Bilateral consecutive choroidal neovascularization in Best vitelliform macular dystrophy.

Best vitelliform macular dystrophy (BVMD) is a slowly progressive macular disease caused by a pathogenic variant of the Bestrophin (BEST1) gene. Examination coupled with multimodal imaging and genetic testing are used to guide diagnosis and treatment. A 12-year-old girl was examined for decreased vision in the left eye and showed bilateral "egg-yolk"-like macular lesions with choroidal neovascularization (CNV) in the left eye. Six months later, she experienced decreased vision with appearance of CNV on optical coherence tomography angiography in the right eye. Injections of anti-vascular endothelial growth factor helped restore vision from 20/125 to 20/20 in the right eye with stabilization of her left eye (vision 20/40). Genetic testing revealed c.851A > G (p.Tyr284Cys), a heterozygous variant of the BEST1 gene. The same variant was found in her father, who was initially misdiagnosed with toxoplasmosis due to a peripheral retinal lesion in the left eye. This is the first report of bilateral consecutive CNV secondary to BVMD. Additionally, it highlights the likely pathogenic role of a novel variant of the BEST1 gene.

Cerebral aquaporin-4 expression is independent of seizures in tuberous sclerosis complex.

Astrocytes serve many functions in the human brain, many of which focus on maintenance of homeostasis. Astrocyte dysfunction in Tuberous Sclerosis Complex (TSC) has long been appreciated with activation of the mTORC1 signaling pathway resulting in gliosis and possibly contributing to the very frequent phenotype of epilepsy. We hypothesized that aberrant expression of the astrocyte protein aquaporin-4 (AQP4) may be present in TSC and contribute to disease pathology. Characterization of AQP4 expression in epileptic cortex from TSC patients demonstrated a diffuse increase in AQP4. To determine if this was due to exposure to seizures, we examined Aqp4 expression in mouse models of TSC in which Tsc1 or Tsc2 inactivation was targeted to astrocytes or glial progenitors, respectively. Loss of either Tsc1 or Tsc2 from astrocytes resulted in a marked increase in Aqp4 expression which was sensitive to mTORC1 inhibition with rapamycin. Our findings in both TSC epileptogenic cortex and in a variety of astrocyte culture models demonstrate for the first time that AQP4 expression is dysregulated in TSC. The extent to which AQP4 contributes to epilepsy in TSC is not known, though the similarities in AQP4 expression between TSC and temporal lobe epilepsy supports further studies targeting AQP4 in TSC.