Chenjin Jin

MACULAR BUCKLING USING A THREE-ARMED SILICONE CAPSULE FOR FOVEOSCHISIS ASSOCIATED WITH HIGH MYOPIA.

Purpose: To investigate the safety and efficacy of a novel macular buckling technique on foveoschisis in highly myopic eyes. Methods: Highly myopic eyes with foveoschisis, posterior staphyloma, and axial length greater than 26.5 mm, but without a full-thickness macular hole, were included. Macular buckling was performed in the included eyes using a three-armed adjustable silicon capsule. Results: Eight eyes from eight patients (five women) were enrolled in this study. The mean follow-up period was 11.6 (range 9–14) months. After surgery, the best-corrected visual acuity was improved in 7/8 (87.5%) eyes, optical coherence tomography imaging showed gradual anatomic improvement of macula over time. The final best-corrected visual acuity gained 21.5 early treatment diabetes retinopathy study letters from baseline on average (P = 0.014). Postoperatively, the most common complications were transiently elevated intraocular pressure (62.5%) and asymptomatic abduction limitation (100%), and the most serious complication was hemorrhagic choroidal detachment (25%). Conclusion: Macular buckling with a three-armed adjustable silicone capsule resulted in anatomic and visual improvement in eyes with myopic foveoschisis.

C278F mutation in FGFR2 gene causes two different types of syndromic craniosynostosis in two Chinese patients

The current study was performed with aim to investigate the fibroblast growth factor receptor 2 (FGFR2) gene in two Chinese families with two different forms of syndromic craniosynostosis, and to characterize their associated clinical features. Two families underwent complete ophthalmic examinations, and two patients from each family were diagnosed with craniosynostosis. Genomic DNA was extracted from leukocytes of peripheral blood collected from these two families and from 200 unrelated subjects within the same population as controls. Exons 8 and 10 of the FGFR2 gene were amplified by polymerase chain reaction and directly sequenced. Ophthalmic examinations of the two patients revealed shallow orbits and ocular proptosis, accompanied by midface hypoplasia and craniosynostosis. Case 1 had retinal detachment, abnormal limbs and hands, while case 2 exhibited normal hands and feet upon clinical examination. A heterozygous FGFR2 missense mutation c.833G>T (C278F) in exon 8 was identified in these two patients, but not in unaffected family members or the normal controls. Although FGFR2 gene mutations and polymorphisms have been studied in various ethnic groups, we report a mutation of FGFR2 in two different Chinese patients with two different types of syndromic craniosynostosis.

Two heterozygous mutations identified in one Chinese patient with bilateral macular coloboma

Congenital macular coloboma is characterized by defined punched out atrophic lesions of the macula. The present study aimed to investigate the genetic alterations of one Chinese sporadic patient with bilateral large macular coloboma. Complete ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, fundus photograph and fundus fluorescein angiography imaging, Pentacam, and optical coherence tomography were performed on the patient. Genomic DNA was extracted from leukocytes in a peripheral blood sample collected from the patient, the patients unaffected family members and from 200 unrelated control subjects from the same population. Next-generation sequencing of the known genes involved in ocular disease was performed. The functional effects of the mutation were analyzed using Polymorphism Phenotyping (PolyPhen) and Sorting Intolerant From Tolerant (SIFT). One heterozygous bestrophin 1 (BEST1) mutation c.1037C>A (p.Pro346His, p.P346H) in exon 9 and one heterozygous regulating synaptic membrane exocytosis 1 (RIMS1) mutation c.3481A>G (p.Arg1161Gly, p.R1161G) in exon 23 were identified in the patient being investigated, but not in the unaffected family members or unrelated control subjects. Polyphen and SIFT predicted that the amino acid substitution p.P346H in the BEST1 protein is damaging. In addition, Polyphen predicted that the amino acid substitution p.R1161G in the RIM1 protein is damaging. The results of the current study have increased the mutation spectrums of BEST1 and RIMS1, and are valuable for improving the current genetic counseling process and developing novel therapeutic interventions for patients with macular coloboma.

