Understanding the structural changes following photodynamic and transpupillary thermotherapy for choroidal hemangioma using optical coherence tomography and optical coherence tomography angiography

Purpose: To study optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) features of circumscribed choroidal hemangioma (CCH) following treatment with photodynamic therapy (PDT) and transpupillary thermotherapy (TTT). Methods: A retrospective chart review of consecutive patients treated for CCH over 2 years (May 2016�April 2018). The investigations, in addition to comprehensive eye examination, included color fundus photography, B-scan ultrasonography, OCT, and OCT-A. Results: The study included 16 eyes of 16 patients (9 males and 7 females). The mean age at presentation was 43.5 � 9 years (range 33�62 years). Macula (n = 6) and superior arcade (n = 5) were the common tumor locations. Twelve eyes received multiple treatment sessions: TTT (seven eyes; mean 2.4 sessions) and PDT (five eyes; mean 2 sessions). Four eyes were observed because vision was not threatened. Pretreatment OCT features were Bruch's membrane atrophy (15 eyes), retinal pigment epithelial atrophy (13 eyes), outer retinal abnormalities (12 eyes), and macular subretinal fluid (12 eyes). Pretreatment OCT-A features were complete loss of choriocapillaris (16 eyes), irregularly arranged fine arborizing vessels (11 eyes), and more than 50% signal void hyporeflective areas (12 eyes). Posttreatment OCT-A showed persistence of choriocapillaris loss, flat scar with fibrosis and thinning of choroid in all eyes treated with TTT, and persistence of deeper choroidal vessels and no loss of choriocapillaris in eyes treated with PDT. Conclusion: OCT and OCT-A help understand the structural outcome following PDT and TTT in circumscribed choroidal hemangioma.

Circumscribed choroidal hemangioma: An overview of clinical manifestation, diagnosis and management

Circumscribed choroidal hemangioma is a benign vascular tumor which presents in middle-aged adults with progressive diminution of vision, metamorphopsia, floaters, and visual field defects. Diagnosis is based on the characteristic clinical features. It is an orange-red, usually solitary, tumor situated in the posterior pole. The visual symptoms are because of the associated subretinal fluid, cystoid macular edema, and, in long-standing cases, retinal pigment epithelium changes, subretinal fibrosis and retinoschisis. It must be distinguished from the more ominous amelanotic melanoma and choroidal metastasis. Diagnostic tools such as ultrasound, fundus fluorescein angiography, indocyanine green angiography, and optical coherence tomography are helpful in cases with diagnostic dilemma. Treatment is indicated in symptomatic cases. The management of choroidal hemangioma has evolved over the years beginning with laser photocoagulation to transpupillary thermotherapy, photodynamic therapy, plaque brachytherapy and external beam radiotherapy. No one therapeutic option holds superiority over the other. In this article, we review the epidemiology, clinical manifestations and treatment of the circumscribed variant of choroidal hemangioma.

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.

Papillary Thyroid Carcinoma: Bilateral Choroidal Metastases with Extrascleral Extension

Here, we present the case of a patient with bilateral choroidal metastases with extraocular extension in one eye. Metastasis of papillary thyroid carcinoma to the uvea is extremely rare, with only 6 patients reported in the literature. A 62-year-old man with a prior history of papillary thyroid carcinoma suffered the rapid loss of vision in his right eye. He had neovascular glaucoma, total retinal detachment, and a solitary choroidal mass. A month later, his left visual acuity also decreased because of a small macular choroidal mass. The right eye was enucleated and a nodular lesion over the sclera representing extraocular extension was observed. This tumor and the intraocular lesion were composed of papillary excrescences and cystic spaces and stained positively for thyroid transcription factor 1 and thyroglobulin, all confirming the diagnosis of metastatic papillary thyroid carcinoma. The tumor in the left eye was successfully treated with diode laser transpupillary thermotherapy. The patient expired within a month as a result of widespread pulmonary metastases. Papillary thyroid carcinoma may metastasize to the uvea bilaterally, cause rapid visual function loss, erode the sclera, and may extend outside the globe similar to choroidal melanoma. This aggressive ocular involvement was associated with a dismal prognosis in our patient.

Intravitreal bevacizumab (avastin) for circumscribed choroidal hemangioma.

Circumscribed choroidal hemangiomas are rare ophthalmic entities that cause diminution in vision due to accumulation of subretinal and/or intraretinal fluid in the macular area. Various treatment options ranging from conventional laser to photodynamic therapy have been employed to destroy the tumor and reduce the exudation; however, either the inability to penetrate through the exudative fluid or the collateral retinal damage induced by these treatment modalities make them unsuitable for lesions within the macula. We evaluated the role of intravitreal bevacizumab, a pan-vascular endothelial growth factor (VEGF) inhibitor, in reducing the sub- and intraretinal fluid in three patients with circumscribed choroidal hemangiomas. All the patients had complete resolution of the serous retinal detachment that was maintained till at least 12 months after the first injection. Intravitreal bevacizumab may be used in combination with thermal laser or photodynamic therapy in treating circumscribed choroidal hemangiomas with subretinal fluid.

