Autosomal Dominant Vitreoretinochoroidopathy

A rare, genetic, vitreous-retinal disease characterized by ocular developmental anomalies such as microcornea, a shallow anterior chamber, glaucoma and cataract. Abnormal chorioretinal pigmentation is present, usually lying between the vortex veins and the ora serrata for 360 degrees.

Epidemiology

At least 3 pedigrees have been reported to have ADVIRC.

Clinical description

Age of onset is variable, but can occur in childhood. ADVIRC is associated with developmental ocular anomalies including microphthalmos/nanophthalmos, microcornea, hypermetropia/high myopia, shallow anterior chamber, angle closure glaucoma, iris dysgenesis, abnormal pupillary ruff, microspherophakia with mild lens opacities (congenital or early-onset posterior/subcapsular cataract), disc gliosis and optic nerve dysplasia. Some patients may experience vision loss. Color vision is generally normal. Discrete rotatory nystagmus may be present. Retinal edema due to vascular incompetence may also be observed. ADVIRC is characterized by a peripheral retinal circumferential hyperpigmented band, punctuate white retinal opacities, fibrillar condensation of the vitreous, vascular abnormalities and neovascularisation. There are no identifiable systemic or skeletal abnormalities.

Etiology

ADVIRC is caused by mutations in BEST1 (11q12) (Val86Met, Val235Ala and Tyr236Cys), which encodes bestrophin-1 (expressed specifically in the retinal pigment epithelium (RPE)) forming a calcium activated chloride channel involved in regulation of voltage-dependent calcium channels. These mutations may alter normal splicing of BEST1 and result in in-frame alteration of bestrophin-1. However, functional consequences of such in-frame protein alterations remain undefined.

Diagnostic methods

Diagnosis of ADVIRC is based on low normal to non-recordable amplitudes of cones and rods on full-field electroretinogram (generalized rod and cone dysfunction), an abnormal electro-oculogram (EOG) (the light rise of EOG is decreased giving a reduced Arden ratio), and normal macular thickness on optical coherence tomography. Funduscopy typically reveals a concentric band of hyperpigmentation in the extreme periphery of one quadrant, with well-defined posterior demarcation, midperipheral chorioretinal atrophy and optic nerve dysplasia. Fundus autofluorescence imaging may show a normal autofluorescence pattern. Goldmann perimetry is often initially normal; however visual field tends to constrict mildly with age. Diagnosis is confirmed by genetic screening of BEST1.

Differential diagnosis

MRCS syndrome (see this term) is generally more severe than ADVIRC. However, both of these BEST1-related conditions show retinal pigmentary abnormalities, retinal dystrophy, microcornea, and early-onset cataract, conditions that overlap and likely form a continuum. Differential diagnosis also includes Best vitelliform macular dystrophy (BVMD), adult-onset foveomacular vitelliform dystrophy and autosomal recessive bestrophinopathy (see these terms).

Genetic counseling

Transmission is autosomal dominant and genetic counseling is possible.

Management and treatment

Management is mainly symptomatic. When choroidal neovascularization occurs, treatment may require laser photocoagulation or intravitreal delivery of anti-vascular endothelial growth factor agents such as bevacizumab and ranibizumab. Cystoid macular edema can be treated with conventional carbonic anhydrase inhibitors (CAIs) either systemically or topically. If presentation is complicated by glaucoma, conventional treatment may require topical agents to lower intraocular pressure, such as CAIs. Laser iridotomy may be advocated if angle closure glaucoma is a risk. Some cases may require additional surgical intervention.

Prognosis

Most patients retain a fairly good visual acuity throughout life, although visual acuity may decrease considerably due to macular edema, chorioretinal atrophy, or rarely, retinal detachment and vitreous hemorrhage.