Comparison of the therapeutic effects of photodynamic therapy, transpupillary thermotherapy, and their combination on circumscribed choroidal haemangioma.

OBJECTIVE: To characterize the clinical and imaging features of circumscribed choroidal hemangioma (CCH), and to evaluate individualized treatment efficiency of photodynamic therapy (PDT), transpupillary thermotherapy (TTT), or their combination, followed by retrobulbar injection of betamethasone on CCH resolvement. METHODS: Forty-nine patients with CCHs who underwent PDT, TTT or PDT+TTT treatments were retrospectively analyzed. Their treatment efficacy was compared by analyzing the change of best corrected visual acuity (BCVA), subretinal fluid (SRF) and CCH lesion characteristics. RESULTS: PDT, TTT and PDT+TTT were respectively administrated in 17, 11 and 21 patients. No significant difference in age, gender, affected eyes and tumor location across the three groups. Baseline BCVA were 0.41 ± 0.28, 0.62 ± 0.30 and 0.24 ± 0.24 for PDT, TTT and PDT+TTT groups, respectively (F = 6.572, P = 0.003). CCH treated by three strategies showed significant difference in maximum tumor basal diameter, SRF areas and macula involvement prior to the treatment (P < 0.05). Patients receiving PDT+TTT exhibited larger tumor basal diameter, more SRF, higher ratio of macular involvement than other groups. A total of 38 (77.6 %) cases had good visual acidity with final BCVA ≥0.5 after treatments. PDT and PDT+TTT treatment groups acquired more vision improvement (0.27 ± 0.23 and 0.31 ± 0.26) in BCVA than TTT group (0.09 ± 0.13). All SRF were resolved within two weeks of treatment and no recurrent SRF were found. CONCLUSION: The three treatments showed good performance in improving visual function and controlling SRF, and individualized treatment should be selected primarily by the tumor location, and then the tumor size and presence of SRF.

Recent Advances in Photodynamic Therapy for Vascular Abnormalities.

Background: Photodynamic therapy (PDT) is a minimally invasive therapy that was gradually established as a first-line treatment for vascular abnormalities. Its action depends on the appropriate wavelength of light and photosensitizer to produce toxic oxygen species and cause cell death. Objective: Several new clinical improvements and trends in PDT have been described in recent years. The aim of this review is to provide an overview of the current data from clinical trials. Methods: In this review, we introduce and generalize the wavelength, duration, dose, strength, and photosensitizer of PDT for the treatment of vascular abnormalities, such as circumscribed choroidal hemangiomas (CCH), choroidal neovascularization (CNV) and capillary malformation (CM). Results: The systematic review findings indicate that the application of PDT is a safe effective method to treat CCH, CNV and CM. However, PDT also has early onset side effects and late onset side effects. Conclusions: Based on the discussion of the effectiveness of PDT, we conclude that PDT has great potential for clinical use, although PDT has possible side effects.

Oral Sirolimus for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome.

This case report describes an 8-year-old girl who received oral sirolimus as an adjuvant therapy for pulse dye laser of her port-wine stain and as an off-label treatment of exudative retinal detachment secondary to diffuse choroidal hemangioma.

Bilateral choroidal osteoma: long-term follow-up of secondary choroidal neovascularization in a child using antiangiogenic therapy.

Choroidal osteoma is a rare condition, and its treatment is not well established, especially in the pediatric population, where use of antiangiogenics for choroidal neovascularization is poorly studied. Few studies have reported the long-term follow-up of pediatric patients with bilateral choroidal osteomas. We report the case of a girl who was diagnosed at the age of 3, with the appearance of bilateral secondary choroidal neovascularization, and has been under strict observation for 12 years. The effectiveness of antiangiogenic agents as a long-term therapeutic option for secondary choroidal neovascularization in pediatric patients with symptomatic choroidal osteomas is discussed.

