The African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of Genotype to Glaucoma Phenotype in African Americans: Study Design and Baseline Data.

PURPOSE: To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States. METHODS: Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review. MAIN OUTCOME MEASURES: Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded. RESULTS: The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients. CONCLUSIONS: With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III.

PURPOSE: To find genetic contributions to glaucoma in African Americans. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: One thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine. METHODS: MegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs). MAIN OUTCOME MEASURES: Primary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946). RESULTS: Eighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 ß, 0.36; standard error, 0.065; P < 3×10-8). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10-5) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10-5) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively. CONCLUSIONS: A novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

Surgical repair of large cyclodialysis clefts.

PURPOSE: To describe a new surgical technique to effectively close large (>180 degrees) cyclodialysis clefts. METHODS: Our method involves the use of procedures commonly associated with repair of retinal detachment and complex cataract extraction: phacoemulsification with placement of a capsular tension ring followed by pars plana vitrectomy and gas tamponade with light cryotherapy. We also used anterior segment optical coherence tomography (OCT) as a noninvasive mechanism to determine the extent of the clefts and compared those results with ultrasound biomicroscopy (UBM) and gonioscopy. RESULTS: This technique was used to repair large cyclodialysis clefts in 4 eyes. All 4 eyes had resolution of hypotony and improvement of visual acuity. One patient had an intraocular pressure spike requiring further surgical intervention. Anterior segment OCT imaging in all 4 patients showed a more extensive cleft than UBM or gonioscopy. CONCLUSIONS: This technique is effective in repairing large cyclodialysis clefts. Anterior segment OCT more accurately predicted the extent of each cleft, while UBM and gonioscopy both underestimated the size of the cleft.

Risk factors associated with retinal hemorrhage in suspected abusive head trauma.

PURPOSE: To determine risk factors associated with retinal hemorrhage (RH) in pediatric abusive head trauma (AHT) suspects. METHODS: Records of children aged 0-3 years hospitalized for suspected AHT from January 2007 to November 2011 were retrospectively reviewed in this case-control study. Children were classified into case and control groups based on RH presence. Medical history, presenting symptoms, reasons, and characteristics of injury were recorded. Logistic regression analysis was performed to identify risk factors. RESULTS: A total of 168 children (104 males) were included. Of these, 103 were classified as cases and 65 as controls. The mean age (with standard deviation) was 9.3 ± 8.3 months (range, 1 day-36 months). Of the 103 cases, 22 (21%) had subretinal hemorrhage, 9 (9%) had retinoschisis, and 1 (1%) had vitreous hemorrhage. Children presenting with lethargy or altered mental status (P < 0.0001), subdural hemorrhage (P < 0.0001), and other radiologic findings (eg, cerebral ischemia, diffuse axonal injury, hydrocephalus, or solid organ injury; P = 0.01546) were likely to have RH. All 23 children with skull or nonskull fracture without intracranial hemorrhage did not have RH (P < 0.0001 both categories). CONCLUSIONS: Retinal hemorrhages were almost never found in the absence of intracranial hemorrhage and not found in the setting of fracture without intracranial hemorrhage.

A comparison of two-way text versus conventional paging systems in an academic ophthalmology department.

