Department of Ophthalmology and Neuroscience, University of Bari "Aldo Moro", Medical School, Bari, Italy.
Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Medical School, Polyclinic, Piazza Giulio Cesare 11, 70124, Bari, Italy.
Int Ophthalmol. 2022 Feb;42(2):689-711. doi: 10.1007/s10792-021-02058-8. Epub 2021 Nov 21.
To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs.
A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors' departments were examined.
Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin's lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to "bull's eye" maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment.
The level of evidence for most of the drug reactions described herein is restricted to the "likely" or "possible" rather than to the "certain" category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.
概述类风湿关节炎（RA）的眼部特征，以及可能与抗风湿药物治疗相关的眼部药物不良反应（ADR）。
通过 PubMed、MEDLINE 和 EMBASE 数据库进行系统文献检索。此外，还对在作者所在科室就诊的 489 例 RA 患者进行了检查。
在上述队列中，分别诊断出 29%、6%、5%、2%和 10%的患者患有干燥性角结膜炎、表层巩膜炎、巩膜炎、周边溃疡性角膜炎（PUK）和前葡萄膜炎。非甾体抗炎药的眼部 ADR 很少见，包括结膜下出血和出血性视网膜病变。在服用吲哚美辛的患者中，观察到涡状角膜沉积物和色素性视网膜病变。糖皮质激素常引起后发性囊下白内障和开角型青光眼。甲氨蝶呤是疾病修饰抗风湿药物（DMARDs）的原型，与缺血性视神经病变、视网膜棉絮斑和眼眶非霍奇金淋巴瘤的发病有关。偶尔有报道称，接受来氟米特治疗的患者出现轻度的囊样黄斑水肿和点状角膜炎。羟氯喹最常见的 ADR 是涡状角膜病变，可能进展为“牛眼”黄斑病变。服用合成 DMARD 托法替尼的患者更常发生带状疱疹病毒（HZV）再激活，包括眼部 HZV。肿瘤坏死因子抑制剂与葡萄膜炎或结节病的反常发作或复发、视神经炎、脱髓鞘性视神经病变、视交叉病变和动眼神经麻痹有关。接受托珠单抗治疗的患者偶尔会出现 PUK 反复发作、多发性棉絮斑和视网膜出血，也可能与 HZV 再激活有关，可能涉及眼部。最后，抗 CD20 单克隆抗体利妥昔单抗很少与坏死性巩膜炎、黄斑水肿和视力损害有关。
本文所述大多数药物反应的证据水平仅限于“可能”或“可能”，而不是“确定”类别。然而，缺乏预示眼部 ADR 潜在风险的生物标志物，阻碍了它们的预防，并强调需要对每位患者进行这些治疗的风险与获益评估。
