A medication-wide association study to identify medications associated with incident clinically significant diabetic retinopathy

Ruilin Xiong; Wei Wang; Xianwen Shang; Yixiong Yuan; Yifan Chen; Lei Zhang; Katerina V Kiburg; Zhuoting Zhu; Mingguang He

doi:10.1177/25158414221139002

A medication-wide association study to identify medications associated with incident clinically significant diabetic retinopathy

Ther Adv Ophthalmol. 2023 Feb 24:15:25158414221139002. doi: 10.1177/25158414221139002. eCollection 2023 Jan-Dec.

Authors

Ruilin Xiong¹, Wei Wang¹, Xianwen Shang^{2

3}, Yixiong Yuan¹, Yifan Chen⁴, Lei Zhang^{2

5

6

7

8}, Katerina V Kiburg², Zhuoting Zhu^{9

10}, Mingguang He^{11

2

3

10}

Affiliations

¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, Guangdong, China.
² Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia.
³ Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
⁴ John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁵ China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
⁶ Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia.
⁷ Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC, Australia.
⁸ Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
⁹ Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Level 7, 32 Gisborne St, East Melbourne, VIC 3002, Australia.
¹⁰ Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia.
¹¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, No.54S Xianlie Road, Yuexiu District, Guangzhou, Guangdong 510000, China.

Abstract

Background: Diabetic retinopathy, a common microvascular complication of diabetes mellitus, is one of the leading causes of vision loss worldwide. Although some oral drugs have been suggested to affect the risk of diabetic retinopathy, systematic evaluation about the associations between medications and diabetic retinopathy is still absent.

Objective: To comprehensively investigate associations of systemic medications with incident clinically significant diabetic retinopathy (CSDR).

Design: Population-based cohort study.

Methods: From 2006 to 2009, more than 26 000 participants residing in New South Wales were enrolled in the 45 and Up study. Diabetic participants with self-reported physician diagnosis or records of anti-diabetic medication prescriptions were finally included in the current analysis. CSDR was defined as diabetic retinopathy cases requiring retinal photocoagulation recorded in the Medicare Benefits Schedule database from 2006 to 2016. Prescriptions of systemic medication from 5 years to 30 days prior to CSDR were retrieved from the Pharmaceutical Benefits Scheme. The study participants were equally split into training and testing datasets. Logistic regression analyses were performed for the association between each of systemic medication and CSDR in the training dataset. After controlling the false discovery rate (FDR), significant associations were further validated in the testing dataset.

Results: The 10-year incidence of CSDR was 3.9% (n = 404). A total of 26 systemic medications were found to be positively associated with CSDR, among which 15 were validated by the testing dataset. Additional adjustments for pertinent comorbidities suggested that isosorbide mononitrate (ISMN) (OR: 1.87, 95%CI: 1.00-3.48), calcitriol (OR: 4.08, 95% CI: 2.02-8.24), three insulins and analogues (e.g., intermediate-acting human insulin, OR: 4.28, 95% CI: 1.69-10.8), five anti-hypertensive medications (e.g., furosemide, OR: 2.53, 95% CI: 1.77-3.61), fenofibrate (OR: 1.96, 95% CI: 1.36-2.82) and clopidogrel (OR: 1.72, 95% CI: 1.15-2.58) were independently associated with CSDR.

Conclusion: This study investigated the association of a full spectrum of systemic medications with incident CSDR. ISMN, calcitriol, clopidogrel, a few subtypes of insulin, anti-hypertensive and cholesterol-lowering medications were found to be associated with incident CSDR.

Keywords: 45 and Up Study; diabetic retinopathy; medication-wide association study.