Alphanumeric paging systems are unidirectional without prioritization capabilities. Newer electronic communication devices such as two-way text paging systems are capable of bidirectional paging and prioritization. While previous studies have evaluated alphanumeric paging systems in academic hospital settings, bidirectional two-way text paging systems have not been investigated. The goal of this study was to evaluate efficiency and impact on patient care delivery of a two-way text paging system compared to conventional one-way alphanumeric pagers. This unmasked, crossover prospective study was divided into three phases. In phase one, surveys were distributed to all ophthalmology attending physicians, residents, clinical technicians, and secretaries to assess the conventional alphanumeric paging system. In phase two, these participants used two-way text pagers without instruction (unstructured format) that they subsequently compared to the alphanumeric system with devised surveys assessing (on a scale of 0 to 100) time saved, increased daily efficiency, facilitation in patient care, and overall impression (helpfulness).In phase three, participants used a specific communication prioritization protocol (structured format) with the two-way text pagers with subsequent comparison and assessment with the same surveys. Compared to traditional alphanumeric pagers, new digital two-way text pagers were found to be statistically (p < 0.0001) more helpful by participants in all categories: as a time saver (80.33 vs. 56.95) p < 0.0001, increased daily efficiency (78.15 vs. 57.13) p < 0.0001, facilitation in patient care (78.79 vs. 56.95) p < 0.0001, and overall impression (helpfulness) (61.82 vs. 84.33) p < 0.0001. When compared to the alphanumeric pager, the two-way text pager was found to decrease subjectively call backs (73.6% to 45.6%, p < 0.0001), reduce interruptions of learning activities (43.63% to 26.6%, p < 0.0001) and enabled better patient care (59.8% to 42.2%, p < 0.0001). No significant statistical difference was found between the structured and unstructured system. Two-way text paging (structured versus unstructured guidance) was preferred over the conventional one-way alphanumeric paging system in every participant category. Two-way text paging is an effective alternative to alphanumeric paging, demonstrating saved time, increased daily efficiency, reduced call backs and interruptions of educational activities, and facilitation in patient care.

Symptomatic posterior vitreous detachment and the incidence of delayed retinal breaks: case series and meta-analysis.

PURPOSE: To establish the necessity for an early follow-up examination after an initial funduscopic examination with negative results for patients with acute, symptomatic posterior vitreous detachment (PVD). DESIGN: Retrospective case-control study and meta-analysis. METHODS: Records were reviewed of patients seeking treatment over a 4.5-year period who were diagnosed with an acute, symptomatic PVD. A MEDLINE search to identify all published observational case studies reporting vitreoretinal pathologic features after acute, symptomatic PVD. RESULTS: The incidence of retinal tears in eyes with a symptomatic PVD was 8.2%. The overall rate of retinal break in the meta-analysis portion of the study was 21.7%. In total, 1.8% of patients had retinal tears that were not seen on initial examination. Of the 29 patients with delayed-onset retinal breaks, 24 (82.8%) had at least one of the following: vitreous hemorrhage at initial examination, hemorrhage in the peripheral retina at initial examination, or new symptoms. CONCLUSIONS: If the results of an initial examination of a patient with an acute, symptomatic PVD are negative for retinal tears, the necessity of early follow-up may be best determined by the presence of pigmented cells in the vitreous, vitreous hemorrhage, or retinal hemorrhage. Most patients with symptomatic PVD may not need an early follow-up examination.

Lens clarity after 3-port lens-sparing vitrectomy in stage 4A and 4B retinal detachments secondary to retinopathy of prematurity.

OBJECTIVE: To assess lens clarity after 3-port lens-sparing vitrectomy for stages 4A and 4B tractional retinal detachment secondary to retinopathy of prematurity. METHODS: In a retrospective, interventional, consecutive clinical case series, 108 eyes of 102 patients who underwent lens-sparing vitrectomy for stages 4A and 4B tractional retinal detachment from February 1, 1998, through January 31, 2004, were reviewed. All procedures and follow-up examinations were performed by a single surgeon. Lens clarity was assessed at the final follow-up examination. RESULTS: Of the 108 eyes reviewed, 102 (94.4%) maintained clear lenses at the final follow-up examination, which ranged from 6 to 48 months (mean, 32 months) after the procedure. Thirty-two eyes had stage 4A detachments and 76 eyes had stage 4B. CONCLUSIONS: Three-port lens-sparing vitrectomy may be performed with relatively low risk of cataract formation during the early postoperative period. Maintenance of a clear crystalline lens during the critical period of visual development may lead to better functional outcomes.