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Research Letter |

Increased Fundus Autofluorescence Related to Outer Retinal Disruption

K. Bailey Freund, MD1,2,3; Sarah Mrejen, MD1,2,3; Jesse Jung, MD1,2; Lawrence A. Yannuzzi, MD1,2,3; Camiel J. F. Boon, MD, PhD4,5
[+] Author Affiliations
1LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York
2Department of Ophthalmology, New York University, New York
3Vitreous Retina Macula Consultants of New York, New York
4Institute of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
5Oxford Eye Hospital, John Radcliffe Hospital, University of Oxford, Oxford, England
JAMA Ophthalmol. 2013;131(12):1645-1649. doi:10.1001/jamaophthalmol.2013.5030.
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Fundus autofluorescence (FAF) imaging is able to map metabolic changes at the level of the retinal pigment epithelium (RPE) noninvasively in vivo. However, the observed autofluorescence signal is a summation of not only the autofluorescence originating from the RPE but also that from more anterior ocular structures including the overlying neuroretina.1 Retinal photopigments within the photoreceptor outer segments have absorption properties, and illumination with blue light decreases the optical pigment density by photobleaching.2 After blue light irradiation, there is photoisomerization of the opsin proteins from the 11-cis to all-trans conformation in the photoreceptor outer segments. This photoisomerization to the all-trans configuration causes a decrease in the optical density of the photopigment in the outer segments of the photoreceptors, resulting in a temporary loss of light absorption properties. Theelen et al3 have shown that in healthy and diseased eyes, the illumination of a retinal area with blue light produces a relative hyperautofluorescence as compared with the surrounding nonilluminated area. The mechanism involved is a window defect due to the relative loss of photopigment density in the outer segments of the photoreceptors after bleaching of these photopigments.

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Figure 1.
Multimodal Imaging of a 30-Year-Old Man With Multifocal Choroiditis and a 50-Year-Old Woman With Multiple Evanescent White Dot Syndrome

A-D, Multimodal imaging of a 30-year-old man with multifocal choroiditis in the left eye. A fundus autofluorescence (FAF) image at presentation using the Optos system showed multiple hypoautofluorescent spots and a peripapillary zonal hyperautofluorescent area (A), colocalizing with an area of disruption of both the ellipsoid and retinal pigment epithelium–photoreceptor interdigitation zones in the corresponding spectral-domain optical coherence tomographic (SD-OCT) image (B). A FAF image 7 months later (C) showed resolution of the peripapillary zonal hyperautofluorescent area concomitant with near-complete restoration of both the ellipsoid and the digitation zones in the corresponding SD-OCT image (D). E-H, Multimodal imaging of a 50-year-old woman with multiple evanescent white dot syndrome. A 30° FAF image using the confocal scanning laser ophthalmoscope system showed multiple hyperautofluorescent spots (white arrow) (E), which corresponded to areas of focal disruption (arrow) of both the ellipsoid and retinal pigment epithelium–photoreceptor interdigitation zones on a horizontal SD-OCT scan (F). After bleaching, the FAF signal of the surrounding retinal areas increased more than the FAF signal of the spots, resulting in a markedly decreased difference in autofluorescence level between the pathological spots and the relatively normal-appearing surrounding retinal tissue (G). However, on the corresponding SD-OCT images before (F) and after (H) bleaching, the retinal structure looked identical. One hour later, the hyperautofluorescent spots reappeared just as in E (image not shown). The green arrows in A, C, E, and G indicate the levels of the SD-OCT scans in B, D, F, and H, respectively.

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Figure 2.
Multimodal Imaging of a 35-Year-Old Woman With Central Serous Chorioretinopathy

Multimodal imaging of a 35-year-old woman with central serous chorioretinopathy in the left eye, at presentation (A-D) and after complete resolution of the subretinal fluid (E-H). Transit phase of fluorescein angiography (A) and midphase of indocyanine green angiography (B) both showed the focal leak point with typical inkblot diffusion. C, The spectral-domain optical coherence tomographic scan at the level of the arrow in A showed subretinal fluid. D, The spectral-domain optical coherence tomographic thickness map showed an area of retinal thickening (red) around the focal leak point corresponding to the subretinal fluid. E, After resolution of the subretinal fluid, the 55° fundus autofluorescence image showed an area of increased fundus autofluorescence superior to the optic disc, corresponding to the area where the subretinal fluid was previously detected. The bleaching experiment was performed twice: first temporal to the hyperautofluorescent area (E) and then including most of the abnormal hyperautofluorescent area (F). The second time, the lesion became much less distinguishable from the bleached background, presumably due to a lack of bleaching in this retinal area that shows a disruption of both the ellipsoid and retinal pigment epithelium–photoreceptor interdigitation zones on the corresponding spectral-domain optical coherence tomographic image (arrows) (G) (taken at the level of the arrow in E). The same area corresponds to retinal thinning (blue) in the corresponding retinal thickness map (H).

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Figure 3.
Multimodal Imaging of a 50-Year-Old Man With Resolved Central Serous Chorioretinopathy

Multimodal imaging of the left eye of a 50-year-old man with resolved central serous chorioretinopathy. The infrared reflectance image (same in A-C), the fundus autofluorescence (FAF) image (same in D-F), and the spectral-domain optical coherence tomographic (OCT) transverse sections (G-I) and B scans (J-L) were acquired with the confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph; Heidelberg Engineering). The segmentation for the transverse OCT was between the superior border of the ellipsoid zone and the superior border of the retinal pigment epithelial band. The level of segmentation is shown by the red lines in the OCT B scans in M-O. E and H, Note that there were 2 autofluorescent patterns within the previously detached retinal area (dotted lines). A-I, First, there are focal granular hyperautofluorescent spots (arrows) appearing bright in the infrared image, hyperautofluorescent in the FAF image, and bright in the transverse OCT image. J-O, These granular hyperautofluorescent spots correspond to hyperreflective deposits at the level of the retinal pigment epithelium in the corresponding OCT B scans (white lines). Second, there is a diffuse hyperautofluorescent area in the FAF image (E, dotted line) colocalizing precisely with a hyporeflective area in the transverse OCT image (H, dotted line). This demonstrates that the diffuse hyperautofluorescence in the FAF image colocalizes precisely with the disruption of both the ellipsoid and interdigitation zones in the corresponding OCT B scans.

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