History of present illness
A 60-year-old White male patient (proband case I-1) presented with blurred vision in both eyes, the right having begun to blur 30 years earlier, and the left having begun to blur more recently, impairing his ability to drive or work.
Ocular examination findings
On examination, his visual acuity was 20/400 in the right eye and 20/100 in the left eye. Dilated fundus examination showed a central area of excavation with atrophy surrounded by irregular hyperpigmentation and subretinal fibrosis in each eye ( Fig. 17.1 ). Nasal to the area of atrophy in the left eye was a small subretinal hemorrhage ( Fig. 17.1 A and B).
Imaging
Questions to ask
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What was the age of onset of vision loss in one or both eyes?
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What is the extent of vision loss (e.g., driving or work impairment)?
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Is there a family history of eye disease or vision loss/functional restriction at an early age?
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Is there a history of nyctalopia?
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Is there a history of color vision abnormality/loss?
Assessment
A 60-year-old male patient reports with decreasing vision in the left eye and persistently deceased central vision in the right eye.
Differential diagnosis and associated confirmatory tests
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Toxoplasmosis: serum antibodies
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Best macular dystrophy: DNA sequencing, electroretinogram (ERG), electrooculogram (EOG)
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Cone dystrophy: ERG, DNA sequencing
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Age-related macular degeneration (AMD): optical coherence tomography (OCT), fluorescein (FA), indocyanine green angiography (ICG)
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Myopic macular degeneration with staphyloma and choroidal neovascularization (CNV): OCT, FA
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North Carolina macular dystrophy (NCMD): DNA sequencing, ERG, EOG
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CNV secondary to AMD: OCT, FA, ICG
Working diagnosis
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CNV secondary to NCMD.
Multimodal testing and results
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Fundus imaging, FA, OCT, and genetic testing were obtained.
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OCT showed intraretinal and subretinal fluid consistent with CNV.
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OCT images showed central excavated atrophy with overlying central intraretinal and subretinal fluid along with intrachoroidal lacunae in both eyes. There was the appearance of macular pseudohole in the right eye, and the left eye exhibited mild subretinal fluid nasal to the excavation ( Fig. 17.1 E and F).
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FA showed late staining but no definite CNV in either eye ( Fig. 17.1 C and D).
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Genetic testing molecular analysis of the MCDR1 locus revealed a pathogenic heterozygous point mutation in the noncoding region of the DNASE1 hypersensitivity site “V1 variant,” chr6:100040906 G>T (hg19) upstream of PRDM13 consistent with a diagnosis of NCMD.1.
Management
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The CNV was treated with an intravitreal anti–vascular endothelial growth factor (VEGF) agent (1.25 mg/0.05 mL bevacizumab) according to a treat-and-extend protocol.
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After five monthly injections in the right eye and eight in the left eye, visual acuity improved to 20/50 and 20/150, respectively. OCT was stable for the right eye and showed decreased intraretinal and subretinal fluid nasal of the excavation for the left eye ( Fig. 17.1 G and H). Family members indicated in the pedigree ( Fig. 17.2 ) were also examined, with select notable findings as follows.
