Faculty Bibliography
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114
Canadian journal of ophthalmology = Journal canadien d'ophtalmologie. 2020:55(3):239-244.DOI: 10.1016/j.jcjo.2019.10.007
Relationship between optic disc hemorrhage and corneal hysteresis
OBJECTIVE:To determine the relationship between optic disc hemorrhage (DH) and corneal hysteresis (CH). METHODS:Consecutive patients with prior or current photographic evidence of unilateral DH who had undergone CH measurement with the Ocular Response Analyzer (ORA; Reichert, Buffalo, NY) were enrolled. Eyes with a history of corneal disease, refractive surgery, or bilateral DH were excluded. Central corneal thickness (CCT), visual field data, 5 consecutive previous intraocular pressures (IOPs), and maximum documented peak IOP were obtained by chart review. Vertical cup-to-disc ratio (VCDR), the presence of neuroretinal rim notching, number of clock hours of beta zone parapapillary atrophy (ßPPA), and eye with greater ßPPA width were determined from photographs by 2 masked expert examiners. RESULTS:We identified and analyzed 49 patients with photographically documented unilateral DH. Compared to fellow non-DH eyes, eyes with DH had lower CH (8.7 ± 1.9 vs 9.2 ± 1.7; p = 0.002), higher IOP (15.6 ± 3.6 vs 14.3 ± 4.1; p = 0.017), and greater VCDR (0.79 ± 0.13 vs 0.68 ± 0.23; p < 0.001), but were similar with respect to CCT, ßPPA extent, rim notching, peak IOP, and visual field damage (all p > 0.05). Using multivariate conditional logistic regression analysis, only CH (p = 0.012) and VCDR (p = 0.004) predicted the laterality of the DH. CONCLUSIONS:Lower CH and greater VCDR are independently associated with DH. This suggests that CH may be a structural biomarker for an abnormality of the optic nerve complex that may be associated with progressive glaucoma. Eyes in which DH were detected had lower CH.
PMID: 31879066
ISSN: 1715-3360
CID: 4244392
Outcomes of the Shunt Tube Exposure Prevention Study: A Randomized Clinical Trial
PURPOSE/OBJECTIVE:To compare the long-term safety and efficacy of amniotic membrane-umbilical cord (AM-UC) and pericardium patch grafts in reducing glaucoma shunt tube exposure. DESIGN/METHODS:Multicenter, prospective, randomized clinical trial. PARTICIPANTS/METHODS:Adults with uncontrolled glaucoma undergoing glaucoma drainage device (GDD) implantation. METHODS:Patients were randomized to receive GDD with either AM-UC or pericardium patch grafts to cover GDD tubes. Patients were followed up clinically with anterior segment (AS) OCT to assess patch graft stability and host-tissue integration prospectively. MAIN OUTCOME MEASURES/METHODS:Tube exposure, graft thinning, and graft-related complications. RESULTS:A total of 81 eyes of 81 patients (50 women, 31 men) with a mean age of 67±13 years underwent GGD implantation using Baerveldt (n = 72) or Ahmed valve (n = 9). Tubes were inserted in the anterior chamber (n = 71), sulcus (n = 6), or pars plana (n = 4). Tube ligation was performed with Baerveldt GDD along with fenestration (n = 51) or orphan trabeculectomy (n = 21). Tubes were covered with AM-UC (n = 41) or pericardium (n = 40). The mean follow-up time was 29±8 months (range, 13-40 months). Tube exposure occurred in 1 eye (2%) in the AM-UC group at 3 months and in 2 eyes (5%) in the pericardium group at 2 and 6 months (P = 0.54). Sequential AS OCT showed better host-tissue integration and significantly less graft thinning in the AM-UC group. Early graft thinning (≤3 months) occurred in 5 eyes (12%) in the AM-UC group and in 17 eyes (43%) in the pericardium group (P = 0.002). Late thinning occurred in 2 eyes (5%) and 11 eyes (28%) in the AM-UC and pericardium groups, respectively (P = 0.007). Graft translucency and cosmetic appearance of the AM-UC graft were superior to those of the pericardium graft. No evidence of graft rejection or infection was associated with the patch grafts in either group. CONCLUSIONS:Amniotic membrane-umbilical cord grafts are well tolerated and offer an alternative to pericardium for safe and stable tube shunt coverage. Its high-tensile strength, low immunogenicity, and excellent host-tissue integration significantly reduced graft thinning.
PMID: 32672570
ISSN: 2589-4196
CID: 4528322
The African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of Genotype to Glaucoma Phenotype in African Americans: Study Design and Baseline Data
PURPOSE/OBJECTIVE:To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN/METHODS:Cross-sectional, case-control study. PARTICIPANTS/METHODS: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/METHODS: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 IIIÂ genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.
