Bietti Crystalline Dystrophy
2018 ICD-10 Code: H35.53: Other dystrophies primarily affecting the sensory retina
Bietti’s Crystalline Dystrophy (BCD), is a rare autosomal recessive ocular disease that involves yellow-white crystalline lipid deposits in the retina and sometimes cornea, degeneration of the retinal pigment epithelium (RPE), and sclerosis of the choroidal vessels. Progression of the disease ultimately results in reduced visual acuity, night blindness, visual field loss, and impaired color vision. Onset of the disease can occur from early teenage years to third decade of life, but can also occur beyond the third decade. As the disease progresses, decreases in peripheral acuity, central acuity, or both ultimately result in legal blindness in most patients.
BCD was first described by Italian Ophthalmologist Dr. G.B. Bietti in 1937. There have been around 100 reported cases documented in the literature (OMIM 210370).
The mode of inheritance for BCD is autosomal recessive. BCD involves the pathologic variant of the CYP4V2 gene. Carrier testing should be considered for at- risk relatives.
Asians, especially those of Chinese ethnicities, have been found to have a relatively higher incidence of BCD.
The pathophysiology of BCD is still unclear. However, biallelic pathologic variations in CYP4V2 have been implicated in the disease. CYP4V2 enzyme has been shown to play a role in fatty acid and steroid metabolism. Dysfunctional lipid metabolism mayresult in complex lipid retinal or corneal deposits in crystalline form. In patients with BCD, lipid inclusions are found systemically, suggesting possible dysfunctional lipid metabolism elsewhere in the body as well.
Diagnosis of BCD is based on ophthalmic evaluation of numerous small glistening yellow-white retinal crystalline deposits in the retinal with or without crystalline deposits in the cornea, retinal pigment epithelium (RPE) atrophy, pigment clumping, and choroidal vessels sclerosis. The corneal crystals are usually isolated in the subepithelial and anterior stroma of the peripheral cornea (25-33%). Reflective white- yellow deposits have also been described in the crystalline lens in patients with BCD.
CYP4V2 is only moderately expressed in the cornea and the conjunctiva; thus, ocular surface findings are not required for diagnosis. Diagnostic tools include electroretinography for evaluating degree of rod and cone dysfunction, Humphrey visual field (HVF) testing for visual field deficits, spectral domain ocular coherence tomography (OCT) for identifying reflective dots, in vivo confocal microscopy, and specular microscopy of the cornea.
If clinical features are equivocal, the disease can be confirmed by the identification of pathologic variants in CYP4V2 by molecular genetic testing.
Typically patients with BCD begin noticing symptoms between the second and third decades of life. Patients experience a progressive reduction in visual acuity, nyctalopia, and visual field loss. Occasionally, color vision may also be impaired. Visual deficits can progress at different rates in each eye, and the severity and rate of progression varies widely among affected individuals. Over time patients, particularly in the fifth or sixth decade, can become legally blind.
The differential diagnosis for BCD includes other diseases that involve crystalline deposits in the retina such as:
- Retinitis Pigmentosa
- Primary hyperoxaluria type 1 and type 2
- Infectious Crystalline Keratopathy
- Sjogren-Larsson Syndrome
- Drug Toxicity from agents such as tamoxifen, talc retinopathy, methoxyflurane, and canthaxanthin
Currently, there are no evidence based surgical treatments or medical treatment specific to BCD available in the existing literature.
Standard of care for BCD patients include follow-up with an ophthalmologist for a yearly exam to monitor disease and to watch for macular hole, edema, and atrophy and choroidal neovascularization (CNV). Anti- vascular endothelial growth factor (VEGF) injection has been described favorably in the treatment of BCD complicated by CNV.
Standard of care for BCD patients with vision impairment includes referral to low vision specialists or state services for the blind.
Genetic testing is available for those that have immediate family diagnosed with BCD in order to identify abnormal CYP4V2 genes. Genetic counseling is offered for those with diagnosed BCD or BCD carriers for family planning, whereas prenatal testing for BCD is possible but controversial.
There is no known cure for this disease. As a result, loss of peripheral visual field and visual acuity can result in legal blindness in patients with the disease.
Bietti’s Crystalline Dystrophy (BCD) is a rare corneo-retinal dystrophy that is characterized by deposition of yellow-white crystals in the retina and sometimes the cornea, degeneration of the retina, and sclerosis of the choroidal vessels that results in the progressive loss of peripheral visual acuity and night blindness. There is currently no specific treatment for BCD. However, early diagnosis and referral to low-vision specialists can help with management of patients with this disease.
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