Measurement of Intraocular Concentrations of Etoposide after Systemic and Local Administration

Retinoblastoma(RB)isthemostcommonint鄄raocularmalignanttumorwhichcanattackinfantsandchildrenintheworld.Inthepastdaysintravenouschemotherapyisbeingusedwithincreasingfrequencytotreatchildrenwithintraocularretinoblastomainanattempttoavoidexternalbeamradiationtherapyandenucleation.Butthelargedoseofchemotherapeuticagentsaftersystemicadministrationmightcausesomeserioussequela.Soweexpecttoalternatetheroutesofdeliveryofchemotherapeuticagentsinsubconjunctivaladministrationtoincreasetheintraocularconce…     

Subconjunctival conbercept for the treatment of corneal neovascularization

AIM: To investigate the effectiveness and safety of subconjunctival injection of conbercept in the treatment of corneal neovascularization (CNV). METHODS: The data on 10 consecutively recruited patients with CNV who received a subconjunctival conbercept (1 mg) once, and measured the area, length, and diameter of neovascularization before and after (1d, 1, 2wk, and 1mo) treatment as well as the occurrence of systemic and ocular complications after treatment were analyzed. RESULTS: There was a statistically significant reduction in the area of CNV one day after treatment (mean±SD: 38.46±11.36 mm2), compared with before treatment (42.46±12.80 mm2, P<0.01). There was also a statistically significant reduction in the length (3.86±1.80 mm vs 4.64±1.77 mm, P<0.01) and diameter (0.044±0.022 vs 0.060±0.026, P<0.05) of CNV, one week after treatment comparing to before treatment. The reduction in all three parameters was maximized at two weeks after treatment (area: 29.49±8.83 mm2, P<0.001; length: 3.50±1.88 mm, P<0.001; and diameter: 0.038±0.017 mm, P<0.01). No severe systemic or ocular complication was observed during the study. CONCLUSION: During the observation period of one-month, subconjunctival injection of conbercept is an effective and safe method for the reduction of CNV. It may be effective as a preoperative drug for neovascular corneal transplantation.     

Pterygia: Pathogenesis and the Role of Subconjunctival Bevacizumab in Treatment

A pterygium is a very common conjunctival degenerative condition. It has been well established that there are different factors that are interrelated and involved in the growth of pterygia. Historically described more as a degenerative process, inflammation and fibrovascular proliferation have proven to be very important factors. Many studies have shown VEGF to be increased in the pathogenesis of pterygia. There are a variety of options for the management of pterygium. The over expression of VEGF in pterygium tissue led us to develop anti-angiogenic/anti-VEGF therapy which could induce regression of blood vessels and hence retard progression of pterygium. The role of angiogenesis and of VEGF in ocular pathology is established including in corneal neovascularization, specifically in pterygial tissue. Evidence suggests that local bevacizumab may be effective in treatment of ocular surface neovascularization. Currently, data in the use of subconjunctival bevacizumab in the treatment of pterygia are not conclusive. New anti-angiogenic therapies will hopefully focus more on facilitating delivery into tissue, increasing the duration of effect while continuing to minimize adverse side effects.     

