedited to minimise image manipulation, and compared to later time points to identify mobile HRDs. Measurements between landmark features with AOdetect software were used to calibrate measurements taken in ImageJ . Macular Spectral Domain OCT scans were obtained in all patients immediately after baseline AOO.

Results : Images from 13 eyes of 12 patients were of adequate quality to assess HRDs. Where individual HRD boundaries were identifiable, mean HRD size was 19.2µm (range: 8.9µm to 36.7µm). Overlapping borders of clustered HRDs made their number, size, and movement challenging to assess in many cases. The majority of HRDs were static within the timeframe of the imaging protocol, but mobile HRDs were found in every image. Assuming linear movement, mobile HRDs travelled at variable speeds, up to 0.036µm/s. Identifying HRFs on OCT corresponding to mobile HRDs was challenging due to clustering and unreliable visibility on OCT, but they were likely outer retinal.

Conclusions : AOO can detect HRD movement in AMD in images captured 1 hour apart. The majority of HRDs were static over periods up to 3 hours, but mobile HRDs were common and faster than previously thought. Mobile HRDs are consistent with activated microglial cells, but the origin of slow HRDs is still unclear.

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

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