Subthreshold Transpupillary Thermotherapy Research Articles

SUBTHRESHOLD TRANSPUPILLARY THERMOTHERAPY IN MANAGEMENT OF FOVEAL SUBRETINAL FLUID IN SMALL PIGMENTED CHOROIDAL LESIONS

To evaluate the effect of subthreshold transpupillary thermotherapy (sTTT) in foveal subretinal fluid of small pigmented choroidal lesions. Retrospective, noncomparative, interventional case series. We reviewed patients with small pigmented choroidal lesions presenting foveal subretinal fluid and treated with sTTT to evaluate fluid regression. We treated 13 patients with small pigmented choroidal lesions with a mean height of 2.02 ± 0.54 mm (range, 1.4-2.9 mm) and a mean largest diameter of 7.60 ± 1.98 mm (range, 5-11 mm). In 11 cases, foveal subretinal fluid was completely resolved (84.6%), with a mean follow-up of 42.46 ± 26.29 months (range, 12-103 months). The mean number of sTTT sessions applied was 1.38 ± 0.77 (range, 1-3 sessions), at a mean spot size of 1,570.59 ± 795.1 μm (range, 500-3,000 μm), and overall exposure time of 2.32 ± 1.2 minutes (range, 1-6 minutes). Mean laser power applied was 370.63 ± 162.87 mW (range, 200 to 600 mW). Best-corrected visual acuity at the time of diagnosis was maintained or improved in 69.3% of patients after sTTT treatment. During follow-up, tumor progression was reported in 5 cases, regardless of the presence of subretinal fluid. These cases were treated promptly with brachytherapy. However, sTTT may be effective in solving foveal subretinal fluid in small pigmented choroidal lesions, attaining satisfactory visual acuity in most cases.

Graded Subthreshold Transpupillary Thermotherapy for Chronic Central Serous Chorioretinopathy

To study the safety and efficacy of "graded" subthreshold transpupillary thermotherapy (TTT), a novel treatment protocol for chronic central serous chorioretinopathy (CSC) and an alternative to photodynamic therapy (PDT). This retrospective pilot study included 10 eyes with chronic CSC that underwent TTT with 810-nm continuous diode laser treatment using a subthreshold power (60% reduced from threshold) for 60 seconds. Treatment was repeated at 20% increase in power from the baseline if submacular fluid persisted on optical coherence tomography (OCT) after 1 month (graded fashion). The mean chronic CSC duration was 20.3 ± 8.3 months. Eight eyes (80%) showed resolution of CSC on OCT. Mean number of TTT sittings required was 1.5. Although 5 eyes (50%) had 3 or more lines of improvement in Snellen visual acuity, 3 eyes (30%) had up to 2 lines of improvement. None of the patients developed macular burn or scar. The safety enhanced graded subthreshold TTT was beneficial in patients with chronic CSC.

Large-spot subthreshold transpupillary thermotherapy for chronic serous macular detachment

Purpose:To report the effect of subthreshold transpupillary thermotherapy (TTT) in treating serous detachment of the neurosensory retina secondary to chronic central serous chorioretinopathy (CCSC).Methods:Seven eyes from five patients with CCSC, persistent serous detachment of the neurosensory retina and a clinical course of between 12 and 60 months were treated. All eyes received large-spot TTT guided by indocyanine green angiography (ICGA). Subthreshold TTT was performed using an 810 nm diode laser with a spot size of 3.0 mm (power was set at 350 mW). Treatment was applied for 60 seconds to the areas of choroidal hyperfluorescence on ICGA.Results:The mean number of TTT sessions was 1.4 ± 0.5. All eyes were followed up for at least 6 months (mean 9.6 ± 3.2 standard deviation; range 6–12 months). The mean logarithm of the minimum angle of resolution best-corrected visual acuity was significantly better compared with baseline. All TTT-treated eyes had stable or improved vision (P < 0.001). Mean optical coherence tomography (OCT) central foveal thickness was significantly lower in all patients (P < 0.001) compared with pretreatment OCT, with a reduction in subretinal fluid and resolution of serous detachment associated with anatomical fovea restoration. No patient had any treatment-related side effects.Conclusion:Modified subthreshold TTT appears to have a beneficial effect in treating patients with CCSC and persistent neurosensory detachment. The encouraging results and lack of visually significant complications suggest that further investigation is warranted.

