Stargardt病(STGD1, OMIM#248200)是最常见的遗传性黄斑营养不良，是由ABCA4基因突变引起的常染色体隐性遗传病。该病通常在儿童晚期或成年早期发病，导致视力进行性、不可逆地损害。近年研究者在STGD1临床和分子特征以及潜在的病理生理学方面取得的重大进展，促成了许多已完成的、正在进行的和计划中的新疗法的人体临床试验。文章聚焦于STGD1的基因治疗研究进展。STGD1基因治疗的主要障碍是ABCA4基因序列过长以及ABCA4基因在光感受器细胞中的特异性转导效率不高。解决这一问题的关键是研究出具有大运载量和能高效将ABCA4基因转导进光感受器细胞的载体。目前STGD1的基因治疗策略主要包括腺相关病毒(adeno-associated viral, AAV)载体、慢病毒载体、纳米颗粒、光遗传学和反义寡核苷酸等。随着研究的深入，未来有望开发出针对STGD1的有效基因治疗方法，为患者带来新的治疗希望。该综述为临床应用和科学研究提供了宝贵的参考和思路。
Stargardt disease (STGD1, OMIM#248200) is the most common hereditary macular dystrophy, caused by mutations in the ABCA4 gene, and is an autosomal recessive inherited disorder. The disease typically manifests in late childhood or early adulthood, leading to progressive and irreversible visual impairment. Significant advances in understanding the clinical and molecular characteristics, as well as the underlying pathophysiology, have ultimately facilitated numerous human clinical trials of new therapies that have been completed, are ongoing, and are planned. This review focuses on the progress in gene therapy research for STGD1. The primary obstacle in STGD1 gene therapy is the lengthy sequence of the ABCA4 gene and the low efficiency of specific transduction of the ABCA4 gene into photoreceptor cells. The key to addressing this issue is to develop a vector with a large carrying capacity that can efficiently transduce the ABCA4 gene into photoreceptor cells. Current gene therapy strategies for STGD1 mainly include adeno-associated viral (AAV) vectors, lentiviral vectors, nanoparticles, optogenetics, and antisense oligonucleotides(AONs). With the deepening of research, it is hoped that effective gene therapy methods for STGD1 will be developed in the future, bringing new therapeutic hope to patients. This review provides valuable references and ideas for clinical applications and scientific research.
肥厚型脉络膜谱系疾病(pachychoroid disease spectrum,PCD)包括肥厚型脉络膜色素上皮病变(pachychoroid pigment epitheliopathy,PPE)、中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)、肥厚型脉络膜新生血管病变(pachychoroid neovasculopathy,PNV)、息肉样脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)、局灶性脉络膜凹陷(focal choroidal excavation,FCE)和盘周肥厚型脉络膜综合征(peripapillary pachychoroid syndrome,PPS)。有学者将PCD看作脉络膜功能障碍引发的一系列连续疾病过程，但关于PCD的发病机制、形态改变尚未明确。该文对PCD的脉络膜、涡静脉及巩膜相关改变做一综述。
Pachychoroid disease spectrum include pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy, focal choroidal excavation, and peripapillary pachychoroid syndrome. Currently, some scholars regard pachychoroid disease spectrum as a series of continuous disease processes caused by choroidal dysfunction, but the pathogenesis and morphological changes of pachychoroid disease spectrum are not yet clear. This paper reviews the changes of choroid, vortex veins and sclera in pachychoroid disease spectrum.
