Very Large Bilateral Lesions Obscuring Diagnosis of Adult-Onset Foveomacular Vitelliform Dystrophy

Case Report

A 61-year-old man was referred to our department for blurred vision. The patient signed a comprehensive consent form according to Good Clinical Practice guidelines prior to a complete ophthalmic examination. Best corrected visual acuity (BCVA) was 20/40 in the right eye (RE) and 20/50 in the left eye (LE). On fundus biomicroscopy, the macula of the RE showed retinal pigment epithelium (RPE) changes associated with a large inhomogeneous dispersion of vitelliform material (Fig. 1A), and the macula of the LE showed a large horizontal sedimentation of vitelliform material (Fig. 1B). The lipofuscinic nature of the lesions was confirmed by fundus autofluorescence (Figs. 1C and 1D). Optical coherence tomography examination (OCT3, Carl Zeiss Meditec, Inc., Dublin, CA) revealed, in the macular region of the RE, apparent residual material in the center of the lesion, as a hypereflective deposit stuck on the outer hypereflective layer, associated with variable photoreceptors, RPE alterations and atrophy (Fig. 1E). In the LE, linear vertical OCT scans showed, in the macular region, on the superior part, an optically empty zone between 2 slightly hypereflective layers, and, on the inferior part of the lesion, the sediment material that appeared as a dense hypereflective structure (Fig. 1F). Interestingly, OCT scan revealed the abrupt transition between the empty area and the vitelliform material, which gravitated inferiorly in the subretinal space, and the neurosensorial retina that maintained a normal thickness and structure (Fig. 1F).

Figure 1. (A) Color Fundus Photographs Show the Retinal Pigment Epithelium (RPE) Changes Associated with a Large Inhomogeneous Dispersion of Vitelliform Material at the Macula of the Right Eye (RE), and (B) the Large Horizontal Sedimentation of Vitelliform Material at the Macula of the Left Eye (LE). (C and D) The Lipofuscinic Nature of the Macular Lesions Is Confirmed by Fundus Autofluorescence. (E) Optical Coherence Tomography Scan (OCT) Reveals in the Macular Region of the RE the Apparent Residual Material in the Center of the Lesion as a Hypereflective Deposit Stuck on the Outer Hypereflective Layer Associated with Variable Photoreceptors Layer/RPE Alterations and Atrophy (F) in the LE, Linear Vertical OCT Scan Shows, in the Macular Region, on the Superior Part, an Optically Empty Zone, Comprised Between 2 Slight Hypereflective Layers, And, on the Inferior Part of the Lesion, the Sediment Material, Which Appears as a Dense Hypereflective Structure. Interestingly, OCT Scan Reveals the Abrupt Transition Between the Empty Area and the Vitelliform Material that Gravitated Inferiorly in the Subretinal Space, and the Neuro-Sensory Retina Maintaining Normal Thickness and Structure.

Fundus-related perimetry (MP-1 Micro Perimeter, Nidek Technologies, Padova, Italy) of the LE revealed an eccentric and unstable fixation located at the level of the superior border of the sediment material (Fig. 2). The electro-oculogram showed an abnormal light peak to dark trough ratio of 1.53 in the RE and 1.64 in the LE (normal 1.85). Genomic DNA was extracted from peripheral blood and mutation screening for the VMD2 gene, usually responsible for vitelliform macular dystrophy (Best’s disease) and rarely associated with adult-onset foveomacular vitelliform dystrophy (AFVD), was performed by direct DNA sequencing. No mutation for VMD2 gene was identified.

Figure 2. Fundus-Related Perimetry of the Left Eye (LE) Reveals an Eccentric and Unstable Fixation Located at the Level of the Superior Border of the Sediment Material. A and B Lines Illustrate 2 Horizontal Cross Sections of the Macular Area, from the Top to the Bottom. On the Superior Part, OCT Scan Demonstrates an Optically Empty Zone Comprised Between 2 Slight Hypereflective Layers. On the Inferior Part of the Lesion, the Sediment Material Appears as a Dense Hypereflective Structure. C Line Illustrates a Vertical Cross Section: the Transition Between the Empty Area and the Material Is Abrupt.

Based on these findings, the patient was diagnosed with possible AFVD, presenting the vitelliruptive/atrophic stage in the RE, and the pseudohypopion stage in the LE. Despite the negative VMD2 genetic testing and late age of onset, Best’s disease remains a possible alternate diagnosis.

Comment

AFVD is a clinically heterogeneous and pleomorphic disease.^1–3 Gass originally described AFVD as a bilateral disease with symmetrical, solitary, round or oval, slightly elevated, yellowish, subretinal lesions, one third to one disc diameter in size, often with a central pigmented spot.⁴ Most cases have a solitary lesion in the macula, others have multifocal vitelliform lesions,⁵ but always reported as less than one disc diameter in size. Our patient’s exceptionally large bilateral macular lesions (by far >1 disc diameter), therefore, represents either a previously unreported presentation for a patient with AFVD, or an elusive case of Best’s disease lacking definitive genetic evidence and presenting at a very late age of onset.