视网膜母细胞瘤并发白内障的手术效果

目的：分析视网膜母细胞瘤（Rb）患儿并发白内障的诊断时间、手术时间,手术方式以及手术效果,并评估其行白内障手术的时机和安全性。方法：回顾性分析2010年1月至2016年12月在北京儿童医院、北京同仁医院和泉州市儿童医院行白内障摘除术的Rb患儿23例（25眼）。其中男11例（11眼）,女12例（14眼）。7眼行透明角膜25G切口,18眼行睫状体平坦部25G或者27G巩膜微切口。随访1～72个月,平均（24±16）个月。统计手术时间,术前Rb治疗方式及次数,术后眼底检查是否有肿瘤复发或转移。结果： 患儿平均手术年龄（35±19）个月。自确诊Rb到发现白内障的时间（中位数）为19 个月,发现白内障到白内障手术时间（中位数）为5个月,最后一次Rb治疗到行白内障手术的时间（中位数）是10个月。行白内障摘除术前全身化疗22例（102次）,局部光凝12眼（62次）,眼内注药11眼（19次）,放疗1眼（1次）,眼外冷冻6眼（10次）,玻璃体切割手术17眼（20次）。2眼在Rb治疗过程中不能查见眼底,而眼B超检查示肿瘤复发,故行白内障手术,术后局部激光治疗复发肿瘤,随访期内未再复发。23眼为肿瘤局限钙化后行白内障手术,术后19眼无肿瘤复发及转移,未做治疗;4眼出现肿瘤晚期并发症（1眼继发青光眼,2 眼前房出血,1 眼眼内肿瘤复发）,行眼球摘除术。术后行病理检查,摘除眼未见眼球外有Rb转移。结论：对于Rb患儿,必要的白内障手术为眼底检查提供了清晰的视野。对于肿瘤局限钙化病情稳定的患眼,在无肿瘤生长的角膜或者睫状体平坦部做切口行白内障手术是安全的。     

The Application of Topical Anesthesia Combined with Subconjunctival Anesthesia for Glaucoma Surgery

Purpose: To evaluate the feasibility, reliability and analgesia effect of topical anesthesia combined with subconjunctival anesthesia in anti-glaucomatous surgery.Methods: Two hundred and four cases (357 eyes) underwent anti-glaucomatous surgeries under topical anesthesia with 0.5％ Alcaine eye drops combined with subconjunctival anesthesia with 2％ Lidocaine. The analgesic effect was analysed with visual analogue pain scale.Results: Among all of 357 eyes, 62 eyes underwent peripheral iridectomy, 67 eyes underwent simple trabeculectomy, 167 eyes underwent compound brabeculectomy and 12 eyes nonpenetrating trabecular surgery. The effects of anesthesia were as follows: 304 eyes (85.2％) were painless (Grade Ⅰ), 50 eyes (14.0％) were slight painful (Grade Ⅱ), and 3 eyes (0.8％) were more painful (Grade Ⅲ) during surgery. And no severe complications were observed in all the cases during surgery and postoperatively. Amaurosis fugax was not observed in the glaucoma patients at the late stage with narrow vi     

结膜下植入物注射装置设计及应用

目的：设计一种结膜下膜片注射植入装置并进行动物实验测试其性能。方法：实验研究。设计并制 作一种结膜下植入物注射装置,并在兔左眼利用该注射装置将可降解明胶膜片注射植入（作为试验 组）,右眼作为对照组仅重复穿刺、进针动作,不植入膜片,分别于植入后0、1、2、3 d各取2只兔子, 处死后摘除眼球,制备冰冻切片后行HE染色观察伤口愈合情况。结果：设计的注射装置的针头弧度 曲率半径为18 mm,内径截面为1.96 mm×0.38 mm。利用此装置注射明胶膜片如兔眼结膜下注射后 兔眼未见出血,膜片未见移位。试验组和对照组在相同时间段伤口愈合程度相近,未见明显区别。 结论：该注射装置操作简便省时,有效地克服了常规植入手术创伤,为新型药物缓控释制剂的临床 应用提供新的辅助。     

Design and Application of a Subconjunctival Implant Injection Device

Objective: To design a subconjunctival implant injection device; to test its performance on rabbits in vivo as the model animal. Methods: A subconjunctival implant injection device was manufactured. Gelatin film was injected via the device into the left eye of rabbits (as the test group), the right eye as the control group just repeat the puncture and insertion actions without implantation of the film. After the implantation, 2 rabbits were selected to be sacrificed at the time points of 0, 1, 2 and 3 d. The eyeballs were removed and the wound healing was observed with hematoxylin-eosin staining. Results: The device with a curvature radius of the 8 mm needle and an inner diameter section of 1.96 mm×0.38 mm. No bleeding at the injection site and no translocation of the gelatin film were observed after injection with this device. The wound healing degree in the same time period between the experimental group and the control group was almost identical without any obvious difference. Conclusions: The injection device is simple and time-saving during film implantation, effectively overcoming the trauma of conventional implant surgery, which might provide new assistance for the clinical application of novel, sustained drug-release formulations.     