Large spot transpupillary thermotherapy: A quicker laser for treatment of high risk prethreshold retinopathy of prematurity - A randomized study.

To compare structural and functional outcome and time efficiency between standard spot sized conventional pulsed mode diode laser and continuous mode large spot transpupillary thermotherapy (LS TTT) for treatment of high risk prethreshold retinopathy of prematurity (ROP). Ten eyes of five preterm babies having bilateral symmetrical high risk prethreshold ROP were included in this study. One eye of each baby was randomized to get either standard spot sized conventional pulsed mode diode laser or continuous mode LS TTT. There was no significant difference between structural or functional outcome in either group. The mean time taken for conventional diode laser was 20.07 minutes, while that for LS TTT was 12.3 minutes. LS TTT was 40% more time efficient than the conventional laser. It may be better suited for the very small fragile premature infants as it is quicker than the conventional laser.

Treatment review of sight threatening circumscribed choroidal haemangioma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To describe our clinical experience in treating circumscribed choroidal haemangioma(CCH)in a tertiary referral centre over a fifteen year period prior to photodynamic therapy.METHODS:The departmental database and photographic records of a tertiary referral center were used to identify patients who were treated for CCH between 1992 and 2007.Their case records were reviewed.RESULTS:Visual acuity improved(＞2 Snellen lines)in eleven patients(69%)remained stable in one patient (6%)and deteriorated in four patients(25%).Six of the seven treated with brachytherapy and three of the four treated with transpupillary thermotherapy achieved better visual acuity after treatment.86% of patients treated within six months of onset of symptoms and 50% of patients treated after six months of onset of symptoms noted an improvement in visual acuity.Only one patient in our series had a final VA of 6/60 or worse.Mean follow-up was thirty-five months.CONCLUSION:Visual outcome is better when treatment is performed within 6 months of symptoms.The majority of patients achieved an improvement in visual acuity without any adverse effect following treatment.

Histopathological Changes by Low-Power-Long-Duration and High-Power-Short-Duration Subthreshold Laser Treatment in the Rabbit Retina

PURPOSE: To compare histopathological and apoptotic changes of ophthalmoscopically similar subthreshold laser burns made by a low power-long duration (LD) and a high power-short duration (SD) subthreshold laser treatment. METHODS: Ophthalmoscopically invisible subthreshold laser burns with a 3.0 mm spot size were made using an 810 nm diode laser on the rabbit retina. Lasers were applied for 60 seconds in the LD group, and 1 second in the SD group. Laser power was adjusted to achieve ophthalmoscopically invisible burns just below the threshold. The rabbits were sacrificed at 6, 12, 24, and 72 hours, 1, 2, and 4 weeks after laser treatment. The eyes were processed for light microscopic examination using hematoxylin and eosin (H&E), toluidine blue, and TdT-dUTP terminal nick-end labeling (TUNEL) staining. Eyes were also processed for electron microscopic examination. RESULTS: The changes in the retina were different between the two groups. The LD group showed abundant TUNEL positive cells in all the retinal layers at 6 hours after laser treatment, and distinct histological changes in the outer nuclear layer. Conversely, in the SD group, apoptosis did not occur and histological alteration in the outer nuclear layer was minimal. CONCLUSIONS: Subthreshold laser treatment for 1 second reduced damage of the inner retinal layer and did not result in apoptosis in the neurosensory retina while maintaining a similar effect on the RPE and its adjacent region.

Long-term efficacy of transpupillary thermotherapy for subfoveal choroidal neovascularization in age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To determine the long-term efficacy of transpupillary thermotherapy (TI-F) in the treatment of subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD).METHODS: Fourteen eyes of 14 patients with subfoveal CNV secondary to AMD were treated with diode laser (810nm) TTT. The mean age was 67.1 years. Complete ophthalmic examination was done, color fundus photographs and macular optical coherence tomography scans were taken, fluorescein and indocyanine green angiography were performed during initial and at subsequent follow-up examinations. Treatment was given in one minute using 2-3ram spot sizes, and laser power settings were between 650-800mW. The follow-up period was between 5 and 64 months and the mean was 28.6 months.RESULTS: There was subfoveal classic CNV in 10, predominantly classic CNV in 2, minimally classic CNV in 1, and type 1 occult CNV in one of the fourteen eyes. Four patients were noted to have post-treatment hemorrhage which was absorbed in a short time. Macular non-perfusion occurred in one patient immediately after treatment. Most of the eyes demonstrated a decrease in exudation during the follow-up. With a mean follow-up of 28.6 months, visual acuity improved in 5, remained the same in 8 and decreased in 1 of the 14 eyes.CONCLUSION: Transpupillary thermotherapy is shown to close subfoveal CNV with rapid resolution of subretinal fluid while maintaining visual function in patients with AMD. It may be performed as an alternative laser treatment in classic and predominantly classic subfoveal choroidal neovascularization due to AMD.

