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Eydie Miller-Ellis

Other affiliations: Scheie Eye Institute
Bio: Eydie Miller-Ellis is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Glaucoma & Intraocular pressure. The author has an hindex of 12, co-authored 37 publications receiving 467 citations. Previous affiliations of Eydie Miller-Ellis include Scheie Eye Institute.

Papers
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Journal ArticleDOI
TL;DR: Blindness and low BMI were significantly associated with POAG, and this population was predominantly recruited from neighborhoods whose population income exists at or near the federal poverty level.

47 citations

Journal Article
TL;DR: These results implicate African mtDNA haplogroups L1c2, L1 c2b, and L2 as risk factors for POAG.
Abstract: Purpose To estimate the population frequencies of all common mitochondrial variants and ancestral haplogroups among 1,999 subjects recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study, including 1,217 primary open-angle glaucoma (POAG) cases and 782 controls, and to identify ancestral subpopulations and mitochondrial mutations as potential risk factors for POAG susceptibility. Methods Subject classification by characteristic glaucomatous optic nerve findings and corresponding visual field defects, as defined by enrolling glaucoma specialists, stereo disc photography, phlebotomy, extraction of total DNA from peripheral blood or saliva, DNA quantification and normalization, PCR amplification of whole mitochondrial genomes, Ion Torrent deep semiconductor DNA sequencing on DNA pools ("Pool-seq"), Sanger sequencing of 3,479 individual mitochondrial DNAs, and bioinformatic analysis. Results The distribution of common African haplogroups within the POAAGG study population was broadly similar to prior surveys of African Americans. However, the POAG case population was found to be enriched in L1c2 haplogroups, which are defined in part by missense mutations m.6150G>A (Val83Ile, odds ratio [OR] 1.8, p=0.01), m.6253C>T (Met117Thr, rs200165736, OR 1.6, p=0.04), and m.6480G>A (Val193Ile, rs199476128, OR 4.6, p=0.04) in the cytochrome c oxidase subunit 1 (MT-CO1) gene and by a variant, m.2220A>G (OR 2.0, p=0.01), in MT-RNR2, which encodes the mitochondrial ribosomal 16s RNA gene. L2 haplogroups were predicted to be overrepresented in the POAG case population by Pool-seq, and the difference was confirmed to be significant with Sanger sequencing, that targeted the L2-associated variants m.2416T>C (rs28358580, OR 1.2, p=0.02) and m.2332C>T (OR 1.2, p=.02) in MT-RNR2. Another variant within MT-RNR2, m.3010G>A (rs3928306), previously implicated in sensitivity to the optic neuropathy-associated antibiotic linezolid, and arising on D4 and J1 lineages, associated with Leber hereditary optic neuropathy (LHON) severity, was confirmed to be common (>5%) but was not significantly enriched in the POAG cases. Two variants linked to the composition of the gut microbiome, m.15784T>C (rs527236194, haplogroup L2a1) and m.16390G>A (rs41378955, L2 haplogroups), were also enriched in the case DNA pools. Conclusions These results implicate African mtDNA haplogroups L1c2, L1c2b, and L2 as risk factors for POAG. Approximately one in four African Americans have these mitochondrial ancestries, which may contribute to their elevated glaucoma risk. These haplogroups are defined in part by ancestral variants in the MT-RNR2 and/or MT-CO1 genes, several of which have prior disease associations, such as MT-CO1 missense variants that have been implicated in prostate cancer.

43 citations

Journal ArticleDOI
01 Jun 2017-Medicine
TL;DR: Pseudoexfoliation glaucoma, combination with phacoemulsification cataract surgery and Hispanic race are factors associated with enhanced Trabectome survival.

40 citations

Journal ArticleDOI
TL;DR: Individuals at greatest risk for POAG should be screened by an ophthalmologist to allow earlier detection and to slow disease progression.
Abstract: Objective: To identify the major risk factors for primary open-angle glaucoma (POAG) in individuals of African descent. Methods: We searched PubMed for relevant articles, with results spanning April 1947 to present. All abstracts were reviewed and, where relevant to POAG and race, articles were catalogued and analyzed. Additional sources were identified through citations in articles returned by our search. Results: Numerous potential POAG risk factors were identified and organized into categories by demographics (age, sex, and skin color), lifestyle choices (smoking, alcohol), comorbidities (hypertension, diabetes, and obesity), ophthalmic findings (eye structure, central corneal thickness, corneal hysteresis, elevated intraocular pressure, myopia, cataract, and vascular abnormalities), family history, socioeconomic status, and adherence. Older age, male sex, lower central corneal thickness, decreased corneal hysteresis, elevated intraocular pressure, myopia, vascular abnormalities, and positive family history were definitively associated with increased risk of POAG. Conclusions: Individuals at greatest risk for POAG should be screened by an ophthalmologist to allow earlier detection and to slow disease progression. Further studies on the genetics of the disease will provide more insight into underlying pathologic mechanisms and could lead to improved therapeutic interventions. Continued research in urban areas with large populations of blacks is especially needed.

