Adult-onset foveomacular vitelliform dystrophy (AFVD) is characterized by gradually loss of vision, subretinal vitelliform macular lesions and retinal pigment epithelium (RPE) atrophy. The electrooculogram (EOG) is usually normal or reduce slightly. On optical coherence tomography (OCT), there are vitelliform substance which deposited between the photoreceptor layer and the RPE layer, and thinner outer nuclear layer above these deposits. OCT angiography can show the superficial and deep retinal capillaries plexus (DCP) above the yolk-like deposits, the choroidal capillary blood flow is reduced and the DCP blood flow is increased near macular. On indocyanine green angiography (ICG), there is choroidal neovascularization under vitelliform substance at early stage and fluorescence leakage in the corresponding retinal region at late stage. There is no effective treatment for AFVD at present, monogenic gene therapy is the most worth looking forward to. Understanding AFVD clinical manifestations, multi-mode imaging features and new advances in treatment can provide a reference for diagnosis and treatment options
ObjectiveTo observe the OCT angiography (OCTA) features of adult-onset foveomacular vitelliform dystrophy (AFVD).MethodsRetrospective clinical observational study. Twelve patients (22 eyes) diagnosed as AFVD by multi-modal imaging in Ophthalmology Department of Yunnan Second People’s Hospital from March 2018 to May 2019 were included in this study. There were 8 males (16 eyes) and 4 females (6 eyes). The patients aged from 33 to 62 years, with the mean age of 48.7±8.9 years. Ten patients were binocular, 2 patients were monocular. The visual acuity was 0.08-0.6. In 22 eyes, the vitelloid-like substance was relatively complete in 8 eyes, the vitelloid-like substance had different degrees of rupture in 14 eyes, secondary choroidal neovascularization (CNV) was observed in 10 eyes. The Heidelberg OCTA instrument was used for OCTA examination. The central wavelength was 840 nm, the acquisition speed was 85,000 times/s. A 3 mm × 3 mm scan was obtained. In the scanning process, eye-tracking technology was adopted to select images with better image quality and position for marking and saving. The image characteristics of vitelloid-like substance, fundus vascular changes and secondary CNV in OCTA were analyzed.ResultsIn 8 eyes with a relatively complete vitelloid-like substance, B-scan images showed dense vitelloid-like substance under the retinal neurocortical layer, which was located between the RPE layer and the ellipsoid zone and had a uniform density. Blood flow signals at the vitelloid-like substance can be seen in the en-face image, which was the artifact of the vitelloid-like substance reflecting the blood vessels above. In the 14 eyes with different degrees of vitellin-like material rupture, the signal of vitellin-like substance between the ellipsoid zone and the RPE layer in the B-scan image was not uniform, and some weak reflected signal lacunae could be seen. In the image of en-face, the relatively intact areas of vitelloid-like substance still showed the artifact of the blood vessels above the reflection, while there was no blood flow signal at the rupture of vitelloid-like substance. In 22 eyes, the morphology of retinal small blood vessels in the superficial and deep capillary arch ring region of retina was abnormal in 10 eyes. Some small blood vessels could be seen to have branch and shape changes, and the anastomosis failed to show a complete arch ring structure.No significant structural changes in retinal capillaries were observed in 12 eyes. Among the 10 eyes with secondary CNV, 8 eyes showed the non-active CNV which was as thick as "wild branches", and 2 eyes showed the active CNV which was composed of dense and small vascular branches.ConclusionAFVD in OCTA can be manifested as abnormal retinal vascular morphology caused by the vitelliform material pushing, vascular artifacts reflected by the vitelliform material itself, and the presence of CNV under the vitelliform material.
