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Kent W Small, Fadi Shaya, Nitin Udar, Leslie Small, Edwin M Stone; Multimodal imaging including OCT-A and functional testing of North Carolina Macular Dystrophy (NCMD) provides new insights into the developmental nature of NCMD and the development of the human macula. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3161.
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© ARVO (1962-2015); The Authors (2016-present)
To describe multimodal imaging and corresponding functional studies in a new family with North Carolina Macular Dystrophy (NCMD/MCDR1) incorporating OCT angiography (OCT-A) for the first time to our knowledge.
A descriptive, retrospective study of a family with NCMD. Diagnostic multimodal imaging and functional testing of the retina included color fundus photographs, fundus auto fluorescence, fluorescein angiography (IVFA), spectral domain OCT, OCT angiography, multifocal ERG, full field ERG, and microperimetry. DNA sequencing was performed using Sanger sequencing. IRB approval was obtained.
Three subjects, representing 3 generations of a single family each demonstrating a different grade of NCMD, underwent clinical and genetic testing. Multimodal imaging helped to demonstrate the developmental nature of the retinal and choroidal lesions in each and the extent of visual function that was suggestive of the stage of development that is affected my methylation at the 6q16 locus. Genetic testing demonstrated the V2 point mutation (French/German mutation) in the DNASE 1 hypersensitivity binding site on chromosome 6q16 causing overexpression of the retinal transcription factor PRDM13. The oldest family member has many similarities to foveal hypoplasia/foveal plana.
NCMD has great phenotypic variability, which can only be appreciated by examining multiple family members. This is the first report to our knowledge showing a correlation of functional studies with multimodal imaging including OCT-A. All layers of the retina and choroid demonstrate mal-development and varying degrees of malfunction. Although PRDM13 is over expressed in the amacrine cells, we have yet to demonstrate an abnormality specific to this cellular layer. The retinal vasculature seems surprisingly well preserved/intact by OCT-A when compared to the IVFA. OCT-A suggests foveal hypoplasia to be a phenocopy of grade 1 NCMD. OCT-A does reveal vascular abnormalities not found with standard IVFA. We propose that the grade of severity is determined by the embryonic stage that methylation occurs at the DNASE1 hypersensitivity binding site which regulates the expression/overexpression of the retinal transcription factor PRDM13. We propose that there is a similar control of expression at the MCDR3/IRX1 site.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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