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Bietti crystalline dystrophy (BCD) is an ultra-rare orphan disorder that can lead to blindness. Because of the variable rates of progression of the disease, it is necessary to identify suitable outcome measurements for tracking progression in BCD. A retrospective analysis of patients with a clinical and genetic diagnosis of BCD was conducted. Four measurements of spectral domain-optical coherence tomography were compared to patients' best corrected visual acuity. We observed that patients with higher measurements of foveolar thickness, choroidal thickness in the foveolar region, ellipsoid zone band length and the outer nuclear layer + area, had on average better visual acuity. Future studies are needed to validate the structural–functional correlations we observed in BCD and to propose a sensitive and clinically meaningful outcome measurement for tracking this rare, variable disease. [ABSTRACT FROM AUTHOR]

Background: To evaluate the long-term progression of autosomal recessive retinitis pigmentosa (RP) due to mutations in KIZ using multimodal imaging and a quantitative analytical approach. Methods: Whole exome sequencing (WES) and targeted capture sequencing were used to identify mutation. Fundus photography, short-wavelength autofluorescence (SW-AF), spectral-domain optical coherence tomography (SD-OCT) imaging, and electroretinography (ERG) were analyzed. Serial measurements of peripheral retinal pigment epithelium (RPE) atrophy area with SW-AF, as well as the ellipsoid zone (EZ) width using SD-OCT were performed. Results: Two homozygous variants in KIZ—a c.226C>T mutation as well as a previously unreported c.119_122delAACT mutation—were identified in four unrelated patients. Fundus examination and ERG revealed classic rod-cone dysfunction, and SD-OCT demonstrated outer retinal atrophy with centrally preserved EZ line. SW-AF imaging revealed hyperautofluorescent rings with surrounding parafoveal, mid-peripheral and widespread loss of autofluorescence. The RPE atrophy area increased annually by 4.9%. Mean annual exponential rates of decline for KIZ patients were 8.5% for visual acuity and 15.9% for 30 Hz Flicker amplitude. The average annual reduction distance of the EZ distance was 66.5 μm per year. Conclusions: RPE atrophy progresses along with a loss of photoreceptors, and parafoveal RPE hypoautofluorescence is commonly seen in KIZ-associated RP patients. KIZ-associated RP is an early-onset severe rod-cone dystrophy. [ABSTRACT FROM AUTHOR]

Background: Mutations in the Kelch-like protein 7 (KLHL7) represent a recently described and, to date, poorly characterized etiology of inherited retinal dystrophy. Dominant mutations in KLHL7 are a cause of isolated, non-syndromic retinitis pigmentosa (RP). In contrast, recessive loss-of-function mutations are known to cause Crisponi or Bohring-Opitz like cold induced sweating syndrome-3 (BOS-3). In this study, the phenotype and progression of five unrelated patients with KLHL7 mediated autosomal dominant RP (adRP) are characterized. Clinical evaluation of these patients involved a complete ophthalmic exam, full-field electroretinography (ffERG), and imaging, including fundus photography, spectral domain optical coherence tomography (SD-OCT), short wavelength fundus autofluorescence (SW-AF), and near-infrared fundus autofluorescence (NIR-AF). Molecular diagnoses were performed using whole-exome sequencing or gene panel testing. Disease progression was monitored in three patients with available data for a mean follow up time of 4.5 ± 2.9 years. Protein modeling was performed for all variants found in this study in addition to those documented in the literature for recessive loss-of-function alleles causing Crisponi or Bohring-Opitz like cold-induced sweating syndrome.Results: Genetic testing in three patients identified two novel variants within the 3-box motif of the BACK domain: c.472 T > C:p.(Cys158Arg) and c.433A > T:p.(Asn145Tyr). Clinical imaging demonstrated hyperautofluorescent ring formation on both SW-AF and NIR-AF in three patients, with diffuse peripheral and peripapillary atrophy seen in all but one case. SD-OCT demonstrated a phenotypic spectrum, from parafoveal atrophy of the outer retina with foveal sparing to widespread retinal thinning and loss of photoreceptors. Incidence of cystoid macular edema was high with four of five patients affected. Protein modeling of dominant alleles versus recessive loss-of-function alleles showed dominant alleles localized to the BTB and BACK domains while recessive alleles were found in the Kelch domain.Conclusions: We report the phenotype in five patients with KLHL7 mediated adRP, two novel coding variants, and imaging biomarkers using SW-AF and NIR-AF. These findings may influence future gene-based therapies for adRP and pave the way for mechanistic studies that elucidate the pathogenesis of KLHL7-mediated RP. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is a category of inherited retinal dystrophies that is best prognosticated using electroretinography (ERG). In this retrospective cohort study of 25 patients with RP, we evaluated the correlation between 30 Hz flicker ERG and structural parameters in the retina. Internationally standardized 30 Hz flicker ERG recordings, short-wavelength autofluorescence (SW-AF), and spectral domain–optical coherence tomography (SD-OCT) were acquired at two visits at least one year apart. Vertical and horizontal hyperautofluorescent ring diameter measurements with SW-AF, as well as ellipsoid zone (EZ) line width measurements with SD-OCT, were used as structural parameters of disease progression. The 30 Hz flicker ERG amplitude decreased by 2.2 ± 0.8 µV/year (p = 0.011), while implicit times remained unchanged. For SD-OCT, the EZ line decreased by 204.1 ± 34.7 µm/year (p < 0.001). Horizontal and vertical hyperautofluorescent ring diameters decreased by 161.9 ± 25.6 µm/year and 146.9 ± 34.6 µm/year, respectively (p = 0.001), with SW-AF. A correlation was found between the progression rates of the 30 Hz flicker amplitude recorded with Burian–Allen electrodes and both the horizontal ring diameter (p = 0.020) and EZ line (p = 0.044). SW-AF and SD-OCT, two readily available imaging techniques, may be used to prognosticate disease progression because of the reliability of their measurements and correlation with functional outcome. [ABSTRACT FROM AUTHOR]