Phenotypic characterization of autosomal dominant progressive cone dystrophies associated with a heterozygous variant c.2512C>T of GUCY2D gene in a large kindred.

PURPOSE: In this study, we described a large family presenting different manifestations of cone dystrophy at different ages associated with GUCY2D gene mutation. METHOD: Sixty-three individuals of a single kindred, including 23 affected with cone dystrophies, were recruited and received ocular examinations, including best corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, color fundus photograph (CFP), fundus autofluorescence, optical coherence tomography, fluorescence fundus angiography, color vision testing, full-field electroretinography, and electro-oculogram. Whole exome sequencing (WES) and Sanger sequencing were performed for underlying mutations associated with cone dystrophy. RESULT: There were 23 affected family members. Clinical analysis showed that the proband and other patients had impaired visual acuity ranging from 20/800 to 20/50 with impaired color vision. Fundus photograph showed retinal pigment epithelium (RPE) granular abnormalities with depressed macular reflex in young patients and macular or retinochoriodal atrophy in older patients. OCT examination confirmed the reduced outer retinal thickness or inner retinal thickness, absence of the ellipsoid zone (EZ) and retinal atrophy to varying degrees. Electroretinography revealed a reduced cone response combined with a relatively maintained rod response. WES and Sanger sequencing revealed a heterozygous variant c.2512C>T in the GUCY2D gene of the affected family members. CONCLUSIONS: We reported cone dystrophy in 23 affected individuals in a five-generation family and demonstrated different macular abnormalities in OCT scans and CFP at different ages. The multimodal ocular records in our study provide physicians and ophthalmologists with a better understanding of cone dystrophy associated with GUCY2D mutation.

A Novel Mutation in the Membrane Frizzled-Related Protein Gene for Posterior Microphthalmia, Non-pigmented Retinitis Pigmentosa, Optic Nerve Drusen, and Retinoschisis in a Consanguineous Family.

Background: Microphthalmos (MCO) is a rare developmental defect characterized by small malformed eyes. Our study aimed to describe the clinical characteristics of posterior microphthalmos syndrome caused by a novel variant in MFRP gene in a Chinese patient. Methods: Complete ophthalmologic examinations were performed for the proband and proband's family members. Whole exon sequencing (WES) and Sanger sequencing were used to identify the mutated genes, and bioinformatic analysis was undertaken to predict the effect of this variant. Results: Clinical analysis showed that the proband had reduced axial length (17.95 and 17.98 mm) with normal-size corneas and shallow anterior chamber depth. Fundus photography showed scattered yellowish-white spots in the whole retina with cup-to-disc ratios of 0.95 in both eyes. Retinoschisis in the inner nuclear layer and reduced outer retina thickness were apparent on OCT examination, and optic nerve drusen demonstrated increased autofluorescence in fundus autofluorescence (FAF). Perimeter examination revealed a tubular visual field for the right eye, and electroretinography (ERG) revealed a moderately reduced rod response combined with compromised cone response. Ocular examinations of the patient's family members were unremarkable. WES revealed that the proband had homozygous mutations in c.55-1 (IVS1) G>A in intron 1 for the MFRP gene. Both the proband's parents and offspring were confirmed to be heterozygous by Sanger sequencing. Bioinformatic analysis showed this mutation was deleterious. Conclusion: We reported autosomal recessive posterior microphthalmia, atypical retinitis pigmentosa, and retinoschisis caused by a novel mutation in the MFRP gene in this consanguineous marriage family. Our study further broadens the mutation and phenotype spectrum of the MFRP gene in microphthalmia.

Macular vascular density and visual function after phacoemulsification in cataract patients with non-pathological high myopia: a prospective observational cohort study.

PURPOSES: This study aimed to evaluate changes in macular vascular density and macular function in patients with high myopia cataract (HMC) after phacoemulsification surgery, using optical coherence tomography angiography (OCTA) and multifocal electroretinography (mfERG). METHODS: Patients with cataracts scheduled for phacoemulsification surgery were divided into a high myopia group (axial length > 26.5 mm) and a control group (22 mm < axial length ≤ 24.5 mm). OCTA examinations were performed before surgery and at 1 day, 1 week, 1 month, and 3-6 months post-surgery, while mfERG was conducted before surgery and at 3-6 months post-surgery. RESULTS: A total of 38 patients were included, of whom 20 were HMC patients and 18 were control patients. The macular vascular density significantly increased after phacoemulsification surgery in both groups, while foveal avascular zone area decreased significantly (HMC group: all p < 0.01; control group: all p < 0.05). Mean changes in macular vascular density were significantly greater in HMC patients than in the control group at 1 day after surgery (all p < 0.05). The amplitude density and latency of P1 wave in all macular rings (Ring1-5) did not differ significantly before or after surgery in either group (all p > 0.1). CONCLUSION: Phacoemulsification may not affect HMC patients' macular mfERG responses within 3-6 months post-surgery, but it may influence macular microcirculation. HMC patients should be closely monitored after surgery, as their retinal vascular density may fluctuate substantially in the early postoperative period.

[Purtscher-like retinopathy associated with antibiotic anaphylaxis].

OBJECTIVE: We report a case of an 18-year-old woman with systemic antibiotic anaphylaxis who presented anasarca and bilateral visual loss two weeks after the intravenous use of pazufloxacin. Ancillary fundus tests revealed bilateral cotton-wool spots, Purtscher flecken, edema, and retinal arteriolar occlusion around the optic disc. After pulse corticosteroid, administration of anti-anaphylactic agent, and general support therapy for one month, the patient showed a favorable change, with the symptoms lessened or free systemically, except the continuous aggravation of fundus ischemic change. After two intravitreal injections of Ranibizumab, there were still a large area of capillary non-perfusion and neovacularizations in the binocular retina, resulting in vitreous hemorrhage. The patient's visual acuity had still light perception after right-eye vitrectomy and presented no improvement during the postoperative follow-up of two years. Literature review revealed that there were many causes associated with Purtscher-like retinopathy, and the consequent visual impairment varied significantly. Prompt management of the underlying condition is crucial in giving the patient the best chance to restore vision.

[Molecular genetic analysis and clinical phenotype of a pedigree with familial dominant drusen].

OBJECTIVE: To analyze clinical features and mutations of EFEMP1 gene in a Chinese pedigree with familial dominant drusen. METHODS: Clinical features of the pedigree were studied with fundus photography, fundus fluorescein angiography and optical coherence tomography. Molecular genetic analysis was performed on the patients and unaffected individuals from the family. All coding exons of the EFEMP1 gene were amplified by polymerase chain reaction (PCR) and sequenced. The results were compared with wild-type sequences from NCBI. The proband who had suffered from choroidal neovascularization and preretinal hemorrhage received an intravitreal injection of an anti-vascular endothelial growth factor (VEGF) preparation. RESULTS: A heterozygous mutation C>T (R345W) was identified in exon 10 of the EFEMP1 gene in two affected individuals from the family. The same mutation was not detected in unaffected family members and 100 healthy individuals. Postoperative follow-up of the patient receiving intravitreal injection of anti-VEGF drug showed that visual acuity was improved and fundus appeared to be stable. CONCLUSION: The R345W mutation in EFEMP1 is responsible for the dominant drusen in this family. Intravitreal injection of anti-VEGF drug is a promising treatment for the improvement in vision.