本文根据上海鹰瞳医疗科技有限公司的创新产品《糖尿病视网膜病变眼底图像辅助诊断软件》在国家药品监督管理局(NMPA，原CFDA)历时两年半的上市前创新申报与注册申报经历，介绍了人工智能类医疗器械产品的产品研发、注册申报流程及相关重点难点，并且列明了在整个过程中需要遵循和参考的法律法规，为此类产品的上市前注册工作提供参考。
Based on the NMPA premarket application through two and a half years for the computer aided diagnosis software using fundus images of diabetic retinopathy, which is an innovative medical device of Shanghai EagleVision Medical Technology Co., Ltd. (Airdoc), this article introduced the development process, the premarket application, and the key points in the application of this artificial intelligence device, also lists the related regulations and guidelines as references to provide some ideas for the follow-up premarketing application of such kind of products.
目的：探讨医用自交联透明质酸钠凝胶对鼻内窥镜下泪囊鼻腔吻合术(endonasal endoscopic dacryocystorhinostomy，En-DCR)后的影响。方法：将219例单侧慢性泪囊炎(chronic dacryocystitis CD)患者随机分为医用自交联透明质酸钠凝胶组(A组)和对照组(B组)。所有患者行En-DCR。A组将医用自交联透明质酸钠凝胶填充吻合口，B组不做任何处理。随访12个月。比较创面黏膜上皮化、肉芽形成情况、渗血情况及吻合口通畅成功率。结果：A组98例，B组102例。随访2周，A组86例患者鼻腔吻合口黏膜上皮完整，B组77例患者鼻腔吻合口黏膜上皮完整。随访12个月，A组有7例患者存在瘢痕(7.1%)，8例患者出现肉芽肿(8.2%)，而B组有17例患者存在瘢痕(16.7%)，18例患者出现肉芽肿(17.6%)。两组瘢痕形成及出现肉芽肿差异均有统计学意义(P<0.05)。A组的吻合口通畅成功率达到90.8%(89/98)，而B组的成功率为78.4%(80/102)(P<0.05)。B组患者术后渗血情况A组相当(P>0.05)。结论：医用自交联透明质酸钠凝胶填充吻合口可通过促进En-DCR术后吻合口黏膜上皮愈合和降低伤口瘢痕及肉芽肿生成率，提高En-DCR治疗CD的成功率。
Objective: To investigate the effect of medical self-crosslinking sodium hyaluronate gel on endonasal endoscopic dacryocystorhinostomy (En-DCR). Methods: A total of 219 patients with unilateral chronic dacryocystitis (CD) were selected and randomly divided into two groups: medical self-crosslinking sodium hyaluronate gel group (group A) and control group (group B). All patients underwent En-DCR. Group A received medical self-crosslinking sodium hyaluronate gel filling the ostium at the end of En-DCR, whereas group B received no treatment. Patients were followed-up for 12 months. The mucosal epithelialization of the wound, the granulation formation, bleeding, and the success rate of ostial patency were compared in the two groups. Results: Our study included 98 patients in group A and 102 patients in group B. After 2 weeks, the number of absorbable hemostatic patients who had intact mucosal epithelium lining the ostia was 86 in group A and 77 in group B. At 12 months follow up, there were 7 patients with scar (7.1%) and 8 patients with granuloma (8.2%) in group A, compared with 17 patients with scar (16.7%) and 18 patients with granuloma (17.6%) in group B. There were significant differences in scar formation and granuloma between the two groups (P<0.05). The success rate of anastomotic patency reached 90.8% (89/98) in group A whereas the success rate was 78.4% (80/102) in group B (P<0.05). The situation of postoperative bleeding in group B was similar to that in group A (P>0.05). Conclusion: The medical self-crosslinking sodium hyaluronate gel can improve the success rate of En-DCR treatment of CD through promoting the healing of anastomotic mucosa and reducing the rate of wound scar and granuloma formation.
