A Reappraisal of the Clinical Spectrum of North Carolina Macular Dystrophy

Purpose To characterize the clinical phenotypes and genotype of a large family with North Carolina macular dystrophy (NCMD). Design Observational, retrospective case series. Participants Thirteen participants who were at risk of inheriting a dominantly transmitted disease gene from a 4-generation family from Baltimore were examined. Methods Thirteen participants underwent ophthalmic examination and genomic linkage analysis. Fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, ultrasonography, full-field electroretinography, and electro-oculography were performed on some patients. Main Outcome Measures Description of clinical phenotypes with genomic linkage to the MCDR1 locus. Results Nine of 13 participants were affected with NCMD. There are variable and previously unreported clinical manifestations among affected individuals with NCMD, including drusen, macular staphyloma, choroidal neovascularization, a retinal pigment epithelial tear, and geographic atrophy. The distinctive and virtually pathognomonic grade 3 lesions in NCMD are neither staphylomas nor colobomas, as previously thought. As shown by ultrasonography and SD-OCT, they are deep chorioretinal excavations not involving the sclera, for which the authors propose a new term: macular caldera . Linkage analysis was performed, and the disease-causing gene in this family was mapped to the MCDR1 locus. Conclusions North Carolina macular dystrophy has a wide spectrum of clinical phenotypes that resemble age-related macular degeneration except for their early age of onset. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.