目的：应用广角扫频源光学相干断层扫描成像(swept-source optical coherence tomography, SS-OCT)的en face结构投射图研究玻璃体早期液化特征。方法：使用SS-OCT进行18 mm×18 mm 的容积（Cube）扫描，创建并分析健康未成年人（年龄5~18岁）70眼的系列玻璃体en face结构投射图。 结果：在未成年人中，视网膜前的玻璃体包含4种液化结构，分别为后皮质前玻璃体囊袋（posterior precortical vitreous pocket, PPVP）、视盘前Martegiani区（the area of Martegiani, AM）、血管前液化裂隙（prevascular vitreous fissures，PVF）和液化池（cistern）。所有研究眼均能检出PPVP、AM和PVF，其中22眼（31.4%）的PPVP和AM连通。41眼（58.6%）可检出液化池，且其年龄大于未检出液化池的个体（P =0.01），液化池的发生与年龄呈正相关（rs=0.315，P =0.008）。液化池的象限空间分布频率依次为颞上（90.2%）、鼻上（58.5%）、颞下（36.6%）、鼻下（24.4%），最常累及颞上象限（P＜0.001）。 结论：PPVP、AM和PVF是健康人群视网膜前玻璃体早期液化过程中均出现的特征。液化池的发生与年龄呈正相关，最常出现在颞上象限，可能是年龄相关性玻璃体液化变性的结果。
Objective: To investigate the early vitreous liquefaction characteristics using en face structural projection images obtained by wide-angle swept-source optical coherence tomography (SS-OCT). Methods: SS-OCT was employed to perform 18*18mm volumetric (Cube) scans. A series of en face structural projection images of the vitreous were created and analyzed for 70 eyes from healthy minors aged between 5 and 18 years. Results: In minors, four types of vitreous liquefaction structures were identified anterior to the retina: pre-posterior vitreous pocket (PPVP), the preoptic area of Martegiani (AM), pre-vascular liquefaction fissures (PVF), and cisterns. PPVP, AM, and PVF were detectable in all studied eyes, with PPVP and AM being interconnected in 22 eyes (31.4%). Cisterns were observed in 41 eyes (58.6%), and the mean age of individuals with cisterns was higher than those without (P =0.01). The occurrence of cisterns positively correlated with age (r=0.315; P=0.008). The frequency of cistern quadrant distribution was highest in the superotemporal quadrant (90.2%), followed by the superonasal quadrant (58.5%), inferotemporal quadrant (36.6%), and inferonasal quadrant (24.4%). The superotemporal quadrant was the most frequently affected (P <0.001). Conclusion: PPVP, AM, and PVF are features consistently observed in the early vitreous liquefaction process anterior to the retina in healthy individuals. The occurrence of cisterns positively correlates with age and is most common in the superotemporal quadrant, possibly representing the result of age-related vitreous liquefaction degeneration. These findings provide a theoretical foundation for studying the pathogenesis of vitreoretinal interface diseases.
Aim: The objective of this study was to investigate the prognosis of massive vitreous hemorrhage(VH) secondary to polypoidal choroidal vasculopathy(PCV) after vitrectomy.
Methods: Forty-nineeyes in 48 patients with PCV and breakthrough VH who underwent 23-gauge pars plana vitrectomy between January 2015 and December 2020 were enrolled. The main outcome parameters were best-corrected visual acuity, postoperative adverse events, and reoperation.
Results:The average follow-up time was 20.0±15.82 months. The average preoperative best-corrected visual acuity (BCVA) was 2.12±0.65 logarithm of the minimum angle of resolution (logMAR), the BCVA at six monthswas 1.65±0.64 logMAR, and the six-month follow-up BCVA was 1.67±0.76 logMAR. Compared to the average preoperative BCVA, the six-months and last follow-up BCVA after vitrectomy improved (P<0.05). The BCVAat the fnal follow-up was better than 1.3logMAR only in 14 eyes (28.6%). Postoperative complications were observed in 10 eyes (20.4%), including recurrent retinal detachment, recurrent vitreous hemorrhage, macular hole, hyphema and lens dislocation. Fourteen eyes(28.6%) underwent cataract surgery procedure an average of 10.16±5.14 months after vitrectomy. BCVAone week and three monthsafter cataract surgery improved compared toBCVAbefore cataract surgery (P<0.05). Hypertension was associated with BCVAsix months after vitrectomy (P=0.017). The BCVA at baseline and three months after PPV were worse in patients who underwent vitrectomy combined with silicone oil filling (P<0.05). Eyes with postoperative complications had worse BCVA at six months, 12 months, and at the final follow-up after PPV (P<0.05).The duration of VH is related to the BCVA12 months after PPV visual acuity after surgery. Patients who underwent vitrectomy within one month of the onset of vitreous hemorrhage had better BCVA 12 months after vitrectomy than those who underwent vitrectomy surgery one month later (P=0.015).
Conclusions: Although the prognosis of vitrectomy varies greatly, cataract surgery could be considered to improve BCVAif polypoidal lesions are inactive six months after vitrectomy.
