Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Perfluorocarbon liquid-assisted intraocular foreign body removal

We describe the benefits of perfluoro-N-octane (PFO), a perfluorocarbon liquid, in the removal of nonmagnetic intraocular foreign bodies (IOFBs) from the macula and posterior segment. Two consecutive cases of posterior segment IOFB were reviewed. An 18-year-old male presented to the emergency room after a motor vehicle accident with a zone 1 open globe injury and large glass IOFB in the left eye. A 53-year-old male presented to the emergency room with a history of a 3-week delayed presentation of a zone 1 open globe injury from a nail to the right eye. He was found to have a metallic IOFB. In both cases, PFO was used to slide the nonmagnetic IOFBs outside of the macula for safer retrieval. PFO was also able to protect the posterior pole from IOFB drops during early attempts at removal. PFO can be a useful surgical adjunct to pars plana vitrectomy in the removal of certain nonmagnetic IOFBs

Degenerative “Senile” Retinoschisis: Observations From Ultra-Widefield Imaging

Purpose : To explore the imaging characteristics, including ultra wide-field color fundus photography, autofluorescence and angiography of patients with senile retinoschisis (SR) using Optomap technology. Methods : This is a multi-center, retrospective, non-comparative, consecutive case series of patients who were examined at four institutions. All patients underwent ultra-widefield fundus imaging (UWFI) using the Optos 200Tx or P200dTx imaging system. Inclusion criteria were presence of degenerative peripheral retinoschisis in either eye. Exclusion criteria included any evidence (by history or examination) of congenital X-linked retinoschisis, retinal detachment surgery, or retinal vascular disease causing retinal capillary nonperfusion, including diabetic retinopathy, familial exudative vitreoretinopathy, and sickle cell retinopathy. Results : A total of 35 consecutive patients (58 eyes) with SR were identified who underwent 55 sessions of UWF imaging, including color fundus photography, fundus autofluorescence and fluorescein angiography. Ultra widefield fundus autofluorescence images illustrated the extent of the schisis cavity in 67% of cases with variable features. A crescent of hypo-autofluorescence was often evident at the edge of the schisis cavity aiding in its identification. A total of 31 UWF fluorescein angiograms (UWFFA) were reviewed and 90% of these studies illustrated abnormalities in the area affected by the schisis. The most common finding was retinal vascular leakage observed in 29 (93.5%) eyes. Conclusions : UWF color fundus photography and fundus autofluorescence are reliable noninvasive tools that can aid in the diagnosis and objective monitoring of patients with SR.The breadth of retinal vascular abnormalities that were identified in areas of SR using UWF fluorescein angiography may indicate the presence of a vascular component in the pathogenesis of this condition

NOD2 genetic variants and sarcoidosis-associated uveitis

Purpose: Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood. We determine if variants in NOD2 confer an increased risk of developing uveitis in adults with sarcoidosis. Methods: In this genetic case-control study, 51 total subjects were enrolled: 39 patients diagnosed with sarcoid-related uveitis and 12 patients with systemic sarcoidosis without ocular involvement as controls. Sanger sequencing of the eleven exons of the NOD2 gene was performed on DNA obtained from whole blood. Sanger sequencing data were aligned against the NOD2 NCBI-RefSeq reference sequence to identify novel mutations in uveitis patients. For common variants, allele frequencies in cases versus controls were compared using the chi-square test. Results: There were no significant differences in NOD2 common variant allele frequencies between sarcoidosis patients with and without uveitis, and none of the pathogenic NOD2 mutations associated with Blau syndrome were found in this cohort. However, four rare, non-synonymous variants were identified in four patients with ocular sarcoidosis and none of the controls. Variants rs149071116, rs35285618, and 16:g.50745164T > C have never been previously reported to be associated with any disease and may be pathogenic. The fourth variant, rs2066845, is associated with Crohn’s disease and psoriatic arthritis. Conclusions: Despite the phenotypic overlap between sarcoidosis and Blau syndrome, none of the established pathogenic NOD2 variants were present in adults with sarcoidosis. However, four novel, rare, non-synonymous variants were identified in four cases with ocular sarcoidosis. Further investigation is needed to explore the potential clinical significance of these polymorphisms