眶尖部肿瘤为眼科罕见疾病，但因其所处位置特殊，对机体，特别是视神经功能危害极大，错误的诊断、不规范合理的治疗不仅不能解决问题，甚至会对机体造成严重的不可挽回的损害。目前针对眶尖部肿瘤的诊断、治疗多建立在医生的主观认知与经验的基础上，尚未达成共识。本文通过分析眶尖部肿瘤的临床特点，结合以往漏诊、误诊、误治的临床案例，阐述眶尖肿瘤正确诊断的关键要点；同时，结合不同临床案例，客观分析治疗方案，尤其是手术方式、路径，为眶尖部肿瘤的合理化治疗提供依据，以期规范眶尖部肿瘤的诊断和治疗，提高治疗成功率。
Although orbital apical tumor is a rare ophthalmic disease, its special location can cause great harm to the body, especially to the function of the optic nerve. Misdiagnosis and improper treatment are not only unable to solve the problem, but also irretrievably harmful to the body. At present, there is no consensus on the diagnosis and treatment of orbital apical tumors, which are mostly based on subjective cognition and experience of doctors. In this paper, the clinical characters of orbital apical tumors were analyzed through the past clinical cases of misdiagnosis and mistreatment, and the key points of proper diagnosis of orbital apical tumors were expounded. Meanwhile, by combining with different clinical cases, the treatment plans, especially the surgical approaches, were analysed to provide a basis for the appropriate treatment of orbital apical tumors, in order to standardize the diagnosis and treatment of orbital apex tumor, and improve the success rate of treatment.
鼻内镜外科技术延伸到鼻眼相关疾病的诊断和治疗已经有二十余年的历史。随着鼻眼相关解剖研究、影像诊断技术和手术器械的进步和手术临床经验的积累，大量临床和基础研究不断涌现，逐渐形成了相对成熟的内镜鼻眼相关外科理论与实践体系。本文概述了内镜鼻眼相关外科的发展现状，对几种主要手术提供经验总结并提出展望。
Nasal endoscopic surgery technology has gradually developed and involved into the diagnosis and treatment of nose-eye related disease for more than 20 years. With the improvement of anatomical studies on nose-eye, imaging diagnostic technology and surgical instruments, the accumulation of surgical clinical experience, as well as the increasing emergence of a large number of clinical and basic studies on endoscopic rhino-orbital related surgery, a well-established theoretical and practical system of endoscopic nose-eye surgery has gradually been formed. This article summarized the development of endoscopic rhino-orbital surgery, and the advantages and limitations of several major surgical methods. Also, the further research was prospected.
目的：探究短期周边遮盖对成年视皮层双眼优势平衡的作用。方法：对12名正常成年人的各眼 (24只眼)分别进行单眼短期周边遮盖。遮盖方式为单眼佩戴90 min的环形、半透明的塑料遮盖板，遮盖板仅能透光，中央留有1 0°~15°视野范围的圆孔，从而实现周边遮盖。受试者在周边遮盖前、遮盖后的0~3、3~6、6~9、9~12、12~15、30、60和90 min均完成双眼竞争任务 (binocular rivalry task)。记录并分析各时间段中各眼的占优时间、双眼竞争在眼别间切换周期数和各眼占优概率随时间改变的特点等。每位受试者左右眼测试间隔1周进行。结果：在遮盖前，12名正常成年受试者被遮盖眼的占优时间与非遮盖眼的差异无统计学意义(92.78±6.33 s vs 87.22±6.23 s，P>0.05)，提示眼优势平衡。遮盖去除后的0~3 min，被遮盖眼占优比例显著增加至 0.721±0.11(P<0.001)，该效应在遮盖去除后的3~30 min均存在(P<0.05)，直至60 min(P=0.445)双眼基本恢复优势平衡。双眼优势转换周期在周边遮盖前后差异无统计学意义(P=0.064)。主导眼在去除周边遮盖后的0~3 min遮盖眼占优时间比例相对基线的改变幅度与遮盖非主导眼的差异无统 计学意义(P=0.835)。结论：短期的周边遮盖可改变成年双眼优势平衡，有望应用于视觉关键期后的弱视治疗中。视觉关键期后双眼视功能仍保留有一定的可塑性。
Objective: To study the effect of short-term peripheral patching on binocular dominance in adult visual cortex. Methods: Monocular short-term peripheral patching was performed on each eye (24 eyes) of 12 normal adults. The patching was achieved by monocularly wearing a ring-shaped, translucent and plastic patch for 90 minutes. The patch could only transmit light, but not pattern, and there was a circular hole with a visual field of 10°–15°, so as to achieve peripheral patching. Participants completed the binocular rivalry task at baseline and 0–3, 3–6, 6–9, 9–12, 12–15, 30, 60 and 90 min after peripheral patching. The dominance duration of each eye and the number of dominance switches between eyes were recorded. The probability of perceiving stimulus of each eye was calculated in each time period. Each participant’s both left and right eyes performed peripheral patching one week apart. Results: Before patching, the dominance duration of the patched eye was not significantly different from the non-patched eye (92.78±6.33 s vs 87.22±6.23 s, P>0.05), which suggests that the eye dominance was balanced. At 0–3 min after the removal of the patch, the dominance duration of the patched eye was increased significantly (P<0.001), and this effect existed until 30 min after the removal of the patch (P<0.05). The dominance duration of the patched eye at post-60 min was not significantly different from the baseline (P=0.445). There was no significant difference in the dominance switches among baseline and each period after patching (P=0.064). After the removal of patch on the dominant eye, the amplitude of change in the dominance duration of the patched eye at 0–3 min was not significantly different from that after the removal of patch on the non-dominant eyes (P=0.835). Conclusion: Short-term peripheral patching can also change the binocular dominance in adults, and it has the potential to be applied in treatment of adult amblyopia. After the critical period for visual development, binocular vision function still retains plasticity.
