INTRAVITREAL MELPHALAN FOR TREATMENT OF VITREOUS SEEDING FROM CHOROIDAL MELANOMA.

PURPOSE: To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan. METHODS: Case report. RESULTS: A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 µg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications. CONCLUSION: Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.

PHOTODYNAMIC THERAPY AS PRIMARY TREATMENT FOR SMALL CHOROIDAL MELANOMA.

PURPOSE: To report outcomes of photodynamic therapy (PDT) as primary treatment for small amelanotic choroidal melanoma. METHODS: Retrospective interventional case series of 12 patients with small choroidal melanoma treated with standard-fluence PDT (83 seconds; 50 J/cm) using verteporfin. OUTCOME MEASURES: Tumor regression, subretinal fluid resolution, best-corrected visual acuity, and PDT complications. RESULTS: There were 12 eyes with melanoma, demonstrating amelanotic (10 [83%]) or lightly pigmented (n = 2, 17%) appearance. The mean tumor thickness was 2.7 mm (median, 2.8; range 1.8-3.7 mm). After PDT, mean follow-up was 56 months (median, 53; range, 14-91). Outcomes revealed complete tumor regression after 1 session (n = 3, 25%), 2 sessions (n = 3, 25%), and 3 sessions (n = 2, 17%) of PDT, reduced to mean thickness of 2.1 mm (median, 2.0; range 1.2-3.4 mm). Tumors that failed to regress (n = 4, 33%) were further controlled with transpupillary thermotherapy (n = 1) or plaque brachytherapy (n = 3). Subretinal fluid, present in six eyes, demonstrated resolution (n = 5) or progression (n = 1), and one tumor developed new subretinal fluid after PDT (n = 1). Visual outcome was stable (n = 11 eyes) or improved (n = 1). Photodynamic therapy complications included local retina pigment epithelium atrophy at the site of treatment in 3 (25%) eyes, with no effect on macular or optic nerve function. CONCLUSION: Primary PDT resulted in complete tumor regression of small amelanotic choroidal melanoma in 67% at mean 5 years, with no major effect on visual acuity.

Photodynamic therapy for symptomatic circumscribed choroidal hemangioma in 22 Chinese patients: A retrospective study.

The purpose of this study is to describe the effects and complications of photodynamic therapy (PDT) on Chinese patients with circumscribed choroidal hemangioma (CCH). In this retrospective study, 22 CCH patients who underwent PDT performed 15 min after the injection of intravenous verteporfin (6 mg/m2)with multiple 83-second laser spots at 689 nm (50 J/cm2) were studied. Fluorescein angiography and/or indocyanine green angiography, B-scan ultrasonography and optical coherence tomography were performed in all patients. Follow-up was performed until 12 months post-treatment. All patients were treated with one session, except 1 case with prior transpupillary thermotherapy history. At the 12-month follow-up, the mean of the best corrected visual acuity (BCVA) increased from 0.40 ± 0.38 to 0.56 ± 0.42 (p < 0.05), tumors became thinner (1.96 ± 2.65 mm vs. 4.31 ± 2.04 mm) (p < 0.05), and exudative detachment were diminished. The mean fovea center thickness (FCT) decreased from 540.1 ± 470.6 to 171.6 ± 79.3 µm at the 3-month follow-up. The 12-month BCVA was correlated with prior laser treatment, symptom duration, baseline CCH diameter and thickness, baseline FCT and cystoid macular edema. One patient developed a branch retinal artery occlusion. In conclusion, PDT is an effective and safe treatment for CCH. Specific PDT protocols for CCH should be standardized. The retinal arteriole should be spared during the treatment.

Mistletoe and Garlic Extracts as Polyurethane Carriers - A Possible Remedy for Choroidal Melanoma.

