Study Protocol

Experimental models of retinopathy of prematurity

Experimental models of retinopathy of prematurity

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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.

Original Article
Editorial
综述

息肉状脉络膜血管病变继发玻璃体积血的治疗及预后

Treatment modalities and visual prognosis of polypoidal choroidal vasculopathy with breakthrough vitreous hemorrhage

:658-664
 
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 PCV
patients 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.
论著

高度近视有晶状体眼后房型人工晶状体术后孔源性视网膜脱离的临床特征及预后分析

Clinical presentation and outcomes of rhegmatogenous retinal detachment in phakic eyes after posterior chamber phakic intraocular lens implantation for high-myopia

:111-116
 
目的:分析高度近视有晶状体眼后房型人工晶状体植入术后孔源性视网膜脱离的临床特征及预后。方法:回顾分析2012年4月至2021年6月中山眼科中心收治的9例(9只眼)行后房型人工晶状体植入术后孔源性视网膜脱离患者的临床特征、手术方式及疗效,随访(4.96±4.78)个月。结果:患者年龄(30.44±20.11)岁,屈光手术至发病时间(32.10±17.80)个月。4例(44.4%)马蹄形裂孔,1例(11.1%)萎缩性裂孔,4例(44.4%)巨大裂孔;9眼裂孔均位于赤道部前,除2眼(22.2%)为单个巨大裂孔,1眼(11.1%)单个马蹄孔,余6眼(66.7%)均有视网膜周边变性区存在;视网膜脱离范围(3.0±1.12)个象限,8例累及黄斑;增殖性玻璃体视网膜病变C级以上4眼。视网膜初始复位率为77.8%,最终视网膜复位率100%。末次随访最佳矫正视力优于术前(P<0.05)。随访期间,2例硅油填充眼发生并发性白内障,4眼发生术后早期高眼压。结论:有晶状体眼后房型人工晶状体植入术前存在的视网膜变性或术后玻璃体牵引的存在可能是孔源性视网膜脱离发生的危险因素。
Objective: To analyze the clinical presentation, surgical management, and outcomes of rhegmatogenous retinal detachment (RRD) in patients with high-myopia corrected by posterior chamber phakic (PCP) intraocular lens (IOL) implantation. Methods: Nine eyes of 9 patients in whom RRD developed after PCPIOL implantation from April 2012 to June 2021 in Zhongshan Ophthalmic Center were retrospectively studied. Mean follow-up after retinal detachment surgery was (4.96±4.78)months. Results: Mean patient age was (30.44±20.11) years old. RRD occurred (32.10±17.80) months after PCPIOL implantation. Four (44.4%) breaks were horseshoe tear, 1 (11.1%) was atrophic hole and 4 participants (44.4%) had a giant retinal tear. Nine cases had causative breaks located anterior to the equator while peripheral retina lattice degeneration was found in 6 eyes. RRD extended from 1 to 4 quadrants (3.0±1.12 quadrants) and 8 cases were macula-off retinal detachments. Four eyes’ proliferative vitreoretinopathy were more severe than level C. Initial reattachment rate was 77.80%. Final retinal reattachment was 100%. Final follow-up BCVA was significantly better than baseline (P<0.05). Furthermore, concurrent cataract occurred in 2 eyes in which silicone oil was used as tamponade. Ocular hypertension was detected in 4 eyes after surgery. Conclusion: The existed lattice degeneration and postoperative vitreous traction may be risk factors for RRD after PCPIOL implantation.
“筑梦·铸人”专题

糖尿病性视网膜病变脂质代谢的研究进展

Emerging insights into lipid metabolism in diabetic retinopathy

:93-99
 
脂质代谢异常是糖尿病性视网膜病变可能的危险因素。糖尿病性视网膜病变被认为是致盲的主要原因。近年来研究认为总胆固醇、三酰甘油等血脂与糖尿病性视网膜病变及糖尿病黄斑水肿的进展有关,降脂药物的应用能够延缓糖尿病性视网膜病变进展。随着色谱分离和质谱分析等脂质组学分析方法的发展,除了常规的血清脂质标志物以外的各种脂质成分也被发现可能与糖尿病性视网膜病变进展有关。现总结脂质及其衍生物在糖尿病性视网膜病变发病机制中的作用,阐述糖尿病性视网膜病变脂质代谢治疗的潜在靶点和前景。
Abstract Abnormal lipid metabolism is a possible risk factor for diabetic retinopathy. Diabetic retinopathy is considered to be the main cause of blindness. In recent years, studies have shown that serum lipids, such as total cholesterol, triglycerides, are related to the progress of diabetic retinopathy and diabetic macular edema, and lipid-lowering drugs can delay the progress of diabetic retinopathy. With the development of lipidomics analysis methods such as chromatographic separation and mass spectrometry, lipid components other than conventional serum lipid markers have also been found to be related to the progression of diabetic retinopathy. The review summarizes the role of lipids and their derivatives in the pathogenesis of diabetic retinopathy, and highlights the potential targets and prospects of lipid metabolism treatment for diabetic retinopathy.
“眼科再生医学”专题

