Hallaj Shahin, Shalaby Wesam Shamseldin, Sinha Sapna, Myers Jonathan S, Razeghinejad Reza
Glaucoma Service, Wills Eye Hospital, Sidney Kimmel Medical College, Thomas Jefferson University, 840 Walnut St, Suite 1140, Philadelphia, PA 19107 USA.
Division of Ophthalmology Informatics and Data Sciences, Hamilton Glaucoma Center and Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, La Jolla, CA USA.
Curr Ophthalmol Rep. 2025;13(1):9. doi: 10.1007/s40135-025-00332-x. Epub 2025 Jul 8.
This paper provides a detailed overview of systemic carbonic anhydrase inhibitors (CAIs) and their application in managing ophthalmic conditions, including glaucoma, cystoid macular edema, and idiopathic intracranial hypertension. Despite their recognized clinical benefits, the potential for severe systemic adverse effects often discourages clinicians from prescribing these agents. By examining the pharmacology, pharmacokinetics, safety profile, and clinical indications of systemic CAIs, this review highlights strategies to mitigate treatment challenges, particularly in patients with comorbidities and complex medical backgrounds.
New insights into the diverse roles and distribution of carbonic anhydrase (CA) isozymes have expanded our understanding of both the mechanisms and clinical implications of systemic CAIs. In the eye, CA-II and CA-IV are key contributors to aqueous humor production and ocular blood flow modulation, with dose-dependent improvements in choroidal perfusion observed upon enzyme inhibition. Beyond mechanism of action, tissue-bound drug concentration is a key factor in achieving maximal intraocular pressure (IOP) reduction. Moreover, some CAIs exhibit activity independent of CA blockade, such as inhibiting aquaporin-4. Clinical data further indicate that despite theoretical risks of systemic toxicity-particularly in individuals with comorbidities-severe adverse events are relatively rare.
In specific ocular diseases, the use of systemic CAIs is vital for maintaining vision. Although systemic CAIs carry risk of systemic adverse events, with higher risk, the incidence of severe adverse events is low and in some studies were comparable to that of topical therapy. It's important to be aware of potential side effects and ensure the correct usage of oral CAIs, especially in individuals with other systemic diseases. A tailored evaluation of risks and benefits carried out for each individual, particularly in case of prolonged usage, should decrease the risk of adverse events.
本文详细概述了全身用碳酸酐酶抑制剂（CAIs）及其在治疗眼科疾病中的应用，包括青光眼、黄斑囊样水肿和特发性颅内高压。尽管它们具有公认的临床益处，但严重全身不良反应的可能性常常使临床医生不愿开具这些药物。通过研究全身用CAIs的药理学、药代动力学、安全性概况和临床适应症，本综述强调了应对治疗挑战的策略，特别是在患有合并症和复杂医学背景的患者中。
对碳酸酐酶（CA）同工酶的不同作用和分布的新见解扩展了我们对全身用CAIs的作用机制和临床意义的理解。在眼睛中，CA-II和CA-IV是房水生成和眼血流调节的关键因素，酶抑制后脉络膜灌注呈剂量依赖性改善。除作用机制外，组织结合药物浓度是实现最大眼压（IOP）降低的关键因素。此外，一些CAIs表现出独立于CA阻断的活性，如抑制水通道蛋白-4。临床数据进一步表明，尽管存在全身毒性的理论风险，特别是在合并症患者中，但严重不良事件相对较少。
在特定的眼部疾病中，全身用CAIs对维持视力至关重要。尽管全身用CAIs存在全身不良事件的风险，且风险较高，但严重不良事件的发生率较低，在一些研究中与局部治疗相当。重要的是要意识到潜在的副作用，并确保正确使用口服CAIs，尤其是在患有其他全身性疾病的个体中。对每个个体进行风险和益处的量身定制评估，特别是在长期使用的情况下，应降低不良事件的风险。
