Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization

ABSTRACT

Purpose: 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).

Methods: 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).

Results: 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).

Conclusion: 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.

KEYWORDS:

• Bietti crystalline dystrophy
• CNV
• CYP4V2
• OCT
• RPE

Acknowledgments

Thanks are due to Melissa Eihborn, Sonia Zhu, Jessica Barr, and Denise Pearson for their critical help.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

This study was supported by grants from the National Institutes of Health (NEI-K12EY015398-10), Research to Prevent Blindness, Foundation Fighting Blindness, Hope for Vision, Macula Vision Research, the Paul and Evanina Bell Mackall Foundation Trust, The Pennsylvania Lions Sight Conservation and Research Foundation. BPL is a Senior Clinical Investigator of the Research Foundation – Flanders (Belgium) (FWO), and is further supported by FWO Flanders grant OZP 3G004306.

Additional information

Funding

This study was supported by grants from the National Institutes of Health (NEI-K12EY015398-10), Research to Prevent Blindness, Foundation Fighting Blindness, Hope for Vision, Macula Vision Research, the Paul and Evanina Bell Mackall Foundation Trust, The Pennsylvania Lions Sight Conservation and Research Foundation. BPL is a Senior Clinical Investigator of the Research Foundation – Flanders (Belgium) (FWO), and is further supported by FWO Flanders grant OZP 3G004306.