Heat shock protein hyperexpression on chorioretinal layers after transpupillary thermotherapy.

PURPOSE: To assess a biological effect induced by temperature elevation during transpupillary thermotherapy (TTT). METHODS: Six pigmented rabbits were anesthetized, and TTT was performed on the right eye using an 810-nm diode laser installed on a slit lamp (spot size, 1.3 mm; duration, 60 seconds; power, 92-150 mW). A series of laser pulses were aimed at the posterior pole of the retina. The left eyes were used as the control. Twenty-four hours after laser irradiation, a histologic study was performed on the chorioretinal layers. Tissue samples were fixed in formalin and embedded in paraffin. A monoclonal antibody was used to detect heat shock protein (Hsp)70 immunoreactivity, followed by a biotinylated goat anti-mouse antibody, revealed by the avidin-biotin complex and the 3-amino-9-ethyl-carbazole (AEC) chromogen. Retinal structures were further identified by hematoxylin erythrosin saffron (HES) coloration. RESULTS: The photocoagulation threshold was found to be at the 150-mW laser power. Under this threshold, Hsp70 immunostaining was the strongest at the 127-mW power, with staining of some choroidal cells, including capillary endothelial cells. No Hsp70 immunoreactivity was observed on the retina. At the 107-mW power, Hsp70 reactivity was observed only in occasional choroidal cells. At the 98-mW power, only mild, diffuse Hsp70 immunoreactivity was observed in the choroid. At the 92-mW power, as in nonirradiated eyes, no Hsp70 immunoreactivity was detected. CONCLUSIONS: Subthreshold transpupillary 810-nm laser irradiation induces choroidal Hsp hyperexpression. This confirms that choroidal Hsp hyperexpression can be induced during TTT, as has been recently hypothesized by several investigators.     

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。     

经瞳孔温热疗法后视网膜和脉络膜的细胞凋亡研究

目的探讨经瞳孔温热疗法（TTT）对视网膜、脉络膜层细胞凋亡表达的影响。方法利用恒河猴做动物模型，于治疗后不同时间点摘除双眼。应用组织学及TUNNEL检测技术，研究TTT治疗与细胞凋亡的相互关系，及对视网膜、脉络膜的组织病理学影响。结果正常猴眼视网膜及脉络膜均未见细胞凋亡发生。TTT治疗后，可见光斑中央细胞坏死、周边细胞凋亡发生。1h至4周，均可见凋亡阳性细胞，4个月时，仍可见少量凋亡细胞存在。同时，TTT治疗可引起视网膜不同程度的组织病理学损害。结论TTT可引起视网膜组织病理学损害。局部温度的升高会诱导视网膜脉络膜细胞凋亡的产生，减少坏死和炎症的程度。     

不同激光强度经瞳孔温热疗法对色素兔视网膜细胞凋亡的影响

目的 观察不同激光能量的经瞳孔温热疗法（TTT）对色素兔视网膜的病理损伤及对细胞凋亡的影响。 方法 将14只有色家兔随机按不同激光能量分为空白组、50、70、90、110、130、150 mW组，每组2只兔4只眼行TTT治疗照射后,分别于24、48 h后取视网膜组织进行光学显微镜检查及用原位末端转移酶标记（TUNEL）技术和流式细胞仪检测细胞凋亡。 结果 直接检眼镜下激光反应斑颜色随能量增加由灰变白逐渐变浅，即由灰白——白——浓白，直径逐渐增大。苏木素 伊红（HE）染色：50~70 mW组光学显微镜下视网膜各层结构无明显改变；90~130 mW组视网膜结构完整,视锥、视杆细胞肿胀，内颗粒层可见少量的固缩核和细胞浆空泡化。以上能量组激光照射后24、48 h，光学显微镜下视网膜结构与空白对照组无明显差别。150 mW组激光照射后24 h视网膜组织各层肿胀、变性，感光细胞内外节部分缺失；而激光照射后48 h视网膜组织可见明显坏死，全层均可见细胞缺失。TUNEL检测结果显示，各能量组外颗粒层均可见阳性细胞，随激光能量的增加而增加，并逐渐累及内颗粒层和神经节细胞层。流式细胞仪检测结果显示，激光照射后24 h，各能量组均可见细胞凋亡峰。 结论 兔视网膜在能量为50~70 mW的TTT照射后，视网膜组织未见明显改变，但感光细胞凋亡显著增加。随着TTT激光能量增加，视网膜组织出现肿胀、变性甚至坏死。细胞凋亡逐渐累及内颗粒层和神经节细胞层。 (中华眼底病杂志, 2006, 22: 249-252)     