Retinoblastoma: Achieving new standards with methods of chemotherapy

The management of retinoblastoma (RB) has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC) is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC) is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms “RB,” and “treatment,” “chemotherapy,” “systemic chemotherapy,” “IVC,” “IAC,” “periocular chemotherapy,” or “intravitreal chemotherapy.” Relevant English language articles were extracted, reviewed, and referenced appropriately.     

Topical vs Subconjunctival Treatment of Bacterial Corneal Ulcers

The efficacy of eye drops and subconjunctival injections in the treatment of bacterial corneal ulcers for each of the following combinations were compared: cefazolin for staphylococcal ulcers, gentamicin for staphylococcal ulcers, and gentamicin for pseudomonal ulcers. Topical and subconjunctival therapy were equally effective in reducing the numbers of viable bacteria in experimental corneal ulcers. Subconjunctival injections produced high but transient peaks followed by persistent low troughs. In contrast, eye drops produced moderate but sustained concentrations throughout the treatment period. Under the conditions of this study, it appears that transient high peaks are not needed to eliminate bacteria effectively from a corneal ulcer. Since eye drops and subconjunctival injections are equally effective, other factors should determine the preferred route or routes of therapy.     

Subconjunctival injection of low-dose Mitomycin-C for treatment of failing human trabeculectomies

Purpose: To evaluate the safety and efficacy of a low-dose Mitomycin C injected subconjunctivally after a guarded filtration operation in humans. Methods: Fourteen patients with failing filters received an injection of 0.01 mg Mitomycin C (0.25 ml of 0.04 mg/ml solution) into the filtering bleb. Eyes with end stage glaucoma of patients with healthy or successfully operated fellow eye were selected for the treatment. In 6 of the cases 2 to 5 days later a needle revision of the bleb was performed. Results: In 12 of the treated eyes (86%) we found a lowering of the IOP with a mean of 8.08 mmHg (range, 4 to 13 mmHg) and a development of a typical wide, pale, avascular filtering bleb. Complications, such as conjunctival, scierai or corneal necrosis, wound dehiscence, bleb leaks, hypotony or any clinically detectable signs of toxic damage of the anterior segment of the eye were not observed. Conclusion: Subconjunctival injection of low-dose Mitomycin C in the early postoperative period may offer a useful option for improving the outcome in some cases of failing trabeculectomies. This alternative method of application seems to enhance the effect of a subsequent needle revision. With the concentration used we did not find any undesirable complications after a follow-up of 1 to 9 months.Abbreviations 5-FU 5-Fluorouracil - HM hand movements - IOP intraocular pressure - MMC Mitomycin-C - PL perception of light - TE trabeculectomy - VA visual acuity     

Establishment of Retinoblastoma Model in NOD-SCID Mice and Study of Metastasis

Purpose: To establish model of retinoblastoma subcutaneously in NOD-SCID mice and study rules of formation and distribution of retinoblastoma metastasis. Methods: Retinoblastoma cells SO-RB50 were inoculated subcutaneously in NOD-SCID mice. Animal acts and tumor formation, growth and metastasis in NOD-SCID mice were observed. Primary and metastatic tumors were studied pathohistologically by HE and immunohistochemical staining. Results: The latent periods of tumor growth were 12-19 days and the taken rate of tumor was 100%. 32 days later, 5 NOD-SCID mice were found with tumors that had metasta sized to areas mainly located in the abdominal cavity and the side of the kidney; the metastatic time of tumors in the mice also differed. The tumor cells of the primary nodules and the metastasis were similar with human retinoblastoma cells and positive in immunohistochemical staining of NSE. Conclusion: The subcutaneous model of retinoblastoma in NOD-SCID mice showed a high taken rate and a short latent period of tumor, which had a high metastatic rate and was the best model in research of behaviors of retinoblastoma at present. Eye Science 2005 ;21:185-191.     

