Tetracyclines and Risk of Proliferative Vitreoretinopathy after Rhegmatogenous Retinal Detachment

IF 5.9 Q1 OPHTHALMOLOGY

Ophthalmology. Retina Pub Date : 2026-10-01 Epub Date: 2026-04-28 DOI:10.1016/j.oret.2026.04.017

Itay Nitzan MD, MPH, Yossi Eshel MD, Tehila Shlomov MD, Shoham Kubovsky MD, Nadav Shemesh MD, MHA, Jaime Levy MD, Itay Chowers MD, Samer Khateb MD, PhD

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After 1:1 propensity score matching, 2886 patients with documented systemic tetracycline administration were compared with 2886 matched controls.</div></div><div>Adults aged 18 years or older with RRD were identified within a multicenter federated electronic health record network. After 1:1 propensity score matching, 2886 patients with documented systemic tetracycline administration were compared with 2886 matched controls.</div><div><h3>Methods</h3><div>Systemic tetracycline exposure was defined as a recorded prescription from 1 month before to 6 months after RRD-related cohort entry. Propensity score matching was performed on demographics, socioeconomic determinants, systemic and ophthalmic comorbidities, medications, laboratory values, and health care utilization. Time-to-event analyses were conducted using Kaplan–Meier estimation and Cox proportional hazards models. 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Reoperation was evaluated as a secondary outcome.</div></div><div>Hazard ratios (HRs) for PVR-related outcomes, defined as complex retinal detachment repair, nondiabetic proliferative retinopathy, and tractional retinal detachment. Reoperation was evaluated as a secondary outcome.</div><div><h3>Results</h3><div>Baseline characteristics were well balanced after matching. During comparable follow-up, systemic tetracycline administration was associated with a lower risk of complex retinal detachment repair (HR, 0.33; 95% confidence interval [CI], 0.25–0.43), nondiabetic proliferative retinopathy (HR, 0.63; 95% CI, 0.45–0.89), and tractional retinal detachment (HR, 0.57; 95% CI, 0.43–0.75). Reoperation was also less frequent among tetracycline-exposed patients (HR, 0.34; 95% CI, 0.26–0.46). Findings remained consistent across prespecified sensitivity analyses, including alternative exposure definitions, follow-up durations, doxycycline-only exposure, and active comparator analyses. 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Abstract

Objective

To evaluate the association between documented systemic tetracycline administration and the risk of proliferative vitreoretinopathy (PVR)–related outcomes after rhegmatogenous retinal detachment (RRD).

Design

Retrospective cohort study with 1-year follow-up.

Participants

Adults aged 18 years or older with RRD were identified within a multicenter federated electronic health record network. After 1:1 propensity score matching, 2886 patients with documented systemic tetracycline administration were compared with 2886 matched controls.

Methods

Systemic tetracycline exposure was defined as a recorded prescription from 1 month before to 6 months after RRD-related cohort entry. Propensity score matching was performed on demographics, socioeconomic determinants, systemic and ophthalmic comorbidities, medications, laboratory values, and health care utilization. Time-to-event analyses were conducted using Kaplan–Meier estimation and Cox proportional hazards models. Prespecified sensitivity analyses and active comparator analyses were performed to assess robustness.

Main Outcome Measures

Hazard ratios (HRs) for PVR-related outcomes, defined as complex retinal detachment repair, nondiabetic proliferative retinopathy, and tractional retinal detachment. Reoperation was evaluated as a secondary outcome.

Results

Baseline characteristics were well balanced after matching. During comparable follow-up, systemic tetracycline administration was associated with a lower risk of complex retinal detachment repair (HR, 0.33; 95% confidence interval [CI], 0.25–0.43), nondiabetic proliferative retinopathy (HR, 0.63; 95% CI, 0.45–0.89), and tractional retinal detachment (HR, 0.57; 95% CI, 0.43–0.75). Reoperation was also less frequent among tetracycline-exposed patients (HR, 0.34; 95% CI, 0.26–0.46). Findings remained consistent across prespecified sensitivity analyses, including alternative exposure definitions, follow-up durations, doxycycline-only exposure, and active comparator analyses. E-values suggested robustness to unmeasured confounding, and positive and negative control outcomes supported the internal validity of the observed associations.

Conclusions

Documented systemic tetracycline administration was associated with a lower risk of PVR-related outcomes after RRD. These findings support further prospective evaluation of tetracyclines as a potential adjunctive strategy for PVR prevention.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.

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四环素与孔源性视网膜脱离后增生性玻璃体视网膜病变的风险。

目的：评估系统性四环素给药与孔源性视网膜脱离（RRD）后增殖性玻璃体视网膜病变（PVR）相关结果的风险之间的关系。设计：回顾性队列研究，随访1年。参与者：在多中心联合电子健康记录网络中确定的18岁或以上的RRD成年人。在1:1倾向评分匹配后，2886例记录在案的全身性四环素用药患者与2886例匹配的对照组进行了比较。方法：全身性四环素暴露被定义为rrd相关队列进入前1个月至6个月的记录处方。对人口统计学、社会经济决定因素、系统和眼科合并症、药物、实验室值和医疗保健利用进行倾向评分匹配。使用Kaplan-Meier估计和Cox比例风险模型进行时间-事件分析。进行预先指定的敏感性分析和主动比较分析来评估稳健性。主要结局指标：pvr相关结局的风险比（hr），定义为复杂视网膜脱离修复、非糖尿病性增殖性视网膜病变和牵引性视网膜脱离。再次手术作为次要结果进行评估。结果：基线特征匹配后平衡良好。在可比较的随访中，全身性四环素治疗与复杂性视网膜脱离修复（HR, 0.33; 95% CI, 0.25-0.43）、非糖尿病性增生性视网膜病变（HR, 0.63; 95% CI, 0.45-0.89）和牵拉性视网膜脱离（HR, 0.57; 95% CI, 0.43-0.75）的较低风险相关。四环素暴露患者的再手术发生率也较低（HR, 0.34; 95% CI, 0.26-0.46）。在预先指定的敏感性分析中，研究结果保持一致，包括替代暴露定义、随访时间、单剂量多西环素暴露和活性比较分析。e值表明对未测量混杂的稳健性，阳性和阴性对照结果支持观察到的关联的内部有效性。结论：记录在案的全身性四环素服用与RRD后pvr相关结局的较低风险相关。这些发现支持对四环素作为预防PVR的潜在辅助策略进行进一步的前瞻性评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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