Aim: The objective of this study was to investigate the prognosis of massive vitreous hemorrhage(VH) secondary to polypoidal choroidal vasculopathy(PCV) after vitrectomy.
Methods: Forty-nineeyes in 48 patients with PCV and breakthrough VH who underwent 23-gauge pars plana vitrectomy between January 2015 and December 2020 were enrolled. The main outcome parameters were best-corrected visual acuity, postoperative adverse events, and reoperation.
Results:The average follow-up time was 20.0±15.82 months. The average preoperative best-corrected visual acuity (BCVA) was 2.12±0.65 logarithm of the minimum angle of resolution (logMAR), the BCVA at six monthswas 1.65±0.64 logMAR, and the six-month follow-up BCVA was 1.67±0.76 logMAR. Compared to the average preoperative BCVA, the six-months and last follow-up BCVA after vitrectomy improved (P<0.05). The BCVAat the fnal follow-up was better than 1.3logMAR only in 14 eyes (28.6%). Postoperative complications were observed in 10 eyes (20.4%), including recurrent retinal detachment, recurrent vitreous hemorrhage, macular hole, hyphema and lens dislocation. Fourteen eyes(28.6%) underwent cataract surgery procedure an average of 10.16±5.14 months after vitrectomy. BCVAone week and three monthsafter cataract surgery improved compared toBCVAbefore cataract surgery (P<0.05). Hypertension was associated with BCVAsix months after vitrectomy (P=0.017). The BCVA at baseline and three months after PPV were worse in patients who underwent vitrectomy combined with silicone oil filling (P<0.05). Eyes with postoperative complications had worse BCVA at six months, 12 months, and at the final follow-up after PPV (P<0.05).The duration of VH is related to the BCVA12 months after PPV visual acuity after surgery. Patients who underwent vitrectomy within one month of the onset of vitreous hemorrhage had better BCVA 12 months after vitrectomy than those who underwent vitrectomy surgery one month later (P=0.015).
Conclusions: Although the prognosis of vitrectomy varies greatly, cataract surgery could be considered to improve BCVAif polypoidal lesions are inactive six months after vitrectomy.
息肉样脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)是一种以脉络膜异常分支血管网和血管末端息肉状脉络膜血管扩张灶为特征的眼底疾病。(indocyanine green angiography,ICGA)是诊断PCV的金标准，可见异常分支血管网、息肉样高荧光。(optical coherence tomography,OCT)可见色素上皮脱离(pigment epithelial detachments,PED)、双层征、指状突起、PED切迹、脉络膜增厚等。基于 OCT 的影像学研究表明，PCV属于肥厚型脉络膜谱系疾病(pachychoroid disease spectrum,PCD)，其特征是脉络膜增厚、脉络膜大血管层(Haller层)扩张，伴有毛细血管层(Ruysch层)和中血管层(Sattler层)变薄，其发病机制可能涉及脉络膜、涡静脉、巩膜等相关改变。
孔源性视网膜脱离(rhegmatogenous retinal detachment,RRD)是一种严重威胁视力的眼部疾病，目前治疗手段以手术为主，手术方式主要有视网膜气体填充术(pneumatic retinopexy,PR)、巩膜扣带术(scleral buckling,SB)以及经睫状体扁平部玻璃体切割术(pars plana vitrectomy,PPV)。目前对于RRD手术术式的选择仍然存在争议，因此研究及制定RRD手术方式抉择的临床策略具有重要的临床意义。而临床上制定RRD患者手术方案往往与患者的年龄、视网膜脱离时间、裂孔的类型、位置、数量、大小等等临床因素有关，该文就影响孔源性视网膜脱离手术抉择的相关临床因素进行综述。
Rhegmatogenous retinal detachment (RRD) is a serious eye disease threatening vision. Surgery is main treatment currently, and surgery approaches include pneumatic retinopexy (PR), scleral buckling (SB), and pars plana vitrectomy(PPV). There is still controversy over the selection of RRD surgery approaches, so it is great significant to study and develop clinical strategies for RRD surgery approaches. The surgical plans for RRD patients are often related to clinical factors, such as the patient’s age, retinal detachment time, type, location, quantity, size, etc. This article reviews the related clinical factors affecting the surgical decision for rhegmatogenous retinal detachment.
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.