BACKGROUND: Melanoma is known as the most dangerous form of skin cancer; whereas the malignant choroidal melanoma is an orphan disease known as the most common primary intraocular malignancy in adults. Literature suggests that the consumption of garlic and mistletoe leads to a reduced risk of developing cancer. OBJECTIVE: The aim of this study was the obtaining and the characterization of polymer structures containing mistletoe or garlic extract. METHODS: The structures were obtained in a polyaddition process combined with a spontaneous emulsification; they were characterized by pH, size, Zeta potential and DSC measurements, evaluation of encapsulation efficacy, penetrability through membranes and in vitro cytotoxicity tests. RESULTS: The microstructures present sizes between 1.05 and 2.60 µm and Zeta potentials between -7 and +36 mV. A good encapsulation was observed on different evaluations (88-92%). It was determined that approx. 30% of polymer microstructures containing vegetal extracts pass through an artificial membrane in 4 days. An in vitro cytotoxicity test revealed that these products are safe for administration. The analysis of antitumor efficacy indicates that garlic extracts have important effects after 48 and 72 hours on A375 cells; however, polymer microstructures with herbal extracts did not reveal antiproliferative activities on A375 cells because these polymer structures present a slow degradation. CONCLUSION: Sterile eye drops solutions based on polymer microstructures containing garlic or mistletoe extracts were obtained; the sample based on garlic extracts may be used in the pharmaceutical field as drug carrier with an antiproliferative effect which occurs after a prolong period.

Choroidal haemangioma and photodynamic therapy. Anatomical and functional response of patients with choroidal hemangioma treated with photodynamic therapy. / Hemangioma coroideo y terapia fotodinámica. Respuesta anatómica y funcional de los pacientes con hemangioma coroideo tratados con terapia fotodinámica.

OBJECTIVE: To study the effectiveness and limitations of photodynamic therapy (PDT) as treatment of choice in patients with symptomatic circumscribed choroidal haemangioma. METHODS: A retrospective study was conducted on 16 patients (13 men and 3 women, with mean age of 54.88 years) with circumscribed choroidal haemangioma, who attended our centre and were treated with PDT in the last 7 years. RESULTS: All patients had circumscribed choroidal haemangioma, which caused a decrease in visual acuity (VA) secondary to the presence of intraretinal microcystic oedema or neurosensory detachment. The mean initial VA was 0.23, and the final mean VA after performing PDT was 0.38 (all the VA were measured in decimal scale). It should be noted that patients needed a mean of 1.69 PDT sessions. Three of the patients needed rescue treatment with trans-pupillary thermotherapy, intravitreal injection of anti-vascular endothelial growth factor (ranibizumab, aflibercept) or a dexamethasone intravitreal implant (Ozurdex®). The indication for a change of treatment was the persistence of intraretinal microcystic oedema and/or neurosensory detachment (or incomplete resolution) after 3 PDT sessions. As overall results, 62.5% of patients evolved into anatomical and functional (increase in AV or stability) resolution. CONCLUSIONS: PDT is a straight forward and fast procedure, with a good anatomical and functional response, causing minimal damage to adjacent vessels.

Photosensitizers and Photodynamic Therapy: Verteporfin.

Photodynamic therapy (PDT) is a phototherapy in which a photosensitive dye is injected into a peripheral vein and activated by light in order to occlude choroidal vessels or change their permeability. PDT has been largely applied in the treatment of choroidal neovascularization (CNV), especially CNV related to age-related macular degeneration, but was also of benefit in other diseases, including central serous chorioretinopathy and choroidal hemangioma.

Lapatinib and platinum-based chemotherapy ameliorate breast cancer with choroidal metastasis and restore visual acuity.

Involvement of the central nervous system in metastatic breast cancer is a particularly dismal occurrence because of its effects on mortality and quality of life. Development of choroidal metastasis in a breast cancer patient indicates poor prognosis and has become the major life-limiting problem. Various treatment modalities for choroidal metastasis have been applied with different efficacy. Here we describe a patient with HER2-overexpressing breast cancer and limited choroidal metastasis who responded to an HER2 tyrosine kinase inhibitor after failure of radiotherapy and chemotherapy. Her visual acuity was completely and durably restored after the targeted therapy. This case provides a unique treatment experience of breast cancer with choroidal metastasis.

Treatment of serous macular detachment associated with circumscribed choroidal hemangioma.

