REVIEW article
Front. Neurol.
Sec. Neuro-Ophthalmology
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1659264
This article is part of the Research TopicAdvances in Understanding Visual Disorders Linked to Cortical DysfunctionView all 10 articles
Fluorescence Lifetime Imaging Ophthalmoscopy [FLIO] adds the Retina to Cortical Pathology for Visual Dysfunction in Neurodegenerative Diseases
Provisionally accepted
- 1William H. Annesley, EyeBrain Center, Vicky and Jack Farber Neuroscience Institute, Thomas Jefferson University, Partnered with Wills Eye Hospital, Philadelphia, PA, United States
- 2Department of Ophthalmology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
- 3Drexel University College of Medicine, Philadelphia, United States
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Because neurodegenerative diseases such as Parkinson’s and Alzheimer’s Diseases [AD and PD] as well as the progressive forms of multiple sclerosis [MS] are invariably associated with clinically significant cortical symptoms such as language difficulties, motor skill deficits and cognitive impairments, especially memory, a tacit assumption evolved that visual disorders related to cortical dysfunction must localize only to the temporal, parietal and occipital lobes. Based upon our current understanding, retinal changes in MS are most likely secondary to optic neuropathy, whereas in AD and PD, they appear to represent primary retinal changes. The paradigm was reinforced by the lack of retinal findings using ophthalmoscopy. Spectral domain optical coherence tomography [OCT], optical coherence angiography [OCT-A], and fundus autofluorescence [FAF] have challenged this creed by uncovering structural changes within the retina over and above what can occur as a consequence of optic neuropathy in the case of MS. Still, definitive diagnostic and prognostic data have yet to emerge. Fluorescence lifetime imaging ophthalmoscopy [FLIO], a non-invasive, non-contact, painless imaging technology, measures nanosecond lifetimes of endogenous retinal fluorophores, some of which are linked to mitochondrial activity. Therefore, FLIO is a metabolic, not a structural imaging modality. Because mitochondrial dysfunction occurs in many neurodegenerative diseases, FLIO offers a unique strategy for investigating retinal metabolism in AD, PD, and MS. This article reviews the basic biomedical engineering of FLIO and reports preliminary data from these diseases, correlated with disease duration. These functional in vivo data are consistent with retinal metabolic changes in AD, PD, and progressive MS that were “hiding in plain sight” from structural examinations.
Keywords: fluorescence lifetime imaging ophthalmoscopy, Neurodegenerative diseasaes, Alzheimer's disease, Parkinson's disease, Multiple Sclerosis
Received: 03 Jul 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Nimworaphan, Markowitz and Sergott. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Robert C. Sergott, rcs220@comcast.net
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