恒河猴经瞳孔温热疗法与热休克蛋白相关研究

目的探讨恒河猴经瞳孔温热疗法（transpupillary thermotherapy，TTT）治疗后视网膜和脉络膜组织热休克蛋白70（heat shock protein 70，HSPT0）表达。方法利用恒河猴做动物模型。于1TIrr治疗后不同时间点（1h、1d、1周、2周、1月、4月）摘除双眼固定。应用免疫组化技术，分析TTT治疗对猴眼视网膜和脉络膜组织HSP70的影响。结果TTT治疗后，于1d起，在强反应光斑边缘视网膜和脉络膜有HSP70的表达，4个月时仍有弱表达。弱反应光斑1d时，在视网膜全层及脉络膜均有HSP70表达，4个月时消失。同时,TTT治疗可以引起视网膜不同程度组织病理学的损害。结论TTT可以引起视网膜、脉络膜组织病理学损害。局部温度的升高会诱导视网膜、脉络膜内源性HSP70的产生，并且这种表达在激光治疗后1～4个月的猴眼中仍可以存在。     

兔眼经瞳孔温热疗法阈值能量治疗的组织病理反应和细胞凋亡

目的:观察兔眼视网膜经瞳孔温热疗法(transpupillary thermotherapy,TTT)阈值能量照射后组织病理反应和细胞凋亡情况.方法:健康青紫兰兔20只,采用阈值能量对实验眼采用1.2mm光斑的810nm激光照射60s.采用眼底镜和眼底照相对光斑进行形态学研究,采用光镜和电镜的方法研究光斑的组织病理和超微结构的改变,采用TUNEL法、荧光素标记Annexin Ⅴ-FITC/PI双染色流式细胞测定法观察视网膜细胞的凋亡.结果:TTT后1d可见视网膜轻度灰白色水肿,后视网膜逐渐出现色素沉着.组织病理学切片显示神经节细胞无显著性破坏.TUNEL染色可见视网膜全层均有细胞凋亡的发生,以内颗粒层为主,流式细胞双染测定显示以凋亡为主.结论:阈能级TTT照射未引起神经节细胞严重损伤,较安全,其作用机制以细胞凋亡为主.     

兔视网膜脉络膜经瞳孔温热疗法生物学效应初探

目的：探讨经瞳孔温热疗法（TTT）对灰兔视网膜脉络膜的生物学效应,为临床合理应用提供参考依据.方法：使用半导体激光器对8只灰兔视网膜进行照射,光斑直径1.2mm,曝光时间1min,激光功率分别为150,200,250,300mW,分别于激光后1h及1mo行光、电镜观察.结果：150mW激光照射时,仅使视网膜色素上皮（RPE）轻度变化;200mW时除RPE变化外,脉络膜细胞变性,毛细血管内红细胞淤滞、变形;随能量加大（250mW）,RPE受损加重,外层视网膜也同时受累,晚期视细胞层及外颗粒层消失;当激光能量达到300mW时,全层视网膜均受到损伤,并可引起脉络膜出血,甚至出现新生血管内皮细胞.结论：TTT对正常灰兔视网膜脉络膜的效应与激光能量成正比,RPE及邻近脉络膜是TTT的主要作用部位.     

兔视网膜脉络膜经瞳孔温热疗法组织病理学改变

经瞳孔温热疗法（transpupillary thermotherapy,TTT)是一种治疗局部疾疾的热疗技术。初步临床结果表明，TTT治疗脉络膜黑色素瘤、视网膜母细胞瘤、脉络膜血管瘤以及脉络膜新生血管（choroidal ncovascularization,CNV)等疾病，具有效率高而组织损伤小的优点。但目前临床判断TTT治疗的激光终反应均以视网膜的颜色改变为依据，有时为获得合     