PURPOSE: To evaluate the effects of transpupillary thermotherapy and intravitreal bevacizumab injection on serous macular detachment and cystoid macular edema (CME) associated with circumscribed choroidal hemangioma. DESIGN: Retrospective, interventional case series. METHODS: We reviewed the records of 12 patients with circumscribed choroidal hemangioma treated with transpupillary thermotherapy and/or intravitreal injection of bevacizumab. We assessed changes in best-corrected visual acuity (BCVA), central foveal thickness by optical coherence tomography, and resolution of serous macular detachment and CME. RESULTS: Six of 8 patients treated with transpupillary thermotherapy showed complete resolution of serous macular detachment and CME and the median minimal angle of resolution (logMAR) BCVA improved from 0.85 to 0.35 (P = .026). Among these 6 patients, 1 had no recurrence for 86 months and 5 had sustained resolution of serous macular detachment for a mean duration of 32.8 months before recurrence. Among the 9 patients treated with bevacizumab (including 5 patients who had transpupillary thermotherapy as a primary treatment), 5 showed resolution of serous macular detachment and the median logMAR BCVA improved from 0.7 to 0.5 (P = .042). Among these 5 patients, 3 had sustained resolution for a mean duration of 5.7 months and 2 showed recurrent serous macular detachment after 3 and 12 months. CONCLUSION: Transpupillary thermotherapy and intravitreal bevacizumab appear effective in the management of symptomatic circumscribed choroidal hemangioma, although recurrence of serous macular detachment and CME developed after long-term follow-up of transpupillary thermotherapy, and the duration of treatment effectiveness appears to be short with bevacizumab.

Photodynamic therapy for circumscribed choroidal haemangioma: a case report.

Choroidal haemangioma is a benign tumour with visual acuity diminution due to subretinal fluid accumulation. There are many modalities of treatment of this visually disabling syndrome, some of them being argon laser photocoagulation, cryotherapy, external beam irradiation, proton beam radiotherapy, episcleral plaque radiotherapy and transpupillary thermotherapy. Another new modality of treatment with remarkable success rate is photodynamic therapy. In this modality a photosensitiser is injected intravenously followed by irradiation of a specific wave length for a specified time period. The photosensitiser concentrates within the vascular channels and after irradiation these channels are irreversibly obliterated. A 62 years old female patient of choroidal haemangioma, who presented in eye outpatient department was treated with the standard protocol used for photodynamic therapy. On follow-up of this patient it was found that there was improvement in the visual acuity from 6/12 in the left eye (affected eye) to 6/9. Not only was there an improvement in the visual acuity but there was anatomical improvement too as was evident by regressed cystoid macular oedema and circumscribed choroidal haemangioma. After six months of follow-up there was no leakage of dye with digital fluorescein angiography and indocyanine green.

Microcirculation patterns in indocyanine green angiography and the results of plaque therapy in choroidal melanoma.

PURPOSE: To determine the effect of radioactive plaque therapy on blood vessel behaviour in choroidal melanomas using indocyanine green (ICG) angiography. MATERIAL AND METHODS: Fifty-five patients with choroidal melanoma were studied. Ruthenium-106 plaques were used in 30 eyes, in 11 the "sandwich method" (Ruthenium-106 plaque with transpupillary thermotherapy), was applied and 14 tumours were treated with Iodine-125. In all cases ICG angiography was performed prior to treatment and 12 months after, and at different time afterwards. Baseline tumour microcirculation patterns (MCPs) were studied prior to treatment and post-treatment blood vessels changes were evaluated. Total follow-up period ranged from 14-22 months (mean: 16 months). RESULTS: Pre-treatment ICG angiography revealed complex MCPs, combining parallel with cross-linking, arcs with branching, loops and networks patterns in 23 (41.8%) and non-complex MCPs, including straight, parallel without cross-linking and arcs without branching patterns in 32 (58.2%) melanomas. Twelve months after treatment, 38 tumours (69.1%) showed a significant changes in their MCPs. The mean ultrasonographic regression rate in tumours with complex MCPs was 57.4% as opposed to 36.2% in the group with non-complex MCPs (p = 0.01). No statistically significant correlation in the height regression rate was found among the various methods of therapy, however a significant difference between the type of therapy and MCPs changes was observed (p < 0.001). Melanomas treated with Ruthenium-106 and TTT demonstrated slight or no MCPs changes, while tumours treated with Ruthenium-106 and Iodine-125 plaques alone showed a significant MCPs changes (p < 0.001). The statistical analysis showed the correlation between the type of baseline MCPs and the degree of their changes after treatment (p < 0.001). Tumours with networks, loops, arcs with branching and parallel with crossing showed an increased regression as compared to other MCPs. Twelve patients whose tumours contained complex MCPs developed metastatic disease. CONCLUSIONS: This study suggests that the response of choroidal melanoma to irradiation is related to MCPs as identified by ICG angiography; the presence of complex MCPs is associated with a high regression rate after plaque therapy and a high risk of development of systemic metastatic disease.

