Functional and Anatomic Changes in Bilateral Choroidal Neovascularization Associated with Vitelliform Macular Dystrophy After Intravitreal Bevacizumab

Introduction

Vitelliform macular dystrophy, also known as Best's disease, is a form of progressive macular dystrophy. It is an autosomal-dominant disease caused by a mutation in the gene localized on chromosome 11 that encodes bestrophin, a Ca²⁺-sensitive Cl⁻ channel protein located on the basolateral membrane of retinal pigment epithelial cells.^1,2 Best's disease has a highly variable phenotypic expression. Choroidal neovascularization (CNV) is a rare complication of Best's disease. ³ Here, we report the case of a young man affected by CNV associated with Best's disease in whom bilateral intravitreal injection of bevacizumab resulted in a progressive improvement of visual acuity, which reached 10/10 1 month after treatment.

Case Report

A 17-year-old white male presented for a routine ocular examination because of reduced visual acuity in both eyes, and was found to be affected by bilateral Best's disease. His best corrected visual acuity was 5/10 in the right eye and 6/10 in the left eye. Biomicroscopy of the anterior segment was unremarkable in both eyes. Fundus ophthalmoscopic examination showed a hypopigmented macula with an egg yolk-like appearance, subretinal hemorrhage, and subretinal fluid in both eyes (Fig. 1A, B, G, H). These findings were suggestive of CNV. Fluorescein angiography was performed and revealed blocking hypofluorescence resulting from subretinal hemorrhage, and early hyperfluorescence with intense late leakage thereby confirming CNV (Fig. 1C, I). These findings were confirmed by indocyanine green angiography late frame showing focal hyperfluorescence corresponding to the CNV (Fig. 1D, J). Frequency domain-optical coherence tomography (FD-OCT) showed a moderately reflective mass protruding from the retinal pigment epithelium (RPE), corresponding to the CNV, associated with neurosensory retina elevation in the macular area and the presence of intraretinal fluid (Fig. 1E, K). Microperimetry showed an eccentric, unstable retinal fixation in the right eye (12% of the fixation points were inside the 2° diameter circle and 45% of the fixation points were inside the 4° diameter circle), and an eccentric, relatively unstable retinal fixation in the left eye (43% of the fixation points were inside the 2° diameter circle and 82% of the fixation points were inside the 4° diameter circle). Microperimetry also showed a reduction of the retinal sensitivity threshold (sensitivity average 13.5 dB in the right eye and 11.0 dB in the left eye) in the paramacular region (Fig. 1F, L). Electro-oculographic findings were consistent with the diagnosis of Best's disease.

OPEN IN VIEWER

FIG. 1.

Baseline evaluation in both eyes: (A, B, G, H) Retinography showing a hypopigmented macula with an egg yolk-like appearance and subretinal fluid. (C, I) Fluorescein angiography reveals classic subfoveal choroidal neovascularization (CNV). (D, J) Indocyanine green angiography confirmed the diagnosis of CNV. (E, K) Frequency domain-optical coherence tomography showing subfoveal tissue proliferation, subretinal fluid, and intraretinal edema. (F, L) Microperimetry showing eccentric, unstable retinal fixation, and reduction of retinal sensitivity.

After discussing treatment options, the parents of the patient opted for intravitreal injection of bevacizumab. Thus, after obtaining informed consent, we injected 1.0 mg bevacizumab (0.05-mL solution prepared from Avastin 100 mg/4 mL; Avastin™; Genentech, Inc., South San Francisco, CA) via the pars plana first in the right eye, and 1 month later in the left eye. We administered 1.0 mg bevacizumab because this dosage resulted in regression of a CNV in an eye related to Best's disease in a 13-year-old child. ⁴ At 4 weeks follow-up, visual acuity improved to 10/10 in both eyes. FD-OCT examination showed a reduction of the serous retinal detachment and as a result of CNV regression. Eighteen months after the bevacizumab injection, visual acuity was 10/10 in both eyes, and fundus biomicroscopy revealed resolution of the subretinal hemorrhage (Fig. 2A, B, G, H). Fluorescein angiography and indocyanine green angiography revealed total regression of the CNV (Fig. 2C, D, I, J). The FD-OCT shows the absence of macular edema and neurosensory retinal elevation in the macular area and an optically empty zone between two moderately hyper-reflective layers, consequent to partial resorption of the vitelliform material (Fig. 2E, K).

OPEN IN VIEWER

FIG. 2.

Post-treatment evaluation in both eyes (18 months): (A–D, G, H, I, J) Retinography, fluorescein angiography, and indocyanine green angiography revealed total regression of choroidal neovascularization. (E, K) Frequency domain-optical coherence tomography showing the absence of neurosensory retinal elevation in the macular area and an optically empty zone between two moderately hyper-reflective layers, consequent to partial resorption of the vitelliform material (arrow). (F, L) Microperimetry showing stable fixation with reduction of eccentricity and improvement of retinal sensitivity.

Microperimetry showed stable fixation with a reduction of eccentricity (96% inside the 2° diameter circle and 100% inside the 4° diameter circle in the right eye; 99% inside the 2° diameter circle and 100% inside the 4° diameter circle in the left eye) and an improvement of retinal sensitivity (average sensitivity 13.8 dB in the right eye and 18.6 dB in the left eye) (Fig. 2F, L). No complications of the intravitreal injection of bevacizumab occurred during follow-up (18 months).

Discussion

Vitelliform macular dystrophy was identified by Friedrich Best in 1905, who described the various stages of the disease in eight related individuals. ⁵ It is a clinically heterogeneous and pleomorphic disease. ⁶ Usually, a gradual loss of visual acuity occurs over a period of years.

Five stages have been described, based on the findings of fundus examination: the previtelliform stage (normal macula or subtle alteration of the RPE), the vitelliform stage (a well-circumscribed lesion resembling an egg yolk, 0.5–2 disc diameters in size), the pseudohypopyon stage (yellow material accumulated inferiorly), the vitelliruptive stage (partial resorption of the yellow material), and the atrophic stage. Extensive white-yellowish fibrosis may also occur, possibly due to an increase of vitelliform macular dystrophy. This cicatricial aspect can appear with or without the occurrence of CNV. ³ The lesions appear to have two distinct fluidic components in the subretinal space—clear fluid and yellowish material. Morphologically, the yellow vitelliform material accumulates within the RPE and the subretinal space, mainly in the macular area. Histopathologic examination shows extensive deposition of lipofuscin in the RPE and accumulation of fibrillar material under the RPE and in the choroid.^7–9 CNV is a complication of Best's disease.

As suggested by Leu et al., ⁴ because bevacizumab is an antivascular endothelial growth factor (VEGF) agent, and VEGF is implicated in the pathogenesis of CNV secondary to vitelliform dystrophy of the fovea, this could account for bevacizumab's efficacy in our patient.

To our knowledge, our report is the first to show that a single intravitreal injection of bevacizumab can induce morphologic (investigated with FA, ICG, and FD-OCT) and functional improvement (studied with microperimetry) in a young man suffering from bilateral CNV secondary to Best's disease in a long-term follow-up (18 months).