培养皿中的眼睛:眼组织类器官技术发展与应用

An eye in a culture dish: ocular organoids and their application

:100-110
 
眼睛是人体最重要的感觉器官之一,主要由角膜和晶状体构成的屈光系统和视网膜构成的视觉神经系统2个部分构成。眼睛各组织的发育和功能异常都可影响视功能,甚至致盲。现有的致盲眼病的治疗方式均存在各自瓶颈问题,新的诊治方法亟待开发。近年来,得益于干细胞和组织工程学的发展,结合现有眼各组织的发育理论知识,研究者们利用多种来源的干细胞在体外成功诱导出具有组织特异结构和功能的眼类器官。眼类器官研究为利用干细胞研究眼组织发育和眼病发病机制、药物筛选以及替代治疗创造了新机遇,将干细胞治疗眼病的转化研究推向了一个更高平台。本文将对现有眼类器官的技术发展及应用进行综述。
Being one of the most important sensory organs, the eye is composed of the cornea, the lens, which are responsible for refraction, and the retina, which is the neural sensory part of the eye. Various kinds of developmental abnormalities and functional defects could lead to visual dysfunctions, and even blindness. Current treatments for blindness-causing eye diseases all have their own limitations, awaiting new efficient diagnostic and treating methods. Thanks to the development in stem cell biology and bioengineering, taking advantage of the rich knowledge accumulated on the mechanisms governing eye development, researchers have successfully generated various ocular organoids using multiple sources of stem cells in vitro, which resemble their counterparts in vivo on both the structural level and functional level. Ocular organoids provide valuable material and models for studying eye development, pathology, drug screening, and cell replacement therapy, pushing translational studies of ocular stem cell to a new era. Here, the paper reviews the development and application of ocular organoid technologies.
论著

有晶体眼人工晶状体植入术后视疲劳症状及影响因素

Outcomes of asthenopia after implantable collamer lens implantation and its related factors

:620-626
 
目的:评估屈光不正患者有晶体眼后房型人工晶体(implantable collamer lens,ICL)植入术后视疲劳症状及调节集合功能、眼表、像差的变化,并探讨其对视疲劳症状的影响。方法:前瞻性病例观察分析。连续收集在沧州市中心医院行ICL手术并完成3个月随访的患者,测定术前、术后1周、1个月、3个月时的视疲劳评分、调节幅度(amplitude of accommodation,AA)、正相对调节和负相对调节(positive/negative relative accommodation,PRA/NRA)、调节灵敏度(accommodative facility,AF)、调节性集合(accommodative convergence,AC)与调节(accommodation,A)比率(AC/A),Schirmer实验、非侵入性泪膜破裂时间(noninvasive breakup time,NBUT)及高阶像差(higher order aberration,HOA),进行统计学分析。结果:ICL术后第1周视疲劳症状较术前明显加重,随时间推移逐渐减轻,术后1个月仍高于术前,术后3个月时恢复。AA术后1周时较术前降低,术后1个月、3个月时明显高于术前;AF术后1周时较术前下降,术后1个月比术前水平稍好,3个月时明显高于术前;PRA、NRA无明显变化;AC/A术后1周时较术前下降,术后1个月回复到术前水平,术后3个月较术前提高。术后1周、1个月及3个月的NBUT值均较术前明显下降,术后1周时最低;Schiermer值术后1周时轻度下降,术后1个月、3个月时基本恢复。术后的总HOA均较术前有所增加,但各个时间点之间无明显变化。相关性分析显示ICL术后AF越差、NBUT越低,视疲劳症状越重。结论:ICL术后视疲劳症状一过性加重,AF和NBUT是影响视疲劳变化的重要因素。
Objective: To evaluate the changes of visual fatigue symptoms, accommodative functions, ocular surface conditions, and high-order aberrations (HOA) after implantation of implantable collamer lens (ICL), and to explore their effects on asthenopia. Methods: It was a prospective observational case series. Patients with ametropia who underwent ICL surgeries and completed 3-month follow-up in our hospital were enrolled.Asthenopia scores, amplitude of accommodation (AA), positive/negative relative accommodation (PRA/NRA),accommodative facility (AF), the ratio of accommodative convergence and accommodation (AC/A), Schirmer test, non-invasive breakup time (NBUT), and HOA were examined before surgeries and at 1 week, 1 month and 3 months after surgeries, then statistically analyzed. Results: Symptoms of asthenopia were significantly worse at 1 week after ICL surgeries than those before surgeries, but increased gradually as time went by, eventually recovered at 3 months postoperatively. Among regulatory indicators, AA decreased 1 week postoperatively, but was significantly higher at 1 and 3 months after surgeries; AF was lower 1 week after surgery than baseline, slightly better at 1 month postoperatively, and significantly higher at 3 months postoperatively; PRA and NRA had no significant change; AC/A decreased 1 week after surgeries, returned to the baseline at 1 month postoperatively, and increased 3 months postoperatively. Tears and meibomian gland function index: NBUT values at 1 week, 1 month and 3 months after surgeries were significantly decreased compared with those before surgeries, and NBUT at 1 week postoperatively was the lowest; Schiermer values had a slight decrease at 1 week after surgeries, and basically recovered at 1 and 3 months after surgeries. HOA after surgeries were increased compared with those before surgeries, but there was no significant change between each time point. Correlation analysis showed that the lower AF and NBUT after ICL surgeries, the more severe the asthenopia symptoms. Conclusion: The symptoms of asthenopia aggravated transiently after ICL implantation surgeries, but improved gradually with time. AF and NBUT were important factors affecting the changes of asthenopia.
论著

