PMC8532547_01
Multimodal ophthalmic imaging of the father of the proband with autosomal dominant vitreoretinochoroidopathy (p.Val239Met in BEST1). (A) Fundus photography of the right eye showing disc pallor with glial material peripapillary, and inferior, blunted macula with pigmentary changes, vascular attenuation and a sharp classical between a region of normal retina and a region of pigmented changes and yellowish deposits in the periphery 360 degrees. (B) The fluorescein angiography shows early proximal arterial hyperfluorescence with late perivascular staining and late cystoid macular oedema and scattered few chorioretinal hypofluorescent spots in the periphery. (C) Fundus autofluorescence of right eye shows circumferential peripheric hypoautofluorescence and an irregular hyperautofluorescence in posterior pole. (D) The horizontal line scan from the optical coherence tomography of the macula in the right eye reveals cystoid macular oedema and epiretinal membrane. (E) Kinetic visual field of the right eye demonstrates constriction of peripheral isopters down to 100 degrees central island to V4e. (F) Full-field electroretinography shows a generalised retinal dysfunction with a pattern of a moderate cone-rod dysfunction. DA 0.01, scotopic dim; DA 6.0, scotopic bright; LA 6.0, photopic single; LA 30.0 Hz, photopic 30 Hz.
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F3
The fundus examination revealed bilateral disc pallor with prepapillary fibrous tissue, blunted macular reflex with pigmentary mottling, vascular attenuation and a well-demarcated region of retinal atrophy and pigment changes 360 degrees in the retinal periphery (figure 3A). The FA showed window defects in the periphery with a few scattered chorioretinal hypofluorescent spots in both eyes (figure 3B). The autofluorescence showed bilateral diffuse hyperautofluorescence in the posterior pole and peripheral hypoautofluorescence, that was consistent with RPE atrophy (figure 3C). The OCT images showed cystoid macular oedema and epiretinal membrane in both eyes (figure 3D). Kinetic perimetry demonstrated constriction of the V4e isopters down to about 100 degrees horizontal diameter in each eye (figure 3E). FfERG showed a generalised retinal dysfunction with a pattern of a moderate cone and rod dysfunction (figure 3F).
PMC8532547_02
Multimodal ophthalmic imaging of the paternal grandmother with autosomal dominant vitreoretinochoroidopathy (p.Val239Met in BEST1). All pictures in the left at 59-year-old compared with old pictures in the right. (A) Fundal photomontage (FF450 Zeiss) of the right eye at 49-year-old showing the mild and far peripheral pigmentary changes. (B) Widefield photograph (Optos California) at 59-year-old of right eye demonstrates clear media, waxy disc pallor, attenuated vessels with associated pigment clumping and bone spicules in the mid periphery and periphery that increased compared with 10 years ago. (C) Fundus autofluorescence (FAF) of the right eye at 54-year-old compared with FAF (D) at 59-year-old showing irregular area of central hyperautofluorescence and a circumferential hypoautofluorescence surrounding the disc and temporal arcades in a centripetal progression of the hypoautofluorescence beyond posterior pole. Expanded pictures of fluorescein angiogram (FA) at 49-year-old (E) showing petaloid macular hyperfluorescence in late phase due to staining and oedema and a hyperfluorescence due to a window defect temporal to the fovea area. FA repeated at 59-year-old (F) showing the enlargement of the foveal hyperfluorescence due to increased macular oedema as well as increased diffuse hyperfluorescence due to window defect and decreased relative hypofluorescence of the residually intact retina in the posterior pole. The attenuated vessels are not perfused early or late during the examination. There is also a hypofluorescent bone-spicule pattern in the periphery. (G) The horizontal line scan from the optical coherence tomography (OCT) of the macula in the right eye at 49-year-old reveals cystoid macular oedema and epiretinal membrane (ERM). OCT at 59-year-old (H) showing sustained ERM and increased macular oedema.
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F4
Atrophy of retinal pigment epithelium, and cystoid macular oedema, increased over the years as shown on multimodal ophthalmic imaging from different ages (figure 4A-H).
Functional tests over decades. (A) The first Goldmann perimetry was done in her 30s. (B) The octopus 101 was done in her 40s. (C) Octopus 900 was done in her 50s. All isopters to all targets decreased over years remaining less than 40 continuous horizontal degrees to V4e in both eyes in her last kinetic visual field. (D) The response amplitudes of three different full-field electroretinography over two decades were compared into a data base of age-matched controls. Amplitudes were the average of the right and left eye responses for all measurements and are presented as a percentage of the lower limit of age-matched normal response. All amplitudes decreased to minimal responses in both scotopic and photopic revealing a progression of the disease and severe retinal rod and cone dysfunction in both eyes in late-stage autosomal dominant vitreoretinochoroidopathy.
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F5
These anatomical changes were correlated with function loss on perimetry and electrophysiology (figure 5A-D). Over three decades, her visual fields progressively constricted (figure 5A-C), and the ffERG showed progressively rod-cone dysfunction (figure 5D).