June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Prolonged Fluorescence Lifetimes of the Retinal Pigment Epithelium in Human Subjects with Pentosan Polysulfate Sodium Toxicity.
Author Affiliations & Notes
  • Kristen E Bowles Johnson
    School of Optometry, Indiana University, Bloomington, Indiana, United States
    Flaum Eye Institute & Center for Visual Science, University of Rochester Medical Center, Rochester, New York, United States
  • Janet Anne Hrdina Tang
    The Institute of Optics, University of Rochester, Rochester, New York, United States
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Karteek Kunala
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Keith Parkins
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Qiang Yang
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Jennifer J. Hunter
    School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada
    Flaum Eye Institute & Center for Visual Science, University of Rochester Medical Center, Rochester, New York, United States
  • Footnotes
    Commercial Relationships   Kristen Bowles Johnson None; Janet Tang None; Karteek Kunala None; Keith Parkins University Rochester, Code P (Patent); Qiang Yang University Rochester, Code P (Patent), Canon Inc., Code P (Patent), Montana State University, Code P (Patent); Jennifer Hunter University Rochester, Code P (Patent)
  • Footnotes
    Support  Research reported in this publication was supported by the National Eye Institute of the National Institutes of Health under Awards No. P30 EY001319 & R01 EY032116 and the Bright Focus Foundation under award M2022007F. This study was supported by an Unrestricted Grant to the University of Rochester Department of Ophthalmology from Research to Prevent Blindness, New York, New York
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1054. doi:
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      Kristen E Bowles Johnson, Janet Anne Hrdina Tang, Karteek Kunala, Keith Parkins, Qiang Yang, Jennifer J. Hunter; Prolonged Fluorescence Lifetimes of the Retinal Pigment Epithelium in Human Subjects with Pentosan Polysulfate Sodium Toxicity.. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1054.

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

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Abstract

Purpose : A major limiting factor of successful treatment trials in advanced nonexudative age-related macular degeneration (AMD) is the lack of biomarkers of geographic atrophy formation and progression. Clinical fluorescence lifetime imaging ophthalmoscopy (FLIO) has shown variations from normal in subjects with drusen and AMD, however the origin of FL changes remains unclear. The clinical characteristics of pentosan polysulfate sodium toxicity (PPST), drusen-like nodular lesions of the retinal pigment epithelium (RPE) and retinal atrophy, are similar to AMD. FL with adaptive optics (AO) provides the ability to optically isolate the FL from the RPE layer. This study explores the changes in FL of RPE in PPST, an ideal model to study AMD-like changes at the cellular level in vivo with AOFLIO.

Methods : AOFLIO (λ_ex 532 nm, λ_em 575-725 nm) was performed on 2 PPST subjects (57 and 67 YO) and 6 controls (50 - 64 YO). For each image, histograms of mean FLs were generated from the parameters of a double exponential decay fit to the recorded photon timing data at each pixel. Intra-visit absolute agreement at 6 locations in PPST was assessed by intraclass correlation coefficient (ICC).

Results : Most histograms of PPST subjects and aged-matched controls were bimodal (peaks P1 & P2). Unimodal histograms had peaks within the range of the longer FL bimodal distribution (P2). ICC between images at the same location was fair at P1 (0.66) and excellent at P2 (0.93). Both P1 and P2 were significantly longer in PPST than controls (P1 = 355 ± 44 ps vs 261 ± 55 ps, p < 0.001; P2= 549 ± 157 ps vs 427 ± 33 ps, p = 0.013 by 2-tailed t-test, n=10 vs 13). In PPST, 9 of 10 locations had P2 peaks above the age matched 95% confidence limit. Clinically normal PPST locations had longer FL than controls. Within images, FL at nodular lesions and at the border of retinal atrophy had even longer FL; extending past 800 ps.

Conclusions : AFOLIO is a promising cellular-scale tool to track biomarkers of disease formation and progression. In our study, prolonged lifetimes were seen at locations that appeared clinically normal in subjects with PPST. RPE nodular lesions had longer FL than the surrounding RPE mosaic. Our findings correlate with clinical FLIO findings in AMD. Longitudinal studies in PPST would determine how prolonged FL of the RPE mosaic correlates with clinical disease progression.

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

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