Neuroprotective effect on retinal ganglion cells by transpupillary laser irradiation of the optic nerve head

This study demonstrates that subthreshold transpupillary thermotherapy (TTT) laser irradiation on optic nerve head protects retinal ganglion cells (RGCs) in an optic nerve crush (ONC) model. TTT was performed in right eyes with an 810-nm diode laser aimed at the center of the optic nerve head, using the following protocol: power 60 mW, duration 60 s, spot size 500 μm. Fluoro-Gold was injected into bilateral superior colliculi 5 days before sacrifice and fluorescent gold labeled RGCs were counted under fluorescence microscopy. In the ONC group, a progressive loss of RGCs was observed; however, in comparison with the ONC group, RGCs density was significantly higher ( P = 0.001, independent samples t-test) at day 7 postoperative and only borderline significances were obtained at days 14 and 28 postoperative ( P = 0.044 and P = 0.045, respectively, independent samples t-test) in ONC + TTT group, which implies the potential neuroprotective role of TTT. This protective effect seems to be heat shock proteins (HSPs) related, because intraperitoneal Quercetin (an inhibitor of HSPs, 4 mg/kg/day for 7 days) could completely abolish this protective effect at days 7, 14 and 28 postoperative ( P = 0.012, P = 0.002, and P = 0.000, respectively, independent samples t-test). Minimal collateral damage of TTT on optic nerve head tissue, peripapillary RGCs and the myelin sheath of the optic nerve were observed under transmission electron microscopy. These findings suggested that subthreshold TTT might be a safe and practical approach to protect RGCs. The underlying mechanisms may involve TTT-induced HSPs in RGCs.

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

To perform a safety and efficacy study of subthreshold transpupillary thermotherapy (TTT) in Chinese patients with choroidal neovascularization (CNV) secondary to pathologic myopia. In a prospective study, patients with subfoveal or juxtafoveal CNV secondary to high myopia underwent subthreholdTTT 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. 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 subthresholdTTT included laserrelated 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). 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.

SUBTHRESHOLD TRANSPUPILLARY THERMOTHERAPY FOR EARLY RESOLUTION OF FOVEAL SUBRETINAL FLUID IN CHOROIDAL METASTASIS

To report the effectiveness of subthreshold transpupillary thermotherapy (TTT) in the early resolution of subretinal fluid at the fovea in solitary choroidal metastasis. : 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. 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. 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.

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

To study the effect of subthreshold transpupillary thermotherapy (TTT) on the retina and experimental choroidal neovascularization (CNV) in the rat. 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. 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. 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 Alone and Enhanced by Standard Doses of Indocyanine Green in Pigmented Rabbits

To evaluate the chorioretinal effects of transpupillary thermotherapy (TTT) and TTT enhanced by standard doses of indocyanine green (ICG) in pigmented rabbits. In 25 eyes, two retinal areas were irradiated using identical subthreshold diode laser irradiation. The subthreshold diode laser irradiation level was first determined using the other eye. ICG (0.5 mg/kg) was injected before irradiation of the second area. Red-free photographs, fluorescein angiography, and ICG videoangiography were performed after TTT. Specimens were prepared for light microscopy. In 35% of the cases, ICG videoangiography revealed a hypofluorescent spot in the area irradiated after injection of ICG that disappeared after ICG re-injection. None of the areas irradiated before ICG injection were hypofluorescent. Red-free photographs and fluorescein angiography were normal in most cases. Light microscopy demonstrated patent choriocapillaris and choroid in most areas. Subthreshold TTT, whether enhanced by ICG or not, did not cause significant choroidal or choriocapillaris vascular occlusion. Standard doses of ICG had no significant effect on TTT.

