Investigation of long-wavelength fundus autofluorescence
Final Report Abstract
Fundus autofluorescence (AF) imaging of the retina with confocal scanning laser ophthalmoscopy is an established non-invasive imaging modality for the diagnosis of retinal diseases. The standard technique uses short wavelength blue excitation light (488 nm excitation light, SW-AF) to visualize different fluorophores of the retina and the underlying retinal pigment epithelium (RPE). Longwavelength near-infrared autofluorescence (excitation: 787 nm, LW-AF) is a new, innovative alternative to the classic autofluorescence imaging. Excitation of the fluorophores at the ocular fundus using a longer wavelength has several advantages: 1. The examination is more comfortable for the patient (reduced or no glare). 2. The image quality is less affected by cataract development facilitating imaging in older subjects. 3. Visualization of the central retina is not affected by macular pigment. 4. The lower energy of the longer wavelength is less likely associated with retinal light toxicity. 5. The different origin of the signal (melanin) offers new pathogenic insights. With the current imaging technique the autofluorescence signal and thus image quality is considerably lower compared to conventional short-wavelength autofluorescence (SW-AF). This may be the main reason for the currently limited application and scarce scientific publications on this technique. Therefore, the objective of this study is to assess the performance of LW-AF, test an optimized setup of longwavelength autofluorescence imaging and compare it with the current gold standard of SW-AF. The first step of the project consisted of the build-up and acquisition of a large data base of images acquired with SW/LW-AF images. The goal was to compare findings of both imaging modalities as starting point for further examinations. The data base consisted of ~500 patients with various retinal diseases and was the foundation for various descriptions of novel AF findings. This included characteristic AF changes in retinal dystrophies using quantitative autofluorescence imaging, nearinfrared autofluorescence changes in retinal laser injuries and near-infrared autofluorescence in ABCA4-related retinopathy. These findings may support the use of autofluorescence imaging for the differential diagnostics in a routine clinical setting to enable more accurate and earlier diagnosis in patients with retinal diseases. As a next step, a prototype device provided by Heidelberg Engineering was transferred to the Oxford Eye Hospital. The prototype included three novel laser sources and filter sets for an optimized acquisition of LW-AF images. Preliminary findings indicate a better signal compared to the conventional settings. This may support the adaption of novel laser sources for future clinical applications, but further evaluation is needed and currently ongoing. In addition, it was planned to quantify the LF-AF comparable to the SW-AF signal. For this purpose, an autofluorescent probe has been identified in collaboration with the Bundesanstalt für Materialforschung und -prüfung (BAM). Unfortunately, the fluorescent characteristics of the selected material did not fit well with the spectrum of the LW-AF images of the human retina. Accordingly, reliable measurements were not possible and further research is needed to identify alternative materials. Taken together, the results of this project underline the advantages of LW-AF including less patient burden, improved differential diagnostics in retinal diseases and potential earlier diagnostics of retinal diseases. Further work is needed to refine the improved laser wavelength setup to overcome the main limitation which is a relatively weak signal.
Publications
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Functional Relevance and Structural Correlates of Near Infrared and Short Wavelength Fundus Autofluorescence Imaging in ABCA4-Related Retinopathy, Transl Vis Sci Technol. 2019 Dec 20;8(6):46
Müller PL, Birtel J, Herrmann P, Holz FG, Charbel Issa P, Gliem M
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Improved Diagnosis of Retinal Laser Injuries Using Near-Infrared Autofluorescence. Am J Ophthalmol. 2019 Dec;208:87-93
De Silva SR, Neffendorf JE, Birtel J, Herrmann P, Downes SM, Patel CK, Hildebrand GD, Gliem M, Charbel Issa P
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Quantitative Fundus Autofluorescence and Genetic Associations in Macular, Cone, and Cone-Rod Dystrophies, Ophthalmol Retina. 2020 Jul;4(7):737-749
Gliem M, Müller PL, Birtel J, Herrmann P, McGuinness MB, Holz FG, Charbel Issa P
