title: Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization.
abstract: To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin®; Genentech/Roche).
  
  
  
  A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA).
  
  
  
  Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in the peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25).
  
  
  
  crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting.
authors.affiliation: a Scheie Eye Institute and Perelman Center for Advanced Medicine, University of Pennsylvania , Philadelphia , Pennsylvania , USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Fuerst
authors.affiliation: a Scheie Eye Institute and Perelman Center for Advanced Medicine, University of Pennsylvania , Philadelphia , Pennsylvania , USA.
authors.forename: Leona
authors.initials: L
authors.lastname: Serrano
authors.affiliation: a Scheie Eye Institute and Perelman Center for Advanced Medicine, University of Pennsylvania , Philadelphia , Pennsylvania , USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Han
authors.affiliation: a Scheie Eye Institute and Perelman Center for Advanced Medicine, University of Pennsylvania , Philadelphia , Pennsylvania , USA.
authors.forename: Jessica I W
authors.initials: JI
authors.lastname: Morgan
authors.affiliation: a Scheie Eye Institute and Perelman Center for Advanced Medicine, University of Pennsylvania , Philadelphia , Pennsylvania , USA.|b Division of Ophthalmology, Children's Hospital of Philadelphia, and Department of Ophthalmology , University of Pennsylvania , Philadelphia , Pennsylvania , USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Maguire
authors.affiliation: b Division of Ophthalmology, Children's Hospital of Philadelphia, and Department of Ophthalmology , University of Pennsylvania , Philadelphia , Pennsylvania , USA.|c Center for Cellular & Molecular Therapeutics, Children's Hospital of Philadelphia , Philadelphia , Pennsylvania , USA.|d Department of Ophthalmology and the Center for Medical Genetics, Ghent University and Ghent University Hospital , Ghent , Belgium.
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.affiliation: a Scheie Eye Institute and Perelman Center for Advanced Medicine, University of Pennsylvania , Philadelphia , Pennsylvania , USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: a Scheie Eye Institute and Perelman Center for Advanced Medicine, University of Pennsylvania , Philadelphia , Pennsylvania , USA.|b Division of Ophthalmology, Children's Hospital of Philadelphia, and Department of Ophthalmology , University of Pennsylvania , Philadelphia , Pennsylvania , USA.
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D020256:Choroidal Neovascularization / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D000072470:Cytochrome P450 Family 4 / Q000235:genetics*; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D009154:Mutation; D010641:Phenotype; D012164:Retinal Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D055214:Retinal Photoreceptor Cell Outer Segment / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4
keywords: Bietti crystalline dystrophy; CNV; CYP4V2; OCT; RPE