A novel duplication of PRMD13 causes North Carolina macular dystrophy: overexpression of PRDM13 orthologue in drosophila eye reproduces the human phenotype.

In this study, we report a novel duplication causing North Carolina macular dystrophy (NCMD) identified applying whole genome sequencing performed on eight affected members of two presumed unrelated families mapping to the MCDR1 locus. In our families, the NCMD phenotype was associated with a 98.4 kb tandem duplication encompassing the entire CCNC and PRDM13 genes and a common DNase 1 hypersensitivity site. To study the impact of PRDM13 or CCNC dysregulation, we used the Drosophila eye development as a model. Knock-down and overexpression of CycC and CG13296, Drosophila orthologues of CCNC and PRDM13, respectively, were induced separately during eye development. In flies, eye development was not affected, while knocking down either CycC or CG13296 mutant models. Overexpression of CycC also had no effect. Strikingly, overexpression of CG13296 in Drosophila leads to a severe loss of the imaginal eye-antennal disc. This study demonstrated for the first time in an animal model that overexpression of PRDM13 alone causes a severe abnormal retinal development. It is noteworthy that mutations associated with this autosomal dominant foveal developmental disorder are frequently duplications always including an entire copy of PRDM13, or variants in one DNase 1 hypersensitivity site at this locus.

Comparison between multifocal ERG and C-Scan SD-OCT ("en face" OCT) in patients with a suspicion of antimalarial retinal toxicity: preliminary results.

PURPOSE: Pericentral visual field changes and disruption of the ellipsoid layer on spectral domain optical coherence tomography (SD-OCT) are the main features of antimalarial retinal toxicity. C-Scan OCT or "en face" enables a topographic frontal view of the changes observed within the different retinal layers in particular the ellipsoid layer. The aim of this prospective study was to compare multifocal ERG (mfERG) responses with the results of C-Scan OCT ("en face" OCT) in patients with abnormal visual field and to analyze relationships between the structural and functional abnormalities. METHODS: In 354 consecutive patients screened for antimalarial toxicity between January 1, 2014 and December 31, 2016, central visual field, mfERG recording, C-Scan OCT and short-wavelength fundus autofluorescent imaging were performed. RESULTS: Among the 17/354 patients with abnormal central visual field results, all presented with abnormalities on the mfERG at least in one eye. In 16/33 eyes, there was a good concordance between focal loss of the mfERG response and the disruption of the ellipsoid layer on C-Scan OCT. In one eye with characteristic changes in the ellipsoid layer on the C-Scan OCT, the mfERG was normal, whereas in three eyes the mfERG was abnormal in eyes with a normal C-Scan OCT. CONCLUSIONS: The contribution of the C-Scan OCT changes remains difficult to establish as there is no strict concordance with the local ERG responses. Although C-Scan OCT technology provides a new approach in analyzing focal abnormalities in the photoreceptor-retinal pigment epithelium interface, the sensitivity of this method compared with mfERG and other tests (central visual field, B-Scan OCT) needs to be evaluated. This study is still ongoing on a larger cohort.

Five-Year Trends in Multifocal Electroretinogram for Patients With Birdshot Chorioretinopathy.

PURPOSE: The aim of this study is to investigate temporal trends in multifocal ERG (mfERG) parameters and analyze their relationships with anatomic and functional markers in patients with birdshot chorioretinopathy (BSCR). DESIGN: Prospective observational case series. METHODS: Sixteen BSCR patients were include and underwent 2 standardized follow-up (FU) visits within 5 years following a baseline examination, including mfERG, visual acuity (VA), visual field (VF), Lanthony desaturated panel D-15 test for color vision, quality of life (QoL), fluorescein and indocyanine green angiography, and optical coherence tomography (OCT). RESULTS: A significant trend toward a decrease in absolute N1 amplitude values was observed over the follow-up period (P < .001) while N1 implicit time remained unchanged. In contrast, P1 amplitude decreased (P < .001) and P1 implicit time increased (P < .001) over the same period. No significant temporal change was found for VA, color vision score, foveal threshold, mean deviation of VF, and QoL. After adjusting for time to FU, increasing N1 and P1 IT were both associated with decreasing values of logMAR, foveal threshold, and QoL and with increasing color vision score and mean deviation of VF. A significant relationship was observed between decreasing P1 amplitude values and increasing mean deviation of VF. Lower absolute values of N1 amplitude were associated with venous vasculitis, whereas lower P1 amplitude values correlated with alteration of the outer retina in OCT. CONCLUSIONS: Progressive deterioration in mfERG during a 5-year period is detected in BSCR, whereas classical functional test results were unchanged. This study suggests a better sensitivity of mfERG in monitoring the retinal function of BSCR patients.