NOD2 genetic variants and sarcoidosis-associated uveitis☆

Purpose Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood. We determine if variants in NOD2 confer an increased risk of developing uveitis in adults with sarcoidosis. Methods: In this genetic case-control study, 51 total subjects were enrolled: 39 patients diagnosed with sarcoid-related uveitis and 12 patients with systemic sarcoidosis without ocular involvement as controls. Sanger sequencing of the eleven exons of the NOD2 gene was performed on DNA obtained from whole blood. Sanger sequencing data were aligned against the NOD2 NCBI-RefSeq reference sequence to identify novel mutations in uveitis patients. For common variants, allele frequencies in cases versus controls were compared using the chi-square test. Results: There were no significant differences in NOD2 common variant allele frequencies between sarcoidosis patients with and without uveitis, and none of the pathogenic NOD2 mutations associated with Blau syndrome were found in this cohort. However, four rare, non-synonymous variants were identified in four patients with ocular sarcoidosis and none of the controls. Variants rs149071116, rs35285618, and 16:g.50745164T > C have never been previously reported to be associated with any disease and may be pathogenic. The fourth variant, rs2066845, is associated with Crohn’s disease and psoriatic arthritis. Conclusions: Despite the phenotypic overlap between sarcoidosis and Blau syndrome, none of the established pathogenic NOD2 variants were present in adults with sarcoidosis. However, four novel, rare, non-synonymous variants were identified in four cases with ocular sarcoidosis. Further investigation is needed to explore the potential clinical significance of these polymorphisms

Degenerative Peripheral Retinoschisis: Observations From Ultra-Widefield Fundus Imaging.

BACKGROUND AND OBJECTIVE: To describe the ultra-widefield (UWF) imaging characteristics of patients with degenerative peripheral retinoschisis (DPR) using Optomap technology. PATIENTS AND METHODS: In this multicenter, retrospective, noncomparative, consecutive case series, eligible patients underwent detailed retinal examination including indirect ophthalmoscopy. UWF fundus imaging, including color fundus photography, autofluorescence, and angiography, was performed using standardized protocols and findings were recorded and reviewed and analyzed. RESULTS: A total of 35 patients (58 eyes) with DPR were identified who underwent 55 sessions of UWF imaging. Mean age was 65 years, and the inferotemporal quadrant was most commonly affected (74% of eyes). Of these patients, 31 underwent fluorescein angiography and 90% of these studies illustrated abnormalities in the area affected by the schisis. The most common finding was retinal vascular leakage originating from the deep capillary plexus observed in 29 eyes (93.5%). CONCLUSIONS: UWF imaging enables a more detailed identification of the clinical features associated with DPR and provides simple, practical, and noninvasive tools to monitor progression of disease. The breadth of retinal vascular complications identified with fluorescein angiography may suggest an important vascular component associated with the pathogenesis of this entity. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:557-564.]

Mapping the Complexities and Benefits of Research-Design Partnerships

Increasingly our field is recognizing the necessity of close, collaborative relationships with educators, policy makers, students and other potential stakeholders if our design and research work is to have a lasting and more equitable impact on education. However, this work is not easy or quick, and we lack both detailed examples of how it is done and training for new (and current) scholars in how to do it. This symposium brings together a group of scholars who actively engage in RPPs and DBIR in order to highlight the lessons that have been learned and extend our discourse into the realities of this work, how to prepare students and current scholars to design their work with partners at the center, and how to accurately plan for work that engages stakeholders

27-GAUGE PARS PLANA/PLICATA VITRECTOMY FOR PEDIATRIC VITREORETINAL SURGERY.

PURPOSE: To report on the feasibility of 27-gauge (G) vitrectomy for pediatric patients. METHODS: This study is an international, multicenter, retrospective, interventional case series. Participants were patients 17 years or younger who underwent 27-G vitrectomy for various indications. RESULTS: The records of 56 eyes from 47 patients were reviewed. Mean age was 5.7 ± 5.2 years. Diagnoses included retinopathy of prematurity (Stages 3 with vitreous hemorrhage, 4A, 4B, and 5), Terson\u27s syndrome, traumatic macular hole, posterior capsular opacification, endophthalmitis, and others. Instruments used were the 27-G infusion, 27-G vitreous cutter, 27-G light pipe, and 27-G internal limiting membrane forceps. Instrument bending was noted in one (1.8%) case. There were no cases with intraoperative complications, infusion issues, or postoperative endophthalmitis. There were 67/145 (46%) sclerotomies that required suturing, of which most (51/145) were sutured out of precaution. There were four cases (7.1%) that required conversion to a larger gauge and three cases (5.3%) that developed postoperative hypotony. Mean visual acuity improved from logarithm of the minimum angle of resolution 1.32 (20/420) to 0.72 (20/105), after a mean follow-up of 125.1 days (P = 0.01). Anatomic success was achieved in 96.4% of eyes after a single surgery. CONCLUSION: Twenty-seven-gauge vitrectomy was safe and feasible in selected pediatric vitreoretinopathies. Further studies are warranted to examine indications and outcomes