当前，药物临床试验面临着两大难题：数据真实性及相关人员操作规范性。现阶段国内外在药物临床试验方面的监管主要以事后监查为主，在数据质量管理以及操作规划标准的监查方面存在一定的时延性。而区块链通过非对称加密、哈希算法及智能合约等技术，可以在保证受试者隐私信息的前提下，提高政府相关监督机构的监管效率，提升药物临床试验数据管理的透明度；同时，与物联网的紧密结合可以实现对标准操作规范的进一步核查，与人工智能的结合有望实现受试者的自动招募。
Clinical drug trials are confronted with two major issues: first, data authenticity, for instance, if any data falsification is conducted during the whole trial; second, whether the standard of procedure is accordingly conducted throughout the whole trial or not. Currently, both domestic and overseas clinical drug trials are not supervised without delay (ex-post inspection). Blockchain technology can improve the efficiency of Food and Drug Administration and the transparency of trials while the rights and safety of human research subjects are guaranteed by the integrated technology such as chained structure, asymmetry key algorithm, hash algorithm, and smart contract. Furthermore, with the assistance of internet of things (IoT) and artificial intelligence (AI), the actual supervision over the whole trial and automatic recruitment of human research subjects are expected to achieve.
近年来随着人类生活方式的改变、用眼频率的增加，眼科药物的市场需求持续增长，但是目前眼病治疗仍面临“缺医少药”的困境。由于新药研发面临成本高、周期长、成功率低的风险，眼科药物创新迭代的进程日趋缓慢。人工智能(artificial intelligence，AI)作为一种全新的技术手段，有望赋能眼科药物研发的全过程，包括药物靶点发现、化合物筛选、药物动力学模型创新与临床试验开展等，以期为眼科药物研发“降本增效”。且随着大数据体系的完善、硬件计算力的提升以及生命科学与智能科学的深度融合，AI在眼科药物研发中的作用将进一步得到提升，助力眼科药物研发实现从精准化到智能化的跨越。
With the change of human lifestyle and overuse of eyes in recent years, the market demand for ophthalmic drugs continues to grow. However, the ocular therapy is still facing the shortage of doctors and drugs. Due to the risk of high cost, long lead time and low success rate, the process of novel ophthalmic drug innovation and iteration is getting slower. As an emerging technology, artificial intelligence is expected to enable the whole process of ophthalmic drug discovery and development, including drug target discovery, compound screening, pharmacokinetic model innovation and clinical trials, thus reducing R&D costs and increase efficiency for ophthalmic drug discovery and development. In addition, with the improvement of big data, hardware calculation and the deep integration of life science and intelligent science, the role of artificial intelligence in ophthalmic drug discovery and development will be significant improved , contributing to achieve the leap from precision to intelligence.
目的：调查抗VEGF药物治疗湿性年龄相关性黄斑变性(wet age-related macular degeneration, wAMD)5年的疗效。方法：2011年至2021年于北京医院眼科诊断为wAMD的患者共84人103只眼进行回顾性分析。抗VEGF治疗采用3+PRN方案。观察5年来的最佳矫正视力(best-corrected visual acuity，BCVA)、玻璃体腔注射次数、随访次数和病灶的解剖学变化。结果：治疗5年后平均BCVA为38.1个字母，与基线相比下降9.4个字母，差异有统计学意义(P<0.001)。23.3%的患眼5年后可维持初始视力。5年内平均注射次数为13.8次，第1年注射次数最多，平均为4.3次。5年内平均随访次数为24.3次，仅有34.0%的患眼可遵循每次随访间隔≤3个月。5年后有68.0%的患眼出现纤维瘢痕，27.2%的患眼出现地图样萎缩，69.0%(71/103)的患眼存在持续的色素上皮脱离(pigment epithelial detachment，PED)。年龄、基线BCVA、是否初始治疗、随访年限、注射次数、中心视网膜厚度 (central retina thickness，CRT)、地图样萎缩等对BCVA有显著影响。结论：多数患者在抗VEGF治疗1年内可维持视力，但5年以上维持效果不佳。早期诊治、提高注射频率，可能是未来改善预后的研究方向。
Objective:To investigate the efficacy of anti-VEGF injection in the treatment of wet age-related macular degeneration (wAMD) for 5 years. Methods: A total of 84 patients (103 eyes) wAMD diagnosed in Department of Ophthalmology in Beijing Hospital from 2011 to 2021 were analyzed retrospectively. 3 + PRN regimen was applied for anti-VEGF treatment. The changes of best corrected visual acuity (BCVA), the number of intravitreal injections and the number of follow-up visits, and the anatomical changes of the lesions in the past 5 years were collected. Results: The average BCVA after 5 years was 38.1 letters, indicating a decrease of 9.4 letters comparing to baseline, which was statistically significant (P<0.001). 23.3% of the eyes could maintain the baseline BCVA after 5 years. The average injection times within 5 years was 13.8, and the injection was concentrated in the first year, with an average of 4.3. The average number of follow-up visits within 5 years was 24.3, and only 34.0% of the affected eyes could keep the follow-up interval ≤3 months. After 5 years, 68.0% of the eyes developed fibrous scar, 27.2% developed geographic atrophy, and 69.0% (71/103) had consistent pigment epithelial detachment. Factors significantly affect BCVA include: age, baseline BCVA, initial treatment, follow-up time, injection times, central retinal thickness, geographic atrophy and so on. Conclusion: Most patients can maintain vision within the first year after anti-VEGF treatment, but the efficacy is poor for more than 5 years. Early diagnosis and treatment, and increased injection frequency may be the research direction for improving prognosis in the future.
单纯疱疹病毒基质型角膜炎是引起角膜盲的主要原因之一，目前以局部使用糖皮质激素联合口服抗病毒药物治疗为主。传统治疗存在生物利用度低、药物不良反应等缺点，因此亟需寻找替代药物、开发新剂型。环孢素A和他克莫司等免疫抑制剂疗效明显、不良反应少，可能是糖皮质激素的潜在替代品。α干扰素联合阿昔洛韦可缩短病程，而单独使用效果有限。基质再生剂具有新的抗病毒机制，值得进一步研究。此外，纳米载体递送系统，如脂质体、纳米胶束、立方液晶纳米粒，由于能够增强药物角膜穿透性和延长药物释放，在治疗基质型单纯疱疹性角膜炎方面具有巨大潜力。
Herpes simplex virus stromal keratitis is one of the leading causes of corneal blindness. A topical corticosteroidagent in conjunction with an oral antiviral agent is the preferred treatment, which has the disadvantages of low bioavailability and drug side effects. Therefore, there is an urgent need to find alternative drugs and develop new dosage forms. Immunosuppressants such as cyclosporine A and tacrolimus have obvious curative effects and few side effects, and may be potential substitutes for glucocorticoids. Interferon-α combined with acyclovir can shorten the course of disease, but the effect is not obvious when used alone. Matrix regenerating agents have new antiviral mechanisms and deserve further study. In addition, nanocarriers delivery systems, such as liposomes, nanomicelles and cubosomes, have great potential in the treatment of herpes simplex virus stromal keratitis due to their ability to enhance drug corneal penetration and prolong drug release.