Background: The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy (DR). It ensures an experimental overview with more complete respect to isolate cells and reduce problems in terms of accessibility and management with respect to in vivo model. In particular, it allows the evaluation of the relationship between retinal cells in response to the typical stressors involved in DR pathogenesis.
Methods: Ex vivo retinal fragments derived from 3- to 5-week-old C57BL/6J mice. In particular, after dissection, the retina is cut into 4 separate fragments and transferred onto inserts placed with ganglion cells up. Once in culture, the explants could be treated in stress conditions typical of DR. In particular, this study protocol describes the procedure for the preparation and the culture of retinal explants with specific metabolic stressors such as high glucose (HG), advanced glycation end product (AGE), and oxidative stress (OS). In the end, this paper provides the protocols to perform molecular analyses in order to evaluate the response of retinal explants to stress and/or neuroprotective treatments.
Discussion: The cultured retinal explants represent an ex vivo experimental model to investigate the molecular mechanisms involved in neurovascular diseases such as DR. Moreover, they could be useful to test the effect of neuroprotective compounds in response to metabolic stressors in a fewer time respect to an in vivo model. In conclusion, retinal explants in culture represent a valuable experimental model to conduct further studies to better understand the pathophysiology of DR.
Background: The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy (DR). It ensures an experimental overview with more complete respect to isolate cells and reduce problems in terms of accessibility and management with respect to in vivo model. In particular, it allows the evaluation of the relationship between retinal cells in response to the typical stressors involved in DR pathogenesis.
Methods: Ex vivo retinal fragments derived from 3- to 5-week-old C57BL/6J mice. In particular, after dissection, the retina is cut into 4 separate fragments and transferred onto inserts placed with ganglion cells up. Once in culture, the explants could be treated in stress conditions typical of DR. In particular, this study protocol describes the procedure for the preparation and the culture of retinal explants with specific metabolic stressors such as high glucose (HG), advanced glycation end product (AGE), and oxidative stress (OS). In the end, this paper provides the protocols to perform molecular analyses in order to evaluate the response of retinal explants to stress and/or neuroprotective treatments.
Discussion: The cultured retinal explants represent an ex vivo experimental model to investigate the molecular mechanisms involved in neurovascular diseases such as DR. Moreover, they could be useful to test the effect of neuroprotective compounds in response to metabolic stressors in a fewer time respect to an in vivo model. In conclusion, retinal explants in culture represent a valuable experimental model to conduct further studies to better understand the pathophysiology of DR.
Background: Retinopathy of prematurity (ROP) is considered as the most common reason for blindness in children, particularly in preterm infants. The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth, leading ultimately to vascular abnormalities and pathological neovascularization (NV). Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP, also characterized by inflammation and retinal cell death.