Combination of Chemotherapy and Transpupillary Thermotherapy for Retinoblastoma

PURPOSE: To evaluate the results of transpupillary thermotherapy combined with chemotherapy for the treatment of retinoblastoma. METHODS: Retinoblastoma patients treated with chemotherapy and transpupillary thermotherapy from November, 2004 to October, 2007 were retrospectively reviewed. Local tumor control was assessed in terms of regression or recurrence, at 1 month after chemotherapy and each session of thermotherapy, as well as the final follow-up period. RESULT: Fifty-nine tumors were treated in 15 eyes of 11 children. Age at diagnosis was 7.4+/-6.9 months. Mean tumor diameter at the time of diagnosis was 2.2+/-2.1 disc diameters (DD) and mean tumor diameter at the time of initial thermotherapy was 1.8+/-1.7DD. Mean number of thermotherapy sessions for each tumor was 1.3+/-0.5. Total tumor regression was obtained for 96.6% of tumors after a mean follow-up of 22.3+/-10.7 months. The initial tumor size before thermotherapy was significantly smaller in the group of tumors showing total regression after the first session of thermotherapy. The time required for total regression after initial thermotherapy was related to the initial tumor size before thermotherapy. CONCLUSIONS: Transpupillary thermotherapy combined with chemotherapy is an effective modality for treating retinoblastoma, and the initial tumor diameter before treatment is a strong predictive factor of successful treatment response.

Results Following Transpupillary Thermotherapy for Choroidal Neovascularization

PURPOSE: To determine whether transpupillary thermotherapy can achieve significant efficacy in maintaining vision without significant adverse effects when used to treat age-related macular degeneration associated with choroidal neovascularization. METHODS: Retrospective chart reviews were made for 33 eyes of 32 patients diagnosed with age-related macular degeneration, and who had received transpupillary thermotherapy due to the development of choroidal neovascularization. Transpupillary thermotherapy was performed 1.4 times on average. RESULTS: Three months after the final therapy, 6 eyes (18%) showed improved vision, 11 eyes (34%) showed no change in vision, and 16 eyes (48%) showed worsening of vision. Of the 21 eyes of 21 patients who were available for optical coherence tomography before and after transpupillary thermotherapy, 19 eyes (90.5%) showed reduced macula thickness, and fundus photographs taken during the latest hospital visit revealed 11 eyes showing fibrosis. CONCLUSIONS: Although it negatively influences subretinal fluid absorption, transpupillary thermotherapy is effective in stabilizing choroidal neovascularization and improving visual accuracy in a short period of time. Thus, further study is warranted.

The Retinal Temperature Rise during Transpupillary Thermotherapy in Albino and Pigmented Rabbits

PURPOSE: we clinically measured the temperature rise in real time and analyzed the difference of albino rabbit and pigmented rabbit in use of the specially designed thermometer. METHODS: Specially designed thermometer was attached into the subretinal pigment epithealial and choroidal space through the suprachoroidal space in three pigment and three albino rabbits, with diode laser of 810 nm wave length, 3 mm spot size. We examined the retinal temperature according to laser irradiance power at each ten seconds during sixty seconds and the laser power setting was 200 mW, 300 mW, 400 mW in pigmeted rabbit and 300 mW, 600 mW, 800 mW in albino rabbit. We analyzed the results based on the measurements at least three times per each irradiance power. RESULTS: In albino rabbit, the maximal range of retinal temperature change was 1.2 degrees C and 1.7 degrees C in 300 mW and 600 mW, 14.1 degrees C in 800 mW power of 810 nm diode laser irradiance. In pigmented rabbit, the maximal range of retinal temperature change was 12.1 degrees C in 200 mW of laser irradiance power, 16.2 degrees C in 300 mW, 24.3 degrees C in 400 mW during sixty seconds in 810 nm diode laser. CONCLUSIONS: We investigated the ratinal temperature at transpupillary thermotherapy in 810 nm wavelength diode laser on rabbits. The difference of retinal temperature change was in accordance with the amount of chorioretinal melanin pigment. Therefore if the laser power setting used in caucasians would be attempted in orientals, it is the point to be considered during transpupillary thermotherapy.