PMCID:6050158
PMID: 29361356
ISSN: 1549-4713
CID: 2988612
Genetic Architecture of Primary Open Angle Glaucoma in Individuals of African Descent: The African Descent & Glaucoma Evaluation Study (ADAGES) III
OBJECTIVE:Find genetic contributions to glaucoma in African Americans. DESIGN/METHODS:Cross-sectional, case-control study. PARTICIPANTS/METHODS:1875 POAG cases and 1709 controls, self-identified as African Descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGESIII) and Wake Forest School of Medicine. METHODS:MegaChip genotypes were imputed to Thousand Genomes data. Association of 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 Characteristics (ROC-AUC). MAIN OUTCOME/RESULTS:POAG defined by visual field loss without other non-ocular conditions (N=1875). Advanced POAG was defined by age-based mean deviation of visual field (N=946). RESULTS:) was observed, not in LD with the previously reported ED SNP. Additional previously identified loci associated with POAG in AD were: 8q22, AFAP1, TMCO1. An AUC of 0.62 was observed with an unweighted genetic risk score composed of 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 ENO4 locus was putatively identified in subjects of African descent. In addition to this finding, this GWAS in AD POAG subjects contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine-mapping of regions due to shorter average linkage disequilibrium (FNDC3B). While not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.
PMID: 30352225
ISSN: 1549-4713
CID: 3384612
Glaucoma Diagnostic Capability of Circumpapillary Retinal Nerve Fiber Layer Thickness in Circle Scans With Different Diameters
PURPOSE/OBJECTIVE:To compare varying circumpapillary optical coherence tomographic (OCT) scan diameters for glaucoma diagnosis. MATERIALS AND METHODS/METHODS:Prospective, cross-sectional, observational study. Circumpapillary retinal nerve fiber layer thickness (RNFLT) was measured using spectral-domain OCT in 1 randomly selected eye. Scans with diameters of 3.5, 4.1, and 4.7 mm were obtained, each with 7 parameters: mean global (G) RNFLT and mean RNFLT for the temporal-inferior (TI), nasal-inferior (NI), temporal-superior (TS), nasal-superior (NS), nasal (N), and temporal (T) sectors. Areas under the receiver operating characteristic curve (AUCs) were calculated. RESULTS:Mean age was 55±18 years in 68 healthy eyes and 59±15 years in 95 glaucomatous eyes (P=0.12). Visual field mean deviation was -7.55±6.61 dB in glaucomatous eyes. In all 3 circle scans, mean TI RNFLT had the greatest AUC (0.974 to 0.983), followed by mean G RNFLT (0.949 to 0.956). The AUC of mean TI RNFLT in the 4.1-mm scan (0.983) was greater than the AUCs of mean TI RNFLTs in the 4.7- (0.978; P=0.128) and 3.5-mm (0.974; P=0.049) scans. The AUC of mean TI RNFLT in the 4.1-mm scan (0.983) was greater than the AUCs of mean G RNFLTs in the 3.5- (0.954; P=0.011), 4.1- (0.956; P=0.016), and 4.7-mm (0.949; P=0.011) scans. In 2 eyes with large parapapillary atrophy, RNFL segmentation error was noted only in the 3.5-mm scan in the area of parapapillary atrophy. CONCLUSIONS:Further investigations to find the spectral-domain OCT circle scan diameter with the best diagnostic capability and the least artifacts are warranted, especially focusing on larger-than-conventional circle scans.
PMID: 28355173
ISSN: 1536-481x
CID: 3081512
Glaucoma Diagnostic Capability of Global and Regional Measurements of Isolated Ganglion Cell Layer and Inner Plexiform Layer
PURPOSE/OBJECTIVE:To compare glaucoma diagnostic capability of global/regional macular layer parameters in different-sized grids. MATERIALS AND METHODS/METHODS:Serial horizontal spectral-domain optical coherence tomography scans of macula were obtained. Automated macular grids with diameters of 3, 3.45, and 6 mm were used. For each grid, 10 parameters (total volume; average thicknesses in 9 regions) were obtained for 5 layers: macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), ganglion cell-inner plexiform layer (GCIPL; GCL+IPL), and ganglion cell complex (GCC; mRNFL+GCL+IPL). RESULTS:Sixty-nine normal eyes (69 subjects) and 87 glaucomatous eyes (87 patients) were included. For the total volume parameter, the area under the receiver operating characteristic curves (AUCs) in 6-mm grid were larger than the AUCs in 3- and 3.45-mm grids for GCL, GCC, GCIPL, and mRNFL (all P<0.020). For the average thickness parameters, the best AUC in 6-mm grid (T2 region for GCL, IPL, and GCIPL; I2 region for mRNFL and GCC) was greater than the best AUC in 3-mm grid for GCL, GCC, and mRNFL (P<0.045). The AUC of GCL volume (0.920) was similar to those of GCC (0.920) and GCIPL (0.909) volume. The AUC of GCL T2 region thickness (0.942) was similar to those of GCC I2 region (0.942) and GCIPL T2 region (0.934) thickness. CONCLUSIONS:Isolated macular GCL appears to be as good as GCC and GCIPL in glaucoma diagnosis, while IPL does not. Larger macular grids may be better at detecting glaucoma. Each layer has a characteristic region with the best glaucoma diagnostic capability.