Subthreshold transpupillary thermotherapy reduces experimental choroidal neovascularization in the mouse without collateral damage to the neural retina

PURPOSE: Transpupillary thermotherapy (TTT) is currently being evaluated for treatment of choroidal neovascularization (CNV) in age-related macular degeneration. To optimize TTT for CNV, the effect was analyzed of invisible (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and on experimental CNV. METHODS: TTT was delivered to the normal retina of 42 mice with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain thermal lesions ranging from invisible (subthreshold) to visible (threshold) burns. CNV was induced in 53 mice by krypton laser photocoagulation of the fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW). Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV complex was evaluated on hematoxylin-eosin stained serial sections by measuring the maximum height of the CNV lesions. Ultrastructural changes were examined by transmission electron microscopy. RESULTS: Increasing the TTT laser power yielded gradually more visible effects. At 50 mW, which induced subthreshold burns, no damage was seen in the neural retina, retinal pigment epithelium (RPE), or choroid at any time point. By contrast, eyes treated with higher power exhibited progressively more damage to the neural retina, including a complete disruption of the outer nuclear layer. When TTT was applied to the laser-induced CNV lesions, the height of lesions was significantly reduced (P < 0.001) in response to all three power settings at 7 days after treatment. The mean relative thickness of the CNV lesion was 3.29 +/- 0.89 in untreated mice, whereas in TTT-treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 0.17 at power settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed no apparent damage with the 50- or 60-mW settings, whereas outer nuclear layer disruption occurred with a power of 80 mW. Electron microscopy confirmed the presence of vascular occlusion at 1 day and a fibrotic scar at 7 days after TTT. CONCLUSIONS: Subthreshold TTT can effectively occlude newly formed vessels and cause regression of the experimental CNV complex without damaging the neural retina. The results demonstrate the importance of using subthreshold laser power in experimental and clinical evaluation of TTT.     

经瞳孔温热疗法对急性高眼压大鼠视网膜神经节细胞的保护作用

目的研究低阈值经瞳孔温热疗法（TTT）对急性高眼压大鼠视网膜神经节细胞（RGC）是否具有保护作用。设计实验研究。研究对象BN大鼠。方法采用810nm二极管激光机对10只大鼠视网膜进行热刺激，照射光斑1．2mm，能量50mW，照射时间20s，干预后3d光镜下观察视网膜形态结构的改变，免疫组化方法检测HSP70、HSP27在视网膜组织表达。采用上述激光参数，照射视网膜后3d，制作急性高眼压模型（TTT＋I/R组，n=10），采用TUNEL法检测RGC层细胞凋亡数量，及计数高倍镜下RGC层细胞数，与未干预的急性高眼压模型组（I/R组，n=10）、单纯TTT干预组（TTT组）及正常对照组（n=6）进行比较。主要指标免疫组化染色RGC细胞数及RGC层细胞凋亡数。结果采用低阈值TTT可诱导BN大鼠视网膜神经节细胞HSP70及HSP27表达，且光镜下未出现明显视网膜脉络膜形态的改变。TTT＋I／R组RGC层细胞凋亡数量明显少于I／R组（P=0．048），且前者RGC层细胞数量明显多于后者（辟0．016）；TTT组与正常对照组比较RGC层细胞凋亡数量无显著性差异（P=0．882），但RGC层细胞数明显少于正常对照组（P=0．001）。结论低阈值TTT可诱导BN大鼠视网膜HSP70、HSP27表达，并在急性高眼压损伤下对大鼠RGC凋亡具有抑制作用。（眼科，2007,16：48—51）     

Transpupillary thermotherapy of juxtafoveal recurrent choroidal neovascularization

