Multimodal Imaging and Functional Testing in a North Carolina Macular Disease Family: Toxoplasmosis, Fovea Plana, and Torpedo Maculopathy Are Phenocopies

Abstract

Purpose: To describe multimodal imaging and corresponding functional studies in a newly found family with North Carolina macular dystrophy (NCMD). To our knowledge, this is an original report using OCT angiography to evaluate persons with NCMD.

Design: A descriptive, retrospective study of a family with NCMD.

Participants: A total of 3 participants, representing 3 generations of a single family, each demonstrating a different grade of NCMD, underwent clinical and genetic testing.

Methods: Diagnostic multimodal imaging and functional testing of the retina included color fundus photography, fundus autofluorescence, intravenous fluorescein angiography, spectral-domain OCT and OCT angiography, multifocal electroretinography, full-field electroretinography, and microperimetry. DNA sequencing was performed using Sanger sequencing techniques.

Main outcome measures: Spectral-domain OCT images, fundus photographs, fundus autofluorescence images, fluorescein angiograms, OCT angiograms, multifocal electroretinography images, full-field electroretinography images, and microperimetry maps. Sanger sequencing was performed for molecular diagnosis.

Results: Multimodal imaging helped to demonstrate the nature of the retinal and choroidal lesions in each participant and the extent of visual function. Genetic testing demonstrated the variant 2 point mutation (chromosome 6: 99593111) in the deoxyribonuclease 1 hypersensitivity binding site on chromosome 6q16 causing overexpression of the retinal transcription factor PRDM13.

Conclusions: NCMD has great phenotypic variability, which can be appreciated only by examining multiple family members. To our knowledge, this is an original report that shows a correlation of functional studies with multimodal imaging. These findings are consistent with NCMD being a developmental abnormality of the macula. All layers of the retina and choroid demonstrate maldevelopment and varying degrees of malfunction. Although PRDM13 is expressed in the amacrine cells, we have yet to identify an abnormality specific to this cellular layer. The retinal vasculature appears to be surprisingly well preserved or intact by OCT angiogram compared with that shown in intravenous fluorescein angiograms. OCT angiograms suggest that foveal hypoplasia is a phenocopy of grade 1 NCMD, torpedo maculopathy is a phenocopy of grade 2 NCMD, and in this single family, congenital toxoplasmosis is a phenocopy of grade 3 NCMD.