Comparison of photodynamic therapy and transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration

Background: The purpose of this study was to compare photodynamic therapy (PDT) against subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Methods: Patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If they declined PDT, then TTT was offered. Results: We evaluated and followed 115 consecutive patients for an average of 1 year. The primary outcome measure was visual acuity, but the interventions were also compared on the basis of lesion size and angiographically determined lesion activity. Baseline comparisons between the 2 treatment groups showed significant differences in pretreatment visual acuity, lesion size, and lesion composition. Univariate analysis of outcomes demonstrated equivalence between the treatment groups in final lesion size,angiographic activity,and visual acuity. Multivariate analysis also demonstrated equivalence between the treatment groups in final visual acuity while controlling for age, pretreatment visual acuity, and lesion category. Predominantly classic lesions were associated with poorer visual outcomes. Interpretation: The PDT and TTT groups were equivalent in terms of all outcome parameters evaluated.

Socioeconomic status and clinical features of patients undergoing photodynamic therapy or transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration

Background: The purpose of this study was to compare baseline clinical and socioeconomic features of patients undergoing self-funded photodynamic therapy (PDT) or government-funded subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Methods: Between July 2000 and August 2001, 115 patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If individuals believed that they could not afford or did not want PDT, then TTT was offered. In masked fashion, leakage pattern and lesion size were determined retrospectively from pretreatment angiograms. Baseline visual acuity was determined with autorefraction and subsequent Snellen testing.The mean income of each treatment group was estimated from the average sex-specific income for each subject's postal code, based on the 1996 Canadian census data.The average education level for each subject's postal code was also determined. Results: The patients who were not willing to pay for PDT had significantly worse macular disease before treatment (larger lesions and poorer visual acuity) and a significantly lower mean income than the patients who were willing to pay for PDT. Interpretation: The severity of exudative choroidal neovascularization appears to be associated with lower socioeconomic status.

Histological Effect and Protein Expression in Subthreshold Transpupillary Thermotherapy in Rabbit Eyes—Correction

Histological Effect and Protein Expression in Subthreshold Transpupillary Thermotherapy in Rabbit Eyes—Correction

Histological effect and protein expression in subthreshold transpupillary thermotherapy in rabbit eyes.

To investigate the histological effect of subthreshold transpupillary thermotherapy (TTT) on the retina. We performed TTT in normal pigmented rabbit eyes using an 810-nm diode laser with spot size of 1.2 mm, power of 50 mW, and varying durations of 15, 30, or 60 seconds. Four weeks later, fluorescein angiography was performed, and the enucleated eyes were examined by means of electron microscopy and immunohistochemical staining. Funduscopy immediately and at 4 weeks showed no discernable changes at TTT sites, and fluorescein angiography at 4 weeks showed no abnormalities. However, electron microscopy showed photoreceptor and retinal pigment epithelium cell disruption, changes more prominent with longer durations of treatment. Immunohistochemical staining was positive for heat shock protein 60, heat shock protein 70, tumor necrosis factor alpha, and vascular cell adhesion molecule 1 in the photoreceptors and retinal pigment epithelium at TTT sites. Untreated control eyes showed no staining. Despite the absence of changes evident by funduscopy and fluorescein angiography, TTT resulted in dose-dependent histological changes in photoreceptors and retinal pigment epithelium. The induction of heat shock proteins, cytokines, and cell adhesion molecules may play a role in the tissue response to subthreshold TTT. Clinical Relevance Unrecognized damage to the retina and retinal pigment epithelium may contribute to visual loss in eyes that undergo subthreshold TTT.

Subthreshold Transpupillary Thermotherapy Reduces Experimental Choroidal Neovascularization in the Mouse without Collateral Damage to the Neural Retina

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. 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. 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. 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.

家兎眼における閾値下経瞳孔温熱療法による組織学的影響と蛋白発現(博士(医学),杏林大学学位論文要旨および審査要旨)

家兎眼における閾値下経瞳孔温熱療法による組織学的影響と蛋白発現(博士(医学),杏林大学学位論文要旨および審査要旨)