Five Cases of Transpupillary Thermotherapy for Intraocular Tumors

PURPOSE: To evaluate the effects of transpupillary thermotherapy(TTT) for several intraocular tumor. METHODS: The 5 intraocular tumors (2 capillary hemangioma, 1 metastatic tumor, 1 retinal angioma, 1 melanocytoma) were treated with transpupillary thermotherapy. We compared preoperative visual acuity, size, fundus finding, ultrasonogram to postoperative data. RESULTS: The one capillary hemangioma and metastatic tumor were improved in fundus finding. The other tumors were not improved. The visual acuity of patient with metastatic tumor was improved from F.C/30cm to 0.15. CONCLUSIONS: Transpupillary thermotherapy was effective tool for intraocular tumors. We may need the guideline for treatment of intraocular tumor by using transpupillary thermotherapy.

Transpupillary Thermotherapy in Circumscribed Choroidal Hemangioma

PURPOSE: We described a patient with decreased vision due to circumscribed choroidal hemangioma and the patient was treated with transpupillary thermotherapy. METHODS: A 40-year-old male with circumscribed choroidal hemangioma combined with serous retinal detachment involving macula was managed by 2 sessions of transpupillary thermotherapy with 810 mm infrared diode laser. RESULTS: Improvement of central visual acuity, atrophy of circumscribed choroidal hemangioma and reabsorption of serous retinal detachment were observed without any complication during 6 months follow up period after 2 sessions of transpupillary thermotherapy. CONCLUSIONS: Transpupillary thermotherapy is a safer and alternatively effective treatment in circumscribed choroidal hemangioma with serous retinal detachment rather than ordinary photocoagulation or radiotherapy.

Comparision of the Effects of Transpupillary Thermotherapy(TTT) of Pigmented and Albino Rabbit Retina

PURPOSE: We compared the clinicopathologic effects of TTT between pigmented and albino rabbits. METHODS: TTT was delivered using infrared diode laser at 810 nm(Iris Medical Instrument, Mountain Veiw, CA, USA) and applied with spot size of 3 mm, duration of 60 seconds. At 1 week and 4 weeks after TTT, fundus photographs and simultaneous FAG/ICG angiogram were taken with SLO(Scanning Laser Ophthalmolscopy, Rodenstock, Munish, Germany). Light and electron microscopic examination were performed. RESULTS: In pigmented rabbits, visible funduscopic change was visible even with minimal power setting(100 mW). Obliteration of choroidal vessels was observed on ICG angiogram. In microscopic examination, entire layers of neural retina, retinal pigment epithelial cells, and deep choroid were severely damaged at the center of treated fields. Whereas, in albino rabbits fundus changes were not observed at any power setting. However, focal thrombosis at margin of lesion was identified on ICG angiogram after power of 300 mW. In microscopic examination, tissue damage was developed up to 600 mW and the lesion extended into the superficial choroid posteriorly and outer neural retina anterioly. CONCLUSIONS: The effect of TTT was increased with fundus pigmentation. Clinically we should adjust TTT power setting according to the amount of melanin pigmentation in the fundus.

Factors Affecting on Determination of Laser Power in Transpupillary Thermotherapy

PURPOSE: To evaluate whether the degree of melanin pigmentation of fundus or intraocular pressure would have influence on the determination of laser power for effective transpupillary thermotherapy(TTT). METHODS: TTT was performed on 6 eyes of each of the brown, yellow and white rabbits. Immediately after diode laser irradiation to posterior pole, retinal periphery, and iris with various power(2 mm, 60 or 120 sec), macular threshold power(MTP), peripheral threshold power(PTP), and iris threshold power(ITP) were defined as a maximum power not causing any ophthalmoscopic change on the respective laser site. To assess the influence of intraocular pressure, TTT was performed with the eyeballs compressed as much as retinal arterial pulsation disppeared. Three weeks after laser irradiation, funduscopic and fluorescein angiographic appearance were correlated with histopathologic findings. RESULTS: We found no difference of MTP between brown and yellow rabbit but their MTP were smaller than that of white one(P<0.05). There was positive correlation between MTP, PTP and ITP in all experimental species. ITP/MTP and PTP/MTP were 3.45+/-0.68, 1.09+/-0.10 in brown rabbit, 3.84+/-0.79, 1.12+/-0.13 in yellow rabbit and 4.13+/-0.43, 1.16+/-0.14 in white rabbit respectively. When TTT was performed with the eyeball compressed, the laser spot looks whiter in all cases than without. Microscopic examination revealed occlusion of choriocapillaris and photoreceptor degeneration in the laser spots formed by MTP. CONCLUSION: When performing TTT, one should reduce the laser power according to the amount of melanin pigmentation of fundus and intraocular pressure. Empirical laser burn to the retinal periphery will be a helpful mean to determine optimal laser power for TTT.