Two Paired Box 6 mutations identified in Chinese patients with classic congenital aniridia and cataract

Congenital aniridia is a rare genetic disorder characterized by a variable degree of hypoplasia or absence of iris. It is frequently associated with keratopathy, cataract, juvenile-onset glaucoma and foveal and optic nerve hypoplasia. Mutations in the Paired Box 6 (PAX6) gene on chromosome 11p13 have been demonstrated to cause aniridia. The aim of the present study was to investigate the genetic variations of PAX6 in two sporadic patients from southern China with classic congenital aniridia and cataract. Complete ophthalmic and physical examinations were performed, including best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus examination, optical coherence tomography, ultrasound biomicroscopy, and Pentacam scanning. Genomic DNA was extracted from leukocytes of peripheral blood collected from the two patients, their unaffected parents and 200 unrelated control subjects from the same population. Exons 4–13 of the PAX6 gene were amplified by polymerase chain reaction and sequenced directly. Patient 1 was affected with aniridia accompanied by congenital cataract and nystagmus. A novel heterozygous PAX6 frameshift mutation c.277delG (p.Glu93SerfsX31) in exon 6 was identified in this patient. Patient 2 was presented with aniridia, congenital cataract, lens subluxation and glaucoma. A recurrent nonsense mutation c.718C>T (p.Arg240X) in exon 9 was identified in this patient. The present results expand the mutation spectrum of PAX6 and will be valuable for genetic counseling in the affected families. Additionally, the identification of these mutations reiterates the importance of PAX6 in ocular development and sheds light on the pathogenesis of congenital aniridia.

Two different initial treatment regimens of ranibizumab in myopic choroidal neovascularization: 12-month results from a randomized controlled study

The optimal treatment regimen for myopic choroidal neovascularization (mCNV) is essential to understand but currently poorly studied.

Bestrophin 1 gene analysis and associated clinical findings in a Chinese patient with Best vitelliform macular dystrophy

The aim of the present study was to investigate the clinical characteristics and the underlying genetic causes of Best vitelliform macular dystrophy (BVMD) in a sporadic case in a Chinese patient. A 10-year-old boy was diagnosed with BVMD; complete ophthalmic examinations were performed, including best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus photograph, optical coherence tomography and fundus fluorescein angiography imaging. Genomic DNA was extracted from leukocytes of the peripheral blood collected from this patient and his family members. DNA samples from 200 unrelated subjects from the Chinese population were used as controls. A total of 11 exons of the bestrophin 1 (BEST1) gene were amplified by polymerase chain reaction and directly sequenced. The results revealed that the patient presented with yellowish lesions in the macular area. Heterozygous mutations c.292G>A (p.Glu98Lys) in exon 4 and c.1608C>T (p.Thr536Thr) in exon 10 of the BEST1 gene were identified in this sporadic case; however, this was not identified in any of his unaffected family members or in the normal controls. The c.292G>A (p.Glu98Lys) mutation has not been previously reported, whereas the c.1608C>T (p.Thr536Thr) mutation is a previously characterized single nucleotide polymorphism (SNP). In conclusion, BEST1 gene mutations and polymorphisms have been reported in diverse ethnic groups, and the present study identified a novel BEST1 gene mutation and an SNP that occurred simultaneously in a Chinese patient with BVMD.

FGFR2 mutations and associated clinical observations in two Chinese patients with Crouzon syndrome

The aim of the present study was to identify mutations in the fibroblast growth factor receptor 2 (FGFR2) gene in patients with Crouzon syndrome and characterize the associated clinical features. A total of two Chinese patients diagnosed with Crouzon syndrome underwent complete examinations, including best-corrected visual acuity, slit-lamp, examination, fundus examination, optical coherence tomography and computed tomography of the skull. Genomic DNA was extracted from peripheral blood samples collected from the patients, as well as their family members and 200 unrelated control subjects from the same population. Exons 8 and 10 in the FGFR2 gene were amplified by polymerase chain reaction and directly sequenced. Patient #1 had a heterozygous missense mutation (c.1025G>A, p.C342Y) in exon 10 of FGFR2. Patient #2 had a heterozygous mutation (c.1084+1 G>T; IVS10+1G>T) in intron 10. The mutations were not present in any of the unaffected family members or unrelated control subjects. These findings expand the mutation spectrum of FGFR2, and are valuable for genetic counseling in addition to prenatal diagnosis in patients with Crouzon syndrome.

