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. 2023 Jul;107(7):1000-1006.
doi: 10.1136/bjophthalmol-2021-320665. Epub 2022 Apr 15.

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials

Collaborators, Affiliations

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials

Jason Q Core et al. Br J Ophthalmol. 2023 Jul.

Abstract

Background: Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

Methods: Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium fluid, and foveal thickness of retinal layers were evaluated at baseline and during 2-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularisation lesion type in multivariable regression models.

Results: Patients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference -6.2 letters; p=0.02), greater proportion with intraretinal fluid (IRF) at year 2 (75% vs 50%, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year 1 (difference -75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year 1 (difference -41.9 um; p=0.001) and year 2 (difference -43.3 um; p=0.001).

Conclusions: In this exploratory analysis, patients with diabetes taking thiazolidinediones and treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and greater proportions with IRF comparing to patients not taking thiazolidinediones.

Trial registration number: ClinicalTrials.gov NCT00593450.

Keywords: Neovascularisation; Retina; Vision.

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Conflict of interest statement

Competing interests: ED is a consultant to Novartis International AG. MGM serves on a data and safety monitoring committee for Genentech/Roche. GJ has a consultancy relationship with Alcon/Novartis, Genentech/Roche, Neurotech, EyePoint Pharmaceuticals and Adverum. G-SY is a consultant to Chengdu Kanghong Biotech, Ziemer Ophthalmic Systems AG and Synergy Research.

Figures

Figure 1
Figure 1
Retinal, subretinal fluid and subretinal tissue complex thickness at the foveal centre over time stratified by baseline use of thiazolidinedione. Mean thickness values of the retina, subretinal fluid and subretinal tissue complex compartments at the foveal centre are shown for key timepoints from baseline to week 104. Mean thickness values are stratified by patients taking (solid lines, N=151) and not taking thiazolidinediones at baseline (dashed lines, N=26).

References

    1. Idris I, Gray S, Donnelly R. Rosiglitazone and pulmonary oedema: an acute dose-dependent effect on human endothelial cell permeability. Diabetologia 2003;46:288–90. - PubMed
    1. Jiang Y, Thakran S, Bheemreddy R, et al. Pioglitazone normalizes insulin signaling in the diabetic rat retina through reduction in tumor necrosis factor α and suppressor of cytokine signaling 3. J Biol Chem 2014;289:26395–405. - PMC - PubMed
    1. Vijay SK, Mishra M, Kumar H, et al. Effect of pioglitazone and rosiglitazone on mediators of endothelial dysfunction, markers of angiogenesis and inflammatory cytokines in type-2 diabetes. Acta Diabetol 2009;46:27–33. - PubMed
    1. Thakran S, Zhang Q, Morales-Tirado V, et al. Pioglitazone restores IGFBP-3 levels through DNA pK in retinal endothelial cells cultured in hyperglycemic conditions. Invest Ophthalmol Vis Sci 2014;56:177–84. - PMC - PubMed
    1. Idris I, Warren G, Donnelly R. Association between thiazolidinedione treatment and risk of macular edema among patients with type 2 diabetes. Arch Intern Med 2012;172:1005–11. - PubMed

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