局部治疗加化疗治疗眼内视网膜母细胞瘤

目的探讨局部治疗加化疗治疗眼内视网膜母细胞瘤的效果。方法对11例眼内视网膜母细胞瘤病人使用联合化疗(长春新碱、卡铂、环磷酰胺、VP 16)加局部治疗。有4例在3个方案的化疗后行眼球摘除术。结果停药后平均随访9.4月,有2例双眼视网膜母细胞瘤复发,其余患眼随访中无新病灶或对侧眼无病灶。结论对于眼内期视网膜母细胞瘤病人使用化疗加局部治疗是有效的,化疗可能有预防肿瘤转移的作用。     

视网膜母细胞瘤综合治疗的预后及其相关因素

目的：研究视网膜母细胞瘤（RB）患儿综合治疗的预后并探讨其相关临床因素。 方法：回顾性系列病例研究。分析在深圳市眼科医院进行综合治疗的65例（92眼）RB患儿的临床资料。综合治疗的方法为以化疗为主联合局部治疗（光凝或冷冻）+眼球摘除治疗。不同结局相关临床因素的比较采用独立样本t检验,其余指标采用Fisher's精准检验。 结果：所有RB患儿的总生存率为92%,不同分期生存率差异无统计学意义。所有患儿总的保眼率为51%,E期和其他4期之问保眼率差异均有统计学意义(P<0.01)。高风险D、E期RB患儿共60例,采用化疗联合局部治疗保眼的共42例,D期18例中11例保眼成功,E期24例中4例保眼成功。治疗成功与失败患儿的初诊时间和随访时间差异无统计学意义。根据眼内肿瘤的位置将42例患儿分为3组,分析显示即周边部（包括中周部）与后极部、后极部+周边部保眼率差异有统计学意义(P=0.009、0.021)。42例患儿中4例死亡,均为肿瘤位置处于后极部的患儿,后极部与后极部+周边部2组之间病死率差异有统计学意义( P=0.045)。 结论：综合治疗提高了RB患儿的生存率,但患儿的生存率和保眼率与其临床分期及肿瘤所处的位置高度相关。     

视网膜母细胞瘤体外集落培养的实验研究

研究了不同的培养条件对视网膜母细胞瘤细胞株Ｙ－７９及Ｓｏ－Ｒｂ５０体外集落形成能力的影响。结果表明，甲基纤维素法优于双琼脂培养法。各种培养条件中以甲基纤维素加胎牛血清为佳。实验还表明，来源于Ｒｂ裸鼠移植瘤的组织标本在体外很难进行集落培养，有待于进一步研究。     

马法兰在视网膜母细胞瘤治疗中的应用

马法兰（melphalan）是目前治疗视网膜母细胞瘤（retinoblastoma,RB）较有效的药物,主要给药方式是经眼动脉化疗和玻璃体腔注药治疗。经眼动脉化疗后70．0％的患者在2年内无不良事件发生,并且因其全身毒性小而得到广泛应用。在 RB 的治疗中,对出现玻璃体种植者的治疗具有挑战性。在玻璃体腔注射马法兰技术出现后,对有玻璃体种植的 RB 保留眼球率远远超过了既往的任何治疗手段。因此马法兰经眼动脉化疗和玻璃体腔注药治疗是治疗 RB 的有效手段之一。（国际眼科纵览,2016,40：187-191）     