PURPOSE: To evaluate the effectiveness of low power transpupillary thermotherapy (TTT) in treating juxtafoveal recurrent choroidal neovascularization (CNV) after laser photocoagulation in patients with age-related macular degeneration (ARMD). METHODS: Eight eyes of eight patients with ARMD and juxtafoveal recurrent CNV were treated with low power TTT, delivered using an 810-nm diode laser with 350 mW, 2.0 mm spot, and 1-minute duration. Visual acuity (VA) ranged from 20/100 to 20/50. Treatment effect was evaluated by fluorescein angiography, indocyanine green angiography, and VA measurements (Early Treatment Diabetic Retinopathy Study) at 1-week, 2-week, and monthly follow-up visits. RESULTS: No retinal damage was visible ophthalmoscopically during treatment. At the first follow-up visit, seven eyes had obliteration of CNV and one eye required a second TTT application. VA was unchanged in six eyes, improved in one eye, and worsened in one eye. Recurrences occurred in all eyes between 1 and 7 months after TTT and were treated with photodynamic therapy (PDT). More than two PDT treatments were performed in each eye in the year after recurrence. CONCLUSIONS: Low power TTT is as able to close juxtafoveal recurrent CNV as is high power conventional laser photocoagulation but does not prevent recurrences. Further intervention with TTT in order to treat recurrences is under investigation.     

微脉冲半导体激光照射对正常大鼠视网膜损伤的观察

目的观察810 nm微脉冲半导体激光照射对正常棕色挪威大鼠（BN 大鼠）视网膜的损伤。方法使用不同能量及负载系数（duty cycle, D C）的810 nm微脉冲半导体激光对130只BN大鼠眼进行照射。分别于激光照射后第1、3、7、1 4、28 d进行彩色眼底照相、荧光素眼底血管造影及组织病理学观察，并检测热休克蛋白(HSP-70)在视网膜的表达情况，用TdT介导dUTP缺口末端标记法(TUNEL)检查细胞凋亡 。结果阈值及阈上能量条件下，低DC时激光照射部位无光学显微镜下的组织病理学改变，高DC时出现可累及视网膜内核层组织的严重损伤；微脉冲半导体激光照 射后1 d大鼠视网膜内核层细胞HSP-70阳性表达细胞即较正常视网膜明显增加，3 d时达到高峰，以后逐渐下降，14 d时恢复近正常水平。HSP-70阳性细胞数量 随激光能量提高而增加。TUNEL染色可见激光照射部位凋亡细胞主要存在于视网膜色素上皮（RPE）层、外核层、内核层，甚至脉络膜层，其数量随激光能量增高而增多。在激光照射后第3 d，凋亡细胞数量最多。结论810 nm微脉冲半导体激光照射后，视网膜损伤程度与激光能量及DC呈正相关。低能量高负载系数（50 mW，50％）或高能量低负载系数（100 mW，5％～15％）时，损伤限于RPE层，避免了神经上皮层的损伤。激光照射后HSP-70高表达及细胞凋亡可能在组织损伤修复过程发挥重要作用。 （中华眼底病杂志，2008，24：122-126）     

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。     

Indocyanine green enhanced photocoagulation in the pigmented rabbit]

We performed histological studies of rabbit eyes after intravenous administration of indocyanine green (ICG) and fundus endophotocoagulation with diode laser at the wavelength of 810 nm. As continuation of our previous experiments in albino rabbits, we used 10 eyes of 5 pigmented rabbits which more simulate human eyes. We created weak photocoagulation spots 5 to 30 seconds after intravenous ICG, 4 mg/kg. Each photocoagulation lasted 0.2 sec and its irradiation power was averaged 170 mW. One hour after photocoagulation, there were no changes in the inner retinal layers. In the choroid, we observed occlusion of the choriocapillaris, destruction or loss of endothelial cells of large choroidal vessels, and stromal edema. One month after photocoagulation, large choroidal vessels had disappeared. Whole choroidal layers were replaced by fibrous scar tissue. The findings seemed to indicate that ICG enhanced photocoagulation effect can be observed in eyes with pigmented retinal pigment epithelium and that irreversible choroidal damages can be induced throughout the whole thickness of the choroid. The observed choroidal damages were less in intensity than those in albino rabbits.     