右美托咪定复合舒芬太尼用于老年青光眼患者经巩膜二极管激光睫状体光凝术术后自控静脉镇痛的临床效果

Effect of dexmedetomidine combined with sufentanil on patient-controlled intravenous analgesia after transscleral diode laser cyclophotocoagulation in elderly glaucoma patients

:740-746
 
目的:评估右美托咪定复合舒芬太尼用于老年青光眼患者经巩膜二极管激光睫状体光凝术 (transscleral diode laser cyclophotocoagulation,TDLC)术后自控静脉镇痛(patient-controlled intravenous analgesia,PCIA)的安全性和有效性。方法:选择行TDLC术老年青光眼患者80例,采用随机数字表法将患者分为SD组(n=40)和S组(n=40)。SD组术后PCIA采用舒芬太尼1.5μg/kg+右美托咪定1.5 μg/kg+托烷司琼4mg;S组采用舒芬太尼2μg/kg+托烷司琼4mg。将相应药物置入生理盐水配成100mL混合液加入电子镇痛泵,手术结束即刻行PCIA至术后24h。观察比较两组患者基本情况和手术情况,比较术前(T0)、术后即刻(T1)、术后6h(T2)、术后12h(T3)和术后24h(T4)患者的收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、心率(heart rate,HR)、NRS疼痛评分、Ramsay镇静评分及非手术眼的眼内压(intraocular pressure,IOP),比较术后恶心呕吐、呼吸抑制、躁动等不良反应及使用其他辅助镇痛药物的情况。结果:两组患者基本情况和手术情况的差异无统计学意义。两组各时点DBP、非手术眼IOP及NRS评分差异无统计学意义。SD组T3、T4时点SBP,T2、T3、T4时点HR以及T2、T3时点Ramsay评分均低于S组,差异有统计学意义(P<0.05)。两组患者发生不良反应的总例数差异无统计学意义,但SD组恶心呕吐(1例)和烦躁(2例)发生率均低于S组(分别为6例和9例),差异有统计学意义(P<0.05)。两组患者呼吸抑制和眩晕嗜睡发生率以及使用其他辅助镇痛药物例数差别无统计学意义,SD组舒芬太尼使用量低于S组(P<0.05)。结论:采用右美托咪定1.5μg/kg复合舒芬太尼1.5μg/kg行PCIA时不影响非手术眼IOP,可安全有效地应用于老年青光眼患者TDLC术后镇痛。
Objective: To evaluate the safety and efficacy of dexmedetomidine combined with sufentanil for postoperative patient-controlled intravenous analgesia (PCIA) after transscleral diode laser cyclophotocoagulation (TDLC) in elderly patients with glaucoma. Methods: Eighty elderly glaucoma patients undergoing TDLC were selected and randomly divided into a SD group (n=40) and a S group (n=40) by random number table method. In SD group (n=40), sufentanil 1.5 μg/kg, dexmedetomidine 1.5 μg/kg and tropisetron 4 mg were used for postoperative PCIA, and sufentanil 2 μg/kg and tropisetron 4 mg were used in S Group (n=40). The corresponding drugs in saline solution was added into 100 mL solution with electronic analgesia pump. PCIA was performed immediately after the operation until 24 h after the operation. The basic condition and operation situation of the two groups were observed and compared, and systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), NRS pain score, Ramsay sedation score and non-operation eye intraocular pressure (IOP) at preoperative (T0), after operation (T1), postoperative 6 h (T2), 12 h after operation (T3) and 24 h after operation (T4) were compared, and postoperative adverse reactions such as nausea and vomiting, respiratory depression, restlessness and use of other auxiliary analgesic drug were also compared. Results: There was no significant difference between two groups of patients’ basic and surgical conditions. There was no significant difference between two groups at each time point DBP, non-operation eye IOP and NRS score. SBP at T3 and T4, HR at T2, T3 and T4, and Ramsay score at T2 and T3 in SD group were lower than the S group, the difference was statistically significant. There was no significant difference in the total number of adverse reactions between two groups, but the incidence of nausea and vomiting and restlessness in group SD were lower than those in group respectively, the difference was statistically significant (P<0.05). There was no significant difference between the two groups in the incidence of respiratory depression, dizziness, lethargy and the use of other auxiliary analgesics. The sufentanil usage in group SD was lower than that in group S (P<0.05). Conclusion: PCIA with dexmedetomidine 1.5 g/kg combined with sufentanil 1.5 g/kg does not affect the non-operation eye IOP. It can be safely and effectively applied to postoperative analgesia for elderly patients with glaucoma after TDLC
论著