Forget-Me-Nots in the Care of Children with Retinoblastoma

The management of retinoblastoma has gradually evolved over the past years from enucleation to radiotherapy to current techniques of chemotherapy. Eyes with massive retinoblastoma filling the globe are still managed with enucleation, whereas those with small, medium, or even large tumors can be managed with chemoreduction followed by tumor consolidation with thermotherapy or cryotherapy. Despite multiple or large tumors, visual acuity can reach 20/40 or better in many cases, particularly those eyes with extramacular tumors. Previous complications of dry eye, cataract, retinopathy, and facial deformity that were found following external beam radiotherapy are not anticipated following chemoreduction. Recurrence from subretinal and vitreous seeds can be problematic. Long-term follow up for second cancers is advised.     

Effect of Cauterization on the Subconjunctival Fibrovascular Reaction in Rabbit Eyes

ABSTRACT

Objective: The purpose of our study is to investigate the effect of episcleral cauterization during conjunctival autograft surgery on subconjunctival fibrovascular reaction in rabbit eyes. Methods: Twenty-four healthy male New Zealand white rabbits were divided into Control Group (n?=?12) and Cautery Group (n?=?12). In the Control Group, a 4?×?4?mm free conjunctival graft was elevated, the underlying Tenon’s capsule was excised, and the free graft was sutured back to its original place with 10-0 nylon sutures. In the Cautery Group, in addition to the same surgical steps, the episclera was cauterized with six gentle touches before the conjunctival graft was sutured back to its original place. The scleroconjunctival block of the operated area was excised at the first month. The sections were stained with hematoxylin and eosine and Masson trichrome and were evaluated using light microscopy. Results: Subconjunctival collagen fibers were increased, and the fibroblast density increased more significantly in the Cautery Group than in the Control Group. The groups were similar regarding vascularization, lymphocytic, and plasmocytic infiltration. Macrophage density was normal in all animals in both groups. Conclusion: Our histopathological examinations indicate that cauterization seems to lead to an increase in subconjunctival fibrosis at the first postoperative month in rabbit eyes.     

EDWARD COTLIER AND ROBERT WEINREB, EDITORS Retinoblastoma in Transgenic Mice: Models of Hereditary Retinoblastoma

Retinoblastoma, the most common intraocular malignancy in childhood, has served as a paradigm for the study of genetic mechanisms of oncogenesis. The retinoblastoma susceptibility gene RB1 was the first tumor suppressor gene to be cloned, and genetic and molecular biologic studies of this tumor have greatly expanded the understanding of the mechanics of tumorigenesis. Human retinoblastoma has essentially no naturally occurring animal counterpart. The development of transgenic murine models of retinoblastoma have created an experimental tool for manipulation of a tumor gene system in vivo. These models have also enabled studies of new therapeutic modalities. This review outlines the development of the transgenic murine models of retinoblastoma, together with the genetic mechanisms of retinoblastoma origin. Current therapeutic innovations developed by means of the transgenic models are described.     

The Drug Sensitivity of Cyclosporine A Combined with Antineoplastic Drugs in Retinoblastoma in Vitro

Purpose: To study cyelosporine A inhibition on the fresh retinoblastoma cells in vitro and increasing the drug sensitivity after combined with different antineoplastic drugs. Methods : To study the growth curve of cyelosporine A on 27 samples of primary retinoblastoma cells by MTT assay and to study the change of the drug sensitivity by cyelosporine A combined with seven antineoplastic drugs. Results: The average IC50 of cyelosporine A on the 27 retinoblastoma cells is 67.81μg/ ml and the average inhibitive rate of these samples is 26.1% when cyelosporine A is in the concentration of 2μg/ml. The inhibitive rates all got improved after the seven antineoplastic drugs combined with cyelosporine A and the increasing average inhibitive rate is more than 5. Conclusion: Cyelosporine A can inhibit retinoblastoma cells in vitro and its inhibitive effect is dose dependent. Moreover it can enhance the inhibition of multiple antineoplastic drugs on retinoblastoma cells. Eye Science 2005;21;62-66.