经瞳孔温热疗法治疗孤立性脉络膜血管瘤

目的
观察经瞳孔温热疗法(transpupillary thermotherapy，TTT)治疗孤立性脉络膜血管瘤的疗效。
方法
回顾分析12例孤立性脉络膜血管瘤患者12只患眼采用TTT治疗的临床疗效。治疗使用Iris810 nm红外激光，能量220~1000 mW，光斑直径1.2、2.0、3.0 mm，照射时间1~2 min。观察治疗前后视力、视网膜下液、脉络膜血管瘤的厚度及渗漏的变化以及治疗的并发症等情况。随访6～16个月，平均随访10个月。
结果
12例脉络膜血管瘤患者中伴有周边视网膜脱离者8例，经TTT治疗后周边液体完全吸收6例，部分吸收2例。治疗后视力不变者7例、提高者3例、下降者2例。8例治疗前曾行B型超声检查者，治疗后B型超声检查7例瘤体厚度较治疗前降低，其厚度平均下降21.75%。10例治疗前行荧光素眼底血管造影检查者复查均可见瘤体的渗漏明显减轻。治疗的并发症有视网膜出血5例、视网膜皱褶1例。
结论
TTT是治疗脉络膜血管瘤的有效方法，特别适用于伴有明显视网膜脱离的患者。
(中华眼底病杂志, 2002, 18: 190-192)     

脉络膜转移癌的经瞳孔温热疗法观察

目的 观察经瞳孔温热疗法治疗脉络膜转移癌的临床疗效.方法 9例患者中男性2例,女性7例.双眼病人3例,单眼病人6例;共12只眼.年龄37～60岁,平均44.6岁视力≤0.05者1只眼,0.06～0.2者2只眼,≥0.3者9只眼.转移灶呈黄白色扁平隆起,病灶表面均合并有不同程度的浅脱离.病灶数目为单个者2只眼,2个者3只眼,3个或以上者7只眼.转移灶位于后极部者4只眼,位于黄斑及其周者6只眼,位于视盘周者2只眼.原发病灶为肺及支气管肿瘤者5例;乳腺癌者3例;大肠癌者1例.采用眼底检查、荧光素眼底血管造影及B型超声波作检查.治疗采用]经瞳孔温热疗法.波长810μm;所用能量250～1000mw,平均510mw;光斑大小2.0～3.0mm;曝光时间60s或120s.以转移灶处小现灰白色反应斑为宜.治疗点数2～6个点,平均3.7个点.治疗次数1～6次,平均2.9次.治疗间隔时间1～3个月.其中1例转移灶位于黄斑中心合并维替泊芬(visudyne)光动力治疗.结果 经治疗后转移癌处呈扁平瘢痕色素沉着,渗液吸收.视力增进者2只眼;视力不变者4只眼;视力下降者6只眼视力下降缘于转移灶就在黄斑部或存在黄斑继发病变.观察时间1～32个月,平均9.6个月.结论 脉络膜转移癌适宜采用经瞳孔温热疗法.该疗法治疗脉络膜转移癌效果确切而价廉,值得采用.     

应用经瞳孔温热疗法光凝兔眼视网膜即刻组织学观察及凋亡细胞检测

目的 观察经瞳孔温热疗法（TTT）治疗视网膜所引起的即刻组织学反应，同时检测视网膜光斑处细胞凋亡现象。方法 取健康灰色家兔10只，随机将每只兔的左右两眼分为对照眼和实验眼。用波长810nm的激光光凝兔眼视网膜，形成Ⅰ、Ⅱ、Ⅲ级光斑，即刻摘除眼球。取光凝视网膜用石蜡包埋，苏木精-伊红染色，并行细胞凋亡的检测。结果 Ⅰ级光斑视网膜色素上皮细胞、感光细胞和外核层细胞水肿破坏，细胞结构混乱；Ⅱ级光斑上述细胞溶解破坏；Ⅲ级光斑视网膜全层破坏严重。细胞凋亡检测见各级光斑区域光细胞呈阳性表达。结论 不同光斑区的激光引起的视网膜破坏程度及侧重部位不同，而这种破坏表现为细胞凋亡的产生。     

