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.     

Subthreshold transpupillary thermotherapy for subfoveal occult choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. METHODS: 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. RESULTS: All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. CONCLUSION: Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis.     

Subthreshold transpupillary thermotherapy for subfoveal occult choroidal neovascularization secondary to age-related macular degeneration

Purpose. To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. Methods. 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. Results. All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. Conclusion. Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis.     

Low power transpupillary thermotherapy of choroidal neovascularization

PURPOSE: To assess the effectiveness of low power transpupillary thermotherapy (TTT) for choroidal neovascularization (CNV). METHOD: We performed TTT on 55 eyes of 55 patients with subretinal CNV between April 2001 and December 2002, and observed them after therapy for more than 6 months. The laser power ranged from 80 to 320 mW when the spot size was 3 mm. We evaluated visual acuity, subretinal fluid (SRF), and CNV size. RESULTS: Visual acuity improved by 2 lines or more in 16 eyes (29%), was unchanged in 19 eyes (35%), and decreased in 20 eyes (36%). SRF decreased in 30 eyes (54%), was unchanged in 13 eyes (24%), and increased in 12 eyes (22%). CNV diminished in 33 eyes (60%), was unchanged in 10 eyes (18%), and became enlarged in 12 eyes (22%). CONCLUSIONS: Low power TTT can be an effective treatment for subgroups of patients with subfoveal CNV.     

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.     

Macular burn after transpupillary thermotherapy for occult choroidal neovascularization

PURPOSE: To report a case of severe macular burn as a complication of transpupillary thermotherapy treatment for occult choroidal neovascularization. DESIGN: Interventional case report. METHODS: A 65-year-old man developed a severe macular burn following transpupillary thermotherapy treatment. RESULTS: Before treatment, fluorescein angiography and indocyanine green angiography showed a progressive, ill-defined leakage corresponding to the presence of occult choroidal neovascularization. One month after treatment, fundus examination disclosed macular atrophy. The early phases of fluorescein angiography and indocyanine green angiography showed that the macular choroidal filling time had worsened dramatically. At the late phase of indocyanine green angiography, the initial hyperfluorescence of choroidal neovascularization was replaced by a persistent, markedly hypofluorescent area. CONCLUSION: Prolonged choroidal filling may be a risk factor for macular burn and choroidal occlusion after transpupillary thermotherapy. In such cases, we suggest that transpupillary thermotherapy should be considered with caution and, when applied, that its intensity should be reduced.     

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.     

Retinal pigment epithelial tear after transpupillary thermotherapy for choroidal neovascularization

PURPOSE: To describe two patients who developed a retinal pigment epithelial tear after transpupillary thermotherapy for choroidal neovascularization. METHOD: Case reports. RESULTS: Retinal pigment epithelial (retinal pigment epithelium) tear developed in 2 (8%) of 25 eyes after transpupillary thermotherapy for occult choroidal neovascularization associated with age-related macular degeneration. In both eyes, the retinal pigment epithelium tear developed between the treatment session and first post-treatment examination. In both eyes, the visual acuity was unchanged, but the complication of retinal pigment epithelium tear may result in decreased visual acuity when transpupillary thermotherapy is performed in an eye with good initial visual acuity. CONCLUSION: Retinal pigment epithelium tear appears to occur more frequently after transpupillary thermotherapy for poorly defined choroidal neovascularization than after conventional laser photocoagulation for poorly defined choroidal neovascularization.     

经瞳孔温热疗法治疗病理性近视性脉络膜新生血管的临床观察

目的:观察经瞳孔温热疗法(TTT)治疗病理性近视合并中心凹下脉络膜新生血管(CNV)的疗效.方法:采用半导体810nm红外激光对荧光素眼底血管造影(FFA)和吲哚青绿血管造影(ICGA)检查确诊的高度近视合并CNV患者15例15眼进行治疗.治疗后每月复查1次,随访1～3 mo.随访时检查视力、眼底出血和渗出吸收、CNV闭合情况.结果:15眼治疗后均无即刻视力下降或其他不适.末诊时与初诊视力相比,73.3%无变化,26.7%增加.所有病灶渗漏减少或消失,出血基本吸收,CNV部分闭塞并纤维化.OCT检查激光后CNV厚度变薄.有3例患者3眼脉络膜萎缩灶扩大,2例2眼病灶瘢痕化.结论:TTT对治疗高度近视合并CNV有一定效果,但存在病灶疤痕化及脉络膜萎缩灶较治疗前扩大的问题.     

Subthreshold transpupillary thermotherapy for early resolution of foveal subretinal fluid in choroidal metastasis