Transpupillary thermotherapy: effect of wavelength on normal primate retina

PURPOSE: To correlate changes in primate fundus after transpupillary thermotherapy (TTT) at two wavelengths. METHODS: Twelve primate eyes were treated with TTT using a wavelength of 635 nm (n=7) or 810 nm (n=5). Laser parameters were as follows: 635 nm (spot size, 1 mm; duration, 30-8 seconds; and fluence [power over time], 20-91.4 J/cm) and 810 nm (spot size, 2 mm; duration, 60 seconds; and fluence, 96-436 J/cm). Fundus photography, fluorescein and indocyanine green angiography, and enucleation were performed at time 0 or 2 weeks after TTT for histologic analysis. RESULTS: Threshold for fundus lesions (91.4 J/cm at 635 nm and 191 J/cm at 810 nm), acute and chronic retinal damage shown by histologic analysis (79.2 J/cm at 635 nm and 96 J/cm at 810 nm), and choroidal vessel occlusion (50 J/cm at 635 nm and 96 J/cm at 810 nm) were lower at 635 nm. Disorganization of the retina and retinal pigment epithelium was seen for both wavelengths at time 0 and 2 weeks after TTT. Occlusion of the choriocapillaris and choroidal stromal vessels was noted only in specimens obtained 2 weeks after TTT. CONCLUSIONS: TTT resulted in acute and delayed damage to the neurosensory retina that persisted at 2 weeks. The 635-nm wavelength demonstrated a lower threshold fluence for visible fundus lesions, retinal damage, and choroidal vascular occlusion than the 810-nm laser.     

经瞳孔温热疗法对大鼠视神经钳夹视网膜神经节细胞的保护作用

目的探讨经瞳孔温热疗法（TTT）阈下反应对BN大鼠视神经钳夹后视网膜神经节细胞（RGCs）的保护作用。方法采用阈下TTT对BN大鼠视网膜进行照射后3d,通过逆行标记RGCs的方法,对TTT＋视神经钳夹组（A组）、TTT＋假手术组（B组）、单纯视神经钳夹组（C组）和空白对照组（D组）在视神经钳夹后1、2、4周进行RGCs计数并比较;检测视网膜TTT阈下反应的热休克蛋白70（HSP70）表达;观察TTT阈下反应对视网膜的影响。结果视神经钳夹后4周,A组RGCs数显著高于C组（P=0.006）,而1周和2周时2组之间差异无统计学意义（P〉0.05）;各时间点B组和D组的RGCs数差异无统计学意义（P〉0.05）。视网膜经阈下TTT干预后,HSP70表达高于对照眼。阈下TTT照射能引起视网膜组织形态上的改变。结论阈下TTT可显著提高视神经钳夹4周后RGCs的存活数量;其保护机制可能与诱导视网膜内源性HSP70表达、启动内源性保护机制有关。     

Histopathology of retinochoroidal adhesions of diode laser endophotocoagulation lesions in monkey eyes]

Retinochoroidal coagulation effect of 810 nm diode laser was studied using monkey eyes to determine the energy necessary to produce retinochoroidal adhesion safely. Power settings were at 100, 200 and 300 mW. The lesions produced with a power of 100 mW were faint grayish spots. One month after photocoagulation, there was degeneration from the outer granular layer to the superficial choroidal layer. However, chorioretinal adhesion was not obtained due to external limiting membrane formation. The lesions produced with a power of 200 mW were characterized by small whitish spots surrounded by grayish rings and retinochoroidal adhesions were produced by proliferated cells. However choroid were intensely coagulated, and there was a rupture of Bruch's membrane in one lesion. The lesions produced with a power of 300 mW were intense white spots surrounded by grayish rings. Histologically, severe cell loss of the retina was seen and three was no retinochoroidal adhesion. It can be said that it is difficult for 810 nm diode laser to obtain adequate retinochoroidal adhesion safely.     

Retinal temperature increase during transpupillary thermotherapy: effects of pigmentation, subretinal blood, and choroidal blood flow

PURPOSE: To study the risk of adverse events in transpupillary thermotherapy (TTT) for age-related macular degeneration by measuring how laser-induced retinal temperature increase is affected experimentally by subretinal blood, choroidal blood flow, and chorioretinal pigmentation. METHODS: An ultrafine thermocouple technique was developed to measure retinal temperature increase during TTT in albino and pigmented rabbit eyes. TTT was performed with 60-second, 0.78-mm spot size, 810-nm infrared diode laser exposures with power settings ranging from 50 to 950 mW. Intraretinal and subretinal temperature increases were measured in pigmented and albino rabbits, with or without subretinal blood and choroidal blood flow. RESULTS: Threshold power settings for visible lesions in albino and pigmented rabbits were 950 and 90 mW, respectively, corresponding to retinal temperature increases of 11.8 degrees C and 5.28 degrees C, respectively. Power settings required to produce threshold lesions in albino rabbits caused retinal temperature increases in pigmented rabbits that were five times higher than in the albino rabbits. Temperature increases in albino rabbits were 1.5 times higher with subretinal blood than without it. Choroidal blood flow generally did not affect measured retinal temperature increases. CONCLUSIONS: The results confirm prior theoretical recommendations that clinicians should consider decreasing TTT power settings in darkly pigmented eyes and proceed with caution in those with subretinal hemorrhage or pigment clumping.     