经瞳孔温热疗法治疗视网膜大动脉瘤的疗效观察

目的观察经瞳孔温热疗法(TTT)治疗视网膜大动脉瘤的疗效。方法采用经瞳孔温热疗法对视网膜大动脉瘤24例(24只眼)进行治疗。根据荧光素眼底血管造影(FFA)显示的瘤体大小及荧光渗漏情况,采用810 nm激光照射,激光功率、光斑直径和曝光时间为500～1000 mW、800～1200μm和60 s。结果经1年随访,视力增进2行以上者9只眼。视力提高1行者8例,视力不变者5例,视力下降1～2行者2例。3个月后FFA显示:24例瘤体完全萎缩,无荧光素渗漏。结论 TTT治疗视网膜大动脉瘤安全、有效。     

经瞳孔温热疗法治疗视网膜大动脉瘤的疗效观察

目的:观察经瞳孔温热疗法(transpupillary thermotherapy,TTT)治疗视网膜大动脉瘤的疗效。方法:回顾分析24例24眼视网膜大动脉瘤患者行TTT治疗的临床疗效。根据荧光血管造影显示的瘤体大小选择不同的光斑(0.8~1.2mm)和总能量(22.4~36.8mJ),照射时间1min。观察视力、瘤体及管壁恢复情况。结果:所有患者1次治疗后动脉瘤均萎缩,管壁恢复正常,17例视力有提高。结论:TTT是治疗视网膜大动脉瘤的有效方法,尤其适用于伴明显视网膜出血、水肿的患者。     

经瞳孔温热疗法治疗中心性渗出性脉络膜视网膜炎

目的 观察经瞳孔温热疗法(transpupillary thermotherapy,TTT)对中心性渗出性脉络膜视网膜炎(central exudative chorioretinopathy,CEC)的治疗效果。 方法 使用Iris 810 nm 半导体激光对29例CEC患者进行TTT治疗，采用1.2、2.0及3.0 mm光斑，能量80～300 mW，照射时间60 s。随访4～40周，通过视力、直接检眼镜检查、荧光素眼底血管造影(fundus fluorescein angiography,FFA)及吲哚青绿血管造影(indocyanine green angiography,ICGA)观察治疗效果。 结果 治疗后视力提高者8例，占28%；无变化者19例，占65％；视力下降者2例，占7%。12例患者症状有程度不同的改善，眼底检查病变减轻者10例。20例复查眼底血管造影的患者中，12例脉络膜新生血管(choroidal neovascularization,CNV)明显消退、渗漏减轻。 结论 TTT对CEC有较好的治疗效果。 (中华眼底病杂志, 2002, 18: 184-186)     

经瞳孔温热疗法新进展

经瞳孔温热疗法（transpupillary thermotheraphy，TTT）采用810nm激光，治疗后极部多种体积较小的脉络膜视网膜肿瘤。近年来，人们摒弃了治疗时视网膜上需产生不同程度可见光斑的传统光凝治疗观念，TTT试图以不产生可见反应或仅见轻微颜色反应来治疗脉络膜新生血管膜。本文综述了此方法的研究进展。     

经瞳孔温热疗法对正常兔眼视网膜脉络膜的影响

目的 探讨影响经瞳孔温热疗法(TTT)治疗效果的因素。方法 健康成年日本大耳白兔8只、青紫兰兔12只分为3组,麻醉、散瞳并安放全视网膜镜,行TTT。结果 光斑直径为1．2mm,暴露时间为1分钟时,正常白兔进行阈值TTT所需的激光功率为1200mW,正常灰兔进行阈值TTT所需的激光功率为110mW;随激光功率的增加视网膜出现颜色改变的同时,光镜下亦出现相应的改变;照射时给眼球一定的压力,使脉络膜循环发生障碍,会加重激光对视网膜的损坏。结论 TTT是一种阈值治疗,阈值上治疗可引起兔眼视网膜组织的不可逆损伤。眼底色素含量与脉络膜循环状态是影响阈值功率选择的重要因素。     