PMID: 27811573
ISSN: 1536-481x
CID: 3093252
Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
PMID: 27064256
ISSN: 1546-1718
CID: 3231952
Lamina Cribrosa Depth in Different Stages of Glaucoma
Purpose: To compare lamina cribrosa (LC) depth between normal eyes and eyes with different stages of treated glaucoma. Methods: Serial enhanced depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve head were obtained. To generate the mean LC depth for each eye, LC depths were measured in 11 equally spaced horizontal B-scans and averaged. The mean LC depth was compared among normal, pre-perimetric, mild-to-moderate, and severe glaucoma groups. Among patients with visual field (VF) loss, correlation analysis was performed 1) between mean LC depth and VF mean deviation (MD), and 2) between mean LC depth and retinal nerve fiber layer (RNFL) thickness. Results: 86 normal eyes (age, 56+/-14 years), 47 pre-perimetric glaucoma eyes (age, 60+/-16 years), 55 mild-to-moderate glaucomatous eyes (age, 59+/-16 years; VF MD, -6.0+/-3.2 dB), and 60 severe glaucomatous eyes (age, 59+/-17 years; VF MD, -19.7+/-6.1 dB) were included. Mean LC depth was significantly greater in pre-perimetric glaucoma than in normal eyes (390 vs. 344 microm, P=0.004) and in mild-to-moderate than in pre-perimetric glaucoma eyes (448 vs. 390 microm, P=0.001). However, no significant difference was observed between mild-to-moderate and severe glaucoma eyes (448 vs. 437 microm, P=0.52). No correlation was observed between LC depth and VF MD (P=0.56) or RNFL thickness (P=0.90) in glaucomatous eyes with VF loss. Conclusions: In treated glaucoma, posterior LC displacement occurs mostly in the pre-perimetric and mild-to-moderate glaucoma stages. This warrants further investigation of LC depth as a parameter to monitor glaucoma progression in the early stages.
PMID: 25722212
ISSN: 0146-0404
CID: 1474072
Steady State Pattern Electroretinography (ssPERG) in Age-Related Macular Degeneration (AMD) compared to controls. [Meeting Abstract]
ISI:000433203504306
ISSN: 0146-0404
CID: 3566882
Evaluation of steady state pattern electroretinography (ssPERG) in discriminating normal from glaucoma suspect and glaucomatous eyes [Meeting Abstract]
Purpose: To evaluate the ability of ssPERG to discriminate between healthy, glaucoma suspect, and glaucomatous eyes. Methods: We enrolled one eye of each of 15 healthy individuals; 15 glaucoma suspect eyes defined by having at least one of the following optic nerve changes (a cup to disc ratio > 0.6; inter-eye cup to disc ratio asymmetry > 0.2; retinal nerve fiber layer defects; neuroretinal rim notching; disc hemorrhage) plus abnormal nerve fiber layer by OCT and a normal SAP and 30 glaucomatous eyes with visual field (VF) loss) All subjects had VA better than 20/30. Normal subjects had normal VFs. Glaucoma was staged as early (mean deviation, MD>-6.0 dB) and moderate (mean deviation, MD>-6.0 dB) (15 eyes each). Synchronized single-channel ssPERGs were recorded using the Diopsys NOVA System (Diopsys, Inc. Pine Brook, NJ). An area under the curve (AUC) analysis was performed comparing the healthy eyes to the other groups. Results: The AUCs for the healthy eyes compared to the three groups of patients were as follows: 1) glaucoma suspect eyes 0.70(0.50-0.89); early glaucomatous visual field damage 0.91(0.79-1.00); and moderate glaucomatous visual field damage 0.96(0.87-1.00). The sensitivity and specificity for discriminating mild glaucomatous eyes from health eyes was 0.87 and 0.93 respectively. The sensitivity and specificity for discriminating moderate glaucomatous eyes from healthy eyes was 0.93 and 1.00 respectively. The sensitivity and specificity for the glaucoma suspect eyes to healthy eyes was 0.54 and 0.80 respectively. Conclusions: ssPERG is able to discriminate between healthy eyes, glaucoma suspect eyes and glaucomatous eyes and may be able to differentiate between eyes with early and moderate VF loss
EMBASE:616122064
ISSN: 0146-0404
CID: 2565272
