case_images: PMC11250126_01
case_images: Fundus photos and fluorescein angiography. Color fundus photos of the right (a) and left (b) eyes demonstrating macular pigmentary changes. Fluorescein angiography of the right (c) and left (d) eyes illuminating AS, posterior hypofluorescent spots, and macular atrophy.
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case_images: F1
case_images: Fundus examination demonstrated bilateral irregular macular pigmentary changes, localized areas of retinal pigment epithelium (RPE) atrophy, and drusen-like lesions extending from the peripapillary retina, along the vascular arcades, and into the temporal pericentral retina (Fig. 1a, b). Fluorescein angiography revealed hyperfluorescent radial lines emanating from the disc, a large non-homogenous hyperfluorescent area caused by window defects that co-localized with RPE changes, and scattered hypofluorescent foci (Fig. 1c, d).
case_images: Optical coherence tomography. Several horizontal scans are shown for the right (a-e) and left (g-k) eyes as well as a vertical foveal scan for the right (f) and left (l) eye. Diffuse hyperreflective subretinal deposits with outer retinal irregularity is seen. Subretinal fluid was present without evidence of neovascularization (g).
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case_images: F2
case_images: Spectralis HRA system (Heidelberg Engineering GmbH, Heidelberg, Germany). SD-OCT demonstrated hyperreflective subretinal deposits, most obvious near the foveal center, and irregularities of the RPE nasally (Fig. 2a, b). There were segments with abrupt thinning of the photoreceptor outer nuclear layer and interruptions of the inner segment ellipsoid and outer segment interdigitation bands, often crossed by vertical hyperreflective tracks (Fig. 2a, b).
case_images: Visual function and retinal structure in the patient. a Fundus autofluorescence (FAF) imaging with short-wavelength (SW-FAF) and near-infrared (NIR-FAF) excitation lights in each eye of the patient. Insets on the left eye panels are representative normal images for each FAF modality. Overlaid on the NIR-FAF image of the left eye is perimetric sensitivity losses measured in the light-adapted (cone) and dark-adapted (rod) states plotted following a pseudocolor scheme. A diffuse pattern of hyperautofluorescence interrupted by well-circumscribed hypoautofluorescent lesions in areas of RPE atrophy is seen (asterisk). There is a peripheral leading edge of punctate hyperautofluorescent lesions (arrows). b 9 mm SD-OCT cross-section through the patient's left fovea. The temporal parafovea retina shows multiple round hyperreflective foci tracking from the RPE toward the inner retina, likely representative of RPE migration. Outer retinal sublaminae are labeled according to conventional nomenclature: outer nuclear layer (ONL); outer limiting membrane (OLM); inner segment ellipsoid region (EZ or ISe); contact cylinder between the apical RPE microvilli and the photoreceptor outer segments tips, or interdigitation zone (IZ); basal RPE and Bruch's membrane (RPE/BrM). A subretinal deposit replaces a focal EZ and IZ signal laying superficial to the RPR/BrM (arrow). c Light-adapted achromatic and dark-adapted chromatic (500 nm) sensitivity losses (calculated from lower limit of normal = mean - 2 standard deviations) along the horizontal meridian in the patient. Photoreceptor mediation in the dark-adapted state was confirmed rod-mediated for all locations with the use of spectral sensitivity (500 nm-650 nm) differences. Hatched bars denote the location of the blind spot. N, nasal. T, temporal.
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case_images: F3
case_images: SW-FAF demonstrated a mostly diffuse pattern of hyperautofluorescence interrupted by well-circumscribed hypoautofluorescent lesions in areas of RPE atrophy and a peripheral leading edge of punctate hyperautofluorescent lesions (Fig. 3a). Measures of photoreceptor specific sensitivities by two-color dark-adapted perimetry disclosed major rod sensitivity losses along this area of hypoautofluorescence, confirming earlier observations in patients with PXE (Fig. 3a). The sensitivity losses co-localized with outer retinal abnormalities seen in the SD-OCT cross-section (Fig. 3b, c). The greatest abnormalities corresponded to segments of outer nuclear layer thinning in the parafoveal and pericentral nasal retina (Fig. 3b, c). Note the abrupt normalization of the sensitivities for both photoreceptor mechanisms in the temporal well-laminated retina, as well as the relative preservation of light-adapted sensitivities near the foveal center (Fig. 3c).
case_images: External photos of flexural skin biopsy site. a Subtle areas of speckled dermal hyper- and hypopigmentation outlined by surgical marking (purple) at the biopsy location. b Magnification of focal skin lesions outlined by surgical marking (purple) without classic pseudoxanthomatous lesions.
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case_images: F4
case_images: The retinal phenotype and the molecular findings further supported the possibility of PXE prompting a referral back to dermatology for a flexural skin biopsy, upon which a subtle macule (Fig. 4) was positive for fragmented elastic fibers, consistent with a final diagnosis of PXE.