经瞳孔温热疗法治疗渗出型相关性黄斑变性的临床观察

目的 观察经瞳孔温热疗法(TTT)对渗出型老年性黄斑变性(AMD)的临床效果。方法 对19例荧光素眼底血管造影(FFA)和吲哚菁绿血管造影(ICGA)检查确诊为AMD的患者的22只患眼进行TTT治疗。采用810mm半导体激光，光斑0．5～3．0mm，能量200～400mW，照射时间60s。对三面镜眼底检查、FFA、ICGA图像所显示的脉络膜新生血管(CNV)进行照射，照射区未出现颜色变化或旱淡灰白色。对比分析患者治疗前后视力、眼底及OCT检查。结果 22患眼治疗后1～10个月，平均随访观察时间4．8个月，视力不变者13例，占59．1％；进步者7例，占31．8％；下降者2例，占9．1％。20眼OCT复查者中，黄斑水肿不变者11例，占55％；好转者7例，占35％；恶化者2例，占10％。再次行TTT治疗者5眼，占接受TTT治疗者的22．7％。治疗随访期间无明显治疗副作用。结论 TTT治疗能使大部分渗出性AMD患眼视力稳定或提高，使用安全，值得临床推广应用。     

Serum melatonin levels following enucleation and transpupillary thermotherapy in patients with choroidal melanoma

Purpose : To study serum melatonin levels in patients with choroidal melanoma preoperatively and following enucleation and transpupillary thermotherapy. Methods: Forty patients with preoperative choroidal melanoma were included in the study. Of these, 15 patients underwent enucleation (group 1) and 25 patients received transpupillary thermotherapy (group 2). A further 20 patients without melanoma acted as age‐matched controls. Serum melatonin levels were determined 1 day preoperatively, and at the first and sixth months postoperatively using ELISA. Results: Preoperative serum melatonin levels were highest in group 2 followed by group 1, but this was not statistically significant compared to controls. Postoperatively, a constant decrease of serum melatonin was observed in both groups after the first month, which reached statistical significance at the sixth month (P = 0.003). Also, a significant regression in tumour thickness was documented in group 2 (P = 0.003). Three patients in group 1 developed hepatic metastases. Conclusions: Patients with choroidal melanomas had higher levels of serum melatonin compared to individuals without tumours. Smaller tumours were associated with more elevated melatonin levels compared to larger tumours. Serum melatonin levels fell considerably following enucleation and transpupillary thermotherapy.     

The effect of intravitreal bevacizumab and transpupillary thermotherapy on choroidal metastases and literature review

Aims:

To represent the effects of transpupillary thermotherapy (TTT) and intravitreal bevacizumab on choroidal metastases and review the literature.

Settings and Design:

A retrospective, interventional, noncomparative case series.

Materials and Methods:

A retrospective, interventional, noncomparative case series of five eyes in three patients with choroidal metastases was conducted. Fundus findings of choroidal metastases were divided into two types: Solitary or diffuse type. The size of the tumor was termed small (<10 mm diameter), medium (10–15 mm diameter) or large (>15 mm diameter). All eyes received one session of TTT followed by 3 weekly intravitreal bevacizumab injections as an adjuvant therapy. The parameters of treatment for TTT were 1.2–3 mm spot size, 150–300 mW, 60 s with the whole lesion covered confluently. The changes in preoperative and postoperative best-corrected visual acuity (BCVA) were recorded. Serial color fundus photography and optical coherent tomography were performed to measure the treatment efficacy.

Results:

All eight choroidal metastases were solitary type. The size of six tumors was small, the size of one tumor was medium, and the size of one tumor was large. All five eyes of the three patients had improvement of BCVA after treatment. Fundus photos revealed tumor shrinkage and the mean shrinkage percentage was 61.27 ± 21.71%. Optical coherence tomography revealed complete resolution of serous retinal detachment. There was no recurrence after 6 months follow-up.