PHOTODYNAMIC THERAPY-INDUCED ACUTE EXUDATIVE MACULOPATHY IN A CASE SERIES OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: To describe the incidence, features, and clinical outcomes of photodynamic therapy-induced acute exudative maculopathy (PAEM) in circumscribed choroidal hemangioma. METHODS: Prospective series of 10 patients who underwent standard-fluence photodynamic therapy for circumscribed choroidal hemangioma. Best-corrected visual acuity in the Early Treatment Diabetic Retinopathy Score and swept-source optical coherence tomography were performed before PDT and 3 days and 1 month after PDT. Central retinal thickness, circumscribed choroidal hemangioma retinal thickness, and subretinal fluid were measured. Photodynamic therapy-induced acute exudative maculopathy was considered as an increase ≥50 µ m in subretinal fluid or intraretinal fluid or the appearance of fibrin 3 days after photodynamic therapy. RESULTS: Six men and four women were included; median age was 55 years (19-69 years). The incidence rate of PAEM was 7 of 10. Five PAEM patients showed an increase in intraretinal fluid, two in subretinal fluid, and one developed abundant fibrin. Median best-corrected visual acuity at baseline was 57.5 letters (5-76 letters) being stable at 1 month (64 letters; 5-80) ( P = 0.03). Median central retinal thickness increased from 516 µ m (262-1,265 µ m) to 664.5 µ m after 3 days and diminished to 245 µ m after 1 month (156-1,363) ( P ≤ 0.022). In 6 of 7 of PAEM, a complete resolution of the fluid was obtained. CONCLUSION: Photodynamic therapy-induced acute exudative maculopathy was frequent in circumscribed choroidal hemangioma, although a favorable prognosis was observed in most cases.

Long term results of photodynamic therapy in intraocular tumors.

PURPOSE: To report long term results of photodynamic therapy (PDT) as treatment for intraocular tumors METHODS: Retrospective interventional case series of 15 patients. All patients treated with standard-fluence PDT (83 s; 50 J/cm2) using verteporfin. OUTCOME MEASURES: Tumor diameter, tumor thickness, subretinal fluid resolution, best-corrected visual acuity,intraocular pressure and PDT complications. RESULTS: 10 patients (66.7% of total patients) were diagnosed with choroidal hemangioma, 3 patients (20% of total patients) were diagnosed with choroidal melanoma, and 2 patients (13,3% of total patients) were diagnosed with choroidal osteoma.. Mean follow-up time was 33±18 months. The mean visual acuity was determined as 1.29 ± 0.98 logMAR in the examinations just before the PDT application. At the end of the follow-up period, the mean visual acuity was calculated as 1.41 ± 1.07 logMAR. While VA increased in 3 (20%) patients and decreased in 5 (33.3%) patients; It was determined that VA value did not change after treatment in 7 (46.7%) patients. The mean lesion diameter before PDT was 6573 ± 2115 µm (range; 1500-10,000 µm). The mean tumor thickness before PDT was 3624 ± 1404 µm (range; 600-6000 µm). The mean lesion diameter after treatment was 6026 ± 2521 µm (range; 0-9000 µm), and the mean tumor thickness after treatment was 2280 ± 1740 µm (range; 0-6000 µm).After the PDT, tumor size decreased in 8 (53.3%) patients, increased in 3 (20%) patients, and no change in tumor size was observed in 4 (26.7%) patients. Mean IOP values of all patients were 14.06 ± 3.17 mmHg before treatment; after treatment, it was measured as 13.46 ± 1.70 mmHg. After the treatment, geographic atrophy developed in 1 (6.7%) patient, cystoid macular edema developed in 1 (6.7%) patient, Retinal Pigment Epithelium (RPE) and choroidal atrophy developed in 1 (6.7%) patient. CONCLUSION: There are not enough cases of each to clearly distinguish between these 3 types of ocular cancers.However PDT may be a good option in the treatment of intraocular tumors with the chance of selective treatment and successful response.

