ObjectiveTo observe the clinical features of late-onset cone dystrophy (LOCD). MethodsEleven patients (15 eyes) of LOCD were enrolled in this study. The patients included 7 males and 4 females. The age was ranged from 50 to 79 years, with a mean age of 60.2 years. There was no obvious photophobia and hemeralopia. The visual acuity was less than or equal to 0.05 in 4 eyes, 0.06-0.2 in 5 eyes, 0.3-1.0 in 6 eyes. Visual acuity, slit lamp microscope, indirect ophthalmoscopy, flash electroretinogram (FERG) and multifocal electroretinograms (mfERG) were examined for all patients, fundus fluorescein angiography (FFA) for 11 eyes, optical coherence tomography (OCT) and chromoptometry for 6 eyes. ResultsThere were 6 eyes with red/green color blindness, 2 eyes with color weakness. Normal fundus was found in 11 eyes, while derangement of macular pigment epithelial in 4 eyes. FFA results showed that there were 5 eyes with normal fundus, 4 eyes with blocked fluorescent spots, 2 eyes with oval macular atrophy. FERG results showed that in cone response, the amplitude was lower in 6 eyes (including mild decrease in 4 eyes, moderate decrease in 1 eye and severe decrease in 1 eye); both in cone and rod response, the amplitude were lower in 9 eyes. mfERG results showed that central part of the cone (less than 7 degree from the center) was damaged in 5 eyes, both central and peripheral part (outside of 7 degree) of the cone were damaged in 10 eyes. OCT results showed that pigment derangement in 3 eyes, fovea was normal in 8 eyes, thinned in 5 eyes (foveal thickness was 83-111 μm). ConclusionsThe fundus manifestations of LOCD patients are variable, from normal fundus to oval macular atrophy. FERG is abnormal, which mainly in cone response at early stage and both in cone and rod response at late stage. Central part and (or) peripheral part of the cone are abnormal by mfERG.
ObjectiveTo observe the clinical manifestation and gene mutation of a pedigree with Sorsby fundus dystrophy (SFD). Methods Ten members in 3 generations of a pedigree with SFD were included in this study. Four patients were observed in the pedigree, including 2 females and 2 males. All 10 members underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus color photography and spectral domain optical coherence tomography. Genomic DNA was extracted from peripheral venous blood which was collected from all the members. Relevant exons of ocular diseases were detected by the next generation sequencing method from the proband. The other members underwent Sanger verification. Results Among the four patients, fading eyesight was appeared at their 44, 46, 47 and 40 year-old respectively. The two male patients had bilateral morbidity, and the two female patients had monocular symptoms. DNA sequencing results showed that the proband, other 3 patients and 2 members from the Ⅲ generation had heterozygous mutation of TIMP3 gene in exon 5. The amino acid encoded by TIMP3 gene No.204 codon changed from serine to cysteine (TIMP3:NM_000362:Exon5:c.A610T/p.S204C). CoclusionsThe invasion time of all the patients in this pedigree is after their 40 year-old. Heterozygous mutation at c.610A＞T (p.S204C) in TIMP3 gene is the causative gene of SFD in this pedigree.