Methods: During the last decades, many animal models of oxygen-induced retinopathy (OIR) have been recognized as useful tools to study the mechanisms of disease, since they reproduce the hallmarks typical of human ROP. Indeed, modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals, reproducing the main pathological phenotypes of the disease. The easy quantification of abnormal NV and the possibility to perform electrophysiologic, histological and molecular analyses on these models, make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.
Discussion: Here, the most commonly used OIR protocols in rodents, such as mice and rats, are described as well as the main pathological outcomes typical of these models. Despite their limitations and variables which should be considered whilst using these models, OIR models display several characteristics which have also been confirmed in human patients, validating the usefulness of such animals in the pre-clinical research of ROP.
Background: Retinopathy of prematurity (ROP) is considered as the most common reason for blindness in children, particularly in preterm infants. The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth, leading ultimately to vascular abnormalities and pathological neovascularization (NV). Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP, also characterized by inflammation and retinal cell death.
Methods: During the last decades, many animal models of oxygen-induced retinopathy (OIR) have been recognized as useful tools to study the mechanisms of disease, since they reproduce the hallmarks typical of human ROP. Indeed, modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals, reproducing the main pathological phenotypes of the disease. The easy quantification of abnormal NV and the possibility to perform electrophysiologic, histological and molecular analyses on these models, make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.
Discussion: Here, the most commonly used OIR protocols in rodents, such as mice and rats, are described as well as the main pathological outcomes typical of these models. Despite their limitations and variables which should be considered whilst using these models, OIR models display several characteristics which have also been confirmed in human patients, validating the usefulness of such animals in the pre-clinical research of ROP.
息肉状脉络膜血管病变(polypoidal choroidal vasculopathy，PCV)是亚洲人中常见的眼底致盲性疾病，当PCV合并视网膜下出血或玻璃体积血(vitreous hemorrhage，VH)时，患者视力骤然下降，视力预后差异大。但目前聚焦于PCV合并VH的相关文献较少，因此研究和阐明PCV继发VH的治疗方法及预后具有重要的临床意义。目前临床上常选择手术干预，玻璃体切除术(pars plana vitrectomy，PPV)是临床上最常选择的一种术式。其他治疗方式包括玻璃体内注射抗血管内皮生长因子(vascular endothelial growth factor，VEGF)、眼内气体或硅油填充、眼内注射组织纤溶酶原激活剂(tissue plasminogen activator，tPA)和光动力疗法(photodynamic therapy，PDT)。PCV合并VH患者的视力预后决定因素是黄斑视功能的保留程度，也与年龄、术前视力、PCV病变部位、视网膜下出血量、视网膜脱离范围、基线黄斑中心厚度(central macular thickness，CMT)、是否出现术后并发症以及是否形成视网膜瘢痕等因素相关，目前也有研究发现视力预后与单核苷酸多态性(single nucleotide polymorphisms，SNP)相关。本文就PCV继发VH的临床特点、治疗及预后进行综述。
Polypoid choroidal vasculopathy (PCV) is a common fundus blinding disease in Asians. When PCV is associated with subretinal hemorrhage or vitreous hemorrhage (VH), patient's visual acuity decreases suddenly and the visual prognosis varies greatly. There are few relevant literatures focusing on VH secondary to PCV, so it is of great clinical significance to study and clarify the treatment methods and prognosis of VH secondary to PCV. At present, surgical intervention is often selected in clinical practice. Vitrectomy is the most commonly selected surgical procedure in clinical practice. The other treatment modalities include intravitreal injection of antivascular endothelial growth factor (VEGF), intraocular gas or silicone oil filling, intraocular injection of tissue plasminogen activator (tPA) and photodynamic therapy. The prognostic determinant of visual acuity in PCVpatients with VH is the degree of preservation of macular visual function. The prognostic is also related to age, preoperative visual acuity, PCV lesion location, amount of subretinal hemorrhage, extent of retinal detachment, baseline central macular thickness (CMT), postoperative complications and retinal scars. Recent studies also find that the prognosis of visual acuity is related to single nucleotide polymorphisms. This article reviews the clinical characteristics, treatment and visual prognosis of PCV associated with VH.