Therapeutic effect of modified double-dose photodynamic therapy in circumscribed choroidal haemangioma.

AIMS: To retrospectively compare the therapeutic effect of modified double-dose photodynamic therapy (PDT) with standard-dose PDT in patients with circumscribed choroidal haemangioma (CCH). METHODS: Thirty-nine patients with CCH were categorised in two groups by PDT type. The standard-dose group (n=12) was treated with 6 mg/m2 verteporfin and a 689 nm laser for 83 s. The modified double-dose group (n=27) received one vial of verteporfin (15 mg), and the dose was calculated for each patient based on body surface area, then irradiance time was adjusted according to calculated verteporfin dose to achieve a 'double'-dose effect. Treatment outcomes (foveal centre thickness, subretinal fluid, tumour thickness and diameter) were measured at baseline and 1 year post-treatment; subretinal fluid levels were also measured at 1, 3 and 6 months post-treatment. RESULTS: No differences in baseline characteristics were found between the two groups. The modified double-dose group showed a greater reduction in tumour thickness (45.3% vs 20.6%, p=0.013) and tumour volume (60.0% vs 30.0%, p=0.006) at 1 year post-treatment. Recurred or non-complete resolution patients in the standard-dose group tended to show much increased subretinal fluid than those in the modified double-dose group at 1-year post-treatment. CONCLUSION: Modified double-dose PDT is an effective and safe protocol for symptomatic CCH management, greater tumour regression and potentially better resolution of subretinal fluid compared with standard PDT.

Photodynamic therapy in the treatment of circumscribed choroidal hemangioma: Current perspectives.

Photodynamic therapy (PDT) using verteporfin Visudyne®(Novartis International AG, Basel, Switzerland) is widely used to treat various chorio-retinal diseases. PDT targets choroidal vascular abnormalities and induces selective occlusion of vessels. PDT was originally used in combination with full-dose verteporfin to treat neovascular age-related macular degeneration. Currently, the clinical targets of PDT have shifted to other chorioretinal conditions such as central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal hemangioma. Clinical studies have also facilitated the optimization of treatment outcomes in choroidal hemangiomas through changes in protocols including the introduction of reduced treatment settings; such as PDT with half-dose verteporfin and half-fluence PDT. Here, we review various evolving trends in clinical application of PDT and its use for choroidal hemangiomas from a practical perspective.

Long term outcome of adjuvant photodynamic therapy after cyberknife radiotherapy for choroidal melanoma.

PURPOSE: To report the outcome of photodynamic therapy (PDT) for choroidal melanoma as adjuvant treatment with CyberKnife radiotherapy. DESIGN: Retrospective interventional case series. METHODS: Standard-fluence PDT using verteporfin. OUTCOME MEASURES: Regression of tumor; resolution of subretinal fluid (SRF); change in best-corrected visual acuity (BCVA), and complications of PDT. RESULTS: The study included 16 choroidal melanomas (3 pigmented, 4 lightly pigmented, 9 amelanotic) treated with adjuvant PDT after CyberKnife radiotherapy. The mean follow up time was 45.5 months after the initial PDT. 13 patients improved completely with PDT sessions and growth was seen in 3 patients. There was seen completely resolution in SRF in 10 eyes, partial resolution in 3 eyes, and stable in 3 eyes. The mean thickness of tumors was 3.9 mm before PDT and 2.3 mm after PDT. Retina pigment epithelium atrophy in 3 patients and subretinal hemorrhage in 1 patient were seen as complication of PDT. Three patients underwent enucleation for recurrence in the tumor. There was not a higher rate of change in BCVA after PDT (37.5% stable; 25% increase; 37.5% decrease. Poor final visual acuity associated with worse initial visual acuity, proximity of the tumor to the foveola and optic disc, and radiation complications. CONCLUSIONS: PDT seems to offer a good option for posterior pole choroidal melanoma as adjuvant therapy in suitable cases. Future prospective studies with larger number of patients and with longer follow-up are needed to further investigation.

