Jaclyn Kovach - Academia.edu (original) (raw)

Papers by Jaclyn Kovach

Clinical Nuclear Medicine, 2000

Acute graft-versus-host disease (GVHD) usually involves the skin, gastrointestinal tract, and liv... more Acute graft-versus-host disease (GVHD) usually involves the skin, gastrointestinal tract, and liver. A 47-year-old woman with fever of unknown origin was referred for a Ga-67 scan. The study showed diffuse uptake of Ga-67 throughout the skin. Subsequently, a skin biopsy confirmed the diagnosis of acute GVHD. The incidence, diagnosis, and pathophysiology of the dermatitis in acute GVHD are discussed.

To investigate whether female reproductive history and hormone replacement therapy (HRT) or birth... more To investigate whether female reproductive history and hormone replacement therapy (HRT) or birth control pills (BCPs) influence risk for age-related macular degeneration (AMD) and whether genetic factors interact with HRT to modulate AMD risk. METHODS. Related and unrelated female participants (n ϭ 799) were examined and data were analyzed with generalized estimating equations with adjustment for age and smoking. Individuals with AMD grades 1 to 2 were considered to be unaffected (n ϭ 239) and those with grades 3 to 5 were considered affected (n ϭ 560).

Clinical Ophthalmology, 2015

The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in pa... more The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available.

Molecular and cellular pharmacology, 2009

Diabetic retinopathy is the leading cause of vision loss among working-age people in the United S... more Diabetic retinopathy is the leading cause of vision loss among working-age people in the United States. The hallmark of diabetic retinopathy is vascular compromise. Increased vascular permeability leads to the development of diabetic macular edema, which is the major cause of vision loss in patients with diabetic retinopathy. Vascular occlusion causes retinal ischemia and subsequent angiogenesis (proliferative diabetic retinopathy), which increases the risk for vitreous hemorrhage and retinal detachment. Over the past 30 years our understanding of the pathophysiology of diabetic retinopathy has evolved greatly and has fostered the development of many novel treatments for this condition. This article will review promising new local and systemic pharmacologic treatments for diabetic macular edema and proliferative diabetic retinopathy.

Annals of human genetics, 2010

Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by bo... more Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P = 0.035). A significant interaction with smoking was detected at rs2248814 (P = 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible syne...

Investigative Ophthalmology & Visual Science, 2014

Purpose:Age-Related Macular Degeneration (AMD) is the leading cause of irreversible visual loss i... more Purpose:Age-Related Macular Degeneration (AMD) is the leading cause of irreversible visual loss in developed countries. Its etiology includes genetic and environmental factors. Although VEGFA variants are associated with AMD, the joint action of variants within the VEGF pathway and their interaction with non-genetic factors has not been investigated. Methods:Affymetrix 6.0 chipsets were used to genotype 668,238 SNPs in 1,207 AMD cases and 686 controls. Environmental exposures were collected by questionnaire. A set-based test was conducted using the chi-square statistic at each SNP derived from Kraft's 2df joint test. Pathway and gene-based test statistics were calculated as the mean of all independent SNP statistics. Phenotype labels were permuted 10,000 times to generate an empirical p-value. Results: While a main effect of the VEGF pathway was not identified, the pathway was associated with neovascular AMD in women when accounting for birth control pill (BCP) use (P= 0.017). Analysis of VEGF's subpathways found that SNPs in the Proliferation subpathway were associated with neovascular AMD (P=0.029) when accounting for BCP use. Nominally significant genes within this subpathway were also observed. Stratification by BCP use revealed novel significant genetic effects in women who had taken BCPs. Conclusions: These results illustrate that some AMD genetic risk factors may only be revealed when considering complex relationships among risk factors. This shows the utility of exploring pathways of previously associated genes to find novel effects. It also demonstrates the importance of incorporating environmental exposures in tests of genetic association at the SNP, gene, or pathway level.

Ophthalmic Surgery, Lasers, and Imaging, 2009

A patient presented with subfoveal choroidal neovascularization associated with angioid streaks a... more A patient presented with subfoveal choroidal neovascularization associated with angioid streaks and was treated with three intravitreal injections of off-label bevacizumab (1.25 mg) in the right eye. Visual acuity improved from 20/70 to 20/20 and remained at this level for 32 months. In certain patients with choroidal neovascularization from angioid streaks, intravitreal bevacizumab may produce normalization of visual acuity and macular anatomy for an extended period of time.

Journal of ophthalmology, 2012

Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a stand... more Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a standard treatment for neovascular age-related macular degeneration (AMD). During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies.

Experimental Eye Research, 2013

Variations in a locus at chromosome 10q26 are strongly associated with the risk of age-related ma... more Variations in a locus at chromosome 10q26 are strongly associated with the risk of age-related macular degeneration (AMD). The most significantly associated haplotype includes a nonsynonymous SNP rs10490924 in the exon 1 of ARMS2 and rs11200638 in the promoter region of HTRA1. It is under debate which gene(s), ARMS2, HTRA1 or some other genes are functionally responsible for the genetic association. To verify whether the associated variants correlate with a higher HTRA1 expression level as previously reported, HTRA1 mRNA and protein were measured in a larger human retina-RPE-choroid samples (n ¼ 82). Results show there is no significant change of HTRA1 mRNA level among genotypes at rs11200638, rs10490924 or an indel variant of ARMS2. Furthermore, two AMD-associated synonymous SNPs rs1049331 and rs2293870 in HTRA1 exon 1 do not change its protein level either. These results suggest that the AMD-associated variants in the chromosome 10q26 locus do not significantly affect the expression of HTRA1.