39 citations


Cited by
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01 Jan 2011
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

2,187 citations

01 Jan 2011
TL;DR: This paper reported a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls.
Abstract: We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10-10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10-9). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10-14, OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10-14, OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. © 2011 Nature America, Inc. All rights reserved.

347 citations

Journal ArticleDOI
12 Jan 2021-JAMA
TL;DR: Open-angle and narrow-angle forms of glaucoma are reviewed in this article, including a description of the pathophysiology, risk factors, screening, disease monitoring, and treatment options.
Abstract: Importance Glaucoma is the most common cause of irreversible blindness worldwide. Many patients with glaucoma are asymptomatic early in the disease course. Primary care clinicians should know which patients to refer to an eye care professional for a complete eye examination to check for signs of glaucoma and to determine what systemic conditions or medications can increase a patient’s risk of glaucoma. Open-angle and narrow-angle forms of glaucoma are reviewed, including a description of the pathophysiology, risk factors, screening, disease monitoring, and treatment options. Observations Glaucoma is a chronic progressive optic neuropathy, characterized by damage to the optic nerve and retinal nerve fiber layer, that can lead to permanent loss of peripheral or central vision. Intraocular pressure is the only known modifiable risk factor. Other important risk factors include older age, nonwhite race, and a family history of glaucoma. Several systemic medical conditions and medications including corticosteroids, anticholinergics, certain antidepressants, and topiramate may predispose patients to glaucoma. There are 2 broad categories of glaucoma, open-angle and angle-closure glaucoma. Diagnostic testing to assess for glaucoma and to monitor for disease progression includes measurement of intraocular pressure, perimetry, and optical coherence tomography. Treatment of glaucoma involves lowering intraocular pressure. This can be achieved with various classes of glaucoma medications as well as laser and incisional surgical procedures. Conclusions and Relevance Vision loss from glaucoma can be minimized by recognizing systemic conditions and medications that increase a patient’s risk of glaucoma and referring high-risk patients for a complete ophthalmologic examination. Clinicians should ensure that patients remain adherent with taking glaucoma medications and should monitor for adverse events from medical or surgical interventions used to treat glaucoma.

148 citations

Journal ArticleDOI
TL;DR: The gelatin implant effectively reduced IOP and medication needs over 2 years in POAG uncontrolled medically, with an acceptable safety profile.
Abstract: To evaluate the effectiveness of an ab interno subconjunctival gelatin implant as primary surgical intervention in reducing intraocular pressure (IOP) and IOP-lowering medication count in medically uncontrolled moderate primary open-angle glaucoma (POAG). In this prospective, non-randomized, open-label, multicenter, 2-year study, eyes with medicated baseline IOP 18–33 mmHg on 1–4 topical medications were implanted with (phaco + implant) or without (implant alone) phacoemulsification. Changes in mean IOP and medication count at months 12 (primary outcomes) and 24, clinical success rate (eyes [%] achieving ≥ 20% IOP reduction from baseline on the same or fewer medications without glaucoma-related secondary surgical intervention), intraoperative complications, and postoperative adverse events were assessed. The modified intent-to-treat population included 202 eyes (of 218 implanted). Changes (standard deviation) in mean IOP and medication count from baseline were − 6.5 (5.3) mmHg and − 1.7 (1.3) at month 12 and − 6.2 (4.9) mmHg and − 1.5 (1.4) at month 24, respectively (all P < 0.001). Mean medicated baseline IOP was reduced from 21.4 (3.6) to 14.9 (4.5) mmHg at 12 months and 15.2 (4.2) mmHg at 24 months, with similar results in both treatment groups. The clinical success rate was 67.6% at 12 months and 65.8% at 24 months. Overall, 51.1 (12 months) and 44.7% (24 months) of eyes were medication-free. The implant safety profile compared favorably with that published for trabeculectomy and tube shunts. The gelatin implant effectively reduced IOP and medication needs over 2 years in POAG uncontrolled medically, with an acceptable safety profile. ClinicalTrials.gov registration number: NCT02006693 (registered in the USA).

136 citations