Half-fluence photodynamic therapy in peripapillary circumscribed choroidal haemangiomas.

PURPOSE: To evaluate the safety and efficacy of half-fluence photodynamic therapy (PDT) as treatment for symptomatic peripapillary circumscribed choroidal haemangiomas (CCHs). METHODS: In this prospective, interventional case series; 11 patients with symptomatic peripapillary CCHs presenting to a single centre were treated with half-fluence PDT using verteporfin 6 mg/m2 with fluence of 25 mJ/cm2 (standard is 50 mJ/cm2) and other standard settings. Patients were evaluated at baseline, four weeks, twelve weeks and twenty-four weeks post-PDT treatment with best corrected visual acuity (BCVA), ultrasonography, spectral domain optical coherence tomography (SD-OCT), visual evoked potential and angiographic studies. RESULTS: Eleven patients with peripapillary CCHs received half-fluence PDT. The BCVA significantly improved to 0.558 ± 0.118 at four weeks post-treatment (P = 0.014), to 0.494 ± 0.114 at twelve weeks (P = 0.006) and 0.441 ± 0.125 at twenty-four weeks (P = 0.007) from baseline levels of 1.017 ± 0.075 on log MAR scales. Similar improvement was observed in central macular thickness (CMT) of 78.50 ± 13.73 µm (P = 0.001) at four weeks; 114.70 ± 27.73 µm (P = 0.003) at twelve weeks and 174.60 ± 23.13 µm (P = 0.001) at twenty-four weeks post-treatment. A single session of re-treatment was required in 18% (n = 2) of patients which also showed complete resolution at last follow-up. No complications were observed without any significant change in retinal nerve fibre layer (RNFL) thickness at six months follow-up. CONCLUSIONS: Half-fluence PDT can be an effective and safe treatment option for peripapillary CCHs which results in both anatomical and functional improvements with no observable complications.

DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION AFTER TREATMENT WITH PHOTODYNAMIC THERAPY IN A 5-YEAR-OLD FEMALE WITH CHOROIDAL OSTEOMA.

PURPOSE: To describe a patient with a choroidal osteoma treated with photodynamic therapy to prevent tumor growth in whom choroidal neovascularization (CNV) developed after being treated with photodynamic therapy. METHODS: Case report. RESULTS: A 5-year-old Hispanic woman presented with an asymptomatic choroidal osteoma, temporal to the macula of her right eye. According to the patient's mother, her medical, surgical, and family history was unremarkable. At examination, best-corrected visual acuity was 20/30 in both eyes. After 11 months of follow-up, signs of tumor growth toward the fovea without any signs of CNV was noted. Photodynamic therapy was performed to prevent invasion of the foveola. Two months thereafter, the patient developed CNV in the macula region in the right eye, decreasing visual acuity to 20/200. The patient was treated with four total intravitreal injections of 1.25 mg of bevacizumab over 24 weeks, which resulted in inactivation of the CNV and improved visual acuity to 20/20. Choroidal neovascularization had been never reported in her past history and her follow-up visits over 7 years. In addition, no evidence of recurrent neovascular activity or tumor growth was reported. CONCLUSION: Choroidal osteoma is a benign tumor that can result in vision-threatening complications, caused by tumor growth and tumor decalcification. Photodynamic therapy is an effective modality in inducing choroidal osteoma decalcification and stabilization; however, CNV due to reperfusion following photodynamic therapy can be seen in the retina.

ALTERNATIVE MANAGEMENT OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA USING INTRAVITREAL METOPROLOL.