PURPOSE: To report the effectiveness of subthreshold transpupillary thermotherapy (TTT) in the early resolution of subretinal fluid at the fovea in solitary choroidal metastasis. METHODS:: Three consecutive patients who had adenocarcinoma of the lung with choroidal metastasis and macular subretinal fluid were treated by subthreshold TTT. Tumor response and fluorescein angiographic and visual results were recorded. RESULTS: Fluorescein angiography revealed solitary choroidal metastasis at the posterior pole with subretinal fluid in all patients. Initial best-corrected visual acuity in Patient 1, a 57-year-old man, was 40/200. Instead of usual high laser intensity, three applications of TTT, 400-mW power, 3-mm size, and 1-minute duration, were performed over the tumor mass. Repeated treatment with the same regimen was performed after 1 week. Visual acuity improved to 20/25 2 months after treatment. Best-corrected visual acuity in Patient 2, a 68-year-old woman, was 10/200 in the right eye before treatment. Visual acuity improved to 80/200 after treatment and remained stable for 14 months. Visual acuity improved from 20/100 to 20/60 in a third patient 2 months after treatment. The disappearance of subretinal fluid over the fovea was noted by fluorescein angiography 2 months after laser treatment and remained stable until the end of follow-up. CONCLUSION: Improvement of visual acuity and cessation of fluorescein leakage in the tumor showed that subthreshold (i.e., biomicroscopically invisible laser effect) TTT served as an effective treatment modality in the early resolution of macular subretinal fluid in choroidal metastasis. Multiple sessions of subthreshold TTT are safe to apply very close to the macula.     

Indocyanine green dye-enhanced transpupillary thermotherapy of classic subfoveal choroidal neovascularization.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of indocyanine green dye-enhanced transpupillary thermotherapy for the treatment of classic subfoveal choroidal neovascular membrane (CNVM) with differing etiologies. PATIENTS AND METHODS: Nine eyes of 9 patients with classic subfoveal CNVM with different etiologies that was treated with indocyanine green dye-enhanced transpupillary thermotherapy were prospectively studied. All patients underwent pretreatment fluorescein angiography. Three minutes after dye injection (25 mg of indocyanine green), transpupillary thermotherapy was delivered using a modified diode laser at 810 nm, with a variable spot size of 0.8 to 2 mm depending on the size of the CNVM. A power range between 100 and 800 mW was used and treatment was initiated in one spot for 60 seconds; the end point was a barely detectable light gray appearance of the lesion. The outcome measures were assessed by Snellen visual acuity chart and obliteration of the CNVM by fluorescein angiography. Mean follow-up was 16 months. RESULTS: Obliteration of the CNVM was seen in all patients during the last visit. Visual acuity improved in one eye and remained stable (+/-2 line change on Snellen chart) in three eyes. Three eyes revealed a moderate visual loss of 3 to 4 lines and two eyes had a severe decline (> 5 lines) in vision. None of the eyes exhibited recurrence of the CNVM during follow-up. CONCLUSIONS: Indocyanine green dye-enhanced transpupillary thermotherapy was highly effective in closing classic CNVM in all cases without any recurrence. Visual acuity was either stabilized or improved in 4 of 9 eyes (44.5%).     

Optical coherence tomography of subfoveal choroidal neovascularization treated with transpupillary thermotherapy

Transpupillary thermotherapy (TTT) has been proposed as a new treatment modality for choroidal neovascularization (CNV). Most studies conducted show decreased exudation due to CNV and reduction of subretinal elevation. Optical coherence tomography (OCT) shows a dynamic sequence of changes early after treatment. Within 1 hour after TTT, OCT shows increased retinal thickness and intraretinal fluid with retinal elevation. One week after treatment, OCT shows decreased subretinal and intraretinal fluid and diminished retinal elevation. OCT can be a valuable method to assess the early effect of TTT. A placebo-controlled, multi-center trial (TTT4CNV) evaluating the long-term efficacy and visual implications of TTT in occult CNV is underway.     

Optical coherence tomography of subfoveal choroidal neovascularization treated with transpupillary thermotherapy

Transpupillary thermotherapy (TTT) has been proposed as a new treatment modality for choroidal neovascularization (CNV). Most studies conducted show decreased exudation due to CNV and reduction of subretinal elevation. Optical coherence tomography (OCT) shows a dynamic sequence of changes early after treatment. Within 1 hour after TTT, OCT shows increased retinal thickness and intraretinal fluid with retinal elevation. One week after treatment, OCT shows decreased subretinal and intraretinal fluid and diminished retinal elevation. OCT can be a valuable method to assess the early effect of TTT. A placebo-controlled, multi-center trial (TTT4CNV) evaluating the long-term efficacy and visual implications of TTT in occult CNV is underway.     

阈下能量经瞳孔热疗对正常大鼠视网膜的影响

目的 研究正常棕色挪威大鼠(BN大鼠)视网膜在810 nm激光阈下能量经瞳孔热疗(TTT)后的改变。方法 雄性BN大鼠36只，使用810 nm激光，采用不同阈下能量对BN大鼠进行TTT。分别于TTT后第1、3、7、14 d进行彩色眼底照相和眼底荧光造影(FFA)。TTT后6、12h，1、3、7、14d各处死6只大鼠，进行组织病理学观察。6、12h和1 d的组织用TdT介导dUTP缺口末端标记法(TUNEL)检查细胞凋亡。结果 TTT后第1 d可见大部分光斑处视网膜灰白色水肿。第3 d视网膜水肿减轻，RPE脱色素。其后视网膜逐渐出现色素沉着。FFA中可见到不同程度的高荧光。组织病理学切片上可见所有在眼底照相上曾出现灰白水肿的病灶，视网膜结构均有显著破坏。TUNEL染色可见视网膜全层均有细胞凋亡。TTT能量最低组6 h时凋亡细胞最多；激光斑旁视网膜较激光斑中央视网膜凋亡细胞多。结论 TTT阈下能量可引起不可逆的视网膜损伤，即使无病理改变也能引起视网膜细胞的凋亡。