Early vascular changes induced by transpupillary thermotherapy of choroidal neovascularization

OBJECTIVE: To study early direct effects of transpupillary thermotherapy (TTT) on choroidal neovascularization (CNV) and choroid. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS: Sixty-four eyes with subfoveal CNV. INTERVENTION: TTT was delivered using a diode laser at 810 nm through a contact lens. Exposure time was 60 seconds with a power/diameter ratio of 247 mW/mm. The end point was an invisible treatment with no color change at the retina level. MAIN OUTCOME MEASURES: Fluorescein and indocyanine green angiographic findings within 1 hour, and at 1, 2, and 4 weeks after TTT. RESULTS: Fluorescein angiography (FA) and indocyanine green angiography (ICGA) performed within 1 hour after TTT showed increased leakage of CNV and choroidal vessels. Follow-up at 1 and 2 weeks demonstrated a hypofluorescent area corresponding to the laser spot and absence of angiographic leakage seen on FA and ICGA. At 4 weeks after TTT, FA showed mottled hypofluorescence-hyperfluorescence of the TTT-treated area and absence of angiographic leakage. CONCLUSIONS: TTT induces a characteristic dynamic sequence of vascular changes. Treatment with TTT can lead to absence of angiographic (FA and ICGA) leakage for 4 weeks. Determination of the long-term efficacy and visual implications awaits the results of clinical trials.     

经瞳孔温热疗法治疗限局性脉络膜血管瘤

目的探讨经瞳孔温热疗法治疗限局性脉络膜血管瘤的临床效果。方法经眼底检查和荧光素眼底血管造影确诊为限局性脉络膜血管瘤的患者10例（10只眼）,年龄16—48岁,平均34岁。采用经瞳孔温热疗法,以810红外激光对病变区连续照射1～5个光斑,光斑直径3．0mm,将肿物完全覆盖。激光功率为800～1200mw,照射时间60s,或延长10～20s。术后1—3个月随诊。视病情需要可重复治疗1～3次。患者随访期3～36个月,平均14个月。其中4例患者为首次治疗;6例曾接受绿激光（氪和氩）光凝治疗。结果末诊时,有1例脉络膜血管瘤患者病变正位于黄斑中心区,视网膜下尚有积液,眼底有透红光区,需继续治疗,余9例视网膜下积液完全消退,荧光素眼底血管造影和吲哚氰绿脉络膜血管造影检查,肿瘤区无强荧光出现,视力增进;经过半年至2年随诊,患者病情稳定。未发生术后并发症或后遗症。结论经瞳孔温热疗法治疗限局性脉络膜血管瘤的临床效果肯定。无论单独作为首选治疗或用于补充以前光凝治疗的不足,均可获得良好效果。（中华眼科杂志,2005,41：882-886）     

Subthreshold transpupillary thermotherapy of the retina and experimental choroidal neovascularization in a rat model

PURPOSE: To study the effect of subthreshold transpupillary thermotherapy (TTT) on the retina and experimental choroidal neovascularization (CNV) in the rat. METHODS: Subthreshold TTT was performed on normal Brown Norway rats or those with krypton laser-induced CNV and appropriate controls with an 810-nm diode laser coupled to a slit lamp. At different intervals after TTT, fundus fluorescence angiography (FFA) and histopathological examinations were performed. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was used to detect apoptosis. Immunohistochemistry was used to detect heat shock protein 70 (Hsp70) expression. RESULTS: In normal retina, edema and whitening was found on day 1 after TTT. Different degrees of hyperfluorescence could be seen on FFA. Obvious retina damage, especially in the outer layers, was observed by histology in all the lesions that appeared whitened. In the CNV there was congestion and less damage in the overlying retina than in normal retina on day 1 after TTT. Apoptosis was detected in all retinal layers and CNV lesions by TUNEL. In normal eyes, after TTT, Hsp70 expression was increased in the inner layers of the retina and some of the cells in the choroid. Hsp70 was also increased in laser-induced CNV. Two weeks after TTT, the CNV showed a tendency for fibrosis by Masson staining. FFA did not show much change in the CNV lesions 2 weeks after TTT. CONCLUSION: Subthreshold TTT has adverse effects on the overlying retina and thus is likely to cause significant functional and morphological long-term sequelae. Subthreshold TTT can cause apoptosis in laser-induced CNV in rats.     