BACKGROUND/PURPOSE: To describe a patient with visually symptomatic circumscribed choroidal hemangioma (CCH) treated successfully with intravitreal beta-blocker. METHODS: This is an interventional single case report of a 63 year-old man with a juxtafoveal CCH and extensive subretinal fluid (SRF) unsuccessfully treated with intravitreal anti-VEGF. Off-label intravitreal use of metoprolol (50µg/0.05 ml) was then performed. Main outcome measures were resolution or decreased subretinal fluid on OCT, visual stability or improvement, lack of retinal/ocular toxicity. RESULTS: Following 2 intravitreal injections of metoprolol (1 month apart), significant response was observed with decrease of SRF and visual improvement to 20/400 during a 9-week follow-up after the injections. CONCLUSION: These preliminary findings suggest that intravitreal metoprolol can be a safe alternative treatment for patients with CCH. This off-label therapy could represent another option for patients with this condition.

DOUBLE FLUENCE PHOTODYNAMIC THERAPY FOR THE TREATMENT OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: To evaluate the efficacy and safety of double-fluence photodynamic therapy for the treatment of circumscribed choroidal hemangioma. METHODS: Retrospective observational study including patients affected by circumscribed choroidal hemangioma and treated with double-fluence photodynamic therapy. The photodynamic therapy was performed with verteporfin infusion intravenously (dose of 6 mg/m2 body surface area over 10 minutes), followed by the application of two consecutive spots of 50 J/cm2 light at 689 nm for 83 seconds. RESULTS: Twenty-three eyes of 23 patients were included. The mean best-corrected visual acuity increased from 20/45 to 20/28, the mean tumor thickness decreased from 2,758 ± 530 µm to 722 ± 314 µm (P < 0.05), and the mean central retinal thickness decreased from 404 ± 209 µm to 188 ± 56 µm (P < 0.05) in 12 months, respectively. A total reabsorption of macular subretinal fluid, cystoid macular edema, and SRF associated with the tumor was obtained within 6 months in all cases, with persistence of tumor-associated intraretinal fluid up to 12 months only in two patients. No cases of side effects or need for retreatment were reported during the follow-up (average time of 25 months). CONCLUSION: Double-fluence photodynamic therapy is a safe and effective treatment for circumscribed choroidal hemangiomas and should be considered as the first line of treatment for these lesions.

Prostate Cancer Detected by Choroidal Tumor and Complete Response to Hormonal Therapy: Case Report and Literature Review of 24 Patients With Choroidal Metastasis From Prostate Cancer.

Metastatic choroidal tumors derived from prostate cancer are rare. In this study, we report a patient who manifested a choroidal tumor as the initial presenting sign of prostate cancer and review 23 patients with choroidal metastasis of prostate cancer in the literature to answer a clinical question how the choroidal metastases would respond to hormonal therapy. A 73-year-old man presented with a choroidal tumor in the right eye. He was in good health and had no previous history except for current hemodialysis in 3 years due to chronic renal failure as a sequel to glomerulonephritis. With the diagnosis of a probable metastatic tumor, positron emission tomography was performed to disclose high-uptake sites in multiple bones, lymph nodes, and the prostate, together with multiple nodular lesions in bilateral lungs on computed tomography (CT) scan. Serum prostate-specific antigen (PSA) was elevated to 541 ng/mL, which supported prostate cancer as the primary site. He had degarelix injection, and the choroidal tumor resolved rapidly and became flat degeneration in a month. Prostate biopsy showed poorly differentiated adenocarcinoma, and he underwent surgical castration. He had no medication until 3 years later when he showed gradual increase of serum PSA up to 6.05 ng/mL and multiple bony metastases on CT scan. Bicalutamide, switched to enzalutamide and then to abiraterone, led to the undetectable level of serum PSA until the last visit with no relapse of the choroidal metastasis, 6.8 years after the initial visit. In the literature review of 24 patients with choroidal metastasis of prostate cancer, including this patient, 8 patients presented a choroidal tumor as the initial sign and the choroidal lesions mostly showed complete response to hormonal therapy. Among 13 patients who were frequently in the course of hormonal therapy, choroidal metastases showed complete or partial response to external beam radiation to the eye in 11 patients and episcleral plaque radiotherapy in 2 patients. In conclusion, metastatic choroidal tumors of prostate cancer would show good response to hormonal therapy when the therapy has not been initiated. Hormone-resistant choroidal metastases in the therapeutic course of prostate cancer could be managed successfully by external beam radiation to the eye.

