Retinopathies with Metabolic Disorders

Hereditary dystrophies of the posterior segment are the common name for a group of syndromic diseases in which the retina is affected. Until recently, the information available on these diseases has been limited and a wide range of clinical findings was reported. However, recent advances in genetics research suggest a better outlook. Here we review the recent advances in the following: Pseudoxanthoma Elasticum, Refsum Disease, Bietti Crystalline Dystrophy, Alport’s Syndrome

Observation of the characteristics of the natural course of Bietti crystalline dystrophy by fundus fluorescein angiography

Background Bietti crystalline dystrophy (BCD) is an autosomal recessive genetic disorder that causes progressive vision loss. Here, 12 patients were followed up for 1–5 years with fundus fluorescein angiography (FFA) to observe BCD disease progression. Methods FFA images were collected for 12 patients with BCD who visited our clinic twice or more over a 5-year period. Peripheral venous blood was collected to identify the pathogenic gene related to the clinical phenotype. Results We observed two types in FFA images of patients with BCD. Type 1 showed retinal pigment epithelium (RPE) atrophy in the macular area, followed by choriocapillaris atrophy and the subsequent appearance of RPE atrophy appeared at the peripheral retina. Type 2 showed RPE atrophy at the posterior pole and peripheral retina, followed by choriocapillaris atrophy around the macula and along the superior and inferior vascular arcades and the nasal side of the optic disc. The posterior and peripheral lesions of both type 1 and type 2 BCD subsequently extended to the mid-periphery; finally, all the RPEs and choriocapillaris atrophied, exposing the choroid great vessels, but type 2 macular RPE atrophy could last longer. Conclusions The characterization of two different types of BCD development provides a better understanding of the phenotype and the progression of the disease for a precise prognosis and prediction of pathogenesis.

Expanding the Phenotypic and Genotypic Spectrum of Bietti Crystalline Dystrophy

The rare form of retinal dystrophy, Bietti crystalline dystrophy, is associated with variations in CYP4V2, a member of the cytochrome P450 family. This study reports patients affected by typical and atypical Bietti crystalline dystrophy, expanding the spectrum of this disease. This is an observational case series of patients with a clinical and molecular diagnosis of Bietti crystalline dystrophy that underwent multimodal imaging. Four unrelated patients are described with two known variants, c.802-8_810del17insGC and c.518T > G (p.Leu173Trp), and one novel missense variant, c.1169G > T (p.Arg390Leu). The patient with the novel homozygous variant had the most severe phenotype resulting in macular hole formation and retinal detachment in both eyes. To the best of our knowledge, there is no association of these features with Bietti crystalline dystrophy. Patient 1 was the youngest patient and had the mildest phenotype with crystals in the retina without chorioretinal atrophy and visual complaints. Patients 2 and 3 presented with fewer crystals and chorioretinal atrophy. These three patients presented a classic phenotype. The fourth patient presented with an atypical and severe phenotype. This study reveals a new genotype and new phenotype associated with this disorder.

Observation of Natural Course Characteristics of Bietti Crystalline Dystrophy by Fundus Fluorescein Angiography

Background: Bietti crystalline dystrophy (BCD) is an autosomal recessive genetic disorder that causes progressive vision loss. Here, 12 patients were followed up for 1–5 years with fundus fluorescein angiography (FFA) to clarify BCD disease development and its classification. Methods: FFA images were collected for 12 patients with BCD who visited our clinic twice or more in 5 years. Peripheral venous blood was collected to identify a pathogenic gene related to the clinical phenotype.Results: FFA images identified two BCD types. Type 1 showed retinal pigment epithelium (RPE) atrophy at the macular area, followed by choriocapillaris atrophy, then RPE atrophy appeared at the peripheral retina. Type 2 showed RPE atrophy at the posterior pole and peripheral retina, followed by choriocapillaris atrophy around the macula and along the superior and inferior vascular arcades and optic disc nasal side. Then the posterior and peripheral lesions of type 1 and type 2 were extended to the mid-periphery; at last, all the RPE and choriocapillars atrophied, exposed choroid great vessels, but the macular RPE atrophy of type 2 can existed for a long time. Conclusions: The two different BCD development types provide a better understanding of the phenotype and the progression of the disease for a precise prognosis and prediction of pathogenesis.

Predicting visual acuity in Bietti crystalline dystrophy: evaluation of image parameters

Background To analyze multiple imaging modalities in patients with Bietti crystalline dystrophy (BCD) and to investigate which factors from these modalities are associated with best corrected visual acuity (BCVA). Methods In this retrospective study, 40 eyes from 22 patients with BCD were included and were separated into group 1 (BCVA ≤20/200) and group 2 (BCVA > 20/200). Data including BCVA and characteristic findings from near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF), and spectral domain-optic coherence tomography (SD-OCT) were analyzed and compared. The outcome measures of multimodal imaging were evaluated for correlation with BCVA. Results NIR is a good diagnostic tool for detecting either crystalline or sclerotic vessels in BCD. Patients in group 1 tended to have a thinner choroid (P = 0.047) with ellipsoid zone (EZ) disruption (P = 0.011). Calculation of the area under the curve indicated that EZ disruption detected on SD-OCT could be a good predictor of legal blindness in BCD. Conclusion For the diagnosis of BCD, NIR could be a good diagnostic tool. Of the studied imaging modalities, we found that EZ disruption at the fovea were strongly associated with legal blindness, which could be easily assessed by SD-OCT.