Genetic variations in Bestrophin‑1 and associated clinical findings in two Chinese patients with juvenile‑onset and adult‑onset best vitelliform macular dystrophy

Best vitelliform macular dystrophy (BVMD) is a hereditary retinal disease characterized by the bilateral accumulation of large egg yolk-like lesions in the sub-retinal and sub-retinal pigment epithelium spaces. Macular degeneration in BVMD can begin in childhood or adulthood. The variation in the age of onset is not clearly understood. The present study characterized the clinical characteristics of two Chinese patients with either juvenile-onset BVMD or adult-onset BVMD and investigated the underlying genetic variations. A 16-year-old male (Patient 1) was diagnosed with juvenile-onset BVMD and a 43-year-old female (Patient 2) was diagnosed with adult-onset BVMD. Comprehensive ophthalmic examinations were performed, including best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus photography, optical coherence tomography, fundus fluorescein angiography imaging and Espion electrophysiology. Genomic DNA was extracted from peripheral blood leukocytes collected from these patients, their family members, and 200 unrelated subjects within in the same population. The 11 exons of the bestrophin-1 (BEST1) gene were amplified by polymerase chain reaction and directly sequenced. Both patients presented lesions in the macular area. In Patient 1, a heterozygous mutation c.903T>G (p.D301E) in exon 8 of the BEST1 gene was identified. This mutation was not present in any of the unaffected family members or the normal controls. Polymorphism phenotyping and the sorting intolerant from tolerant algorithm predicted that the amino acid substitution D301E in bestrophin-1 protein was damaging. In Patient 2, a single nucleotide polymorphism c.1608C>T (p.T536T) in exon 10 of the BEST1 gene was identified. These findings expand the spectrum of BEST1 genetic variation and will be valuable for genetic counseling and the development of therapeutic interventions for patients with BVMD.

The Combination of Ketorolac with Local Anesthesia for Pain Control in Day Care Retinal Detachment Surgery: A Randomized Controlled Trial

This study aims to evaluate the efficacy of ketorolac with local anesthesia compared to local anesthesia alone for perioperative pain control in day care retinal detachment surgery. The randomized controlled trial included 59 eyes of 59 participants for retinal detachment surgery who were randomly assigned (1 : 1) into the ketorolac (K) group and control (C) group. All participants underwent conventional local anesthesia while patients in the K group received an extra administration of preoperative ketorolac. Participants in the K group had a statistically significantly lower intraoperative NRS score (median 1.0 versus 3.0, P = 0.003), lower postoperative NRS score (median 0 versus 1.0, P = 0.035), fewer proportion of rescue analgesic requirement (10% versus 34.5%, P = 0.023), and lower incidence of postoperative nausea and vomiting (13.3% versus 41.4%, P = 0.015) compared to the C group. Intraocular pressure (IOP) changes (△IOP) were significantly reduced in the K group (median 1.9 versus 3.0, P = 0.038) compared to the C group 24 hours postoperatively. In conclusion, the combination of local anesthesia with ketorolac provides better pain control in retinal detachment surgery compared to local anesthesia alone. The beneficial effect of ketorolac with local anesthesia may contribute to a wider-spread adoption of day care retinal detachment surgery. This trial is registered with ClinicalTrials.gov NCT02729285.

Clinical and next-generation sequencing findings in a Chinese family exhibiting severe familial exudative vitreoretinopathy

Familial exudative vitreoretinopathy (FEVR) is a rare hereditary retinal disorder characterized by the premature arrest of vascularization in the peripheral retina. The aim of the present study was to characterize the clinical presentations of a Chinese family affected by bilateral severe FEVR, and to identify the underlying genetic variations. One family that presented with bilateral FEVR was recruited for this study. Comprehensive ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus photography, fundus fluorescein angiography imaging and electroretinogram were performed. Genomic DNA was extracted from leukocytes of the peripheral blood collected from the affected and unaffected family members, as well as 200 unrelated control subjects from the same population. Next-generation sequencing of the candidate genes associated with ocular diseases was performed, and the identified mutations were validated by conventional polymerase chain reaction-based sequencing. The functional effects of the mutations were analyzed by polymorphism phenotyping (PolyPhen) and sorting intolerant from tolerant (SIFT). One heterozygous ATP binding cassette subfamily A member 4 (ABCA4) c.5693G>A (p.R1898H) mutation in exon 40 and one heterozygous LDL receptor related protein 5 (LRP5) c.260T>G (p.I87S) mutation in exon 2 were identified in this family. To the best of our knowledge, the ABCA4 c.5693G>A (p.R1898H) mutation has not been reported in FEVR, and the LRP5 c.260T>G (p.I87S) mutation is a novel mutation. PolyPhen and SIFT predicted that the amino acid substitution R1898H in protein ABCA4 is benign, whereas the amino acid substitution I87S in protein LRP5 is damaging. A single nucleotide polymorphism c.266A>G (p.Q89R, rs41494349) was identified in exon 2 of LRP5. These findings expand the mutation spectrums of ABCA4 and LRP5, and will be valuable for genetic counseling and development of therapeutic interventions for patients with FEVR.