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. 2022 Aug 29;12(1):14337.
doi: 10.1038/s41598-022-18048-4.

Spectrally resolved autofluorescence imaging in posterior uveitis

Affiliations

Spectrally resolved autofluorescence imaging in posterior uveitis

Maximilian W M Wintergerst et al. Sci Rep. .

Abstract

Clinical discrimination of posterior uveitis entities remains a challenge. This exploratory, cross-sectional study investigated the green (GEFC) and red emission fluorescent components (REFC) of retinal and choroidal lesions in posterior uveitis to facilitate discrimination of the different entities. Eyes were imaged by color fundus photography, spectrally resolved fundus autofluorescence (Color-FAF) and optical coherence tomography. Retinal/choroidal lesions' intensities of GEFC (500-560 nm) and REFC (560-700 nm) were determined, and intensity-normalized Color-FAF images were compared for birdshot chorioretinopathy, ocular sarcoidosis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and punctate inner choroidopathy (PIC). Multivariable regression analyses were performed to reveal possible confounders. 76 eyes of 45 patients were included with a total of 845 lesions. Mean GEFC/REFC ratios were 0.82 ± 0.10, 0.92 ± 0.11, 0.86 ± 0.10, and 1.09 ± 0.19 for birdshot chorioretinopathy, sarcoidosis, APMPPE, and PIC lesions, respectively, and were significantly different in repeated measures ANOVA (p < 0.0001). Non-pigmented retinal/choroidal lesions, macular neovascularizations, and fundus areas of choroidal thinning featured predominantly GEFC, and pigmented retinal lesions predominantly REFC. Color-FAF imaging revealed involvement of both, short- and long-wavelength emission fluorophores in posterior uveitis. The GEFC/REFC ratio of retinal and choroidal lesions was significantly different between distinct subgroups. Hence, this novel imaging biomarker could aid diagnosis and differentiation of posterior uveitis entities.

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Conflict of interest statement

Maximilian W.M. Wintergerst: DigiSight Technologies: travel grant, D-EYE Srl: imaging devices, Heine Optotechnik GmbH: research funding, imaging devices, travel reimbursements, consultant; Eyenuk, Inc: free trial analysis; ASKIN & CO GmbH: travel reimbursement, honoraria; Berlin-Chemie AG: grant, travel reimbursements; Imaging devices were provided by Heidelberg Engineering, Optos, Carl Zeiss Meditec, and CenterVue; Nicholas R. Merten: No financial disclosures; Moritz Berger: No financial disclosures; Chantal Dysli: No financial disclosures; Jan H. Terheyden: Imaging devices were provided by Heidelberg Engineering, Optos, Carl Zeiss Meditec, and CenterVue; Enea Poletti: Employment: Centervue S.p.A.; Frank G. Holz: Research Grant Support: Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, CenterVue, Ellex, Roche/Genentech, Geuder, Kanghong, NightStarx, Novartis, Optos, Zeiss; Consultant: Acucela, Aerie, Allergan, Apellis, Bayer, Boehringer-Ingelheim, ivericbio, Roche/Genentech, Geuder, Grayburg Vision, ivericbio, LinBioscience, Kanghong, Novartis, Pixium Vision, Oxurion, Stealth BioTherapeutics, Zeiss; Valentin S. Schäfer: No financial disclosures; Matthias Schmid: No financial disclosures; Thomas Ach: Research Grant Support: Novartis; Lecture fee: Novartis, Heidelberg Engineering; Advisory Board: Roche; Invest: Macregen; Robert P. Finger: funding was provided by Else Kroener-Fresenius Foundation and the German Scholars Organization (EKFS/GSO 16); financial support: Novartis, Heidelberg Engineering, Optos, Carl Zeiss Meditec, and CenterVue. Consultant: Bayer, Novartis, Roche/Genentech, Boehringer-Ingelheim, Opthea, Santhera, Inositec, Alimera, Allergan, Ellex.

Figures

Figure 1
Figure 1
Eidon Autofluorescence sensor quantum efficiency. Each wavelength from 500 to 750 nm contributes to both, green and red channels with different efficiencies. The single-color component (red or green) of a pixel has to be interpreted as the total contribution of all wavelengths collected by the sensor after they are multiplied by their respective quantum efficiency (QE). The dashed line illustrates the barrier filter with the cut-off at 500 nm.
Figure 2
Figure 2
Comparison of birdshot chorioretinopathy, ocular sarcoidosis, punctate inner choroidopathy (PIC), and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) on spectrally resolved autofluorescence (Color-FAF) imaging. An exemplary eye with birdshot chorioretinopathy (first row), ocular sarcoidosis (second row), PIC (third row), and APMPPE (fourth row) are illustrated. From left to right: color fundus photography (CFP), grayscale fundus autofluorescence image (grayscale FAF), spectrally resolved fundus autofluorescence (Color-FAF) image, intensity-normalized Color-FAF. Lesions of eyes affected by ocular sarcoidosis were more apparent than in eyes with birdshot chorioretinopathy on grayscale FAF, Color-FAF, and intensity-normalized Color-FAF. Lesions of eyes with PIC were clearly apparent in all four modalities. Lesions of eyes affected by APMPPE were hardly visible on CFP and on intensity-normalized Color-FAF, whereas they were easily definable on Color-FAF and grayscale FAF.
Figure 3
Figure 3
Sources of green and red emission fluorescent components in posterior uveitis. Exemplary eyes with a pigmented scar in toxoplasmosis chorioretinitis (top row) and with macular neovascularization (MNV) in multifocal choroiditis and panuveitis (MCP; bottom row). From left to right: color fundus photography (CFP), grayscale fundus autofluorescence (grayscale FAF), spectrally resolved fundus autofluorescence (Color-FAF) image, intensity-normalized Color-FAF. Pigmented parts of the toxoplasmosis lesion features predominantly red emission fluorescent components (REFC) on intensity-normalized Color-FAF. On grayscale FAF and Color-FAF the pigmented parts were hypoautofluorescent and indistinguishable from parts of the lesion without pigmentation. The MNV in the eye with MCP featured mainly GEFC on Color-FAF and intensity-normalized Color-FAF.
Figure 4
Figure 4
Quantitative analysis of GEFC/REFC ratio for posterior uveitis entities. Birdshot chorioretinopathy (left), ocular sarcoidosis (middle-left), punctate inner choroidopathy (PIC; middle-right), acute posterior multifocal placoid pigment epitheliopathy (APMPPE; right). Values over 1.5 interquartile range below the first quartile or above the third quartile were defined as outliers. Multivariable regression analysis showed significant differences (p < .05) among all posterior uveitis entities except for the comparison of birdshot chorioretinopathy and APMPPE (p = .07).

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