Primary treatment of choroidal amelanotic melanoma with photodynamic therapy.

The management of choroidal melanoma involves a delicate balance between preserving vision and preventing metastasis. Plaque brachytherapy has become standard management of most small lesions; however, this can result in radiation retinopathy and optic neuropathy. Transpupillary thermotherapy avoids these side-effects; however, it can also result in visual loss and its effectiveness is limited in amelanotic lesions. Photodynamic therapy with verteporfin has shown promise in animal studies of choroidal melanoma, and has recently been used in the management of lesions that have failed to respond to conventional therapy. The authors report a case of primary treatment of a small choroidal amelanotic melanoma with photodynamic therapy using verteporfin.

HESA-A: new treatment for breast cancer and choroidal metastasis.

BACKGROUND: Breast cancer is one of the main causes of mortality among women worldwide. This type of cancer metastasizes to different body tissues, giving rise to many problems. The effect of HESA-A, a drug of herbal-marine origin, on vision, quality of life, and survival of end-stage breast cancer patients was investigated in this study. MATERIAL/METHODS: In a double-blind study, 24 breast cancer patients with choroidal metastasis, aged between 41 and 49 years, were divided into case and control groups, treated with 50 mg/kg/day of HESA-A and placebo, respectively. The patients were evaluated in respect to the intensity of experienced pain, by assessing their rate of narcotic analgesic use. The patients' vision scale was also evaluated. RESULTS: Notable improvement was seen in the vision of patients treated with HESA-A. Patients receiving HESA-A used narcotics at lower doses, owing to reduced experience of pain. No changes were observed in the vision of control group patients, or their pain experience. CONCLUSIONS: The effects of natural compounds with antioxidant and anticancer properties have been emphasized by different studies. HESA-A is a compound of natural origin, consisting of rare elements and organic materials, which in several animal and cellular studies has shown powerful anticancer effects and less toxicity on normal cells. The results of this study showed considerable improvement in the vision of breast cancer patients treated with HESA-A.

Photodynamic therapy of circumscribed choroidal haemangioma.

AIM: To evaluate efficacy of verteporfin ocular photodynamic therapy (PDT) in treatment of 10 patients with a symptomatic circumscribed choroidal haemangioma. DESIGN: Prospective non-randomised, interventional case series and critical review of previously published studies. METHODS: 10 consecutive patients (seven primary, two failed transpupillary thermotherapy (TTT), and one failed external beam radiotherapy) with symptomatic circumscribed choroidal haemangioma were treated using verteporfin 6 mg/m2 given as an intravenous infusion over 10 minutes. Diode laser (690 nm) with an intensity of 600 mW/cm2 for 83 seconds (50 J/cm2) was applied 5 minutes after completion of infusion. Single or multiple partially overlapping spots were applied based on the tumour basal dimensions. Periodic follow up with ophthalmoscopy, ultrasonography, and angiographic studies was performed. RESULTS: All 10 patients showed evidence of regression with flattening of tumour, resolution of subretinal fluid, and reduction of choroidal vasculature on angiograms. The visual acuity either improved or remained stable in eight (80%) patients. Visual loss due to delayed choroidal atrophy was seen in two patients. CONCLUSIONS: Although verteporfin PDT is an effective treatment for management of symptomatic circumscribed choroidal haemangioma, delayed treatment related effects can lead to visual loss.

[Primary intraocular lymphoma with unusual clinical presentation and poor outcome]. / Primäres intraokuläres Lymphom mit untypischer Klinik und ungünstigem Verlauf.

