@article{86d851080a33448cbbac9b926d40fa3d,
title = "Lack of Longitudinal Association Between Thiazolidinediones and Incidence and Progression of Diabetic Eye Disease: The ACCORD Eye Study",
abstract = "Purpose: To report the longitudinal association between use of thiazolidinediones (TZDs), visual acuity (VA) change, and diabetic eye disease incidence and progression. Design: Cohort study ancillary to a randomized clinical trial. Methods: We analyzed baseline and 4-year follow-up data of 2856 ACCORD trial participants with no history of proliferative diabetic retinopathy. Based on stereoscopic fundus photographs, we evaluated diabetic macular edema (DME) progression and DR progression. We also evaluated 10- and 15-letter change on the ETDRS visual acuity chart. Main outcome measures were incidence or progression of DME or DR and change in visual acuity. Results: TZD use was not associated with DME incidence in either the analysis of any use (adjusted odds ratio [aOR] [95% CI]: 1.22 [0.72–2.05]) or duration of use (aOR: 1.02 [0.99–1.04]). Diabetic retinopathy (DR) incidence/progression was more common in patients with no or mild DR at baseline who were ever treated with TZDs (aOR: 1.68 [1.11–2.55]), but this association disappeared when adjusting for the time on TZD (aOR: 1.02 [1.00–1.04]). DR progression among those with moderate or worse DR at baseline was no different between TZD users and non-users. TZD usage had no effect on the ultimate visual acuity outcome. Conclusion: In this longitudinal study of patients with type 2 diabetes, we found no association between TZD use and visual acuity outcomes or DME progression, and no consistent evidence of increased DR progression in patients ever treated with TZDs vs those never treated with TZDs.",
author = "{ACCORD Study Group} and Gower, {Emily W.} and Lovato, {James F.} and Ambrosius, {Walter T.} and Chew, {Emily Y.} and Danis, {Ronald P.} and Davis, {Matthew D.} and Goff, {David C.} and Greven, {Craig M.} and Gotto, {Antonio M.} and Kent Bailey and Dorothy Gohdes and Steven Haffner and Roland Hiss and Kenneth Jamerson and Kerry Lee and David Nathan and James Sowers and Walters, {Le Roy}",
note = "Funding Information: The association between TZD use and visual acuity change has not been evaluated extensively in previous studies. In the current analysis, we used the broader sample of participants enrolled in the ACCORD trial to evaluate the possibility of clinically significant visual acuity change associated with TZD usage. We found no association between either any TZD use or duration of TZD use and clinically meaningful visual acuity change at 4 years. This result is consistent with our cross-sectional analysis, in which we found less than a 1-letter difference between the TZD-treated and non-TZD-treated participants at baseline. 12 This finding is similar to a cross-sectional study of 59 patients reporting >6 months of TZD usage and 49 without TZD in which no significant differences were seen in best-corrected visual acuity or level of DR for the TZD vs no-TZD group. 20 The strengths of this study are its longitudinal nature, large sample size, direct link to a randomized clinical trial with prespecified outcomes of visual acuity, and use of standardized, centrally interpreted photographs to grade DME and DR progression. Weaknesses include method of determination of quantitative TZD usage and follow-up limited to only 4 years. In addition, because history of TZD exposure prior to study enrollment would constitute an unmeasured exposure, a subject who was taking TZDs and then ceased prior to ACCORD would be analyzed as not having had TZD exposure. This would have the effect of attenuating any differences between TZD exposure and non-exposure as we have measured it. However, prior studies of TZD and DR incidence that showed an association were based mostly on short time frames with similar TZD usage definitions. We assessed DME with stereo photographs because this study was started prior to the widespread availability of OCT at the onset of the ACCORD Eye Study. The lack of OCT technology and the limited number of participants affected with DME are limitations of the current study. Although this study is larger than most prior prospective studies, the ability to examine DME progression in detail is limited by the number of patients (n = 218) with DME at baseline. Of note, however, a recent study examining the role of macular thickness and volume in patients who took TZDs compared with those who did not found no significant difference in mean central retinal thickness between the groups, and the TZD group had significantly lower macular volume. 20 Finally, clinical trials participants may be healthier than the general population, and as such, rates of progression may be lower in our sample. In summary, we did not demonstrate an association between TZD usage and DR or DME incidence or progression, or clinically meaningful visual acuity change, over a 4-year period. It remains possible that exposure to TZD longer than the 4 years of follow-up in our study could be associated with DME progression. Additionally, the possibility of rare idiosyncratic reactions in susceptible patients cannot be ruled out as a potential cause of DME progression. Funding/Support: This work was supported by National Heart Lung and Blood Institute contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, and IAA#Y1-HC-9035 and IAA#Y1-HC-1010. Other components of the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute, contributed funding. The Centers for Disease Control funded substudies within ACCORD on cost-effectiveness and health-related quality of life. General Clinical Research Centers provide support at many sites. Financial Disclosures: The following authors have no financial disclosures: Emily W. Gower, James F. Lovato, Walter T. Ambrosius, Emily Y. Chew, Ronald P. Danis, Matthew D. Davis, David C. Goff Jr, and Craig M. Greven. All authors attest that they meet the current ICMJE criteria for authorship. Other Acknowledgements: Members of the ACCORD Data and Safety Monitoring Board included Antonio M. Gotto, Jr (chair), Kent Bailey, Dorothy Gohdes, Steven Haffner, Roland Hiss, Kenneth Jamerson, Kerry Lee, David Nathan, James Sowers, and LeRoy Walters. The following companies provided study medications, equipment, or supplies: Abbott Laboratories (Abbott Park, IL); Amylin Pharmaceutical (San Diego, CA); AstraZeneca Pharmaceuticals LP (Wilmington, DE); Bayer HealthCare LLC (Tarrytown, NY); Closer Healthcare Inc (Tequesta, FL); GlaxoSmithKline Pharmaceuticals (Philadelphia, PA); King Pharmaceuticals, Inc (Bristol, TN); Merck & Co, Inc (Whitehouse Station, NJ); Novartis Pharmaceuticals, Inc (East Hanover, NJ); Novo Nordisk, Inc (Princeton, NJ); Omron Healthcare, Inc (Schaumburg, IL); Sanofi-Aventis U.S. (Bridgewater, NJ); Schering-Plough Corporation (Kenilworth, NJ); and Takeda Pharmaceuticals (Deerfield, IL). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2018",
month = mar,
doi = "10.1016/j.ajo.2017.12.007",
language = "English (US)",
volume = "187",
pages = "138--147",
journal = "American Journal of Ophthalmology",
issn = "0002-9394",
publisher = "Elsevier",
}