title: Oxidized Low-Density Lipoprotein and the Incidence of Proliferative Diabetic Retinopathy and Clinically Significant Macular Edema Determined From Fundus Photographs.
abstract: OBJECTIVE
  Studies have shown oxidized low-density lipoprotein to be associated with the incidence of proliferative retinopathy and other complications of type 1 diabetes mellitus. Because low-risk interventions are available to modify oxidized low-density lipoprotein, it is important to examine the relationships between this factor and the incidence of proliferative retinopathy and of macular edema, 2 important causes of visual impairment in people with type 1 diabetes.
  
  
  OBJECTIVE
  To determine the association of oxidized low-density lipoprotein with the worsening of diabetic retinopathy and the incidence of proliferative retinopathy and of macular edema.
  
  
  METHODS
  Of 996 participants with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy, 730 were examined up to 4 times (1990-1992, 1994-1996, 2005-2007, and 2012-2014) over 24 years and had assays of oxidized low-density lipoprotein and fundus photographs gradable for diabetic retinopathy and macular edema. Analyses started July 2014 and ended February 2015.
  
  
  METHODS
  Worsening of diabetic retinopathy, incidence of proliferative diabetic retinopathy, and incidence of macular edema as assessed via grading of color stereo film fundus photographs. The levels of oxidized low-density lipoprotein collected from serum samples at the time of each examination were measured in 2013 and 2014 from frozen serum.
  
  
  RESULTS
  The cohort at baseline had a mean (SD) level of oxidized low-density lipoprotein of 30.0 (8.5) U/L. While adjusting for duration of diabetes, glycated hemoglobin A1c level, and other factors, we found that neither the level of oxidized low-density lipoprotein at the beginning of a period nor the change in it over a certain period was associated with the incidence of proliferative diabetic retinopathy (hazard ratio [HR], 1.11 [95% CI, 0.91-1.35], P = .30; odds ratio [OR], 1.77 [95% CI, 0.99-3.17], P = .06), the incidence of macular edema (HR, 1.04 [95% CI, 0.83-1.29], P = .74; OR, 1.08 [95% CI, 0.44-2.61], P = .87), or the worsening of diabetic retinopathy (HR, 0.94 [95% CI, 0.83-1.07], P = .34; OR, 1.32 [95% CI, 0.83-2.09], P = .24).
  
  
  CONCLUSIONS
  Our findings do not provide evidence for a relationship between increasing levels of serum oxidized low-density lipoprotein and the incidence of macular edema or the worsening of diabetic retinopathy in persons with type 1 diabetes. The potential increase in the HR for incident proliferative retinopathy, with an increase in oxidized low-density lipoprotein level over the preceding period, warrants further investigation of this relationship.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Chelsea E
authors.initials: CE
authors.lastname: Myers
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison3Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Cruickshanks
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gangnon
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003930:Diabetic Retinopathy / Q000097:blood / Q000453:epidemiology*; D005260:Female; D005654:Fundus Oculi; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015994:Incidence; D008077:Lipoproteins, LDL / Q000097:blood*; D008269:Macular Edema / Q000097:blood / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D010781:Photography; D012307:Risk Factors; D014922:Wisconsin / Q000453:epidemiology
chemical_list: D002784:Cholesterol; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; C517652:hemoglobin A1c protein, human; C099252:oxidized low density lipoprotein