非去极化肌松药对眼压升高的青光眼患者全身麻醉诱导期眼压的影响

Effects of non-depolarizing muscle relaxants on intraocular pressure of glaucoma patients with elevated intraocular pressure during induction of general anesthesia

:733-739
 
目的:探讨全身麻醉诱导期应用不同种类的非去极化肌松药罗库溴铵、顺式阿曲库铵和米库氯铵对眼压升高的青光眼患者眼内压的影响。方法:将术侧眼眼压>21mmHg青光眼手术患者随机分配到罗库溴铵组、顺式阿曲库铵组和米库氯铵组。靶控输注丙泊酚至患者脑电双频指数(bispectral index,BIS)低于55后,根据组别分别静注0.6mg/kg罗库溴铵、0.1mg/kg顺式阿曲库铵及0.2mg/kg米库氯铵,待4个成串刺激(train of four stimulation,TOF)比值降至0后置入可弯曲喉罩,随后行机械通气并给予芬太尼1.5~2.0μg/kg,2%~3%七氟烷吸入维持麻醉。分别于麻醉诱导前(T0)、镇静后(T1)、肌松后(T2)及喉罩置入后(T3)测量三组青光眼患者术侧眼眼压并记录上述时间点血流动力学参数。结果:罗库溴铵组、顺式阿曲库铵组、米库氯铵组患者的眼压在T1、T2、T3时间点均较T0显著下降,差异有统计学意义(均P<0.001);三组患者T2时间点眼压与T1相比差异均无统计学意义(P=0.337,P=0.520,P=0.062);三组患者给予肌松药前后的眼压差值(T2–T1)分别为(0.68±4.39)、(0.36±3.72)和(1.27±3.91)mmHg,组间比较差异无统计学意义(P=0.353)。结论:非去极化肌松药罗库溴铵、顺式阿曲库铵及米库氯铵对眼压升高的青光眼患者的眼压无明显影响,且3种肌松药之间未见显著差异。
Objective: To compare the effects of different types of non-depolarizing muscle relaxants including rocuronium,cis-atracurium and mivacurium on intraocular pressure of glaucoma patients with elevated intraocular pressure during induction of general anesthesia. Methods: Glaucoma patients with intraocular pressure >21 mmHg were randomly assigned to rocuronium group, cis-atracurium group and mivacurium group. After target controlled infusion of propofol until the bispectral index (BIS) lower than 55, 0.6 mg/kg rocuronium, 0.1 mg/kg cisatracurium and 0.2 mg/kg mivacurium were injected intravenously according to different groups. The flexible laryngeal mask was placed after the train-of-four stimulation (TOF) ratio decreased to 0 and the mechanical ventilation was implemented immediately. General anesthesia was maintained by 1.5–2.0 μg/kg fentanyl and 2%– 3% sevoflurane. Intraocular pressure and hemodynamic parameters were measured before anesthesia induction (T0), after sedation (T1), after muscle relaxation (T2), and after laryngeal mask insertion (T3). Results: The intraocular pressure of patients in rocuronium group, cis-atracurium group and mivacurium group at T1, T2, T3 were lower than baseline (T0), and the difference was statistically significant (P<0.001); There was no significant difference in intraocular pressure at T2 compared with T1 in rocuronium group, cis-atracurium group and mivacurium group (P=0.337, P=0.520 and P=0.062 respectively); The difference of intraocular pressure between T2 and T1 in rocuronium group, cis-atracurium group and mivacurium group were (0.68±4.39), (0.36±3.72) and (1.27±3.91) mmHg respectively and there was no significant difference among the groups (P=0.353). Conclusion: The non-depolarizing muscle relaxants rocuronium, cis-atracurium and mivacurium have no significant effect on the intraocular pressure of glaucoma patients with elevated intraocular pressure, and there is no significant difference among the three muscle relaxants.
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  • 眼科学报

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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