Structural and functional analysis of retinal vasculature in HANAC syndrome with a novel intronic COL4A1 mutation.

PURPOSE: Mutations of the COL4A1 gene, a major structural protein of vessels, may cause hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome. The vascular structure and function of patients with HANAC is poorly known. Here, we report a family with HANAC syndrome associated to a previously unreported mutation in COL4A1. The structure and function of retinal vessels were detailed by adaptive optics ophthalmoscopy (AOO) and optical coherence tomography (OCT) angiography. METHODS: Clinical data from six affected individuals (43 to 72 years old) from a single family comprising two generations were collected. Imaging charts including conventional fundus imaging, OCT-angiography and AOO in static and dynamic (flicker) mode were reviewed. DNA sequencing was done in the proband. RESULTS: DNA sequencing of the proband revealed a heterozygous deletion of COL4A1 (NM_001845) at position 1120 in the intron 20 resulting in the loss of splicing donor site for exon 20 (c.1120 + 2_1120 + 8del heterozygote). Four patients had arterial hypertension, and three had kidney dysfunction, one of which under dialysis. By fundus examination, five had typical retinal arteriolar tortuosity with arteriolar loops. Wall-to-lumen ratio of arteries was within normal limits, that is, lower than expected for hypertensive patients. Several foci of arteriolar irregularities were noted in the two oldest patients. In three affected subjects, evaluation of the neurovascular coupling showed a higher flicker-induced vasodilation than a control population (6 % to 11 %; n < 5 %). CONCLUSIONS: Structural and dynamic analysis of retinal vessels in a HANAC family bearing a previously unreported intronic COL4 mutation was done. In addition to arteriolar tortuosity, we found reduced wall-to-lumen ratio, arteriolar irregularity and increased vasodilatory response to flicker light. These abnormalities were more marked in the oldest subjects. This abnormal flicker response affected also non-tortuous arteries, suggesting that microvascular dysfunction extends beyond tortuosity. Such explorations may help to better vascular dysfunction related to HANAC and hence better understand the mechanisms of end-organ damage.

Peripapillary Intrachoroidal Cavitation in Myopia Evaluated with Multimodal Imaging Comprising "En-Face" Technique.

Objectives. To demonstrate the usefulness of "en-face" Spectral Domain Optical Coherence Tomography (SD-OCT) combined with Fluorescein Angiography (FA) in the investigation of peripapillary intrachoroidal cavitation. Materials and Methods. A 72-year-old man followed for primary open-angle glaucoma (POAG) for 4 years was referred for an asymptomatic "peripapillary lesion." A full ophthalmological examination and conventional imaging of the retina were done. FA, Indocyanine Green Angiography (ICG-A), and SD-OCT using the "en-face" technique were also performed. Results. Best-corrected visual acuity (BCVA) was 20/25 both eyes. Slit-lamp examination revealed no abnormalities of anterior segment. Intraocular pressure (IOP) was normal. Fundus examination showed a triangular yellow-orange thickening at the inferior border of both optic nerves. FA showed early hypofluorescence of the lesion and progressive staining without any dye pooling. SD-OCT with "en-face" technique showed an intrachoroidal hyporeflective space resembling a cavitation below the retinal pigment epithelium (RPE). Conclusions. "En-face" SD-OCT and FA are valuable techniques for the diagnosis of peripapillary intrachoroidal cavitation associated with myopia. Pathophysiological insights regarding SD-OCT findings and angiography behavior are offered.