ObjectiveTo report the BEST1 gene mutations and clinical phenotypes in two pedigrees with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB)．MethodsA retrospective clinical study. From November 2019 to March 2021, in the Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University, the BVMD family (4 patients and 6 family members) and the ARB family (2 patients, 2 family members), a total of 6 patients and 8 normal family members were included in the study. Detailed medical history was obtained; best corrected visual acuity, fundus color photography, electrophysiology, optical coherence tomography and fundus autofluorescence examination were performed. The clinical characteristics for all patients in the two families were analyzed. Three milliliter peripheral venous blood of all participants in the family was collected, and the whole genomic DNA was extracted with gene sequencing using next-generation sequencing technology based on targeted capture. Compared with the database to identify the pathogenicity mutation sites, suspected pathogenic mutation sites were selected, then mutations in other members in the family was assayed by Sanger sequencing. ResultsIn family 1, the proband was demonstrated as typical BVMD, other patients were multifocal vitelliform macular dystrophy. The DNA sequencing result showed that all the 4 patients carried heterozygous missense mutations in exon 3 of BEST1 gene: c.240C>G (p.F80L) (M1) and 2 members carried this mutation, but without clinical phenotype. M1 was a likely-pathogenic mutation reported for the first time. In family 2, the proband and the other patient were diagnosed as ARB. The DNA result showed that the 2 patients carried heterozygous missense mutations in exon 5 and exon 2 of BEST1 gene: c.584C>T (p.A195V) (M2)、c.139C>A (p.R47S) (M3), and a heterozygous frameshift mutation in exon 3 of BEST1 gene: c.235dupT (p.S79Ffs*153) (M4). M2 was a pathogenic mutation reported previously. M3 variant was of undetermined significance. M4 was a first reported pathogenic mutation. ConclusionsThe BEST1 gene mutation is the main cause of BVMD and ARB. Different mutation sites have different clinical phenotypes. BVMD and ARB have genetic and clinical heterogeneity.
Objective To analyze the pathogenic gene and clinical phenotypes of a family affected with rare sector retinitis pigmentosa (sector RP). Methods A retrospective clinical study. A patient with sector RP diagnosed in Renmin Hospital of Wuhan University and his parents were included in the study. Detailed medical history was collected; best corrected visual acuity (BCVA), fundus color photography, autofluorescence (AF), visual field, optical coherence tomography (OCT), electroretinogram, fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) examination were performed. The peripheral venous blood of the patient and his parents were collected, and DNA was extracted. A whole exon sequencing was used for the proband. The mutations were verified by targeted Sanger sequencing and quantitative polymerase chain reaction. Bioinformatics analysis and cosegregation analysis were performed. ResultsThe proband, a 17-year-old male, had presented with gradually decreased vision in the past 2 years with BCVA of 0.4 in both eyes. Retinal vessels attenuation and macular dystrophy without obvious pigmentation on the fundus were observed. AF showed, in bilateral eyes, a symmetrical hypo-autofluorescent region only in the inferonasal quadrant and “petal-like” hyper-AF macula. The visual field examination showed defects in the superotemporal quadrant corresponding to the affected retina. OCT showed loss of the photoreceptor layer except for the foveal region. Electroretinogram examination presented reduced scotopic wave peaks and extinct photopic response. FFA and ICGA showed the atrophy retinal pigment epithelium around the optic disk and in the inferior retina. The clinical phenotypes of the parents were normal. The whole exon sequencing identified one mutation in SPATA7 gene, c.1112T>C (p.Ile371Thr) in exon10 and a copy number variation in trans. The missense mutation resulted in the change of isoleucine to threonine at amino acid 371 in the encoded SPATA7 protein, and the mother carried this heterozygous mutation c.1112T>C. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for classification of genetic variants, the missense mutation was classified as the uncertain significance. The CNV, originating from his father, contributed to the loss of exon10 and was confirmed as the likely pathogenic variant. ConclusionsThe macula can be involved in sector RP, leading to the macular dystrophy. The missense variant in SPATA7 gene, c.1112T>C (p.Ile371Thr), might be a pathogenic mutation site in this pedigree.