Luteolin inhibits the proliferation, adhesion, migration and invasion of choroidal melanoma cells in vitro.

Choroidal melanoma is a devastating disease that causes visual loss and a high mortality rate due to metastasis. Luteolin, a potential anticancer compound, is widely found in natural plants. The aim of this study was to evaluate the antiproliferative, antiadhesive, antimigratory and anti-invasive effects of luteolin on choroidal melanoma cells in vitro and to explore its potential mechanism. Cell counting kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) assays, Cell adhesion, migration, and invasion assays were performed to examine the inhibitory effects of luteolin on cell cell viability, proliferation, adhesion, migration and invasion capacities, respectively. Considering the correlation between Matrix metalloenzymes and tumor metastasis, Enzyme-linked immunosorbent assays (ELISAs) were used to assess matrix metalloproteases MMP-2 and MMP-9 secretion. Western blotting was performed to detect p-PI3K P85, Akt, and p-Akt protein expression. The cytoskeletal proteins vimentin were observed with cell immunofluorescence staining. Luteolin can inhibit OCM-1 cell proliferation, migration, invasion and adhesion and C918 cell proliferation, migration, and invasion through the PI3K/Akt signaling pathway. Therefore, Luteolin may have potential as a therapeutic medication for Choroidal melanoma.

Rapid resolution of choroidal metastatic tumour secondary to lung cancer following treatment with alectinib.

A 64-year-old man presented with reduced vision in the right eye (visual acuity of 6/24 Snellen). The patient reported having a chronic cough and recent weight loss with difficulty in swallowing and abnormal liver function test 8 months prior to his presentation. He was a chronic smoker for 45 years, having quit a year earlier. Fundus examination showed a unifocal large yellow-brown subretinal mass involving the posterior segment of the eye and associated with subretinal fluid. The patient was diagnosed with a choroidal metastasis and was referred urgently to the oncology team who confirmed the presence of non-small cell lung cancer with distant metastases. He started treatment with alectinib (second-generation tyrosine kinase inhibitor). A few weeks later, his vision improved and, on examination, there was complete resolution of the choroidal mass and the associated subretinal fluid. Alectinib led to rapid resolution of his choroidal secondary and has excellent ocular safety profile.

Intravitreal metoprolol for circumscribed choroidal hemangiomas: a phase I clinical trial.

BACKGROUND: Choroidal hemangioma is a visual threatening condition for which treatments is neither uniform nor widely available. New management options are necessary. The purpose of this study is to assess the safety and early outcome of intravitreal metoprolol tartrate in five patients with CCH. METHODS: Five eyes of five patients diagnosed with subfoveal or peripapillary CCH and unsuccessfully treated with intravitreal anti-VEGF agents were enrolled and received off-label intravitreal injections of metoprolol (50µg/0.05 ml). Baseline and follow-up evaluations included best-corrected visual acuity, intraocular pressure measurement, assessment of anterior chamber cellular score/flare and vitritis, retinography, fundus autofluorescence, and ERG. Patients were followed for a period of 30 days. Statistical analysis involved comparison of pre- and post-treatment findings using a paired t-test. RESULTS: There was no significant difference in all ERG parameters regarding a- and b-wave amplitude and implicit time, and oscillatory potentials' maximal amplitude. There were no significant changes in visual acuity. None of the patients developed clinical signs of intraocular inflammation. The subretinal and/or intraretinal fluid improved in 3 out of 5 patients 4 weeks after the metoprolol injection. CONCLUSIONS: Patients with CCH treated with a single injection of 50µg/0.05ml intravitreal metoprolol injections showed no signs of acute ocular toxicity. This pilot study did not assess long-term retinal toxicity, different concentrations, drug resistance, and complications from repeated-intravitreal injections.