Conclusions:

TTT combined with intravitreal bevacizumab injections brought about beneficial effects in reducing tumor size and improving vision in all five eyes of the three patients. Despite the retrospective nature of our study, the absence of control group and the size limitation that, of course, limit the statistical power, TTT combined with intravitreal bevacizumab seems to be efficient in providing another cost-reducing and time-saving treatment option for patients with choroidal metastases. The antineoplastic properties of bevacizumab make it a viable adjunctive therapy. Studies with more cases and a longer follow-up period are warranted.     

Subthreshold transpupillary thermotherapy in Chinese patients with myopic choroidal neovascularization: one- and two-year follow up

Background:  To perform a safety and efficacy study of subthreshold transpupillary thermotherapy (TTT) in Chinese patients with choroidal neovascularization (CNV) secondary to pathologic myopia.
Methods:  In a prospective study, patients with subfoveal or juxtafoveal CNV secondary to high myopia underwent subthrehold TTT with fixed treatment and follow-up protocols. From October 2002 to July 2005, 12 and 24 months of follow up were completed for 21 eyes and 13 eyes respectively.
Results:  The mean best-corrected visual acuities (BCVA) were maintained at the baseline level at 1 and 2 years. Seventy-two per cent of eyes and 63% of eyes had stable or improved BCVA at 12 and 24 months. Thirty-four per cent and 39% of eyes had a moderate gain in vision (improved by three or more lines) at 12 and 24 months respectively. The average number of subthreshold TTT treatments was 1.7. The major complication of subthreshold TTT included laser-related low-grade retinal pigment epithelium atrophy in two eyes of young patients with clear lenses. The final VA was significantly associated with pretreated VA ( r  = 0.614, P  = 0.003). The final VA improvement was significantly associated with pretreatment VA in negative correlation ( r  = −0.731, P  = 0.0002, Person correlation test).
Conclusions:  Subthreshold TTT in Chinese patients with pathologic myopia and subfoveal or juxtafoveal CNV generally maintained vision at 1- and 2-year follow up. Using decreased power of subthreshold TTT, especially in the younger patients with a clear lens, is suggested.     

经瞳孔温热疗法诱导大鼠热休克蛋白60在视盘中的表达

目的探讨经瞳孔温热疗法（TTT）阈下刺激诱导大鼠视盘中热休克蛋白（HSP）60的表达,探讨TTT对视盘组织超微结构的影响。方法采用810nm二极管激光对12周龄的BN大鼠56只右眼视盘进行阈值下TTT照射,选择激光参数为光斑直径0.5mm、持续时间60s、能量60mW;另设8只正常大鼠为对照。实验鼠分别于TTT照射后24h、72h和1周过量麻醉处死,实验眼的视盘组织切片制备后应用免疫组织化学染色法鉴别BN大鼠视盘TTT照射后HSP60的表达;Western blot法对TTT干预后HSP60在视盘组织中的表达进行半定量分析,并以吸光度（A）值表示。透射电镜下观察TTT照射后1周实验眼视盘组织的超微结构变化。结果免疫组织化学染色显示,HSP60在正常大鼠视盘局部呈弱阳性表达,TTT干预后24h、72h及1周HSP60的阳性染色明显增强,72h最强;Western blot蛋白质表达半定量分析显示,HSP60在正常大鼠视盘中的表达量为21458.13±156.32,在TTT干预后24h、72h及1周表达量分别为46907.24±10099.20、61848.02±2714.49、40738.01±5670.12,较正常大鼠视盘中的表达量明显上调,差异均有统计学意义（t=0.002、t=0.000、t=0.001,P〈0.01）,72h表达最强。阈下TTT干预后1周透射电镜下可见视盘神经纤维轴索部分髓鞘板层离散,个别轴索神经微丝、微管有溶解现象,有轻度轴膜下水肿,但神经纤维密度无明显减少。结论 TTT阈下刺激可诱导大鼠视盘中HSP60的表达,并对正常组织的超微结构产生轻度影响。