BACKGROUND: Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the CNS. In general, the primary non-Hodgkin's lymphoma of the CNS is rare, accounting for 1 % of all non-Hodgkin's lymphomas and less than 1 % of all intraocular tumors. HISTORY AND SIGNS: A 70-year-old man was hospitalized in June 2002 because of acute loss of vision on his left eye. A severe vitreous hemorrhage was observed. Ultrasound showed solid subretinal lesions at the posterior fundus. Diagnostic vitreous surgery including a biopsy was performed. An intraocular malignant B-cell lymphoma was determined by immunohistochemistry. General screening revealed no further manifestations of the lymphoma. THERAPY AND OUTCOME: The patient initially refused any therapy until a painful secondary neovascular glaucoma with complete loss of visual function developed, thus prompting us to perform an enucleation. The following immunohistochemical examination confirmed the initial diagnosis. A chemotherapy with high-dose methotrexate and leucovorin rescue was initiated. CONCLUSIONS: Primary intraocular lymphoma can present as diffuse uveitis refractory to corticosteroids. Diagnosis can be difficult and is often delayed.

[Use of indocyanine green for photodynamic therapy of choroidal melanoma--preliminary report]. / Zastosowanie zieleni indocyjaninowej w leczeniu fotodynamicznym czerniaka naczyniówki--doniesienie wstepne.

PURPOSE: To evaluate the usefulness of indocyanine green (ICG) in the photodynamic therapy (iPDT) of choroidal melanoma. MATERIAL AND METHODS: Thirty eight patients with choroidal melanoma were treated with iPDT. Tumor thickness ranged from 2.6 to 4.1 mm in ultrasonography. Before iPDT Ruthenium-106 plaques were used in 18 cases, in 6 cases with additional transpupillary thermotherapy ("sandwich method"), and Iodine-125 plaques in 3 cases. In 11 eyes the iPDT was the only performed treatment. Therapy was performed with 810 nm diode laser after intravenous injection of 25 mg solution of indocyanine green. Six months after iPDT ophthalmological examination was performed with ultrasonography and ICGA images evaluation. RESULTS: The baseline ICG study showed pathological intrinsic vasculature in all examined cases. Six months after iPDT changes in microcirculation, as well as significant decrease of tumors thickness in ultrasonography (mean 38%), were detected in all cases. Complete regression of intrinsic vessels was demonstrated by ICGA in 26 cases, and partial regression of pathological vascularization was found in 12 patients. CONCLUSIONS: Our preliminary study suggests, that ICG mediated iPDT can be a new and promising way, to treat choroidal melanoma.

Treatment of choroidal melanoma using photodynamic therapy.

PURPOSE: To InternetAdvance publication at ajo.com Feb 26, 2002. investigate the effect of photodynamic therapy using verteporfin on choroidal melanoma. DESIGN: Interventional case series. METHOD: Four patients with choroidal melanoma who showed recurrence or no response after previous brachytherapy and transpupillary thermotherapy were treated with photodynamic therapy. RESULTS: One tumor decreased in size and remained stable for 18 months. One tumor had no growth for 11 months. Two melanomas continued to grow, necessitating enucleation. CONCLUSIONS: Of the four eyes that had failed conventional therapies, two would have been salvaged (to date) with photodynamic therapy. However, additional studies are needed to determine if photodynamic therapy can play a role in the management of choroidal melanoma.

Effect of dacarbazine (DTIC) on cultures from malignant melanoma of the choroid: an immunohistochemical and electron microscopic study.

INTRODUCTION: Dacarbazine (DTIC) is a very effective chemotherapeutic agent used in the treatment of cutaneous melanoma; it also could have a potential therapeutic value as an antimetastatic agent in the treatment of choroidal melanoma. OBJECTIVE: To study the HMB-45 and S100 protein expression in choroidal melanoma cultures with and without DTIC, and compare the immunohistochemical and electron microscopic changes in both groups. METHODS: Five- and seven-day cultures of choroidal melanoma (n = 21) were cultivated in diffusion chambers. The cultures were divided in two groups: I group (control group)--the cells were grown in 199-medium; II group--the cells were in 199-medium supplemented with 0.03 mg/ml of DTIC. Immunohistochemical studies were performed with paraffin-embedded material of the cultures by the avidin-biotin-alkaline phosphatase technique. Araldit-embedded material was studied by electron microscopy. RESULTS: The expression of HMB-45 and S100 protein in the cultures with DTIC ranged from slightly positive to negative. The tumor cells were severely damaged. Electron microscopy in this group showed presence only of cellular fragments. In the DTIC-free group the HMB-45 and S100 expressions were strongly positive. There were no electron microscopic evidence of cellular death. CONCLUSION: DTIC suppresses the growth of choroidal melanoma in vitro. These results indicate that further studies are warranted to elucidate the effect of DTIC in vivo.