Ophthalmic Surgery, Lasers and Imaging Retina, 2013

Clinical Nuclear Medicine, 2000

Acute graft-versus-host disease (GVHD) usually involves the skin, gastrointestinal tract, and liv... more Acute graft-versus-host disease (GVHD) usually involves the skin, gastrointestinal tract, and liver. A 47-year-old woman with fever of unknown origin was referred for a Ga-67 scan. The study showed diffuse uptake of Ga-67 throughout the skin. Subsequently, a skin biopsy confirmed the diagnosis of acute GVHD. The incidence, diagnosis, and pathophysiology of the dermatitis in acute GVHD are discussed.

To investigate whether female reproductive history and hormone replacement therapy (HRT) or birth... more To investigate whether female reproductive history and hormone replacement therapy (HRT) or birth control pills (BCPs) influence risk for age-related macular degeneration (AMD) and whether genetic factors interact with HRT to modulate AMD risk. METHODS. Related and unrelated female participants (n ϭ 799) were examined and data were analyzed with generalized estimating equations with adjustment for age and smoking. Individuals with AMD grades 1 to 2 were considered to be unaffected (n ϭ 239) and those with grades 3 to 5 were considered affected (n ϭ 560).

Clinical Ophthalmology, 2015

The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in pa... more The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available.

Molecular and cellular pharmacology, 2009

Diabetic retinopathy is the leading cause of vision loss among working-age people in the United S... more Diabetic retinopathy is the leading cause of vision loss among working-age people in the United States. The hallmark of diabetic retinopathy is vascular compromise. Increased vascular permeability leads to the development of diabetic macular edema, which is the major cause of vision loss in patients with diabetic retinopathy. Vascular occlusion causes retinal ischemia and subsequent angiogenesis (proliferative diabetic retinopathy), which increases the risk for vitreous hemorrhage and retinal detachment. Over the past 30 years our understanding of the pathophysiology of diabetic retinopathy has evolved greatly and has fostered the development of many novel treatments for this condition. This article will review promising new local and systemic pharmacologic treatments for diabetic macular edema and proliferative diabetic retinopathy.

Annals of human genetics, 2010

Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by bo... more Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P = 0.035). A significant interaction with smoking was detected at rs2248814 (P = 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible syne...

Investigative Ophthalmology & Visual Science, 2014

Purpose:Age-Related Macular Degeneration (AMD) is the leading cause of irreversible visual loss i... more Purpose:Age-Related Macular Degeneration (AMD) is the leading cause of irreversible visual loss in developed countries. Its etiology includes genetic and environmental factors. Although VEGFA variants are associated with AMD, the joint action of variants within the VEGF pathway and their interaction with non-genetic factors has not been investigated. Methods:Affymetrix 6.0 chipsets were used to genotype 668,238 SNPs in 1,207 AMD cases and 686 controls. Environmental exposures were collected by questionnaire. A set-based test was conducted using the chi-square statistic at each SNP derived from Kraft's 2df joint test. Pathway and gene-based test statistics were calculated as the mean of all independent SNP statistics. Phenotype labels were permuted 10,000 times to generate an empirical p-value. Results: While a main effect of the VEGF pathway was not identified, the pathway was associated with neovascular AMD in women when accounting for birth control pill (BCP) use (P= 0.017). Analysis of VEGF's subpathways found that SNPs in the Proliferation subpathway were associated with neovascular AMD (P=0.029) when accounting for BCP use. Nominally significant genes within this subpathway were also observed. Stratification by BCP use revealed novel significant genetic effects in women who had taken BCPs. Conclusions: These results illustrate that some AMD genetic risk factors may only be revealed when considering complex relationships among risk factors. This shows the utility of exploring pathways of previously associated genes to find novel effects. It also demonstrates the importance of incorporating environmental exposures in tests of genetic association at the SNP, gene, or pathway level.

Ophthalmic Surgery, Lasers, and Imaging, 2009

A patient presented with subfoveal choroidal neovascularization associated with angioid streaks a... more A patient presented with subfoveal choroidal neovascularization associated with angioid streaks and was treated with three intravitreal injections of off-label bevacizumab (1.25 mg) in the right eye. Visual acuity improved from 20/70 to 20/20 and remained at this level for 32 months. In certain patients with choroidal neovascularization from angioid streaks, intravitreal bevacizumab may produce normalization of visual acuity and macular anatomy for an extended period of time.

Journal of ophthalmology, 2012

Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a stand... more Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a standard treatment for neovascular age-related macular degeneration (AMD). During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies.

Experimental Eye Research, 2013

Variations in a locus at chromosome 10q26 are strongly associated with the risk of age-related ma... more Variations in a locus at chromosome 10q26 are strongly associated with the risk of age-related macular degeneration (AMD). The most significantly associated haplotype includes a nonsynonymous SNP rs10490924 in the exon 1 of ARMS2 and rs11200638 in the promoter region of HTRA1. It is under debate which gene(s), ARMS2, HTRA1 or some other genes are functionally responsible for the genetic association. To verify whether the associated variants correlate with a higher HTRA1 expression level as previously reported, HTRA1 mRNA and protein were measured in a larger human retina-RPE-choroid samples (n ¼ 82). Results show there is no significant change of HTRA1 mRNA level among genotypes at rs11200638, rs10490924 or an indel variant of ARMS2. Furthermore, two AMD-associated synonymous SNPs rs1049331 and rs2293870 in HTRA1 exon 1 do not change its protein level either. These results suggest that the AMD-associated variants in the chromosome 10q26 locus do not significantly affect the expression of HTRA1.

Ophthalmic Surgery, Lasers and Imaging Retina, 2013