Transpupillary thermotherapy threshold parameters: effect of indocyanine green pretreatment

PURPOSE: To evaluate the effect of combined treatment with systemic indocyanine green (ICG) on threshold fluence levels of transpupillary thermotherapy (TTT) in rabbits. METHODS: Four pigmented rabbits and 13 nonpigmented rabbits were studied. TTT was performed on normal rabbit choriocapillaris using an 810-nm diode laser via slit-lamp biomicroscope delivery through a Goldmann macular lens. Laser spot size, power, and duration of laser exposure were varied to achieve a range of TTT fluences for threshold testing in both albino and pigmented rabbit fundi. Intravenous ICG pretreatment at doses of 0.41 to 10 mg/kg was initiated at varying times before TTT treatment. After the experiment, the eyes were enucleated under deep anesthesia, the animals were killed, and the eyes were prepared for light microscopy. RESULTS: When intravenous ICG pretreatment was employed, there was a dose-dependent decrease in the TTT fluence threshold as compared with known threshold values. At threshold fluences, histopathologic sections revealed damage to all layers of the retina in addition to choriocapillaris damage. CONCLUSION: Intravenous ICG pretreatment can be used to lower the TTT threshold fluence and irradiance required to create angiographically visible lesions in the normal rabbit choriocapillaris. Damage was seen in all layers of the retina and choriocapillaris at threshold levels when TTT was used alone or in combination with ICG pretreatment.     

Irradiation of rabbit retina with diode and Nd:YAG lasers.

AIMS--This study was carried out to compare the effects of continuous wave infrared laser radiation on pigmented and albino rabbit retinas at two wavelengths: 810 nm (diode) and 1064 nm (Nd:YAG). METHODS--Transpupillary laser pulses were applied with a spot size of 200 microns and durations of 200 ms (pigmented rabbits) and 0.5-1 s (albino rabbits). Light and electron microscopic analyses were performed immediately after exposure. RESULTS--In pigmented rabbits, threshold lesions were induced using a power of 100 mW with the diode and 200 mW with the Nd:YAG lasers. Damage was incurred by the retinal pigment epithelium with extension into the superficial and mid choroid posteriorly and into the outer retina anteriorly. In albino rabbits, lesions of comparable anteroposterior extension were identified using a power of 10 W with the Nd:YAG laser. Using diode laser irradiation, a maximum power output of 1.2 W failed to produce discernible lesions. CONCLUSIONS--The observed patterns of morphological damage are produced by complex tissue radiation interactions. In pigmented animals, this was primarily related to absorption of radiant energy by melanin within the retinal pigment epithelium and the choroidal melanocytes. In albino rabbits, laser induced effects occurred as a consequence of multiple scattering, together with absorption within haemoglobin and possibly also within tissue water. The data obtained provide further insight into the biological mechanisms arising from retinal photocoagulation with near infrared lasers.     

Expression of transforming growth factor-beta receptors in normal rat retina and experimental choroidal neovascularization

PURPOSE: Transforming growth factor-beta (TGF-beta) plays an important role in the development of choroidal neovascularization. TGF-beta transduces signals through the mediation of type I and type II receptors. We investigated the expression of TGF-beta receptors in a normal rat retina and a model of experimentally induced choroidal neovascularization. METHODS: Choroidal neovascularization was induced by laser photocoagulation in rat eyes. The expression of TGF-beta receptors was determined using immunohistochemical and in situ hybridization methods. RESULTS: In normal adult rat retinas, immunoreactivity and mRNA expression of TGF-beta receptor type I (TbetaRI) and TGF-beta receptor type II (TbetaRII) were found in the ganglion cells. During the process of neovascularization, immunoreactivity and mRNA expression of TbetaRI and TbetaRII were widely distributed in laser lesions soon after photocoagulation; thereafter, these receptors were specifically detected in the endothelial cells of choroidal neovascularization. CONCLUSIONS: The expression of TGF-beta receptors in normal rat retinas suggests that TGF-beta plays an important role in the homeostasis of normal retina. The upregulation of TGF-beta receptors in choroidal neovascularization strongly suggests that TGF-beta is most likely transduced through specific receptors and plays an important role in the development of choroidal neovascularization.